Inflammation and cholesterol associated residual cardiovascular risk and its dependence on chronic kidney disease in statin treated patients with coronary artery disease

Abstract Background/Aim In statin-treated patients with chronic coronary syndrome (CCS) there is uncertainty about the relative contribution of inflammation and dyslipidaemia to residual cardiovascular risk, particularly in the presence of chronic kidney disease. We thus aimed to evaluate high sensitive C-reactive protein (hsCRP) and low density lipoprotein-cholesterol (LDL-C) as predictors of future events in these patients, stratified by estimated glomerular filtration rate (eGFR). Methods We identified patients with CCS on stable statin treatment from a contemporary all-comers cohort recruited at a large tertiary care center in Germany. We excluded patients with active malignancy, infectious disease or in a post-operative state. Cox regression for major adverse cardiovascular events (MACE, composite of cardiovascular death, myocardial infarction, stroke) and all-cause death was performed adjusting for age, sex, arterial hypertension, diabetes mellitus, active smoking, body mass index and change in the intensity of statin therapy at discharge, with log(hsCRP) or LDL-C as the exposure variables. Interaction with eGFR (< vs. ≥ 60 ml/min/1.73m²) was investigated. Results 937 patients with CCS (mean age 71.1 years, 78.7% male, median hsCRP 2.0 mg/L, median LDL-C 73.0 mg/dl, median eGFR 71.3 ml/min/1.73m²) were followed-up over 4 years, with 101 cases of MACE and 171 cases of all-cause death recorded. The hazard ratios (HR) for MACE per standard deviation (SD) increase were as follows: log(hsCRP) 1.08 (95% confidence interval (CI) 0.87, 1.34; p = 0.48), LDL-C 1.10 (95% CI 0.89, 1.35; p = 0.37). For all-cause death the HRs for log(hsCRP) and LDL-C were 1.60 (95% CI 1.36, 1.88; p <0.001) and 0.88 (95% CI 0.74, 1.04; p = 0.14), respectively. Kaplan-Meier curves stratifying the cohort by median values of LDL-C and hsCRP consistently demonstrated a significantly higher risk of death in the subgroups with elevated hsCRP (Figure 1). Contrastingly for LDL-C, levels below (vs. above) the median were associated with a higher mortality rate. This is in part a reflection of a higher prevalence of high-intensity statin therapy in this subgroup (21.0 vs. 14.2%, p = 0.0081), in turn a reflection of greater severity of coronary artery disease (history of myocardial infarction 43.9 vs. 31.9%, p <0.001). Further confounding by unadjusted for diseases with a catabolic metabolism is possible. Interaction analysis with eGFR revealed that log(hsCRP) was predictive of all-cause mortality both in the presence and absence of chronic kidney disease, whilst lower LDL-C values were found to be predictive only at eGFR <60 ml/min/1.73m² (Table 1). Conclusion Residual inflammation as measured by hsCRP predicts all-cause mortality in statin-treated patients with CCS in this contemporary all-comers cohort, both in the presence and absence of chronic kidney disease. The predictive utility of LDL-C is limited, likely due to confounding e.g. by the intensity of lipid lowering medication.Kaplan-Meier curves (all-cause death)Interaction analysis with eGFR