👤 Pierre Sabouret

Reducing residual cardiovascular risk following acute coronary syndrome (ACS) remains a major unmet clinical need. Despite substantial advances in lipid-lowering therapies, the risk of recurrent major adverse cardiovascular events (MACEs) after ACS remains high, with an estimated incidence of approximately 33.4% at 5 years. Residual cardiovascular risk is driven by multiple mechanisms, including persistent inflammation, a prothrombotic status, metabolic disturbances, and the presence of atherogenic lipoproteins beyond low-density lipoprotein cholesterol (LDL-C). Lipoprotein(a) (Lp(a)) is a pro-inflammatory, prothrombotic, and pro-atherosclerotic lipoprotein that appears to play a major role in residual risk after ACS or ischemic stroke. Elevated Lp(a) is a well-established independent and causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Nevertheless, evidence regarding its prognostic value specifically after ACS remains limited, with marked heterogeneity across studies, which complicates direct comparisons and interpretation. In addition, while Lp(a) levels are predominantly genetically determined, recent studies have reported intra-individual variability, although their clinical significance remains uncertain. Finally, current therapeutic options specifically targeting Lp(a) are limited. Novel RNA-based therapies, including antisense oligonucleotides, small interfering RNAs, and emerging gene-editing approaches, have demonstrated profound and sustained reductions in circulating Lp(a) levels. Yet, whether this biological effect translates into reductions in hard clinical endpoints is under evaluation in ongoing clinical trials. This review aims to synthesize current evidence on the role of Lp(a) as a major contributor to residual cardiovascular risk following ACS. Show less

Dyslipidemia remains a major contributor to atherosclerosis and cardiovascular events. While low-density lipoprotein cholesterol (LDL-C) lowering is the primary treatment target, lipoprotein(a) [Lp(a)] has emerged as an independent, genetically determined risk factor, often unaffected by standard treatment. This study aimed to analyze the relationship between body composition parameters and lipid profile, including Lp(a). Clinically stable high cardiovascular risk patients (n = 207) receiving lipid-lowering pharmacotherapy were enrolled in this cross-sectional study. Anthropometric data and body composition were assessed using bioelectrical impedance analysis, including body mass index (BMI), fat mass (FM%) and fat-free mass percentage (FFM%). Lp(a) and lipid profile were measured. Patients were stratified by Lp(a) concentration: <75 nmol/L, 75-125 nmol/L, and >125 nmol/L. Lp(a) levels showed no significant association with body composition, age, and sex. In contrast, HDL-C was significantly inversely correlated with BMI (R = -0.25, p < 0.001) and this relationship was independent of sex (β = -0.68, p < 0.001), while triglycerides were positively correlated with FM% (R = 0.17, p = 0.02) and BMI (R = 0.28, p < 0.001) and negatively with FFM% (R = -0.17, p = 0.02). LDL-C was not associated with body composition. No significant differences in lipid profile or body composition were observed across Lp(a) strata. In high cardiovascular risk patients, Lp(a) appears unrelated to body composition, supporting its role as a non-modifiable, genetically driven risk factor. Conversely, despite pharmacotherapy, HDL-C and triglycerides demonstrated significant associations with body fat distribution. These findings suggest clinical role of body composition assessment in cardiovascular risk management, particularly in addressing residual risk beyond LDL-C. Show less