PLoS ONE (Jan 2021)

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

  • Regitze Skals,
  • Maria Lukács Krogager,
  • Emil Vincent R Appel,
  • Theresia M Schnurr,
  • Christian Theil Have,
  • Gunnar Gislason,
  • Henrik Enghusen Poulsen,
  • Lars Køber,
  • Thomas Engstrøm,
  • Steen Stender,
  • Torben Hansen,
  • Niels Grarup,
  • Christina Ji-Young Lee,
  • Charlotte Andersson,
  • Christian Torp-Pedersen,
  • Peter E Weeke

DOI
https://doi.org/10.1371/journal.pone.0252855
Journal volume & issue
Vol. 16, no. 6
p. e0252855

Abstract

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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, pConclusionsAmong 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.