Impact of cardiometabolic risk factors on coronary atherosclerotic disease phenotypes, plaque burden and composition in patients with chronic coronary syndromes

Background Coronary artery disease (CAD) is still the major cause of cardiovascular mortality and morbidity. Despite progresses in treatment a substantial residual risk (RR) of CAD and associated events persists. The role of cardiometabolic determinants of RR is emerging but the relationship with CAD risk phenotypes in patients with chronic coronary syndromes (CCS) under treatment remains undefined. Purpose To assess the association of established and emerging risk factors with CAD phenotypes and coronary plaque burden in patients with CCS from the HURRICANE study (Health improvement by Understanding RR In CAd and NEw targets for treatment). Methods Among the 561 patients enrolled, 411 (64.8±10.7 yrs, 72.7% male) underwent high quality computerized tomography angiography (CTA) and full clinical characterization. CAD-RADS2 scores were adjudicated and plaque volumes (PV) were quantitatively measured in coronary segments (≥ 2 mm in diameter) to provide whole heart dense-calcium (HU>300) and non-dense-calcium (HU < 300) PVs. Obstructive CAD (CADRADS2 score 3-5), extensive CAD (P score 3-4) and PVs (mm3) were the end-points. Multivariate linear regression models included age, sex, family history of CAD, current smoking, hypertension, dyslipidaemia, obesity (BMI>30 kg/m2), diabetes (fasting glucose ≥126 mg/dL or known diabetes), pre-diabetes (fasting glucose 100–125 mg/dL), high triglycerides (TG) (>150 mg/dL), low HDL cholesterol (HDL-C) (<40 mg/dL in males and <50 mg/dL in females) and low or high LDL cholesterol (LDL-C) (<70 or ≥130 mg/dL). All models were adjusted for medical treatments. Results History of previous CAD (revascularization, myocardial infarction) was present in 29% of patients, 40% had obstructive and 33% extensive CAD. Dyslipidaemia (76%), hypertension (75%), type 2 diabetes or pre-diabetes (47%) were the most prevalent risk factors. Statins (63%), antiplatelets (54%), ACE or ARB inhibitors (53%) and beta-blockers (47%) were the most frequent medications. At multivariable analyses, older age and male sex were associated with all end-points, pre-diabetes with obstructive CAD (t-Value 2.71, P=0.007), low LDL-C with obstructive (t-Value 4.04, P<0.0001) and extensive (t-Value 3.11, P=0.002) CAD. Diabetes was associated with dense-calcium PV (t-Value 2.49, P=0.013), high TG (t-Value 2.98, P=0.003) and low LDL-C (t-Value 2.35, P=0.019) with non-dense-calcium PV. In the 291 patients without history of CAD, the associations of low LDL-C with extensive CAD (t-Value 3.15, P=0.002), of low LDL-C and high TG with non-dense-calcium PV (t-Value 2.82, P=0.005; t-Value 2.78, P=0.006) were confirmed. Conclusions Impaired glucose metabolism is associated with obstructive CAD and higher dense-calcium plaque burden in patients with CCS. Low LDL-C and high TG levels are independent determinants of extensive and non-calcified coronary atherosclerosis suggesting a potential framework to understand residual risk.