HDL cholesterol subclasses, myocardial infarction, and mortality in secondary prevention

The lipoprotein investigators collaborative

Seth S. Martin, Arif A. Khokhar, Heidi T. May, Krishnaji R. Kulkarni, Michael J. Blaha, Parag H. Joshi, Peter P. Toth, Joseph B. Muhlestein, Jeffrey L. Anderson, Stacey Knight, Yan Li, John A. Spertus, Steven R. Jones

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Aims High-density lipoprotein (HDL) is highly heterogeneous and the link of its subclasses to prognosis remains controversial. We aimed to rigorously examine the associations of HDL subclasses with prognosis in secondary prevention. Methods and results We collaboratively analysed data from two, complementary prospective cohorts: the TRIUMPH study of 2465 acute myocardial infarction patients, and the IHCS study of 2414 patients who underwent coronary angiography. All patients had baseline HDL subclassification by vertical-spin density gradient ultracentrifugation. Given non-linearity, we stratified by tertiles of HDL-C and its two major subclasses (HDL2-C, HDL3-C), then compared multivariable-adjusted hazard ratios for mortality and mortality/myocardial infarction. Patients were middle-aged to elderly (TRIUMPH: 58.2 ± 12.2 years; IHCS: 62.6 ± 12.6 years), and the majority were men (TRIUMPH: 68.0%; IHCS: 65.5%). IHCS had lower mean HDL-C levels (34.6 ± 10.1 mg/dL) compared with TRIUMPH (40 ± 10.6 mg/dL). HDL3-C accounted for >3/4 of HDL-C (mean HDL3-C/HDL-C 0.78 ± 0.05 in both cohorts). During 2 years of follow-up in TRIUMPH, 226 (9.2%) deaths occurred, while death/myocardial infarction occurred in 401 (16.6%) IHCS patients over 5 years. No independent associations with outcomes were observed for HDL-C or HDL2-C. In contrast, the lowest tertile of HDL3-C was independently associated with >50% higher risk in each cohort (TRIUMPH: with middle tertile as reference, fully adjusted HR for mortality of HDL3-C, 1.57; 95% CI, 1.13-2.18; IHCS: fully adjusted HR for mortality/myocardial infarction, 1.55; 95% CI, 1.20-2.00). Conclusion In secondary prevention, increased risk for long-term hard clinical events is associated with low HDL3-C, but not HDL2-C or HDL-C, highlighting the potential value of subclassifying HDL-C.

Original languageEnglish (US)
Pages (from-to)22-30
Number of pages9
JournalEuropean Heart Journal
Volume36
Issue number1
DOIs
StatePublished - Jan 1 2015

Fingerprint

HDL Lipoproteins
Secondary Prevention
HDL Cholesterol
Lipoproteins
Myocardial Infarction
Research Personnel
Mortality
HDL3 Lipoprotein
Ultracentrifugation
Coronary Angiography
Cohort Studies

Keywords

  • Acute myocardial infarction
  • Coronary heart disease
  • HDL subclasses
  • HDL2
  • HDL3
  • High-density lipoprotein cholesterol
  • Lipids
  • Mortality
  • Secondary prevention

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

HDL cholesterol subclasses, myocardial infarction, and mortality in secondary prevention : The lipoprotein investigators collaborative. / Martin, Seth S.; Khokhar, Arif A.; May, Heidi T.; Kulkarni, Krishnaji R.; Blaha, Michael J.; Joshi, Parag H.; Toth, Peter P.; Muhlestein, Joseph B.; Anderson, Jeffrey L.; Knight, Stacey; Li, Yan; Spertus, John A.; Jones, Steven R.

In: European Heart Journal, Vol. 36, No. 1, 01.01.2015, p. 22-30.

Research output: Contribution to journalArticle

Martin, SS, Khokhar, AA, May, HT, Kulkarni, KR, Blaha, MJ, Joshi, PH, Toth, PP, Muhlestein, JB, Anderson, JL, Knight, S, Li, Y, Spertus, JA & Jones, SR 2015, 'HDL cholesterol subclasses, myocardial infarction, and mortality in secondary prevention: The lipoprotein investigators collaborative', European Heart Journal, vol. 36, no. 1, pp. 22-30. https://doi.org/10.1093/eurheartj/ehu264
Martin, Seth S. ; Khokhar, Arif A. ; May, Heidi T. ; Kulkarni, Krishnaji R. ; Blaha, Michael J. ; Joshi, Parag H. ; Toth, Peter P. ; Muhlestein, Joseph B. ; Anderson, Jeffrey L. ; Knight, Stacey ; Li, Yan ; Spertus, John A. ; Jones, Steven R. / HDL cholesterol subclasses, myocardial infarction, and mortality in secondary prevention : The lipoprotein investigators collaborative. In: European Heart Journal. 2015 ; Vol. 36, No. 1. pp. 22-30.
@article{edcb100af29341c89311648816e17acc,
title = "HDL cholesterol subclasses, myocardial infarction, and mortality in secondary prevention: The lipoprotein investigators collaborative",
abstract = "Aims High-density lipoprotein (HDL) is highly heterogeneous and the link of its subclasses to prognosis remains controversial. We aimed to rigorously examine the associations of HDL subclasses with prognosis in secondary prevention. Methods and results We collaboratively analysed data from two, complementary prospective cohorts: the TRIUMPH study of 2465 acute myocardial infarction patients, and the IHCS study of 2414 patients who underwent coronary angiography. All patients had baseline HDL subclassification by vertical-spin density gradient ultracentrifugation. Given non-linearity, we stratified by tertiles of HDL-C and its two major subclasses (HDL2-C, HDL3-C), then compared multivariable-adjusted hazard ratios for mortality and mortality/myocardial infarction. Patients were middle-aged to elderly (TRIUMPH: 58.2 ± 12.2 years; IHCS: 62.6 ± 12.6 years), and the majority were men (TRIUMPH: 68.0{\%}; IHCS: 65.5{\%}). IHCS had lower mean HDL-C levels (34.6 ± 10.1 mg/dL) compared with TRIUMPH (40 ± 10.6 mg/dL). HDL3-C accounted for >3/4 of HDL-C (mean HDL3-C/HDL-C 0.78 ± 0.05 in both cohorts). During 2 years of follow-up in TRIUMPH, 226 (9.2{\%}) deaths occurred, while death/myocardial infarction occurred in 401 (16.6{\%}) IHCS patients over 5 years. No independent associations with outcomes were observed for HDL-C or HDL2-C. In contrast, the lowest tertile of HDL3-C was independently associated with >50{\%} higher risk in each cohort (TRIUMPH: with middle tertile as reference, fully adjusted HR for mortality of HDL3-C, 1.57; 95{\%} CI, 1.13-2.18; IHCS: fully adjusted HR for mortality/myocardial infarction, 1.55; 95{\%} CI, 1.20-2.00). Conclusion In secondary prevention, increased risk for long-term hard clinical events is associated with low HDL3-C, but not HDL2-C or HDL-C, highlighting the potential value of subclassifying HDL-C.",
keywords = "Acute myocardial infarction, Coronary heart disease, HDL subclasses, HDL2, HDL3, High-density lipoprotein cholesterol, Lipids, Mortality, Secondary prevention",
author = "Martin, {Seth S.} and Khokhar, {Arif A.} and May, {Heidi T.} and Kulkarni, {Krishnaji R.} and Blaha, {Michael J.} and Joshi, {Parag H.} and Toth, {Peter P.} and Muhlestein, {Joseph B.} and Anderson, {Jeffrey L.} and Stacey Knight and Yan Li and Spertus, {John A.} and Jones, {Steven R.}",
year = "2015",
month = "1",
day = "1",
doi = "10.1093/eurheartj/ehu264",
language = "English (US)",
volume = "36",
pages = "22--30",
journal = "European Heart Journal",
issn = "0195-668X",
publisher = "Oxford University Press",
number = "1",

}

TY - JOUR

T1 - HDL cholesterol subclasses, myocardial infarction, and mortality in secondary prevention

T2 - The lipoprotein investigators collaborative

AU - Martin, Seth S.

AU - Khokhar, Arif A.

AU - May, Heidi T.

AU - Kulkarni, Krishnaji R.

AU - Blaha, Michael J.

AU - Joshi, Parag H.

AU - Toth, Peter P.

AU - Muhlestein, Joseph B.

AU - Anderson, Jeffrey L.

AU - Knight, Stacey

AU - Li, Yan

AU - Spertus, John A.

AU - Jones, Steven R.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Aims High-density lipoprotein (HDL) is highly heterogeneous and the link of its subclasses to prognosis remains controversial. We aimed to rigorously examine the associations of HDL subclasses with prognosis in secondary prevention. Methods and results We collaboratively analysed data from two, complementary prospective cohorts: the TRIUMPH study of 2465 acute myocardial infarction patients, and the IHCS study of 2414 patients who underwent coronary angiography. All patients had baseline HDL subclassification by vertical-spin density gradient ultracentrifugation. Given non-linearity, we stratified by tertiles of HDL-C and its two major subclasses (HDL2-C, HDL3-C), then compared multivariable-adjusted hazard ratios for mortality and mortality/myocardial infarction. Patients were middle-aged to elderly (TRIUMPH: 58.2 ± 12.2 years; IHCS: 62.6 ± 12.6 years), and the majority were men (TRIUMPH: 68.0%; IHCS: 65.5%). IHCS had lower mean HDL-C levels (34.6 ± 10.1 mg/dL) compared with TRIUMPH (40 ± 10.6 mg/dL). HDL3-C accounted for >3/4 of HDL-C (mean HDL3-C/HDL-C 0.78 ± 0.05 in both cohorts). During 2 years of follow-up in TRIUMPH, 226 (9.2%) deaths occurred, while death/myocardial infarction occurred in 401 (16.6%) IHCS patients over 5 years. No independent associations with outcomes were observed for HDL-C or HDL2-C. In contrast, the lowest tertile of HDL3-C was independently associated with >50% higher risk in each cohort (TRIUMPH: with middle tertile as reference, fully adjusted HR for mortality of HDL3-C, 1.57; 95% CI, 1.13-2.18; IHCS: fully adjusted HR for mortality/myocardial infarction, 1.55; 95% CI, 1.20-2.00). Conclusion In secondary prevention, increased risk for long-term hard clinical events is associated with low HDL3-C, but not HDL2-C or HDL-C, highlighting the potential value of subclassifying HDL-C.

AB - Aims High-density lipoprotein (HDL) is highly heterogeneous and the link of its subclasses to prognosis remains controversial. We aimed to rigorously examine the associations of HDL subclasses with prognosis in secondary prevention. Methods and results We collaboratively analysed data from two, complementary prospective cohorts: the TRIUMPH study of 2465 acute myocardial infarction patients, and the IHCS study of 2414 patients who underwent coronary angiography. All patients had baseline HDL subclassification by vertical-spin density gradient ultracentrifugation. Given non-linearity, we stratified by tertiles of HDL-C and its two major subclasses (HDL2-C, HDL3-C), then compared multivariable-adjusted hazard ratios for mortality and mortality/myocardial infarction. Patients were middle-aged to elderly (TRIUMPH: 58.2 ± 12.2 years; IHCS: 62.6 ± 12.6 years), and the majority were men (TRIUMPH: 68.0%; IHCS: 65.5%). IHCS had lower mean HDL-C levels (34.6 ± 10.1 mg/dL) compared with TRIUMPH (40 ± 10.6 mg/dL). HDL3-C accounted for >3/4 of HDL-C (mean HDL3-C/HDL-C 0.78 ± 0.05 in both cohorts). During 2 years of follow-up in TRIUMPH, 226 (9.2%) deaths occurred, while death/myocardial infarction occurred in 401 (16.6%) IHCS patients over 5 years. No independent associations with outcomes were observed for HDL-C or HDL2-C. In contrast, the lowest tertile of HDL3-C was independently associated with >50% higher risk in each cohort (TRIUMPH: with middle tertile as reference, fully adjusted HR for mortality of HDL3-C, 1.57; 95% CI, 1.13-2.18; IHCS: fully adjusted HR for mortality/myocardial infarction, 1.55; 95% CI, 1.20-2.00). Conclusion In secondary prevention, increased risk for long-term hard clinical events is associated with low HDL3-C, but not HDL2-C or HDL-C, highlighting the potential value of subclassifying HDL-C.

KW - Acute myocardial infarction

KW - Coronary heart disease

KW - HDL subclasses

KW - HDL2

KW - HDL3

KW - High-density lipoprotein cholesterol

KW - Lipids

KW - Mortality

KW - Secondary prevention

UR - http://www.scopus.com/inward/record.url?scp=84926389606&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84926389606&partnerID=8YFLogxK

U2 - 10.1093/eurheartj/ehu264

DO - 10.1093/eurheartj/ehu264

M3 - Article

VL - 36

SP - 22

EP - 30

JO - European Heart Journal

JF - European Heart Journal

SN - 0195-668X

IS - 1

ER -