TY - JOUR
T1 - Insulin resistance genetic risk score and burden of coronary artery disease in patients referred for coronary angiography
AU - Skals, Regitze
AU - Krogager, Maria Lukács
AU - Appel, Emil Vincent R
AU - Schnurr, Theresia M
AU - Have, Christian Theil
AU - Gislason, Gunnar
AU - Poulsen, Henrik Enghusen
AU - Køber, Lars
AU - Engstrøm, Thomas
AU - Stender, Steen
AU - Hansen, Torben
AU - Grarup, Niels
AU - Lee, Christina Ji-Young
AU - Andersson, Charlotte
AU - Torp-Pedersen, Christian
AU - Weeke, Peter E
PY - 2021/6/18
Y1 - 2021/6/18
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85108195644&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0252855
DO - 10.1371/journal.pone.0252855
M3 - Journal article
C2 - 34143812
SN - 1932-6203
VL - 16
SP - e0252855
JO - PLoS One
JF - PLoS One
IS - 6
M1 - e0252855
ER -