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1.  1999–2009 Trends in Prevalence, Unawareness, Treatment and Control of Hypertension in Geneva, Switzerland 
PLoS ONE  2012;7(6):e39877.
Background
There are no time trends in prevalence, unawareness, treatment, and control of hypertension in Switzerland. The objective of this study was to analyze these trends and to determine the associated factors.
Methods/Findings
Population-based study conducted in the Canton of Geneva, Switzerland, between 1999 and 2009. Blood pressure was measured thrice using a standard protocol. Hypertension was defined as mean systolic or diastolic blood pressure ≥140/90 mmHg or self-reported hypertension or anti-hypertensive medication. Unawareness, untreated and uncontrolled hypertension was determined by questionnaires/blood pressure measurements. Yearly age-standardized prevalences and adjusted associations for the 1999–2003 and 2004–2009 survey periods were reported. The 10-year survey included 9,215 participants aged 35 to 74 years. Hypertension remained stable (34.4%). Hypertension unawareness decreased from 35.9% to 17.7% (P<0.001). The decrease in hypertension unawareness was not paralleled by a concomitant absolute increase in hypertension treatment, which remained low (38.2%). A larger proportion of all hypertensive participants were aware but not treated in 2004–2009 (43.7%) compared to 1999–2003 (33.1%). Uncontrolled hypertension improved from 62.2% to 40.6% between 1999 and 2009 (P = 0.02). In 1999–2003 period, factors associated with hypertension unawareness were current smoking (OR = 1.27, 95%CI, 1.02–1.59), male gender (OR = 1.56, 1.27–1.92), hypercholesterolemia (OR = 1.31, 1.20–1.44), and older age (OR 65–74yrs vs 35–49yrs  = 1.56, 1.21–2.02). In 1999–2003 and 2004–2009, obesity and diabetes were negatively associated with hypertension unawareness, high education was associated with untreated hypertension (OR = 1.45, 1.12–1.88 and 1.42, 1.02–1.99, respectively), and male gender with uncontrolled hypertension (OR = 1.49, 1.03–2.17 and 1.65, 1.08–2.50, respectively). Sedentarity was associated with higher risk of hypertension and uncontrolled hypertension in 1999–2003.
Conclusions
Hypertension prevalence remained stable since 1999 in the canton of Geneva. Although hypertension unawareness substantially decreased, more than half of hypertensive subjects still remained untreated or uncontrolled in 2004–2009. This study identified determinants that should guide interventions aimed at improving hypertension treatment and control.
doi:10.1371/journal.pone.0039877
PMCID: PMC3384604  PMID: 22761919
2.  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
3.  Trends in prevalence, awareness, treatment, and control of hypertension, and the risk of mortality among middle-aged Lithuanian urban population in 1983–2009 
Background
Arterial hypertension (AH) is a main risk factor for the risk from cardiovascular (CVD) and stroke mortality. Only few data was published on prevalence, awareness and management of AH in Lithuania. Development of objective approaches to the treatment and control of AH reduces the risk of mortality. The aim of this study was to evaluate time trends, the prevalence, awareness, treatment and control of AH and risk of mortality among Lithuanian urban population aged 45–64 years during the period of 1983–2009.
Methods
Time trends of AH and risk of mortality were examined in three MONICA health surveys in 1983, 1986, 1992, and in one health survey according to MONICA protocol in 2002 included randomly recruited of 2,218 men and 2,491 women. AH was defined as systolic blood pressure (BP) ≥140 mmHg and/or diastolic BP of ≥90 mmHg or current use of antihypertensive medication. The main outcome measures were all-cause mortality, mortality from CVD, coronary heart disease (CHD) and stroke. The mean duration of follow-up was 11.8 ± 9.2 years. All survey periods were age standardized to the year 2006 of Kaunas population. The estimates of hazard ratio and 95% confidence interval were based on the multivariate Cox proportional hazards regression.
Results
In men during 1983–2002 period hypertension prevalence was 52.1–58.7% and did not significantly change whereas in women decreased from 61.0 to 51.0%. There was a significant increase in hypertension awareness among hypertensive men and women (45.0 to 64.4% and 47.7 to 72.3%, respectively) and in treated hypertensives (55.4 to 68.3% in men and 65.6 to 86.2% in women). Adjusted Cox proportional hazard regression analyses revealed a strong dose–response association between blood-pressure level and all-cause, CVD, CHD and stroke-mortality risk in both men and women groups.
Conclusion
In Lithuanian urban population the prevalence of hypertension remains high. Despite positive changes in hypertension awareness and treatment, hypertension control remains poor. A strong dose–response association between the level of BP and all-cause, CVD, CHD and stroke mortality risk was indicated.
doi:10.1186/1471-2261-12-68
PMCID: PMC3480954  PMID: 22937997
Hypertension; Awareness; Treatment; Control; Risk of mortality
4.  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
5.  Prevalence, Awareness, Treatment, and Control of Hypertension in United States Counties, 2001–2009 
PLoS ONE  2013;8(4):e60308.
Hypertension is an important and modifiable risk factor for cardiovascular disease and mortality. Over the last decade, national-levels of controlled hypertension have increased, but little information on hypertension prevalence and trends in hypertension treatment and control exists at the county-level. We estimate trends in prevalence, awareness, treatment, and control of hypertension in US counties using data from the National Health and Nutrition Examination Survey (NHANES) in five two-year waves from 1999–2008 including 26,349 adults aged 30 years and older and from the Behavioral Risk Factor Surveillance System (BRFSS) from 1997–2009 including 1,283,722 adults aged 30 years and older. Hypertension was defined as systolic blood pressure (BP) of at least 140 mm Hg, self-reported use of antihypertensive treatment, or both. Hypertension control was defined as systolic BP less than 140 mm Hg. The median prevalence of total hypertension in 2009 was estimated at 37.6% (range: 26.5 to 54.4%) in men and 40.1% (range: 28.5 to 57.9%) in women. Within-state differences in the county prevalence of uncontrolled hypertension were as high as 7.8 percentage points in 2009. Awareness, treatment, and control was highest in the southeastern US, and increased between 2001 and 2009 on average. The median county-level control in men was 57.7% (range: 43.4 to 65.9%) and in women was 57.1% (range: 43.0 to 65.46%) in 2009, with highest rates in white men and black women. While control of hypertension is on the rise, prevalence of total hypertension continues to increase in the US. Concurrent increases in treatment and control of hypertension are promising, but efforts to decrease the prevalence of hypertension are needed.
doi:10.1371/journal.pone.0060308
PMCID: PMC3618269  PMID: 23577099
6.  Alcohol Intake and Blood Pressure: A Systematic Review Implementing a Mendelian Randomization Approach 
PLoS Medicine  2008;5(3):e52.
Background
Alcohol has been reported to be a common and modifiable risk factor for hypertension. However, observational studies are subject to confounding by other behavioural and sociodemographic factors, while clinical trials are difficult to implement and have limited follow-up time. Mendelian randomization can provide robust evidence on the nature of this association by use of a common polymorphism in aldehyde dehydrogenase 2 (ALDH2) as a surrogate for measuring alcohol consumption. ALDH2 encodes a major enzyme involved in alcohol metabolism. Individuals homozygous for the null variant (*2*2) experience adverse symptoms when drinking alcohol and consequently drink considerably less alcohol than wild-type homozygotes (*1*1) or heterozygotes. We hypothesise that this polymorphism may influence the risk of hypertension by affecting alcohol drinking behaviour.
Methods and Findings
We carried out fixed effect meta-analyses of the ALDH2 genotype with blood pressure (five studies, n = 7,658) and hypertension (three studies, n = 4,219) using studies identified via systematic review. In males, we obtained an overall odds ratio of 2.42 (95% confidence interval [CI] 1.66–3.55, p = 4.8 × 10−6) for hypertension comparing *1*1 with *2*2 homozygotes and an odds ratio of 1.72 (95% CI 1.17–2.52, p = 0.006) comparing heterozygotes (surrogate for moderate drinkers) with *2*2 homozygotes. Systolic blood pressure was 7.44 mmHg (95% CI 5.39–9.49, p = 1.1 × 10−12) greater among *1*1 than among *2*2 homozygotes, and 4.24 mmHg (95% CI 2.18–6.31, p = 0.00005) greater among heterozygotes than among *2*2 homozygotes.
Conclusions
These findings support the hypothesis that alcohol intake has a marked effect on blood pressure and the risk of hypertension.
Using a mendelian randomization approach Sarah Lewis and colleagues find strong support for the hypothesis that alcohol intake has a marked effect on blood pressure and the risk of hypertension.
Editors' Summary
Background.
High blood pressure (hypertension) is a common medical condition that affects nearly a third of US and UK adults. Hypertension has no symptoms but can lead to heart attacks or strokes. It is diagnosed by measuring blood pressure—the force that blood moving around the body exerts on the inside of large blood vessels. Blood pressure is highest when the heart is pumping out blood (systolic pressure) and lowest when it is filling up with blood (diastolic pressure). Normal blood pressure is defined as a systolic pressure of less than 130 millimeters of mercury (mmHg) and a diastolic pressure of less than 85 mmHg (a blood pressure of 130/85). A reading of more than 140/90 indicates hypertension. Many factors affect blood pressure, but overweight people and individuals who eat too much salty or fatty foods are at high risk of developing hypertension. Mild hypertension can often be corrected by lifestyle changes, but many people also take antihypertensive drugs to reduce their blood pressure.
Why Was This Study Done?
Another modifiable lifestyle factor thought to affect blood pressure is alcohol intake. Observational studies that ask people about their drinking habits and measure their blood pressure suggest that alcohol intake correlates with blood pressure, but they cannot prove a causal link because of “confounding”—other risk factors associated with alcohol drinking, such as diet, might also affect the study participant's blood pressures. A trial that randomly assigns people to different alcohol intakes could provide this proof of causality, but such a trial is impractical. In this study, therefore, the researchers have used “Mendelian randomization” to investigate whether alcohol intake affects blood pressure. An inactive variant of aldehyde dehydrogenase 2 (ALDH2; the enzyme that removes alcohol from the body) has been identified. People who inherit the variant form of this gene from both parents have an ALDH2 *2*2 genotype (genetic makeup) and become flushed and nauseated after drinking. Consequently, they drink less than people with a *1*2 genotype and much less than those with a *1*1 genotype. Because inheritance of these genetic variants does not affect lifestyle factors other than alcohol intake, an association between ALDH2 genotypes and blood pressure would indicate that alcohol intake has an effect on blood pressure without any confounding.
What Did the Researchers Do and Find?
The researchers identified ten published studies (mainly done in Japan where the ALDH2 gene variant is common) on associations between ALDH2 genotype and blood pressure or hypertension using a detailed search protocol (a “systematic review”). A meta-analysis (a statistical method for combining the results of independent studies) of the studies that had investigated the association between ALDH2 genotype and hypertension showed that men with the *1*1 genotype (highest alcohol intake) and those with the *1*2 genotype (intermediate alcohol intake) were 2.42 and 1.72 times more likely, respectively, to have hypertension than those with the *2*2 genotype (lowest alcohol intake). There was no association between ALDH2 genotype and hypertension among the women in these studies because they drank very little. Systolic and diastolic blood pressures showed a similar relationship to ALDH2 genotype in a second meta-analysis of relevant studies. Finally, the researchers estimated that for men the lifetime effect of drinking 1 g of alcohol a day (one unit of alcohol contains 8 g of alcohol in the UK and 14 g in the US; recommended daily limits in these countries are 3–4 and 1–2 units, respectively) would be an increase in systolic blood pressure of 0.24 mmHg.
What Do These Findings Mean?
These findings support the suggestion that alcohol has a marked effect on blood pressure and hypertension. Consequently, some cases of hypertension could be prevented by encouraging people to reduce their daily alcohol intake. Although the Mendelian randomization approach avoids most of the confounding intrinsic to observational studies, it is possible that a gene near ALDH2 that has no effect on alcohol intake affects blood pressure, since genes are often inherited in blocks. Alternatively, ALDH2 could affect blood pressure independent of alcohol intake. The possibility that ALDH2 could effect blood pressure independently of alcohol is intake made unlikely by the fact that no effect of genotype on blood pressure is seen among women who drink very little. Additional large-scale studies are needed to address these possibilities, to confirm the current finding in more people, and to improve the estimates of the effect that alcohol intake has on blood pressure.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050052.
The MedlinePlus encyclopedia has a page on hypertension (in English and Spanish)
The American Heart Association provides information for patients and health professionals about hypertension
The UK Blood Pressure Association provides information for patients and health professionals on all aspects of hypertension, including information about alcohol affects blood pressure
The Explore@Bristol science center (a UK charity) provides an alcohol unit calculator and information on the effects of alcohol
The International Center for Alcohol Policies provides drinking guidelines for countries around the world
doi:10.1371/journal.pmed.0050052
PMCID: PMC2265305  PMID: 18318597
7.  The association between concurrent and remote blood pressure and disability in older adults 
Hypertension  2007;50(6):1026-1032.
The objective of this study was to investigate the association between blood pressure and disability in older adults. Stroke-free participants in the Charleston Heart Study (n=999, mean age= 68.5± standard error 0.2 years, 57% women, and 39% African Americans) were followed between 1960 and 1993. Functional measures including Nagi’s Congruency in Medical and Self Assessment of Disability scale, the Rosow-Breslaw scale and Katz’ Activities of Daily Living scale, in addition to systolic and diastolic blood pressures were collected in 1984–1985, 1987–1990, and 1990–1993. Additional systolic and diastolic blood pressures from 1960–63 were also available. We defined remote blood pressure change as the change from 1960 to 1984–85 and concurrent blood pressure change as the change from 1984–85 to the follow-up periods. Hypertension was defined as blood pressure ≥140/90 mm Hg or receiving antihypertensives, and it was considered uncontrolled if subjects were receiving antihypertensives and blood pressure ≥140/90 mm Hg. Greater remote and concurrent systolic blood pressure increases but not diastolic blood pressure were associated with greater declines in all three functional measures. Participants with hypertension were also at increased risk of developing new disability (hazard ratio= 1.28, 95% confidence interval (CI) (1.04–1.59) for Nagi scale, 1.28, 95%CI (1.02–1.59) for Rosow-Breslaw scale, and 1.3, 95%CI (1.01–1.69)) for Katz scale). Participants with uncontrolled hypertension were at greatest risk of disability compared to normotensives. In stroke-free older adults, remote and concurrent SBP increases are associated with greater functional decline. Older adults with uncontrolled hypertension are at a particularly increased risk for disability.
doi:10.1161/HYPERTENSIONAHA.107.097667
PMCID: PMC2424316  PMID: 18025294
Hypertension; disability; blood pressure; aged; southeast
8.  Long-term Follow-up of Blood Pressure in Family Members of Soldiers Killed During the War in Bosnia and Herzegovina 
Croatian medical journal  2006;47(3):416-423.
Aim
To asses prevalence of essential arterial hypertension in family members of soldiers killed in 1992-1995 war in Bosnia and Herzegovina.
Methods
The study enrolled 1144 subjects who lost a family member in the war and 582 of their close neighbors who experienced no such loss. Data on their medical history and habits were collected, and their blood pressure was recorded in 1996 and 2003. Arterial hypertension was defined as systolic blood pressure ≥140 mm Hg (≥130 mm Hg in patients with diabetes mellitus), or diastolic blood pressure ≥90 mm Hg (≥80 mm Hg in patients with diabetes mellitus), or taking antihypertensive therapy. Additional laboratory and clinical tests were performed in subjects with hypertension.
Results
The prevalence of hypertension at both time points was higher in the group with a killed family member than in the group without the loss (55.1% vs 42.1%, P<0.001 in 1996, and 50.7% vs 39.0%, P<0.001 in 2003, respectively). However, there was also a significant decrease in the prevalence of hypertension in the group with the loss in 2003 (P<0.001), but not in group without the loss. Posttraumatic stress disorder (PTSD), smoking, and alcohol consumption were more prevalent in the group with a killed family member, but not cholesterol and triglyceride blood concentrations. In both groups, hypertension was more prevalent in subjects with PTSD and smoking or drinking habit. Proportion of subjects with hypertension who smoked and used alcohol was similar in both groups. Proportion of subjects with hypertension who did not smoke or drink was higher in the group with the loss (51.1% vs 36.7%, P<0.001; 46.2% vs 35.0%, P = 0.006; respectively).
Conclusion
This study showed higher prevalence of hypertension in family members of killed soldiers, regardless of the presence of other cardiovascular risk factors. Only the stress of mourning was associated with higher prevalence of hypertension. Over time, proportion of hypertensive subjects with the loss decreased in the group with a killed family member, further suggesting that at least a part of their hypertension might have been of psychological origin.
PMCID: PMC2080420  PMID: 16758520
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.  Prevalence, awareness and risk factors of hypertension in a large cohort of Iranian adult population 
Journal of hypertension  2013;31(7):1364-1371.
Background
There is considerable variation in hypertension prevalence and awareness, and their correlates, across different geographic locations and ethnic groups. We performed this cross-sectional analysis on data from the Golestan Cohort Study (GCS).
Methods
Enrollment in this study occurred in 2004–2008, and included 50,045 healthy subjects from Golestan Province in northeastern Iran. Hypertension was defined as a systolic blood pressure (SBP) ≥140, a diastolic blood pressure (DBP) ≥90, a prior diagnosis of hypertension, or the use of antihypertensive drugs. Potential correlates of hypertension and its awareness were analyzed by logistic regression adjusted for sex, age, BMI, place of residence, literacy, ethnicity, physical activity, smoking, black and green tea consumption and wealth score.
Results
Of the total cohort participants, 21,350 (42.7%) were hypertensive. Age-standardized prevalence of hypertension, using the 2001 WHO standard world population, was 41.8% (95%CI: 38.3%–45.2%). Hypertension was directly associated with female sex, increased BMI, Turkmen ethnicity, and lack of physical activity, and inversely associated with drinking black tea and wealth score. Among hypertensive subjects, 46.2% were aware of their disease, 17.6% were receiving antihypertensive medication, and 32.1% of the treated subjects had controlled hypertension. Hypertension awareness was greater among women, the elderly, overweight and obese subjects, and those with a higher wealth score.
Conclusions
Hypertension is highly prevalent in rural Iran, many of the affected individuals are unaware of their disease, and the rate of control by antihypertensive medications is low. Increasing hypertension awareness and access to health services, especially among less privileged residents are recommended.
doi:10.1097/HJH.0b013e3283613053
PMCID: PMC3766446  PMID: 23673348
hypertension; awareness; obesity; smoking; socioeconomic status
11.  Results of the Ontario Survey on the Prevalence and Control of Hypertension 
Background
Available information on the prevalence and management of hypertension in the Canadian population dates back to 1986–1992 and probably does not reflect the current status of this major risk factor for cardiovascular disease. We sought to evaluate the current prevalence and management of hypertension among adults in the province of Ontario.
Methods
Potential respondents from randomly selected dwellings within target neighbourhoods in 16 municipalities were contacted at their homes to request participation in the study. For potential respondents who agreed to participate, blood pressure was measured with an automated device. Estimation weights were used to obtain representative estimates of population parameters. Responses were weighted to the total adult population in Ontario of 7 996 653.
Results
From 6436 eligible dwellings, contact was made with 4559 potential participants, of whom 2992 agreed to participate. Blood pressure measurements were obtained for 2551 of these respondents (age 20–79 years). Hypertension, defined as systolic blood pressure of 140 mm Hg or more, diastolic blood pressure of 90 mm Hg or more, or treatment with an antihypertensive medication, was identified in 21.3% of the population overall (23.8% of men and 19.0% of women). Prevalence increased with age, from 3.4% among participants 20–39 years of age to 51.6% among those 60–79 years of age. Hypertension was more common among black people and people of South Asian background than among white people; hypertension was also associated with higher body mass index. Among participants with hypertension, 65.7% were undergoing treatment with control of hypertension, 14.7% were undergoing treatment but the hypertension was not controlled, and 19.5% were not receiving any treatment (including 13.7% who were unaware of their hypertension). The extent of control of hypertension did not differ significantly by age, sex, ethnic background or comorbidities.
Interpretation
In Ontario, the overall prevalence of hypertension is high in the older population but appears not to have increased in recent decades. Hypertension management has improved markedly among all age groups and for both sexes.
doi:10.1503/cmaj.071340
PMCID: PMC2374854  PMID: 18490640
12.  The Effects of Mandatory Prescribing of Thiazides for Newly Treated, Uncomplicated Hypertension: Interrupted Time-Series Analysis 
PLoS Medicine  2007;4(7):e232.
Background
The purpose of our study was to evaluate the effects of a new reimbursement rule for antihypertensive medication that made thiazides mandatory first-line drugs for newly treated, uncomplicated hypertension. The objective of the new regulation was to reduce drug expenditures.
Methods and Findings
We conducted an interrupted time-series analysis on prescribing data before and after the new reimbursement rule for antihypertensive medication was put into effect. All patients started on antihypertensive medication in 61 general practices in Norway were included in the analysis. The new rule was put forward by the Ministry of Health and was approved by parliament. Adherence to the rule was monitored only minimally, and there were no penalties for non-adherence. Our primary outcome was the proportion of thiazide prescriptions among all prescriptions made for persons started on antihypertensive medication. Secondary outcomes included the proportion of patients who, within 4 mo, reached recommended blood-pressure goals and the proportion of patients who, within 4 mo, were not started on a second antihypertensive drug. We also compared drug costs before and after the intervention. During the baseline period, 10% of patients started on antihypertensive medication were given a thiazide prescription. This proportion rose steadily during the transition period, after which it remained stable at 25%. For other outcomes, no statistically significant differences were demonstrated. Achievement of treatment goals was slightly higher (56.6% versus 58.4%) after the new rule was introduced, and the prescribing of a second drug was slightly lower (24.0% versus 21.8%). Drug costs were reduced by an estimated Norwegian kroner 4.8 million (€0.58 million, US$0.72 million) in the first year, which is equivalent to Norwegian kroner 1.06 per inhabitant (€0.13, US$0.16).
Conclusions
Prescribing of thiazides in Norway for uncomplicated hypertension more than doubled after a reimbursement rule requiring the use of thiazides as the first-choice therapy was put into effect. However, the resulting savings on drug expenditures were modest. There were no significant changes in the achievement of treatment goals or in the prescribing of a second antihypertensive drug.
Atle Fretheim and colleagues found that the prescribing of thiazides in Norway for uncomplicated hypertension more than doubled after a rule requiring their use as first-choice therapy was put into effect.
Editors' Summary
Background.
High blood pressure (hypertension) is a common medical condition, especially among elderly people. It has no obvious symptoms but can lead to heart attacks, heart failure, strokes, or kidney failure. It is diagnosed by measuring blood pressure—the force that blood moving around the body exerts on the inside of arteries (large blood vessels). Many factors affect blood pressure (which depends on the amount of blood being pumped round the body and on the size and condition of the arteries), but overweight people and individuals who eat fatty or salty food are at high risk of developing hypertension. Mild hypertension can often be corrected by making lifestyle changes, but many patients also take one or more antihypertensive agents. These include thiazide diuretics and several types of non-thiazide drugs, many of which reduce heart rate or contractility and/or dilate blood vessels.
Why Was This Study Done?
Antihypertensive agents are a major part of national drug expenditure in developed countries, where as many as one person in ten is treated for hypertension. The different classes of drugs are all effective, but their cost varies widely. Thiazides, for example, are a tenth of the price of many non-thiazide drugs. In Norway, the low use of thiazides recently led the government to impose a new reimbursement rule aimed at reducing public expenditure on antihypertensive drugs. Since March 2004, family doctors have been reimbursed for drug costs only if they prescribe thiazides as first-line therapy for uncomplicated hypertension, unless there are medical reasons for selecting other drugs. Adherence to the rule has not been monitored, and there is no penalty for non-adherence, so has this intervention changed prescribing practices? To find out, the researchers in this study analyzed Norwegian prescribing data before and after the new rule came into effect.
What Did the Researchers Do and Find?
The researchers analyzed the monthly antihypertensive drug–prescribing records of 61 practices around Oslo, Norway, between January 2003 and November 2003 (pre-intervention period), between December 2003 and February 2004 (transition period), and between March 2004 and January 2005 (post-intervention period). This type of study is called an “interrupted time series”. During the pre-intervention period, one in ten patients starting antihypertensive medication was prescribed a thiazide drug. This proportion gradually increased during the transition period before stabilizing at one in four patients throughout the post-intervention period. A slightly higher proportion of patients reached their recommended blood-pressure goal after the rule was introduced than before, and a slightly lower proportion needed to switch to a second drug class, but both these small differences may have been due to chance. Finally, the researchers estimated that the observed change in prescribing practices reduced drug costs per Norwegian by US$0.16 (€0.13) in the first year.
What Do These Findings Mean?
Past attempts to change antihypertensive-prescribing practices by trying to influence family doctors (for example, through education) have largely failed. By contrast, these findings suggest that imposing a change on them (in this case, by introducing a new reimbursement rule) can be effective (at least over the short term and in the practices included in the study), even when compliance with the change is not monitored nor noncompliance penalized. However, despite a large shift towards prescribing thiazides, three-quarters of patients were still prescribed non-thiazide drugs (possibly because of doubts about the efficacy of thiazides as first-line drugs), which emphasizes how hard it is to change doctors' prescribing habits. Further studies are needed to investigate whether the approach examined in this study can effectively contain the costs of antihypertensive drugs (and of drugs used for other common medical conditions) in the long term and in other settings. Also, because the estimated reduction in drug costs produced by the intervention was relatively modest (although likely to increase over time as more patients start on thiazides), other ways to change prescribing practices and produce savings in national drug expenditures should be investigated.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040232.
MedlinePlus encyclopedia page on hypertension (in English and Spanish)
UK National Institute for Health and Clinical Excellence information on hypertension for patients, carers, and professionals
American Heart Association information for patients on high blood pressure
An open-access research article describing the potential savings of using thiazides as the first-choice antihypertensive drug
A previous study in Norway, published in PLoS Medicine, examined what happened when doctors were actively encouraged to make more use of thiazides. There was also an economic evaluation of what this achieved
doi:10.1371/journal.pmed.0040232
PMCID: PMC1904466  PMID: 17622192
13.  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
14.  Awareness, Treatment, and control of Hypertension among Adult Population in the Federation of Bosnia and Herzegovina over the Past Decade 
Background
Many studies throughout the world show that hypertension is not effectively treated and controlled, which continued to pose an important challenge in health systems in the world.
Design and methods
Population surveys were carried out in 2002 and 2012 in the Federation of Bosnia and Herzegovina (FBIH) on representative sample at the age of 25-64. The surveys used systematic stratified sample. Questionnaires and anthropometric measure protocols were adapted from internationally recommended surveys.
Results
In the past ten years there has been a slight increase in hypertension prevalence in researched population (41% vs. 42%). Percentage of hypertensive male and female respondents who are not aware of their hypertension actually dropped in the past decade from 54.3% to 51.4%. In 2002 total number of hypertensive respondents aware of their hypertension included 8.1% of male respondents and 10.3% female respondents whose condition was not treated and this rate effectively dropped during the 10-year period. Number of hypertensive, treated, and uncontrolled respondents dropped as reported in the 2012 survey; consequently percentage of hypertensive, treated, and controlled respondents in the 2012 survey increased, in particular in female population.
Conclusions
Investments in primary health care, improved availability, and improved quality of health care in the FBIH in the past 10 years can explain increased rate of hypertension detection and treatment; however, efforts should be continued to introduce hypertension screening programs and hypertension control programs.
Significance for public healthIn spite of wide knowledge of pathophysiology and epidemiology in development of hypertension, ability to easily diagnose it, availability of efficient medications, hypertension continues to have high prevalence and setting up hypertension controls poses significant public health challenge. Recently conducted cross-sectional population surveys in the Federation of Bosnia and Herzegovina give us opportunity to follow the trend for hypertension and implement public health measures to reduce or eliminate causes of high blood pressure in population and at the same time with implementation of medical treatment.
doi:10.4081/jphr.2014.323
PMCID: PMC4274498  PMID: 25553314
blood pressure; hypertension awareness; hypertension control; Bosnia and Herzegovina
15.  Changes in left ventricular structure and function in patients with white coat hypertension: cross sectional survey 
BMJ : British Medical Journal  1998;317(7158):565-570.
Objectives: To assess the relation between white coat hypertension and alterations of left ventricular structure and function.
Design: Cross sectional survey.
Setting: Augsburg, Germany.
Subjects: 1677 subjects, aged 25 to 74 years, who participated in an echocardiographic substudy of the monitoring of trends and determinants in cardiovascular disease Augsburg study during 1994-5.
Outcome measures: Blood pressure measurements and M mode, two dimensional, and Doppler echocardiography. After at least 30 minutes’ rest blood pressure was measured three times by a technician, and once by a physician after echocardiography. Subjects were classified as normotensive (technician <140/90 mm Hg, physician <160/95 mm Hg; n=849), white coat hypertensive (technician <140/90 mm Hg, physician ⩾160/95 mm Hg; n=160), mildly hypertensive (technician ⩾140/90 mm Hg, physician <160/95 mm Hg; n=129), and sustained hypertensive (taking antihypertensive drugs or blood pressure measured by a technican ⩾140/90 mm Hg, and physician ⩾160/95 mm Hg; n=538).
Results: White coat hypertension was more common in men than women (10.9% versus 8.2% respectively) and positively related to age and body mass index. After adjustment for these variables, white coat hypertension was associated with an increase in left ventricular mass and an increased prevalence of left ventricular hypertrophy (odds ratio 1.9, 95% confidence interval 1.2 to 3.2; P=0.009) compared with normotensive patients. The increase in left ventricular mass was secondary to significantly increased septal and posterior wall thicknesses whereas end diastolic diameters were similar in both groups with white coat hypertension or normotension. Additionally, the systolic white coat effect (difference between blood pressures recorded by a technician and physician) was associated with increased left ventricular mass and increased prevalence of left ventricular hypertrophy (P<0.05 each). Values for systolic left ventricular function (M mode fractional shortening) were above normal in subjects with white coat hypertension whereas diastolic filling and left atrial size were similar to those in normotension.
Conclusion: About 10% of the general population show exaggerated inotropic and blood pressure responses when mildly stressed. This is associated with an increased risk of left ventricular hypertrophy.
Key messages About 10% of the general population display white coat hypertension After adjustment for age, body mass index, and baseline blood pressure, white coat hypertension is associated with increased left ventricular mass and increased risk of left ventricular hypertrophy In white coat hypertension, after adjustment for covariates, systolic function has values above normal whereas diastolic filling is unchanged White coat hypertension cannot be dismissed as a benign condition
PMCID: PMC28649  PMID: 9721112
16.  The epidemiology and management of severe hypertension 
Journal of Human Hypertension  2009;24(1):9-18.
Hypertension guidelines stress that patients with severe hypertension (systolic blood pressure (BP)⩾180 or diastolic BP⩾110 mm Hg) require multiple drugs to achieve control and should have close follow-up to prevent adverse outcomes. However, little is known about the epidemiology or actual management of these patients. We retrospectively studied 59 207 veterans with hypertension. Patients were categorized based on their highest average BP over an 18-month period (1 July 1999 to 31 December 2000) as controlled (<140/90 mm Hg), mild (140–159/90–99 mm Hg), moderate (160–179/100–109 mm Hg) and severe hypertension. We examined severe hypertension prevalence, pattern, duration, associated patient characteristics, time to subsequent visit, percentage of visits with a medication increase, and final BP control and antihypertensive medication adequacy. Twenty-three per cent had ⩾1 visit with severe hypertension, 42% of whom had at least two such visits; median day with severe hypertension was 80 (range 1–548). These subjects were significantly older, more likely black, and with more comorbidities than other hypertension subjects. Medication increases occurred at 20% of visits with mild hypertension compared to 40% with severe hypertension; P<0.05). At study end, 76% of patients with severe hypertension remained uncontrolled; severe hypertension subjects with uncontrolled BP were less likely to be on adequate therapy than those with controlled BP (43.7 vs 45.4%). Among hypertensive veterans, severe hypertension episodes are common. Many subjects had relatively prolonged elevations, with older, sicker subjects at highest risk. Although, follow-up times are shorter and antihypertensive medication use greater in severe hypertension subjects, they are still not being managed aggressively enough. Interventions to improve providers' management of these high-risk patients are needed.
doi:10.1038/jhh.2009.37
PMCID: PMC3011090  PMID: 19440209
epidemiology; chronic hypertension; therapy
17.  Hypertension knowledge, attitudes, and behavior: 1985 NHIS findings. 
Public Health Reports  1986;101(6):599-606.
Data from the Health Promotion/Disease Prevention Supplement to the 1985 National Health Interview Survey provide an indication of progress made toward achieving the 1990 objectives for the nation. Survey results showed remarkably high levels of knowledge concerning the increased risks associated with uncontrolled high blood pressure. Nine of 10 adults in the United States knew that high blood pressure increases the risk of heart disease, and 3 of 4 knew that high blood pressure is the most significant risk factor for stroke. The majority of both the general public and the subgroup of the population identified as hypertensives reported knowing the results of their last blood pressure measurement; and, most importantly, almost two-thirds of the identified hypertensives reported that their pressures were under control at last measurement. Data examining professional advice, given and acted upon to achieve blood pressure goals, show that almost two-thirds of the hypertensives currently report taking antihypertensive medication. Results also suggest a degree of willingness by both professionals and hypertensives to attempt nondrug approaches to controlling pressures. The large majority of hypertensives who were advised by a health professional to cut down on sodium, lose weight, and exercise reported they were following this advice. These findings will be used to further refine high blood pressure education strategies and advance the progress toward meeting the 1990 hypertension objectives.
PMCID: PMC1477684  PMID: 3097740
18.  Pattern of declining blood pressure across replicate population surveys of the WHO MONICA project, mid-1980s to mid-1990s, and the role of medication 
BMJ : British Medical Journal  2006;332(7542):629-635.
Objective Declining mean systolic and diastolic blood pressures were observed in most populations of the World Health Organization MONICA (monitoring trends and determinants in cardiovascular disease) project from the mid-1980s to mid-1990s. We tested whether pooled results would show mean change associated with decline in high readings only, resulting from better antihypertensive medication, or with similar falls in low, middle, and high readings, implying other causes.
Design Independent, random sample, cross sectional population surveys, each end of the MONICA decade.
Setting 38 populations in 21 countries across four continents.
Participants Design target in each survey of 200 participants in each 10 year age and sex group from age 35 to 64
Main outcome measures Changes in the population in mean systolic and diastolic blood pressure, and in low, middle, and high readings—the 20th, 50th, and 80th centiles—and the differences between these changes.
Results Individual populations differed considerably, but pooling the 38 population results gave mean changes in systolic blood pressure of -2.2 mm Hg in men, -3.3 mm Hg in women, and in diastolic blood pressure of -1.4 mm Hg in men and -2.2 mm Hg in women (overall average -2.26 mm Hg, population median -1.55 mm Hg). Antihypertensive medication, associated with high readings, rose by 0.5% to 11.4%. However, average falls in low and middle blood pressure readings were so similar to those in high readings and in the mean that no effect from improving treatment of hypertension was detected. Results in contrasted subgroups were consistent.
Conclusions Blood pressure fell across 38 MONICA populations at all levels of readings, with no differential fall in high readings attributable to better control of hypertension. Despite the importance of medication to individuals, in that decade other determinants of blood pressure lowering must have been more pervasive and powerful in whole populations.
doi:10.1136/bmj.38753.779005.BE
PMCID: PMC1403225  PMID: 16531419
19.  Study of urban community survey in India: growing trend of high prevalence of hypertension in a developing country 
The prevalence pattern of hypertension in developing countries is different from that in the developed countries. In India, a very large, populous and typical developing country, community surveys have documented that between three and six decades, prevalence of hypertension has increased by about 30 times among urban dwellers and by about 10 times among the rural inhabitants. Various factors might have contributed to this rising trend and among others, consequences of urbanization such as change in life style pattern, diet and stress, increased population and shrinking employment have been implicated. In this paper, we study the prevalence of hypertension in an urban community of India using the JNC VII criteria, with the aim of identifying the risk factors and suggesting intervention strategies. A total of 1609 respondents out of 1662 individuals participated in our cross-sectional survey of validated and structured questionnaire followed by blood pressure measurement. Results showed pre-hypertensive levels of blood pressures among 35.8% of the participants in systolic group (120-139mm of Hg) and 47.7% in diastolic group (80-89 mm of Hg). Systolic hypertension (140 mm of Hg) was present in 40.9% and diastolic hypertension (90 mm of Hg) in 29.3% of the participants. Age and sex-specific prevalence of hypertension showed progressive rise of systolic and diastolic hypertension in women when compared to men. Men showed progressive rise in systolic hypertension beyond fifth decade of life. Bivariate analysis showed significant relationship of hypertension with age, sedentary occupation, body mass index (BMI), diet, ischemic heart disease, and smoking. Multivariate analysis revealed age and BMI as risk factors, and non-vegetarian diet as protective factor with respect to hypertension. Prevalence of prehypertensives was high among younger subjects - particularly students and laborers who need special attention. Role of non-vegetarian diet as a protective factor might have been related to fish-eating behavior of the sample population, who also use mustard oil as cooking medium - both of which have significant level of essential polyunsaturated fatty acids. The observed prevalence of hypertension in this study and other studies suggest the need for a comprehensive national policy to control hypertension in India, and, in other similar developing countries.
PMCID: PMC1145137  PMID: 15968343
Hypertension; eastern India; urban study; JNC-VII criteria; prehypertensives; non-vegetarian diet; developing countries
20.  Hypertension among Mexican Americans in Starr County, Texas. 
Public Health Reports  1996;111(Suppl 2):15-17.
THE MEXICAN-AMERICAN POPULATION in the United States has generally elevated frequencies of several chronic conditions, including non-insulin-dependent diabetes mellitus (NIDDM), gallbladder disease, and obesity. Prevalence of cardiovascular disease and hypertension is less clear. To document prevalence and risk factors of hypertension in this population, we measured blood pressure in 1004 randomly selected Mexican Americans in Starr County, Texas, ages 15 to 74. We defined hypertension as systolic blood pressure greater than or equal to 140 mmHg or diastolic pressure greater than or equal to 90 mmHg or current (within the last 48 hours) use of antihypertensive medications. Prevalences by age and gender are elevated in this population group compared with those in the general population. In addition to age and gender, body mass and diabetes status were also predictors of hypertension. Comparison of the Starr County results with those reported from the Third National Health and Nutrition Examination Survey (NHANES III) sampling of Mexican Americans indicates a slight increase in frequency of hypertension in Starr County, while comparison with results from San Antonio Mexican Americans indicates a marked increase in frequency in Starr County. These differences are not simple functions of measurement protocols, but are likely to be caused by differences in population structure, employment and socioeconomic status, education, and other such factors.
PMCID: PMC1381654  PMID: 8898763
21.  Evaluation of Patients Cooperation in Hypertension Control 
Materia Socio-Medica  2014;26(2):109-111.
Introduction:
Hypertension (high blood pressure) is one of the most widely spread diseases of our time and one of the leading risk factors for heart and vascular diseases, particularly stroke and coronary heart disease. According to the World Health Organization (WHO) cardiovascular diseases are the leading cause of death in the world of who dies each year about 17 million persons, of which 5 million in Europe. The World Health Organization estimates based on monitoring of demographic trends, trends in mortality and morbidity as economic models, further growth of cardiovascular diseases, especially in developing countries.
Goal:
Correlate the success of antihypertensive therapy and provoking factors, and to determine the degree of satisfaction with the effect of antihypertensive therapy of the patient.
Material and methods:
The study was conducted at the Primary Health Care Center Stari Grad - Sarajevo. Conducted is study that included 80 patients. Data for this study were collected by a questionnaire. The questionnaire was completed by the examiner using interviews with patients and their relatives (parents, guardians).After sorting, control and grouping the data were imported into the statistical software package SPSS 20.0, where after defining variables was performed statistical analysis.
Results:
The average age of male respondents was 60.80±13.03 and 63.50 ± 7.48 years of female respondents. The average value of systolic blood pressure amounted to 148mmHg (130-180), while the average value of diastolic blood pressure was 88.75mmHg (70-120). Student's t test showed that the average value of systolic pressure was statistically significantly different from the reference value (t=2.387, DF=19, p=0.028), and also the average values of diastolic blood pressure were statistically significantly different compared to baseline (p=3.561, DF=19, p=0.002). Of the total number of subjects included in this study good blood pressure control had 58 participants, and the average value of systolic blood pressure was 122mmHg and diastolic 74mmHg. With poor regulation of blood pressure were 22 patients, with average values of systolic pressure of 155.5mmHg and diastolic 92 mmHg. The most common additional factor influencing the increase in blood pressure of patients surveyed was stress is 65 % (n=52), followed by heat 20% (n=16), and salty foods was a provoking factor in 15% (n=12) subjects. By analyzing the frequency of controlling blood pressure has been determined that respondents on average control blood pressure once a week, and control frequency is in range from daily to monthly. The average value of the blood pressure of subjects who regularly used antihypertensive therapy amounted to 125/69 mmHg, while the respondents who did not regularly use the antihypertensive therapy that value was 157/96 mmHg.
doi:10.5455/msm.2014.26.109-111
PMCID: PMC4035142  PMID: 24944534
patient; hypertension; therapy
22.  Blood Pressure in Children with Chronic Kidney Disease: A Report from the Chronic Kidney Disease in Children Study 
Hypertension  2008;52(4):631-637.
To characterize the distribution of blood pressure (BP), prevalence and risk factors for hypertension in pediatric chronic kidney disease (CKD), we conducted a cross-sectional analysis of baseline BP's in 432 children (mean age 11y; 60% male; mean glomerular filtration rate [GFR] 44 ml/min/1.73m2) enrolled in the Chronic Kidney Disease in Children cohort study. BP's were obtained using an aneroid sphygmomanometer. GFR was measured by iohexol disappearance. Elevated BP was defined as BP≥90th percentile for age, gender and height. Hypertension was defined as BP≥95th percentile or as self-reported hypertension plus current treatment with antihypertensive medications.
For systolic BP, 14% were hypertensive and 11% were pre-hypertensive (BP 90-95th percentile); 68% of subjects with elevated SBP were taking antihypertensive medications. For diastolic BP, 14% were hypertensive, and 9% were pre-hypertensive; 53% of subjects with elevated DBP were taking antihypertensive medications. 54% of subjects had either systolic or diastolic BP≥95th percentile or a history of hypertension plus current antihypertensive use.
Characteristics associated with elevated BP included black race, shorter duration of CKD, absence of antihypertensive medication use, and elevated serum potassium. Among subjects receiving antihypertensive treatment, uncontrolled BP was associated with male sex, shorter CKD duration and absence of ACE inhibitor or ARB use.
37% of children with CKD had either elevated systolic or diastolic BP, and 39% of these were not receiving antihypertensives, indicating that hypertension in pediatric CKD may be frequently under- or even un-treated. Treatment with ACE inhibitors or ARB's may improve BP control in these patients.
doi:10.1161/HYPERTENSIONAHA.108.110635
PMCID: PMC3136362  PMID: 18725579
kidney disease; children; adolescents; hypertension; blood pressure; ACE inhibitors
23.  Apparent and true resistant hypertension: definition, prevalence and outcomes 
Journal of human hypertension  2014;28(8):463-468.
Resistant hypertension, defined as blood pressure (BP) remaining above goal despite the use of ≥3 antihypertensive medications at maximally tolerated doses (one ideally being a diuretic) or BP that requires ≥4 agents to achieve control, has received more attention with increased efforts to improve BP control rates and the emergence of device-based therapies for hypertension. This classically defined resistant group consists of patients with true resistant hypertension, controlled resistant hypertension and pseudo-resistant hypertension. In studies where pseudo-resistant hypertension cannot be excluded (for example, 24-h ambulatory BP not obtained), the term apparent resistant hypertension has been used to identify ‘apparent’ lack of control on ≥3 medications. Large, well-designed studies have recently reported the prevalence of resistant hypertension. Pooling prevalence data from these studies and others within North America and Europe with a combined sample size of >600 000 hypertensive participants, the prevalence of resistant hypertension is 14.8% of treated hypertensive patients and 12.5% of all hypertensives. However, the prevalence of true resistant hypertension, defined as uncontrolled both by office and 24-h ambulatory BP monitoring with confirmed medication adherence, may be more meaningful in terms of identifying risk and estimating benefit from newer therapies like renal denervation. Rates of cardiovascular events and mortality follow mean 24-h ambulatory BPs in patients with resistant hypertension, and true resistant hypertension represents the highest risk. The prevalence of true resistant hypertension has not been directly measured in large trials; however, combined data from smaller studies suggest that true resistant hypertension is present in half of the patients with resistant hypertension who are uncontrolled in the office. Our pooled analysis shows prevalence rates of 10.1% and 7.9% for uncontrolled resistant hypertension among individuals treated for hypertension and all hypertensive individuals, respectively.
doi:10.1038/jhh.2013.140
PMCID: PMC4090282  PMID: 24430707
resistant; hypertension; epidemiology; blood pressure; control; prevalence
24.  Changes in the rates of awareness, treatment and control of hypertension in Canada over the past two decades 
Background
Analyses of medication databases indicate marked increases in prescribing of antihypertensive drugs in Canada over the past decade. This study was done to examine the trends in the prevalence of hypertension and in control rates in Canada between 1992 and 2009.
Methods
Three population-based surveys, the 1986–1992 Canadian Heart Health Surveys, the 2006 Ontario Survey on the Prevalence and Control of Hypertension and the 2007–2009 Canadian Health Measures Survey, collected self-reported health information from, and measured blood pressure among, community-dwelling adults.
Results
The population prevalence of hypertension was stable between 1992 and 2009 at 19.7%–21.6%. Hypertension control improved from 13.2% (95% confidence interval [CI] 10.7%–15.7%) in 1992 to 64.6% (95% CI 60.0%–69.2%) in 2009, reflecting improvements in awareness (from 56.9% [95% CI 53.1%–60.5%] in 1992 to 82.5% [95% CI 78.5%–86.0%] in 2009) and treatment (from 34.6% [95% CI 29.2%–40.0%] in 1992 to 79.0% [95% CI 71.3%–86.7%] in 2009) among people with hypertension. The size of improvements in awareness, treatment and control were similar among people who had or did not have cardiovascular comorbidities Although systolic blood pressures among patients with untreated hypertension were similar between 1992 and 2009 (ranging from 146 [95% CI 145–147] mm Hg to 148 [95% CI 144–151] mm Hg), people who did not have hypertension and patients with hypertension that was being treated showed substantially lower systolic pressures in 2009 than in 1992 (113 [95% CI 112–114] v. 117 [95% CI 117–117] mm Hg and 128 [95% CI 126–130] v. 145 [95% CI 143–147] mm Hg).
Interpretation
The prevalence of hypertension has remained stable among community-dwelling adults in Canada over the past two decades, but the rates for treatment and control of hypertension have improved markedly during this time.
doi:10.1503/cmaj.101767
PMCID: PMC3114892  PMID: 21576297
25.  Incidence of extra-articular rheumatoid arthritis in Olmsted County, Minnesota in 1995–2007 vs 1985–1994: a population-based study 
The Journal of rheumatology  2011;38(6):983-989.
Objective
To assess incidence and mortality impact of extra-articular rheumatoid arthritis (ExRA) in patients with incident rheumatoid arthritis (RA) in 1995–2007 vs 1985–1994.
Methods
Data on incident ExRA were abstracted from medical records of RA patients, Olmsted County, Minnesota residents who first met the 1987 ACR criteria for RA between 1/1/1995 and 12/31/2007. Patients were followed until death, migration from Olmsted County, or 12/31/2008. ExRA were classified using the predefined criteria and compared to the corresponding 1985–1994 inception RA cohort (n=147).
Results
The 1995–2007 cohort included 463 RA patients followed for a mean of 6.3 years. Mean age was 55.6 years (69% female; 67% rheumatoid factor [RF] positive). The 10-year cumulative incidence of any ExRA (50.1%) and severe ExRA (6.7%) in 1995–2007 cohort was similar to the 1985–1994 cohort (46.2% and 9.7%, respectively). The 10-year cumulative incidence of vasculitis, but not other ExRA, was significantly lower in 1995–2007 cohort (0.6%) compared to the 1985–1994 cohort (3.6%). RF positivity, erosions/destructive changes, use of methotrexate, other disease-modifying antirheumatic drugs and systemic corticosteroids were significantly associated with ExRA in the 1995–2007 cohort. ExRA were associated with mortality risk (HR 2.1, 95%CI 1.2, 3.7) in the 1995–2007 cohort. The decrease in mortality following ExRA in the 1995–2007 cohort vs 1985–1994 cohort did not reach statistical significance (HR 0.6, 95%CI 0.3, 1.2, p=0.16).
Conclusions
ExRA remain a common complication associated with increased mortality in RA. The occurrence of vasculitis appears to be decreasing in the recent years.
doi:10.3899/jrheum.101133
PMCID: PMC3193155  PMID: 21459933
rheumatoid arthritis; extra-articular manifestations; incidence; mortality; risk factors

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