Background
Remnants are partially-hydrolyzed, triglyceride-rich lipoproteins that, like other apolipoprotein B-containing lipoproteins, are atherogenic. Prior observational studies suggest paradoxically better outcomes in hypercholesterolemic patients who sustain an acute myocardial infarction (AMI), one of several known recurrent risk paradoxes. To date, the association of directly-measured remnant lipoprotein cholesterol (RLP-C) with survival has not been examined after an AMI.
Methods
We examined 2,465 AMI survivors in TRIUMPH, a prospective, 24-center US study of AMI outcomes. Lipoprotein cholesterol subfractions were directly measured by ultracentrifugation. RLP-C was defined as IDL-C+VLDL3-C. Given a linear relationship between RLP-C and mortality, we examined RLP-C by tertiles and continuously. Cox regression hazard ratios were adjusted for the GRACE score and 23 other co-variates.
Results
Participants were 58±12 years old (mean±SD) and 68% were men. After 2 years of follow-up, 226 (9%) participants died. The mortality proportion was 12.4% in the lowest tertile of RLP-C (0–15 mg/dL), 8.5% in the middle tertile (16–23 mg/dL), and 6.8% in the highest tertile (24–120 mg/dL) (p<0.001). A one SD increase in RLP-C (11 mg/dL) predicted a 24% lower adjusted risk of 2-year mortality (HR, 0.76; 95% CI 0.64–0.91). Similar results were found for a one SD increase in IDL-C (HR per 8 mg/dL, 0.80; 0.67–0.96), VLDL3-C (HR per 4 mg/dL, 0.74; 0.61–0.89), and VLDL-C (HR per 8 mg/dL, 0.69; 0.55–0.85).
Conclusion
In conclusion, higher RLP-C levels were associated with lower mortality 2 years after AMI despite rigorous adjustment for known confounders. Unknown protective factors, or a lead-time bias, likely explain the paradox.