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Polygenetic risk for coronary artery disease increases hospitalization burden and mortality.

ABSTRACT: Background:Coronary artery disease (CAD) is a leading cause of death worldwide and increasing cost for society. Genome wide association studies (GWAS) have identified common variants associated with CAD. Combining single nucleotide polymorphisms (SNPs) into a genetic risk score (GRS) can estimate an individual's genetic burden. Objectives:To investigate whether GRS for CAD can predict hospitalization and mortality. Methods:23,594 individuals without CAD at baseline and with full data for all covariates from the population based prospective study Malmö diet and cancer study were investigated. The association between hospitalizations was calculated by negative binomial regression and risk of mortality was calculated by Cox proportional hazards regression. The GRS was constructed from 50 SNPs. Results:The study population was divided into quintiles according to the value of GRS. During the mean follow-up time of 17.8?years, 17,254 individuals were hospitalized at least once. Individuals in the highest quintile of GRS were hospitalized 10% more often than individuals in the lowest quintile (IRR: 1.10 [95% CI 1.04-1.16], p?=?0.001), mainly for cardiovascular reasons (IRR: 1.31 [95% CI 1.20-1.43], p?=?5.17?×?10-10). These individuals had highly increased risk of CVD mortality (HR: 1.44 [1.25-1.66], p?=?6.56?×?10-7) but not the risk of mortality due to other causes. Conclusion:Our results suggest that genetic predisposition for CAD can predict hospitalization burden and mortality, especially due to cardiovascular causes, independently of traditional risk factors. As the risk conferred by the GRS is partially modifiable, our results may help to reduce societal costs, individual suffering and prolong life.

SUBMITTER: Sjogren M

PROVIDER: S-EPMC6639589 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Polygenetic risk for coronary artery disease increases hospitalization burden and mortality.

Sjögren Marketa M Almgren Peter P Melander Olle O

International journal of cardiology. Heart & vasculature 20190716

<h4>Background</h4>Coronary artery disease (CAD) is a leading cause of death worldwide and increasing cost for society. Genome wide association studies (GWAS) have identified common variants associated with CAD. Combining single nucleotide polymorphisms (SNPs) into a genetic risk score (GRS) can estimate an individual's genetic burden.<h4>Objectives</h4>To investigate whether GRS for CAD can predict hospitalization and mortality.<h4>Methods</h4>23,594 individuals without CAD at baseline and with ...[more]

PMID: 31360760

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Project description:AimsInsulin resistance associates with development of metabolic syndrome and risk of cardiovascular disease. The link between insulin resistance and cardiovascular disease is complex and multifactorial. Confirming the genetic link between insulin resistance, type 2 diabetes, and coronary artery disease, as well as the extent of coronary artery disease, is important and may provide better risk stratification for patients at risk. We investigated whether a genetic risk score of 53 single nucleotide polymorphisms known to be associated with insulin resistance phenotypes was associated with diabetes and burden of coronary artery disease.Methods and resultsWe genotyped patients with a coronary angiography performed in the capital region of Denmark from 2010-2014 and constructed a genetic risk score of the 53 single nucleotide polymorphisms. Logistic regression using quartiles of the genetic risk score was performed to determine associations with diabetes and coronary artery disease. Associations with the extent of coronary artery disease, defined as one-, two- or three-vessel coronary artery disease, was determined by multinomial logistic regression. We identified 4,963 patients, of which 17% had diabetes and 55% had significant coronary artery disease. Of the latter, 27%, 14% and 14% had one, two or three-vessel coronary artery disease, respectively. No significant increased risk of diabetes was identified comparing the highest genetic risk score quartile with the lowest. An increased risk of coronary artery disease was found for patients with the highest genetic risk score quartile in both unadjusted and adjusted analyses, OR 1.21 (95% CI: 1.03, 1.42, p = 0.02) and 1.25 (95% CI 1.06, 1.48, p<0.01), respectively. In the adjusted multinomial logistic regression, patients in the highest genetic risk score quartile were more likely to develop three-vessel coronary artery disease compared with patients in the lowest genetic risk score quartile, OR 1.41 (95% CI: 1.10, 1.82, p<0.01).ConclusionsAmong patients referred for coronary angiography, only a strong genetic predisposition to insulin resistance was associated with risk of coronary artery disease and with a greater disease burden.

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Polygenetic risk for coronary artery disease increases hospitalization burden and mortality.

Publications

Polygenetic risk for coronary artery disease increases hospitalization burden and mortality.

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