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1.  Effects of Intensive Blood Pressure Lowering on Cardiovascular and Renal Outcomes: A Systematic Review and Meta-Analysis 
PLoS Medicine  2012;9(8):e1001293.
In a systematic review and meta-analysis Vlado Perkovic and colleagues investigate whether more intensive blood pressure lowering regimens are associated with greater reductions in the risk of major cardiovascular events and end stage kidney disease.
Background
Guidelines recommend intensive blood pressure (BP) lowering in patients at high risk. While placebo-controlled trials have demonstrated 22% reductions in coronary heart disease (CHD) and stroke associated with a 10-mmHg difference in systolic BP, it is unclear if more intensive BP lowering strategies are associated with greater reductions in risk of CHD and stroke. We did a systematic review to assess the effects of intensive BP lowering on vascular, eye, and renal outcomes.
Methods and Findings
We systematically searched Medline, Embase, and the Cochrane Library for trials published between 1950 and July 2011. We included trials that randomly assigned individuals to different target BP levels.
We identified 15 trials including a total of 37,348 participants. On average there was a 7.5/4.5-mmHg BP difference. Intensive BP lowering achieved relative risk (RR) reductions of 11% for major cardiovascular events (95% CI 1%–21%), 13% for myocardial infarction (0%–25%), 24% for stroke (8%–37%), and 11% for end stage kidney disease (3%–18%). Intensive BP lowering regimens also produced a 10% reduction in the risk of albuminuria (4%–16%), and a trend towards benefit for retinopathy (19%, 0%–34%, p = 0.051) in patients with diabetes. There was no clear effect on cardiovascular or noncardiovascular death. Intensive BP lowering was well tolerated; with serious adverse events uncommon and not significantly increased, except for hypotension (RR 4.16, 95% CI 2.25 to 7.70), which occurred infrequently (0.4% per 100 person-years).
Conclusions
Intensive BP lowering regimens provided greater vascular protection than standard regimens that was proportional to the achieved difference in systolic BP, but did not have any clear impact on the risk of death or serious adverse events. Further trials are required to more clearly define the risks and benefits of BP targets below those currently recommended, given the benefits suggested by the currently available data.
Please see later in the article for the Editors' Summary.
Editors' Summary
Background
About a third of US and UK adults have high blood pressure (hypertension). Although hypertension has no obvious symptoms, it can lead to heart attacks, stroke, and other forms of cardiovascular disease, to kidney failure, and to retinopathy (blindness caused by damage to the blood vessels in the back of the eye). Hypertension is diagnosed by measuring blood pressure (BP)—the force that blood moving around the body exerts on the inside of large blood vessels. BP is highest when the heart is pumping out blood (systolic BP) and lowest when it is refilling with blood (diastolic BP). A normal adult BP is defined as a systolic BP of less than 130 millimeters of mercury (mmHg) and a diastolic BP of less than 85 mmHg (a BP of 130/85). A reading of more than 140/90 indicates hypertension. Many factors affect BP, but overweight people and individuals who eat fatty or salty food are at high risk of developing hypertension. Mild hypertension can be corrected by making lifestyle changes, but people often take antihypertensive drugs to reduce their BP.
Why Was This Study Done?
Doctors usually try to reduce the BP of their hypertensive patients to 140/90 mmHg. However, some treatment guidelines now advocate a target BP of 130/80 mmHg for individuals at high risk of life-threatening cardiovascular events, such as people with diabetes or kidney impairment. But does more intensive BP lowering actually reduce the risk of heart attacks and stroke? Although placebo-controlled randomized trials of BP lowering have suggested that a 10 mmHg fall in systolic BP is associated with a 22% reduction in the risk in coronary heart disease and a 41% reduction in the risk of stroke, it is unclear whether intensive BP lowering strategies are associated with greater reductions in the risk of cardiovascular disease than standard strategies. In this systematic review (a search that uses predefined criteria to identify all the research on a given topic) and meta-analysis (a statistical method for combining the results of studies), the researchers investigate the effects of intensive BP lowering on cardiovascular, eye, and renal outcomes.
What Did the Researchers Do and Find?
The researchers identified 15 randomized controlled trials in which more than 37,000 participants were randomly assigned to antihypertensive drug-based strategies designed to achieve different target BPs. On average, the more intensive strategies reduced the BP of participants by 7.5/4.5 mmHg more than the less intensive strategies. Compared to standard BP lowering strategies, more intensive BP lowering strategies reduced the risk of major cardiovascular events (a composite endpoint comprising heart attack, stroke, heart failure, and cardiovascular death) by 11%, the risk of heart attack by 13%, the risk of stroke by 24%, the risk of end-stage kidney disease by 11%, and the risk of albuminuria (protein in the urine, a sign of kidney damage) by 10%. There was also a trend towards a reduced risk for retinopathy with more intensive BP lowering but no clear reduction in cardiovascular or noncardiovascular deaths. Finally, aiming for a lower BP target did not increase the rate of drug discontinuation or the risk of serious adverse events apart from hypotension (very low BP).
What Do These Findings Mean?
These findings suggest that, although intensive BP lowering regimens have no clear effect on the risk of death, they may provide greater protection against cardiovascular events than standard BP lowering regimens. Indeed, the researchers calculate that among every thousand hypertensive patients with a high cardiovascular risk, more intensive BP lowering could prevent two of the 20 cardiovascular events expected to happen every year. Although intensive BP lowering did not seem to increase the risk of severe adverse effects, the accuracy of this finding is limited by inconsistent reporting of adverse events in the trials included in this study. Moreover, because most of the trial participants had additional risk factors for cardiovascular events such as diabetes and chronic kidney disease, these findings may not be generalizable to people with hypertension alone. Thus, although this study suggests that a target BP of 130/80 is likely to produce an additional overall benefit compared to a target of 140/90, more trials are needed to confirm this conclusion and to determine the best way to reach the lower target.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001293.
The US National Heart Lung and Blood Institute has patient information about high blood pressure (in English and Spanish)
The American Heart Association provides information on high blood pressure and on cardiovascular diseases (in several languages); it also provides personal stories from people dealing with high blood pressure
The UK National Health Service (NHS) Choices website also provides detailed information for patients about hypertension, cardiovascular disease and kidney disease; the NHS Local website has a collection of personal stories about hypertension and a series of films that explain hypertension
MedlinePlus provides links to further information about high blood pressure, heart disease, stroke, and kidney disease (in English and Spanish)
doi:10.1371/journal.pmed.1001293
PMCID: PMC3424246  PMID: 22927798
2.  The Influence of Health Systems on Hypertension Awareness, Treatment, and Control: A Systematic Literature Review 
PLoS Medicine  2013;10(7):e1001490.
Will Maimaris and colleagues systematically review the evidence that national or regional health systems, including place of care and medication co-pays, influence hypertension awareness, treatment, and control.
Please see later in the article for the Editors' Summary
Background
Hypertension (HT) affects an estimated one billion people worldwide, nearly three-quarters of whom live in low- or middle-income countries (LMICs). In both developed and developing countries, only a minority of individuals with HT are adequately treated. The reasons are many but, as with other chronic diseases, they include weaknesses in health systems. We conducted a systematic review of the influence of national or regional health systems on HT awareness, treatment, and control.
Methods and Findings
Eligible studies were those that analyzed the impact of health systems arrangements at the regional or national level on HT awareness, treatment, control, or antihypertensive medication adherence. The following databases were searched on 13th May 2013: Medline, Embase, Global Health, LILACS, Africa-Wide Information, IMSEAR, IMEMR, and WPRIM. There were no date or language restrictions. Two authors independently assessed papers for inclusion, extracted data, and assessed risk of bias. A narrative synthesis of the findings was conducted. Meta-analysis was not conducted due to substantial methodological heterogeneity in included studies. 53 studies were included, 11 of which were carried out in LMICs. Most studies evaluated health system financing and only four evaluated the effect of either human, physical, social, or intellectual resources on HT outcomes. Reduced medication co-payments were associated with improved HT control and treatment adherence, mainly evaluated in US settings. On balance, health insurance coverage was associated with improved outcomes of HT care in US settings. Having a routine place of care or physician was associated with improved HT care.
Conclusions
This review supports the minimization of medication co-payments in health insurance plans, and although studies were largely conducted in the US, the principle is likely to apply more generally. Studies that identify and analyze complexities and links between health systems arrangements and their effects on HT management are required, particularly in LMICs.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
In 2008, one billion people, three-quarters of whom were living in low- and middle-income countries, had high blood pressure (hypertension). Worldwide, hypertension, which rarely has any symptoms, leads to about 7.5 million deaths annually from heart attacks, stroke, other cardiovascular diseases, and kidney disease. Hypertension, selected by the World Health Organization as the theme for World Health Day 2013, is diagnosed by measuring blood pressure, the force that blood circulating in the body exerts on the inside of large blood vessels. Blood pressure is highest when the heart is contracts to pump blood out (systolic blood pressure) and lowest when the heart relaxes and refills (diastolic blood pressure). Normal adult blood pressure is defined as a systolic blood pressure of less than 120 millimeters of mercury (mmHg) and a diastolic blood pressure of less than 80 mmHg (a blood pressure of less than 120/80 mmHg). A blood pressure reading of more than 140/90 mmHg indicates hypertension. Many factors affect blood pressure, but overweight people and individuals who eat fatty or salty foods are at high risk of developing hypertension.
Why Was This Study Done?
Most individuals can achieve good hypertension control, which reduces death and disability from cardiovascular and kidney disease, by making lifestyle changes (mild hypertension) and/or by taking antihypertensive drugs. Yet, in both developed and developing countries, many people with hypertension are not aware of their condition and are not adequately treated. As with other chronic diseases, weaknesses in health care systems probably contribute to the inadequate treatment of hypertension. A health care system comprises all the organizations, institutions, and resources whose primary purpose is to improve health. Weaknesses in health care systems can exist at the national, regional, district, community, and household level. In this systematic review (a study that uses predefined criteria to identify all the research on a given topic), the researchers investigate how national and regional health care system arrangements influence hypertension awareness, treatment, and control. Actions that might influence hypertension care at this level of health care systems include providing treatment for hypertension at no or reduced cost, the introduction of financial incentives to healthcare practitioners for the diagnosis and treatment of hypertension, and enhanced insurance coverage in countries such as the US where people pay for health care through insurance policies.
What Did the Researchers Do and Find?
The researchers identified 53 studies that analyzed whether regional or national health care systems arrangements were associated with patient awareness of hypertension, treatment of hypertension, adherence to antihypertensive medication treatment, and control of hypertension. The researchers used an established conceptual framework for health care systems and an approach called narrative synthesis to analyze the results of these studies, most of which were conducted in the US (36 studies) and other high-income countries (eight studies). Nearly all the studies evaluated the effects of health system financing on hypertension outcomes, although several looked at the effects of delivery and governance of health systems on these outcomes. The researchers' analysis revealed an association between reduced medication co-payments (drug costs that are not covered by health insurance and that are paid by patients in countries without universal free healthcare) and improved hypertension control and treatment adherence, mainly in US settings. In addition, in US settings, health insurance coverage was associated with improved hypertension outcomes, as was having a routine physician or place of care.
What Do These Findings Mean?
These findings suggest that minimizing co-payments for health care and expansion of health insurance coverage in countries without universal free health care may improve the awareness, treatment, and control of hypertension. Although these findings are based mainly on US studies, they are likely to apply more generally but, importantly, these findings indicate that additional, high-quality studies are needed to unravel the impact of health systems arrangements on the management of hypertension. In particular, they reveal few studies in low- and middle-income countries where most of the global burden of hypertension lies and where weaknesses in health systems often result in deficiencies in the care of chronic diseases. Moreover, they highlight a need for studies that evaluate how aspects of health care systems other than financing (for example, delivery and governance mechanisms) and interactions between health care system arrangements affect hypertension outcomes. Without the results of such studies, governments and national and international organizations will not know the best ways to deal effectively with the global public-health crisis posed by hypertension.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001490.
The US National Heart Lung and Blood Institute has patient information about high blood pressure (in English and Spanish)
The American Heart Association provides information on high blood pressure (in several languages) and personal stories about dealing with high blood pressure
The UK National Health Service (NHS) Choices website provides detailed information for patients about hypertension and a personal story about hypertension
The World Health Organization provides information on controlling blood pressure and on health systems (in several languages); its "A Global Brief on Hypertension" was published on World Health Day 2013
MedlinePlus provides links to further information about high blood pressure (in English and Spanish)
doi:10.1371/journal.pmed.1001490
PMCID: PMC3728036  PMID: 23935461
3.  Rational Prescribing in Primary Care (RaPP): A Cluster Randomized Trial of a Tailored Intervention 
PLoS Medicine  2006;3(6):e134.
Background
A gap exists between evidence and practice regarding the management of cardiovascular risk factors. This gap could be narrowed if systematically developed clinical practice guidelines were effectively implemented in clinical practice. We evaluated the effects of a tailored intervention to support the implementation of systematically developed guidelines for the use of antihypertensive and cholesterol-lowering drugs for the primary prevention of cardiovascular disease.
Methods and Findings
We conducted a cluster-randomized trial comparing a tailored intervention to passive dissemination of guidelines in 146 general practices in two geographical areas in Norway. Each practice was randomized to either the tailored intervention (70 practices; 257 physicians) or control group (69 practices; 244 physicians). Patients started on medication for hypertension or hypercholesterolemia during the study period and all patients already on treatment that consulted their physician during the trial were included. A multifaceted intervention was tailored to address identified barriers to change. Key components were an educational outreach visit with audit and feedback, and computerized reminders linked to the medical record system. Pharmacists conducted the visits. Outcomes were measured for all eligible patients seen in the participating practices during 1 y before and after the intervention. The main outcomes were the proportions of (1) first-time prescriptions for hypertension where thiazides were prescribed, (2) patients assessed for cardiovascular risk before prescribing antihypertensive or cholesterol-lowering drugs, and (3) patients treated for hypertension or hypercholesterolemia for 3 mo or more who had achieved recommended treatment goals.
The intervention led to an increase in adherence to guideline recommendations on choice of antihypertensive drug. Thiazides were prescribed to 17% of patients in the intervention group versus 11% in the control group (relative risk 1.94; 95% confidence interval 1.49–2.49, adjusted for baseline differences and clustering effect). Little or no differences were found for risk assessment prior to prescribing and for achievement of treatment goals.
Conclusions
Our tailored intervention had a significant impact on prescribing of antihypertensive drugs, but was ineffective in improving the quality of other aspects of managing hypertension and hypercholesterolemia in primary care.
Editors' Summary
Background.
An important issue in health care is “getting research into practice,” in other words, making sure that, when evidence from research has established the best way to treat a disease, doctors actually use that approach with their patients. In reality, there is often a gap between evidence and practice.
  An example concerns the treatment of people who have high blood pressure (hypertension) and/or high cholesterol. These are common conditions, and both increase the risk of having a heart attack or a stroke. Research has shown that the risks can be lowered if patients with these conditions are given drugs that lower blood pressure (antihypertensives) and drugs that lower cholesterol. There are many types of these drugs now available. In many countries, the health authorities want family doctors (general practitioners) to make better use of these drugs. They want doctors to prescribe them to everyone who would benefit, using the type of drugs found to be most effective. When there is a choice of drugs that are equally effective, they want doctors to use the cheapest type. (In the case of antihypertensives, an older type, known as thiazides, is very effective and also very cheap, but many doctors prefer to give their patients newer, more expensive alternatives.) Health authorities have issued guidelines to doctors that address these issues. However, it is not easy to change prescribing practices, and research in several countries has shown that issuing guidelines has only limited effects.
Why Was This Study Done?
The researchers wanted—in two parts of Norway—to compare the effects on prescribing practices of what they called the “passive dissemination of guidelines” with a more active approach, where the use of the guidelines was strongly promoted and encouraged.
What Did the Researchers Do and Find?
They worked with 146 general practices. In half of them the guidelines were actively promoted. The remaining were regarded as a control group; they were given the guidelines but no special efforts were made to encourage their use. It was decided at random which practices would be in which group; this approach is called a randomized controlled trial. The methods used to actively promote use of the guidelines included personal visits to the practices by pharmacists and use of a computerized reminder system. Information was then collected on the number of patients who, when first treated for hypertension, were prescribed a thiazide. Other information collected included whether patients had been properly assessed for their level of risk (for strokes and heart attacks) before antihypertensive or cholesterol-lowering drugs were given. In addition, the researchers recorded whether the recommended targets for improvement in blood pressure and cholesterol level had been reached.
Only 11% of those patients visiting the control group of practices who should have been prescribed thiazides, according to the guidelines, actually received them. Of those seen by doctors in the practices where the guidelines were actively promoted, 17% received thiazides. According to statistical analysis, the increase achieved by active promotion is significant. Little or no differences were found for risk assessment prior to prescribing and for achievement of treatment goals.
What Do These Findings Mean?
Even in the active promotion group, the great majority of patients (83%) were still not receiving treatment according to the guidelines. However, active promotion of guidelines is more effective than simply issuing the guidelines by themselves. The study also demonstrates that it is very hard to change prescribing practices. The efforts made here to encourage the doctors to change were considerable, and although the results were significant, they were still disappointing. Also disappointing is the fact that achievement of treatment goals was no better in the active-promotion group. These issues are discussed further in a Perspective about this study (DOI: 10.1371/journal.pmed.0030229).
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030134.
• The Web site of the American Academy of Family Physicians has a page on heart disease
• The MedlinePlus Medical Encyclopedia's pages on heart diseases and vascular diseases
• Information from NHS Direct (UK National Health Service) about heart attack and stroke
• Another PLoS Medicine article has also addressed trends in thiazide prescribing
Passive dissemination of management guidelines for hypertension and hypercholesterolaemia was compared with active promotion. Active promotion led to significant improvement in antihypertensive prescribing but not other aspects of management.
doi:10.1371/journal.pmed.0030134
PMCID: PMC1472695  PMID: 16737346
4.  How Evidence-Based Are the Recommendations in Evidence-Based Guidelines? 
PLoS Medicine  2007;4(8):e250.
Background
Treatment recommendations for the same condition from different guideline bodies often disagree, even when the same randomized controlled trial (RCT) evidence is cited. Guideline appraisal tools focus on methodology and quality of reporting, but not on the nature of the supporting evidence. This study was done to evaluate the quality of the evidence (based on consideration of its internal validity, clinical relevance, and applicability) underlying therapy recommendations in evidence-based clinical practice guidelines.
Methods and Findings
A cross-sectional analysis of cardiovascular risk management recommendations was performed for three different conditions (diabetes mellitus, dyslipidemia, and hypertension) from three pan-national guideline panels (from the United States, Canada, and Europe). Of the 338 treatment recommendations in these nine guidelines, 231 (68%) cited RCT evidence but only 105 (45%) of these RCT-based recommendations were based on high-quality evidence. RCT-based evidence was downgraded most often because of reservations about the applicability of the RCT to the populations specified in the guideline recommendation (64/126 cases, 51%) or because the RCT reported surrogate outcomes (59/126 cases, 47%).
Conclusions
The results of internally valid RCTs may not be applicable to the populations, interventions, or outcomes specified in a guideline recommendation and therefore should not always be assumed to provide high-quality evidence for therapy recommendations.
From an analysis of cardiovascular risk-management recommendations in guidelines produced by pan-national panels, McAlister and colleagues concluded that fewer than half were based on high-quality evidence.
Editors' Summary
Background.
Until recently, doctors largely relied on their own experience to choose the best treatment for their patients. Faced with a patient with high blood pressure (hypertension), for example, the doctor had to decide whether to recommend lifestyle changes or to prescribe drugs to reduce the blood pressure. If he or she chose the latter, he or she then had to decide which drug to prescribe, set a target blood pressure, and decide how long to wait before changing the prescription if this target was not reached. But, over the past decade, numerous clinical practice guidelines have been produced by governmental bodies and medical associations to help doctors make treatment decisions like these. For each guideline, experts have searched the medical literature for the current evidence about the diagnosis and treatment of a disease, evaluated the quality of that evidence, and then made recommendations based on the best evidence available.
Why Was This Study Done?
The recommendations made in different clinical practice guidelines vary, in part because they are based on evidence of varying quality. To help clinicians decide which recommendations to follow, some guidelines indicate the strength of their recommendations by grading them, based on the methods used to collect the underlying evidence. Thus, a randomized clinical trial (RCT)—one in which patients are randomly allocated to different treatments without the patient or clinician knowing the allocation—provides higher-quality evidence than a nonrandomized trial. Similarly, internally valid trials—in which the differences between patient groups are solely due to their different treatments and not to other aspects of the trial—provide high-quality evidence. However, grading schemes rarely consider the size of studies and whether they have focused on clinical or so-called “surrogate” measures. (For example, an RCT of a treatment to reduce heart or circulation [“cardiovascular”] problems caused by high blood pressure might have death rate as a clinical measure; a surrogate endpoint would be blood pressure reduction.) Most guidelines also do not consider how generalizable (applicable) the results of a trial are to the populations, interventions, and outcomes specified in the guideline recommendation. In this study, the researchers have investigated the quality of the evidence underlying recommendations for cardiovascular risk management in nine evidence-based clinical practice guides using these additional criteria.
What Did the Researchers Do and Find?
The researchers extracted the recommendations for managing cardiovascular risk from the current US, Canadian, and European guidelines for the management of diabetes, abnormal blood lipid levels (dyslipidemia), and hypertension. They graded the quality of evidence for each recommendation using the Canadian Hypertension Education Program (CHEP) grading scheme, which considers the type of study, its internal validity, its clinical relevance, and how generally applicable the evidence is considered to be. Of 338 evidence-based recommendations, two-thirds were based on evidence collected in internally valid RCTs, but only half of these RCT-based recommendations were based on high-quality evidence. The evidence underlying 64 of the guideline recommendations failed to achieve a high CHEP grade because the RCT data were collected in a population of people with different characteristics to those covered by the guideline. For example, a recommendation to use spironolactone to reduce blood pressure in people with hypertension was based on an RCT in which the participants initially had congestive heart failure with normal blood pressure. Another 59 recommendations were downgraded because they were based on evidence from RCTs that had not focused on clinical measures of effectiveness.
What Do These Findings Mean?
These findings indicate that although most of the recommendations for cardiovascular risk management therapies in the selected guidelines were based on evidence collected in internally valid RCTs, less than one-third were based on high-quality evidence applicable to the populations, treatments, and outcomes specified in guideline recommendations. A limitation of this study is that it analyzed a subset of recommendations in only a few guidelines. Nevertheless, the findings serve to warn clinicians that evidence-based guidelines are not necessarily based on high-quality evidence. In addition, they emphasize the need to make the evidence base underlying guideline recommendations more transparent by using an extended grading system like the CHEP scheme. If this were done, the researchers suggest, it would help clinicians apply guideline recommendations appropriately to their individual patients.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040250.
• Wikipedia contains pages on evidence-based medicine and on clinical practice guidelines (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
• The National Guideline Clearinghouse provides information on US national guidelines
• The Guidelines International Network promotes the systematic development and application of clinical practice guidelines
• Information is available on the Canadian Hypertension Education Program (CHEP) (in French and English)
• See information on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group, an organization that has developed an grading scheme similar to the CHEP scheme (in English, Spanish, French, German, and Italian)
doi:10.1371/journal.pmed.0040250
PMCID: PMC1939859  PMID: 17683197
5.  Barriers to adherence to hypertension guidelines among GPs in southern Sweden: A survey 
Objective
To evaluate barriers to adherence to hypertension guidelines among publicly employed general practitioners (GPs).
Design
Questionnaire-based survey distributed to GPs in 24 randomly selected primary care centres in the Region of Skåne in southern Sweden.
Subjects
A total of 109 GPs received a self-administered questionnaire and 90 of them responded.
Main outcome measures
Use of risk assessment programmes. Reasons to postpone or abstain from pharmacological treatment for the management of hypertension.
Results
Reported managing of high blood pressure (BP) varied. In all, 53% (95% CI 42–64%) of the GPs used risk assessment programmes and nine out of 10 acknowledged blood pressure target levels. Only one in 10 did not inform the patients about these levels. The range for immediate initiating pharmacological treatment was a systolic BP 140–220 (median 170) mmHg and diastolic BP 90–110 (median 100) mmHg. One-third (32%; 95% CI 22–42%) of the GPs postponed or abstained from pharmacological treatment of hypertension due to a patient's advanced age. No statistically significant associations were observed between GPs’ gender, professional experience (i.e. in terms of specialist family medicine and by number of years in practice), and specific reasons to postpone or abstain from pharmacological treatment of hypertension.
Conclusion
These data suggest that GPs accept higher blood pressure levels than recommended in clinical guidelines. Old age of the patient seems to be an important barrier among GPs when considering pharmacological treatment for the management of hypertension.
doi:10.1080/02813430802202111
PMCID: PMC3409603  PMID: 18609250
Barriers; family practice; guidelines; hypertension; primary care; survey
6.  The Blood Pressure "Uncertainty Range" – a pragmatic approach to overcome current diagnostic uncertainties (II) 
A tremendous amount of scientific evidence regarding the physiology and physiopathology of high blood pressure combined with a sophisticated therapeutic arsenal is at the disposal of the medical community to counteract the overall public health burden of hypertension. Ample evidence has also been gathered from a multitude of large-scale randomized trials indicating the beneficial effects of current treatment strategies in terms of reduced hypertension-related morbidity and mortality.
In spite of these impressive advances and, deeply disappointingly from a public health perspective, the real picture of hypertension management is overshadowed by widespread diagnostic inaccuracies (underdiagnosis, overdiagnosis) as well as by treatment failures generated by undertreatment, overtreatment, and misuse of medications.
The scientific, medical and patient communities as well as decision-makers worldwide are striving for greatest possible health gains from available resources.
A seemingly well-crystallised reasoning is that comprehensive strategic approaches must not only target hypertension as a pathological entity, but rather, take into account the wider environment in which hypertension is a major risk factor for cardiovascular disease carrying a great deal of our inheritance, and its interplay in the constellation of other, well-known, modifiable risk factors, i.e., attention is to be switched from one's "blood pressure level" to one's absolute cardiovascular risk and its determinants. Likewise, a risk/benefit assessment in each individual case is required in order to achieve best possible results.
Nevertheless, it is of paramount importance to insure generalizability of ABPM use in clinical practice with the aim of improving the accuracy of a first diagnosis for both individual treatment and clinical research purposes. Widespread adoption of the method requires quick adjustment of current guidelines, development of appropriate technology infrastructure and training of staff (i.e., education, decision support, and information systems for practitioners and patients). Progress can be achieved in a few years, or in the next 25 years.
doi:10.1186/1468-6708-6-5
PMCID: PMC1087497  PMID: 15813971
7.  Risk Stratification by Self-Measured Home Blood Pressure across Categories of Conventional Blood Pressure: A Participant-Level Meta-Analysis 
PLoS Medicine  2014;11(1):e1001591.
Jan Staessen and colleagues compare the risk of cardiovascular, cardiac, or cerebrovascular events in patients with elevated office blood pressure vs. self-measured home blood pressure.
Please see later in the article for the Editors' Summary
Background
The Global Burden of Diseases Study 2010 reported that hypertension is worldwide the leading risk factor for cardiovascular disease, causing 9.4 million deaths annually. We examined to what extent self-measurement of home blood pressure (HBP) refines risk stratification across increasing categories of conventional blood pressure (CBP).
Methods and Findings
This meta-analysis included 5,008 individuals randomly recruited from five populations (56.6% women; mean age, 57.1 y). All were not treated with antihypertensive drugs. In multivariable analyses, hazard ratios (HRs) associated with 10-mm Hg increases in systolic HBP were computed across CBP categories, using the following systolic/diastolic CBP thresholds (in mm Hg): optimal, <120/<80; normal, 120–129/80–84; high-normal, 130–139/85–89; mild hypertension, 140–159/90–99; and severe hypertension, ≥160/≥100.
Over 8.3 y, 522 participants died, and 414, 225, and 194 had cardiovascular, cardiac, and cerebrovascular events, respectively. In participants with optimal or normal CBP, HRs for a composite cardiovascular end point associated with a 10-mm Hg higher systolic HBP were 1.28 (1.01–1.62) and 1.22 (1.00–1.49), respectively. At high-normal CBP and in mild hypertension, the HRs were 1.24 (1.03–1.49) and 1.20 (1.06–1.37), respectively, for all cardiovascular events and 1.33 (1.07–1.65) and 1.30 (1.09–1.56), respectively, for stroke. In severe hypertension, the HRs were not significant (p≥0.20). Among people with optimal, normal, and high-normal CBP, 67 (5.0%), 187 (18.4%), and 315 (30.3%), respectively, had masked hypertension (HBP≥130 mm Hg systolic or ≥85 mm Hg diastolic). Compared to true optimal CBP, masked hypertension was associated with a 2.3-fold (1.5–3.5) higher cardiovascular risk. A limitation was few data from low- and middle-income countries.
Conclusions
HBP substantially refines risk stratification at CBP levels assumed to carry no or only mildly increased risk, in particular in the presence of masked hypertension. Randomized trials could help determine the best use of CBP vs. HBP in guiding BP management. Our study identified a novel indication for HBP, which, in view of its low cost and the increased availability of electronic communication, might be globally applicable, even in remote areas or in low-resource settings.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Globally, hypertension (high blood pressure) is the leading risk factor for cardiovascular disease and is responsible for 9.4 million deaths annually from heart attacks, stroke, and other cardiovascular diseases. Hypertension, which rarely has any symptoms, is diagnosed by measuring blood pressure, the force that blood circulating in the body exerts on the inside of large blood vessels. Blood pressure is highest when the heart is pumping out blood (systolic blood pressure) and lowest when the heart is refilling (diastolic blood pressure). European guidelines define optimal blood pressure as a systolic blood pressure of less than 120 millimeters of mercury (mm Hg) and a diastolic blood pressure of less than 80 mm Hg (a blood pressure of less than 120/80 mm Hg). Normal blood pressure, high-normal blood pressure, and mild hypertension are defined as blood pressures in the ranges 120–129/80–84 mm Hg, 130–139/85–89 mm Hg, and 140–159/90–99 mm Hg, respectively. A blood pressure of more than 160 mm Hg systolic or 100 mm Hg diastolic indicates severe hypertension. Many factors affect blood pressure; overweight people and individuals who eat salty or fatty food are at high risk of developing hypertension. Lifestyle changes and/or antihypertensive drugs can be used to control hypertension.
Why Was This Study Done?
The current guidelines for the diagnosis and management of hypertension recommend risk stratification based on conventionally measured blood pressure (CBP, the average of two consecutive measurements made at a clinic). However, self-measured home blood pressure (HBP) more accurately predicts outcomes because multiple HBP readings are taken and because HBP measurement avoids the “white-coat effect”—some individuals have a raised blood pressure in a clinical setting but not at home. Could risk stratification across increasing categories of CBP be refined through the use of self-measured HBP, particularly at CBP levels assumed to be associated with no or only mildly increased risk? Here, the researchers undertake a participant-level meta-analysis (a study that uses statistical approaches to pool results from individual participants in several independent studies) to answer this question.
What Did the Researchers Do and Find?
The researchers included 5,008 individuals recruited from five populations and enrolled in the International Database of Home Blood Pressure in Relation to Cardiovascular Outcome (IDHOCO) in their meta-analysis. CBP readings were available for all the participants, who measured their HBP using an oscillometric device (an electronic device for measuring blood pressure). The researchers used information on fatal and nonfatal cardiovascular, cardiac, and cerebrovascular (stroke) events to calculate the hazard ratios (HRs, indicators of increased risk) associated with a 10-mm Hg increase in systolic HBP across standard CBP categories. In participants with optimal CBP, an increase in systolic HBP of 10-mm Hg increased the risk of any cardiovascular event by nearly 30% (an HR of 1.28). Similar HRs were associated with a 10-mm Hg increase in systolic HBP for all cardiovascular events among people with normal and high-normal CBP and with mild hypertension, but for people with severe hypertension, systolic HBP did not significantly add to the prediction of any end point. Among people with optimal, normal, and high-normal CBP, 5%, 18.4%, and 30.4%, respectively, had a HBP of 130/85 or higher (“masked hypertension,” a higher blood pressure in daily life than in a clinical setting). Finally, compared to individuals with optimal CBP without masked hypertension, individuals with masked hypertension had more than double the risk of cardiovascular disease.
What Do These Findings Mean?
These findings indicate that HBP measurements, particularly in individuals with masked hypertension, refine risk stratification at CBP levels assumed to be associated with no or mildly elevated risk of cardiovascular disease. That is, HBP measurements can improve the prediction of cardiovascular complications or death among individuals with optimal, normal, and high-normal CBP but not among individuals with severe hypertension. Clinical trials are needed to test whether the identification and treatment of masked hypertension leads to a reduction of cardiovascular complications and is cost-effective compared to the current standard of care, which does not include HBP measurements and does not treat people with normal or high-normal CBP. Until then, these findings provide support for including HBP monitoring in primary prevention strategies for cardiovascular disease among individuals at risk for masked hypertension (for example, people with diabetes), and for carrying out HBP monitoring in people with a normal CBP but unexplained signs of hypertensive target organ damage.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001591.
This study is further discussed in a PLOS Medicine Perspective by Mark Caulfield
The US National Heart, Lung, and Blood Institute has patient information about high blood pressure (in English and Spanish) and a guide to lowering high blood pressure that includes personal stories
The American Heart Association provides information on high blood pressure and on cardiovascular diseases (in several languages); it also provides personal stories about dealing with high blood pressure
The UK National Health Service Choices website provides detailed information for patients about hypertension (including a personal story) and about cardiovascular disease
The World Health Organization provides information on cardiovascular disease and controlling blood pressure; its A Global Brief on Hypertension was published on World Health Day 2013
The UK charity Blood Pressure UK provides information about white-coat hypertension and about home blood pressure monitoring
MedlinePlus provides links to further information about high blood pressure, heart disease, and stroke (in English and Spanish)
doi:10.1371/journal.pmed.1001591
PMCID: PMC3897370  PMID: 24465187
8.  Global cardiovascular risk profiles of untreated hypertensives in an urban, developing community in Africa 
Cardiovascular Journal of Africa  2011;22(5):261-267.
Introduction
Blood pressure (BP) control in people of African descent is poor, largely because of a lack of treatment. Although the requirements for immediate initiation of antihypertensive drug therapy are defined by global cardiovascular risk, the global cardiovascular risk profiles of untreated hypertensives at a community level are uncertain.
Aim
To identify the distribution of global cardiovascular risk profiles of untreated hypertensives in an urban, developing community of African descent in South Africa.
Methods
As part of the African Programme on Genes in Hypertension, we assessed nurse-derived clinic BP (the mean of five standardised BP values obtained according to guidelines), current antihypertensive therapy, and total cardiovascular risk in 1 029 participants older than 16 years of age from randomly selected nuclear families from the South West Township of Gauteng (SOWETO).
Results
Approximately 46% of participants had systolic/diastolic BP values ≥ 140/90 mmHg and ~23% of participants were hypertensives not receiving antihypertensive medication. Approximately 12% of untreated hypertensives had a high added risk and ~18% a very high added risk (6.7% of the total sample). In untreated hypertensives, in contrast to the absence of severe hypertension and diabetes mellitus in those with lower risk profiles, a high cardiovascular risk profile in this group was characterised by severe hypertension in ~52% and diabetes mellitus in ~33%. Based on a high added risk carrying at least a 20% chance and a very high added risk at least a 30% chance of a cardiovascular event in 10 years, this translates into 1 740 events per 100 000 of the population within 10 years, events that could be prevented through antihypertensive drug therapy.
Conclusions
In an urban, developing community of African ancestry, a significant proportion (6.7%) of people may have untreated hypertension and a global cardiovascular risk profile that suggests a need for antihypertensive drug therapy. Cardiovascular risk in this group is driven largely by the presence of severe hypertension or diabetes mellitus.
doi:10.5830/CVJA-2010-094
PMCID: PMC3721881  PMID: 21161117
blood pressure control; antihypertensive treatment; detection of hypertension
9.  Twenty-Four-Hour Ambulatory Blood Pressure Monitoring in Hypertension 
Executive Summary
Objective
The objective of this health technology assessment was to determine the clinical effectiveness and cost-effectiveness of 24-hour ambulatory blood pressure monitoring (ABPM) for hypertension.
Clinical Need: Condition and Target Population
Hypertension occurs when either systolic blood pressure, the pressure in the artery when the heart contracts, or diastolic blood pressure, the pressure in the artery when the heart relaxes between beats, are consistently high. Blood pressure (BP) that is consistently more than 140/90 mmHg (systolic/diastolic) is considered high. A lower threshold, greater than 130/80 mmHg (systolic/diastolic), is set for individuals with diabetes or chronic kidney disease.
In 2006 and 2007, the age-standardized incidence rate of diagnosed hypertension in Canada was 25.8 per 1,000 (450,000 individuals were newly diagnosed). During the same time period, 22.7% of adult Canadians were living with diagnosed hypertension.
A smaller proportion of Canadians are unaware they have hypertension; therefore, the estimated number of Canadians affected by this disease may be higher. Diagnosis and management of hypertension are important, since elevated BP levels are related to the risk of cardiovascular disease, including stroke. In Canada in 2003, the costs to the health care system related to the diagnosis, treatment, and management of hypertension were over $2.3 billion (Cdn).
Technology
The 24-hour ABPM device consists of a standard inflatable cuff attached to a small computer weighing about 500 grams, which is worn over the shoulder or on a belt. The technology is noninvasive and fully automated. The device takes BP measurements every 15 to 30 minutes over a 24-to 28-hour time period, thus providing extended, continuous BP recordings even during a patient’s normal daily activities. Information on the multiple BP measurements can be downloaded to a computer.
The main detection methods used by the device are auscultation and oscillometry. The device avoids some of the pitfalls of conventional office or clinic blood pressure monitoring (CBPM) using a cuff and mercury sphygmomanometer such as observer bias (the phenomenon of measurement error when the observer overemphasizes expected results) and white coat hypertension (the phenomenon of elevated BP when measured in the office or clinic but normal BP when measured outside of the medical setting).
Research Questions
Is there a difference in patient outcome and treatment protocol using 24-hour ABPM versus CBPM for uncomplicated hypertension?
Is there a difference between the 2 technologies when white coat hypertension is taken into account?
What is the cost-effectiveness and budget impact of 24-hour ABPM versus CBPM for uncomplicated hypertension?
Research Methods
Literature Search
Search Strategy
A literature search was performed on August 4, 2011 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 1997 to August 4, 2011. Abstracts were reviewed by a single reviewer. For those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. Articles with unknown eligibility were reviewed with a second clinical epidemiologist and then a group of epidemiologists until consensus was established. The quality of evidence was assessed as high, moderate, low, or very low according to GRADE methodology.
Inclusion Criteria
English language articles;
published between January 1, 1997 and August 4, 2011;
adults aged 18 years of age or older;
journal articles reporting on the effectiveness, cost-effectiveness, or safety for the comparison of interest;
clearly described study design and methods;
health technology assessments, systematic reviews, meta-analyses, or randomized controlled trials.
Exclusion Criteria
non-English papers;
animal or in vitro studies;
case reports, case series, or case-case studies;
studies comparing different antihypertensive therapies and evaluating their antihypertensive effects using 24-hour ABPM;
studies on home or self-monitoring of BP, and studies on automated office BP measurement;
studies in high-risk subgroups (e.g. diabetes, pregnancy, kidney disease).
Outcomes of Interest
Patient Outcomes
mortality: all cardiovascular events (e.g., myocardial infarction [MI], stroke);
non-fatal: all cardiovascular events (e.g., MI, stroke);
combined fatal and non-fatal: all cardiovascular events (e.g., MI, stroke);
all non-cardiovascular events;
control of BP (e.g. systolic and/or diastolic target level).
Drug-Related Outcomes
percentage of patients who show a reduction in, or stop, drug treatment;
percentage of patients who begin multi-drug treatment;
drug therapy use (e.g. number, intensity of drug use);
drug-related adverse events.
Quality of Evidence
The quality of the body of evidence was assessed as high, moderate, low, or very low according to the GRADE Working Group criteria.
As stated by the GRADE Working Group, the following definitions of quality were used in grading the quality of the evidence:
Summary of Findings
Short-Term Follow-Up Studies (Length of Follow-Up of ≤ 1 Year)
Based on very low quality of evidence, there is no difference between technologies for non-fatal cardiovascular events.
Based on moderate quality of evidence, ABPM resulted in improved BP control among patients with sustained hypertension compared to CBPM.
Based on low quality of evidence, ABPM resulted in hypertensive patients being more likely to stop antihypertensive therapy and less likely to proceed to multi-drug therapy compared to CBPM.
Based on low quality of evidence, there is a beneficial effect of ABPM on the intensity of antihypertensive drug use compared to CBPM.
Based on moderate quality of evidence, there is no difference between technologies in the number of antihypertensive drugs used.
Based on low to very low quality of evidence, there is no difference between technologies in the risk for a drug-related adverse event or noncardiovascular event.
Long-Term Follow-Up Study (Mean Length of Follow-Up of 5 Years)
Based on moderate quality of evidence, there is a beneficial effect of ABPM on total combined cardiovascular events compared to CBPM.
Based on low quality of evidence, there is a lack of a beneficial effect of ABPM on nonfatal cardiovascular events compared to CBPM; however, the lack of a beneficial effect is based on a borderline result.
Based on low quality of evidence, there is no beneficial effect of ABPM on fatal cardiovascular events compared to CBPM.
Based on low quality of evidence, there is no difference between technologies for the number of patients who began multi-drug therapy.
Based on low quality of evidence, there is a beneficial effect of CBPM on control of BP compared to ABPM. This result is in the opposite direction than expected.
Based on moderate quality of evidence, there is no difference between technologies in the risk for a drug-related adverse event.
PMCID: PMC3377518  PMID: 23074425
10.  What is a preferred angiotensin II receptor blocker-based combination therapy for blood pressure control in hypertensive patients with diabetic and non-diabetic renal impairment? 
Hypertension has a major associated risk for organ damage and mortality, which is further heightened in patients with prior cardiovascular (CV) events, comorbid diabetes mellitus, microalbuminuria and renal impairment. Given that most patients with hypertension require at least two antihypertensives to achieve blood pressure (BP) goals, identifying the most appropriate combination regimen based on individual risk factors and comorbidities is important for risk management. Single-pill combinations (SPCs) containing two or more antihypertensive agents with complementary mechanisms of action offer potential advantages over free-drug combinations, including simplification of treatment regimens, convenience and reduced costs. The improved adherence and convenience resulting from SPC use is recognised in updated hypertension guidelines. Despite a wide choice of SPCs for hypertension treatment, clinical evidence from direct head-to-head comparisons to guide selection for individual patients is lacking. However, in patients with evidence of renal disease or at greater risk of developing renal disease, such as those with diabetes mellitus, microalbuminura and high-normal BP or overt hypertension, guidelines recommend renin-angiotensin system (RAS) blocker-based combination therapy due to superior renoprotective effects compared with other antihypertensive classes. Furthermore, RAS inhibitors attenuate the oedema and renal hyperfiltration associated with calcium channel blocker (CCB) monotherapy, making them a good choice for combination therapy. The occurrence of angiotensin-converting enzyme (ACE) inhibitor-induced cough supports the use of angiotensin II receptor blockers (ARBs) for RAS blockade rather than ACE inhibitors. In this regard, ARB-based SPCs are available in combination with the diuretic, hydrochlorothiazide (HCTZ) or the calcium CCB, amlodipine. Telmisartan, a long-acting ARB with preferential pharmacodynamic profile compared with several other ARBs, and the only ARB with an indication for the prevention of CV disease progression, is available in two SPC formulations, telmisartan/HCTZ and telmisartan/amlodipine. Clinical studies suggest that in CV high-risk patients and those with evidence of renal disease, the use of an ARB/CCB combination may be preferred to ARB/HCTZ combinations due to superior renoprotective and CV benefits and reduced metabolic side effects in patients with concomitant metabolic disorders. However, selection of the most appropriate antihypertensive combination should be dependent on careful review of the individual patient and appropriate consideration of drug pharmacology.
doi:10.1186/1475-2840-11-32
PMCID: PMC3351968  PMID: 22490507
Amlodipine; Angiotensin receptor II blocker; Diabetes mellitus; Hydrochlorothiazide; Hypertension; Renal impairment; Single-pill combination; Telmisartan
11.  The goal of blood pressure in the hypertensive patient with diabetes is defined: now the challenge is go from recommendations to practice 
The recent Latin American and European guidelines published this year has proposed as a goal for blood pressure control in patients with diabetes type 2 a value similar or inferior to 140/90 mmHg. High blood pressure is the leading cause of cardiovascular diseases and deaths globally. Although once hypertension is detected, 80% of individuals are on a pharmacologic therapy only a minority is controlled. Diabetes also is a risk factor for other serious chronic diseases, including cardiovascular disease. Whether specifically targeting lower fasting glucose levels can reduce cardiovascular outcomes remains unknown. Hypertension is present in 20% to 60% of patients with type 2 diabetes, depending on age, ethnicity, obesity, and the presence of micro or macro albuminuria. High blood pressure substantially increases the risk of both macro and micro vascular complications, doubling the risk of all-cause mortality and stroke, tripling the risk of coronary heart disease and significantly hastening the progression of diabetic nephropathy, retinopathy, and neuropathy. Thus, blood pressure lowering is a major priority in preventing cardiovascular and renal events in patients with diabetes and hypertension. During many years the BP goals recommended in patients with diabetes were more aggressive than in patients without diabetes. As reviewed in this article many clinical trials have demonstrated not only the lack of benefits of lowering the BP below 130/80 mmHg, but also the J-shaped relationship in DM patients. Overall we discuss the importance of define the group of patients in whom significant BP reduction could be particularly dangerous and, on the other hand, those with a high risk of stroke who could benefit most from an intensive hypotensive therapy. In any case, the big challenge now is avoid the therapeutic inertia (leaving diabetic patients with BP values of 140/90 mmHg or higher) at all costs, as this would lead to an unacceptable toll in terms of human lives, suffering, and socioeconomic costs.
doi:10.1186/1758-5996-6-31
PMCID: PMC3973894  PMID: 24594121
Hypertension; Diabetes; Guidelines; Blood pressure
12.  Associations between Active Travel to Work and Overweight, Hypertension, and Diabetes in India: A Cross-Sectional Study 
PLoS Medicine  2013;10(6):e1001459.
Using data from the Indian Migration Study, Christopher Millett and colleagues examine the associations between active travel to work and overweight, hypertension, and diabetes.
Please see later in the article for the Editors' Summary
Background
Increasing active travel (walking, bicycling, and public transport) is promoted as a key strategy to increase physical activity and reduce the growing burden of noncommunicable diseases (NCDs) globally. Little is known about patterns of active travel or associated cardiovascular health benefits in low- and middle-income countries. This study examines mode and duration of travel to work in rural and urban India and associations between active travel and overweight, hypertension, and diabetes.
Methods and Findings
Cross-sectional study of 3,902 participants (1,366 rural, 2,536 urban) in the Indian Migration Study. Associations between mode and duration of active travel and cardiovascular risk factors were assessed using random-effect logistic regression models adjusting for age, sex, caste, standard of living, occupation, factory location, leisure time physical activity, daily fat intake, smoking status, and alcohol use. Rural dwellers were significantly more likely to bicycle (68.3% versus 15.9%; p<0.001) to work than urban dwellers. The prevalence of overweight or obesity was 50.0%, 37.6%, 24.2%, 24.9%; hypertension was 17.7%, 11.8%, 6.5%, 9.8%; and diabetes was 10.8%, 7.4%, 3.8%, 7.3% in participants who travelled to work by private transport, public transport, bicycling, and walking, respectively. In the adjusted analysis, those walking (adjusted risk ratio [ARR] 0.72; 95% CI 0.58–0.88) or bicycling to work (ARR 0.66; 95% CI 0.55–0.77) were significantly less likely to be overweight or obese than those travelling by private transport. Those bicycling to work were significantly less likely to have hypertension (ARR 0.51; 95% CI 0.36–0.71) or diabetes (ARR 0.65; 95% CI 0.44–0.95). There was evidence of a dose-response relationship between duration of bicycling to work and being overweight, having hypertension or diabetes. The main limitation of the study is the cross-sectional design, which limits causal inference for the associations found.
Conclusions
Walking and bicycling to work was associated with reduced cardiovascular risk in the Indian population. Efforts to increase active travel in urban areas and halt declines in rural areas should be integral to strategies to maintain healthy weight and prevent NCDs in India.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Noncommunicable diseases (NCDs) and obesity (excessive body fat) are major threats to global health. Every year, more than 36 million people (including 29 million in LMICs) die from NCDs—nearly two-thirds of the world's annual deaths. Cardiovascular diseases (conditions that affect the heart and the circulation), diabetes, cancer, and respiratory diseases are responsible for most NCD-related deaths. Obesity is a risk factor for all these NCDs and the global prevalence of obesity (the proportion of the world's population that is obese) has nearly doubled since 1980. In 2008, 35% of adults were overweight and 11% were obese. One reason for the growing burden of both obesity and NCDs is increasing physical inactivity. Regular physical activity helps to maintain a healthy body weight and to prevent or delay the onset of NCDs. For an adult, 30 minutes of moderate physical activity—walking briskly or cycling, for example—five times a week is sufficient to promote and maintain health. But the daily lives of people in both developed and developing countries are becoming increasingly sedentary and, nowadays, at least 60% of the world's population does not do even this modest amount of exercise.
Why Was This Study Done?
Strategies to increase physical activity levels often promote active travel (walking, cycling, and using public transport). The positive impact of active travel on physical activity levels and cardiovascular health is well established in high-income countries, but little is known about the patterns of active travel or the health benefits associated with active travel in poorer countries. In this cross-sectional study (an investigation that measures population characteristics at a single time point), the researchers examine the mode and duration of travel to work in rural and urban India and associations between active travel and overweight/obesity, hypertension (high blood pressure, a risk factor for cardiovascular disease), and diabetes. In India, a lower middle-income country, the prevalence of overweight and NCDs is projected to increase rapidly over the next two decades. Moreover, rapid unplanned urbanization and a large increase in registered motor vehicles has resulted in inadequate development of the public transport infrastructure and hazardous conditions for walking and cycling in most Indian towns and cities.
What Did the Researchers Do and Find?
For their study, researchers analyzed physical activity and health data collected from participants in the Indian Migration Study, which examined the association between migration from rural to urban areas and obesity and diabetes risk. People living in rural areas were more likely to cycle to work than people living in towns and cities (68.3% versus 15.9%). Among people who travelled to work by private transport, public transport, walking, and cycling, the prevalence of overweight or obesity was 50.0%, 37.6%, 24.9%, and 24.2%, respectively. Similar patterns were seen for the prevalence of hypertension and diabetes. After adjustment for factors that affect the risk of obesity, hypertension, and diabetes (for example, daily fat intake and leisure time physical activity), people walking or cycling to work were less likely to be overweight or obese than those travelling by public transport, and those cycling to walk were less likely to have hypertension or diabetes. Finally, people with long cycle rides to work had a lower risk of being overweight or having hypertension or diabetes than people with short cycle rides.
What Do These Findings Mean?
These findings suggest that, as in high-income settings, walking and cycling to work are associated with a reduced risk of cardiovascular disease in India. Because this was a cross-sectional study, these findings do not prove that active travel reduces the risk of cardiovascular disease—people who cycle to work may share other unknown characteristics that are actually responsible for their reduced risk of cardiovascular disease. Moreover, this study did not consider non-cardiovascular outcomes associated with active travel that might affect health such as increased exposure to air pollution. Nevertheless, these findings suggest that programs designed to maintain healthy weight and prevent NCDs in India should endeavor to increase active travel in urban areas and to halt declines in rural areas by, for example, increasing investment in public transport and improving the safety and convenience of walking and cycling routes in urban areas.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001459.
This study is further discussed in a PLOS Medicine Perspective by Kavi Bhalla
The US Centers for Disease Control and Prevention provides information on all aspects of healthy living, on chronic diseases and health promotion, on overweight and obesity and on non-communicable diseases around the world; its Physical Activity for Everyone web pages include guidelines, instructional videos and personal success stories (some information in English and Spanish)
The World Health Organization provides information about physical activity and health, about obesity, and about non-communicable diseases (in several languages); its 2010 Global Recommendations on Physical Activity for Health are available in several languages; its Global Noncommunicable Disease Network (NCDnet) aims to help low- and middle- income countries reduce NCD-related illnesses and death through implementation of the 20082013 Action Plan for the Global Strategy for the Prevention and Control of Noncommunicable Diseases (also available in French); Face to face with chronic diseases is a selection of personal stories from around the world about dealing with NCDs
The American Heart Association provides information on many important risk factors for non-communicable diseases and provides tips for becoming more active
Information about the Indian Migration Study is available
doi:10.1371/journal.pmed.1001459
PMCID: PMC3679004  PMID: 23776412
13.  The 2007 Canadian Hypertension Education Program recommendations for the management of hypertension: Part 2 – therapy 
OBJECTIVE:
To provide updated, evidence-based recommendations for the prevention and management of hypertension in adults.
OPTIONS AND OUTCOMES:
For lifestyle and pharmacological interventions, evidence was reviewed from randomized controlled trials and systematic reviews of trials. Changes in cardiovascular morbidity and mortality were the primary outcomes of interest. However, for lifestyle interventions, blood pressure lowering was accepted as a primary outcome given the lack of long-term morbidity and mortality data in this field. For treatment of patients with kidney disease, the progression of kidney dysfunction was also accepted as a clinically relevant primary outcome.
EVIDENCE:
A Cochrane collaboration librarian conducted an independent MEDLINE search from 2005 to August 2006 to update the 2006 Canadian Hypertension Education Program recommendations. In addition, reference lists were scanned and experts were contacted to identify additional published studies. All relevant articles were reviewed and appraised independently by both content and methodological experts using prespecified levels of evidence.
RECOMMENDATIONS:
Dietary lifestyle modifications for prevention of hypertension, in addition to a well-balanced diet, include a dietary sodium intake of less than 100 mmol/day. In hypertensive patients, the dietary sodium intake should be limited to 65 mmol/day to 100 mmol/day. Other lifestyle modifications for both normotensive and hypertensive patients include: performing 30 min to 60 min of aerobic exercise four to seven days per week; maintaining a healthy body weight (body mass index of 18.5 kg/m2 to 24.9 kg/m2) and waist circumference (less than 102 cm in men and less than 88 cm in women); limiting alcohol consumption to no more than 14 units per week in men or nine units per week in women; following a diet reduced in saturated fat and cholesterol, and one that emphasizes fruits, vegetables and low-fat dairy products, dietary and soluble fibre, whole grains and protein from plant sources; and considering stress management in selected individuals with hypertension.
For the pharmacological management of hypertension, treatment thresholds and targets should take into account each individual’s global atherosclerotic risk, target organ damage and any comorbid conditions: blood pressure should be lowered to lower than 140/90 mmHg in all patients and lower than 130/80 mmHg in those with diabetes mellitus or chronic kidney disease. Most patients require more than one agent to achieve these blood pressure targets. In adults without compelling indications for other agents, initial therapy should include thiazide diuretics; other agents appropriate for first-line therapy for diastolic and/or systolic hypertension include angiotensin-converting enzyme (ACE) inhibitors (except in black patients), long-acting calcium channel blockers (CCBs), angiotensin receptor blockers (ARBs) or beta-blockers (in those younger than 60 years of age). First-line therapy for isolated systolic hypertension includes long-acting dihydropyridine CCBs or ARBs. Certain comorbid conditions provide compelling indications for first-line use of other agents: in patients with angina, recent myocardial infarction, or heart failure, beta-blockers and ACE inhibitors are recommended as first-line therapy; in patients with cerebrovascular disease, an ACE inhibitor plus diuretic combination is preferred; in patients with nondiabetic chronic kidney disease, ACE inhibitors are recommended; and in patients with diabetes mellitus, ACE inhibitors or ARBs (or, in patients without albuminuria, thiazides or dihydropyridine CCBs) are appropriate first-line therapies. All hypertensive patients with dyslipidemia should be treated using the thresholds, targets and agents outlined in the Canadian Cardiovascular Society position statement (recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease). Selected high-risk patients with hypertension who do not achieve thresholds for statin therapy according to the position paper should nonetheless receive statin therapy. Once blood pressure is controlled, acetylsalicylic acid therapy should be considered.
VALIDATION:
All recommendations were graded according to strength of the evidence and voted on by the 57 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. All recommendations reported here achieved at least 95% consensus. These guidelines will continue to be updated annually.
PMCID: PMC2650757  PMID: 17534460
Antihypertensive drugs; Blood pressure; Guidelines; High blood pressure; Hypertension; Lifestyle interventions
14.  Molecular sources of residual cardiovascular risk, clinical signals, and innovative solutions: relationship with subclinical disease, undertreatment, and poor adherence: implications of new evidence upon optimizing cardiovascular patient outcomes 
Residual risk, the ongoing appreciable risk of major cardiovascular events (MCVE) in statin-treated patients who have achieved evidence-based lipid goals, remains a concern among cardiologists. Factors that contribute to this continuing risk are atherogenic non-low-density lipoprotein (LDL) particles and atherogenic processes unrelated to LDL cholesterol, including other risk factors, the inherent properties of statin drugs, and patient characteristics, ie, genetics and behaviors. In addition, providers, health care systems, the community, public policies, and the environment play a role. Major statin studies suggest an average 28% reduction in LDL cholesterol and a 31% reduction in relative risk, leaving a residual risk of about 69%. Incomplete reductions in risk, and failure to improve conditions that create risk, may result in ongoing progression of atherosclerosis, with new and recurring lesions in original and distant culprit sites, remodeling, arrhythmias, rehospitalizations, invasive procedures, and terminal disability. As a result, identification of additional agents to reduce residual risk, particularly administered together with statin drugs, has been an ongoing quest. The current model of atherosclerosis involves many steps during which disease may progress independently of guideline-defined elevations in LDL cholesterol. Differences in genetic responsiveness to statin therapy, differences in ability of the endothelium to regenerate and repair, and differences in susceptibility to nonlipid risk factors, such as tobacco smoking, hypertension, and molecular changes associated with obesity and diabetes, may all create residual risk. A large number of inflammatory and metabolic processes may also provide eventual therapeutic targets to lower residual risk. Classically, epidemiologic and other evidence suggested that raising high-density lipoprotein (HDL) cholesterol would be cardioprotective. When LDL cholesterol is aggressively lowered to targets, low HDL cholesterol levels are still inversely related to MCVE. The efflux capacity, or ability to relocate cholesterol out of macrophages, is believed to be a major antiatherogenic mechanism responsible for reduction in MCVE mediated in part by healthy HDL. HDL cholesterol is a complex molecule with antioxidative, anti-inflammatory, anti-thrombotic, antiplatelet, and vasodilatory properties, among which is protection of LDL from oxidation. HDL-associated paraoxonase-1 has a major effect on endothelial function. Further, HDL promotes endothelial repair and progenitor cell health, and supports production of nitric oxide. HDL from patients with cardiovascular disease, diabetes, and autoimmune disease may fail to protect or even become proinflammatory or pro-oxidant. Mendelian randomization and other clinical studies in which raising HDL cholesterol has not been beneficial suggest that high plasma levels do not necessarily reduce cardiovascular risk. These data, coupled with extensive preclinical information about the functional heterogeneity of HDL, challenge the “HDL hypothesis”, ie, raising HDL cholesterol per se will reduce MCVE. After the equivocal AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes) study and withdrawal of two major cholesteryl ester transfer protein compounds, one for off-target adverse effects and the other for lack of efficacy, development continues for two other agents, ie, anacetrapib and evacetrapib, both of which lower LDL cholesterol substantially. The negative but controversial HPS2-THRIVE (the Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) trial casts further doubt on the HDL cholesterol hypothesis. The growing impression that HDL functionality, rather than abundance, is clinically important is supported by experimental evidence highlighting the conditional pleiotropic actions of HDL. Non-HDL cholesterol reflects the cholesterol in all atherogenic particles containing apolipoprotein B, and has outperformed LDL cholesterol as a lipid marker of cardiovascular risk and future mortality. In addition to including a measure of residual risk, the advantages of using non-HDL cholesterol as a primary lipid target are now compelling. Reinterpretation of data from the Treating to New Targets study suggests that better control of smoking, body weight, hypertension, and diabetes will help lower residual risk. Although much improved, control of risk factors other than LDL cholesterol currently remains inadequate due to shortfalls in compliance with guidelines and poor patient adherence. More efficient and greater use of proven simple therapies, such as aspirin, beta-blockers, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, combined with statin therapy, may be more fruitful in improving outcomes than using other complex therapies. Comprehensive, intensive, multimechanistic, global, and national programs using primordial, primary, and secondary prevention to lower the total level of cardiovascular risk are necessary.
doi:10.2147/VHRM.S37119
PMCID: PMC3808150  PMID: 24174878
cardiovascular prevention; low-density lipoprotein; high-density lipoprotein; statin drugs; metabolic syndrome; obesity; diabetes; niacin; AIM-HIGH study; cholesteryl ester transfer protein; endothelial progenitor cells; fibrate drugs
15.  The 2008 Canadian Hypertension Education Program recommendations for the management of hypertension: Part 2 – therapy 
OBJECTIVE:
To update the evidence-based recommendations for the prevention and management of hypertension in adults.
OPTIONS AND OUTCOMES:
For lifestyle and pharmacological interventions, evidence was preferentially reviewed from randomized controlled trials and systematic reviews of trials. Changes in cardiovascular morbidity and mortality were the primary outcomes of interest. However, for lifestyle interventions, blood pressure lowering was accepted as a primary outcome given the lack of long-term morbidity and mortality data in this field. Progression of kidney dysfunction was also accepted as a clinically relevant primary outcome among patients with chronic kidney disease.
EVIDENCE:
A Cochrane collaboration librarian conducted an independent MEDLINE search from 2006 to August 2007 to update the 2007 recommendations. To identify additional published studies, reference lists were reviewed and experts were contacted. All relevant articles were reviewed and appraised independently by content and methodological experts using prespecified levels of evidence.
RECOMMENDATIONS:
For lifestyle modifications to prevent and treat hypertension, restrict dietary sodium intake to less than 100 mmol/day (and 65 mmol/day to 100 mmol/day in hypertensive patients); perform 30 min to 60 min of aerobic exercise four to seven days per week; maintain a healthy body weight (body mass index 18.5 kg/m2 to 24.9 kg/m2) and waist circumference (smaller than 102 cm for men and smaller than 88 cm for women); limit alcohol consumption to no more than 14 units per week in men or nine units per week in women; follow a diet that is reduced in saturated fat and cholesterol, and one that emphasizes fruits, vegetables and low-fat dairy products, dietary and soluble fibre, whole grains and protein from plant sources; and consider stress management in selected individuals with hypertension. For the pharmacological management of hypertension, treatment thresholds and targets should be predicated on by the patient’s global atherosclerotic risk, target organ damage and comorbid conditions. Blood pressure should be decreased to lower than 140/90 mmHg in all patients, and to lower than 130/80 mmHg in those with diabetes mellitus or chronic kidney disease. Most patients will require more than one agent to achieve these target blood pressures. For adults without compelling indications for other agents, initial therapy should include thiazide diuretics. Other agents appropriate for first-line therapy for diastolic and/or systolic hypertension include angiotensin-converting enzyme (ACE) inhibitors (in nonblack patients), long-acting calcium channel blockers (CCBs), angiotensin receptor antagonists (ARBs) or beta-blockers (in those younger than 60 years of age). A combination of two first-line agents may also be considered for initial treatment of hypertension if systolic blood pressure is 20 mmHg above target or if diastolic blood pressure is 10 mmHg above target. Other agents appropriate for first-line therapy for isolated systolic hypertension include long-acting dihydropyridine CCBs or ARBs. In patients with angina, recent myocardial infarction or heart failure, beta-blockers and ACE inhibitors are recommended as first-line therapy; in patients with cerebrovascular disease, an ACE inhibitor/diuretic combination is preferred; in patients with protein-uric nondiabetic chronic kidney disease, ACE inhibitors are recommended; and in patients with diabetes mellitus, ACE inhibitors or ARBs (or, in patients without albuminuria, thiazides or dihydropyridine CCBs) are appropriate first-line therapies. All hypertensive patients with dyslipidemia should be treated using the thresholds, targets and agents outlined in the Canadian Cardiovascular Society position statement (recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease). Selected high-risk patients with hypertension but who do not achieve thresholds for statin therapy according to the position paper should nonetheless receive statin therapy. Once blood pressure is controlled, acetylsalicylic acid therapy should be considered.
VALIDATION:
All recommendations were graded according to strength of the evidence and voted on by the 57 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. All recommendations reported here achieved at least 95% consensus. These guidelines will continue to be updated annually.
PMCID: PMC2643190  PMID: 18548143
Antihypertensive drugs; Blood pressure; Guidelines; High blood pressure; Hypertension; Lifestyle interventions
16.  The 2009 Canadian Hypertension Education Program recommendations for the management of hypertension: Part 2 – therapy 
OBJECTIVE:
To update the evidence-based recommendations for the prevention and management of hypertension in adults for 2009.
OPTIONS AND OUTCOMES:
For lifestyle and pharmacological interventions, evidence from randomized controlled trials and systematic reviews of trials was preferentially reviewed. Changes in cardiovascular morbidity and mortality were the primary outcomes of interest. However, for lifestyle interventions, blood pressure lowering was accepted as a primary outcome given the lack of long-term morbidity and mortality data in this field. Progression of kidney dysfunction was also accepted as a clinically relevant primary outcome among patients with chronic kidney disease.
EVIDENCE:
A Cochrane collaboration librarian conducted an independent MEDLINE search from 2007 to August 2008 to update the 2008 recommendations. To identify additional published studies, reference lists were reviewed and experts were contacted. All relevant articles were reviewed and appraised independently by both content and methodological experts using prespecified levels of evidence.
RECOMMENDATIONS:
For lifestyle modifications to prevent and treat hypertension, restrict dietary sodium to less than 2300 mg (100 mmol)/day (and 1500 mg to 2300 mg [65 mmol to 100 mmol]/day in hypertensive patients); perform 30 min to 60 min of aerobic exercise four to seven days per week; maintain a healthy body weight (body mass index 18.5 kg/m2 to 24.9 kg/m2) and waist circumference (smaller than 102 cm for men and smaller than 88 cm for women); limit alcohol consumption to no more than 14 units per week in men or nine units per week in women; follow a diet that is reduced in saturated fat and cholesterol, and that emphasizes fruits, vegetables and low-fat dairy products, dietary and soluble fibre, whole grains and protein from plant sources; and consider stress management in selected individuals with hypertension. For the pharmacological management of hypertension, treatment thresholds and targets should be predicated on by the patient’s global atherosclerotic risk, target organ damage and comorbid conditions. Blood pressure should be decreased to lower than 140/90 mmHg in all patients, and to lower than 130/80 mmHg in those with diabetes mellitus or chronic kidney disease. Most patients will require more than one agent to achieve these target blood pressures. Antihypertensive therapy should be considered in all adult patients regardless of age (caution should be exercised in elderly patients who are frail). For adults without compelling indications for other agents, initial therapy should include thiazide diuretics. Other agents appropriate for first-line therapy for diastolic and/or systolic hypertension include angiotensin-converting enzyme (ACE) inhibitors (in patients who are not black), long-acting calcium channel blockers (CCBs), angiotensin receptor antagonists (ARBs) or beta-blockers (in those younger than 60 years of age). A combination of two first-line agents may also be considered as the initial treatment of hypertension if the systolic blood pressure is 20 mmHg above the target or if the diastolic blood pressure is 10 mmHg above the target. The combination of ACE inhibitors and ARBs should not be used. Other agents appropriate for first-line therapy for isolated systolic hypertension include long-acting dihydropyridine CCBs or ARBs. In patients with angina, recent myocardial infarction or heart failure, beta-blockers and ACE inhibitors are recommended as first-line therapy; in patients with cerebrovascular disease, an ACE inhibitor/diuretic combination is preferred; in patients with proteinuric nondiabetic chronic kidney disease, ACE inhibitors or ARBs (if intolerant to ACE inhibitors) are recommended; and in patients with diabetes mellitus, ACE inhibitors or ARBs (or, in patients without albuminuria, thiazides or dihydropyridine CCBs) are appropriate first-line therapies. All hypertensive patients with dyslipidemia should be treated using the thresholds, targets and agents outlined in the Canadian Cardiovascular Society position statement (recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease). Selected high-risk patients with hypertension who do not achieve thresholds for statin therapy according to the position paper should nonetheless receive statin therapy. Once blood pressure is controlled, acetylsalicylic acid therapy should be considered.
VALIDATION:
All recommendations were graded according to strength of the evidence and voted on by the 57 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. All recommendations reported here achieved at least 95% consensus. These guidelines will continue to be updated annually.
PMCID: PMC2707169  PMID: 19417859
Antihypertensive drugs; Blood pressure; Guidelines; High blood pressure; Hypertension; Lifestyle interventions
17.  The Effect of Tobacco Control Measures during a Period of Rising Cardiovascular Disease Risk in India: A Mathematical Model of Myocardial Infarction and Stroke 
PLoS Medicine  2013;10(7):e1001480.
In this paper from Basu and colleagues, a simulation of tobacco control and pharmacological interventions to prevent cardiovascular disease mortality in India predicted that Smokefree laws and increased tobacco taxation are likely to be the most effective measures to avert future cardiovascular deaths in India.
Please see later in the article for the Editors' Summary
Background
We simulated tobacco control and pharmacological strategies for preventing cardiovascular deaths in India, the country that is expected to experience more cardiovascular deaths than any other over the next decade.
Methods and Findings
A microsimulation model was developed to quantify the differential effects of various tobacco control measures and pharmacological therapies on myocardial infarction and stroke deaths stratified by age, gender, and urban/rural status for 2013 to 2022. The model incorporated population-representative data from India on multiple risk factors that affect myocardial infarction and stroke mortality, including hypertension, hyperlipidemia, diabetes, coronary heart disease, and cerebrovascular disease. We also included data from India on cigarette smoking, bidi smoking, chewing tobacco, and secondhand smoke. According to the model's results, smoke-free legislation and tobacco taxation would likely be the most effective strategy among a menu of tobacco control strategies (including, as well, brief cessation advice by health care providers, mass media campaigns, and an advertising ban) for reducing myocardial infarction and stroke deaths over the next decade, while cessation advice would be expected to be the least effective strategy at the population level. In combination, these tobacco control interventions could avert 25% of myocardial infarctions and strokes (95% CI: 17%–34%) if the effects of the interventions are additive. These effects are substantially larger than would be achieved through aspirin, antihypertensive, and statin therapy under most scenarios, because of limited treatment access and adherence; nevertheless, the impacts of tobacco control policies and pharmacological interventions appear to be markedly synergistic, averting up to one-third of deaths from myocardial infarction and stroke among 20- to 79-y-olds over the next 10 y. Pharmacological therapies could also be considerably more potent with further health system improvements.
Conclusions
Smoke-free laws and substantially increased tobacco taxation appear to be markedly potent population measures to avert future cardiovascular deaths in India. Despite the rise in co-morbid cardiovascular disease risk factors like hyperlipidemia and hypertension in low- and middle-income countries, tobacco control is likely to remain a highly effective strategy to reduce cardiovascular deaths.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Cardiovascular diseases (CVDs) are conditions that affect the heart and/or the circulation. In coronary heart disease, for example, narrowing of the heart's blood vessels by fatty deposits slows the blood supply to the heart and may eventually cause a heart attack (myocardial infarction). Stroke, by contrast, is a CVD in which the blood supply to the brain is interrupted. CVD has been a major cause of illness and death in high-income countries for many years, but the burden of CVD is now rapidly rising in low- and middle-income countries. Indeed, worldwide, three-quarters of all deaths from heart disease and stroke occur in low- and middle-income countries. Smoking, high blood pressure (hypertension), high blood cholesterol (hyperlipidemia), diabetes, obesity, and physical inactivity all increase an individual's risk of developing CVD. Prevention strategies and treatments for CVD include lifestyle changes (for example, smoking cessation) and taking drugs that lower blood pressure (antihypertensive drugs) or blood cholesterol levels (statins) or thin the blood (aspirin).
Why Was This Study Done?
Because tobacco use is a key risk factor for CVD and for several other noncommunicable diseases, the World Health Organization has developed an international instrument for tobacco control called the Framework Convention on Tobacco Control (FCTC). Parties to the FCTC (currently 176 countries) agree to implement a set of core tobacco control provisions including legislation to ban tobacco advertising and to increase tobacco taxes. But will tobacco control measures reduce the burden of CVD effectively in low- and middle-income countries as other risk factors for CVD are becoming more common? In this mathematical modeling study, the researchers investigated this question by simulating the effects of tobacco control measures and pharmacological strategies for preventing CVD on CVD deaths in India. Notably, many of the core FCTC provisions remain poorly implemented or unenforced in India even though it became a party to the convention in 2005. Moreover, experts predict that, over the next decade, this middle-income country will contribute more than any other nation to the global increase in CVD deaths.
What Did the Researchers Do and Find?
The researchers developed a microsimulation model (a computer model that operates at the level of individuals) to quantify the likely effects of various tobacco control measures and pharmacological therapies on deaths from myocardial infarction and stroke in India between 2013 and 2022. They incorporated population-representative data from India on risk factors that affect myocardial infarction and stroke mortality and on tobacco use and exposure to secondhand smoke into their model. They then simulated the effects of five tobacco control measures—smoke-free legislation, tobacco taxation, provision of brief cessation advice by health care providers, mass media campaigns, and advertising bans—and increased access to aspirin, antihypertensive drugs, and statins on deaths from myocardial infarction and stroke. Smoke-free legislation and tobacco taxation are likely to be the most effective strategies for reducing myocardial infarction and stroke deaths over the next decade, according to the model, and the effects of these strategies are likely to be substantially larger than those achieved by drug therapies under current health system conditions. If the effects of smoke-free legislation and tobacco taxation are additive, the model predicts that these two measures alone could avert about 9 million deaths, that is, a quarter of the expected deaths from myocardial infarction and stroke in India over the next 10 years, and that a combination of tobacco control policies and pharmacological interventions could avert up to a third of these deaths.
What Do These Findings Mean?
These findings suggest that the implementation of smoke-free laws and the introduction of increased tobacco taxes in India would yield substantial and rapid health benefits by averting future CVD deaths. The accuracy of these findings is likely to be affected by the many assumptions included in the mathematical model and by the quality of the data fed into it. Importantly, however, these finding suggest that, despite the rise in other CVD risk factors such as hypertension and hyperlipidemia, tobacco control is likely to be a highly effective strategy for the reduction of CVD deaths over the next decade in India and probably in other low- and middle-income countries. Policymakers in these countries should, therefore, work towards fuller and faster implementation of the core FCTC provisions to boost their efforts to reduce deaths from CVD.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001480.
The American Heart Association provides information on all aspects of cardiovascular disease; its website includes personal stories about heart attacks and stroke
The US Centers for Disease Control and Prevention has information on heart disease and on stroke (in English and Spanish
The UK National Health Service Choices website provides information about cardiovascular disease and stroke
MedlinePlus provides links to other sources of information on heart diseases, vascular diseases, and stroke (in English and Spanish)
The World Health Organization provides information (in several languages) about the dangers of tobacco, about the Framework Convention on Tobacco Control, and about noncommunicable diseases; its Global Noncommunicable Disease Network (NCDnet) aims to help low- and middle- income countries reduce illness and death caused by CVD and other noncommunicable diseases
SmokeFree, a website provided by the UK National Health Service, offers advice on quitting smoking and includes personal stories from people who have stopped smoking
Smokefree.gov, supported by the US National Cancer Institute and other US agencies, offers online tools and resources to help people quit smoking
doi:10.1371/journal.pmed.1001480
PMCID: PMC3706364  PMID: 23874160
18.  1999 Canadian recommendations for the management of hypertension 
OBJECTIVE: To provide updated, evidence-based recommendations for health care professionals on the management of hypertension in adults. OPTIONS: For patients with hypertension, there are both lifestyle options and pharmacological therapy options that may control blood pressure. For those patients who are using pharmacological therapy, a range of antihypertensive drugs is available. The choice of a specific antihypertensive drug is dependent upon the severity of the hypertension and the presence of other cardiovascular risk factors and concurrent diseases. OUTCOMES: The health outcomes considered were changes in blood pressure and in morbidity and mortality rates. Because of insufficient evidence, no economic outcomes were considered. EVIDENCE: MEDLINE searches were conducted from the period of the last revision of the Canadian Recommendations for the Management of Hypertension (January 1993 to May 1998). Reference lists were scanned, experts were polled and the personal files of the authors were used to identify other studies. All relevant articles were reviewed, classified according to study design and graded according to levels of evidence. VALUES: A high value was placed on the avoidance of cardiovascular morbidity and premature death caused by untreated hypertension. BENEFITS: Harms and costs: The diagnosis and treatment of hypertension with pharmacological therapy will reduce the blood pressure of patients with sustained hypertension. In certain settings, and for specific drugs, blood pressure lowering has been associated with reduced cardiovascular morbidity and mortality. RECOMMENDATIONS: This document contains detailed recommendations pertaining to all aspects of the diagnosis and pharmacological therapy of hypertensive patients. With respect to diagnosis, the recommendations endorse the greater use of non-office-based measures of blood pressure control (i.e., using home blood pressure and automatic ambulatory blood pressure monitoring equipment) and greater emphasis on the identification of other cardiovascular risk factors, both in the assessment of prognosis in hypertension and in the choice of therapy. On the treatment side, lower targets for blood pressure control are advocated for some subgroups of hypertensive patients, in particular, those with diabetes and renal disease. Implicit in the recommendations for therapy is the principle that for the vast majority of hypertensive patients treated pharmacologically, practitioners should not follow a stepped-care approach. Instead, therapy should be individualized, based on consideration of concurrent diseases, both cardiovascular and noncardiovascular. VALIDATION: All recommendations were graded according to the strength of the evidence and the consensus of all relevant stakeholders. SPONSORS: The Canadian Hypertension Society and the Canadian Coalition for High Blood Pressure Prevention and Control.
PMCID: PMC1253506  PMID: 10624417
19.  Personalized Prediction of Lifetime Benefits with Statin Therapy for Asymptomatic Individuals: A Modeling Study 
PLoS Medicine  2012;9(12):e1001361.
In a modeling study conducted by Myriam Hunink and colleagues, a population-based cohort from Rotterdam is used to predict the possible lifetime benefits of statin therapy, on a personalized basis.
Background
Physicians need to inform asymptomatic individuals about personalized outcomes of statin therapy for primary prevention of cardiovascular disease (CVD). However, current prediction models focus on short-term outcomes and ignore the competing risk of death due to other causes. We aimed to predict the potential lifetime benefits with statin therapy, taking into account competing risks.
Methods and Findings
A microsimulation model based on 5-y follow-up data from the Rotterdam Study, a population-based cohort of individuals aged 55 y and older living in the Ommoord district of Rotterdam, the Netherlands, was used to estimate lifetime outcomes with and without statin therapy. The model was validated in-sample using 10-y follow-up data. We used baseline variables and model output to construct (1) a web-based calculator for gains in total and CVD-free life expectancy and (2) color charts for comparing these gains to the Systematic Coronary Risk Evaluation (SCORE) charts. In 2,428 participants (mean age 67.7 y, 35.5% men), statin therapy increased total life expectancy by 0.3 y (SD 0.2) and CVD-free life expectancy by 0.7 y (SD 0.4). Age, sex, smoking, blood pressure, hypertension, lipids, diabetes, glucose, body mass index, waist-to-hip ratio, and creatinine were included in the calculator. Gains in total and CVD-free life expectancy increased with blood pressure, unfavorable lipid levels, and body mass index after multivariable adjustment. Gains decreased considerably with advancing age, while SCORE 10-y CVD mortality risk increased with age. Twenty-five percent of participants with a low SCORE risk achieved equal or larger gains in CVD-free life expectancy than the median gain in participants with a high SCORE risk.
Conclusions
We developed tools to predict personalized increases in total and CVD-free life expectancy with statin therapy. The predicted gains we found are small. If the underlying model is validated in an independent cohort, the tools may be useful in discussing with patients their individual outcomes with statin therapy.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Cardiovascular disease (CVD) affects the heart and/or the blood vessels and is a major cause of illness and death worldwide. In the US, for example, coronary heart disease—a CVD in which narrowing of the heart's blood vessels by fatty deposits slows the blood supply to the heart and may eventually cause a heart attack—is the leading cause of death, and stroke—a CVD in which the brain's blood supply is interrupted—is the fourth leading cause of death. Established risk factors for CVD include smoking, high blood pressure, obesity, and high blood levels of a fat called low-density lipoprotein (“bad cholesterol”). Because many of these risk factors can be modified by lifestyle changes and by drugs, CVD can be prevented. Thus, physicians can assess a healthy individual's risk of developing CVD using a CVD prediction model (equations that take into account the CVD risk factors to which the individual is exposed) and can then recommend lifestyle changes and medications to reduce that individual's CVD risk.
Why Was This Study Done?
Current guidelines recommend that asymptomatic (healthy) individuals whose likely CVD risk is high should be encouraged to take statins—cholesterol-lowering drugs—as a preventative measure. Statins help to prevent CVD in healthy people with a high predicted risk of CVD, but, like all medicines, they have some unwanted side effects, so it is important that physicians can communicate both the benefits and drawbacks of statins to their patients in a way that allows them to make an informed decision about taking these drugs. Telling a patient that statins will reduce his or her short-term risk of CVD is not always helpful—patients really need to know the potential lifetime benefits of statin therapy. That is, they need to know how much longer they might live if they take statins. Here, the researchers use a mathematical model to predict the personalized lifetime benefits (increased total and CVD-free life expectancy) of statin therapy for individuals without a history of CVD.
What Did the Researchers Do and Find?
The researchers used the Rotterdam Ischemic Heart Disease & Stroke Computer Simulation (RISC) model, which simulates the life courses of individuals through six health states, from well through to CVD or non-CVD death, to estimate lifetime outcomes with and without statin therapy in a population of healthy elderly individuals. They then used these outcomes and information on baseline risk factors to develop a web-based calculator suitable for personalized prediction of the lifetime benefits of statins in routine clinical practice. The model estimated that statin therapy increases average life expectancy in the study population by 0.3 years and average CVD-free life expectancy by 0.7 years. The gains in total and CVD-free life expectancy associated with statin therapy increased with blood pressure, unfavorable cholesterol levels, and body mass index (an indicator of body fat) but decreased with age. Notably, the web-based calculator predicted that some individuals with a low ten-year CVD risk might achieve a similar or larger gain in CVD-free life expectancy with statin therapy than some individuals with a high ten-year risk. So, for example, both a 55-year-old non-smoking woman with a ten-year CVD mortality risk of 2% (a two in a hundred chance of dying of CVD within ten years) and a 65-year-old male smoker with a ten-year CVD mortality risk of 15% might both gain one year of CVD-free life expectancy with statin therapy.
What Do These Findings Mean?
These findings suggest that statin therapy can lead on average to small gains in total life expectancy and slightly larger gains in CVD-free life expectancy among healthy individuals, and show that life expectancy benefits can be predicted using an individual's risk factor profile. The accuracy and generalizability of these findings is limited by the assumptions included in the model (in particular, the model did not allow for the known side effects of statin therapy) and by the data fed into it—importantly, the risk prediction model needs to be validated using an independent dataset. If future research confirms the findings of this study, the researchers' web-based calculator could provide complementary information to the currently recommended ten-year CVD mortality risk assessment. Whether communication of personalized outcomes will ultimately result in better clinical outcomes remains to be seen, however, because patients may be less likely to choose statin therapy when provided with more information about its likely benefits.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001361.
The web-based calculator for personalized prediction of lifetime benefits with statin therapy is available (after agreement to software license)
The American Heart Association provides information about many types of cardiovascular disease for patients, carers, and professionals, including information about drug therapy for cholesterol and a heart attack risk calculator
The UK National Health Service Choices website provides information about cardiovascular disease and about statins
Information is available from the British Heart Foundation on heart disease and keeping the heart healthy; information is also available on statins, including personal stories about deciding to take statins
The US National Heart Lung and Blood Institute provides information on a wide range of cardiovascular diseases
The European Society of Cardiology's cardiovascular disease risk assessment model (SCORE) is available
MedlinePlus provides links to many other sources of information on heart diseases, vascular diseases, stroke, and statins (in English and Spanish)
doi:10.1371/journal.pmed.1001361
PMCID: PMC3531501  PMID: 23300388
20.  Risk Models to Predict Chronic Kidney Disease and Its Progression: A Systematic Review 
PLoS Medicine  2012;9(11):e1001344.
A systematic review of risk prediction models conducted by Justin Echouffo-Tcheugui and Andre Kengne examines the evidence base for prediction of chronic kidney disease risk and its progression, and suitability of such models for clinical use.
Background
Chronic kidney disease (CKD) is common, and associated with increased risk of cardiovascular disease and end-stage renal disease, which are potentially preventable through early identification and treatment of individuals at risk. Although risk factors for occurrence and progression of CKD have been identified, their utility for CKD risk stratification through prediction models remains unclear. We critically assessed risk models to predict CKD and its progression, and evaluated their suitability for clinical use.
Methods and Findings
We systematically searched MEDLINE and Embase (1 January 1980 to 20 June 2012). Dual review was conducted to identify studies that reported on the development, validation, or impact assessment of a model constructed to predict the occurrence/presence of CKD or progression to advanced stages. Data were extracted on study characteristics, risk predictors, discrimination, calibration, and reclassification performance of models, as well as validation and impact analyses. We included 26 publications reporting on 30 CKD occurrence prediction risk scores and 17 CKD progression prediction risk scores. The vast majority of CKD risk models had acceptable-to-good discriminatory performance (area under the receiver operating characteristic curve>0.70) in the derivation sample. Calibration was less commonly assessed, but overall was found to be acceptable. Only eight CKD occurrence and five CKD progression risk models have been externally validated, displaying modest-to-acceptable discrimination. Whether novel biomarkers of CKD (circulatory or genetic) can improve prediction largely remains unclear, and impact studies of CKD prediction models have not yet been conducted. Limitations of risk models include the lack of ethnic diversity in derivation samples, and the scarcity of validation studies. The review is limited by the lack of an agreed-on system for rating prediction models, and the difficulty of assessing publication bias.
Conclusions
The development and clinical application of renal risk scores is in its infancy; however, the discriminatory performance of existing tools is acceptable. The effect of using these models in practice is still to be explored.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Chronic kidney disease (CKD)—the gradual loss of kidney function—is increasingly common worldwide. In the US, for example, about 26 million adults have CKD, and millions more are at risk of developing the condition. Throughout life, small structures called nephrons inside the kidneys filter waste products and excess water from the blood to make urine. If the nephrons stop working because of injury or disease, the rate of blood filtration decreases, and dangerous amounts of waste products such as creatinine build up in the blood. Symptoms of CKD, which rarely occur until the disease is very advanced, include tiredness, swollen feet and ankles, puffiness around the eyes, and frequent urination, especially at night. There is no cure for CKD, but progression of the disease can be slowed by controlling high blood pressure and diabetes, both of which cause CKD, and by adopting a healthy lifestyle. The same interventions also reduce the chances of CKD developing in the first place.
Why Was This Study Done?
CKD is associated with an increased risk of end-stage renal disease, which is treated with dialysis or by kidney transplantation (renal replacement therapies), and of cardiovascular disease. These life-threatening complications are potentially preventable through early identification and treatment of CKD, but most people present with advanced disease. Early identification would be particularly useful in developing countries, where renal replacement therapies are not readily available and resources for treating cardiovascular problems are limited. One way to identify people at risk of a disease is to use a “risk model.” Risk models are constructed by testing the ability of different combinations of risk factors that are associated with a specific disease to identify those individuals in a “derivation sample” who have the disease. The model is then validated on an independent group of people. In this systematic review (a study that uses predefined criteria to identify all the research on a given topic), the researchers critically assess the ability of existing CKD risk models to predict the occurrence of CKD and its progression, and evaluate their suitability for clinical use.
What Did the Researchers Do and Find?
The researchers identified 26 publications reporting on 30 risk models for CKD occurrence and 17 risk models for CKD progression that met their predefined criteria. The risk factors most commonly included in these models were age, sex, body mass index, diabetes status, systolic blood pressure, serum creatinine, protein in the urine, and serum albumin or total protein. Nearly all the models had acceptable-to-good discriminatory performance (a measure of how well a model separates people who have a disease from people who do not have the disease) in the derivation sample. Not all the models had been calibrated (assessed for whether the average predicted risk within a group matched the proportion that actually developed the disease), but in those that had been assessed calibration was good. Only eight CKD occurrence and five CKD progression risk models had been externally validated; discrimination in the validation samples was modest-to-acceptable. Finally, very few studies had assessed whether adding extra variables to CKD risk models (for example, genetic markers) improved prediction, and none had assessed the impact of adopting CKD risk models on the clinical care and outcomes of patients.
What Do These Findings Mean?
These findings suggest that the development and clinical application of CKD risk models is still in its infancy. Specifically, these findings indicate that the existing models need to be better calibrated and need to be externally validated in different populations (most of the models were tested only in predominantly white populations) before they are incorporated into guidelines. The impact of their use on clinical outcomes also needs to be assessed before their widespread use is recommended. Such research is worthwhile, however, because of the potential public health and clinical applications of well-designed risk models for CKD. Such models could be used to identify segments of the population that would benefit most from screening for CKD, for example. Moreover, risk communication to patients could motivate them to adopt a healthy lifestyle and to adhere to prescribed medications, and the use of models for predicting CKD progression could help clinicians tailor disease-modifying therapies to individual patient needs.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001344.
This study is further discussed in a PLOS Medicine Perspective by Maarten Taal
The US National Kidney and Urologic Diseases Information Clearinghouse provides information about all aspects of kidney disease; the US National Kidney Disease Education Program provides resources to help improve the understanding, detection, and management of kidney disease (in English and Spanish)
The UK National Health Service Choices website provides information for patients on chronic kidney disease, including some personal stories
The US National Kidney Foundation, a not-for-profit organization, provides information about chronic kidney disease (in English and Spanish)
The not-for-profit UK National Kidney Federation support and information for patients with kidney disease and for their carers, including a selection of patient experiences of kidney disease
World Kidney Day, a joint initiative between the International Society of Nephrology and the International Federation of Kidney Foundations, aims to raise awareness about kidneys and kidney disease
doi:10.1371/journal.pmed.1001344
PMCID: PMC3502517  PMID: 23185136
21.  Awareness, treatment, and control of major cardiovascular risk factors in a small-scale Italian community: results of a screening campaign 
Introduction
Hypertension, hypercholesterolemia, and diabetes are the main causes of cardiovascular diseases in developed countries. However, these conditions are still poorly recognized and treated.
Objective
This study aimed at estimating the prevalence, awareness, treatment, and control rates of major cardiovascular risk factors in an unselected sample of individuals of a small community located in northern Italy.
Methods
We screened 344 sequential subjects in this study. Data collection included family and clinical history, anthropometric data, blood pressure, blood glucose, and serum cholesterol values. Individual cardiovascular risk profiles were assessed by risk charts of the Progetto Cuore.
Results
Based on personal history and/or measured values, 78.2% of subjects had hypercholesterolemia (total cholesterol levels > 190 mg/dL), 61.0% had central obesity (waist circumference ≥ 94 cm for men and ≥80 cm for women), 51.2% had arterial hypertension (blood pressure ≥ 140/90 mmHg), 8.1% had diabetes (blood glucose ≥ 126 mg/dL), 22.7% had impaired fasting glucose (blood glucose 100–125 mg/dL), and 35.5% were overweight (body mass index 25–29 kg/m2). Alcohol drinkers and smokers accounted for 46.2% and 22.4% of subjects, respectively. Awareness of hypertension, hypercholesterolemia, and diabetes was poor, and control of these risk factors, except for diabetes, was even worse. Prevalence of high blood pressure, high serum cholesterol, overweight, and obesity significantly increased with aging. Hypercholesterolemia and obesity were significantly more common in women, while overweight and diabetes in men. In 15.4% of participants, the risk of a major cardiovascular event in the next 10 years was either high or very high.
Conclusion
In a small community in a wealthy region of Italy, the prevalence of major cardiovascular risk factors is high, while awareness, treatment, and control are poor. Such a result highlights the importance of screening campaigns as a strategy to improve early diagnosis and access to treatment, and thus effective prevention of cardiovascular diseases in the general population.
doi:10.2147/VHRM.S40925
PMCID: PMC3646473  PMID: 23662063
hypertension; hypercholesterolemia; diabetes; obesity; cardiovascular risk; Italy
22.  Diabetes: managing dyslipidaemia 
Clinical Evidence  2008;2008:0610.
Introduction
Dyslipidaemia is a major contributor to the increased risk of heart disease found in people with diabetes. An increase of 1 mmol/L LDL-C is associated with a 1.57-fold increase in the risk of coronary heart disease (CHD) in people with type 2 diabetes. A diagnosis of diabetic dyslipidaemia requiring pharmacological treatment is determined by the person's lipid profile and level of cardiovascular risk.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of interventions for dyslipidaemia in people with diabetes? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 21 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: anion exchange resins, combined treatments (for lipid modification), ezetimibe, fibrates, fish oil (for lipid modification), intensive multiple intervention treatment programmes (for lipid modification), nicotinic acid (for lipid modification), and statins.
Key Points
Dyslipidaemia is characterised by decreased circulating levels of high-density lipoprotein cholesterol (HDL-C) and increased circulating levels of triglycerides and low-density lipoprotein cholesterol (LDL-C). Dyslipidaemia is a major contributor to the increased risk of heart disease found in people with diabetes.An increase of 1 mmol/L LDL-C is associated with a 1.57-fold increase in the risk of CHD in people with type 2 diabetes.A diagnosis of diabetic dyslipidaemia requiring pharmacological treatment is determined by the person's lipid profile and level of cardiovascular risk. The classification of cardiovascular risk and lipid targets for drug treatment differ between the USA and the UK, and the rest of Europe. We used the United Kingdom Prospective Diabetes Study (UKPDS) risk calculator to estimate 10-year cardiovascular risk, and categorised a 15% or more risk as "higher risk", and 15% or less as "lower risk" according to the UK clinical guidelines. We found no RCTs of a solely lower-risk population, although some studies were excluded because of insufficient data to calculate risk. In clinical practice, most people with diabetes are increasingly considered at high cardiovascular risk, regardless of the presence or absence of other risk factors.
Statins are highly effective at improving cardiovascular outcomes in people with diabetes. Statins reduce cardiovascular mortality in people with type 2 diabetes with and without known CVD, and regardless of baseline total and LDL-C concentrations.Different statins seem to have similar efficacy at reducing LDL-C.
Combining statins with other treatments (such as ezetimibe or a fibrate) seems to reduce LDL-C more than statin treatments alone. Combinations could be useful in people with mixed dyslipidaemia where one drug fails to control all lipid parameters.
Fibrates seem to have a beneficial effect on cardiovascular mortality and morbidity by reducing triglyceride levels. In people with mixed dyslipidaemia, statins may also be required.
Intensive-treatment programmes involving multiple interventions (people seen by a nurse every 4-6 weeks) seem better at reducing cholesterol than usual-care programmes.
Fish oils may reduce triglyceride levels, but also seem to increase LDL-C levels, making them of limited benefit to most diabetic patients.
Nicotinic acid seems effective at increasing HDL-C and may reduce triglycerides. However, in clinical practice, nicotinic acid alone is not the preferred treatment for hypertriglyceridaemia, but may be used in combination with a statin in people with mixed dyslipidaemia, or in those unable to tolerate fibrates. Nicotinic acid seems to increase the incidence of flushing, particularly in female patients.
We don't know whether anion exchange resins or ezetimibe are useful in treating dyslipidaemia in people with diabetes, but they could be used in combination with a statin if the statin alone fails to achieve lipid targets.
PMCID: PMC2907966  PMID: 19450295
23.  Implementing the European guidelines for cardiovascular disease prevention in the primary care setting in Cyprus: Lessons learned from a health care services study 
Background
Recent guidelines recommend assessment and treatment of the overall risk for cardiovascular disease (CVD) through management of multiple risk factors in patients at high absolute risk. The aim of our study was to assess the level of cardiovascular risk in patients with known risk factors for CVD by applying the SCORE risk function and to study the implications of European guidelines on the use of treatment and goal attainment for blood pressure (BP) and lipids in the primary care of Cyprus.
Methods
Retrospective chart review of 1101 randomly selected patients with type 2 diabetes mellitus (DM2), or hypertension or hyperlipidemia in four primary care health centres. The SCORE risk function for high-risk regions was used to calculate 10-year risk of cardiovascular fatal event. Most recent values of BP and lipids were used to assess goal attainment to international standards. Most updated medications lists were used to compare proportions of current with recommended antihypertensive and lipid-lowering drug (LLD) users according to European guidelines.
Results
Implementation of the SCORE risk model labelled overall 39.7% (53.6% of men, 31.3% of women) of the study population as high risk individuals (CVD, DM2 or SCORE ≥5%). The SCORE risk chart was not applicable in 563 patients (51.1%) due to missing data in the patient records, mostly on smoking habits. The LDL-C goal was achieved in 28.6%, 19.5% and 20.9% of patients with established CVD, DM2 (no CVD) and SCORE ≥5%, respectively. BP targets were achieved in 55.4%, 5.6% and 41.9% respectively for the above groups. There was under prescription of antihypertensive drugs, LLD and aspirin for all three high risk groups.
Conclusion
This study demonstrated suboptimal control and under-treatment of patients with cardiovascular risk factors in the primary care in Cyprus. Improvement of documentation of clinical information in the medical records as well as GPs training for implementation and adherence to clinical practice guidelines are potential areas for further discussion and research.
doi:10.1186/1472-6963-8-148
PMCID: PMC2503957  PMID: 18631389
24.  A general practice-based study examining the absolute risk of cardiovascular disease in treated hypertensive patients. 
BACKGROUND: When managing hypertension, the assessment of the absolute risk of a cardiovascular' event is now advocated as the most accurate way in which the risks and benefits of anti-hypertensive therapy should be judged. Most studies that have examined control of hypertension have relied solely on the blood pressure level attained after treatment, with no measurement of the likely absolute risk in individual patients. AIM: To assess control of hypertension by quantifying the 10-year absolute risk of cardiovascular disease in patients treated by their general practitioners, and to assess which risk factors are associated with uncontrolled hypertension in this group of patients. METHOD: A cross-sectional study was made of patients on drug treatment for hypertension in 18 Oxfordshire general practices subscribing to the VAMP (value-added medical products) computer system. The absolute risk of suffering a cardiovascular event in the following 10 years was measured according to each individual's risk factor profile. Factors associated with uncontrolled hypertension were ascertained using multiple logistic regression analysis. RESULTS: Overall, 40.9% (37.6% to 44.1%) of the hypertensive population had an absolute risk exceeding 20% of having a cardiovascular event in the following 10 years. The distribution of risk factors varies throughout the population. A higher blood pressure reading was strongly associated with an increased likelihood of high absolute risk, but high blood pressure readings in individual patients did not necessarily equate to a high absolute risk. The factors independently associated with uncontrolled hypertension were age, sex, past history of stroke, ischaemic heart disease and transient ischaemic attack, a body mass index greater than 30, diabetes, and current smoking. CONCLUSIONS: Absolute risk assessment maximizes the risk-benefit ratio in treated hypertensive patients. Individual control and management requires multifactorial assessment and management. Treatment of hypertension according to blood pressure reading alone is not a reliable way of reducing the absolute risk of cardiovascular disease.
PMCID: PMC1239819  PMID: 8978111
25.  Effect of an Educational Toolkit on Quality of Care: A Pragmatic Cluster Randomized Trial 
PLoS Medicine  2014;11(2):e1001588.
In a pragmatic cluster-randomized trial, Baiju Shah and colleagues evaluated the effectiveness of printed educational materials for clinician education focusing on cardiovascular disease screening and risk reduction in people with diabetes.
Please see later in the article for the Editors' Summary
Background
Printed educational materials for clinician education are one of the most commonly used approaches for quality improvement. The objective of this pragmatic cluster randomized trial was to evaluate the effectiveness of an educational toolkit focusing on cardiovascular disease screening and risk reduction in people with diabetes.
Methods and Findings
All 933,789 people aged ≥40 years with diagnosed diabetes in Ontario, Canada were studied using population-level administrative databases, with additional clinical outcome data collected from a random sample of 1,592 high risk patients. Family practices were randomly assigned to receive the educational toolkit in June 2009 (intervention group) or May 2010 (control group). The primary outcome in the administrative data study, death or non-fatal myocardial infarction, occurred in 11,736 (2.5%) patients in the intervention group and 11,536 (2.5%) in the control group (p = 0.77). The primary outcome in the clinical data study, use of a statin, occurred in 700 (88.1%) patients in the intervention group and 725 (90.1%) in the control group (p = 0.26). Pre-specified secondary outcomes, including other clinical events, processes of care, and measures of risk factor control, were also not improved by the intervention. A limitation is the high baseline rate of statin prescribing in this population.
Conclusions
The educational toolkit did not improve quality of care or cardiovascular outcomes in a population with diabetes. Despite being relatively easy and inexpensive to implement, printed educational materials were not effective. The study highlights the need for a rigorous and scientifically based approach to the development, dissemination, and evaluation of quality improvement interventions.
Trial Registration
http://www.ClinicalTrials.gov NCT01411865 and NCT01026688
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Clinical practice guidelines help health care providers deliver the best care to patients by combining all the evidence on disease management into specific recommendations for care. However, the implementation of evidence-based guidelines is often far from perfect. Take the example of diabetes. This common chronic disease, which is characterized by high levels of sugar (glucose) in the blood, impairs the quality of life of patients and shortens life expectancy by increasing the risk of cardiovascular diseases (conditions that affect the heart and circulation) and other life-threatening conditions. Patients need complex care to manage the multiple risk factors (high blood sugar, high blood pressure, high levels of fat in the blood) that are associated with the long-term complications of diabetes, and they need to be regularly screened and treated for these complications. Clinical practice guidelines for diabetes provide recommendations on screening and diagnosis, drug treatment, and cardiovascular disease risk reduction, and on helping patients self-manage their disease. Unfortunately, the care delivered to patients with diabetes frequently fails to meet the standards laid down in these guidelines.
Why Was This Study Done?
How can guideline adherence and the quality of care provided to patients be improved? A common approach is to send printed educational materials to clinicians. For example, when the Canadian Diabetes Association (CDA) updated its clinical practice guidelines in 2008, it mailed educational toolkits that contained brochures and other printed materials targeting key themes from the guidelines to family physicians. In this pragmatic cluster randomized trial, the researchers investigate the effect of the CDA educational toolkit that targeted cardiovascular disease screening and treatment on the quality of care of people with diabetes. A pragmatic trial asks whether an intervention works under real-life conditions and whether it works in terms that matter to the patient; a cluster randomized trial randomly assigns groups of people to receive alternative interventions and compares outcomes in the differently treated “clusters.”
What Did the Researchers Do and Find?
The researchers randomly assigned family practices in Ontario, Canada to receive the educational toolkit in June 2009 (intervention group) or in May 2010 (control group). They examined outcomes between July 2009 and April 2010 in all patients with diabetes in Ontario aged over 40 years (933,789 people) using population-level administrative data. In Canada, administrative databases record the personal details of people registered with provincial health plans, information on hospital visits and prescriptions, and physician service claims for consultations, assessments, and diagnostic and therapeutic procedures. They also examined clinical outcome data from a random sample of 1,592 patients at high risk of cardiovascular complications. In the administrative data study, death or non-fatal heart attack (the primary outcome) occurred in about 11,500 patients in both the intervention and control group. In the clinical data study, the primary outcome―use of a statin to lower blood fat levels―occurred in about 700 patients in both study groups. Secondary outcomes, including other clinical events, processes of care, and measures of risk factor control were also not improved by the intervention. Indeed, in the administrative data study, some processes of care outcomes related to screening for heart disease were statistically significantly worse in the intervention group than in the control group, and in the clinical data study, fewer patients in the intervention group reached blood pressure targets than in the control group.
What Do These Findings Mean?
These findings suggest that the CDA cardiovascular diseases educational toolkit did not improve quality of care or cardiovascular outcomes in a population with diabetes. Indeed, the toolkit may have led to worsening in some secondary outcomes although, because numerous secondary outcomes were examined, this may be a chance finding. Limitations of the study include its length, which may have been too short to see an effect of the intervention on clinical outcomes, and the possibility of a ceiling effect—the control group in the clinical data study generally had good care, which left little room for improvement of the quality of care in the intervention group. Overall, however, these findings suggest that printed educational materials may not be an effective way to improve the quality of care for patients with diabetes and other complex conditions and highlight the need for a rigorous, scientific approach to the development, dissemination, and evaluation of quality improvement interventions.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001588.
The US National Diabetes Information Clearinghouse provides information about diabetes for patients, health care professionals, and the general public (in English and Spanish)
The UK National Health Service Choices website provides information (including some personal stories) for patients and carers about type 2 diabetes, the commonest form of diabetes
The Canadian Diabetes Association also provides information about diabetes for patients (including some personal stories about living with diabetes) and health care professionals; its latest clinical practice guidelines are available on its website
The UK National Institute for Health and Care Excellence provides general information about clinical guidelines and about health care quality standards in the UK
The US Agency for Healthcare Research and Quality aims to improve the quality, safety, efficiency, and effectiveness of health care for all Americans (information in English and Spanish); the US National Guideline Clearinghouse is a searchable database of clinical practice guidelines
The International Diabetes Federation provides information about diabetes for patients and health care professionals, along with international statistics on the burden of diabetes
doi:10.1371/journal.pmed.1001588
PMCID: PMC3913553  PMID: 24505216

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