Individual and combined prognostic value of LDL-C, Lp(a), and hsCRP for cardiovascular and cerebrovascular events in post-PCI patients: evidence from two large contemporary cohorts

Background Substantial residual cardiovascular risk persists in patients with coronary artery disease (CAD) despite contemporary secondary prevention. While combined assessment of low-density lipoprotein cholesterol (LDL-C), lipoprotein(a) [Lp(a)], and high-sensitivity C-reactive protein (hsCRP) has demonstrated prognostic value in primary prevention settings, evidence in patients with established CAD remains limited. Purpose To evaluate the independent and combined predictive value of hsCRP, LDL-C, and Lp(a) in two large CAD cohorts undergoing secondary prevention after PCI, and to determine whether a multimarker strategy improves risk stratification. Methods This study included two large, real-world cohorts of CAD patients. Cohort 1 prospectively enrolled 10,724 consecutive patients undergoing PCI in 2013, of whom 9,070 with complete biomarker data were included and served as the derivation cohort. Cohort 2 was derived from the PROMISE registry and included 10,492 eligible patients as an external validation cohort. Associations with major adverse cardiovascular and cerebrovascular events (MACCE) were assessed using progressively adjusted Cox models, and a multimarker risk indicator integrating hsCRP, LDL-C, and Lp(a) was constructed. Results Among 9,070 patients in the derivation cohort (mean age 58.5±10.2 years; 77.2% male), LDL-C, hsCRP, and Lp(a) were each independently associated with increased 10-year MACCE risk, as both continuous and categorical variables, in fully adjusted Cox models. The risk of MACCE increased with the number of elevated biomarkers; compared with patients with none, those with two or three elevated markers had significantly higher risk (adjusted HR 1.25 and 1.32, respectively). The integrated risk indicator (IRRI) was strongly associated with MACCE (adjusted HR 3.19, 95% CI 2.15-4.75). These associations were consistently observed in the validation cohort during 2-year follow-up. No significant interactions were identified across major clinical subgroups. Conclusion LDL-C, Lp(a), and hsCRP were independently and additively associated with long-term outcomes after PCI, and integration of these biomarkers into a residual risk indicator further improved risk discrimination. These findings support a multimarker approach to residual risk stratification in secondary prevention.Figure 1Figure 2