Insulin resistance genetic risk score and burden of coronary artery disease in patients referred for coronary angiography

Abstract

Aims Insulin 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 results We 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). Conclusions Among 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.

Association between the triglyceride-glucose index and in-hospital major adverse cardiovascular events in patients with acute coronary syndrome: results from the Improving Care for Cardiovascular Disease in China (CCC)-Acute Coronary Syndrome project

“…Recent studies have demonstrated that IR is independent of the onset and progression of CVD and chronic kidney disease (CKD) [4]. According to a study conducted on patients referred for coronary angiography, only a predisposition to IR (i.e., a high genetic risk score burden) was associated with coronary artery disease risk [5]. Another study revealed that compared with hypertension, obesity, and smoking, IR appears to be the strongest risk factor for premature onset of coronary heart disease [6].…”

Identification of novel prognostic targets in coronary artery disease and related complications using bioinformatics and next generation sequencing data analysis

“…Myocardial infarction [4], atherosclerosis [5], arrhythmias [6], heart failure [7], atrial fibrillation [8] and dilated cardiomyopathy [9] are associated with CAD. Insulin resistance [10], type 1 and type 2 diabetes mellitus [11–12], non-alcoholic fatty liver disease [13], hypertension [14], obesity [15] and hypercholesterolemia [16] are thought to be the contributing complications to CAD. However, the molecular mechanism underlying many CAD cases remains unclear, resulting in a lack of effective treatment [17].…”