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1.  The Cost-Effectiveness of Low-Cost Essential Antihypertensive Medicines for Hypertension Control in China: A Modelling Study 
PLoS Medicine  2015;12(8):e1001860.
Background
Hypertension is China’s leading cardiovascular disease risk factor. Improved hypertension control in China would result in result in enormous health gains in the world’s largest population. A computer simulation model projected the cost-effectiveness of hypertension treatment in Chinese adults, assuming a range of essential medicines list drug costs.
Methods and Findings
The Cardiovascular Disease Policy Model-China, a Markov-style computer simulation model, simulated hypertension screening, essential medicines program implementation, hypertension control program administration, drug treatment and monitoring costs, disease-related costs, and quality-adjusted life years (QALYs) gained by preventing cardiovascular disease or lost because of drug side effects in untreated hypertensive adults aged 35–84 y over 2015–2025. Cost-effectiveness was assessed in cardiovascular disease patients (secondary prevention) and for two blood pressure ranges in primary prevention (stage one, 140–159/90–99 mm Hg; stage two, ≥160/≥100 mm Hg). Treatment of isolated systolic hypertension and combined systolic and diastolic hypertension were modeled as a reduction in systolic blood pressure; treatment of isolated diastolic hypertension was modeled as a reduction in diastolic blood pressure. One-way and probabilistic sensitivity analyses explored ranges of antihypertensive drug effectiveness and costs, monitoring frequency, medication adherence, side effect severity, background hypertension prevalence, antihypertensive medication treatment, case fatality, incidence and prevalence, and cardiovascular disease treatment costs. Median antihypertensive costs from Shanghai and Yunnan province were entered into the model in order to estimate the effects of very low and high drug prices. Incremental cost-effectiveness ratios less than the per capita gross domestic product of China (11,900 international dollars [Int$] in 2015) were considered cost-effective. Treating hypertensive adults with prior cardiovascular disease for secondary prevention was projected to be cost saving in the main simulation and 100% of probabilistic simulation results. Treating all hypertension for primary and secondary prevention would prevent about 800,000 cardiovascular disease events annually (95% uncertainty interval, 0.6 to 1.0 million) and was borderline cost-effective incremental to treating only cardiovascular disease and stage two patients (2015 Int$13,000 per QALY gained [95% uncertainty interval, Int$10,000 to Int$18,000]). Of all one-way sensitivity analyses, assuming adherence to taking medications as low as 25%, high Shanghai drug costs, or low medication efficacy led to the most unfavorable results (treating all hypertension, about Int$47,000, Int$37,000, and Int$27,000 per QALY were gained, respectively). The strengths of this study were the use of a recent Chinese national health survey, vital statistics, health care costs, and cohort study outcomes data as model inputs and reliance on clinical-trial-based estimates of coronary heart disease and stroke risk reduction due to antihypertensive medication treatment. The limitations of the study were the use of several sources of data, limited clinical trial evidence for medication effectiveness and harms in the youngest and oldest age groups, lack of information about geographic and ethnic subgroups, lack of specific information about indirect costs borne by patients, and uncertainty about the future epidemiology of cardiovascular diseases in China.
Conclusions
Expanded hypertension treatment has the potential to prevent about 800,000 cardiovascular disease events annually and be borderline cost-effective in China, provided low-cost essential antihypertensive medicines programs can be implemented.
In a Markov-style simulation model, Andrew Moran and colleagues estimate the reduction in cardiovascular disease and cost-effectiveness of broad provision of antihypertensive medications in China.
Editors' Summary
Background
Worldwide, in 2008, more than one billion people had high blood pressure (hypertension), a condition that is responsible for about 10 million deaths annually from heart attacks, stroke, and other cardiovascular diseases (CVDs). Hypertension, which rarely has any symptoms, is diagnosed by measuring blood pressure (BP), the force that blood circulating in the body exerts on the inside of large blood vessels. BP is highest when the heart contracts to pump blood out (systolic BP) and lowest when the heart relaxes and refills (diastolic BP). Normal adult BP is defined as a systolic BP of less than 120 millimeters of mercury (mm Hg) and a diastolic BP of less than 80 mm Hg (a BP of <120/80 mm Hg). A BP of 140–159/90–99 mm Hg indicates mild (stage one) hypertension; a BP of ≥160/≥100 mg Hg indicates severe (stage two) hypertension. Many factors affect BP, but overweight people and individuals who eat fatty or salty food are at high risk of developing hypertension. Lifestyle changes and/or antihypertensive drugs can be used to control the condition.
Why Was This Study Done?
Hypertension is the leading cardiovascular risk factor in China, the world’s most populous country. About 325 million adults in China have hypertension, but less than half are aware of their condition, only 34% of Chinese adults with hypertension are treated with antihypertensive drugs, and only 28% of treated individuals achieve a BP of <140/90 mm Hg. Improved hypertension control would yield enormous health gains in China, but would these gains outweigh the costs of this intervention? The World Health Organization defines a “highly cost-effective” intervention as one for which the incremental cost effectiveness ratio (ICER; in this case, the ratio of the cost difference between the intervention and no intervention to the difference in outcomes) is less than a country’s gross domestic product (GDP) per capita (a country’s total economic output divided by its number of inhabitants) per quality-adjusted life year gained (a QALY is a measure of disease burden that considers both the quality and quantity of life lived). Here, the researchers use a computer simulation model to project the cost-effectiveness of hypertension treatment in Chinese adults using the low-cost antihypertensive drugs included on the national essential medicines list. In China, most patients pay for drugs out-of-pocket, but several antihypertensive medications with affordable prices are available in government-sponsored primary health facilities.
What Did the Researchers Do and Find?
The researchers used a computer model called the “Cardiovascular Disease Policy Model-China” to simulate the costs of hypertension screening, essential medicines program implementation, hypertension control program administration, drug treatment and monitoring, and the QALYs gained by preventing CVD in Chinese adults with untreated hypertension aged 35–84 y between 2015 and 2025. According to the model, treating hypertension for both primary prevention of CVD (reduction of hypertension in healthy individuals to prevent the development of CVD) and secondary prevention (reduction of hypertension in people who already have CVD to prevent further heart attacks or strokes) would prevent between 600,000 and a million CVD events annually. Treating only patients with CVD and patients with severe hypertension was borderline cost-effective. The ICER of this intervention was between Int$10,000 and Int$18,000 per QALY gained; China’s GDP per capita is Int$11,900.
What Do These Findings Mean?
These findings suggest that an expanded program of treatment for hypertension could prevent about 800,000 cardiovascular events every year in China. Such a program should be borderline cost-effective, provided low-cost essential antihypertensive drugs are used to control hypertension. As with all computer simulation studies, the numerous assumptions incorporated into the model limit the accuracy of these findings. For example, some model inputs were derived from studies of non-Chinese patients and may not accurately represent the Chinese population. Moreover, the model only considers the cost-effectiveness of using medications to control hypertension and does not consider the potential effects of lifestyle changes. Importantly, additional simulations indicate that the cost-effectiveness of the intervention would be greatly reduced if adherence to treatment were lowered or drug costs were increased. Thus, full implementation of the essential medicinesprogram and subsidized drug costs program will be needed to reap the full benefits of improved hypertension control in China.
Additional Information
This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001860.
The US National Heart Lung and Blood Institute has patient information about high BP (in English and Spanish) and a guide to lowering BP through diet
The American Heart Association provides information on hypertension and on CVDs (in several languages); it also provides personal stories about dealing with high BP
The UK National Health Service (NHS) Choices website provides detailed information for patients about hypertension (including a personal story) and about CVD
The World Health Organization provides information on CVD and controlling hypertension; "A Global Brief on Hypertension" was publi shed on World Health Day 2013; WHO-CHOICE provides information on choosing cost-effective interventions
MedlinePlus provides links to further information about high BP, heart disease, and stroke (in English and Spanish)
doi:10.1371/journal.pmed.1001860
PMCID: PMC4524696  PMID: 26241895
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.  Effects of angiotensin II-receptor blockers on soluble cell adhesion molecule levels in uncomplicated systemic hypertension: An observational, controlled pilot study in Taiwanese adults* 
Background:
Controversy exists as to whether individuals with hypertension without risk factors for atherosclerosis (eg, diabetes mellitus, dyslipidemia,
Objective:
The aim of this study was to determine whether (1) levels of solubleCAMs (sCAMs) (soluble E-selectin [sE-selectin], soluble intercellular adhesion molecule-1 [sICAM-1 ], soluble vascular cell adhesion molecule-1 [sVCAM-1 ], and von Willebrand factor [vWF]) are elevated in Taiwanese adults with uncomplicated essential hypertension without other risk factors; (2) CAM levels increase with severity (stage) of hypertension; and (3) monotherapy with the angiotensin II-receptor blocker (ARB) irbesartan modulates CAM expression in a subgroup of these patients.
Methods:
This observational, controlled pilot study was conducted at the Hypertension Clinic, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. Adult patients with uncomplicated essential hypertension without other risk factors (eg, diabetes mellitus, dyslipidemia, obesity) and normotensive controls were eligible. Blood pressure (BP) was determined using 24-hour ambulatory BP monitoring (ABPM) in all participants, and the staging of hypertension was classified based on criteria in The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (normotensive, prehypertension, stage I hypertension, and stage II hypertension). The SCAM levels and 24-hour ABPM were measured before and after 8 weeks of open-label irbesartan monotherapy in a subgroup of the patients with hypertension. Patients who had difficulty achieving the target BP values on irbesartan monotherapy were treated with combination therapy (2 or 3 antihypertensive agents); levels of sCAMs were not measured in these patients. Plasma levels of sE-selectin, the sCAMs, and vWF were measured using enzyme-linked immunosorbent assay.
Results:
The study comprised 61 patients with uncomplicated essentialhypertension (33 men and 28 women; mean [SD] age, 51 [12] years) and 17 normotensive controls (11 men, 6 women; mean [SD] age, 52 [ 11 ] years). The mean (SD) dose of irbesartan was 243 (63) mg. Hypertensive patients had significantly higher circulating levels of sICAM-1 compared with normotensive controls (P = 0.009). No significant differences in levels of sVCAM-1, sE-selectin, or vWF were found between hypertensive patients and controls. The mean sICAM-1 level was significantly higher in the prehypertensive patients compared with normotensive controls (P = 0.03). The mean sE-selectin level was significantly higher in the patients with stage I hypertension compared with the prehypertensive group (P = 0.01). The 18 patients given 8 weeks of irbesartan monotherapy showed a significant decrease from baseline in systolic and diastolic BP (both, P = 0.001) and sE-selectin (P= 0.006), but not in sVCAM-1 or sICAM. Forty-three patients did not reach target BP on irbesartan monotherapy and thus were treated with combination therapy.
Conclusions:
Based on the results of this observational, controlled pilotstudy in Taiwanese patients, we suggest that ARB therapy, in addition to reducing BP, has the potential to suppress CAM expression and to improve endothelial dysfunction in hypertension.
doi:10.1016/j.curtheres.2005.06.005
PMCID: PMC3964542  PMID: 24672122
soluble cell adhesion molecule; ambulatory blood pressuremonitoring; systemic hypertension; angiotensin 11-receptor blockers
4.  Functional Inducible Nitric Oxide Synthase Gene Variants Associate With Hypertension 
Medicine  2015;94(46):e1958.
Abstract
Increased inducible nitric oxide synthase (iNOS) activity and expression has been associated with hypertension, but less is known whether the 2 known functional polymorphic sites in the iNOS gene (g.–1026 C/A (rs2779249), g.2087 G/A (rs2297518)) affect susceptibility to hypertension. The objective of this study was to investigate the association between the genetic variants of iNOS and diagnosed hypertension in a Finnish cohort.
This study included 320 hypertensive cases and 439 healthy controls. All participants were 50-year-old men and women and the data were collected from the Tampere adult population cardiovascular risk study (TAMRISK). DNA was extracted from buccal swabs and iNOS single nucleotide polymorphisms (SNPs) were analyzed using KASP genotyping PCR. Data analysis was done by logistic regression.
At the age of 50 years, the SNP rs2779249 (C/A) associated significantly with hypertension (P = 0.009); specifically, subjects carrying the A-allele had higher risk of hypertension compared to those carrying the CC genotype (OR = 1.47; CI = 1.08–2.01; P = 0.015). In addition, a 15-year follow-up period (35, 40, and 45 years) of the same individuals showed that carriers of the A-allele had more often hypertension in all of the studied age-groups. The highest risk for developing hypertension was obtained among 35-year-old subjects (odds ratio [OR] 3.83; confidence interval [CI] = 1.20–12.27; P = 0.024). Those carrying variant A had also significantly higher readings of both systolic (P = 0.047) and diastolic (P = 0.048) blood pressure during the follow-up. No significant associations between rs2297518 (G/A) variants alone and hypertension were found. However, haplotype analysis of rs2779249 and rs2297518 revealed that individuals having haplotype H3 which combines both A alleles (CA–GA, 19.7% of individuals) was more commonly found in the hypertensive group than in the normotensive group (OR = 2.01; CI = 1.29–3.12; P = 0.002).
In conclusion, there was a significant association between iNOS genetic variant (rs2779249) and hypertension in the genetically homogenous Finnish population. Those who carried the rare A-allele of the gene had higher risk for hypertension already at the age of 35 years.
doi:10.1097/MD.0000000000001958
PMCID: PMC4652812  PMID: 26579803
5.  E-selectin gene polymorphisms are associated with essential hypertension: a case-control pilot study in a Chinese population 
BMC Medical Genetics  2010;11:127.
Background
Genetic variation is thought to contribute to the etiology of hypertension, and E-selectin is a candidate essential hypertension-associated gene. This study thus sought to investigate possible genetic associations between the T1880C, C602A and T1559C polymorphisms of E-selectin and essential hypertension.
Methods
Hypertensive patients (n = 490) and healthy normotensive subjects (n = 495) were screened for the genotypes T1880C, C602A and T1559C using real-time quantitative polymerase chain reaction after DNA extraction to identify representative variations in the E-selectin gene. The associations between genotypes and alleles of the three mutations and essential hypertension were then analyzed using a case-control study.
Results
Hypertensive patients and normotensive subjects were significantly different with respect to the genotypes CC, CA and AA (P = 0.005) and the C-allele frequency of C602A (P = 0.001). A comparison of dominant versus recessive models also revealed significant differences between the two groups (P = 0.004 and P = 0.02). When subgrouped by gender, these indexes differed significantly between normotensive and essential hypertensive males, but not in females. The additive model of the T1559C genotype did not differ between essential hypertensive and normotensive groups overall (P = 0.39), but it was different between hypertensive and normotensive males (P = 0.046) and females (P = 0.045). The CC + TC versus TT frequency of T1559C was also different in the recessive model of male hypertensive and normotensive groups (P = 0.02). Further analysis showed that C602A and T1559C were significantly associated with hypertension (C602A: OR = 7.58, 95%CI = 1.53-11.97, P < 0.01; and T1559C: OR = 6.77, 95%CI = 1.07-1.83, P < 0.05). The frequency of the C-C-C haplotype was significantly higher in hypertensive patients than in control individuals as well as in hypertensive and normotensive males (P = 0.008 and 0.01). The frequency of the C-A-T haplotype was higher only in male hypertensives and normotensives (P = 0.015). Furthermore, there was a significant interaction between E-selectin and gender (P = 0.02 for C602A and 0.04 for T1559C).
Conclusion
C602A and T1559C may be independent risk factors for essential hypertension in the Chinese population, whereas T1880C is not.
doi:10.1186/1471-2350-11-127
PMCID: PMC2940768  PMID: 20796317
6.  Bariatric Surgery in the United Kingdom: A Cohort Study of Weight Loss and Clinical Outcomes in Routine Clinical Care 
PLoS Medicine  2015;12(12):e1001925.
Background
Bariatric surgery is becoming a more widespread treatment for obesity. Comprehensive evidence of the long-term effects of contemporary surgery on a broad range of clinical outcomes in large populations treated in routine clinical practice is lacking. The objective of this study was to measure the association between bariatric surgery, weight, body mass index, and obesity-related co-morbidities.
Methods and Findings
This was an observational retrospective cohort study using data from the United Kingdom Clinical Practice Research Datalink. All 3,882 patients registered in the database and with bariatric surgery on or before 31 December 2014 were included and matched by propensity score to 3,882 obese patients without surgery. The main outcome measures were change in weight and body mass index over 4 y; incident diagnoses of type 2 diabetes mellitus (T2DM), hypertension, angina, myocardial infarction (MI), stroke, fractures, obstructive sleep apnoea, and cancer; mortality; and resolution of hypertension and T2DM. Weight measures were available for 3,847 patients between 1 and 4 mo, 2,884 patients between 5 and 12 mo, and 2,258 patients between 13 and 48 mo post-procedure. Bariatric surgery patients exhibited rapid weight loss for the first four postoperative months, at a rate of 4.98 kg/mo (95% CI 4.88–5.08). Slower weight loss was sustained to the end of 4 y. Gastric bypass (6.56 kg/mo) and sleeve gastrectomy (6.29 kg/mo) were associated with greater initial weight reduction than gastric banding (2.77 kg/mo). Protective hazard ratios (HRs) were detected for bariatric surgery for incident T2DM, 0.68 (95% CI 0.55–0.83); hypertension, 0.35 (95% CI 0.27–0.45); angina, 0.59 (95% CI 0.40–0.87);MI, 0.28 (95% CI 0.10–0.74); and obstructive sleep apnoea, 0.55 (95% CI 0.40–0.87). Strong associations were found between bariatric surgery and the resolution of T2DM, with a HR of 9.29 (95% CI 6.84–12.62), and between bariatric surgery and the resolution of hypertension, with a HR of 5.64 (95% CI 2.65–11.99). No association was detected between bariatric surgery and fractures, cancer, or stroke. Effect estimates for mortality found no protective association with bariatric surgery overall, with a HR of 0.97 (95% CI 0.66–1.43). The data used were recorded for the management of patients in primary care and may be subject to inaccuracy, which would tend to lead to underestimates of true relative effect sizes.
Conclusions
Bariatric surgery as delivered in the UK healthcare system is associated with dramatic weight loss, sustained at least 4 y after surgery. This weight loss is accompanied by substantial improvements in pre-existing T2DM and hypertension, as well as a reduced risk of incident T2DM, hypertension, angina, MI, and obstructive sleep apnoea. Widening the availability of bariatric surgery could lead to substantial health benefits for many people who are morbidly obese.
In a UK cohort study, Ian Douglas and colleagues investigate weight, BMI, and related health outcomes after bariatric surgery.
Editors' Summary
Background
Obesity—having an unhealthy amount of body fat—is a growing threat to global public health. Worldwide, 13% of adults are obese, and, in the UK and the US, the statistics are even worse. A quarter and a third, respectively, of adults in these countries are obese. Obesity is defined as having a body mass index (BMI; an indicator of body fat calculated by dividing a person’s weight in kilograms by their height in meters squared) of ≥30 kg/m2. Compared to people with a healthy weight (a BMI of 18.5–24.9 kg/m2), overweight and obese people have an increased risk of developing type 2 diabetes, cardiovascular conditions such as hypertension (high blood pressure), myocardial infarction (heart attack), angina, and stroke, and they tend to die younger. People become overweight, and eventually obese, by consuming food and drink that contain more energy (calories) than they need for their daily activities. So, obesity can be prevented and reversed by eating less and exercising more.
Why Was This Study Done?
People with severe obesity (BMI of 40 kg/m2 or more) who have tried but failed to control their weight through lifestyle changes sometimes undergo bariatric surgery (weight loss surgery). In the UK and the US, this approach is also recommended for obese individuals who have an obesity-related illness such as type 2 diabetes with a lower BMI of 35 kg/m2 or more. Techniques such as gastric band surgery, gastric bypass, and sleeve gastrectomy all lead to reduced energy intake, and in randomized controlled trials comparing bariatric surgery and lifestyle interventions, bariatric surgery is associated with greater weight loss. However, the results of clinical trials are not always replicated in routine clinical practice. Here, the researchers investigate whether there is an association between bariatric surgery and weight, BMI, and obesity-related co-morbidities (illnesses) in the UK by undertaking a retrospective cohort study (an observational study that compares recorded clinical outcomes in non-randomized groups of patients who received different treatments).
What Did the Researchers Do and Find?
The researchers used the UK Clinical Practice Research Datalink, which contains anonymized clinical information about patients provided by general practitioners (primary care physicians), to identify 3,882 patients who had had bariatric surgery. They matched each patient (average BMI 44.7 kg/m2), according to the patient’s medications and constellation of risk factors, to an obese individual from the dataset who had not had bariatric surgery. This “propensity matching” technique is used in studies where patients are not allocated at random to receive a treatment, and is meant to control for confounding—the possibility that patients who receive the treatment may be otherwise distinct from patients who do not. According to this analysis, patients who had had bariatric surgery lost weight rapidly during the first four post-operative months (4.98 kg/month); their weight loss was sustained at a slower rate for up to four years. By contrast, there were no weight changes in the patients who did not have surgery. Notably, bariatric surgery was associated with a lower risk of type 2 diabetes onset, hypertension onset, angina onset, myocardial infarction, and obstructive sleep apnea (a sleep disorder) onset, and with the resolution of both type 2 diabetes and hypertension in those who already had these conditions when they underwent surgery. However, over an average of 3.4 years of follow-up, there was no evidence of any difference in the risk of death.
What Do These Findings Mean?
These findings show that bariatric surgery delivered in routine clinical practice in the UK is associated with a substantial initial weight loss that is sustained for at least four years after surgery. They also show that bariatric surgery is associated with improvements in pre-existing type 2 diabetes and hypertension and with a reduced risk of developing several obesity-related co-morbidities. Because the data used in the study were recorded for patient management by primary care physicians, the researchers were unable to use strict diagnostic criteria for some outcomes, which may limit the accuracy of these findings. Nevertheless, these results suggest that widening the availability of bariatric surgery in the UK could provide substantial health benefits for many people who are morbidly obese. Indeed, the researchers calculate that, if the associations seen in this study are causal (an observational study cannot prove that a treatment causes a specific outcome), bariatric surgery could prevent and/or resolve many tens of thousands of cases of hypertension and type 2 diabetes and prevent similar numbers of cases of other obesity-related illnesses among the 1.4 million morbidly obese people living in the UK.
Additional Information
This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001925.
The World Health Organization provides information on obesity (in several languages)
The Institute for Health Metrics and Evaluation website provides the latest details about global obesity trends; the World Obesity Federation also provides information about the global obesity epidemic
The UK National Health Service Choices website provides information about obesity (including some real stories), bariatric surgery (including some comments from patients), and healthy eating
The US Centers for Disease Control and Prevention has information on all aspects of overweight and obesity
ChooseMyPlate.gov is a resource provided by the US Department of Agriculture that provides individuals and healthcare professionals with user-friendly information on nutrition and physical exercise
The US National Institute of Diabetes and Digestive and Kidney Diseases provides information on bariatric surgery and on weight control and healthy living
MedlinePlus provides links to other sources of information on obesity and bariatric surgery (in English and Spanish)
doi:10.1371/journal.pmed.1001925
PMCID: PMC4687869  PMID: 26694640
7.  Survival in treated hypertension: follow up study after two decades 
BMJ : British Medical Journal  1998;317(7152):167-171.
Objective: To compare survival and cause specific mortality in hypertensive men with non-hypertensive men derived from the same random population, and to study mortality and morbidity from cardiovascular diseases in the hypertensive men in relation to effects on cardiovascular risk factors during 22-23 years of follow up.
Design: Prospective, population based observational study.
Subjects and methods: 686 hypertensive men aged 47-55 at screening compared with 6810 non-hypertensive men. The hypertensive men were having stepped care treatment with either β adrenergic blocking drugs, thiazide diuretics, or combination treatment. Mortality, morbidity, and adverse effects were registered at yearly examinations and from death certificates.
Main outcome measures: All cause mortality and cause specific mortality.
Results: Treated hypertensive men had significantly impaired probability of total survival as well as survival from coronary heart disease and stroke. All cause mortality as well as coronary heart disease and stroke mortality were very similar in hypertensive men and normotensive men during the first decade, but increased steadily thereafter despite continuous good blood pressure control. Smoking, signs of target organ damage, and high serum cholesterol levels, but not blood pressure at screening, were significantly related to the incidence of coronary heart disease during follow up. In time dependent Cox’s regression analysis, the incidence of coronary heart disease was significantly related only to serum cholesterol concentrations in the study. Cancer mortality was almost similar in treated hypertensive men (61/686, 8.9%) and non-hypertensive men (732/6810, 10.8%).
Conclusion: Treated hypertensive men had impaired survival and increased mortality from cardiovascular disease compared with non-hypertensive men of similar age. These differences were observed during the second decade of follow up. During an observation period of 22-23 years—about 15 000 patient years—hypertensive men receiving diuretics and β blockers had no increased risk of cancer or non-cardiovascular disease.
Key messages Hypertension is a prevalent (10-20%) and important risk factor for cardiovascular disease. In controlled trials over 3-5 years drug treatment for hypertension prevents these complications, but little is known about long term prognosis During 20-22 years treated hypertensive men had a significantly increased mortality, especially from coronary heart disease, compared with non-hypertensive men from the same population The high incidence of myocardial infarction was related to organ damage, smoking, and cholesterol at the time of entry to the study, and to achieved serum cholesterol concentrations during follow up The poor prognosis for mortality from coronary heart disease is dependent upon strict monitoring of serum cholesterol concentrations
PMCID: PMC28606  PMID: 9665894
8.  Lifestyle modifications to prevent and control hypertension. 1. Methods and an overview of the Canadian recommendations. Canadian Hypertension Society, Canadian Coalition for High Blood Pressure Prevention and Control, Laboratory Centre for Disease Control at Health Canada, Heart and Stroke Foundation of Canada 
OBJECTIVE: To provide updated, evidence-based recommendations for health care professionals on lifestyle changes to prevent and control hypertension in otherwise healthy adults (except pregnant women). OPTIONS: For people at risk for hypertension, there are a number of lifestyle options that may avert the condition--maintaining a healthy body weight, moderating consumption of alcohol, exercising, reducing sodium intake, altering intake of calcium, magnesium and potassium, and reducing stress. Following these options will maintain or reduce the risk of hypertension. For people who already have hypertension, the options for controlling the condition are lifestyle modification, antihypertensive medications or a combination of these options; with no treatment, these people remain at risk for the complications of hypertension. 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: A MEDLINE search was conducted for the period January 1996 to September 1996 for each of the interventions studied. 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 level 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: Lifestyle modification by means of weight loss (or maintenance of healthy body weight), regular exercise and low alcohol consumption will reduce the blood pressure of appropriately selected normotensive and hypertensive people. Sodium restriction and stress management will reduce the blood pressure of appropriately selected hypertensive patients. The side effects of these therapies are few, and the indirect benefits are well known. There are certainly costs associated with lifestyle modification, but they were not measured in the studies reviewed. Supplementing the diet with potassium, calcium and magnesium has not been associated with a clinically important reduction in blood pressure in people consuming a healthy diet. RECOMMENDATIONS: (1) It is recommended that health care professionals determine the body mass index (weight in kilograms/[height in metres]2) and alcohol consumption of all adult patients and assess sodium consumption and stress levels in all hypertensive patients. (2) To reduce blood pressure in the population at large, it is recommended that Canadians attain and maintain a healthy body mass index. For those who choose to drink alcohol intake should be limited to 2 or fewer standard drinks per day (maximum of 14/week for men and 9/week for women). Adults should exercise regularly. (3) To reduce blood pressure in hypertensive patients, individualized therapy is recommended. This therapy should emphasize weight loss for overweight patients, abstinence from or moderation in alcohol intake, regular exercise, restriction of sodium intake and, in appropriate circumstances, individualized cognitive behaviour modification to reduce the negative effects of stress. VALIDATION: The recommendations were reviewed by all of the sponsoring organizations and by participants in a satellite symposium of the fourth international Conference on Preventive Cardiology. They are similar to those of the World Hypertension League and the Joint National committee, with the exception of the recommendations on stress management, which are based on new information. They have not been clinically tested. SPONSORS: The Canadian Hypertension Society, the Canadian Coalition for High Blood Pressure Prevention and Control, the Laboratory Centre for Disease Control at health Canada, and the Heart and Stroke Foundation of Canada.
PMCID: PMC1230333  PMID: 10333847
9.  hs-CRP: A potential marker for hypertension in Kashmiri population 
Hypertension is the most important public health problem in developing countries and one of the major risk factors for cardiovascular diseases, and it has been reported that hypertension is in part an inflammatory disorder and several workers have reported elevated levels of CRP in hypertensive individuals. The main aim of the present study was to evaluate the association between blood pressure and serum CRP levels across the range of blood pressure categories including prehypertension. A total of 104 patients and 63 control subjects were included in the present study. The level of CRP in the serum samples was estimated by a high sensitivity immunoturbidometric assay. Standard unpaired student’s ‘t’ test was used for comparison of hs-CRP levels between hypertensive patients and normotensive control subjects and between patient groups with different grades of hypertension and different durations of hypertensive histories. The mean serum hs-CRP level in hypertensive patients was 3.26 mg/L compared with 1.36 mg/L among normotensive control subjects (P<0.001). On comparison with normotensive control subjects, the hs-CRP levels vary significantly both with grades and duration of hypertension, with most significant difference found in patients with prehypertension (P<0.001), followed by Stage-I (P=0.01) and Stage-II(P=0.02) hypertensives. Significant difference in hs-CRP levels was also found in patients with shorter duration of hypertensive history (≤ 1year) when compared with those with ≥5 years of hypertensive history (P<0.01). Our study reveals a graded association between blood pressure and CRP elevation in people with hypertension. Individuals with prehypertension or with shorter duration of hypertension (≤1 Year) had significantly a greater likelihood of CRP elevation in comparison to chronic stage-I or stage-II hypertensives.
doi:10.1007/s12291-010-0037-7
PMCID: PMC3453101  PMID: 23105911
Hypertension; Inflammatory disorder; hs-CRP; Stage I
10.  Trends of blood pressure levels and management in Västerbotten County, Sweden, during 1990–2010 
Global Health Action  2012;5:10.3402/gha.v5i0.18195.
Background
Availability of longitudinal data on hypertension and blood pressure levels are important to assess changes over time at the population level. Moreover, detailed information in different population sub-groups is important to understand inequity and social determinants of blood pressure distribution in the population.
Objectives
The objectives of this study are to: (1) describe the trends of population blood pressure levels in men and women between different educational levels and geographic areas in Sweden during 1990–2010; (2) identify prevalences of hypertension, awareness, treatment, and control in the population; and (3) assess the 10-year risk of developing hypertension among individuals with normal and high normal blood pressures.
Methods
This study is based on data from the Västerbotten Intervention Program (VIP) in Västerbotten County, Sweden. The cross-sectional analysis includes 133,082 VIP health examinations among individuals aged 30, 40, 50, and 60 years from 1990 to 2010. The panel analysis includes 34,868 individuals who were re-examined 10 years after the baseline examination. Individuals completed a self-administered health questionnaire that covers demographic and socio-economic information, self-reported health, and lifestyle behaviours. Blood pressure measurement was obtained prior to the questionnaire. In the cross-sectional analysis, trends of blood pressure by sex, and between educational groups and geographic areas are presented. In the panel analysis, the 10-year risk of developing hypertension is estimated using the predicted probability from logistic regression analysis for each sex, controlling for age and educational level.
Results
The prevalence of hypertension decreased from 1990 to 2010; from 43.8 to 36.0% (p < 0.001) among men, and 37.6 to 27.5% among women (p < 0.001). Individuals with basic education had a significantly higher prevalence of hypertension compared to those with medium or high education. Although the decreases were observed in all geographic areas, individuals in rural inland areas had a much higher prevalence compared to those who lived in Umeå City. The proportion of hypertensive women who were aware of their hypertension (61.7%) was significantly higher than men (51.6%). About 34% of men and 42% of women with hypertension reported taking blood pressure medication. Over time, awareness and control of hypertension improved (from 46.5% in 1990 to 69% in 2010 and from 30 to 65%, respectively). The gaps between educational groups diminished. This study shows a significantly higher risk of developing hypertension for men and women with high normal blood pressure compared to those with normal blood pressure at baseline in all age cohorts and educational groups. The average risks of developing hypertension among men with high normal blood pressure were 21.5, 45.8, and 56.3% in the 30, 40, and 50-year cohorts, respectively. Corresponding numbers for women were 22.6, 47.4, and 57.9%.
Conclusions
Levels of blood pressure and hypertension decreased significantly among the Västerbotten population in the last 21 years. Hypertension management has improved and there is increased awareness, treatment, and control of blood pressure. Despite these achievements, the persisting social gaps in blood pressure levels and management demand further investigation and action from policy makers. Future research should attempt to identify and address the root causes of these health inequities to ensure better and equal health for the whole population.
doi:10.3402/gha.v5i0.18195
PMCID: PMC3409341  PMID: 22855645
hypertension; awareness; treatment; control; Sweden; Västerbotten Intervention Program; high normal; prehypertension
11.  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
12.  Hypertension Prevalence, Awareness and Blood Pressure Control in Matao, Brazil: A Pilot Study in Partnership With the Brazilian Family Health Strategy Program 
Background
Around 30% of Brazilian population is hypertensive. Brazilian’s Family Health Strategy (FHS) is a community-based approach to provide primary health care and control chronic disease as hypertension. The aims of this pilot study were to study hypertension prevalence and awareness and to analyze the feasibility of FHS program with community healthy agents (CHA) to collect data about hypertensive subjects in Matao, Brazil.
Methods
A cross-sectional study was conducted in subjects equal or older than 40 years old in a neighborhood belonging to FHS program. CHA were trained to collect data and to assess blood pressure (BP) with an automated device. Hypertension diagnosis was defined if systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg or subject had previous use of hypertensive drug. Chi-square test and univariate logistic regression analysis were applied with significance level of 5% and a confidence interval of 95%.
Results
In 625 subjects, hypertension prevalence was 68.8% and women (71.9%) were more hypertensive than men (63.2%) (P = 0.02). Prevalence of hypertension increased with age group, from 46.3% (40 - 49 years) to 82.5% (70 - 79 years) (P < 0.001). The overall prevalence of pre-hypertension was 40.1%: stage 1, 25.7% and stage 2, 17.0%. Hypertension awareness was 81.8% and 79.8% reported use of anti-hypertensive drugs. BP was not controlled in 61.8% and 67.7% of them was using anti-hypertensive drugs. CHA reported no difficulties to collect data and BP assessment with the automated device.
Conclusion
We observed a high hypertension prevalence rate, awareness, and subjects with uncontrolled hypertension even with use of anti-hypertensive drugs. CHA from FHS program are a feasible option to BP control in future studies involving larger populations.
doi:10.14740/jocmr2582w
PMCID: PMC4894022  PMID: 27298661
Hypertension; Epidemiology; Non-communicable diseases; Brazil
13.  Common variants of the beta and gamma subunits of the epithelial sodium channel and their relation to plasma renin and aldosterone levels in essential hypertension 
Background
Rare mutations of the epithelial sodium channel (ENaC) result in the monogenic hypertension form of Liddle's syndrome. We decided to screen for common variants in the ENaC βand γ subunits in patients with essential hypertension and to relate their occurrence to the activity of circulating renin-angiotensin-aldosterone system.
Methods
Initially, DNA samples from 27 patients with low renin/low aldosterone hypertension were examined. The DNA variants were subsequently screened for in 347 patients with treatment-resistant hypertension, 175 male subjects with documented long-lasting normotension and 301 healthy Plasma renin and aldosterone levels were measured under baseline conditions and during postural and captopril challenge tests.
Results
Two commonly occurring βENaC variants (G589S and a novel intronic i12-17CT substitution) and one novel γENaC variant (V546I) were detected. One of these variants occurred in a heterozygous form in 32 patients, a prevalence (9.2%) significantly higher than that in normotensive males (2.9%, p = 0.007) and blood donors (3.0%, p = 0.001). βENaC i12-17CT was significantly more prevalent in the hypertension group than in the two control groups combined (4.6% vs. 1.1%, p = 0.001). When expressed in Xenopus oocytes, neither of the two ENaC amino acid-changing variants showed a significant difference in activity compared with ENaC wild-type. No direct evidence for a mRNA splicing defect could be obtained for the βENaC intronic variant. The ratio of daily urinary potassium excretion to upright and mean (of supine and upright values) plasma renin activity was higher in variant allele carriers than in non-carriers (p = 0.034 and p = 0.048).
Conclusions
At least 9% of Finnish patients with hypertension admitted to a specialized center carry genetic variants of β and γENaC, a three times higher prevalence than in the normotensive individuals or in random healthy controls. Patients with the variant alleles showed an increased urinary potassium excretion rate in relation to their renin levels.
doi:10.1186/1471-2350-6-4
PMCID: PMC547905  PMID: 15661075
14.  Serum uric acid level in newly diagnosed essential hypertension in a Nepalese population: A hospital based cross sectional study 
Objective
To develop the missing link between hyperuricemia and hypertension.
Methods
The study was conducted in Department of Biochemistry in collaboration with Nephrology Unit of Internal Medicine Department. Hypertension was defined according to blood pressure readings by definitions of the Seventh Report of the Joint National Committee. Totally 205 newly diagnosed and untreated essential hypertensive cases and age-sex matched normotensive controls were enrolled in the study. The potential confounding factors of hyperuricemia and hypertension in both cases and controls were controlled. Uric acid levels in all participants were analyzed.
Results
Renal function between newly diagnosed hypertensive cases and normotensive healthy controls were adjusted. The mean serum uric acid observed in newly diagnosed hypertensive cases and in normotensive healthy controls were (290.05±87.05) µmol/L and (245.24±99.38) µmol/L respectively. A total of 59 (28.8%) participants of cases and 28 (13.7%) participants of controls had hyperuricemia (odds ratio 2.555 (95% CI: 1.549-4.213), P<0.001).
Conclusions
The mean serum uric acid levels and number of hyperuricemic subjects were found to be significantly higher in cases when compared to controls.
doi:10.1016/S2221-1691(14)60209-4
PMCID: PMC3819497  PMID: 24144132
Newly diagnosed hypertension; Serum uric acid; Hyperuricemia; Joint National Committee
15.  Assessment of antioxidant enzyme activities in erythrocytes of pre-hypertensive and hypertensive women 
BACKGROUND:
Few studies that have investigated hypertension have considered a state of oxidative stress that can contribute to the development of atherosclerosis and other hypertension induced organ damage. The aim of this study was to investigate whether pre-hypertension and hypertension status is associated with activities of erythrocyte antioxidant enzymes in a random sample of cardiovascular disease-free women.
METHODS:
In this case-control study, 53 pre-hypertensive women, 32 hypertensive women and 75 healthy controls were included. General information was gathered using questionnaires and face-to-face interviews. Blood pressure and anthropometric measurements were measured for each subject. Venous blood samples were drawn from subjects and plasma was separated. Activities of erythrocyte antioxidant enzymes were also evaluated by measuring activities of copper zinc-superoxide dismutase (CuZn-SOD), glutathione peroxidase (GPX) and catalase (CAT) in selected subjects.
RESULTS:
Fifty-three (33.1%) and 32 (20%) participants were pre-hypertensive and hypertensive, respectively. The hypertensive and pre-hypertensive women had lower CuZn-SOD (p < 0.001) and GPX (p < 0.01) activities compared to normotensives. Furthermore, hypertensive women had lower CAT activity compared to pre-hypertensive and normotensive women (p < 0.001). Moreover, significant differences were also observed between hypertensive and pre-hypertensive women in erythrocyte CAT activity (p < 0.01).
CONCLUSIONS:
The present findings show that activities of erythrocyte antioxidant enzymes decrease in pre-hypertensive and hypertensive women, which may eventually lead to atherosclerosis and other high blood pressure related health problems.
PMCID: PMC3082824  PMID: 21526095
High Blood Pressure; Antioxidants; Biocatalysts; Woman
16.  The Role of the Endogenous Antioxidant Enzymes and Malondialdehyde in Essential Hypertension 
Context: Oxidative Stress is caused by an imbalance between the production of reactive oxygen species and a biological system’s ability to readily detoxify the reactive intermediates.
Aims: 1. To compare the levels of Malondialdehyde (MDA), in hypertensive and normotensive subjects.
2. To compare the levels of the antioxidant enzymes, namely, Catalase, Glutathione peroxidase (GPX) and Superoxide Dismutase (SOD) in hypertensive and normotensive subjects.
3. To determine the correlation between the MDA levels and the mean arterial pressure (MAP) among hypertensive subjects.
4. To determine the correlation between the antioxidant enzyme levels and MAP among the hypertensive subjects and to evaluate the effect of 6 months of antihypertensive therapy with a tight blood pressure control on the MDA levels.
Materials and Methods : In this cross sectional study, 25 normotensive and 40 hypertensive subjects were recruited. The hypertensive subjects were further subdivided into three subgroups: Prehypertensives, Stage I hypertensives and Stage II hypertensives. All the subjects underwent a blood pressure measurement and the markers of oxidative stress in their sera were estimated. The subjects of Stage I hypertension and Stage II hypertension were given antihypertensive treatment for 6 months and their blood pressures were tightly regulated and brought to the normotensive state. After 6 months, the estimations of the markers of oxidative stress were done again.
Results: The MDA levels were significantly increased in the stage I and stage II hypertension groups as compared to those of the control group (p<0.05). The antioxidant enzymes (SOD, Catalase and GPX) were significantly decreased (p<0.05) in the prehypertension and in the stage I and stage II hypertension groups as compared to those in the control group. There was a significant increase in the levels of the antioxidant enzymes after 6 months of a tight regulation and bringing of the blood pressure to the normotensive state by giving antihypertensive therapy.
Conclusion: On comparison of the present study with other studies in which the use of antioxidants were found to be ineffective in the blood pressure reduction, it can be concluded that oxidative stress is an effect rather than a cause of essential hypertension.
doi:10.7860/JCDR/2013/5829.3091
PMCID: PMC3708256  PMID: 23905086
Essential hypertension; Oxidative Stress; Catalase; Glutathione peroxidase; Superoxide Dismutase Antihypertensive therapy
17.  Good knowledge about hypertension is linked to better control of hypertension; A multicentre cross sectional study in Karachi, Pakistan 
BMC Research Notes  2012;5:579.
Background
According to the National Health survey only 3% of the population has controlled hypertension. This study was designed to elucidate the knowledge about hypertension in hypertensive patients at three tertiary care centers in Karachi. Secondly we sought to compare the knowledge of those with uncontrolled hypertension and controlled hypertension.
Methods
It was a cross-sectional study conducted at The Aga Khan University hospital (AKUH), Ziauddin Hospital (ZH) and Civil hospital, Karachi (CHK. All diagnosed Hypertensive patients (both inpatients and outpatients) coming to a tertiary care hospital in Pakistan aged > 18 years were included. Patients were categorized into 2 groups: controlled and uncontrolled hypertension based on their initial BP readings on presentation Uncontrolled Hypertension was defined as average BP ≥ 140/90 mm Hg in patients on treatment. Controlled Hypertension (HTN) was defined as average BP <140/90 mm Hg in patients on treatment. Standardized methods were used to record BP in the sitting position. Knowledge was recorded as a15 item question. Primary outcome was knowledge about hypertension.
Results
A total of 650 participants were approached and consented 447 were found eligible. 284(63.5%) were from Aga Khan University, 101(22.6) from Dow University of health sciences and 62(13.9) were from Ziauddin University. Mean (SD) age of participants was 57.7(12) years, 50.1(224) were men. Controlled hypertension was present in 323(72.3) and uncontrolled hypertension was present in 124(27.4). The total mean (SD) Knowledge score was 20.97(4.93) out of a maximum score of 38. On comparison of questions related to knowledge between uncontrolled and controlled hypertension, there was statistically significant different in; meaning of hypertension (p <0.001), target SBP(p0.001), target DBP(p 0.001), importance of SBP versus DBP, improvement of health with lowering of blood pressure (p 0.002), high blood pressure being asymptomatic (p <0.001), changing lifestyle improves blood pressure(p 0.003),hypertension being a lifelong disease (<0.001), lifelong treatment with antihypertensives(<0.001) and high blood pressure being part of aging(<0.001). On comparison of knowledge as a composite score between uncontrolled and controlled hypertensive; Mean (SD) score was 21.85(4.74) v18.67 (4.70) (p value: < 0.001). On multivariate analysis; gender β (95% CI) 1.67(0.75, 2.59) p <0.001, uncontrolled blood pressure; -2.70(−3.76,-1.67) p <0.001, Sindhi ethnicity; -1.79(−3.25,-3.27) p 0.01 and pukhtoon ethnicity; -2.72(−4.13,-1.32) p <0.001 were significantly associated with knowledge score.
Conclusion
Knowledge about hypertension in hypertensive patients is not adequate and is alarmingly poor in patients with uncontrolled hypertension. More emphasis needs to be made on target blood pressure and need for taking antihypertensives for life to patients by physicians.
doi:10.1186/1756-0500-5-579
PMCID: PMC3534478  PMID: 23095492
Hypertension; Knowledge; Uncontrolled hypertension
18.  Prevalence of Hypertension among Adults in Remote Rural Areas of Xinjiang, China 
Objective: The present study aimed to estimate prevalence of hypertension among adults in rural remote areas of Xinjiang, China and evaluate the associated factors of hypertension. Methods: The survey was based on questionnaire interviews and clinical measurements of 11,340 individuals (≥18 years old), and was conducted during 2009–2010 via a stratified cluster random sampling method in the remote rural areas of Xinjiang, about 4407 km away from the capital Beijing. Hypertension was defined according to WHO/ISH criteria. Results: Systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the population were (126.3 ± 21.4) and (80.9 ± 13.4) mmHg. Compared with Han nationality subjects, SBP and DBP of Kazakh nationality subjects were significantly high (p < 0.05), while the SBP and DBP of Uyghur subjects were significantly low (Kazakh: (128.7 ± 23.9) and (83.0 ± 14.6) mmHg, Uyghur: (123.6 ± 19.3) and (77.4 ± 12.7) mmHg, Han: (126.5 ± 20.5) and (82.6 ± 11.9) mmHg, p < 0.05). Prevalence of hypertension of the population was 32.1%, and was greater among Kazakhs and lower among Uyghur than Han (Kazakh: 36.9%, Uyghur: 26.1%, Han: 33.7%, p < 0.05). The age-standardized prevalence of hypertension was 30.2%, and was greater among Kazakhs while lower among Uyghurs than Han subjects (Kazakh: 37.0%, Uyghur: 26.0%, Han: 33.8%, p < 0.05, p < 0.05). Multivariate logistic regression analyses showed Gender (OR = 1.324), age (OR = 2.098, 3.681, 6.794, 9.473, 14.646), nationality (OR = 1.541), occupation (OR = 1.659, 1.576), education (OR = 1.260), BMI (OR = 1.842), WC (OR = 1.585), WHR (OR = 1.188), WHR (OR = 1.188), diabetes (OR = 1.879), hypertriglyceridemia (OR = 1.361), hypercholesterolemia (OR = 1.131) and high blood low density lipoprotein cholesterol (LDL-C) (OR = 1.956) were all positively correlated with hypertension, while low blood high density lipoprotein cholesterol (HDL-C) (OR = 0.765) was negatively correlated with hypertension. Conclusions: Prevalence of hypertension among adults in remote rural areas of Xinjiang was higher than the national average. Prevalence of hypertension was greater among Kazakhs and lower among Uyghurs than Han nationals, thus indicating significant differences between regions and nationalities. Gender, age, nation, occupation, education, overweight or obesity, abdominal obesity, diabetes, hyperlipidemia, hypercholesterolemia, high LDL-C were positively correlated with hypertension, low HDL-C was negatively correlated with hypertension.
doi:10.3390/ijerph13060524
PMCID: PMC4923981  PMID: 27231924
hypertension; prevalence; epidemiological studies; rural; nation
19.  Arterial hypertension assessed “out-of-office” in a contemporary cohort of rheumatoid arthritis patients free of cardiovascular disease is characterized by high prevalence, low awareness, poor control and increased vascular damage-associated “white coat” phenomenon 
Arthritis Research & Therapy  2013;15(5):R142.
Introduction
Rheumatoid arthritis (RA) is associated with a high cardiovascular disease (CVD) risk, whereas arterial hypertension is a major modifiable CVD risk factor with still unclear prevalence in RA disease. We conducted a comprehensive study on hypertension characteristics evaluating for the first time out-of-office blood pressure (BP) in a typical contemporary RA cohort.
Methods
Assessment of office and out-of-office BP (when office systolic/diastolic BP was >129/79) and vascular studies including evaluation of aortic stiffness, carotid hypertrophy/plaques and ankle-brachial index, were performed in 214 consecutive, consenting RA patients free of CVD (aged 58.4 ± 12.3 years, 82% women). As comparators regarding office hypertension measurements, data from 214 subjects (1:1 matched for age and gender with the RA patients) derived from a cohort designed to assess the prevalence of hypertension in the general population were used.
Results
The prevalence of declared known hypertension in the RA population was 44%. Of the remaining RA patients, 2 in every 5 individuals had abnormal office BP (systolic/diastolic >139/89 mmHg), contributing to almost double the prevalence of declared/office hypertension compared to the general matched population (67% vs. 34%). Out-of-office (home or ambulatory 24 hour) BP measurements revealed that: (i) a 54% prevalence of actual hypertension in RA, in other words almost 10% of the patients were unaware of having hypertension and (ii) 29% of the RA patients with known hypertension were not well controlled. Actual hypertension was positively associated with age and body mass index, and inversely with the use of biologic drugs. Overall, almost 1 out of 5 presented the 'white coat’ phenomenon. An intermediately compromised vascular phenotype was evident in this “white coat” subgroup (lying between patients with sustained normotension and sustained hypertension) in terms of aortic stiffness, carotid hypertrophy and ankle-brachial index, even after adjustment for confounders.
Conclusion
Beyond any doubt on the basis of out-of-office evaluation, arterial hypertension in RA has a high prevalence, low awareness and poor control, as well as substantial and vascular damage-associated “white coat” phenomenon. Thus, correct diagnosis and effective treatment of hypertension is of key importance in RA for CVD risk reduction.
doi:10.1186/ar4324
PMCID: PMC3978881  PMID: 24286134
20.  Association of a Methylene Tetrahydrofolate Reductase C677T Polymorphism with Several Blood Chemical Levels in a Chinese Population 
Background: The methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism is associated with hypertension in certain populations. This study investigated the relationship between the MTHFR polymorphism and hypertension and correlated blood lipid indexes, including homocysteine (HCY), lipoprotein (a) [Lp (a)], high-density lipoprotein (HDL), low-density lipoprotein (LDL), apolipoprotein A I (Apo AI), Apo B, glucose (GLU), total cholesterol (TC), and triglyceride (TG), in a Chinese population. Materials and Methods: A total of 174 patients with hypertension and 634 healthy control individuals from Jiangxi Province were recruited between June 2012 and September 2012 for genotyping of the MTHFR C677T polymorphism using polymerase chain reaction-restriction fragment length polymorphism. Biochemical parameters were also assessed in these subjects and statistically compared to the MTHFR C677T polymorphism and the risk for hypertension. Results: HCY and Lp (a) levels were significantly higher in subjects with a MTHFR 677TT genotype than in those with a CC/CT genotype, independent of hypertension. The frequency of the TT genotype and the T allele in hypertension patients was significantly higher than in the healthy controls. Furthermore, in the male hypertension patient group, the average levels of HCY, HDL, Apo AI, and TC were significantly different from those in female hypertension patients (pHCY=0.001, pHDL=0.004, pApo AI<0.001, pTC=0.012). In the male control group, the average levels of HCY, HDL, Apo AI, GLU, and TC were significantly different from those of female controls (pHCY<0.001, pHDL<0.001, pApo AI<0.001, pGLU=0.001, and pTC=0.004). Conclusion: Our data demonstrate that the MTHFR C677T polymorphism is positively correlated with an increased risk of hypertension through an increase in HCY levels. The blood lipid correlative index was different between male and female hypertension patients and controls.
doi:10.1089/gtmb.2014.0213
PMCID: PMC4278168  PMID: 25489783
21.  Increased Circulating ANG II and TNF-α Represents Important Risk Factors in Obese Saudi Adults with Hypertension Irrespective of Diabetic Status and BMI 
PLoS ONE  2012;7(12):e51255.
Central adiposity is a significant determinant of obesity-related hypertension risk, which may arise due to the pathogenic inflammatory nature of the abdominal fat depot. However, the influence of pro-inflammatory adipokines on blood pressure in the obese hypertensive phenotype has not been well established in Saudi subjects. As such, our study investigated whether inflammatory factors may represent useful biomarkers to delineate hypertension risk in a Saudi cohort with and without hypertension and/or diabetes mellitus type 2 (DMT2). Subjects were subdivided into four groups: healthy lean controls (age: 47.9±5.1 yr; BMI: 22.9±2.1 Kg/m2), non-hypertensive obese (age: 46.1±5.0 yr; BMI: 33.7±4.2 Kg/m2), hypertensive obese (age: 48.6±6.1 yr; BMI: 36.5±7.7 Kg/m2) and hypertensive obese with DMT2 (age: 50.8±6.0 yr; BMI: 35.3±6.7 Kg/m2). Anthropometric data were collected from all subjects and fasting blood samples were utilized for biochemical analysis. Serum angiotensin II (ANG II) levels were elevated in hypertensive obese (p<0.05) and hypertensive obese with DMT2 (p<0.001) compared with normotensive controls. Systolic blood pressure was positively associated with BMI (p<0.001), glucose (p<0.001), insulin (p<0.05), HOMA-IR (p<0.001), leptin (p<0.01), TNF-α (p<0.001) and ANG II (p<0.05). Associations between ANG II and TNF-α with systolic blood pressure remained significant after controlling for BMI. Additionally CRP (p<0.05), leptin (p<0.001) and leptin/adiponectin ratio (p<0.001) were also significantly associated with the hypertension phenotype. In conclusion our data suggests that circulating pro-inflammatory adipokines, particularly ANG II and, TNF-α, represent important factors associated with a hypertension phenotype and may directly contribute to predicting and exacerbating hypertension risk.
doi:10.1371/journal.pone.0051255
PMCID: PMC3520992  PMID: 23251471
22.  Polysomnography in Patients With Obstructive Sleep Apnea 
Executive Summary
Objective
The objective of this health technology policy assessment was to evaluate the clinical utility and cost-effectiveness of sleep studies in Ontario.
Clinical Need: Target Population and Condition
Sleep disorders are common and obstructive sleep apnea (OSA) is the predominant type. Obstructive sleep apnea is the repetitive complete obstruction (apnea) or partial obstruction (hypopnea) of the collapsible part of the upper airway during sleep. The syndrome is associated with excessive daytime sleepiness or chronic fatigue. Several studies have shown that OSA is associated with hypertension, stroke, and other cardiovascular disorders; many researchers believe that these cardiovascular disorders are consequences of OSA. This has generated increasing interest in recent years in sleep studies.
The Technology Being Reviewed
There is no ‘gold standard’ for the diagnosis of OSA, which makes it difficult to calibrate any test for diagnosis. Traditionally, polysomnography (PSG) in an attended setting (sleep laboratory) has been used as a reference standard for the diagnosis of OSA. Polysomnography measures several sleep variables, one of which is the apnea-hypopnea index (AHI) or respiratory disturbance index (RDI). The AHI is defined as the sum of apneas and hypopneas per hour of sleep; apnea is defined as the absence of airflow for ≥ 10 seconds; and hypopnea is defined as reduction in respiratory effort with ≥ 4% oxygen desaturation. The RDI is defined as the sum of apneas, hypopneas, and abnormal respiratory events per hour of sleep. Often the two terms are used interchangeably. The AHI has been widely used to diagnose OSA, although with different cut-off levels, the basis for which are often unclear or arbitrarily determined. Generally, an AHI of more than five events per hour of sleep is considered abnormal and the patient is considered to have a sleep disorder. An abnormal AHI accompanied by excessive daytime sleepiness is the hallmark for OSA diagnosis. For patients diagnosed with OSA, continuous positive airway pressure (CPAP) therapy is the treatment of choice. Polysomnography may also used for titrating CPAP to individual needs.
In January 2005, the College of Physicians and Surgeons of Ontario published the second edition of Independent Health Facilities: Clinical Practice Parameters and Facility Standards: Sleep Medicine, commonly known as “The Sleep Book.” The Sleep Book states that OSA is the most common primary respiratory sleep disorder and a full overnight sleep study is considered the current standard test for individuals in whom OSA is suspected (based on clinical signs and symptoms), particularly if CPAP or surgical therapy is being considered.
Polysomnography in a sleep laboratory is time-consuming and expensive. With the evolution of technology, portable devices have emerged that measure more or less the same sleep variables in sleep laboratories as in the home. Newer CPAP devices also have auto-titration features and can record sleep variables including AHI. These devices, if equally accurate, may reduce the dependency on sleep laboratories for the diagnosis of OSA and the titration of CPAP, and thus may be more cost-effective.
Difficulties arise, however, when trying to assess and compare the diagnostic efficacy of in-home PSG versus in-lab. The AHI measured from portable devices in-home is the sum of apneas and hypopneas per hour of time in bed, rather than of sleep, and the absolute diagnostic efficacy of in-lab PSG is unknown. To compare in-home PSG with in-lab PSG, several researchers have used correlation coefficients or sensitivity and specificity, while others have used Bland-Altman plots or receiver operating characteristics (ROC) curves. All these approaches, however, have potential pitfalls. Correlation coefficients do not measure agreement; sensitivity and specificity are not helpful when the true disease status is unknown; and Bland-Altman plots measure agreement (but are helpful when the range of clinical equivalence is known). Lastly, receiver operating characteristics curves are generated using logistic regression with the true disease status as the dependent variable and test values as the independent variable. Thus, each value of the test is used as a cut-point to measure sensitivity and specificity, which are then plotted on an x-y plane. The cut-point that maximizes both sensitivity and specificity is chosen as the cut-off level to discriminate between disease and no-disease states. In the absence of a gold standard to determine the true disease status, ROC curves are of minimal value.
At the request of the Ontario Health Technology Advisory Committee (OHTAC), MAS has thus reviewed the literature on PSG published over the last two years to examine new developments.
Methods
Review Strategy
There is a large body of literature on sleep studies and several reviews have been conducted. Two large cohort studies, the Sleep Heart Health Study and the Wisconsin Sleep Cohort Study, are the main sources of evidence on sleep literature.
To examine new developments on PSG published in the past two years, MEDLINE, EMBASE, MEDLINE In-Process & Other Non-Indexed Citations, the Cochrane Database of Systematic Reviews and Cochrane CENTRAL, INAHTA, and websites of other health technology assessment agencies were searched. Any study that reported results of in-home or in-lab PSG was included. All articles that reported findings from the Sleep Heart Health Study and the Wisconsin Sleep Cohort Study were also reviewed.
Diffusion of Sleep Laboratories
To estimate the diffusion of sleep laboratories, a list of sleep laboratories licensed under the Independent Health Facility Act was obtained. The annual number of sleep studies per 100,000 individuals in Ontario from 2000 to 2004 was also estimated using administrative databases.
Summary of Findings
Literature Review
A total of 315 articles were identified that were published in the past two years; 227 were excluded after reviewing titles and abstracts. A total of 59 articles were identified that reported findings of the Sleep Heart Health Study and the Wisconsin Sleep Cohort Study.
Prevalence
Based on cross-sectional data from the Wisconsin Sleep Cohort Study of 602 men and women aged 30 to 60 years, it is estimated that the prevalence of sleep-disordered breathing is 9% in women and 24% in men, on the basis of more than five AHI events per hour of sleep. Among the women with sleep disorder breathing, 22.6% had daytime sleepiness and among the men, 15.5% had daytime sleepiness. Based on this, the prevalence of OSA in the middle-aged adult population is estimated to be 2% in women and 4% in men.
Snoring is present in 94% of OSA patients, but not all snorers have OSA. Women report daytime sleepiness less often compared with their male counterparts (of similar age, body mass index [BMI], and AHI). Prevalence of OSA tends to be higher in older age groups compared with younger age groups.
Diagnostic Value of Polysomnography
It is believed that PSG in the sleep laboratory is more accurate than in-home PSG. In the absence of a gold standard, however, claims of accuracy cannot be substantiated. In general, there is poor correlation between PSG variables and clinical variables. A variety of cut-off points of AHI (> 5, > 10, and > 15) are arbitrarily used to diagnose and categorize severity of OSA, though the clinical importance of these cut-off points has not been determined.
Recently, a study of the use of a therapeutic trial of CPAP to diagnose OSA was reported. The authors studied habitual snorers with daytime sleepiness in the absence of other medical or psychiatric disorders. Using PSG as the reference standard, the authors calculated the sensitivity of this test to be 80% and its specificity to be 97%. Further, they concluded that PSG could be avoided in 46% of this population.
Obstructive Sleep Apnea and Obesity
Obstructive sleep apnea is strongly associated with obesity. Obese individuals (BMI >30 kg/m2) are at higher risk for OSA compared with non-obese individuals and up to 75% of OSA patients are obese. It is hypothesized that obese individuals have large deposits of fat in the neck that cause the upper airway to collapse in the supine position during sleep. The observations reported from several studies support the hypothesis that AHIs (or RDIs) are significantly reduced with weight loss in obese individuals.
Obstructive Sleep Apnea and Cardiovascular Diseases
Associations have been shown between OSA and comorbidities such as diabetes mellitus and hypertension, which are known risk factors for myocardial infarction and stroke. Patients with more severe forms of OSA (based on AHI) report poorer quality of life and increased health care utilization compared with patients with milder forms of OSA. From animal models, it is hypothesized that sleep fragmentation results in glucose intolerance and hypertension. There is, however, no evidence from prospective studies in humans to establish a causal link between OSA and hypertension or diabetes mellitus. It is also not clear that the associations between OSA and other diseases are independent of obesity; in most of these studies, patients with higher values of AHI had higher values of BMI compared with patients with lower AHI values.
A recent meta-analysis of bariatric surgery has shown that weight loss in obese individuals (mean BMI = 46.8 kg/m2; range = 32.30–68.80) significantly improved their health profile. Diabetes was resolved in 76.8% of patients, hypertension was resolved in 61.7% of patients, hyperlipidemia improved in 70% of patients, and OSA resolved in 85.7% of patients. This suggests that obesity leads to OSA, diabetes, and hypertension, rather than OSA independently causing diabetes and hypertension.
Health Technology Assessments, Guidelines, and Recommendations
In April 2005, the Centers for Medicare and Medicaid Services (CMS) in the United States published its decision and review regarding in-home and in-lab sleep studies for the diagnosis and treatment of OSA with CPAP. In order to cover CPAP, CMS requires that a diagnosis of OSA be established using PSG in a sleep laboratory. After reviewing the literature, CMS concluded that the evidence was not adequate to determine that unattended portable sleep study was reasonable and necessary in the diagnosis of OSA.
In May 2005, the Canadian Coordinating Office of Health Technology Assessment (CCOHTA) published a review of guidelines for referral of patients to sleep laboratories. The review included 37 guidelines and associated reviews that covered 18 applications of sleep laboratory studies. The CCOHTA reported that the level of evidence for many applications was of limited quality, that some cited studies were not relevant to the recommendations made, that many recommendations reflect consensus positions only, and that there was a need for more good quality studies of many sleep laboratory applications.
Diffusion
As of the time of writing, there are 97 licensed sleep laboratories in Ontario. In 2000, the number of sleep studies performed in Ontario was 376/100,000 people. There was a steady rise in sleep studies in the following years such that in 2004, 769 sleep studies per 100,000 people were performed, for a total of 96,134 sleep studies. Based on prevalence estimates of the Wisconsin Sleep Cohort Study, it was estimated that 927,105 people aged 30 to 60 years have sleep-disordered breathing. Thus, there may be a 10-fold rise in the rate of sleep tests in the next few years.
Economic Analysis
In 2004, approximately 96,000 sleep studies were conducted in Ontario at a total cost of ~$47 million (Cdn). Since obesity is associated with sleep disordered breathing, MAS compared the costs of sleep studies to the cost of bariatric surgery. The cost of bariatric surgery is $17,350 per patient. In 2004, Ontario spent $4.7 million per year for 270 patients to undergo bariatric surgery in the province, and $8.2 million for 225 patients to seek out-of-country treatment. Using a Markov model, it was concluded that shifting costs from sleep studies to bariatric surgery would benefit more patients with OSA and may also prevent health consequences related to diabetes, hypertension, and hyperlipidemia. It is estimated that the annual cost of treating comorbid conditions in morbidly obese patients often exceeds $10,000 per patient. Thus, the downstream cost savings could be substantial.
Considerations for Policy Development
Weight loss is associated with a decrease in OSA severity. Treating and preventing obesity would also substantially reduce the economic burden associated with diabetes, hypertension, hyperlipidemia, and OSA. Promotion of healthy weights may be achieved by a multisectorial approach as recommended by the Chief Medical Officer of Health for Ontario. Bariatric surgery has the potential to help morbidly obese individuals (BMI > 35 kg/m2 with an accompanying comorbid condition, or BMI > 40 kg/m2) lose weight. In January 2005, MAS completed an assessment of bariatric surgery, based on which OHTAC recommended an improvement in access to these surgeries for morbidly obese patients in Ontario.
Habitual snorers with excessive daytime sleepiness have a high pretest probability of having OSA. These patients could be offered a therapeutic trial of CPAP to diagnose OSA, rather than a PSG. A majority of these patients are also obese and may benefit from weight loss. Individualized weight loss programs should, therefore, be offered and patients who are morbidly obese should be offered bariatric surgery.
That said, and in view of the still evolving understanding of the causes, consequences and optimal treatment of OSA, further research is warranted to identify which patients should be screened for OSA.
PMCID: PMC3379160  PMID: 23074483
23.  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
24.  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
25.  Cardiovascular mortality among a cohort of hypertensive and normotensives in Rio de Janeiro - Brazil - 1991–2009 
BMC Public Health  2015;15:623.
Background
Although there is strong evidence of the benefits of antihypertensive treatment, the high prevalence of this important cardiovascular risk factor and its complications, as well as the low control rates of hypertension observed in many studies justify the investigation of these relationships in population studies. The objective was to investigate the ratio of cardiovascular disease mortality between hypertensives (non-treated, controlled and uncontrolled) and non-hypertensives in a cohort of a population sample of adults living in Ilha do Governador, Rio de Janeiro state, Brazil, who were classified in a survey conducted in 1991 and 1992 and whose death certificates were sought 19 years later.
Methods
A cohort study was performed on probabilistic linkage between data from an epidemiological study of hypertension performed in Ilha do Governador, in Rio de Janeiro, Brazil (1991 to 1992) and data from the Mortality Information System of Rio de Janeiro (1991 to 2009). The survey aimed to estimate the prevalence of hypertension and other cardiovascular risk factors in 1,270 adults aged 20 years or older selected through a probabilistic sampling of households at three economic levels (low, middle and high income). We performed a probabilistic record linkage of these databases and estimated the risk of cardiovascular death using Kaplan-Meier method to plot survival curves and Cox proportional hazards models comparing hypertensive subjects all together, and by hypertension subgroups: untreated, controlled, and uncontrolled hypertensives with non-hypertensive ones.
Results
A total of 170 deaths occurred, of which 31.2 % attributed to cardiovascular causes. The hazard ratio for cardiovascular death was 6.1 times higher (95 % CI 2.7 – 13.7) in uncontrolled hypertensive patients relative to non-hypertensive patients. The hazard ratios for untreated hypertensive and controlled hypertensive patients were 2.7 times (95 % CI 1.1 – 6.3) and 2.1 times (95 % CI 0.38 – 11.5) higher than for normotensive patients, respectively.
Conclusion
The present study demonstrated a higher cardiovascular death risk among hypertensive than among non-hypertensive ones that is not associated uniquely to treatment, because uncontrolled hypertensives demonstrated a greater risk than untreated ones. Although the subgroups of hypertensive individuals were susceptible to changes in their classification over the 19 years of the study, the baseline classification was consistent with a worse prognosis in these individuals.
doi:10.1186/s12889-015-1999-4
PMCID: PMC4495630  PMID: 26152148
Hypertension; Blood pressure; Cardiovascular diseases; Mortality; Survival analysis; Proportional hazards models

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