Cumulative LDL-cholesterol exposure after Index percutaneous coronary intervention and subsequent major adverse cardiac and cerebrovascular events
S KageyamaAbstract
Background
Cumulative low-density lipoprotein cholesterol (LDL-C) exposure ("cholesterol burden") is causally linked to atherosclerotic cardiovascular disease and is increasingly recognised as a lifetime determinant of risk. (1) Contemporary concepts of coronary artery disease emphasise atheroma burden and prevention rather than ischemia alone. (2) However, real-world evidence directly relating measured cumulative LDL-C after percutaneous coronary intervention (PCI) to subsequent clinical events remains limited, partly because calculating cumulative exposure requires dense longitudinal LDL-C data.
Purpose
To evaluate whether higher cumulative LDL-C exposure during secondary prevention after index PCI is associated with major adverse cardiovascular and cerebrovascular events (MACCE).
Methods
We studied consecutive PCI patients at a single tertiary centre. Eligible patients had ≥1 year of follow-up and ≥3 LDL-C measurements, with no interval between measurements >400 days. Cumulative LDL-C was calculated as the area under the LDL-C–time curve (AUC, mg/dL·year). Using a matched nested case–control design, MACCE cases were matched 1:1 to event-free controls on follow-up duration (matched population: 544 pairs; 1,088 patients). Group distributions were compared using paired non-parametric testing and the Kolmogorov–Smirnov statistic. Dose–response was explored using conditional logistic regression with a restricted cubic spline. LDL-C targets and treatment intensity during follow-up were guided by contemporary European dyslipidaemia recommendations for secondary prevention. (3)
Results
Among 544 matched pairs (1,088 patients), median follow-up was 4.7 years (interquartile range, 2.5 to 7.5), and matching on follow-up was tight (median absolute difference, 9 days). Median cumulative LDL-C exposure was 490 mg/dL·year in MACCE cases and 180 mg/dL·year in controls (P<0.001); the Hodges–Lehmann median paired difference was 261 mg/dL·year, and 79% of pairs had higher exposure in cases (Figure 1). The distribution of cumulative LDL-C exposure was right-shifted in cases (Kolmogorov–Smirnov D=0.369; P<0.001). In restricted cubic spline conditional logistic regression, MACCE risk increased nonlinearly; at 400 mg/dL·year, the odds ratio was 2.80 (95% confidence interval, 2.32 to 3.39, Figure 2). Sensitivity analyses with follow-up time-truncation yielded qualitatively similar paired associations.
Conclusions
Among PCI patients with serial LDL-C measurements, higher measured cumulative LDL-C exposure during follow-up was strongly associated with MACCE. These findings support cumulative LDL-C as a practical risk marker and reinforce the need for sustained LDL-C lowering in secondary prevention. An AUC-derived cumulative LDL-C threshold near 400 mg/dL·year may help refine risk stratification and guide long-term lipid-lowering strategies beyond conventional LDL-C targets.Distribution of cumulative LDL-CCumulative LDL-C Exposure and MACCE