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1.  Effects of simvastatin on blood pressure in hypercholesterolemic patients: An open-label study in patients with hypertension or normotension 
Background
Simvastatin has been reported to improve endotheliumdependent vascular relaxation in patients with hypercholesterolemia. The consequent decrease in arterial stiffness might be associated with a decrease in blood pressure (BP).
Objective
The aim of this study was to determine whether simvastatin 20 and 40 mg/d have an effect on systolic and diastolic blood pressure (SBP and DBP, respectively) in patients with hypercholesterolemia, and, if so, whether the effect is dose dependent and/or is related to the changes in the serum lipid profile.
Methods
This 6-month, open-label study was conducted at the Lipid Clinics of the Department of Internal Medicine, University of Milan, Maggiore Hospital IRCCS, and of the Department of Internal Medicine 1, G. Salvini Hospital, Garbagnate Milanese (Milan, Italy). Patients aged 18 to 80 years with primary hypercholesterolemia who were following a low-fat, low-cholesterol diet for >2 months before the study were enrolled. Patients at high risk for cardiovascular disease (CVD), according to the National Cholesterol Education Program Adult Treatment Panel II guidelines, were given simvastatin 20 mg (tablet) QD for 3 months, and those at low risk for CVD continued with diet only for 3 months (controls). Efficacy variables included body weight, SBP, DBP, and serum lipid levels (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high density lipoprotein cholesterol [HDL-C], and triglycerides [TG]). At 3 months, patients in the simvastatin + diet group who reached their therapeutic goal continued to receive simvastatin 20 mg/d for 3 additional months. In simvastatintreated patients who were normotensive at baseline or who became normotensive at 3 months but who did not reach the therapeutic goal, the simvastatin dosage was increased to 40 mg/d. Patients in both groups who remained hypertensive at 3 months were switched to hypotensive therapy. In the diet-only group, patients who were formerly normotensive or who became normotensive at 3 months but who did not reach their therapeutic goal continued with diet only or started lipid-lowering therapy. All other patients in the diet-only group continued to be treated with diet only, for 3 additional months. Efficacy variables were measured again at 6 months. Tolerability of simvastatin was assessed at each visit using patient interview and measurement of serum aminotransferase and creatine phosphokinase levels.
Results
The study population comprised 222 patients (132 women, 90 men; mean [SEM] age, 53.9 [0.95] years [range, 23–76 years]); 115 high-risk patients (57 with untreated stage 1 hypertension) were assigned to the simvastatin + diet group, and 107 low-risk patients (29 with untreated stage 1 hypertension) were assigned to the diet-only group. In the simvastatin group, after 3 months of therapy, mean SBP was decreased by 3.9 (1.49) mm Hg (change, −2.9%), mean DBP decreased by 3.0 (0.87) mm Hg (change, −3.7%), mean TC decreased by 90.6 (3.98) mg/dL (change, −27.0%), mean LDL-C decreased by 88.9 (3.88) mg/dL (change, −35.6%), and mean TG decreased by 26.3 (7.34) mg/dL (change, −15.8%) (all, P < 0.001). Mean HDL-C increased by 3.6 (1.16) mg/dL (change, 6.9%; P < 0.001). The BP-lowering effect was found only in patients with hypertension at baseline (n = 57); in these patients, mean SBP decreased by 7.2 (2.44) mm Hg (change, −4.8%; P < 0.005 vs baseline) and DBP decreased by 4.8 (1.29) mm Hg (change, −5.6%; P < 0.001 vs baseline). Also in the simvastatin group, 26 patients (22.6%) achieved their target SBP/DBP. In patients with normotension at baseline (n = 58), neither SBP nor DBP was changed significantly (changes, −0.8 [1.65] and −1.4 [1.15] mm Hg, respectively [−0.6% and −1.8%, respectively]). The changes in serum lipid levels were similar between hypertensive and normotensive patients in the simvastatin group. Forty-one patients (18 hypertensive and 23 normotensive at baseline) were treated with simvastatin 40 mg/d plus diet between months 3 and 6. At 6 months, no further significant decrease was observed in mean BP. In contrast, the expected dose-dependent response was observed for TC and LDL-C levels. In the diet-only group, no significant changes occurred in BP or serum lipid levels. Changes in BP, TC, LDL-C, TG, and HDL-C were significantly greater in the simvastatin + diet group than in the diet-only group (all, P < 0.001). Body weight did not change significantly in either group.
Conclusions
In this group of patients with hypercholesterolemia, the starting dosage of simvastatin (20 mg/d) was associated with reductions in SBP and DBP within 3 months of treatment in patients with hypertension, and this effect was independent of the lipid-lowering properties of the drug. Although the decrease in BP was modest, it is likely clinically relevant. Further studies on this topic are advisable.
doi:10.1016/S0011-393X(04)80057-2
PMCID: PMC3964554  PMID: 24672080
2.  Pre-hypertension in Uganda: a cross-sectional study 
Background
Persons with a systolic blood pressure (BP) of 120 to < 140 or diastolic BP of 80 to < 90 mm hg are classified as having pre-hypertension. Pre-hypertension is associated with cardiovascular disease (CVD) risk factors, incident CVD and CVD mortality. Understanding determinants of pre-hypertension especially in low income countries is a pre-requisite for improved prevention and control.
Methods
Data were analyzed for 4142 persons aged 18 years and older with BP measured in a community cross sectional survey in Uganda. The prevalence of pre-hypertension was estimated and a number of risk factors e.g. smoking, use of alcohol, overweight, obesity, physical activity, sex, age, marital status, place of residence, and consumption of vegetables and fruits were compared among different groups (normotension, pre-hypertension, and hypertension) using bivariate and multivariable logistic regression.
Results
The age standardized prevalence of normal blood pressure was 37.6%, pre-hypertension 33.9%, hypertension 28.5% and raised blood pressure 62%. There was no difference between the prevalence of hypertension among women compared to men (28.9% versus 27.9%). However, the prevalence of pre-hypertension was higher among men (41.6%) compared to women (29.4%). Compared to people with normal blood pressure, the risk of pre-hypertension was increased by being 40 years and above, smoking, consumption of alcohol, not being married, being male and being overweight or obese. Compared to pre-hypertension, hypertension was more likely if one was more than 40 years, had infrequent or no physical activity, resided in an urban area, and was obese or overweight.
Conclusions
More than one in three of adults in this population had pre-hypertension. Preventive and public health interventions that reduce the prevalence of raised blood pressure need to be implemented.
doi:10.1186/1471-2261-13-101
PMCID: PMC3833647  PMID: 24228945
Cardiovascular diseases; Non communicable diseases; Low income countries; Risk factors; Prevalence
3.  Younger age of escalation of cardiovascular risk factors in Asian Indian subjects 
Background
Cardiovascular risk factors start early, track through the young age and manifest in middle age in most societies. We conducted epidemiological studies to determine prevalence and age-specific trends in cardiovascular risk factors among adolescent and young urban Asian Indians.
Methods
Population based epidemiological studies to identify cardiovascular risk factors were performed in North India in 1999–2002. We evaluated major risk factors-smoking or tobacco use, obesity, truncal obesity, hypertension, dysglycemia and dyslipidemia using pre-specified definitions in 2051 subjects (male 1009, female 1042) aged 15–39 years of age. Age-stratified analyses were performed and significance of trends determined using regression analyses for numerical variables and Χ2 test for trend for categorical variables. Logistic regression was used to identify univariate and multivariate odds ratios (OR) for correlation of age and risk factors.
Results
In males and females respectively, smoking or tobacco use was observed in 200 (11.8%) and 18 (1.4%), overweight or obesity (body mass index, BMI ≥ 25 kg/m2) in 12.4% and 14.3%, high waist-hip ratio, WHR (males > 0.9, females > 0.8) in 15% and 32.3%, hypertension in 5.6% and 3.1%, high LDL cholesterol (≥ 130 mg/dl) in 9.4% and 8.9%, low HDL cholesterol (<40 mg/dl males, <50 mg/dl females) in 16.2% and 49.7%, hypertriglyceridemia (≥ 150 mg/dl) in 9.7% and 6%, diabetes in 1.0% and 0.4% and the metabolic syndrome in 3.4% and 3.6%. Significantly increasing trends with age for indices of obesity (BMI, waist, WHR), glycemia (fasting glucose, metabolic syndrome) and lipids (cholesterol, LDL cholesterol, HDL cholesterol) were observed (p for trend < 0.01). At age 15–19 years the prevalence (%) of risk factors in males and females, respectively, was overweight/obesity in 7.6, 8.8; high WHR 4.9, 14.4; hypertension 2.3, 0.3; high LDL cholesterol 2.4, 3.2; high triglycerides 3.0, 3.2; low HDL cholesterol 8.0, 45.3; high total:HDL ratio 3.7, 4.7, diabetes 0.0 and metabolic syndrome in 0.0, 0.2 percent. At age groups 20–29 years in males and females, ORs were, for smoking 5.3, 1.0; obesity 1.6, 0.8; truncal obesity 4.5, 3.1; hypertension 2.6, 4.8; high LDL cholesterol 6.4, 1.8; high triglycerides 3.7, 0.9; low HDL cholesterol 2.4, 0.8; high total:HDL cholesterol 1.6, 1.0; diabetes 4.0, 1.0; and metabolic syndrome 37.7, 5.7 (p < 0.05 for some). At age 30–39, ORs were- smoking 16.0, 6.3; overweight 7.1, 11.3; truncal obesity 21.1, 17.2; hypertension 13.0, 64.0; high LDL cholesterol 27.4, 19.5; high triglycerides 24.2, 10.0; low HDL cholesterol 15.8, 14.1; high total:HDL cholesterol 37.9, 6.10; diabetes 50.7, 17.4; and metabolic syndrome 168.5, 146.2 (p < 0.01 for all parameters). Multivariate adjustment for BMI, waist size and WHR in men and women aged 30–39 years resulted in attenuation of ORs for hypertension and dyslipidemias.
Conclusion
Low prevalence of multiple cardiovascular risk factors (smoking, hypertension, dyslipidemias, diabetes and metabolic syndrome) in adolescents and rapid escalation of these risk factors by age of 30–39 years is noted in urban Asian Indians. Interventions should focus on these individuals.
doi:10.1186/1471-2261-9-28
PMCID: PMC2713196  PMID: 19575817
4.  High prevalence of undiagnosed diabetes and abnormal glucose tolerance in the Iranian urban population: Tehran Lipid and Glucose Study 
BMC Public Health  2008;8:176.
Background
To estimate the prevalence of diagnosed and undiagnosed diabetes mellitus, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and combined IFG/IGT in a large urban Iranian population aged ≥ 20 years.
Methods
The study population included 9,489 participants of the Tehran Lipid and Glucose Study with full relevant clinical data. Age-standardized prevalence of diabetes and glucose intolerance categories were reported according to the 2003 American Diabetes Association definitions. Age-adjusted logistic regression models were used to estimate the numbers needed to screen (NNTS) to find one person with undiagnosed diabetes.
Results
The prevalence of diagnosed and undiagnosed diabetes, isolated IFG, isolated IGT, and combined IFG/IGT were 8.1%, 5.1%, 8.7%, 5.4% and 4.0% in men and 10%, 4.7%, 6.3%, 7.6%, and 4.5% in women respectively. Participants with undiagnosed diabetes had higher age, body mass index (BMI), waist circumference, systolic and diastolic blood pressures, triglycerides (all p values <0.001) and lower HDL-cholesterol (only in women, p < 0.01) compared to normoglycemic subjects. Undiagnosed diabetes was associated with family history of diabetes, increased BMI (≥ 25 kg/m2), abdominal obesity, hypertriglyceridemia, hypertension and low HDL-cholesterol levels. Among men, a combination of increased BMI, hypertension, and family history of diabetes led to a NNTS of 1.6 (95% CI: 1.57–1.71) and among women a combination of family history of diabetes and abdominal obesity, yielded a NNTS of 2.2 (95% CI: 2.1–2.4).
Conclusion
In conclusion, about one third of Tehranian adults had disturbed glucose tolerance or diabetes. One- third of total cases with diabetes were undiagnosed. Screening individuals with BMI ≥ 25 kg/m2 (men), hypertension (men), abdominal obesity (women) and family history of diabetes may be more efficient.
doi:10.1186/1471-2458-8-176
PMCID: PMC2413226  PMID: 18501007
5.  Impact of Hypertension on the Association of BMI with Risk and Age at Onset of Type 2 Diabetes Mellitus: Age- and Gender-Mediated Modifications 
PLoS ONE  2014;9(4):e95308.
Aims
Given that BMI correlates with risk of Type 2 diabetes mellitus (T2DM), and that hypertension is a common comorbid condition, we hypothesize that hypertension augments significantly the impact of obesity on T2DM onset.
Methods
We obtained data on T2DM in Kuwaiti natives from Kuwait Health Network Registry. We considered 1339 comorbid individuals with onset of hypertension preceding that of T2DM, and 3496 non-hypertensive individuals but with T2DM. Multiple linear regressions, ANOVA tests, and Cox proportional hazards models were used to quantify the impact of hypertension on correlation of BMI with age at onset and risk of T2DM.
Results
Impact of increasing levels of BMI on age at onset ot T2DM is seen augmented in patients diagnosed with hypertension. We find that the slope of the inverse linear relationship between BMI and onset age of T2DM is much steep in hypertensive patients (−0.69, males and −0.39, females) than in non-hypertensive patients (−0.36, males and −0.17, females). The decline in onset age for an unit increase of BMI is two-fold in males than in females. Upon considering BMI as a categorical variable, we find that while the mean onset age of T2DM in hypertensive patients decreases by as much as 5–12 years in every higher BMI categories, significant decrease in non-hypertensive patients exists only when severely obese. Hazard due to hypertension (against the baseline of non-hypertension and normal weight) increases at least two-fold in every obese category. While males have higher hazard due to hypertension in early adulthood, females have higher hazard in late adulthood.
Conclusion
Pre-existing condition of hypertension augments the association of BMI with Type 2 diabetes onset in both males and females. The presented results provide health professionals directives on the extent of weight-loss required to delay onset of Type 2 diabetes in hypertensive versus non-hypertensive patients.
doi:10.1371/journal.pone.0095308
PMCID: PMC3990699  PMID: 24743162
6.  Obesity and elevated blood pressure among adolescents in Lagos, Nigeria: a cross-sectional study 
BMC Public Health  2012;12:616.
Background
Childhood obesity and associated hypertension are major public health concerns globally. This study aimed to determine the prevalence of obesity and the associated risk of high blood pressure among Nigerian adolescents.
Methods
A cross-sectional school-based study of 885 apparently healthy adolescents was performed. Weight, height and blood pressure (BP) were measured using standard methods. Body mass index (BMI) was calculated and categorized by age, sex and percentile. Obesity and overweight were defined as: ≥ 95th and 85th to < 95th percentiles, respectively, for age, sex and height. Subjects were sub-categorized into age 10–13 years (A) and 14–17 years (B). The odds ratio for pre-hypertensive and hypertensive range BP by age and BMI were generated. Significance was set at P < 0.05.
Results
The prevalence of overweight and obesity were 13.8% and 9.4%, respectively. The prevalence of hypertensive range systolic BP in obese versus normal BMI females was 16% versus 23% (p=0.00) and 12.1% versus 6.4% (p=0.27) in males. The prevalence of hypertensive range diastolic BP in obese versus normal BMI females was 12% versus 1.4% (p=0.00) and 15.2% versus 3.5% (p=0.01) in males. BMI in group B was significantly associated with pre-hypertensive and hypertensive range systolic BP in overweight (P = 0.01, P = 0.002) and obese subjects (P = 0.00, P = 0.00) and with hypertensive range diastolic BP (P = 0.00) only in obese subjects. The only significant association in group A was between obesity and pre-hypertensive range diastolic BP (P = 0.00).
Conclusion
The prevalence of hypertensive range BP among obese Nigerian adolescents was high. Screening for childhood obesity and hypertension, and long-term follow-up of obese adolescents into adulthood are recommended.
doi:10.1186/1471-2458-12-616
PMCID: PMC3490830  PMID: 22867531
Adolescents; Blood pressure; Body mass index; Obesity; Overweight
7.  Risk Stratification by Self-Measured Home Blood Pressure across Categories of Conventional Blood Pressure: A Participant-Level Meta-Analysis 
PLoS Medicine  2014;11(1):e1001591.
Jan Staessen and colleagues compare the risk of cardiovascular, cardiac, or cerebrovascular events in patients with elevated office blood pressure vs. self-measured home blood pressure.
Please see later in the article for the Editors' Summary
Background
The Global Burden of Diseases Study 2010 reported that hypertension is worldwide the leading risk factor for cardiovascular disease, causing 9.4 million deaths annually. We examined to what extent self-measurement of home blood pressure (HBP) refines risk stratification across increasing categories of conventional blood pressure (CBP).
Methods and Findings
This meta-analysis included 5,008 individuals randomly recruited from five populations (56.6% women; mean age, 57.1 y). All were not treated with antihypertensive drugs. In multivariable analyses, hazard ratios (HRs) associated with 10-mm Hg increases in systolic HBP were computed across CBP categories, using the following systolic/diastolic CBP thresholds (in mm Hg): optimal, <120/<80; normal, 120–129/80–84; high-normal, 130–139/85–89; mild hypertension, 140–159/90–99; and severe hypertension, ≥160/≥100.
Over 8.3 y, 522 participants died, and 414, 225, and 194 had cardiovascular, cardiac, and cerebrovascular events, respectively. In participants with optimal or normal CBP, HRs for a composite cardiovascular end point associated with a 10-mm Hg higher systolic HBP were 1.28 (1.01–1.62) and 1.22 (1.00–1.49), respectively. At high-normal CBP and in mild hypertension, the HRs were 1.24 (1.03–1.49) and 1.20 (1.06–1.37), respectively, for all cardiovascular events and 1.33 (1.07–1.65) and 1.30 (1.09–1.56), respectively, for stroke. In severe hypertension, the HRs were not significant (p≥0.20). Among people with optimal, normal, and high-normal CBP, 67 (5.0%), 187 (18.4%), and 315 (30.3%), respectively, had masked hypertension (HBP≥130 mm Hg systolic or ≥85 mm Hg diastolic). Compared to true optimal CBP, masked hypertension was associated with a 2.3-fold (1.5–3.5) higher cardiovascular risk. A limitation was few data from low- and middle-income countries.
Conclusions
HBP substantially refines risk stratification at CBP levels assumed to carry no or only mildly increased risk, in particular in the presence of masked hypertension. Randomized trials could help determine the best use of CBP vs. HBP in guiding BP management. Our study identified a novel indication for HBP, which, in view of its low cost and the increased availability of electronic communication, might be globally applicable, even in remote areas or in low-resource settings.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Globally, hypertension (high blood pressure) is the leading risk factor for cardiovascular disease and is responsible for 9.4 million deaths annually from heart attacks, stroke, and other cardiovascular diseases. Hypertension, which rarely has any symptoms, is diagnosed by measuring blood pressure, the force that blood circulating in the body exerts on the inside of large blood vessels. Blood pressure is highest when the heart is pumping out blood (systolic blood pressure) and lowest when the heart is refilling (diastolic blood pressure). European guidelines define optimal blood pressure as a systolic blood pressure of less than 120 millimeters of mercury (mm Hg) and a diastolic blood pressure of less than 80 mm Hg (a blood pressure of less than 120/80 mm Hg). Normal blood pressure, high-normal blood pressure, and mild hypertension are defined as blood pressures in the ranges 120–129/80–84 mm Hg, 130–139/85–89 mm Hg, and 140–159/90–99 mm Hg, respectively. A blood pressure of more than 160 mm Hg systolic or 100 mm Hg diastolic indicates severe hypertension. Many factors affect blood pressure; overweight people and individuals who eat salty or fatty food are at high risk of developing hypertension. Lifestyle changes and/or antihypertensive drugs can be used to control hypertension.
Why Was This Study Done?
The current guidelines for the diagnosis and management of hypertension recommend risk stratification based on conventionally measured blood pressure (CBP, the average of two consecutive measurements made at a clinic). However, self-measured home blood pressure (HBP) more accurately predicts outcomes because multiple HBP readings are taken and because HBP measurement avoids the “white-coat effect”—some individuals have a raised blood pressure in a clinical setting but not at home. Could risk stratification across increasing categories of CBP be refined through the use of self-measured HBP, particularly at CBP levels assumed to be associated with no or only mildly increased risk? Here, the researchers undertake a participant-level meta-analysis (a study that uses statistical approaches to pool results from individual participants in several independent studies) to answer this question.
What Did the Researchers Do and Find?
The researchers included 5,008 individuals recruited from five populations and enrolled in the International Database of Home Blood Pressure in Relation to Cardiovascular Outcome (IDHOCO) in their meta-analysis. CBP readings were available for all the participants, who measured their HBP using an oscillometric device (an electronic device for measuring blood pressure). The researchers used information on fatal and nonfatal cardiovascular, cardiac, and cerebrovascular (stroke) events to calculate the hazard ratios (HRs, indicators of increased risk) associated with a 10-mm Hg increase in systolic HBP across standard CBP categories. In participants with optimal CBP, an increase in systolic HBP of 10-mm Hg increased the risk of any cardiovascular event by nearly 30% (an HR of 1.28). Similar HRs were associated with a 10-mm Hg increase in systolic HBP for all cardiovascular events among people with normal and high-normal CBP and with mild hypertension, but for people with severe hypertension, systolic HBP did not significantly add to the prediction of any end point. Among people with optimal, normal, and high-normal CBP, 5%, 18.4%, and 30.4%, respectively, had a HBP of 130/85 or higher (“masked hypertension,” a higher blood pressure in daily life than in a clinical setting). Finally, compared to individuals with optimal CBP without masked hypertension, individuals with masked hypertension had more than double the risk of cardiovascular disease.
What Do These Findings Mean?
These findings indicate that HBP measurements, particularly in individuals with masked hypertension, refine risk stratification at CBP levels assumed to be associated with no or mildly elevated risk of cardiovascular disease. That is, HBP measurements can improve the prediction of cardiovascular complications or death among individuals with optimal, normal, and high-normal CBP but not among individuals with severe hypertension. Clinical trials are needed to test whether the identification and treatment of masked hypertension leads to a reduction of cardiovascular complications and is cost-effective compared to the current standard of care, which does not include HBP measurements and does not treat people with normal or high-normal CBP. Until then, these findings provide support for including HBP monitoring in primary prevention strategies for cardiovascular disease among individuals at risk for masked hypertension (for example, people with diabetes), and for carrying out HBP monitoring in people with a normal CBP but unexplained signs of hypertensive target organ damage.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001591.
This study is further discussed in a PLOS Medicine Perspective by Mark Caulfield
The US National Heart, Lung, and Blood Institute has patient information about high blood pressure (in English and Spanish) and a guide to lowering high blood pressure that includes personal stories
The American Heart Association provides information on high blood pressure and on cardiovascular diseases (in several languages); it also provides personal stories about dealing with high blood pressure
The UK National Health Service Choices website provides detailed information for patients about hypertension (including a personal story) and about cardiovascular disease
The World Health Organization provides information on cardiovascular disease and controlling blood pressure; its A Global Brief on Hypertension was published on World Health Day 2013
The UK charity Blood Pressure UK provides information about white-coat hypertension and about home blood pressure monitoring
MedlinePlus provides links to further information about high blood pressure, heart disease, and stroke (in English and Spanish)
doi:10.1371/journal.pmed.1001591
PMCID: PMC3897370  PMID: 24465187
8.  1999–2009 Trends in Prevalence, Unawareness, Treatment and Control of Hypertension in Geneva, Switzerland 
PLoS ONE  2012;7(6):e39877.
Background
There are no time trends in prevalence, unawareness, treatment, and control of hypertension in Switzerland. The objective of this study was to analyze these trends and to determine the associated factors.
Methods/Findings
Population-based study conducted in the Canton of Geneva, Switzerland, between 1999 and 2009. Blood pressure was measured thrice using a standard protocol. Hypertension was defined as mean systolic or diastolic blood pressure ≥140/90 mmHg or self-reported hypertension or anti-hypertensive medication. Unawareness, untreated and uncontrolled hypertension was determined by questionnaires/blood pressure measurements. Yearly age-standardized prevalences and adjusted associations for the 1999–2003 and 2004–2009 survey periods were reported. The 10-year survey included 9,215 participants aged 35 to 74 years. Hypertension remained stable (34.4%). Hypertension unawareness decreased from 35.9% to 17.7% (P<0.001). The decrease in hypertension unawareness was not paralleled by a concomitant absolute increase in hypertension treatment, which remained low (38.2%). A larger proportion of all hypertensive participants were aware but not treated in 2004–2009 (43.7%) compared to 1999–2003 (33.1%). Uncontrolled hypertension improved from 62.2% to 40.6% between 1999 and 2009 (P = 0.02). In 1999–2003 period, factors associated with hypertension unawareness were current smoking (OR = 1.27, 95%CI, 1.02–1.59), male gender (OR = 1.56, 1.27–1.92), hypercholesterolemia (OR = 1.31, 1.20–1.44), and older age (OR 65–74yrs vs 35–49yrs  = 1.56, 1.21–2.02). In 1999–2003 and 2004–2009, obesity and diabetes were negatively associated with hypertension unawareness, high education was associated with untreated hypertension (OR = 1.45, 1.12–1.88 and 1.42, 1.02–1.99, respectively), and male gender with uncontrolled hypertension (OR = 1.49, 1.03–2.17 and 1.65, 1.08–2.50, respectively). Sedentarity was associated with higher risk of hypertension and uncontrolled hypertension in 1999–2003.
Conclusions
Hypertension prevalence remained stable since 1999 in the canton of Geneva. Although hypertension unawareness substantially decreased, more than half of hypertensive subjects still remained untreated or uncontrolled in 2004–2009. This study identified determinants that should guide interventions aimed at improving hypertension treatment and control.
doi:10.1371/journal.pone.0039877
PMCID: PMC3384604  PMID: 22761919
9.  The prevalence of pre-hypertension and its association to established cardiovascular risk factors in south of Iran 
BMC Research Notes  2012;5:386.
Background
Pre-hypertension is associated with an increased risk of the development of hypertension and subsequent cardiovascular disease and raises mortality risk. The aim of this study was to determine the prevalence of pre-hypertension and to explore the associations between pre-hypertension and established cardiovascular risk factors in a population-based sample of Iranian adults.
Methods
In this cross-sectional study a representative sample of 892 participants aged ≥30 years was selected using a multistage cluster sampling method. After completion of a detailed demographic and medical questionnaire (gender, age, history of diabetes mellitus and hypertension, taking antihypertensive or hypoglycemic agents and history of smoking), all participants were subjected to physical examination, blood lipid profile, blood glucose, anthropometric and smoking assessments, during the years 2009 and 2010. Variables were considered significant at a p-value ≤ 0.05. Statistical analysis was performed using SPSS version 11.5 software.
Results
Pre-hypertension was observed among 300 (33.7%) subjects, 36.4% for men and 31.4% for women (p > 0.05). The pre-hypertensive group had higher levels of blood glucose and triglycerides, higher body mass index and lower percentage of smoking than did the normotensive group. Multivariate logistic regression analysis showed that obesity and overweight were the strongest predictors of pre-hypertension [odds ratio, 2.74: 95% CI (Confidence Interval), 1.62 to 4.62 p < 0.001; odds ratio, 2.56, 95% CI, 1.74 to 3.77, p < 0.001 respectively].
Conclusions
Overweight and obesity are major determinants of the high prevalence rate of pre-hypertension detected in Iranian population. Therefore, primary prevention strategies should concentrate on reducing overweight and obesity if the increased prevalence of pre-hypertension is to be diminished in Iranian adults.
doi:10.1186/1756-0500-5-386
PMCID: PMC3506467  PMID: 22838639
Pre-hypertension; Cardiovascular risk factor; Obesity; BMI
10.  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
11.  Study of urban community survey in India: growing trend of high prevalence of hypertension in a developing country 
The prevalence pattern of hypertension in developing countries is different from that in the developed countries. In India, a very large, populous and typical developing country, community surveys have documented that between three and six decades, prevalence of hypertension has increased by about 30 times among urban dwellers and by about 10 times among the rural inhabitants. Various factors might have contributed to this rising trend and among others, consequences of urbanization such as change in life style pattern, diet and stress, increased population and shrinking employment have been implicated. In this paper, we study the prevalence of hypertension in an urban community of India using the JNC VII criteria, with the aim of identifying the risk factors and suggesting intervention strategies. A total of 1609 respondents out of 1662 individuals participated in our cross-sectional survey of validated and structured questionnaire followed by blood pressure measurement. Results showed pre-hypertensive levels of blood pressures among 35.8% of the participants in systolic group (120-139mm of Hg) and 47.7% in diastolic group (80-89 mm of Hg). Systolic hypertension (140 mm of Hg) was present in 40.9% and diastolic hypertension (90 mm of Hg) in 29.3% of the participants. Age and sex-specific prevalence of hypertension showed progressive rise of systolic and diastolic hypertension in women when compared to men. Men showed progressive rise in systolic hypertension beyond fifth decade of life. Bivariate analysis showed significant relationship of hypertension with age, sedentary occupation, body mass index (BMI), diet, ischemic heart disease, and smoking. Multivariate analysis revealed age and BMI as risk factors, and non-vegetarian diet as protective factor with respect to hypertension. Prevalence of prehypertensives was high among younger subjects - particularly students and laborers who need special attention. Role of non-vegetarian diet as a protective factor might have been related to fish-eating behavior of the sample population, who also use mustard oil as cooking medium - both of which have significant level of essential polyunsaturated fatty acids. The observed prevalence of hypertension in this study and other studies suggest the need for a comprehensive national policy to control hypertension in India, and, in other similar developing countries.
PMCID: PMC1145137  PMID: 15968343
Hypertension; eastern India; urban study; JNC-VII criteria; prehypertensives; non-vegetarian diet; developing countries
12.  Effects of Verapamil Slow Release Plus Trandolapril Combination Therapy on Essential Hypertension 
Background: Fixed-dose combination antihypertensive therapy has been recommended for patients with essential hypertension who are unresponsive to monotherapy or as a first-line treatment.
Objective: We investigated the effects of a fixed-dose combination of the phenylalkylamine-type calcium channel blocker verapamil slow release (SR)plus the angiotensin-converting enzyme inhibitor trandolapril on blood pressure (BP), serum lipid profile, urinary albumin excretion (UAE), left ventricular mass (LVM), and LVM index (LVMI), as well as the adverse events associated with this treatment.
Methods: Patients aged 30 to 65 years with mild to moderate essential hypertension were included in the study. All of the patients received capsules containing combination treatment with verapamil SR 180 mg plus trandolapril 2 mg orally, daily for 12 weeks. Mean arterial pressure (MAP), systolic BP (SBP), diastolic BP (DBP), and heart rate (HR) were measured at baseline and at 4, 8, and 12 weeks of treatment. Serum lipid profile, UAE, LVM, LVMI, and body mass index (BMI) were determined at baseline and at the end of the study period. All patients underwent electrocardiography and echocardiography at baseline and week 12. The primary end point of the study was to achieve an SBP/DBP ≤140/≤90 mm Hg (ie, normotensive) during week 12. All adverse events were assessed as mild, moderate, or severe at each visit. According to the response rate at week 12, patients were divided into 2 groups: those who became normotensive (responders) or those who remained hypertensive (SBP/DBP >140/>90 mm Hg; nonresponders).
Results: Forty-one patients (29 women, 12 men; mean [SD] age, 47.7 [7.8] years; mean [SD] BMI, 29.4 [3.5] kg/m2) were enrolled. The median durationof hypertension prior to enrollment was 5 months. Mean MAP, SBP, DBP, UAE, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), LDL-C/highdensity lipoprotein cholesterol (HDL-C) ratio, LVM, LVMI, and BMI decreased significantly after 12 weeks of combination treatment; HR and triglyceride level did not change significantly. Treatment-related adverse events occurred in 31.7% of patients, and none were severe or caused any patient to withdraw from the study. The most common adverse events were cough, constipation, headache, and dryness in the throat. Microalbuminuria, which may be a marker of endothelial dysfunction, was found in 7 (17.1%) patients at baseline and regressed significantly after 12 weeks.
Conclusions: In this study population, the fixed-dose combination of verapamil–trandolapril was an effective and well-tolerated antihypertensive therapy. This combination significantly reduced MAP, BP, TC, LDL-C, LDL-C/HDL-C ratio, UAE, LVM, and LVMI. Also, microalbuminuria decreased after this treatment. Verapamil–trandolapril may be useful in preventing microalbuminuria and left ventricular hypertrophy in patients with essential hypertension.
doi:10.1016/S0011-393X(03)00007-9
PMCID: PMC4053024  PMID: 24944353
essential hypertension; combination therapy; trandolapril; verapamil
13.  Serum lipid profile and correlates in newly presenting Nigerians with arterial hypertension 
Background
Arterial hypertension and dyslipidemia are modifiable cardiovascular risk factors. The multiplicative effect of these risk factors may worsen the atherogenic index of an individual. The objective of this study was to determine the pattern and prevalence of dyslipidemia in newly presenting Nigerians with arterial hypertension, as well as determine some of its correlates.
Methods
This cross-sectional study compared 115 newly presenting, age- and sex-matched individuals with arterial hypertension with 115 normotensive individuals. Fasting lipids, total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and fasting plasma glucose were estimated.
Results
Patients with arterial hypertension had higher body mass index (t=7.64; P=0.000), TC (t=2.95; P=0.006), and HDL-C (t=−5.18; P=0.000). The most common dyslipidemia was low HDL-C, found in both the hypertensive (44.3%) and normotensive (20.9%) patients. The prevalence of dyslipidemia in hypertensives and controls was 64% and 39%, respectively. In hypertensive patients, TC correlated positively to diastolic blood pressure (r=0.218; P=0.0019). Other positive correlates include LDL-C and age (r=0.217; P=0.020) and fasting plasma glucose (r=0.202; P=0.030) and body mass index (r=0.209; P=0.025). Among normotensive controls, TC correlated positively with LDL-C (r=0.63; P=0.000) but correlated negatively with tri glycerides (r=−0.30; P=0.001).
Conclusion
Lipid abnormalities are common in newly presenting Nigerians with arterial hypertension. Screening of these risk factors, promotion of healthy lifestyle, and the institution of therapy is desirable to reduce their multiplicative effects.
doi:10.2147/VHRM.S50690
PMCID: PMC3857265  PMID: 24348044
healthy lifestyle; screening; high-density lipoprotein cholesterol; cardiovascular; atherogenic index
14.  Hypertension and Its Correlates Among School Adolescents in Delhi 
Background:
Hypertension is fast emerging as a major health problem amongst all school adolescents, particularly in urban areas. Regular screening of the students for this is required for preventing the emergence of complications later in life. Therefore, the present study was undertaken with the objective to determine the prevalence of hypertension amongst urban school adolescents and its correlation with anthropometric measurements.
Methods:
A cross-sectional study was conducted in a school in Central Delhi involving all 315 students of 9th and 11th standard. A preforma was filled by the students and anthropometric measurements along with blood pressure (BP) measurements were taken for each student. Data was analyzed using Epi-info 2005 and SPSS 16.0.
Results:
Out of the total 315 students, 208 (66%) were boys and 107 (34%) were girls and the mean age was 14.31 ± 0.96 years. Overall prevalence of malnutrition was 24% and boys were found to be more obese as compared to girls. There were 5 students (1.6%) who were found to have systolic hypertension while 17 (5.4%) were found to have diastolic hypertension while 4.1% (n = 13) of the participants were systolic pre-hypertensive and 26% (n = 82) were in stage of diastolic pre-hypertension. Body mass index and gender were found to be independent predictor for systolic hypertension.
Conclusions:
Prevalence of hypertension and pre-hypertension was high amongst the school children. BP check-up for children and adolescents is thus recommended to take remedial action on time.
PMCID: PMC3990918  PMID: 24791194
Body mass index; diastolic hypertension; malnutrition; pre-hypertension; systolic hypertension
15.  A study on dietary habits, health related lifestyle, blood cadmium and lead levels of college students 
Nutrition Research and Practice  2012;6(4):340-348.
This study was performed in order to investigate dietary habits, health related lifestyle and blood cadmium and lead levels in female college students. 80 college students (43 males and 37 females) participated in the survey questionnaires. Body weight and height, blood pressure, and body composition were measured. The systolic blood pressure of male and female students were 128.9 ± 13.9 and 109.8 ± 12.0, respectively. The diastolic blood pressure of male and female students were 77.1 ± 10.3 and 66.0 ± 6.9, respectively, showing that male students had significantly higher blood pressure than female students (P < 0.001). The BMI of male and female students were 23.4 ± 3.3 and 20.2 ± 2.3, respectively. Most male students were in the range of being overweight. The dietary habits score of female students was significantly higher than that of male students (P < 0.01).The blood cadmium level of male and female students were 0.54 ± 0.23 and 0.52 ± 0.36, respectively. There was no significant difference between male and female students. The blood lead level of male and female students were 1.09 ± 0.49 and 0.59 ± 0.45, respectively. The blood lead level of male students was significantly higher than that of female students (P < 0.001). The blood cadmium level of smokers and nonsmokers were 0.69 ± 0.29 and 0.49 ± 0.29 respectively (P < 0.05). The blood cadmium level of smokers was significantly higher than that of nonsmokers (P < 0.05). The blood lead level of smokers and nonsmokers were 1.09 ± 0.43 and 0.80 ± 0.54, respectively. The blood lead level of smokers was significantly higher than that of nonsmokers (P < 0.05). Therefore, proper nutritional education programs are required for college students in order to improve their dietary and health related living habits.
doi:10.4162/nrp.2012.6.4.340
PMCID: PMC3439579  PMID: 22977689
Dietary habit; blood cadmium; blood lead; college students
16.  The Use of Obesity Indicators for the Prediction of Hypertension Risk among Youth in the United Arab Emirates 
Background:
Obesity is a significant risk factor for metabolic disorders including increase in blood pressure. Body mass index (BMI), waist circumference (WC) and Waist/Hip ratio (WHR) are simple and effective indicators of obesity. The objectives of this study were to examine the relationships between obesity anthropometric indicators and hypertension and to identify the best anthropometric indicator/s that can predict hypertension risk among youth in the UAE.
Methods:
A 110 first year students in a Medical University in Ajman, UAE, during the year 2009–2010 were included in a cross-sectional study. The height, weight, WC, hip circumference and blood pressure were measured and the BMI and WHR were calculated for each student and used in the analyses.
Results:
The mean values for BMI, WC, hip circumference and WHR, were significantly higher in the Pre/Hypertensive group compared to normal blood pressure group. The risk of Pre/ hypertension was significantly increased by 4.3 times for participants who had general obesity (BMI≥ 30) or abdominal obesity (identified from high WC). Highly significant correlations were noticed between systolic and diastolic blood pressure and all anthropometric indicators except that for Hip circumference and systolic blood pressure. Step-wise linear regression model showed that when all obesity indicators were studied together, the waist circumference was the only indicator which showed significant relationship with both systolic and diastolic blood pressure.
Conclusion:
Waist circumference is the best anthropometric indicator that can predict hypertension risk among youth in the UAE.
PMCID: PMC3481645  PMID: 23113084
Hypertension; Youth; Obesity indicators
17.  Persistent hypertension after adrenalectomy for an aldosterone-producing adenoma: weight as a critical prognostic factor for aldosterone’s lasting effect on the cardiac and vascular systems 
The Journal of surgical research  2012;177(2):241-247.
Background
Primary aldosteronism caused by an aldosterone producing adrenal tumor/aldosteronoma (APA), is a potentially curable form of hypertension, via unilateral adrenalectomy. Resolution of hypertension (HTN) is not as prevalent after tumor resection, as are the normalization of aldosterone secretion, hypokalemia, and other metabolic abnormalities. Here, we review the immediate and long term medical outcomes of laparoscopic adrenalectomy in patients with an APA, and attempt to identify any distinctive gender differences in the management of resistant hypertension.
Materials and Methods
We performed a retrospective review of the prospective Adrenal database at the University of Wisconsin between January 2001 and October 2010. Of the 165 adrenalectomies performed, thirty-two were for the resection of an aldosteronoma (APA). Patients were grouped according to their post-operative hypertension status. Those patients with normal blood pressure (<120/80 mmHg) and on no anti-hypertensive medication (CURE) were compared to those who continued to required medication for blood pressure control (HTN). We evaluated gender, age, body mass index (BMI), tumor size, duration of time with high blood pressure, and the differences in systolic and diastolic blood pressure following adrenalectomy. Statistical analysis was performed utilizing student’s t test. Statistical significance was defined as a p value < 0.05.
Results
We identified 32 patients with an APA based on biochemical and radiographic studies, two patients were excluded, due to missing data. There were 19 males (63%) and 11 (37%) females, with a mean age was 48.3 ± 2.1 years, and mean tumor size was 24 ± 3 mm. Post-operatively, patients required significantly fewer anti-hypertensive medications (1.5 ± 0.2 vs. 3.3 ± 0.3, p<0.001). Nine patients (31%) had complete resolution of their hypertension, requiring no post-operative anti-hypertensive medication. The only significant difference between the genders, was a lower BMI in women (27.6 ± 1.7 versus 33.4 ± 2.1 kg/m2, p=0.04). 90% of the cohort had at least a 20 mmHg decline in their systolic blood pressure post-operatively, placing them in the pre-hypertensive or normal blood pressure categories. 66% of the CURE patients required at least six months for resolution of their hypertension. All twenty patients who presented with hypokalemia, had immediate resolution post-operatively, and did not require continuance of the pre-operative spironolactone or potassium supplementation.
Conclusions
Laparoscopic adrenalectomy for aldosterone producing adenoma results in the normalization of, or more readily manageable blood pressure in 90% of patients, within six months. Metabolic disturbances are immediately corrected with tumor resection. Weight is an important contributing factor in resolving hypertension.
doi:10.1016/j.jss.2012.07.059
PMCID: PMC3474851  PMID: 22921664
Aldosteronoma; persistent hypertension; weight; end organ damage
18.  Prevalence of hypertension and associated cardiovascular risk factors in Central India 
Objectives:
To study the difference in the prevalence of hypertension and associated risk factors in urban and rural populations and the association of hypertension with various determinants.
Materials and Methods:
A community-based cross-sectional study was conducted in 48 villages and 15 urban wards of Jabalpur District of Central India. Nine hundred and thirty-nine individuals aged 20 years and above (624 from rural areas and 315 from urban areas) were included in the study. The prevalence of hypertension and associated cardiovascular risk factors was assessed in the urban and rural populations. A pretested questionnaire was used to collect data on socio-demographic, behavioral, and dietary factors. Anthropometric measurements of weight, height, waist and hip circumference, and blood pressure measurements were taken using the standard methodology. The glucose oxidase–peroxidase and cholesterol oxidase–cholesterol peroxidase methods were used to measure plasma glucose and serum cholesterol, respectively. Bivariate analysis was followed by multivariate analysis to detect the odds of getting hypertension with various risk factors for the urban and rural populations separately. Hypertension was defined as per Joint National Committee (JNC) - VII criteria.
Results:
The response rate was 97%. Overall prevalence of hypertension was 17%, with 21.4% in the urban population and 14.8% in the rural population. Significantly higher mean values of weight, height, body mass index (BMI), hip circumference (HC), waist circumference (WC), waist hip ratio (WHR), systolic blood pressure (SBP), fasting blood sugar (FBS), and serum cholesterol levels were mapped in the urban population in comparison with the rural population. Multivariate logistic regression analysis identified increasing age, parental history of hypertension, tobacco smoking, tobacco chewing, physical inactivity, high estimated per capita salt consumption, and BMI ≥27.5 kg/m2 as independent predictors for hypertension in the urban population, while in the rural population, increasing age, physical inactivity, central obesity, tobacco chewing and tobacco smoking were independent predictors for hypertension.
Conclusion:
The prevalence of hypertension and other cardiovascular risk factors was high in both urban and rural communities. Therefore, there is a need for comprehensive health promotion programs to encourage lifestyle modification.
doi:10.4103/2230-8229.128775
PMCID: PMC3966094  PMID: 24695988
Blood pressure; cardiovascular risk factors; epidemiology; hypertension; lifestyle; screening
19.  A PROSPECTIVE STUDY OF BODY MASS INDEX AND THE RISK OF DEVELOPING HYPERTENSION IN MEN 
American journal of hypertension  2007;20(4):370-377.
Background
Although obesity is known to increase the risk of hypertension, few studies have prospectively evaluated body mass index (BMI) across the range of normal weight and overweight as a primary risk factor.
Methods
In this prospective cohort, we evaluated the association between BMI and risk of incident hypertension. We studied 13,563 initially healthy, non-hypertensive men who participated in the Physicians’ Health Study. We calculated BMI from self-reported weight and height and defined hypertension as self-reported systolic blood pressure (BP) ≥140 mmHg, diastolic BP ≥90 mmHg, or new antihypertensive medication use.
Results
After a median 14.5 years, 4920 participants developed hypertension. Higher baseline BMI, even within the “normal” range, was consistently associated with increased risk of hypertension. Compared to participants in the lowest BMI quintile (<22.4 kg/m2), the relative risks (95% confidence interval) of developing hypertension for men with a BMI of 22.4–23.6, 23.7–24.7, 24.8–26.4, and >26.4 kg/m2 were 1.20 (1.09–1.32), 1.31 (1.19–1.44), 1.56 (1.42–1.72), and 1.85 (1.69–2.03), respectively (P for trend, <0.0001). Further adjustment for diabetes, high cholesterol, and baseline BP did not substantially alter these results. We found similar associations using other BMI categories and after excluding men with smoking history, those who developed hypertension in the first 2 years, and those with diabetes, obesity, or high cholesterol at baseline.
Conclusion
In this large cohort, we found a strong gradient between higher BMI and increased risk of hypertension, even among men within the “normal” and mildly “overweight” BMI range. Approaches to reduce the risk of developing hypertension may include prevention of overweight and obesity.
doi:10.1016/j.amjhyper.2006.10.011
PMCID: PMC1920107  PMID: 17386342
hypertension; obesity; body mass index
20.  Blood pressure in early adulthood, hypertension in middle-age, and future cardiovascular disease mortality: the Harvard Alumni Health Study 
Objectives
To examine the association of early adulthood blood pressure with CVD mortality, while accounting for middle-age hypertension.
Background
Elevated blood pressure in middle-age is an established CVD risk factor, but evidence for association with measurements earlier in life is sparse.
Methods
HAHS is a cohort study of 18,881 male university students who had blood pressure measured at university entry (1914 –1952; mean age 18.3 years) and who responded to a questionnaire mailed in 1962/1966 (mean age 45.8 years) in which physician-diagnosed hypertension status was reported. Study members were subsequently followed for mortality until the end of 1998.
Results
Following adjustment for age, BMI, smoking and physical activity at college entry, compared to men who were normotensive according to JNC-7 criteria (<120/<80mmHg) there was an elevated risk of CHD mortality (1,917 deaths) in those who were pre-hypertensive (120–139/80–89 mmHg) (hazards ratio; 95% confidence intervals: 1.21; 1.07, 1.36), stage 1 (140–159/90–99 mmHg) (1.46; 1.25, 1.70), and stage 2 hypertensive (≥160/≥100 mmHg) (1.89; 1.46, 2.45), incremental across categories (ptrend<0.001). After additional account for middle-age hypertension, estimates were somewhat attenuated but the pattern remained. Similar associations were apparent for total and CVD but not stroke mortality.
Conclusions
Higher blood pressure in early adulthood was associated with elevated risk of mortality from all-causes, CVD and CHD, but not stroke several decades later. Effects largely persisted after taking account of mediation by middle-age hypertension. Thus, the long-term benefits of blood pressure lowering in early adulthood are promising but supporting trial data are required.
doi:10.1016/j.jacc.2011.07.045
PMCID: PMC3253414  PMID: 22115646
blood pressure; cardiovascular disease mortality; epidemiology; blood pressure; lifecourse
21.  The Role of Adiposity in Cardiometabolic Traits: A Mendelian Randomization Analysis 
Fall, Tove | Hägg, Sara | Mägi, Reedik | Ploner, Alexander | Fischer, Krista | Horikoshi, Momoko | Sarin, Antti-Pekka | Thorleifsson, Gudmar | Ladenvall, Claes | Kals, Mart | Kuningas, Maris | Draisma, Harmen H. M. | Ried, Janina S. | van Zuydam, Natalie R. | Huikari, Ville | Mangino, Massimo | Sonestedt, Emily | Benyamin, Beben | Nelson, Christopher P. | Rivera, Natalia V. | Kristiansson, Kati | Shen, Huei-yi | Havulinna, Aki S. | Dehghan, Abbas | Donnelly, Louise A. | Kaakinen, Marika | Nuotio, Marja-Liisa | Robertson, Neil | de Bruijn, Renée F. A. G. | Ikram, M. Arfan | Amin, Najaf | Balmforth, Anthony J. | Braund, Peter S. | Doney, Alexander S. F. | Döring, Angela | Elliott, Paul | Esko, Tõnu | Franco, Oscar H. | Gretarsdottir, Solveig | Hartikainen, Anna-Liisa | Heikkilä, Kauko | Herzig, Karl-Heinz | Holm, Hilma | Hottenga, Jouke Jan | Hyppönen, Elina | Illig, Thomas | Isaacs, Aaron | Isomaa, Bo | Karssen, Lennart C. | Kettunen, Johannes | Koenig, Wolfgang | Kuulasmaa, Kari | Laatikainen, Tiina | Laitinen, Jaana | Lindgren, Cecilia | Lyssenko, Valeriya | Läärä, Esa | Rayner, Nigel W. | Männistö, Satu | Pouta, Anneli | Rathmann, Wolfgang | Rivadeneira, Fernando | Ruokonen, Aimo | Savolainen, Markku J. | Sijbrands, Eric J. G. | Small, Kerrin S. | Smit, Jan H. | Steinthorsdottir, Valgerdur | Syvänen, Ann-Christine | Taanila, Anja | Tobin, Martin D. | Uitterlinden, Andre G. | Willems, Sara M. | Willemsen, Gonneke | Witteman, Jacqueline | Perola, Markus | Evans, Alun | Ferrières, Jean | Virtamo, Jarmo | Kee, Frank | Tregouet, David-Alexandre | Arveiler, Dominique | Amouyel, Philippe | Ferrario, Marco M. | Brambilla, Paolo | Hall, Alistair S. | Heath, Andrew C. | Madden, Pamela A. F. | Martin, Nicholas G. | Montgomery, Grant W. | Whitfield, John B. | Jula, Antti | Knekt, Paul | Oostra, Ben | van Duijn, Cornelia M. | Penninx, Brenda W. J. H. | Davey Smith, George | Kaprio, Jaakko | Samani, Nilesh J. | Gieger, Christian | Peters, Annette | Wichmann, H.-Erich | Boomsma, Dorret I. | de Geus, Eco J. C. | Tuomi, TiinaMaija | Power, Chris | Hammond, Christopher J. | Spector, Tim D. | Lind, Lars | Orho-Melander, Marju | Palmer, Colin Neil Alexander | Morris, Andrew D. | Groop, Leif | Järvelin, Marjo-Riitta | Salomaa, Veikko | Vartiainen, Erkki | Hofman, Albert | Ripatti, Samuli | Metspalu, Andres | Thorsteinsdottir, Unnur | Stefansson, Kari | Pedersen, Nancy L. | McCarthy, Mark I. | Ingelsson, Erik | Prokopenko, Inga
PLoS Medicine  2013;10(6):e1001474.
In this study, Prokopenko and colleagues provide novel evidence for causal relationship between adiposity and heart failure and increased liver enzymes using a Mendelian randomization study design.
Please see later in the article for the Editors' Summary
Background
The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach.
Methods and Findings
We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses.
Age- and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI–trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03–1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1–1.4; all p<0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p<0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimate (p = 0.001).
Conclusions
We provide novel evidence for a causal relationship between adiposity and heart failure as well as between adiposity and increased liver enzymes.
Please see later in the article for the Editors' Summary
Editors' Summary
Cardiovascular disease (CVD)—disease that affects the heart and/or the blood vessels—is a major cause of illness and death worldwide. In the US, for example, coronary heart disease—a CVD in which narrowing of the heart's blood vessels by fatty deposits slows the blood supply to the heart and may eventually cause a heart attack—is the leading cause of death, and stroke—a CVD in which the brain's blood supply is interrupted—is the fourth leading cause of death. Globally, both the incidence of CVD (the number of new cases in a population every year) and its prevalence (the proportion of the population with CVD) are increasing, particularly in low- and middle-income countries. This increasing burden of CVD is occurring in parallel with a global increase in the incidence and prevalence of obesity—having an unhealthy amount of body fat (adiposity)—and of metabolic diseases—conditions such as diabetes in which metabolism (the processes that the body uses to make energy from food) is disrupted, with resulting high blood sugar and damage to the blood vessels.
Why Was This Study Done?
Epidemiological studies—investigations that record the patterns and causes of disease in populations—have reported an association between adiposity (indicated by an increased body mass index [BMI], which is calculated by dividing body weight in kilograms by height in meters squared) and cardiometabolic traits such as coronary heart disease, stroke, heart failure (a condition in which the heart is incapable of pumping sufficient amounts of blood around the body), diabetes, high blood pressure (hypertension), and high blood cholesterol (dyslipidemia). However, observational studies cannot prove that adiposity causes any particular cardiometabolic trait because overweight individuals may share other characteristics (confounding factors) that are the real causes of both obesity and the cardiometabolic disease. Moreover, it is possible that having CVD or a metabolic disease causes obesity (reverse causation). For example, individuals with heart failure cannot do much exercise, so heart failure may cause obesity rather than vice versa. Here, the researchers use “Mendelian randomization” to examine whether adiposity is causally related to various cardiometabolic traits. Because gene variants are inherited randomly, they are not prone to confounding and are free from reverse causation. It is known that a genetic variant (rs9939609) within the genome region that encodes the fat-mass- and obesity-associated gene (FTO) is associated with increased BMI. Thus, an investigation of the associations between rs9939609 and cardiometabolic traits can indicate whether obesity is causally related to these traits.
What Did the Researchers Do and Find?
The researchers analyzed the association between rs9939609 (the “instrumental variable,” or IV) and BMI, between rs9939609 and 24 cardiometabolic traits, and between BMI and the same traits using genetic and health data collected in 36 population-based studies of nearly 200,000 individuals of European descent. They then quantified the strength of the causal association between BMI and the cardiometabolic traits by calculating “IV estimators.” Higher BMI showed a causal relationship with heart failure, metabolic syndrome (a combination of medical disorders that increases the risk of developing CVD), type 2 diabetes, dyslipidemia, hypertension, increased blood levels of liver enzymes (an indicator of liver damage; some metabolic disorders involve liver damage), and several other cardiometabolic traits. All the IV estimators were similar to the BMI–cardiovascular trait associations (observational estimates) derived from the same individuals, with the exception of diabetes, where the causal estimate was higher than the observational estimate, probably because the observational estimate is based on a single BMI measurement, whereas the causal estimate considers lifetime changes in BMI.
What Do These Findings Mean?
Like all Mendelian randomization studies, the reliability of the causal associations reported here depends on several assumptions made by the researchers. Nevertheless, these findings provide support for many previously suspected and biologically plausible causal relationships, such as that between adiposity and hypertension. They also provide new insights into the causal effect of obesity on liver enzyme levels and on heart failure. In the latter case, these findings suggest that a one-unit increase in BMI might increase the incidence of heart failure by 17%. In the US, this corresponds to 113,000 additional cases of heart failure for every unit increase in BMI at the population level. Although additional studies are needed to confirm and extend these findings, these results suggest that global efforts to reduce the burden of obesity will likely also reduce the occurrence of CVD and metabolic disorders.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001474.
The American Heart Association provides information on all aspects of cardiovascular disease and tips on keeping the heart healthy, including weight management (in several languages); its website includes personal stories about stroke and heart attacks
The US Centers for Disease Control and Prevention has information on heart disease, stroke, and all aspects of overweight and obesity (in English and Spanish)
The UK National Health Service Choices website provides information about cardiovascular disease and obesity, including a personal story about losing weight
The World Health Organization provides information on obesity (in several languages)
The International Obesity Taskforce provides information about the global obesity epidemic
Wikipedia has a page on Mendelian randomization (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
MedlinePlus provides links to other sources of information on heart disease, on vascular disease, on obesity, and on metabolic disorders (in English and Spanish)
The International Association for the Study of Obesity provides maps and information about obesity worldwide
The International Diabetes Federation has a web page that describes types, complications, and risk factors of diabetes
doi:10.1371/journal.pmed.1001474
PMCID: PMC3692470  PMID: 23824655
22.  A cross-sectional study of the prevalence and risk factors for hypertension in rural Nepali women 
BMC Public Health  2013;13:55.
Background
The prevalence of hypertension is increasing in much of the South Asian region, including Nepal. This paper reports the prevalence and risk factors of hypertension and pre-hypertension among adult women in a rural community of Nepal.
Methods
Cross-sectional data on socioeconomic status (SES), lifestyle factors and blood pressure (BP) were collected from a cohort of 15,934 women in rural Nepal in 2006–08. Among a subsample (n = 1679), anthropometry and biomarkers of cardiovascular risk were measured.
Results
The mean age of women was 34.2 years (range 16.4-71.2 years). More than three percent (3.3%) had hypertension and 14.4% had pre-hypertension. In an adjusted analysis, lower SES, especially lower household farm assets and storage of food for long term consumption, was associated with increased odds of hypertension (OR = 1.14 for mid-level SES and OR = 1.40 for low SES; p for trend < 0.01). Smoking, alcohol use and not working outside the home were also associated with higher risk. In a subsample, both systolic BP (SBP) and diastolic BP (DBP) were positively associated with high triglycerides (SBP β = 4.1 mm Hg; DBP β =3.6 mm Hg), high HbA1c (SBP β = 14.0; DBP β = 9.2), raised fasting glucose (SBP β = 10.0; DBP β = 6.9), high BMI (SBP β = 6.7; DBP β = 5.1) and high waist circumference (SBP β = 6.2; DBP β = 5.3) after adjusting for potential confounders (p for all <0.01).
Conclusions
Although the prevalence of hypertension was low in this cohort, it was more prevalent among the poorer women and was strongly associated with other cardiovascular risks. These associations at a relatively young age may confer greater risk for cardiovascular disease among women in later life, indicating the need for interventions to reduce the progression from pre-hypertension to hypertension.
doi:10.1186/1471-2458-13-55
PMCID: PMC3566953  PMID: 23336578
Blood pressure; Hypertension; Cardiovascular risk; Nepal; Rural
23.  Prevalence and control of hypertension in a Niger Delta semi urban community, Nigeria 
Pharmacy Practice  2013;11(1):24-29.
Background
Hypertension is a public health problem worldwide, but the prevalence in Amassoma, Southern Ijaw Local Government Area is not known.
Objective
To investigate the prevalence of hypertension in the locality and the extent of control in diagnosed cases.
Methods
It is a prospective study involving interviewing. Four hundred adults aged 20 years and above selected through stratified random sampling across the various compounds called “AMA”; a unit of settlement comprising extended families of common ancestors. A self-developed, validated and pretested interviewer-administered questionnaire on demographics, predisposing factors, and medication history was used. In addition, measurement of respondents’ blood pressure, weight and height was carried out. The Body Mass Index calculated and the data were appropriately analysed.
Results
The response rate of questionnaire distribution was 100.0% being interviewer administered alongside weight, height and blood pressure measurement. Majority of respondents were female. Almost half of respondents (46.5%) had their BMI above normal, 15.3% (61) of which falls within the obese region (>30.0kg/m2). The mean (SD) systolic blood pressure among males was 133.3 (3.2) mmHg and that of females was 127.4 (3.0) while the mean (SD) diastolic blood pressures were 86.2 (1.7) and 83.9 (2.4) for males and females respectively. Crude prevalence rate of hypertension in the community was 15.0% (60) out of which 13.8 % (55) were previously diagnosed. The hypertension was that of Stage I in 11.5% (46) and Stage II in 3.5% (14). Hypertension prevalence was slightly higher in males (18.8%) than that of the females (12.5%) (p= 0.0889), Relative Risk (RR)=1.500 [95%CI 0.9422:2.388]. The prevalence rate among 40 years and above was 41.6% (42/101) who also constituted 70.0% (42/60) of participants with hypertension in the survey and 10.5% (42/400) of the total. Of the previously diagnosed cases of hypertension, only 31% (17/55) were taking their drugs during the survey and only 12.7% (07/55) had regular adherence to medication and adequate BP control was achieved in 7.3% (04/55). Majority of the patients on drugs (21.8%) (12/55) were either taking methydopa as monotherapy or in combination with amiloride and hydrochlorothiazide. Other drugs being taken by patients include lisinopril, propranolol, amlodipine, atenolol, nifedipine and low dose aspirin.
Conclusions
The prevalence of hypertension in the semi urban community is 15.0% with a pre-hypertension in another 23.5%. There was poor control of blood pressure among previously hypertensive patients.
PMCID: PMC3780508  PMID: 24155846
Hypertension; Prevalence; Nigeria
24.  High Blood Pressure and Its Association with Body Weight among Children and Adolescents in the United Arab Emirates 
PLoS ONE  2014;9(1):e85129.
Objectives
To estimate the prevalence of high blood pressure (BP) and its relationship with obesity among children and adolescents.
Methodology/Principal Findings
In this cross-sectional population (Emirati) representative study, we invited a random sample of 1600 students (grades 1–12) attending 23 out of all 246 schools in the Emirate of Abu Dhabi, United Arab Emirates. But analysis was restricted to Emirati nationals aged 6–17 years. We measured BP, height, weight, waist circumferences (WC), and calculated body mass index (BMI) by standard methods. BP levels ≥90th percentile but <95th percentile and ≥ 95th for age, sex, and height (CDC percentiles) were classified as pre-hypertension (pre-HTN) and hypertension (HTN), respectively. Associations between BP, age, BMI, WC, and sex, were investigated by (multiple) linear regression methods. A total of 999 (47% girls) students provided complete results. The prevalence of pre-HTN was 10.5% and 11.4% and the prevalence of HTN was 15.4% and 17.8% among boys and girls, respectively. The prevalence of systolic/diastolic HTN was 14.4%/2.5% and 14.8/7.4% among boys and girls, respectively. BMI CDC percentile was positively correlated with WC percentile (r = 0.734, p<0.01), and both systolic (r = 0.34, p<0.001) and diastolic (r = 0.21, p<0.001) standardized BP. WC percentile was less strongly correlated with standardized SBP (r = 0.255, p<0.01) and DBP (r = 0.175, p<0.01) than BMI.
Conclusions/Significance
The prevalence of elevated BP, notably systolic was significantly high among the Emirati children and adolescents in Abu Dhabi. High BP was strongly related to body weight, and appears more strongly associated with BMI than WC. Further studies are required to investigate the impact of childhood obesity on HTN.
doi:10.1371/journal.pone.0085129
PMCID: PMC3896369  PMID: 24465493
25.  Lifestyle modifications to prevent and control hypertension. 5. Recommendations on dietary salt. 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 concerning the effects of dietary salt intake on the prevention and control of hypertension in adults (except pregnant women). The guidelines are intended for use in clinical practice and public education campaigns. OPTIONS: Restriction of dietary salt intake may be an alternative to antihypertensive medications or may supplement such medications. Other options include other nonpharmacologic treatments for hypertension and no treatment. 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 1966-1996 using the terms hypertension, blood pressure, vascular resistance, sodium chloride, sodium, diet, sodium or sodium chloride dietary, sodium restricted/reducing diet, clinical trials, controlled clinical trial, randomized controlled trial and random allocation. Both trials and review articles were obtained, and other relevant evidence was obtained from the reference lists of the articles identified, from the personal files of the authors and through contacts with experts. The articles were reviewed, classified according to study design and graded according to level of evidence. In addition, a systematic review of all published randomized controlled trials relating to dietary salt intake and hypertension was conducted. VALUES: A high value was placed on the avoidance of cardiovascular morbidity and premature death caused by untreated hypertension. BENEFITS, HARMS AND COSTS: For normotensive people, a marked change in sodium intake is required to achieve a modest reduction in blood pressure (there is a decrease of 1 mm Hg in systolic blood pressure for every 100 mmol decrease in daily sodium intake). For hypertensive patients, the effects of dietary salt restriction are most pronounced if age is greater than 44 years. A decrease of 6.3 mm Hg in systolic blood pressure and 2.2 mm Hg in diastolic blood pressure per 100 mmol decrease in daily sodium intake was observed in people of this age group. For hypertensive patients 44 years of age and younger, the decreases were 2.4 mm Hg for systolic blood pressure and negligible for diastolic blood pressure. A diet in which salt is moderately restricted appears not to be associated with health risks. RECOMMENDATIONS: (1) Restriction of salt intake for the normotensive population is not recommended at present, because of insufficient evidence demonstrating that this would lead to a reduced incidence of hypertension. (2) To avoid excessive intake of salt, people should be counselled to choose foods low in salt (e.g., fresh fruits and vegetables), to avoid foods high in salt (e.g., pre-prepared foods), to refrain from adding salt at the table and minimize the amount of salt used in cooking, and to increase awareness of the salt content of food choices in restaurants. (3) For hypertensive patients, particularly those over the age of 44 years, it is recommended that the intake of dietary sodium be moderately restricted, to a target range of 90-130 mmol per day (which corresponds to 3-7 g of salt per day). (4) The salt consumption of hypertensive patients should be determined by interview. VALIDATION: These 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 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: PMC1230337  PMID: 10333851

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