Aging is often associated with increased systolic blood pressure and decreased diastolic blood pressure. Isolated systolic hypertension or an elevated systolic blood pressure without an elevated diastolic blood pressure is a known risk factor for incident heart failure in older adults. In the current study, we examined whether isolated diastolic hypotension, defined as a diastolic blood pressure <60 mm Hg and a systolic blood pressure ≥100 mm Hg, is associated with incident heart failure. Of the 5795 Medicare-eligible community-dwelling adults age ≥65 years in the Cardiovascular Health Study, 5521 were free of prevalent heart failure at baseline. After excluding 145 individuals with baseline systolic blood pressure <100 mm Hg, the final sample included 5376 participants, of whom 751 (14%) had isolated diastolic hypotension. Propensity scores for isolated diastolic hypotension were calculated for each of the 5376 participants and used to match 545 and 2348 participants with and without isolated diastolic hypotension, respectively who were balanced on 58 baseline characteristics. During over 12 years of median follow-up, centrally-adjudicated incident heart failure developed in 25% and 20% of matched participants with and without isolated diastolic hypotension respectively (hazard ratio associated with isolated diastolic hypotension, 1.33; 95% confidence interval, 1.10–1.61; p=0.004). Among the 5376 pre-match individuals, multivariable-adjusted hazard ratio for incident heart failure associated with isolated diastolic hypotension was 1.29 (95% confidence interval, 1.09–1.53; p=0.003). As in isolated systolic hypertension, among community-dwelling older adults without prevalent heart failure, isolated diastolic hypotension is also a significant independent risk factor for incident heart failure.
aging; blood pressure; diastolic; heart failure; pulse pressure
Only one genome scan to date has attempted to make use of the longitudinal data available in the Framingham Heart Study, and this attempt yielded evidence of linkage to a gene for mean systolic blood pressure. We show how the additional information available in these longitudinal data can be utilized to examine linkages for not only mean systolic blood pressure (SBP), but also for its trend with age and its variability. Prior to linkage analysis, individuals treated for hypertension were adjusted to account for right-censoring of SBP. Regressions on age were fitted to obtain orthogonal measures of slope, curvature, and residual variance of SBP that were then used as dependent variables in the model-free linkage program SIBPAL. We included mean age, gender, and cohort as covariates in the analysis. To improve power, sibling pairs were weighted for informativity using weights derived from both the marker and trait. The most significant results from our analyses were found on chromosomes 12, 15, and 17 for mean SBP, and chromosome 20 for both SBP slope and curvature.
Subjects with high normal blood pressure are at high risk of developing hypertension. Thus, the criteria of the Canadian Hypertension Education Program for diagnosis of hypertension and recommendations for follow-up now recommend that patients with high normal blood pressure (130 mmHg to 139 mmHg systolic and/or 85 mmHg to 89 mmHg diastolic) be followed up annually for the development of hypertension. Clinical trial data from subjects with high normal blood pressure show that 40% over two years and 63% over four years developed hypertension (140/90 mmHg or higher). These data are consistent with observational data from the Framingham Heart Study, which found a similar risk. Besides annual follow-up, the Canadian Hypertension Education Program recommends lifestyle therapy for individuals with high normal blood pressure. Ongoing research will establish whether any further management is required.
Clinical practice guidelines; High normal blood pressure; Hypertension; Lifestyle therapy; Prehypertension
Recent cross-sectional studies have suggested that higher serum sodium levels may be a marker of elevated blood pressure. It is unclear whether serum sodium levels are related to the risk of developing hypertension in the community.
We investigated the association of serum sodium with longitudinal blood pressure tracking and incidence of hypertension in 2172 non-hypertensive Framingham Offspring Study participants (mean age 42 years, 54% women). We defined an increase in blood pressure as an increment of ≥ 1 category (as defined by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure), and incident hypertension as a systolic pressure of ≥140 or a diastolic pressure ≥90 mm Hg, or use of antihypertensive medications. Serum sodium was analyzed as a continuous variable, and as categories.
Cross-sectionally, serum sodium was not associated with systolic or diastolic blood pressure (p exceeded 0.10). On follow-up (mean 4.4 years), 805 participants (37 %; 418 women) progressed by ≥ 1 blood pressure category, and 318 (15%; 155 women) developed new-onset hypertension. In multivariable logistic regression analyses (adjusting for age, sex, baseline blood pressure, diabetes, body mass index, weight gain and smoking), serum sodium was not associated with blood pressure progression (Odds ratio [OR] per SD increment 0.93, 95% confidence limits [CI] 0.85–1.03), or with hypertension incidence (OR per SD increment 0.94, 95% CI 0.82–1.08).
In our large community-based sample, serum sodium was not associated with blood pressure cross-sectionally, or with blood pressure tracking or hypertension incidence longitudinally.
Hypertension; blood pressure; serum sodium; metabolism; epidemiology; longitudinal studies
A prediction model, developed in the Framingham Heart Study (FHS), has been proposed for use in estimating a given individual’s risk of hypertension. We compared this model with systolic blood pressure (SBP) alone and age-specific diastolic blood pressure (DBP) categories for the prediction of hypertension. Participants in the Multi-Ethnic Study of Atherosclerosis, without hypertension or diabetes (n=3013), were followed for the incidence of hypertension (SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg and/or the initiation of antihypertensive medication). The predicted probability of developing hypertension between four adjacent study examinations, with a median of 1.6 years between examinations, was determined. The mean (standard deviation) age of participants was 58.5 (9.7) years and 53% were women. During follow-up, 849 incident cases of hypertension occurred. The c-statistic for the FHS model was 0.788 (95% CI: 0.773, 0.804) compared with 0.768 (95% CI: 0.751, 0.785; p=0.096 compared to the FHS model) for SBP alone and 0.699 (95% CI: 0.681, 0.717; p<0.001 compared to the FHS model) for age-specific DBP categories. The relative integrated discrimination improvement index for the FHS model versus SBP alone was 10.0% (95% CI: −1.7%, 22.7%) and versus age-specific DBP categories was 146% (95% CI: 116%, 181%). Using the FHS model, there were significant differences between observed and predicted hypertension risk (Hosmer-Lemeshow goodness of fit p<0.001); re-calibrated and best-fit models produced a better model fit (p=0.064 and 0.245, respectively). In this multi-ethnic cohort of U.S. adults, the FHS model was not substantially better than SBP alone for predicting hypertension.
hypertension; epidemiology; systolic blood pressure; diastolic blood pressure; risk prediction
The heart progressively remodels over the life course, yet longitudinal data characterizing such remodeling in the community are limited.
Methods and Results
Using multilevel modeling, we analyzed up to 4 serial echocardiographic observations obtained over a 16-year period in 4,062 Framingham Study participants (mean age 45 years, 54% women; 11,485 person-observations). We related LV wall thickness (LVWT), LV systolic (LVDS) and diastolic (LVDD) dimensions and fractional shortening (FS) to age, sex, body mass index (BMI), blood pressure (BP, including antihypertensive medication use), smoking, and diabetes (separate analyses for each echocardiographic measure). With advancing age, LV dimensions decreased, whereas FS and LVWT increased concomitantly. Male sex, BMI, and BP indices/hypertension treatment were significantly related to both greater LV dimensions and LVWT. The effect of age on cardiac remodeling was influenced by key covariates (P>0.05 for all interactions): women and individuals with diabetes experienced greater age-associated increases in LVWT; presence of diabetes or a higher BP was associated with a lesser decrease in LV diastolic dimensions with increasing age; antihypertensive medication use was a marker of an attenuated increase in FS with aging.
Cardiac remodeling over the adult life course is characterized by a distinct pattern of increasing LVWT, decreasing LV dimensions and increasing FS with advancing age. Overall, female sex, greater BP load, and presence of diabetes serve to attenuate this remodeling pattern. These observations suggest a mechanism for the preponderance of women with hypertension and individuals with diabetes among patients with diastolic heart failure.
aging; cardiac remodeling; heart failure
We are presenting a review of Isolated Systolic Hypertension (ISH) as a cardiovascular risk factor with emphasis on the perioperative period.
Isolated systolic hypertension is associated with aging and is the most frequent subtype (65%) among patients with uncontrolled hypertension. ISH is strongly associated with increased risks of cardiac and cerebrovascular events exceeding those in comparably aged individuals with diastolic hypertension. Patients with ISH show an increase in left ventricular (LV) mass and an increase in the prevalence of left ventricular hypertrophy (LVH). These LV changes increase cardiovascular events and frequently lead to diastolic dysfunction (DD). Treatment to reduce elevated systolic blood pressure has been shown to reduce the risk of cardiovascular events.
In the perioperative setting, essential hypertension has not been found to be a significant risk factor for cardiac complications. Most of the studies were based on the definition of essential hypertension and underpowered in sample size. The significance of perioperative ISH, however, is not well studied, partly due to its recognition only fairly recently as a cardiovascular risk factor in the non-surgical setting, and partly due to the evolving definition of ISH.
Perioperative cardiac complications remain a significant problem to the healthcare system and to the patient. Although the incidence of perioperative cardiac complications is prominent in high-risk patients as defined by the Revised Cardiac Risk Index (RCRI), the bulk of the cardiac complications actually occur in low-risk group. Currently, little understanding exists on the occurrence of perioperative cardiac complications in low- risk patients. A factor such as ISH, with its known pathophysiological changes, is a potential perioperative risk factor.
We believe ISH is an under-recognized perioperative risk factor and deserves further studying. Our research group has recently been funded by the Heart Stroke Foundation (HSF) to examine ISH as a perioperative risk factor (PROMISE Study).
Isolated systolic hypertension; cardiovascular risk factors; perioperative.
OBJECTIVE--To examine the hypothesis that a J curve relation between blood pressure and death from coronary heart disease is confined to high risk subjects with myocardial infarction. DESIGN--Cohort longitudinal epidemiological study with biennial examinations since 1950. SETTING--Framingham, Massachusetts, USA. SUBJECTS--5209 subjects in the Framingham study cohort followed up by a person examination approach. MAIN OUTCOME MEASURES--Coronary heart disease deaths and non-cardiovascular disease deaths in men and women with or without myocardial infarction relative to blood pressure. RESULTS--Among subjects without myocardial infarction non-cardiovascular disease deaths were twice to three times as common as coronary heart disease deaths. Furthermore, there was no significant relation between non-cardiovascular disease death and diastolic or systolic blood pressure. Also coronary heart disease deaths were linearly related to diastolic and systolic blood pressures. Among high risk patients (that is, people with myocardial infarction but free of congestive heart failure) death from coronary heart disease was more common than non-cardiovascular disease death. There was a significant U shaped relation between coronary heart disease death and diastolic blood pressure. Although there was an apparent U shaped relation between coronary heart disease death and systolic blood pressure, it did not attain statistical significance when controlling for age and change in systolic blood pressure from the pre-myocardial infarction level. None of the above conclusions changed when adjustments were made for risk factors such as serum cholesterol concentration, antihypertensive treatment, and left ventricular function. The U shaped relation between diastolic blood pressure and high risk subjects existed for both those given antihypertensive treatment and those not. CONCLUSIONS--These data suggest that an age and sex independent U curve relation exists for diastolic blood pressure and coronary heart disease deaths in patients with myocardial infarction but not for low risk subjects without myocardial infarction. The relation seems to be independent of left ventricular function and antihypertensive treatment.
One of the great strengths of the Framingham Heart Study data, provided for the Genetic Analysis Workshop 13, is the long-term survey of phenotypic data. We used this unique data to create new phenotypes representing the pattern of longitudinal change of the provided phenotypes, especially systolic blood pressure and body weight. We performed a linear regression of body weight and systolic blood pressure on age and took the slopes as new phenotypes for quantitative trait linkage analysis using the SOLAR package. There was no evidence for heritability of systolic blood pressure change. Heritability was estimated as 0.15 for adult life "body weight change", measured as the regression slope, and "body weight gain" (including only individuals with a positive regression slope), and as 0.22 for body weight "change up to 50" (regression slope of weight on age up to an age of 50). With multipoint analysis, two regions on the long arm of chromosome 8 showed the highest LOD scores of 1.6 at 152 cM for "body weight change" and of >1.9 around location 102 cM for "body weight gain" and "change up to 50". The latter two LOD scores almost reach the threshold for suggestive linkage. We conclude that the chromosome 8 region may harbor a gene acting on long-term body weight regulation, thereby contributing to the development of the metabolic syndrome.
Quantitative trait linkage analysis; longitudinal change; weight change; regression slope; metabolic syndrome
We used an approach for detecting genotype × environment interactions to detect and characterize genotype × age interaction in longitudinal measures of three well known cardiovascular risk factors: total plasma cholesterol (TC), systolic blood pressure (SBP), and body weight (Wgt). Our objectives were to determine if the same gene or suite of genes influences quantitative variation in each of these phenotypes in the 4th and 6th decades of life, to assess the impact of additive gene effects in these two decades, and to evaluate the stability of pleiotropic relationships among these phenotypes. Using the Framingham Heart Study data, we constructed two cross-sectional samples comprising individuals on whom these phenotypes were measured at ages 30-39 years (Original Cohort: exam 1, Offspring Cohort: exam 2) and at ages 50-59 years (Original Cohort: exam 11, Offspring Cohort: exam 5). We also constructed a longitudinal sample from the cross-sectional sample members for whom measures on these traits were available at both ages (i.e., 4th and 6th decades of life). Patterns of pleiotropy, inferred from genetic correlations between traits, differ between the two age classes. Further, additive genetic variance in SBP during the 4th decade of life is attributable to a different gene or suite of genes than during the 6th. The magnitude of the effect increases for SBP. Variation in TC and Wgt appear to be influenced by the same gene or genes in both decades. The magnitude of the effect is stable for TC, but increases dramatically with age for Wgt.
Exercise blood pressure (BP) is an important marker of left ventricular hypertrophy, incident hypertension and future cardiovascular events. Although impaired vascular function is hypothesized to influence the BP response during exercise, limited data exist on the association of vascular function with exercise BP in the community.
Methods and Results
Framingham Offspring cohort participants (n=2115, 53% women, mean age 59 years) underwent a submaximal exercise test (first 2 stages of the Bruce protocol), applanation tonometry and brachial artery flow-mediated dilation (FMD) testing. We related exercise systolic and diastolic BP at second stage of the Bruce protocol to standard cardiovascular risk factors and to vascular function measures. In multivariable linear regression models, exercise systolic BP was positively related to age, standing BP, standing heart rate, smoking, body mass index, and the total cholesterol-to-high-density cholesterol (HDL) ratio (p≤0.01 for all). Similar associations were observed for exercise diastolic BP. Carotid-femoral pulse wave velocity (p=0.02), central pulse pressure (p<0.0001), mean arterial pressure (p=0.04) and baseline brachial flow (p=0.002) were positively associated with exercise systolic BP, whereas FMD was negatively associated (P<0.001). For exercise diastolic BP, forward pressure wave amplitude was negatively related (p<0.0001) whereas mean arterial pressure was positively related (p<0.0001).
Increased arterial stiffness and impaired endothelial function are significant correlates of a higher exercise systolic BP response. Our findings suggest that impaired vascular function may contribute to exaggerated BP responses during daily living, resulting in repetitive increments in load on the heart and vessels and increased cardiovascular disease risk.
blood pressure; endothelial function; exercise; vascular function; vascular stiffness
Isolated systolic hypertension, an elevation in systolic but not diastolic pressure, is the most prevalent type of hypertension in those aged 50 or over, occurring either de novo or as a development after a long period of systolic‐diastolic hypertension with or without treatment. The increase in blood pressure with age is mostly associated with structural changes in the arteries and especially with large artery stiffness. It is known from various studies that rising blood pressure is associated with increased cardiovascular risk. In the elderly, the most powerful predictor of risk is increased pulse pressure due to decreased diastolic and increased systolic blood pressure. All evidence indicates that treating the elderly hypertensive patient will reduce the risk of cardiovascular events. However, there is no evidence yet for the very elderly. This population is particularly susceptible to side effects of treatments and the reduction of blood pressure, although reducing the risk of cardiovascular events such as stroke, may result in increased mortality.
ageing; blood pressure; hypertension
Isolated systolic hypertension, characterized by elevated systolic blood pressure (greater than 150 to 165 mm Hg), normal diastolic blood pressure (less than 90 to 95 mm Hg) and, often, atherosclerosis, is now recognized as an important risk factor for cardiovascular disease. When the systolic pressure is 200 mm Hg or greater, or when it is 180 mm Hg or greater and accompanied by target organ damage, therapeutic intervention may be of value in patients under the age of 80 years. Low doses of thiazide diuretics have been shown to be safe and effective in lowering the systolic pressure. If the blood pressure remains high, treatment with methyldopa may be added.
Leukocyte telomere length (LTL) decreases over the adult life course due to the cumulative burden of oxidative stress, inflammation, and exposure to vascular risk factors. Left ventricular (LV) mass is a biomarker of long-standing exposure to cardiovascular disease risk factors. We hypothesized that LTL is related inversely to LV mass.
Methods and Results
We related LTL (measured by Southern blot analysis) to echocardiographic LV mass and its components (LV diastolic dimension, LVDD; LV wall thickness, LVWT) in 850 Framingham Heart Study participants (mean age 58 years, 58% women) using multivariable linear regression adjusting for age, sex, height, weight, systolic blood pressure, hypertension treatment, and smoking. Overall, multivariable-adjusted LTL was positively related to LV mass (beta coefficient per SD increase [β]=0.072; p= 0.001), LVWT (β=0.053; p= 0.01), and LVDD (β=0.035; p= 0.09). We observed effect modification by hypertension status (p for interaction =0.02 for LV mass); LTL was more strongly associated with LV mass and LVWT in individuals with hypertension (β per SD increment of 0.10 and 0.08, respectively; p<0.01 for both). Participants with hypertension who were in the top quartile of LV mass had LTL that was 250 base pairs longer relative to those in the lowest quartile (p for trend across quartiles 0.009).
In contrast to our expectation, in our community-based sample, LTL was positively associated with LV mass and wall thickness, especially so in participants with hypertension. These data are consistent with the hypothesis that longer LTL may be a marker of propensity to LV hypertrophy.
Telomere; Left ventricular mass; Hypertension; Epidemiology; Association
The recessive disorder trimethylaminuria is caused by defects in the FMO3 gene, and may be associated with hypertension. We investigated whether common polymorphisms of the FMO3 gene confer an increased risk for elevated blood pressure and/or essential hypertension.
FMO3 genotypes (E158K, V257M, E308G) were determined in 387 healthy subjects with ambulatory systolic and diastolic blood pressure measurements, and in a cardiovascular disease population of 1649 individuals, 691(41.9%) of whom had a history of hypertension requiring drug treatment. Haplotypes were determined and their distribution noted.
There was no statistically significant association found between any of the 4 common haplotypes and daytime systolic blood pressure in the healthy population (p = 0.65). Neither was a statistically significant association found between the 4 common haplotypes and hypertension status among the cardiovascular disease patients (p = 0.80).
These results suggest that the variants in the FMO3 gene do not predispose to essential hypertension in this population.
Atrial fibrillation (AF) contributes to substantial increases in morbidity and mortality. Our aim was to develop a risk prediction model to assess individuals’ absolute risk for incident AF; to offer clinicians a tool to communicate risk; and to provide researchers a framework to evaluate new risk markers.
We examined 4764 Framingham Heart Study individuals (8044 person-exams; mean age 60.9 years, 55% women) aged 45–95 years. Multivariable Cox regression related clinical variables to 10-year AF incidence (n=457). Secondary analyses incorporated routine echocardiographic data (person-exams=7156, 445 events) for reclassifying individuals’ AF risk.
Age, sex, significant murmur, heart failure, systolic blood pressure, hypertension treatment, body mass index, and electrocardiographic PR interval were associated with incident AF (p<0.05; clinical model C statistic=0.78, 95% confidence interval [CI] 0.76–0.80). Ten-year AF risk varied with age; >15% 10-year AF risk was observed in 1.0% of individuals <65 years versus 26.9% of participants ≥65 years. Predicted 10-year risk deciles for developing AF were similar to observed risks (calibration Chi-square statistic, 4.16, p=0.90). Additional incorporation of echocardiographic features minimally improved the C statistic from 0.78 (0.75, 0.80) to 0.79 (95% CI 0.77–0.82), p=0.005. Echocardiographic variables did not significantly improve net reclassification (p=0.18). We provide a point score for estimating AF risk with variables easily-measured in primary care.
The Framingham AF risk score may help risk stratify individuals in the community, and may provide a framework to evaluate new biological or genetic markers for AF risk prediction and help target individuals destined to develop AF for preventive measures.
atrial fibrillation; risk score; epidemiology; echocardiography; cohort study
The association of blood lead (B-Pb) concentration to blood pressure was investigated in men aged 55 to 75 years living in the Rome area, who had no history of exposure to lead in the workplace and who participated between 1989 and 1990 in an epidemiologic survey for coronary heart disease (New Risk Factor Project). Of the 1856 individuals eligible for the study, 59 were excluded from analyses because not all relevant data were available; and 478 were excluded because they were treated for hypertension. In the remaining subjects (n = 1319) the median B-Pb concentration was 113 micrograms/l (range: 40-442 micrograms/l). Systolic blood pressure (SBP) averaged 140 +/- 18 (standard deviation) mm Hg (range 98-220) and diastolic blood pressure (DBP) 84 +/- 9 mm Hg (range 56-118). Median B-Pb values increased significantly from 111 micrograms/l in subjects with normal blood pressure (n = 668) to 113.5 micrograms/l in subjects with borderline high blood pressure (n = 373) and to 120 micrograms/l in subjects with increased blood pressure (n = 278). After log-normal conversion of B-Pb, the linear correlation coefficient between In[B-Pb(ug/l)] and both SBP and DBP was statistically significant (r = 0.1332, p < 0.001 and r = 0.0737, p = 0.007, respectively). The linear regression coefficient was 6.8 mm Hg/In(micrograms/l) for SBP and 1.8 mm Hg/In(microgram/l) for DBP. Multiple regression analyses revealed that, after correction for body mass index (BMI), age, heart rate, skinfold thickness, serum lipids, and glucose levels; blood lead was still a significant predictor of increased SBP and DBP.(ABSTRACT TRUNCATED AT 250 WORDS)
About one quarter of adults are hypertensive and high blood pressure carries increased risk for heart disease, stroke, kidney disease and death. Increased arterial stiffness is a key factor in the pathogenesis of systolic hypertension and cardiovascular disease. Substantial heritability of blood-pressure (BP) and arterial-stiffness suggests important genetic contributions.
In Framingham Heart Study families, we analyzed genome-wide SNP (Affymetrix 100K GeneChip) associations with systolic (SBP) and diastolic (DBP) BP at a single examination in 1971–1975 (n = 1260), at a recent examination in 1998–2001 (n = 1233), and long-term averaged SBP and DBP from 1971–2001 (n = 1327, mean age 52 years, 54% women) and with arterial stiffness measured by arterial tonometry (carotid-femoral and carotid-brachial pulse wave velocity, forward and reflected pressure wave amplitude, and mean arterial pressure; 1998–2001, n = 644). In primary analyses we used generalized estimating equations in models for an additive genetic effect to test associations between SNPs and phenotypes of interest using multivariable-adjusted residuals. A total of 70,987 autosomal SNPs with minor allele frequency ≥ 0.10, genotype call rate ≥ 0.80, and Hardy-Weinberg equilibrium p ≥ 0.001 were analyzed. We also tested for association of 69 SNPs in six renin-angiotensin-aldosterone pathway genes with BP and arterial stiffness phenotypes as part of a candidate gene search.
In the primary analyses, none of the associations attained genome-wide significance. For the six BP phenotypes, seven SNPs yielded p values < 10-5. The lowest p-values for SBP and DBP respectively were rs10493340 (p = 1.7 × 10-6) and rs1963982 (p = 3.3 × 10-6). For the five tonometry phenotypes, five SNPs had p values < 10-5; lowest p-values were for reflected wave (rs6063312, p = 2.1 × 10-6) and carotid-brachial pulse wave velocity (rs770189, p = 2.5 × 10-6) in MEF2C, a regulator of cardiac morphogenesis. We found only weak association of SNPs in the renin-angiotensin-aldosterone pathway with BP or arterial stiffness.
These results of genome-wide association testing for blood pressure and arterial stiffness phenotypes in an unselected community-based sample of adults may aid in the identification of the genetic basis of hypertension and arterial disease, help identify high risk individuals, and guide novel therapies for hypertension. Additional studies are needed to replicate any associations identified in these analyses.
Increased left atrial diameter (LAD) is associated with elevated risk of atrial fibrillation (AF) and cardiovascular disease. Information is limited regarding the short- or long-term correlates of LAD.
Methods and Results
We evaluated clinical correlates of LAD over a 16-year period in 4,403 Framingham Study participants (mean age 45 years, 52% women; median observations/participant=3) using multi-level modeling. We related age, sex, body mass index (BMI), systolic and diastolic blood pressure (BP), diabetes and anti-hypertensive treatment to LAD. Sex-specific growth curves for LAD were estimated for individuals with low, intermediate and high risk factor burden. We also related risk factors to changes in LAD over a 4-year period in 3,365 participants.
Age, male sex (+3.83 mm compared to women), greater BMI, higher systolic BP (0.24 mm per 10 mmHg increment), and anti-hypertensive treatment (+0.54 mm) were associated positively with LAD (p<0.001). Men had a greater increase in LAD with BMI than women (+2.02 vs. +1.77 mm in women, per 5-unit increment) and individuals on anti-hypertensive treatment experienced a greater increase in LAD with age (0.95 vs. 0.63 mm per 10–year age increment). Overall, greater risk factor burden was positively associated with LAD. These risk factors were also associated positively with 4-year change in LAD (p<0.001).
Our longitudinal study of a large community-based sample identified higher BP and greater BMI as key modifiable correlates of LAD, suggesting that maintaining optimal levels of these risk factors over the life course may prevent atrial remodeling and AF.
left atrial diameter; atrial enlargement; serial measurements; epidemiology; multi-level modeling; echocardiography
Non-pharmacological treatment options for hypertension have the potential to reduce the risk of cardiovascular disease at a population level. Animal studies have suggested that garlic reduces blood pressure, but primary studies in humans and non-systematic reviews have reported mixed results. With interest in complementary medicine for hypertension increasing, it is timely to update a systematic review and meta-analysis from 1994 of studies investigating the effect of garlic preparations on blood pressure.
We searched the Medline and Embase databases for studies published between 1955 and October 2007. Randomised controlled trials with true placebo groups, using garlic-only preparations, and reporting mean systolic and/or diastolic blood pressure (SBP/DBP) and standard deviations were included in the meta-analysis. We also conducted subgroup meta-analysis by baseline blood pressure (hypertensive/normotensive), for the first time. Meta-regression analysis was performed to test the associations between blood pressure outcomes and duration of treatment, dosage, and blood pressure at start of treatment.
Eleven of 25 studies included in the systematic review were suitable for meta-analysis. Meta-analysis of all studies showed a mean decrease of 4.6 ± 2.8 mm Hg for SBP in the garlic group compared to placebo (n = 10; p = 0.001), while the mean decrease in the hypertensive subgroup was 8.4 ± 2.8 mm Hg for SBP (n = 4; p < 0.001), and 7.3 ± 1.5 mm Hg for DBP (n = 3; p < 0.001). Regression analysis revealed a significant association between blood pressure at the start of the intervention and the level of blood pressure reduction (SBP: R = 0.057; p = 0.03; DBP: R = -0.315; p = 0.02).
Our meta-analysis suggests that garlic preparations are superior to placebo in reducing blood pressure in individuals with hypertension.
Blood pressure ranges associated with cardiovascular disease (CVD) events in advanced type 2 diabetes are not clear. Our objective was to determine whether baseline and follow-up (On-Study) systolic blood pressure (SBP), diastolic blood pressure (DBP), and SBP combined with DBP predict CVD events in the Veterans Affairs Diabetes Trial (VADT).
RESEARCH DESIGN AND METHODS
Participants in the VADT (n = 1,791) with hypertension received stepped treatment to maintain blood pressure below the target of 130/80 mmHg in standard and intensive glycemic treatment groups. Blood pressure levels of all subjects at baseline and On-Study were analyzed to detect associations with CVD risk. The primary outcome was the time from randomization to the first occurrence of myocardial infarction, stroke, congestive heart failure, surgery for vascular disease, inoperable coronary disease, amputation for ischemic gangrene, or CVD death.
Separated SBP ≥140 mmHg had significant risk at baseline (hazards ratio [HR] 1.508, P < 0.001) and On-Study (HR 1.469, P = 0.002). DBP <70 mmHg increased CVD events at baseline (HR 1.482, P < 0.001) and On-Study (HR 1.491, P < 0.001). Combined blood pressure categories indicated high risk for CVD events for SBP ≥140 with DBP <70 mmHg at baseline (HR 1.785, P = 0.03) and On-Study (HR 2.042, P = 0.003) and nearly all SBP with DBP <70 mmHg.
Increased risk of CVD events with SBP ≥140 mmHg emphasizes the urgency for treatment of systolic hypertension. Increased risk with DBP <70 mmHg, even when combined with SBP in guideline-recommended target ranges, supports a new finding in patients with type 2 diabetes. The results emphasize that DBP <70 mmHg in these patients was associated with elevated CVD risk and may best be avoided.
OBJECTIVE: The risk of cardiovascular and renal diseases has been shown to be higher for systolic blood pressure than diastolic blood pressure. The aim of this study was to assess the differential control of systolic and diastolic blood pressure in Nigerians with primary hypertension. DESIGN AND SETTING: This was a prospective observational study carried out at the Medical Outpatient Department of the State Hospital, Abeokuta, Nigeria. Ethical approval for the study was obtained from the ethical committee of the hospital. METHODOLOGY: The study population consisted of 185 consecutive patients (65 males, 120 females), aged 35-85 years with primary hypertension who had been on drugs one- to 25 years prior to the onset of the study. Clinic blood pressure control was assessed during a year period. Six consecutive clinic blood pressure readings were recorded for each patient and the average calculated (systolic blood pressure and diastolic blood pressure separately). Patients were classified into subgroups based on the pattern of blood pressure control. RESULTS: Clinic systolic blood pressure and diastolic blood pressure was controlled in 58 patients (31.4%). Systolic blood pressure control was less frequent than diastolic blood pressure control (35.7% versus 51.4%, p<0.05). Patients with uncontrolled systolic blood pressure were significantly older than patients with only uncontrolled diastolic blood pressure (66.7+/-7.4 versus 52.9+/-8.7 years, p<0.001). CONCLUSION: Systolic blood pressure is less frequently controlled than diastolic blood pressure in Nigerians treated for primary hypertension. This may increase the patient's risk of developing stroke, and cardiovascular and renal complications.
OBJECTIVE: To compare the prevalence of modifiable risk factors for cardiovascular disease among hypertensive and nonhypertensive adults and to estimate the effect of treating hyperlipidemia or hypertension to reduce the risk of death from coronary artery disease. METHODS: The authors evaluated a sample of 7814 subjects aged 35-74 years free of clinical cardiovascular disease from the Canadian Heart Health Surveys to estimate the prevalence of cardiovascular risk factors. They identified hyperlipidemic subjects (ratio of total cholesterol to high-density lipoprotein cholesterol [total-C/HDL-C] 6.0 [corrected] or more for men and 5.0 [corrected] or more for women) and hypertensive subjects (systolic or diastolic blood pressure 160/90 mm Hg or greater, or receiving pharmacologic or nonpharmacologic treatment). A life expectancy model was used to estimate the rate of death from coronary artery disease following specific treatments. RESULTS: An elevated total-C/HDL-C ratio was significantly more common among hypertensive than nonhypertensive men aged 35-64 (rate ratio [RR] 1.56 for age 35-54, 1.28 for age 55-64) and among hypertensive than nonhypertensive women of all ages (RR 2.73 for age 35-54, 1.58 for age 55-64, 1.31 for age 65-74). Obesity and a sedentary lifestyle were also more common among hypertensive than among nonhypertensive subjects. According to the model, more deaths from coronary artery disease could be prevented among subjects with treated but uncontrolled hypertension by modifying lipids rather than by further reducing blood pressure for men aged 35-54 (reduction of 50 v. 29 deaths per 100,000) and 55-64 (reduction of 171 v. 104 deaths per 100,000) and for women aged 35-54 (reduction of 44 v. 39 deaths per 100,000). Starting antihypertensive therapy in subjects aged 35-74 with untreated hypertension would achieve a greater net reduction in deaths from coronary artery disease than would lipid lowering. Nonetheless, the benefits of lipid therapy were substantial: lipid intervention among hypertensive subjects aged 35-74 represented 36% of the total benefits of treating hyperlipidemia in the total hyperlipidemic population. INTERPRETATION: The clustering of hyperlipidemia and the potential benefits of treatment among hypertensive adults demonstrate the need for screening and treating other cardiovascular risk factors beyond simply controlling blood pressure.
Hypertension is an important cardiovascular risk factor worldwide. It is associated with left ventricular hypertrophy (LVH). Both diastolic and systolic dysfunction may occur in hypertensive heart disease. The ventricles are structurally and functionally interdependent on each other. This was an echocardiographic study intended to describe the impact of left ventricular pressure overload and hypertrophy due to hypertension on right ventricular morphology and function.
One hundred subjects with systemic hypertension and 50 age- and gender-matched normotensive control subjects were used for this study. Two-dimensional (2-D), M-mode and Doppler echocardiographic studies were done to evaluate the structure and function of both ventricles. Data analysis was done using the SPSS 16.0 (Chicago, Ill). Statistical significance was taken as p < 0.05.
Age and gender were comparable between the two groups. Hypertensive subjects had significantly increased left ventricular end-diastolic dimensions, posterior wall thickness, interventricular septal thickness, left atrial dimensions and left ventricular mass and index. The mitral valve E/A ratio was reduced among hypertensive subjects when compared to normal controls (1.15 ± 0.75 vs 1.44 ± 0.31, respectively; p < 0.05). A similar pattern was found in the tricuspid E/A ratio (1.14 ± 0.36 vs 1.29 ± 0.30, respectively; p < 0.05). Hypertensive subjects also had reduced right ventricular internal dimensions (20.7 ± 8.0 vs 23.1 ± 3.1 mm, respectively; p < 0.001) but similar peak pulmonary systolic velocity. The mitral e/a ratio correlated well with the tricuspid e/a ratio.
Systemic hypertension is associated with right ventricular morphological and functional abnormalities. Right ventricular diastolic dysfunction may be an early clue to hypertensive heart disease.
hypertension; right ventricular function; echocardiography; systolic dysfunction; diastolic dysfunction
Morning hypertension is a risk factor for cardiovascular and cerebrovascular events, and consequently diagnosis and control of morning hypertension are considered very important. We previously reported the results of the Azelnidipine Treatment for Hypertension Open-label Monitoring in the Early morning (At-HOME) Study, which indicated that azelnidipine effectively controlled morning hypertension.
The objective of this At-HOME subgroup analysis was to evaluate the sustained blood pressure (BP)-lowering effect of azelnidipine, using mean morning and evening systolic BP [ME average] and morning systolic BP minus evening systolic BP (ME difference).
We analyzed the self-measured home BP data (measured in the morning and at bedtime) from this 16-week prospective observational study to clarify the effect of morning dosing of azelnidipine (mean [± standard deviation] maximum dose 14.3 ± 3.6 mg/day). A subgroup of patients from the At-HOME Study who had an evening home BP measurement within 28 days prior to the baseline date were used for efficacy analysis (n = 2,546; mean age, 65.1 years; female, 53.6 %).
Home systolic BP/diastolic BP levels in the morning and evening were significantly lowered (p < 0.0001) by −19.4 ± 17.1/−10.3 ± 10.6 and −16.9 ± 17.0/−9.4 ± 10.6 mmHg, respectively. Home pulse rates in the morning and evening were also significantly lowered (p < 0.0001) by −3.5 ± 7.8 and −3.5 ± 7.3 beats/min, respectively. At baseline, patients whose ME average was ≥135 mmHg and whose ME difference was ≥15 mmHg (defined as morning-predominant hypertension) accounted for 20.4 % of the study population. However, at the end of the study, the number of such patients was significantly reduced to 7.9 % (p < 0.0001). Patients whose ME average was ≥135 mmHg and whose ME difference was <15 mmHg (defined as sustained hypertension) accounted for 71.1 % of the study population at baseline. This was reduced significantly to 42.8 % at the end of the study (p < 0.0001). ME average decreased significantly from 153.8 ± 15.5 mmHg to 135.6 ± 11.9 mmHg, and ME difference also decreased significantly from 6.7 ± 13.1 mmHg to 4.7 ± 10.8 mmHg (both p < 0.0001).
These results suggest that azelnidipine improved morning hypertension with its sustained BP-lowering effect.
Electronic supplementary material
The online version of this article (doi:10.1007/s40268-013-0007-7) contains supplementary material, which is available to authorized users.