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.

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.

Walking compared with vigorous exercise for the prevention of cardiovascular events in women.

BACKGROUND: The role of walking, as compared with vigorous exercise, in the prevention of cardiovascular disease remains controversial. Data for women who are members of minority racial or ethnic groups are particularly sparse. METHODS: We prospectively examined the total physical-activity score, walking, vigorous exercise, and hours spent sitting as predictors of the incidence of coronary events and total cardiovascular events among 73,743 postmenopausal women 50 to 79 years of age in the Women's Health Initiative Observational Study. At base line, participants were free of diagnosed cardiovascular disease and cancer, and all participants completed detailed questionnaires about physical activity. We documented 345 newly diagnosed cases of coronary heart disease and 1551 total cardiovascular events. RESULTS: An increasing physical-activity score had a strong, graded, inverse association with the risk of both coronary events and total cardiovascular events. There were similar findings among white women and black women. Women in increasing quintiles of energy expenditure measured in metabolic equivalents (the MET score) had age-adjusted relative risks of coronary events of 1.00, 0.73, 0.69, 0.68, and 0.47, respectively (P for trend, <0.001). In multivariate analyses, the inverse gradient between the total MET score and the risk of cardiovascular events remained strong (adjusted relative risks for increasing quintiles, 1.00, 0.89, 0.81, 0.78, and 0.72, respectively; P for trend <0.001). Walking and vigorous exercise were associated with similar risk reductions, and the results did not vary substantially according to race, age, or body-mass index. A brisker walking pace and fewer hours spent sitting daily also predicted lower risk. CONCLUSIONS: These prospective data indicate that both walking and vigorous exercise are associated with substantial reductions in the incidence of cardiovascular events among postmenopausal women, irrespective of race or ethnic group, age, and body-mass index. Prolonged sitting predicts increased cardiovascular risk.

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.

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.

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.

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.

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.

Tissue plasminogen activator antigen and D-dimer as markers for atherothrombotic risk among healthy postmenopausal women.

BACKGROUND: Plasma markers of fibrinolytic function are associated with incident coronary events among several, but not all, prospective epidemiologic investigations of healthy individuals. Few studies have evaluated this relationship in women. In addition, although menopausal hormone therapy (HT) may alter markers of fibrinolytic function, the relevance of this effect for coronary risk assessment has not been studied. METHODS AND RESULTS: In a prospective, nested case-control study among 75 343 postmenopausal women without prior cardiovascular disease or cancer, we evaluated the relationships of elevated tissue plasminogen activator (tPA) antigen and D-dimer with subsequent first coronary heart disease events over a median period of 2.9 years. Baseline levels of both biomarkers were higher among 304 cases compared with 304 controls matched on age, smoking status, ethnicity, and length of follow-up; median values were 9.0 versus 7.4 ng/mL (P<0.001) for tPA antigen and 27.6 versus 23.4 ng/mL (P=0.001) for D-dimer. In matched-pairs analyses, the odds ratio in the highest versus lowest quartile of tPA antigen was 3.5 (95% CI, 2.1 to 5.8; P trend <0.001) and for D-dimer was 2.0 (95% CI, 1.2 to 3.2; P trend=0.005). After adjustment for lipid and nonlipid risk factors, including C-reactive protein, tPA antigen remained a significant predictor. Multivariable-adjusted associations for D-dimer, although attenuated, largely remained statistically significant. When stratified by HT, the relationship between tPA antigen and incident coronary heart disease was similar among nonusers, estrogen-only users, and current users of any HT. CONCLUSIONS: Elevated tPA antigen and, to a lesser extent, D-dimer are independently associated with incident coronary events among postmenopausal women. In analyses stratified by HT, tPA antigen remained a consistent marker of increased coronary risk.

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.

Evidence for a gene influencing fasting LDL cholesterol and triglyceride levels on chromosome 21q.

High levels of low-density lipoprotein (LDL) cholesterol, low levels of high-density lipoprotein (HDL) cholesterol, and high levels of triglycerides (TG) are strong predictors of cardiovascular disease risk. Motivated by previous evidence for pleiotropy between cholesterol and TG levels, we conducted bivariate linkage analysis of LDL cholesterol and TG concentration among participants of the Hypertension Genetic Epidemiolgy Network (HyperGEN), one of four networks in the NHLBI sponsored Family Blood Pressure Program Project. All available hypertensive siblings and their first-degree relatives were recruited. Both phenotypes were similarly adjusted for ethnicity, study center, sex, age, age-by-sex interactions, smoking, alcohol consumption, hormone use, diabetes medication use, and waist circumference. Variance component linkage analysis was performed as implemented in SOLAR, using ethnicity-specific marker allele frequencies derived from founders and multipoint IBDs calculated in MERLIN. A maximum genome-wide empirical LOD score of 3.9 was detected on chromosome 21 at 54cM, between markers D21S2055 and D21S1446. This signal overlaps with suggestive and/or significant linkages for total cholesterol, LDL cholesterol, and apolipoprotein B in three other studies and is suggestive of one or more genes on chromosome 21q jointly regulating LDL cholesterol and TG concentration.

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.

Aortic valve sclerosis is associated with preclinical cardiovascular disease in hypertensive adults: the Hypertension Genetic Epidemiology Network study.

RATIONALE: Aortic valve sclerosis (AVS) has been associated with atherosclerosis and increased all-cause and cardiovascular death. However, whether AVS is associated with preclinical cardiovascular disease among adults at high risk because of hypertension has not been determined in a population-based sample. METHODS AND RESULTS: Clinical and echocardiographic parameters were measured in 1624 hypertensive participants (54 +/- 11 years, 65% women, 63% black, 17% diabetic, 19% smokers) without significant valvular or cardiovascular diseases in the population-based Hypertension Genetic Epidemiology Network study. The 152 participants with AVS (9.4%), compared with participants without AVS, were older, more often white, male, treated for hypertension or hypercholesteromia (all P < 0.05) and had longer duration and worse hypertension, but did not differ in diabetes status, smoking or fenfluramine use. Adjusting for age, gender and race, the AVS group had higher total cholesterol/high-density lipoprotein-cholesterol (P < 0.05). Controlling for age, gender, race and other clinical covariates, AVS was independently associated with higher septal, posterior and relative wall thicknesses, isovolumic relaxation time and left atrial diameter, and with mild aortic regurgitation and mitral annular calcification (all P < 0.05). CONCLUSIONS: In a population-based sample of hypertensive adults, AVS was prevalent (9.4%) and associated with a proatherogenic clinical profile and abnormal left ventricular geometry and filling, increased left atrial size and mitral annular calcification, which may contribute to the adverse prognosis associated with AVS.

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.

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.

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.

Physical activity and diabetes risk in postmenopausal women.

BACKGROUND: To evaluate the hypothesis that physical activity independently predicts type 2 diabetes risk in postmenopausal African-American, Hispanic, Asian, and Caucasian women. METHODS: We prospectively evaluated the relationship between incident type 2 diabetes, walking, and total physical activity at baseline in the Women's Health Initiative Observational Study. Baseline data were collected between September 1994 and December 1998; incident diabetes was identified through August 2002. Hazard ratios for self-reported diabetes adjusted for body mass index (BMI) and other variables were evaluated across categories of physical activity in Caucasian, African-American, Hispanic, and Asian/Pacific Islander women. RESULTS: Incident diabetes was reported by 2.2% of Caucasian, 6.2% of African-American, 4.5% of Hispanic, 3% of Asian, and 5.7% of American Indian women (p <0.0001 across ethnic groups) during 458,018 woman-years of follow-up. Among Caucasian women, walking (multivariate-adjusted hazard ratios 1.00, 0.85, 0.87, 0.75, 0.74; p <0.001 for trend across exercise quintiles) and total physical activity score (hazard ratios 1.00, 0.88, 0.74, 0.80, 0.67; p =0.002) demonstrated a strong inverse relationship with diabetes risk. In BMI-adjusted models, African-American women in higher physical activity categories were less likely to develop diabetes than women in the lowest physical activity category. After adjusting for age and multiple risk factors, however, no significant association between physical activity and diabetes risk was apparent for African-American, Hispanic, or Asian women. CONCLUSIONS: These findings suggest a stronger and more independent association of physical inactivity with development of diabetes in Caucasian women than in minority women, but could also be explained by less precise risk estimates in minority women or the role of chance.

Prevalence and correlates of panic attacks in postmenopausal women: results from an ancillary study to the Women's Health Initiative.

BACKGROUND: Panic attacks are known to be more common in women than in men, but the prevalence and correlates of panic in the postmenopausal period have not been well defined. METHODS: Cross-sectional survey of 3369 community-dwelling postmenopausal women enrolled between December 1, 1997, and November 30, 2000, in the Myocardial Ischemia and Migraine Study, a 10-center ancillary study of the 40-center Women's Health Initiative. Participants, aged 50 to 79 years and predominantly white (73%), completed questionnaires about the occurrence of panic attacks in the previous 6 months and about migraine headaches and underwent 24-hour ambulatory electrocardiographic monitoring. The 6-month prevalences of full-blown and limited-symptom panic attacks were calculated, and their associations with other sociodemographic and clinical variables were examined in multivariate analyses. RESULTS: One of the panic attack types was reported by 17.9% (95% confidence interval, 16.6%-19.2%) of women (full-blown attacks, 9.8%; limited-symptom attacks, 8.1%). Adjusting for age and race or ethnicity, full-blown panic attacks were more common in women with a history of migraine, emphysema, cardiovascular disease, chest pain during ambulatory electrocardiography, and symptoms of depression. Full-blown panic attacks were associated in a dose-response manner with negative life events during the past year. Panic attacks were associated with functional impairment even after adjusting for comorbid medical conditions and depression. There was no significant association with self-reported use of hormone replacement therapy. CONCLUSIONS: Panic attacks may be relatively common among postmenopausal women and seem to be associated with stressful life events, medical comorbidity, and functional impairment.

Appetite suppressants and valvular heart disease in a population-based sample: the HyperGEN study.

PURPOSE: Previous studies of the association between the use of appetite suppressants and valvular heart disease have not accounted for the effects of valvular structure and aortic root diameter, which are associated with obesity. We assessed whether the use of the appetite suppressants fenfluramine/dexfenfluramine, either alone or with phentermine, was associated with aortic regurgitation while adjusting for these variables. SUBJECTS AND METHODS: The sample included 2524 adult participants in the population-based Hypertension Genetic Epidemiology Network study. Information regarding current drug use was assessed during a clinical examination. Medication use was continued at the time of echocardiographic study. Expert readers blinded to current therapy read echocardiograms centrally at Cornell Medical Center. Analyses of the associations between use of fenfluramine/dexfenfluramine (alone or with phentermine) and aortic regurgitation adjusted for potential confounders, including aortic root dilatation and valve fibrocalcification. RESULTS: Nineteen participants, all of whom had hypertension, were being treated with fenfluramine or dexfenfluramine (5 on these agents alone, 14 also with phentermine). Aortic regurgitation was present in 32% (n = 6) of those taking fenfluramine or dexfenfluramine versus 6% (162/2505) of remaining subjects (P = 0.001). In multivariate-adjusted analyses, treatment with fenfluramine or dexfenfluramine was associated with aortic regurgitation (odds ratio [OR] = 4.9; 95% confidence interval [CI]: 1.7 to 14) and aortic fibrocalcification (OR = 5.2; 95% CI: 1.9 to 15). CONCLUSION: In a population-based sample, use of fenfluramine or dexfenfluramine, alone or in combination with phentermine, was associated with aortic regurgitation independent of aortic dilatation or fibrocalcification.