Remnant lipoprotein cholesterol and mortality after acute myocardial infarction: Further evidence for a hypercholesterolemia paradox from the TRIUMPH registry

Seth S. Martin, Kamil F. Faridi, Parag H. Joshi, Michael J. Blaha, Krishnaji R. Kulkarni, Arif A. Khokhar, Thomas M. Maddox, Edward P. Havranek, Peter P. Toth, Fengming Tang, John A. Spertus, Steven R. Jones

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)660-667
Number of pages8
JournalClinical Cardiology
Volume38
Issue number11
DOIs
StatePublished - Nov 1 2015

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Hypercholesterolemia
Registries
Myocardial Infarction
Mortality
Confidence Intervals
VLDL Cholesterol
Lipoproteins
lipoprotein cholesterol
Ultracentrifugation
Apolipoproteins B
Observational Studies
Survivors
Triglycerides
Survival

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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Remnant lipoprotein cholesterol and mortality after acute myocardial infarction : Further evidence for a hypercholesterolemia paradox from the TRIUMPH registry. / Martin, Seth S.; Faridi, Kamil F.; Joshi, Parag H.; Blaha, Michael J.; Kulkarni, Krishnaji R.; Khokhar, Arif A.; Maddox, Thomas M.; Havranek, Edward P.; Toth, Peter P.; Tang, Fengming; Spertus, John A.; Jones, Steven R.

In: Clinical Cardiology, Vol. 38, No. 11, 01.11.2015, p. 660-667.

Research output: Contribution to journalArticle

Martin, SS, Faridi, KF, Joshi, PH, Blaha, MJ, Kulkarni, KR, Khokhar, AA, Maddox, TM, Havranek, EP, Toth, PP, Tang, F, Spertus, JA & Jones, SR 2015, 'Remnant lipoprotein cholesterol and mortality after acute myocardial infarction: Further evidence for a hypercholesterolemia paradox from the TRIUMPH registry', Clinical Cardiology, vol. 38, no. 11, pp. 660-667. https://doi.org/10.1002/clc.22470
Martin, Seth S. ; Faridi, Kamil F. ; Joshi, Parag H. ; Blaha, Michael J. ; Kulkarni, Krishnaji R. ; Khokhar, Arif A. ; Maddox, Thomas M. ; Havranek, Edward P. ; Toth, Peter P. ; Tang, Fengming ; Spertus, John A. ; Jones, Steven R. / Remnant lipoprotein cholesterol and mortality after acute myocardial infarction : Further evidence for a hypercholesterolemia paradox from the TRIUMPH registry. In: Clinical Cardiology. 2015 ; Vol. 38, No. 11. pp. 660-667.
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title = "Remnant lipoprotein cholesterol and mortality after acute myocardial infarction: Further evidence for a hypercholesterolemia paradox from the TRIUMPH registry",
abstract = "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.",
author = "Martin, {Seth S.} and Faridi, {Kamil F.} and Joshi, {Parag H.} and Blaha, {Michael J.} and Kulkarni, {Krishnaji R.} and Khokhar, {Arif A.} and Maddox, {Thomas M.} and Havranek, {Edward P.} and Toth, {Peter P.} and Fengming Tang and Spertus, {John A.} and Jones, {Steven R.}",
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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.

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.

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