Abstract
Background: A significant proportion of post-myocardial infarction (MI) patients do not reach target low-density lipoprotein cholesterol (LDL-C) levels. Suboptimal LDL-C reduction is often attributed to poor adherence to pharmacological therapy and lifestyle recommendations. Methods: In a prospective registry of 179 post-MI patients who completed a Phase 2 Cardiac Rehabilitation Program (CRP), we evaluated the characteristics and predictors of suboptimal LDL-C reduction. Key indicators were assessed before and after CRP: adherence to the Mediterranean diet (using the PREDIMED questionnaire), weekly physical activity (via the IPAQ questionnaire), therapeutic adherence (using the Morisky-Green questionnaire), and peak oxygen consumption (VO(2)) on exercise testing. Lipid-lowering therapy (LLT) and LDL-C were recorded prior to MI and both before and after Phase 2 CRP. At the end of Phase 2, we analyzed the difference between measured and theoretical LDL-C (basal LDL-C minus expected LDL-C reduction by LLT), which was defined as "residual difference in LDL-C" (RD-LDL-C). We analyzed the predictors of positive RD-LDL-C (lower than theoretically expected). Results: After CRP, 54 (30.2%) patients exhibited positive RD-LDL-C. Within this subgroup, LLT was uptitrated, and patients received more potent LLT at the conclusion of CRP (theoretical potency: 69.81 ± 7.07 vs. 66.41 ± 7.48%, p = 0.005). However, they were less likely to reach the target LDL-C level <55 mg/dL (66.7% vs. 93.6%, p < 0.001). Male sex (HR 17.96 [2.15, 149.92], p = 0.008) and higher lipoprotein (a) levels (HR 1.02 [1.01, 1.03] per mg/dL, p = 0.001) were associated with a positive RD-LDL-C. Conversely, diabetes mellitus (HR 0.17 [0.06, 0.51], p = 0.002), higher corrected basal LDL-C levels (HR 0.98 [0.97, 0.99] per mg/dL, p = 0.001), and supervised in-hospital training during CRP (HR 0.28 [0.09, 0.86], p = 0.03) were associated with a reduced probability of positive RD-LDL-C. No association was found with adherence to the Mediterranean diet (88.1%), therapeutic adherence (89.1%), reported weekly physical activity (median 3545 [1980, 6132] metabolic equivalents per week), or change in peak VO(2). Conclusions: More than one-third of post-MI patients demonstrated lower than expected LDL-C reduction (positive RD-LDL-C) following CRP, a finding that could not be attributed to poor adherence to pharmacological therapy or lifestyle recommendations. These findings suggest that a personalized approach to prescribing and uptitrating LLT may help achieve LDL-C targets, particularly in MI patients with healthy lifestyle habits who exhibit a lower response to LLT.