Cumulative LDL cholesterol exposure after percutaneous coronary intervention is associated with major adverse cardiovascular events

BACKGROUND AND AIMS We assessed whether AUC-derived cumulative low-density lipoprotein cholesterol (LDL-C) exposure after percutaneous coronary intervention (PCI) was associated with subsequent major adverse cardiac and cerebrovascular events (MACCE), and compared this longitudinal metric with the latest LDL-C measurement. METHODS We conducted a retrospective, single-centre, matched case-control study of consecutive patients undergoing successful PCI from 2010 to 2020. Cases with major adverse cardiac and cerebrovascular events (MACCE) were matched 1:1 to event-free controls by follow-up duration. Cumulative LDL-C exposure was calculated from serial LDL-C measurements by the trapezoidal rule. Conditional logistic regression with restricted cubic splines was used, with prespecified multivariable adjustment for available baseline clinical characteristics. RESULTS Among 544 matched pairs, cumulative LDL-C exposure was higher in MACCE cases than controls (median 489.8 vs 179.5 mg/dL·year; p < 0.001), whereas the latest LDL-C was modestly lower in cases (74.3 ± 26.6 vs 81.2 ± 26.4 mg/dL; p < 0.001). In the multivariable-adjusted spline model, the odds ratio at 400 mg/dL·year was 2.73 (95% CI, 2.24-3.32) relative to the median exposure in controls. Associations were consistent in time-truncated and component-specific exploratory analyses. CONCLUSIONS In secondary prevention after PCI, AUC-derived cumulative LDL-C exposure was associated with MACCE beyond available baseline clinical characteristics and may complement snapshot LDL-C assessment. The apparent 400 mg/dL·year range is exploratory and hypothesis-generating, not a clinically actionable treatment target.