Showing papers by "Gerardo Heiss published in 2009"

Genome-wide association study of blood pressure and hypertension

Abstract: Blood pressure is a major cardiovascular disease risk factor. To date, few variants associated with interindividual blood pressure variation have been identified and replicated. Here we report results of a genome-wide association study of systolic (SBP) and diastolic (DBP) blood pressure and hypertension in the CHARGE Consortium (n = 29,136), identifying 13 SNPs for SBP, 20 for DBP and 10 for hypertension at P < 4 × 10(-7). The top ten loci for SBP and DBP were incorporated into a risk score; mean BP and prevalence of hypertension increased in relation to the number of risk alleles carried. When ten CHARGE SNPs for each trait were included in a joint meta-analysis with the Global BPgen Consortium (n = 34,433), four CHARGE loci attained genome-wide significance (P < 5 × 10(-8)) for SBP (ATP2B1, CYP17A1, PLEKHA7, SH2B3), six for DBP (ATP2B1, CACNB2, CSK-ULK3, SH2B3, TBX3-TBX5, ULK4) and one for hypertension (ATP2B1). Identifying genes associated with blood pressure advances our understanding of blood pressure regulation and highlights potential drug targets for the prevention or treatment of hypertension.

Association of Multiple Anthropometrics of Overweight and Obesity With Incident Heart Failure The Atherosclerosis Risk in Communities Study

Abstract: Background— The association of central adiposity with incident heart failure (HF) has yet to be studied in a large population-based study. Methods and Results— The Atherosclerosis Risk in Communities study is an ongoing biracial population-based cohort of those aged 45 to 64 years from 4 US communities with 16 years’ median follow-up for incident, hospitalized, or fatal HF. Waist-hip ratio, waist circumference, and body mass index (BMI) were measured at baseline (1987–1989). After exclusions, the sample size was 14 641. BMI was categorized as <25, 25 to 29.9, and ≥30 kg/m2. Waist circumference and waist-hip ratio were divided into gender-specific tertiles. A first occurrence of International Classification of Diseases, 9th Revision, Clinical Modification, codes of HF, either hospital discharge (428.0 to 428.9; n=1451) or on a death certificate (428.0 to 428.9 or I50.0 to I50.9; n=77) was considered an HF event. Cox models were adjusted for alcohol use, smoking, age, center, and educational level. The adju...

Heart Rate Variability, Ambient Particulate Matter Air Pollution, and Glucose Homeostasis: The Environmental Epidemiology of Arrhythmogenesis in the Women's Health Initiative

Abstract: Metabolic neuropathophysiology underlying the prediabetic state may confer susceptibility to the adverse health effects of ambient particulate matter <10 microm in diameter (PM(10)). The authors therefore examined whether impaired glucose homeostasis modifies the effect of PM(10) on heart rate variability in a stratified, random sample of 4,295 Women's Health Initiative clinical trial participants, among whom electrocardiograms and fasting blood draws were repeated at 3-year intervals from 1993 to 2004. In multilevel, mixed models weighted for sampling design and adjusted for clinical and environmental covariables, PM(10) exposure was inversely associated with heart rate variability. Inverse PM(10)-heart rate variability associations were strongest for the root mean square of successive differences in normal-to-normal RR intervals (RMSSD). Among participants with impaired fasting glucose, there were -8.3% (95% confidence interval: -13.9, -2.4) versus -0.6% (95% confidence interval: -2.4, 1.3), -8.4% (95% confidence interval: -13.8, -2.7) versus -0.3% (95% confidence interval: -2.1, 1.6), and -4.3% (95% confidence interval: -9.4, 1.0) versus -0.8% (95% confidence interval: -2.7, 1.0) decreases in the RMSSD per 10-microg/m(3) increase in PM(10) at high versus low levels of insulin (P < 0.01), insulin resistance (P < 0.01), and glucose (P = 0.16), respectively. These associations were stronger among participants with diabetes and weaker among those without diabetes or impaired fasting glucose. The findings suggest that insulin and insulin resistance exacerbate the adverse effect of PM(10) on cardiac autonomic control and thus risk of coronary heart disease among nondiabetic, postmenopausal women with impaired fasting glucose.

Repeatability and measurement error in the assessment of choline and betaine dietary intake: the Atherosclerosis Risk in Communities (ARIC) study.

Abstract: The repeatability of a risk factor measurement affects the ability to accurately ascertain its association with a specific outcome. Choline is involved in methylation of homocysteine, a putative risk factor for cardiovascular disease, to methionine through a betaine-dependent pathway (one-carbon metabolism). It is unknown whether dietary intake of choline meets the recommended Adequate Intake (AI) proposed for choline (550 mg/day for men and 425 mg/day for women). The Estimated Average Requirement (EAR) remains to be established in population settings. Our objectives were to ascertain the reliability of choline and related nutrients (folate and methionine) intakes assessed with a brief food frequency questionnaire (FFQ) and to estimate dietary intake of choline and betaine in a bi-ethnic population. We estimated the FFQ dietary instrument reliability for the Atherosclerosis Risk in Communities (ARIC) study and the measurement error for choline and related nutrients from a stratified random sample of the ARIC study participants at the second visit, 1990–92 (N = 1,004). In ARIC, a population-based cohort of 15,792 men and women aged 45–64 years (1987–89) recruited at four locales in the U.S., diet was assessed in 15,706 baseline study participants using a version of the Willett 61-item FFQ, expanded to include some ethnic foods. Intraindividual variability for choline, folate and methionine were estimated using mixed models regression. Measurement error was substantial for the nutrients considered. The reliability coefficients were 0.50 for choline (0.50 for choline plus betaine), 0.53 for folate, 0.48 for methionine and 0.43 for total energy intake. In the ARIC population, the median and the 75th percentile of dietary choline intake were 284 mg/day and 367 mg/day, respectively. 94% of men and 89% of women had an intake of choline below that proposed as AI. African Americans had a lower dietary intake of choline in both genders. The three-year reliability of reported dietary intake was similar for choline and related nutrients, in the range as that published in the literature for other micronutrients. Using a brief FFQ to estimate intake, the majority of individuals in the ARIC cohort had an intake of choline below the values proposed as AI.

Conjugated Equine Estrogen Influence on Mammographic Density in Postmenopausal Women in a Substudy of the Women's Health Initiative Randomized Trial

Abstract: Purpose Increased mammographic density is associated with increased breast cancer risk and reduced sensitivity of screening mammography and is related to hormone exposure. However, the effects of conjugated equine estrogens (CEEs) alone on mammographic density in diverse racial/ethnic populations are not established. We examined the effect of CEE alone on mammographic density in a subsample of the Women's Health Initiative (WHI) clinical trial participants. Patients and Methods In the WHI trial, women were randomly assigned to daily CEE 0.625 mg or placebo. The effect of CEE on mammographic percent density was determined over 1 and 2 years in a stratified random sample of 435 racially and ethnically diverse participants from 15 of 40 WHI clinics. Results Use of CEE resulted in mean increase in mammographic percent density of 1.6 percentage points (95% CI, 0.8 to 2.4) at year 1 compared with a mean decrease of 1.0 percentage point (95% CI, −1.7 to −0.4) in the placebo group (P < .001). The effect persisted...

Transcription factor 7-like 2 (TCF7L2) polymorphism and context-specific risk of type 2 diabetes in African American and caucasian adults: The atherosclerosis risk in communities study

Abstract: OBJECTIVE: Although variants in the transcription factor 7-like 2 ( TCF7L2 ) gene are consistently associated with type 2 diabetes mellitus (T2DM), large population-based studies of African Americans are lacking. Moreover, few studies have investigated the effects of TCF7L2 on T2DM in the context of metabolic risk factors of T2DM. RESEARCH DESIGN AND METHODS: We investigated the association between the TCF7L2 rs7903146 polymorphism and T2DM in 2,727 African American and 9,302 Caucasian participants without diabetes inducted into the Atherosclerosis Risk in Communities Study in 1987-1989 and followed for 9 years. RESULTS: A total of 485 and 923 cases of T2DM were identified in African-Americans and Caucasians, respectively. Compared to homozygous CC individuals, heterozygous CT and homozygous TT individuals had higher cumulative incidence (95%CI) of T2DM over 9 years of follow-up, 11.3% (CI=10.2, 12.4%) vs. 21.1% (20.8, 21.4%) and 27.9% (19.3, 36.5%) in African-Americans, 9.7% (8.8, 10.6%) vs. 11.3% (10.2, 12.4%) and 13.6% (11.1, 16.1%) in Caucasians. Individuals with the risk allele had the highest hazards of diabetes if they were obese and had low HDL, followed by individuals with any one, and none of the traits. CONCLUSIONS: Our study provides the first significant evidence of association between the TCF7L2 rs7903146 polymorphism and T2DM risk in a large African American population, and also demonstrates that the diabetes risk conveyed by the rs7903146 risk allele is substantially increased in the context of some metabolic risk factors for T2DM. Our study findings need to be replicated in other large, population-based studies.

Abstract 1454: Classification of Heart Failure in the Atherosclerosis Risk in Communities (ARIC) Study: A Comparison With Other Diagnostic Criteria

Abstract: Introduction: Population-based research on heart failure (HF) is hindered by lack of consensus on diagnostic criteria. In addition, established criteria such as Framingham (FRM), National Health an...

Abstract 1808: Duffy Antigen Receptor for Chemokines (Darc) Polymorphism Regulates Circulating Concentrations of Monocyte Chemoattractant Protein-1 and Other Circulating Inflammatory Mediators

Abstract: Background: Monocyte chemoattractant protein (MCP)-1 is a cytokine central to the inflammatory process. The genetics of MCP-1 are little understood. Methods and Results: To identify the genetic bas...