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A genetic risk score is associated with incident cardiovascular disease and coronary artery calcium: the Framingham Heart Study.

ABSTRACT: BACKGROUND:Limited data exist regarding the use of a genetic risk score (GRS) for predicting risk of incident cardiovascular disease (CVD) in US-based samples. METHODS AND RESULTS:By using findings from recent genome-wide association studies, we constructed GRSs composed of 13 genetic variants associated with myocardial infarction or other manifestations of coronary heart disease (CHD) and 102 genetic variants associated with CHD or its major risk factors. We also updated the 13 single-nucleotide polymorphism (SNP) GRSs with 16 SNPs recently discovered by genome-wide association studies. We estimated the association, discrimination, and risk reclassification of each GRS for incident cardiovascular events and prevalent coronary artery calcium (CAC). In analyses adjusted for age, sex, CVD risk factors, and parental history of CVD, the 13 SNP GRSs were significantly associated with incident hard CHD (hazard ratio, 1.07; 95% CI, 1.00-1.15; P=0.04), CVD (hazard ratio per allele, 1.05; 95% CI, 1.01-1.09; P=0.03), and high CAC (defined as >75(th) age- and sex-specific percentile; odds ratio per allele, 1.18; 95% CI, 1.11-1.26; P=3.4×10(-7)). The GRS did not improve discrimination for incident CHD or CVD but led to modest improvements in risk reclassification. However, significant improvements in discrimination and risk reclassification were observed for the prediction of high CAC. The addition of 16 newly discovered SNPs to the 13 SNP GRSs did not significantly modify these results. CONCLUSIONS:A GRS composed of 13 SNPs associated with coronary disease is an independent predictor of cardiovascular events and of high CAC, modestly improves risk reclassification for incident CHD, and significantly improves discrimination for high CAC. The addition of recently discovered SNPs did not significantly improve the performance of this GRS.

SUBMITTER: Thanassoulis G

PROVIDER: S-EPMC3292865 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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A genetic risk score is associated with incident cardiovascular disease and coronary artery calcium: the Framingham Heart Study.

Thanassoulis George G Peloso Gina M GM Pencina Michael J MJ Hoffmann Udo U Fox Caroline S CS Cupples L Adrienne LA Levy Daniel D D'Agostino Ralph B RB Hwang Shih-Jen SJ O'Donnell Christopher J CJ

Circulation. Cardiovascular genetics 20120110 1

<h4>Background</h4>Limited data exist regarding the use of a genetic risk score (GRS) for predicting risk of incident cardiovascular disease (CVD) in US-based samples.<h4>Methods and results</h4>By using findings from recent genome-wide association studies, we constructed GRSs composed of 13 genetic variants associated with myocardial infarction or other manifestations of coronary heart disease (CHD) and 102 genetic variants associated with CHD or its major risk factors. We also updated the 13 s ...[more]

PMID: 22235037

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Project description:PurposeTo extract radiomic features from coronary artery calcium (CAC) on CT images and to determine whether this approach could improve the ability to identify individuals at risk for a composite endpoint of clinical events.Materials and methodsParticipants from the Offspring and Third Generation cohorts of the community-based Framingham Heart Study underwent noncontrast cardiac CT (2002-2005) and were followed for more than a median of 9.1 years for composite major events. A total of 624 participants with CAC Agatston score (AS) of greater than 0 and good or excellent CT image quality were included for manual CAC segmentation and extraction of a predefined set of radiomic features reflecting intensity, shape, and texture. In a discovery cohort (n = 318), machine learning was used to select the 20 most informative and nonredundant CAC radiomic features, classify features predicting events, and define a radiomic-based score (RS). Performance of the RS was tested independently for the prediction of events in a validation cohort (n = 306).ResultsThe RS had a median value of 0.08 (interquartile range, 0.007-0.71) and a weak and modest correlation with Framingham risk score (FRS) (r = 0.2) and AS (r = 0.39), respectively. The continuous RS unadjusted, adjusted for age and sex, FRS, AS, and FRS plus AS were significantly associated with events (hazard ratio [HR] = 2.2, P < .001; HR = 1.8, P = .002; HR = 2.0, P < .001; HR = 1.7, P = .02; and HR = 1.8, P = .01, respectively). In participants with AS of less than 300, RS association with events remained significant when unadjusted and adjusted for age and sex, FRS, AS, and FRS plus AS (HR = 2.4, 2.8, 2.8, 2.3, and 2.6; P < .001, respectively). In the same subgroup of participants, adding the RS to AS resulted in a significant improvement in the discriminatory ability for events as compared with the AS (area under the receiver operating curve: 0.80 vs 0.68, respectively; P = .03).ConclusionA radiomic-based score, including the complex properties of CAC, may constitute an imaging biomarker to be further developed to identify individuals at risk for major adverse cardiovascular events in a community-based cohort. Supplemental material is available for this article. © RSNA, 2020.

Dataset Information

A genetic risk score is associated with incident cardiovascular disease and coronary artery calcium: the Framingham Heart Study.

Publications

A genetic risk score is associated with incident cardiovascular disease and coronary artery calcium: the Framingham Heart Study.

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