Abstract 033: Directly Measured Triglyceride-Rich Lipoprotein Cholesterol and Small Dense LDL-Cholesterol Concentrations Associate With Incident Cardiovascular Disease: Prospective Data From the Women’s Health Study

Abstract

Background: Elevated triglyceride rich lipoproteins (TRLs) and small dense LDL (sdLDL) levels are hallmarks of atherogenic dyslipidemia and the cholesterol content of these particles is hypothesized to drive atherosclerotic risk. However, laboratory quantitation has thus far been impractical with limited prospective clinical data utilizing directly measured levels of this cholesterol burden. Methods: We conducted a prospective case-cohort study within the Women’s Health Study. Randomly selected CVD case subjects (n=500) were compared to a reference subcohort (n=496). TRL-C and sdLDL-C (mg/dl) were directly measured in baseline blood specimens. Cox proportional hazards models were used to compute quartile-specific multivariable-adjusted HRs for total CVD and individual outcomes of coronary and cerebrovascular disease (CCVD) and peripheral artery disease (PAD). Clinical models also adjusted for LDL-C and hsCRP. Results: TRL-C and sdLDL-C were strongly correlated ( ρ =0.716, p<0.001) and levels were higher in case subjects than in the reference risk set. The risk of each outcome increased across quartiles of TRL-C (HR adj Q4 vs Q1: total events 1.87, 95% CI 1.14 - 3.06, p=0.012; CCVD 1.81, 95% CI 1.05 - 3.09, p = 0.030; PAD 2.43, 95% CI 1.11 - 5.31, p=0.039). In contrast, elevated sdLDL-C associated with incident CCVD but not PAD (HR adj Q4 vs Q1: total events 1.85, 95% CI 1.04 - 3.31, p=0.014; CCVD 2.17, 95% CI 1.14 - 4.13, p = 0.006; PAD 1.34, 95% CI 0.54 - 3.33, p=0.389). Conclusion: Directly measured TRL-C and sdLDL-C concentrations are strongly linked to incident CVD with potentially differential effects for PAD. These findings may indicate a greater potential benefit of therapeutics targeting TRL-C rather than LDL in the prevention of PAD.