Residual coronary atherosclerotic risk and low LDL-cholesterol in chronic coronary syndromes

Aims: Metabolic syndrome (Mes) and diabetes are emerging cardiometabolic determinants of coronary atherosclerotic disease (CAD) risk besides LDL-cholesterol (LDL-C) and established risk factors. We aimed to assess whether, in patients with chronic coronary syndrome (CCS), cardiometabolic risk is prevalent and independently associated with residual CAD risk in subjects with low LDL-C. Methods and results: The cross-sectional HURRICANE study (Health improvement by Understanding RR In CAd and NEw targets for treatment) included 479 patients with CCS (mean age 65 ± 11 years, 70% male), undergoing cardiac computed tomography angiography (CCTA). A severe/extensive CAD or a moderate-high CAD risk were defined, on patient level, by CCTA-derived CAD-RADS2 and Leiden scores. Metabolic syndrome was present in 31% of patients, diabetes or pre-diabetes in 21% and 26%, severe/extensive CAD and moderate-high Leiden score in 51% and in 61%, more frequently in the two lower LDL-C categories. Multivariate logistic regression models, included age, sex, smoking status, family history, LDL-C categories (<70, 70-99 100-129, and ≥130 mg/dL), MeS, or its components and medications. Independent predictors of moderate-high Leiden score were age, male sex, the lowest LDL-C category and MeS (OR 2.12, 95% CI: 1.26-3.56) or pre-diabetes (OR 1.90, 95% CI: 1.12-3.21) and diabetes (OR 6.13, 95% CI: 1.93-19.45). In the lowest LDL-C group, higher CAD-RADS2 and Leiden scores were more frequent in patients with cardiometabolic risk. Conclusion: Results of this cross-sectional study suggest that dysregulation of glucose metabolism is the prevalent component of residual cardiometabolic and coronary atherosclerotic risk in patients with CCS and low LDL-C under current treatment.