Association between achieved cholesterol levels and the risk of major adverse cardiovascular events after acute coronary syndromes

Abstract Background European guidelines recommend reducing lipid levels to defined targets to lower cardiovascular risk after acute coronary syndromes (ACS). Purpose This study aims to evaluate the association of achieved and reduced lipid levels one year post-ACS with the risk of subsequent major adverse cardiovascular events (MACE) in a real-world setting. Methods Data from SPUM-ACS, a Swiss multicentric cohort of patients hospitalized with ACS between 2007 and 2021, were used to assess the association between lipid levels (LDL-C, non-HDL-C, HDL-C, triglycerides), relative difference from baseline lipid levels, and lipid targets achievement (LDL-C <1.8 and ≥50% reduction from baseline, non-HDL-C <2.2 and triglycerides <1.7mmol/l) one year after ACS with the risk of MACE (myocardial infarction, stroke, coronary revascularization, and cardiovascular death). The observation period for MACE started after a follow-up visit one year post-ACS, during which lipid levels were measured, extending over a median duration of 5.5 years. Cox proportional hazards models, adjusted age, sex, BMI, smoking status, statin therapy intensity, diabetes, systemic inflammatory disease, and creatinine were used. Predicted adjusted hazard ratios (HR) were represented graphically for continuous exposures. Analyses were repeated with interaction terms for predefined subgroups. Results 2579 ACS survivors (mean age 62 years; 80% male), primarily undergoing percutaneous revascularization, attended a follow-up visit one year after ACS and were followed up for a median of 5.5 years. 98% were prescribed statin therapy (59% high-intensity) at discharge. During the first year post-ACS, median LDL-C decreased from 3.7 to 2.4 mmol/l (-34%, p<0.001), non-HDL-C from 3.9 to 2.6 mmol/l (-32%, p<0.001), and triglycerides from 1.21 to 1.16 mmol/l (-6%, p<0.001); HDL-C increased from 1.1 to 1.2 mmol/l (+6%, p<0.001). 92% of patients were on statin therapy (50% high-intensity) one year after ACS. In log-linear models, one year after ACS, a 1 mmol/l reduction of LDL-C, non-HDL-C, and triglycerides levels to the target was associated with a lower risk of subsequent MACE by 23%, 24%, and 14%, respectively (p values <0.001). A 10% relative reduction from baseline levels of LDL-C, non-HDL-C and triglycerides was associated with a lower risk of MACE by 8%, 9%, and 4%, respectively (p values <0.001). Achieving LDL-C <1.8 mmol/l (21%, HR=0.71 [0.54, 0.93]), LDL-C reduction ≥50% from baseline (26%, HR=0.63 [0.48, 0.84]), non-HDL-C <2.2 mmol/l (30%, HR=0.65 [0.51, 0.83]), and triglycerides <1.7 mmol/l (76%, HR=0.76 [0.62, 0.94]) were all associated with a reduction in the risk of MACE. Neither age, sex, BMI, diabetes, or smoking status affected the results (p for interaction ≥0.05). Conclusion These findings affirm current recommendations and underscore lipid reduction and targets achievement as critical strategies for mitigating residual cardiovascular risk in patients with ACS.