Cluster-Based Analysis of Lipid-Derived Profiles and Clinical Presentation in Premature Acute Coronary Syndrome

Objective: Premature acute coronary syndrome (ACS) is clinically heterogeneous, and routine lipid parameters may not fully capture lipid-related risk profiles in young patients. We investigated whether lipid-derived indices could identify clusters associated with index ACS presentation and long-term outcomes.
Method: This retrospective, single-center observational cohort study included patients aged ≤50 years who presented with first documented angiographically obstructive premature ACS and had complete lipid data. Standardized non-HDL-C, remnant cholesterol, TG/HDL-C ratio, and atherogenic index of plasma were analyzed using k-means clustering. Associations with STEMI presentation and a composite cardiovascular/cerebrovascular endpoint were evaluated using logistic and Cox regression analyses.
Results: Of 1106 screened records, 195 were excluded because of incomplete lipid data or implausible lipid values, leaving 911 patients for analysis. At presentation, 152 patients (16.7%) had unstable angina, 224 (24.6%) had NSTEMI, and 535 (58.7%) had STEMI. Two clusters were identified: a lower atherogenic pattern (n=673, 73.9%) and a high atherogenic pattern (n=238, 26.1%). STEMI was less frequent in the high atherogenic pattern than in the lower atherogenic pattern (51.7% vs. 61.2%; p=0.010) and remained independently associated after adjustment (OR, 0.69; 95% CI, 0.50–0.93; p=0.016). In the MI-only sensitivity analysis, this association was attenuated and was no longer statistically significant. Sensitivity clustering yielded similar results. During a median clinical follow-up of 1370 days (IQR, 706–1991), 228 patients (25.0%) experienced the composite endpoint; the high atherogenic pattern was not independently associated with this outcome (HR, 1.11; 95% CI, 0.83–1.48; p=0.496).
Conclusion: Lipid-derived clustering identified two phenotypic patterns associated with index ACS presentation but not with long-term composite outcomes. Prospective external validation is required.

Keywords: Atherogenic index of plasma, cluster analysis, lipid-derived phenotypic patterns, non-HDL cholesterol, premature acute coronary syndrome, remnant cholesterol, STEMI.