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

Autor: Skals R; Unit of Clinical Biostatistics, Aalborg University Hospital, Aalborg, Denmark., Krogager ML; Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark., Appel EVR; Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark., Schnurr TM; Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark., Have CT; Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark., Gislason G; Department of Cardiology, Copenhagen University Hospital Gentofte, Hellerup, Denmark., Poulsen HE; Department of Clinical Pharmacology, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark., Køber L; Department of Cardiology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark., Engstrøm T; Department of Cardiology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark., Stender S; Department of Clinical Biochemistry, Copenhagen University Hospital Gentofte, Copenhagen, Denmark., Hansen T; Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark., Grarup N; Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark., Lee CJ; Unit of Clinical Biostatistics, Aalborg University Hospital, Aalborg, Denmark., Andersson C; Department of Cardiology, Copenhagen University Hospital Gentofte, Hellerup, Denmark., Torp-Pedersen C; Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark., Weeke PE; Department of Cardiology, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2021 Jun 18; Vol. 16 (6), pp. e0252855. Date of Electronic Publication: 2021 Jun 18 (Print Publication: 2021).
DOI: 10.1371/journal.pone.0252855
Abstrakt: 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.
Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: The Novo Nordisk Foundation Center for Basic Metabolic Research performed genotyping, quality control of the genotypes and genotype imputation. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
Databáze: MEDLINE
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