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Albert Oberman

Publications and source records attributed to Albert Oberman.

At least 19 recordsLinked to original sources
PubMed2007

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.

Adult↗
PubMed2006

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.

Activities of Daily Living↗
PubMed2006

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.

Journal Article↗
PubMed2006

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.

Age Factors↗
PubMed2005

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.

Adult↗
PubMed2005

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.

Age Factors↗
PubMed2005

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.

Black or African American↗
PubMed2005

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.

Adult↗
PubMed2005

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.

Adult↗
PubMed2005

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.

Adult↗
PubMed2005

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.

Adipose Tissue↗
PubMed2005

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.

Adult↗
PubMed2005

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.

Adult↗
PubMed2004

Association between cardiovascular outcomes and antihypertensive drug treatment in older women.

CONTEXT: Diuretic-based therapy is at least as effective as newer classes of agents for hypertension. However, many patients with hypertension require treatment with more than 1 drug class to achieve blood pressure control. The relative benefits or risks of 2-drug-class combinations are not well known. OBJECTIVE: To prospectively evaluate if there are differences in cardiovascular mortality among postmenopausal women with hypertension but no history of cardiovascular disease (CVD) treated with different classes of antihypertensive agents, singly or in combination. DESIGN, SETTING, AND PARTICIPANTS: Women with hypertension enrolled in the Women's Health Initiative Observational Study, a longitudinal multicenter cohort study of 93 676 women aged 50 to 79 years at baseline (1994-1998), assessed for a mean of 5.9 years. MAIN OUTCOME MEASURES: Relationship between baseline use of ACE inhibitors, beta-blockers, calcium channel blockers, or diuretics, or a combination of these, and incidence of coronary heart disease, stroke, and CVD mortality. RESULTS: Among 30,219 women with hypertension but no history of CVD, 19,889 were receiving pharmacological antihypertensive treatment, of whom 11,294 (57%) [corrected] were receiving monotherapy with an ACE inhibitor, beta-blocker, calcium channel blocker, or diuretic, and 4493 (23%) were treated at baseline with a combination of diuretic plus either ACE inhibitor, beta-blocker, or calcium channel blocker or ACE inhibitor plus calcium channel blocker. Monotherapy with calcium channel blockers vs diuretics was associated with greater risk of CVD death (hazard ratio, 1.55; 95% confidence interval, 1.02-2.35), controlling for multiple covariates. Women treated with a diuretic plus a calcium channel blocker had an 85% greater risk of CVD death vs those treated with a diuretic plus a beta-blocker, after adjustment for age, race, smoking, high cholesterol levels requiring medication, body mass index, physical activity, use of hormone therapy, and diabetes. After exclusion of women with diabetes the hazard ratio was 2.16 (95% confidence interval, 1.16-4.03). Analyses adjusting for propensity to be receiving a particular treatment did not change the results. For morbid events of coronary heart disease or stroke, diuretics plus ACE inhibitors or calcium channel blockers did not differ from diuretics plus beta-blockers. CONCLUSIONS: Among women with hypertension but no history of CVD, a 2-drug-class regimen of calcium channel blockers plus diuretics was associated with a higher risk of CVD mortality vs beta-blockers plus diuretics. Risks were similar for ACE inhibitors plus diuretics and beta-blockers plus diuretics. Monotherapy with diuretics was equal or superior to other monotherapy in preventing CVD complications of high blood pressure.

Adrenergic beta-Antagonists↗
PubMed2004

Left ventricular concentric geometry is associated with impaired relaxation in hypertension: the HyperGEN study.

AIMS: We tested the hypothesis that abnormal left ventricular (LV) relaxation is associated with concentric LV geometry. METHODS AND RESULTS: Doppler LV filling properties were studied in 1384 hypertensive participants without cardiovascular disease, from the HyperGEN population (731 women, 784 obese, 236 diabetic) and compared in four LV geometry groups; normal, concentric remodelling (3.5%), eccentric (23%), and concentric LV hypertrophy (4%), based on echocardiographic LV mass index (in g/m(2.7)). Abnormal LV relaxation was identified by European Society of Cardiology criteria in 275 subjects (20%). After accounting for significant confounders, E/A ratio and isovolumic relaxation time were not related to the presence of LV hypertrophy, but indicated abnormal relaxation when LV geometry was concentric (both P<0.0001). Deceleration time of E velocity was prolonged with LV hypertrophy (P<0.03), but the behaviour in relation to concentric LV geometry differed in the presence (prolonged) or absence (reduced) of LV hypertrophy (P=0.05), a difference independently related to the magnitude of both transmitral gradients and stroke volume (all P<0.05). Logistic regression showed that, compared with normal LV geometry, the odds of abnormal LV relaxation was 2.3-fold greater when LV geometry was concentric and that LV hypertrophy conferred a borderline higher risk than normal LV mass. CONCLUSIONS: In hypertensive individuals without prevalent cardiovascular disease from a multi-ethnic population-based sample, delayed LV relaxation is independently associated with concentric LV geometry.

Blood Flow Velocity↗
PubMed2004

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.

Aged↗
PubMed2004

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.

Aged↗
PubMed2004

Differences in left ventricular structure between black and white hypertensive adults: the Hypertension Genetic Epidemiology Network study.

The degree to which ethnic differences in left ventricular structure among hypertensive adults are independent of clinical and hemodynamic factors remains uncertain. We assessed whether left ventricular mass and geometry differ between black and white hypertensives after accounting for differences in such factors. Our study group comprised 1060 black and 580 white hypertensive participants free of valvular or coronary disease in a population-based cohort. Blood pressure was measured during a clinic visit and echocardiography was performed using standardized protocols. After controlling for clinical and hemodynamic parameters (cardiac index, peripheral resistance index, and pulse pressure/stroke index), both left ventricular mass and relative wall thickness were higher in blacks than whites (173.9+/-30.9 versus 168.3+/-24.3 grams, P=0.006, and 0.355+/-0.055 versus 0.340+/-0.055 grams, P<0.001). Similarly, the adjusted risk of having left ventricular hypertrophy, whether indexed by height(2.7) or by body surface area, was greater for blacks than for whites (odds ratio: 1.80; 95% CI: 1.29 to 2.51; and odds ratio: 2.50; 95% CI: 1.58 to 3.96, respectively), and this was also true for concentric geometry (odds ratio: 2.28; 95% CI: 1.22 to 4.25). Further adjustment for relatedness in this genetic epidemiological study did not attenuate these differences. Our findings confirm the strong association between black ethnicity and increased left ventricular mass and relative wall thickness in hypertensive adults and demonstrate that these differences are independent of standard clinical and hemodynamic parameters. Whether such differences relate to distinct ambulatory pressure profiles or an ethnic propensity to cardiac hypertrophy requires further investigation.

Adult↗