Exploring residual cardiovascular risk beyond LDL cholesterol in patients with acute destabilisation of known significant atherosclerosis

Background High LDL cholesterol (LDLc) is a well-established risk factor for coronary and peripheral atherosclerosis. The European Society of Cardiology recommends lowering LDLc to below 55 mg/dL in patients with established atherosclerotic cardiovascular disease (ASCVD). However, many patients do not achieve such a stringent target, and even in those who do, an acute coronary syndrome is not uncommon. Aim To assess the residual risk beyond LDLc in patients with known ASCVD and acute coronary syndrome. Methods Patients with acute myocardial infarction (AMI) and known ASCVD (previous ischaemic stroke, peripheral atherosclerotic disease, or known coronary atherosclerosis) from the AMIPE registry were included. The population was stratified based on admission LDLc with a cut-off of 55 mg/dL. The modified Duke Jeopardy Score (mDJS) was used to quantify coronary artery disease. Logistic regression was used to assess predictors of in-hospital mortality. Patients were followed up for at least 12 months, considering all-cause death and a composite of major adverse cardiac events (MACE; all-cause death, acute coronary syndrome, stroke, or heart failure). Cox regression models were used to calculate the hazard ratio (HR) and 95% confidence intervals (95% CI) for death and MACE. An interaction term was included in the regression models to assess possible risk factors specific to the population with LDLc <55 mg/dL. Results 1742 subjects admitted for AMI, with known ASCVD, and available LDLc on admission were enrolled. 242 (14%) patients had LDLc <55 mg/dL. These patients were more often male, diabetic, have lower haemoglobin (Hb), higher white blood count and creatinine (p<0.05 for all), while mDJS was comparable (p=0.169). 46 patients (3%) died in hospital. LDLc <55 mg/dL was associated with in- hospital mortality (odds ratio 2.00, 95% CI 1.00-3.99), but not after adjustment for other risk factors including GRACE score, left ventricle ejection fraction, Hb, and atrial fibrillation. Percutaneous revascularisation was more beneficial in patients with LDLc <55 mg/dL (p for interaction = 0.045). After a 60-month follow-up, 430 (27%) patients died and 690 (43%) had a MACE. An LDLc <55 mg/dL on admission was associated with a higher risk of both death (HR 1.46, 95% CI 1.11-1.91) and MACE (HR 1.27, 95% CI 1.02-1.59), but these findings were not confirmed after adjustment for confounders. Conclusions Many patients with known ASCVD who experienced an AMI had not achieved the recommended LDLc target. However, experimenting an AMI while having LDLc <55 mg/dL was associated with a higher risk of in-hospital and long-term adverse outcomes, possibly due to the residual risk which may not be adequately targeted. In these patients, revascularisation was more beneficial probably due to the lack of other mechanism-directed therapeutic options. Specific management for patients who experience an AMI in spite of having reached the recommended LDLc target is required.survival curves subgroup analysis