Small Dense Low-Density Lipoprotein Cholesterol Predicts Long-Term Coronary Artery Disease Recurrence in Patients Without Metabolic Dyslipidemia

BACKGROUND: This study investigated whether small dense low-density lipoprotein cholesterol (sdLDL-C) can predict long-term coronary artery disease (CAD) events in patients with stable CAD without metabolic dyslipidemia. METHODS AND RESULTS: Directly measured sdLDL-C was evaluated in 396 male and 144 female patients with stable CAD who had high-density lipoprotein cholesterol (HDL-C) ≥40 mg/dL and triglyceride <150 mg/dL. CAD events, which were defined as sudden cardiac death, acute coronary syndrome onset, and/or a need for coronary revascularization, were monitored for 12 years. First-time CAD events were observed in 110 men and 44 women. Kaplan-Meier event-free survival curves showed that patients with sdLDL-C ≥32.5 mg/dL (top quartile) had an increased risk of CAD events (log-rank P=0.009). The multivariate-adjusted hazard ratio (HR) in the top sdLDL-C quartile was 1.632 (95% confidence interval 1.159-2.297) and remained significant in 354 patients treated with statins (HR 1.582; P=0.041), whereas the risk in the top quartiles of LDL-C, non-HDL-C, apolipoprotein B, and triglyceride was not significantly higher relative to lower quartiles. Receiver operating characteristic curve analyses indicated that risk increased at cut-off values of sdLDL-C ≥32.2 mg/dL (HR 1.566; P=0.011) and sdLDL-C/LDL-C ratio ≥0.316 (HR 1.569; P=0.018). CONCLUSIONS: Although sdLDL is a feature of metabolic dyslipidemia, high sdLDL-C can predict long-term recurrence of CAD events even in patients without metabolic dyslipidemia.