Subclinical, hemodynamic, and echocardiographic abnormalities of high pulse pressure in hypertensive and non-hypertensive adults.

BACKGROUND: High pulse pressure (PP) is associated with cardiovascular events, but subclinical abnormalities in cardiac structure and function in relation to high pulse pressure are not well described. METHODS AND RESULTS: 2225 hypertensive and 1380 non-hypertensive participants with adequate echocardiographic left ventricular measurements were evaluated. Non-hypertensives in the highest PP tertile (compared to the lower tertiles) were older (44 years vs. 40 years, p<0.009), had higher systolic pressure [(SBP) 136 mmHg vs. 108 mmHg] and lower diastolic pressure [(DBP) 54 vs. 71 mmHg (p=.0001)], greater BMI (27 vs. 25 kg/m2, p<.001) and more diabetes (4% vs. 2.25%, p<.001). In the hypertensive group, subjects in the highest PP tertile were older (52 vs 42 years), had higher SBP (157 vs. 116 mmHg) but lower DBP (65 vs. 83 mmHg). In the non-hypertensive group, higher PP (>60 mmHG) was associated with a higher frequency of echocardiographic structural and functional abnormalities, specifically, greater posterior and relative wall thickness, longer isovolumic relaxation time, and concentric left ventricular (LV) hypertrophy. CONCLUSION: In a population-based sample of hypertensive and non-hypertensive participants, higher PP was associated with subclinical abnormalities of cardiac structure and function, which exist even in the absence of hypertension and/or the use of antihypertensive treatment.

High-fat meal effect on LDL, HDL, and VLDL particle size and number in the Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN): an interventional study.

BACKGROUND: Postprandial lipemia (PPL) is likely a risk factor for cardiovascular disease but these changes have not been well described and characterized in a large cohort. We assessed acute changes in the size and concentration of total and subclasses of LDL, HDL, and VLDL particles in response to a high-fat meal. Participants (n = 1048) from the Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN) Study who ingested a high-fat meal were included in this analysis. Lipids were measured at 0 hr (fasting), 3.5 hr, and 6 hr after a standardized fat meal. Particle size distributions were determined using nuclear magnetic resonance spectroscopy. Analyses were stratified by baseline triglycerides (normal vs. elevated) and gender. The effect of PPL on changes in lipoprotein subclasses was assessed using repeated measures ANOVA. RESULTS: Postprandially, LDL-C, HDL-C, VLDL-C, and triglycerides increased regardless of baseline triglyceride status, with the largest increases in VLDL-C and TG; however, those with elevated triglycerides demonstrated larger magnitude of response. Total LDL particle number decreased over the 6-hour time interval, mostly from a decrease in the number of small LDL particles. Similarly, total VLDL particle number decreased due to reductions in medium and small VLDL particles. Large VLDL particles and chylomicrons demonstrated the largest increase in concentration. HDL particles demonstrated minimal overall changes in total particle number. CONCLUSIONS: We have characterized the changes in LDL and VLDL particle number, and their subclass patterns following a high-fat meal.

Fish intake and the risk of incident heart failure: the Women's Health Initiative.

BACKGROUND: Whether fish or the fatty acids they contain are independently associated with risk for incident heart failure (HF) among postmenopausal women is unclear. METHODS AND RESULTS: The baseline Women's Health Initiative Observational Study cohort consisted of 93 676 women ages 50 to 79 years of diverse ethnicity and background, of which 84 493 were eligible for analyses. Intakes of baked/broiled fish, fried fish, and omega-3 fatty acid (eicosapentaenoic acid+docosahexaenoic acid, α-linolenic acid), and trans-fatty acid were determined from the Women's Health Initiative food frequency questionnaire. Baked/broiled fish consumption was divided into 5 frequency categories: <1/mo (referent), 1 to 3/mo, 1 to 2/wk, 3 to 4/wk, ≥5/wk. Fried fish intake was grouped into 3 frequency categories: <1/mo (referent), 1-3/mo, and ≥1/wk. Associations between fish or fatty acid intake and incident HF were determined using Cox models adjusting for HF risk factors and dietary factors. Baked/broiled fish consumption (≥5 servings/wk at baseline) was associated with a hazard ratio of 0.70 (95% confidence interval, 0.51 to 0.95) for incident HF. In contrast, fried fish consumption (≥1 serving/wk at baseline) was associated with a hazard ratio of 1.48 (95% confidence interval, 1.19 to 1.84) for incident HF. No significant associations were found between eicosapentaenoic acid+docosahexaenoic acid, α-linolenic acid, or trans-fatty acid intake and incident HF. CONCLUSIONS: Increased baked/broiled fish intake may lower HF risk, whereas increased fried fish intake may increase HF risk in postmenopausal women.

Aspirin use, dose, and clinical outcomes in postmenopausal women with stable cardiovascular disease: the Women's Health Initiative Observational Study.

BACKGROUND: Despite compelling evidence that aspirin reduces fatal and nonfatal vascular events among the overall population in various settings, women have frequently been underrepresented and their data underreported. We sought to evaluate the relationship between aspirin use, dose (81 or 325 mg), and clinical outcomes among postmenopausal women with stable cardiovascular disease (CVD). METHODS AND RESULTS: Women with CVD (n=8928) enrolled in the Women's Health Initiative Observational Study were used for this analysis. The primary outcome was the incidence of all-cause mortality and cardiovascular events (myocardial infarction, stroke, and cardiovascular death). Among 8928 women with stable CVD, 4101 (46%) reported taking aspirin, of whom 30% were on 81 mg and 70% were on 325 mg. At 6.5 years of follow-up, no significant association was noted for aspirin use and all-cause mortality or cardiovascular events. However, after multivariate adjustment, aspirin use was associated with a significantly lower all-cause (adjusted hazard ratio, 0.86 [0.75 to 0.99]; P=0.04) and cardiovascular-related mortality (adjusted hazard ratio, 0.75 [0.60 to 0.95]; P=0.01) compared with no aspirin. Aspirin use was associated with a lower risk of cardiovascular events (adjusted hazard ratio, 0.90 [0.78 to 1.04]; P=0.14), which did not meet statistical significance. Compared with 325 mg, use of 81 mg was not significantly different for all-cause mortality, cardiovascular events, or any individual end point. CONCLUSIONS: After multivariate adjustment, aspirin use was associated with significantly lower risk of all-cause mortality, specifically, cardiovascular mortality, among postmenopausal women with stable CVD. No significant difference was noted between 81 mg and 325 mg of aspirin. Overall, aspirin use was low in this cohort of women with stable CVD.

Identification of a pleiotropic locus on chromosome 7q for a composite left ventricular wall thickness factor and body mass index: the HyperGEN Study.

BACKGROUND: Left ventricular (LV) mass and wall thickness are closely associated with measures of body size and blood pressure and also correlated with systolic and diastolic function, suggesting a contribution of common physiologic mechanisms, including pleiotropic genes, to their covariation. METHODS: Doppler echocardiography was performed in 434 African-American (1344 individuals) and 284 white families (1119 individuals). We conducted a genome-wide linkage scan for LV mass, LV structure and function, and composite factors derived from a factor analysis of LV structure and function in the HyperGEN Study population. RESULTS: Factor analysis identified (i) a LV wall thickness factor correlated strongly with interventricular septal thickness (IVSTd) and posterior wall thickness (PWTd) and (ii) a LV diastolic filling factor strongly correlated with early and atrial phase peak transmitral filling velocities. The LV phenotypes and composite factor scores were analyzed in multipoint variance components linkage model implemented in SOLAR with 387 microsatellite markers. In whites, the two highest LODs were 3.42 for LV atrial phase peak filling velocity at 144 cM on chromosome 1 and 3.12 for the LV wall thickness factor at 160 cM on chromosome 7. The peak LODs of the component traits (IVSTd and PWTd) clustered at the same region as the composite factor. Adjusting the factor score for body mass index (BMI) substantially reduced the peak LOD at this region (LOD = 1.92). Bivariate linkage analysis of the composite factor with BMI improved LOD to 3.42 at 158 cM. Also in whites, suggestive linkage was observed on chromosomes 2 and 4 for LV mass, chromosomes 3, 5, 10, and 17 for LV atrial phase peak filling velocity, and chromosome 10 for LV diastolic filling factor. In African Americans, suggestive linkage was observed on chromosome 12 for LV mass, chromosome 21 for IVSTd, and chromosome 3 for LV internal diameter at end-diastole. CONCLUSION: Our study suggests that a region on chromosome 7 contains pleiotropic genes contributing to the variations of both LV wall thickness and BMI in whites.

Panic attacks and risk of incident cardiovascular events among postmenopausal women in the Women's Health Initiative Observational Study.

CONTEXT: Previous studies have documented an association of depression and phobic anxiety with cardiovascular morbidity and mortality, but little is known about the cardiovascular sequelae of panic anxiety. OBJECTIVE: To determine whether panic attacks are associated with risk of cardiovascular morbidity and mortality in postmenopausal women. DESIGN: Prospective cohort survey. SETTING: Ten clinical centers of the 40-center Women's Health Initiative. PARTICIPANTS: A total of 3369 community-dwelling, generally healthy postmenopausal women (aged 51-83 years) enrolled between 1997 and 2000 in the Myocardial Ischemia and Migraine Study who completed a questionnaire about occurrence of panic attacks in the previous 6 months. MAIN OUTCOME MEASURES: Cardiovascular/cerebrovascular outcomes (fatal and nonfatal myocardial infarction and stroke) and all-cause mortality were ascertained after a mean of 5.3 years of follow-up. RESULTS: A 6-month history of full-blown panic attacks, endorsed by 10% of postmenopausal women in this cohort, was associated with both coronary heart disease (hazard ratio, 4.20; 95% confidence interval, 1.76-9.99) and the combined end point of coronary heart disease or stroke (hazard ratio, 3.08; 95% confidence interval, 1.60-5.94) after controlling for multiple potential confounders. The hazard ratio for all-cause mortality, excluding those with a history of cardiovascular/cerebrovascular events, was 1.75 (95% confidence interval, 1.04-2.94). CONCLUSION: Panic attacks are relatively common among postmenopausal women and appear to be an independent risk factor for cardiovascular morbidity and mortality in older women.

Plasma adiponectin concentrations and correlates in African Americans in the Hypertension Genetic Epidemiology Network (HyperGEN) study.

Adiponectin has demonstrated insulin-sensitizing, antiatherogenic, and anti-inflammatory properties, and may be an important risk factor for coronary heart disease and diabetes. Relatively few previous studies of plasma adiponectin have included sizable numbers of African Americans. The objective of the study was to investigate plasma concentrations of adiponectin and correlates of these concentrations in African Americans. This was a cross-sectional analysis that took place within the Hypertension Genetic Epidemiology Network. This study included 211 normotensive offspring (aged 22-37 years) of hypertensive siblings recruited by the Hypertension Genetic Epidemiology Network Birmingham, AL, field center. In addition to measuring plasma adiponectin, demographic and lifestyle data were collected, and anthropometric, clinical, and laboratory measurements were obtained. Mean plasma adiponectin concentration was 5.5+/-3.8 microg/mL. Adiponectin was 55% higher in women than in men: 6.5+/-4.4 vs 4.2+/-2.5 microg/mL, respectively (P<.0001). In a multivariable analysis, high-density lipoprotein cholesterol concentration was positively associated and male sex and insulin concentration were negatively associated with plasma adiponectin concentration. Plasma adiponectin concentrations in these African Americans were lower than those reported in other racial/ethnic groups, including Japanese, whites, and Pima Indians. The directions of the associations of plasma adiponectin with other factors were in agreement with results in other racial/ethnic groups.

Circulating levels of endothelial adhesion molecules and risk of diabetes in an ethnically diverse cohort of women.

Elevated circulating levels of soluble adhesion molecules as markers of endothelial dysfunction have been related to insulin resistance and its associated metabolic abnormalities. However, their associations with type 2 diabetes remain inconclusive. We conducted a prospective nested case-control study to examine the associations between plasma levels of E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) and diabetes risk among 82,069 initially healthy women aged 50-79 years from the Women's Health Initiative Observational Study. During a median follow-up of 5.9 years, 1,584 incident diabetes case subjects were matched with 2,198 control subjects by age, ethnicity, clinical center, time of blood draw, and follow-up time. Baseline median levels of the biomarkers were each significantly higher among case subjects than among control subjects (E-selectin, 49 vs. 37 ng/ml; ICAM-1, 324 vs. 280 ng/ml; and VCAM-1, 765 vs. 696 ng/ml [all P values <0.001]). After adjustment for risk factors, the relative risks of diabetes among women in the highest quartile versus those in the lowest quartile were 3.46 for E-selectin (95% CI 2.56-4.68; P for trend <0.0001), 2.34 for ICAM-1 (1.75-3.13; P for trend <0.0001), and 1.48 for VCAM-1 (1.07-2.04; P for trend = 0.009). E-selectin and ICAM-1 remain significant in each ethnic group. In conclusion, higher levels of E-selectin and ICAM-1 were consistently associated with increased diabetes risk in a multiethnic cohort of U.S. postmenopausal women, implicating an etiological role of endothelial dysfunction in the pathogenesis of type 2 diabetes.

A whole genome scan for pulse pressure/stroke volume ratio in African Americans: the HyperGEN study.

BACKGROUND: Arterial stiffness is reported in numerous family studies to be heritable. Linkage analysis has identified genomic regions that likely harbor genes contributing to its phenotypic expression. We sought to identify loci contributing to arterial stiffness in a large group of African-American hypertensive families. METHODS: We performed a genome scan on 1251 African Americans in families participating in the HyperGEN (Hypertension Genetic Epidemiology Network) study. Children of the hypertensive proband generation were also included in the analysis. Arterial stiffness was estimated as pulse pressure (PP; systolic - diastolic blood pressure [BP]) divided by echocardiographically determined stroke volume (SV). The PP/SV ratio was adjusted for several nongenetic sources of variation, including demographic and lifestyle factors. The residual phenotype was analyzed using multipoint variance components linkage implemented in SOLAR 2.0.3. RESULTS: Arterial stiffness was 20% heritable in African Americans. Two regions were highly suggestive of linkage, one between markers D1S1665 and D1S1728 in the 215-cM region of chromosome 1 (LOD = 3.08), and another between D14S588 and D14S606 in the 85-cM region of chromosome 14 (LOD = 2.42). Two candidate genes (GPR-25, SMOC-1) are located in the linked regions. SMOC-1 is of physiological interest because it codes a secreted glycoprotein with five domains, each containing regions homologous to those on other proteins that mediate cell-matrix interactions. GPR-25 is homologous to receptors involved in BP regulation. CONCLUSIONS: At least two chromosomal regions in humans are likely to harbor genes contributing to interindividual variation in PP/SV ratio, an index of arterial stiffness, in African Americans.

Genome-wide linkage mapping for valve calcification susceptibility loci in hypertensive sibships: the Hypertension Genetic Epidemiology Network Study.

It remains unclear whether genetic factors contribute to the susceptibility to valve calcification. Accordingly, echocardiograms and genotyping were performed in 1871 hypertensive siblings who participated in the Hypertension Genetic Epidemiology Network Study. Genome-wide affected sibpair nonparametric linkage analysis was conducted using the allele-sharing method implemented in the Merlin computer program. A total of 1014 sibships from 858 families were evaluated for aortic valve sclerosis or mitral annular calcification. Of these, 78 sibships from 68 families contained > or =2 affected siblings with > or =1 type of valve calcification (142 affected siblings). All 3 of the traits showed a modest degree of familial aggregation, with sibling recurrence risk (SD) and sibling recurrence risk ratio (95% CI) being 0.25 (0.035) and 2.31 (1.72 to 3.11) for aortic valve sclerosis, 0.25 (0.035) and 1.78 (1.36 to 2.33) for mitral annular calcification, and 0.31 (0.030) and 1.52 (1.24 to 1.85) for aortic valve sclerosis and mitral annular calcification, respectively. Affected sibpair linkage analysis revealed the highest logarithm of odds score (3.14) in chromosome 16 at 105.6 cM for aortic valve sclerosis. Other chromosomal regions with logarithm of odds score > or =1.9 were found in chromosomes 19 (2.88), 16 (2.63), 1 (2.12), and 2 (2.03) for aortic valve sclerosis and chromosome 13 (2.12) for any valve calcification. There was no logarithm of odds score > or =1.9 for mitral annular calcification. Our study shows strong linkage of aortic valve sclerosis to chromosome 16q22.1-q22.3 and suggestive linkage to chromosome 19p13.11-p11 and identifies several other promising genomic regions that may contain specific susceptibility loci for valve calcification.

Panic attacks, daily life ischemia, and chest pain in postmenopausal women.

BACKGROUND: Chest pain is a common symptom of panic attacks, but little is known about the relationship in older women among panic attacks, chest pain, and daily life ischemia. METHODS: The authors conducted a cross-sectional survey of 3063 community-dwelling, generally healthy postmenopausal women enrolled between 1997 and 2000 in the Myocardial Ischemia and Migraine Study in 10 clinical centers of the 40-center Women's Health Initiative. Participants, ages 50 to 79 years, completed a questionnaire about occurrence of panic attacks in the previous 6 months and underwent 24-hour ambulatory electrocardiogram monitoring (AECG); 2705 women had valid AECG recordings and panic attack questionnaires. ST depression on AECG, heart rate variability (HRV), and chest pain episodes were compared among women with and without a 6-month history of panic attack. RESULTS: There was no difference in overall prevalence of ischemic episodes during AECG between women with and without panic attacks. Women with a recent history of panic were more likely to experience chest pain during AECG after controlling for potential confounders (odds ratio [OR] = 2.01; 95% confidence interval [CI] = 1.40-2.88), including both nonischemic (OR = 1.83; 95% CI = 1.26-2.65) and ischemic chest pain (OR = 4.94; 95% CI = 1.41-17.30). Although mean HRV was lower in those with panic attacks (p = .017), this was not significant after controlling for confounders. CONCLUSIONS: Postmenopausal women with a recent history of panic attacks do not appear to have more daily life ischemia as measured by occurrence of ST depression during 24-hour monitoring, but do have more chest pain and possibly lower HRV, suggesting that even sporadic panic attacks may be related to cardiovascular risk.

Impact of cyclooxygenase inhibitors in the Women's Health Initiative hormone trials: secondary analysis of a randomized trial.

OBJECTIVES: We evaluated the hypothesis that cyclooxygenase (COX) inhibitor use might have counteracted a beneficial effect of postmenopausal hormone therapy, and account for the absence of cardioprotection in the Women's Health Initiative hormone trials. Estrogen increases COX expression, and inhibitors of COX such as nonsteroidal anti-inflammatory agents appear to increase coronary risk, raising the possibility of a clinically important interaction in the trials. DESIGN: The hormone trials were randomized, double-blind, and placebo-controlled. Use of nonsteroidal anti-inflammatory drugs was assessed at baseline and at years 1, 3, and 6. SETTING: The Women's Health Initiative hormone trials were conducted at 40 clinical sites in the United States. PARTICIPANTS: The trials enrolled 27,347 postmenopausal women, aged 50-79 y. INTERVENTIONS: We randomized 16,608 women with intact uterus to conjugated estrogens 0.625 mg with medroxyprogesterone acetate 2.5 mg daily or to placebo, and 10,739 women with prior hysterectomy to conjugated estrogens 0.625 mg daily or placebo. OUTCOME MEASURES: Myocardial infarction, coronary death, and coronary revascularization were ascertained during 5.6 y of follow-up in the estrogen plus progestin trial and 6.8 y of follow-up in the estrogen alone trial. RESULTS: Hazard ratios with 95% confidence intervals were calculated from Cox proportional hazard models stratified by COX inhibitor use. The hazard ratio for myocardial infarction/coronary death with estrogen plus progestin was 1.13 (95% confidence interval 0.68-1.89) among non-users of COX inhibitors, and 1.35 (95% confidence interval 0.86-2.10) among continuous users. The hazard ratio with estrogen alone was 0.92 (95% confidence interval 0.57-1.48) among non-users of COX inhibitors, and 1.08 (95% confidence interval 0.69-1.70) among continuous users. In a second analytic approach, hazard ratios were calculated from Cox models that included hormone trial assignment as well as a time-dependent covariate for medication use, and an interaction term. No significant interaction was identified. CONCLUSIONS: Use of COX inhibitors did not significantly affect the Women's Health Initiative hormone trial results.

Prevalence and determinants of electrocardiographic left ventricular hypertrophy among a multiethnic population of postmenopausal women (The Women's Health Initiative).

Our objectives were to determine the prevalence and factors related to left ventricular hypertrophy (LVH) among older women for commonly used electrocardiographic criteria. LVH is a potent risk factor for cardiovascular disease, especially among women. However, its value has been limited, in part, by the use of different electrocardiographic criteria and the lack of a clearly defined standard for the general population. A total of 3,613 eligible women, aged 50 to 79 years, underwent medical history, physical measurements, and biochemical determinations and had behavioral factors recorded at baseline. Three LVH indexes were derived from computer measurement of the electrocardiogram: hypertrophied left ventricular mass > or =171.04 g (HLVM); Cornell voltage > or =2,200 microV; and Minnesota Code items. The prevalence of LVH ranged from <1% to 13% when stratified by age, ethnicity, and scoring technique. Baseline traits differed significantly for those meeting the LVH criteria. Predictors (p <0.01) of HLVM were age (odds ratio 0.66), height (odds ratio 1.47), waist/hip ratio (odds ratio 1.30), systolic blood pressure (odds ratio 1.18); low-density lipoprotein cholesterol (odds ratio 0.97), log insulin (odds ratio 2.10), dietary kilocalories (odds ratio 1.16), weekly energy expenditure (odds ratio 0.53), hypertension (odds ratio 1.61), current estrogen use (odds ratio 0.60), and current smoker (odds ratio 0.47). The presence of the metabolic syndrome was related to all LVH indexes, with odds ratios of 4.95, 2.24, and 2.35, respectively, for HLVM, Cornell voltage, and Minnesota Code. In conclusion, the prevalence of LVH varied by ethnicity and the electrocardiographic index used. However, the baseline traits, especially the factors associated with the metabolic syndrome, were consistently and strongly related to all LVH indexes, particularly HLVM. Intervention on these factors may provide strategies for reducing LVH, a strong independent risk factor for cardiovascular morbidity and mortality among women.

Genome-wide linkage analysis for loci affecting pulse pressure: the Family Blood Pressure Program.

Pulse pressure, the difference between systolic and diastolic blood pressure, is an independent risk factor for cardiovascular disease. Increased pulse pressure reflects reduced compliance of arteries and is a marker of atherosclerosis. To locate genes that affect pulse pressure, a genome-wide linkage scan for quantitative trait loci influencing pulse pressure was performed using variance components methods as implemented in sequential oligogenic linkage analysis routines. The analysis sample included 10 798 participants in 3320 families who were recruited as part of the Family Blood Pressure Program and were phenotyped with an oscillometric blood pressure measurement device using a consistent protocol across centers. Pulse pressure was adjusted for the effects of sex, age, age2, age-by-sex interaction, age2-by-sex interaction, body mass index, and field center to remove sources of variation other than the genetic effects related to pulse pressure. Significant linkage was observed on chromosome 18 (logarithm of odds [LOD]=3.2) in a combined racial sample, chromosome 20 (LOD=4.4), and 17 (LOD=3.6) in Hispanics, chromosome 21 (LOD=4.3) in whites, chromosome 19 (LOD=3.1) in a combined sample of blacks and whites, and chromosome 7 (logarithm of odds [LOD]=3.1) in blacks from the GenNet Network. Our genome scan shows significant evidence for linkage for pulse pressure in multiple areas of the genome, supporting previous published linkage studies. The identification of these loci for pulse pressure and the apparent congruence with other blood pressure phenotypes provide increased support that these regions contain genes influencing blood pressure phenotypes.

Left atrial systolic force and cardiac markers of preclinical disease in hypertensive patients: the Hypertension Genetic Epidemiology Network (HyperGEN) Study.

BACKGROUND: Left atrial systolic force (LASF) has been recently reported to be associated with prolonged left ventricular (LV) relaxation and concentric LV geometry in a clinical setting. This study analyzes the association of increased LASF to LV geometry and function in hypertensive patients from a population study. METHODS: Doppler echocardiographic findings were examined in 684 subjects with treated hypertension and without prevalent cardiovascular disease from the Hypertension Genetic Epidemiology Network (HyperGEN) Study (426 African American, 448 female, 125 diabetic, 174 obese; age 53.8+/-10.8 years). The LASF was assessed from the mitral orifice area and pulse-wave Doppler peak A flow velocity. The LASF was defined as being high if >14.33 kdynes (90th percentile of the normal distribution in 246 normal adults). RESULTS: The LASF was high in 269 participants (39.3% of study population), who were older and had higher mean body mass index (all P<.01). Participants with high LASF had higher systolic BP and heart rate (both P<.01) but similar diastolic BP. After controlling for covariates, participants with high LASF exhibited higher LV dimensions and mass than those with normal LASF (all P<.01). The prevalence of LV hypertrophy was also higher (P<.001). Participants with high LASF exhibited normal ejection fraction, higher stroke volume, cardiac output, E and A velocities, slower E deceleration, and lower E/A ratio than those with normal LASF (all P<.01). CONCLUSIONS: Enhanced LASF is associated with LV hypertrophy, normal LV chamber function, increased cardiac output, and prolonged relaxation. The LASF is a preload-dependent measure.

Depressive symptoms and heart rate variability in postmenopausal women.

BACKGROUND: Depressive symptoms have been associated with increased cardiac morbidity and mortality rates, but the pathophysiologic mechanism linking depressive symptoms to cardiovascular outcome has yet to be fully understood. Lower heart rate variability has also been associated with increased risk of cardiac events in healthy individuals and in patients with coronary artery disease. Findings regarding a relationship between depressive symptoms and heart rate variability that could explain increased cardiovascular risk have been inconsistent across studies. METHODS: As an ancillary study to the Women's Health Initiative Observational Study, 3372 postmenopausal women aged 50 to 83 years were enrolled for further evaluation using 24-hour ambulatory electrocardiographic monitoring. A shortened version of the Center for Epidemiological Studies Depression Scale and the Diagnostic Interview Schedule were administered. Women with adequate electrocardiographic data and depressive symptom information and without coronary artery disease were analyzed (n = 2627). RESULTS: Two hundred sixty-nine women (10.2%) had depressive symptoms as measured using the 2 instruments. Women with depressive symptoms had a higher mean +/- SD heart rate (77.4 +/- 9.6 vs 75.5 +/- 8.5 beats/min) and lower heart rate variability than women without depressive symptoms. All differences remained significant after adjusting for age (P<.01). CONCLUSIONS: Women with depressive symptoms had significant reductions in heart rate variability and higher heart rates, suggestive of increased sympathetic tone. These findings may contribute to the increased cardiac morbidity and mortality rates associated with depression in other studies.

Interarm differences in seated systolic and diastolic blood pressure: the Hypertension Genetic Epidemiology Network study.

OBJECTIVE: To examine whether blood pressure (BP) differs between arms in hypertensive siblings and randomly selected volunteers, and whether this difference is explained by cardiovascular risk factors. METHODS: The Hypertension Genetic Epidemiology Network recruited 2395 hypertensive siblings and 854 volunteers. BP was measured six times (three measurements per arm) in seated participants using a Dinamap monitor. The average of three measurements was calculated per arm and the difference taken between arms (i.e. interarm BP differences). RESULTS: The mean age of the subjects was 56 years, and about one-half of the sample was male. More than one-half of the sample was African-American. The mean diastolic BP was equal in the two arms in the random sample (68.8 versus 68.7 mmHg) and in hypertensive siblings (73.4 versus 73.1 mmHg), as was systolic BP (random, 119.6 versus 119.3 mmHg; hypertensives, 130.8 versus 130.7 mmHg). The mean interarm diastolic and systolic BP differences were 2.96 +/- 2.51 and 4.61 +/- 4.10 mmHg, respectively, in the random sample and were 3.09 +/- 2.73 and 5.35 +/- 4.98 mmHg, respectively, in hypertensive siblings. Few (random, 1.6%; hypertensives, 2.8%) had interarm diastolic BP differences > 10 mmHg, but 9.2% of the random sample and 14.2% of hypertensive siblings had systolic BP differences > 10 mmHg. Obesity, higher heart rate, and higher systolic BP were associated with larger interarm BP differences. These results have implications for blood pressure measurement in research settings and in screening programs.

A genome scan for linkage with aortic root diameter in hypertensive African Americans and whites in the Hypertension Genetic Epidemiology Network (HyperGEN) study.

BACKGROUND: Aortic root dilation is a prominent feature in several cardiovascular diseases. This study seeks to identify genomic regions linked to variation in the aortic root diameter (ARD) in hypertensive African American and white individuals. METHODS: We performed a genome scan for ARD in the Hypertension Genetic Epidemiology Network Study, one of four networks in the National Heart, Lung, and Blood Institute Family Blood Pressure Program (FBPP). Data were collected from 1129 African American siblings from 504 hypertensive sibships and 883 white siblings from 374 hypertensive sibships. Standardized residual values of ARD were calculated using linear regression, adjusting for effects of age, age2, and field center (ie, minimally adjusted model), separately in groups composed by sex and ethnicity. The ARD was additionally adjusted for height, weight, diastolic BP, and systolic BP in a fully adjusted model. Multipoint linkage analysis was performed using the GENEHUNTER2 variance components method. RESULTS: Suggestive evidence for linkage was found on chromosome 5 at 85 cM in African Americans, with a maximal log of the odds (LOD) score of 2.07. Suggestive evidence for linkage was found on chromosome 1 at 157 cM in whites, with a maximal LOD score of 2.40. CONCLUSIONS: Our findings suggest that genes present on chromosomes 1 and 5 might influence inter-individual variation in aortic root diameter.

Further evidence of a quantitative trait locus on chromosome 18 influencing postural change in systolic blood pressure: the Hypertension Genetic Epidemiology Network (HyperGEN) Study.

BACKGROUND: Postural change in systolic blood pressure (SBP) is prospectively associated with several disease outcomes including hypertension, stroke, and coronary heart disease. The objective of this study was to characterize further a possible quantitative trait locus on chromosome 18q21 influencing SBP response to a postural challenge. METHODS: A prior genome scan of postural SBP response in 636 subjects of white ethnicity from 285 hypertensive sibships in the Hypertension Genetic Epidemiology Network (HyperGEN) indicated suggestive evidence for linkage on chromosome 18q21. This study included a de novo set of 452 African American pedigrees from the HyperGEN study and an expanded set of 372 white pedigrees. Variance components linkage analysis of postural SBP change was conducted using microsatellite markers on chromosome 18, and association studies were performed with a common single nucleotide polymorphism (variant 13) in the gene encoding NEDD4L, a key regulator of fine sodium reabsorption in the distal nephron. RESULTS: Combined analysis of all white and African American pedigrees yielded a LOD score of 4.25 at 80 cM on chromosome 18q21, with at least nominal evidence of linkage at this position in both white (LOD: 3.43) and African American (LOD: 1.14) subjects. Postural SBP response was associated with variant 13 of the NEDD4L in a subset of white subjects taking medications effective in treating sodium volume-dependent hypertension (alpha1-blockers, calcium channel blockers, and/or diuretics). CONCLUSION: These data provide further evidence for a quantitative trait locus on chromosome 18q21 influencing postural change in SBP.

Body composition and fat distribution influence systemic hemodynamics in the absence of obesity: the HyperGEN Study.

BACKGROUND: We have shown that increased cardiac output is related to both fat-free mass and fat mass in obesity. OBJECTIVE: We studied the association of body fat distribution and body composition with flow-resistance relations in overweight. DESIGN: We studied 521 overweight, nonobese participants in the Hypertension Genetic Epidemiology Network (HyperGEN) Study-a component of the National Heart, Lung, and Blood Institute Family Blood Pressure Program, designed to assess the genetic basis of hypertension. Participants had normal ventricular function and no cardiovascular disease: 261 with central fat distribution (CFD) (waist girth >88 cm in women and >102 cm in men) and 260 with peripheral fat distribution (PFD). Fat-free mass (FFM) and fat mass (FM) were measured by bioelectric impedance. Body composition was estimated as FM/FFM. Echocardiographic stroke volume (SV) and cardiac output (CO) were measured. RESULTS: Hypertension was present in 73% of the subjects with PFD and in 78% with CFD. Overweight with CFD was associated with greater FM/FFM in both normotensive and hypertensive participants. After FFM, age, sex, and race were controlled for, SV and CO were higher in subjects overweight with CFD than in those with PFD, whereas peripheral resistance was not significantly different. Differences in CO between CFD and PFD were reduced after further adjustment for FM. After the covariates were controlled for, hypertensive subjects had higher peripheral resistance and lower arterial compliance than did normotensive participants, but cardiac output was not significantly different. CONCLUSION: CFD is associated with more severe abnormalities in body composition and with higher CO independently of FFM in overweight, nonobese subjects.