TY - JOUR
T1 - Remnant lipoprotein cholesterol and mortality after acute myocardial infarction
T2 - Further evidence for a hypercholesterolemia paradox from the TRIUMPH registry
AU - Martin, Seth S.
AU - Faridi, Kamil F.
AU - Joshi, Parag H.
AU - Blaha, Michael J.
AU - Kulkarni, Krishnaji R.
AU - Khokhar, Arif A.
AU - Maddox, Thomas M.
AU - Havranek, Edward P.
AU - Toth, Peter P.
AU - Tang, Fengming
AU - Spertus, John A.
AU - Jones, Steven R.
N1 - Funding Information:
This work was supported by the National Heart, Lung, and Blood Institute (P50 HL 077113). S.S.M. and P.H.J. were supported by the Pollin Cardiovascular Prevention Fellowship and by National Institutes of Health training grants (T32HL07024 and T32HL007227, respectively). S.S.M. was also supported by the Marie-Josée and Henry R. Kravis endowed fellowship.
Publisher Copyright:
© 2015 Wiley Periodicals, Inc.
PY - 2015/11/1
Y1 - 2015/11/1
N2 - 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 after an AMI has not been examined. Hypothesis Higher RLP-C levels may be paradoxically associated with lower mortality. Methods We examined 2465 AMI survivors in a prospective, 24-center US study of AMI outcomes. Lipoprotein cholesterol subfractions were directly measured by ultracentrifugation. RLP-C was defined as intermediate-density lipoprotein cholesterol (IDL-C) + very-low-density lipoprotein cholesterol subfraction 3 (VLDL3-C). Given a linear relationship between RLP-C and mortality, we examined RLP-C by tertiles and continuously. Cox regression hazard ratios (HRs) were adjusted for the Global Registry of Acute Coronary Events (GRACE) score and 23 other covariates. Results Participants were age 58 ± 12 years (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 1-SD increase in RLP-C (11 mg/dL) predicted a 24% lower adjusted risk of 2-year mortality (HR: 0.76, 95% confidence interval [CI]: 0.64-0.91). Similar results were found for a 1-SD increase in IDL-C (HR per 8 mg/dL: 0.80, 95% CI: 0.67-0.96), VLDL3-C (HR per 4 mg/dL: 0.74, 95% CI: 0.61-0.89), and very-low-density lipoprotein cholesterol (VLDL-C; HR per 8 mg/dL: 0.69, 95% CI: 0.55-0.85). Conclusions 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 explains the paradox.
AB - 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 after an AMI has not been examined. Hypothesis Higher RLP-C levels may be paradoxically associated with lower mortality. Methods We examined 2465 AMI survivors in a prospective, 24-center US study of AMI outcomes. Lipoprotein cholesterol subfractions were directly measured by ultracentrifugation. RLP-C was defined as intermediate-density lipoprotein cholesterol (IDL-C) + very-low-density lipoprotein cholesterol subfraction 3 (VLDL3-C). Given a linear relationship between RLP-C and mortality, we examined RLP-C by tertiles and continuously. Cox regression hazard ratios (HRs) were adjusted for the Global Registry of Acute Coronary Events (GRACE) score and 23 other covariates. Results Participants were age 58 ± 12 years (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 1-SD increase in RLP-C (11 mg/dL) predicted a 24% lower adjusted risk of 2-year mortality (HR: 0.76, 95% confidence interval [CI]: 0.64-0.91). Similar results were found for a 1-SD increase in IDL-C (HR per 8 mg/dL: 0.80, 95% CI: 0.67-0.96), VLDL3-C (HR per 4 mg/dL: 0.74, 95% CI: 0.61-0.89), and very-low-density lipoprotein cholesterol (VLDL-C; HR per 8 mg/dL: 0.69, 95% CI: 0.55-0.85). Conclusions 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 explains the paradox.
UR - http://www.scopus.com/inward/record.url?scp=84954552098&partnerID=8YFLogxK
U2 - 10.1002/clc.22470
DO - 10.1002/clc.22470
M3 - Article
C2 - 26459191
AN - SCOPUS:84954552098
SN - 0160-9289
VL - 38
SP - 660
EP - 667
JO - Clinical Cardiology
JF - Clinical Cardiology
IS - 11
ER -