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Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study Offspring Cohort.

ABSTRACT: In order to evaluate the population impact of putative causal genetic variants over the life course of disease, we extended the static estimation of population-attributable risk fraction and developed a novel tool to evaluate how the population impact changes over time using the Framingham Heart Study Offspring Cohort data provided to the Genetic Analysis Workshop 16, Problem 2. A set of population-attributable risk fractions based on survival functions were estimated under the proportional hazards models. The development of this novel measure of population impact creates a more comprehensive estimate of population impact over the life course of disease, which may help us to better understand genetic susceptibility at the population level.

SUBMITTER: Yan Y

PROVIDER: S-EPMC2795890 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study Offspring Cohort.

Yan Yu Y Hu Yijuan Y North Kari E KE Franceschini Nora N Lin Danyu D

BMC proceedings 20091215

In order to evaluate the population impact of putative causal genetic variants over the life course of disease, we extended the static estimation of population-attributable risk fraction and developed a novel tool to evaluate how the population impact changes over time using the Framingham Heart Study Offspring Cohort data provided to the Genetic Analysis Workshop 16, Problem 2. A set of population-attributable risk fractions based on survival functions were estimated under the proportional haza ...[more]

PMID: 20017983

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Project description:BackgroundRemnant lipoproteins (RLPs), the triglyceride-enriched precursors to low-density lipoprotein, are an emerging risk factor for coronary heart disease (CHD). We sought to determine the association of RLP cholesterol (RLP-C) levels with incident CHD in 2 diverse, prospective, longitudinal observational US cohorts.Methods and resultsWe analyzed cholesterol levels from serum lipoprotein samples separated via density gradient ultracentrifugation in 4114 US black participants (mean age 53.8 years, 64% women) from the Jackson Heart Study and a random sample of 818 predominantly white participants (mean age 57.3 years, 52% women) from the Framingham Offspring Cohort Study. Multivariable-adjusted hazard ratios (HRs) for RLP-C (the sum of very low-density lipoprotein3 cholesterol and intermediate-density lipoprotein cholesterol) were derived to estimate associations with incident CHD events consisting of myocardial infarction, CHD death, and revascularizations for each cohort separately and as a combined population. There were 146 CHD events in the combined population. After adjustments for age, sex, body mass index, smoking, blood pressure, diabetes, and lipid-lowering therapy for the combined population, RLP-C (HR 1.23 per 1-SD increase, 95% CI 1.06-1.42, P<0.01) and intermediate-density lipoprotein cholesterol (HR 1.26 per 1-SD increase, 95% CI 1.08-1.47, P<0.01) predicted CHD during an 8-year follow-up. Associations were attenuated by high-density lipoprotein cholesterol and ultimately lost significance with inclusion of real low-density lipoprotein cholesterol, which excludes Lp(a) and IDL cholesterol fractions. Similar associations were seen in multivariable analyses within each cohort.ConclusionRLP-C levels are predictive of incident CHD in this diverse group of primary prevention subjects. Interventions aimed at reducing RLP-C to prevent CHD warrant further intensive investigation.Clinical trial registrationURL: http://www.ClinicalTrials.gov. Unique identifier: NCT00415415.

Project description:BackgroundChronic inflammation is thought to be a major characteristic of aging, which may increase need for substrates, specifically protein, to support anti-inflammatory processes.ObjectivesThe aim of this study was to assess associations between dietary protein and changes in biomarkers of inflammation and oxidative stress over the long term in a community-dwelling population.MethodsIn 2061 participants of the Framingham Heart Study Offspring cohort who attended exams 7 (1998-2001; mean ± SD age 60.0 ± 8.8 y, 56% female) and 8 (2005-2008), total, animal, and plant protein intakes were assessed by food-frequency questionnaire at each exam, energy adjusted, and averaged. We defined an inflammation and oxidative stress score as the sum of rank-normalized values of 9 circulating biomarkers (C-reactive protein, osteoprotegerin, P-selectin, tumor necrosis factor receptor II, soluble intercellular adhesion molecule-1, interleukin 6, monocyte chemoattractant protein 1, and lipoprotein phospholipase A2 mass and activity), and urinary isoprostanes, along with 2 subscores. Adjusted least-square means of changes in the scores and log individual biomarkers in quartile categories of intake were estimated with the use of linear regression models, across mean ± SD 6.6 ± 0.7 y of follow-up.ResultsProtein intake was inversely associated with changes in the inflammation and oxidative stress score (mean ± SE in Q1 compared with Q4: 0.77 ± 0.17 compared with 0.31 ± 0.19; P-trend = 0.02), indicating overall inflammation/oxidative stress increased less in those with the highest intake than in those with the lowest. Favorable associations were observed for plant protein (Q1 compared with Q4: 0.89 ± 0.25 compared with 0.14 ± 0.25; P-trend = 0.001), but only trended toward significance for animal protein (Q1 compared with Q4: 0.70 ± 0.26 compared with 0.31 ± 0.26; P-trend = 0.05). Total protein and plant protein intakes were also inversely associated with changes in monocyte chemoattractant protein 1 (total: Q1 compared with Q4: 0.19 ± 0.01 compared with 0.15 ± 0.01 log-pg/mL; P-trend = 0.03; plant: Q1 compared with Q4: 0.21 ± 0.01 compared with 0.16 ± 0.01 log-pg/mL; P-trend = 0.003).ConclusionsDietary protein, particularly from plant sources, may be associated with beneficial changes in the inflammatory burden in aging populations.

Dataset Information

Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study Offspring Cohort.

Publications

Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study Offspring Cohort.

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