High lipoprotein(a) and LDL-cholesterol goal attainment in cardiac rehabilitation

Abstract Background Elevated lipoprotein(a) Lp(a) is an important, largely genetically determined lipoprotein particle that confers additional atherosclerotic cardiovascular risk on top of traditional risk factors. Cardiac rehabilitation (CR) is a cornerstone of post–myocardial infarction care, providing structured risk-factor optimisation, exercise training and patient education. Despite growing recognition of the prognostic impact of high Lp(a) and guideline calls to consider its measurement at least once in a lifetime, Lp(a) is still not routinely assessed in many clinical pathways. To address this gap, we introduced systematic Lp(a) measurement at entry to our centre-based CR programme in 2021. Purpose The aim of this study was to characterise the distribution of Lp(a) in consecutive patients referred to CR, describe the clinical and lipid profile associated with high Lp(a), and evaluate its relationship with lipid-lowering therapy intensity and low-density lipoprotein cholesterol (LDL-C) goal attainment in a real-world secondary prevention setting. Methods For this analysis, we included all consecutive patients referred to our centre-based CR programme (2021-2024). Demographic characteristics, index diagnosis, cardiovascular risk factors, lipid profile and lipid-lowering therapy (LLT) at entry were extracted from clinical records. Lp(a) was categorised as 30.0, 30–49, 50–99 and ≥100 mg/dL; high Lp(a) was defined as ≥50 mg/dL. Group differences were evaluated using χ² and non-parametric tests, and logistic regression was used to examine associations between high Lp(a), intensive LLT and LDL-C goal attainment. Results We included 889 patients (mean age 61.3 ± 10.9 years, 22.7% women). Median Lp(a) was 20.1 mg/dL (IQR 11.1–71.5). High Lp(a) (≥50 mg/dL) was present in 31.9% of patients, and very high Lp(a) (≥100 mg/dL) in 15.4%. Lp(a) levels were similar in women and men (p=0.49). LDL-C increased stepwise across Lp(a) categories from 1.53 ± 0.81 mmol/L in patients with Lp(a)30 mg/dL to 1.86 ± 0.76 mmol/L in those with Lp(a) ≥100 mg/dL (p0.01). Intensive lipid-lowering therapy was used in 95.5% of patients with Lp(a)50 mg/dL and 95.4% with Lp(a) ≥50 mg/dL; high Lp(a) was not independently associated with intensive therapy (p=0.84). In contrast, LDL-C 1.4 mmol/L was achieved in 53.3% of patients with Lp(a)50 mg/dL vs 33.1% with Lp(a) ≥50 mg/dL (p0.01). Goal attainment across Lp(a) categories is illustrated in Figure 1. Conclusion In our cohort, high Lp(a) was common and associated with markedly lower LDL-C goal attainment despite near-universal intensive LLT. This may partly reflect "masking" of LDL-C by the cholesterol content of Lp(a) particles but also highlights a high-risk phenotype that warrants a more personalised approach. In patients with high Lp(a), maximising conventional LLT and considering PCSK9 inhibitors is rational not only for further LDL-C reduction, but also to address Lp(a)-mediated residual risk.LDL-C goal attainment by Lp(a) categoryFor image description, please refer to the figure legend and surrounding text.