Remnant Lipoprotein Cholesterol and Incident Coronary Heart Disease: The Jackson Heart and Framingham Offspring Cohort Studies

Lipoprotein Investigators Collaborative (LIC) Study Group

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

BACKGROUND: Remnant lipoproteins (RLPs), the triglyceride-enriched precursors to low-density lipoprotein, are an emerging risk factor for coronary heart disease (CHD). We sought to determine the association of RLP cholesterol (RLP-C) levels with incident CHD in 2 diverse, prospective, longitudinal observational US cohorts.

METHODS AND RESULTS: We analyzed cholesterol levels from serum lipoprotein samples separated via density gradient ultracentrifugation in 4114 US black participants (mean age 53.8 years, 64% women) from the Jackson Heart Study and a random sample of 818 predominantly white participants (mean age 57.3 years, 52% women) from the Framingham Offspring Cohort Study. Multivariable-adjusted hazard ratios (HRs) for RLP-C (the sum of very low-density lipoprotein3 cholesterol and intermediate-density lipoprotein cholesterol) were derived to estimate associations with incident CHD events consisting of myocardial infarction, CHD death, and revascularizations for each cohort separately and as a combined population. There were 146 CHD events in the combined population. After adjustments for age, sex, body mass index, smoking, blood pressure, diabetes, and lipid-lowering therapy for the combined population, RLP-C (HR 1.23 per 1-SD increase, 95% CI 1.06-1.42, P<0.01) and intermediate-density lipoprotein cholesterol (HR 1.26 per 1-SD increase, 95% CI 1.08-1.47, P<0.01) predicted CHD during an 8-year follow-up. Associations were attenuated by high-density lipoprotein cholesterol and ultimately lost significance with inclusion of real low-density lipoprotein cholesterol, which excludes Lp(a) and IDL cholesterol fractions. Similar associations were seen in multivariable analyses within each cohort.

CONCLUSION: RLP-C levels are predictive of incident CHD in this diverse group of primary prevention subjects. Interventions aimed at reducing RLP-C to prevent CHD warrant further intensive investigation.

CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00415415.

Original languageEnglish (US)
JournalJournal of the American Heart Association
Volume5
Issue number5
DOIs
StatePublished - Apr 29 2016

Fingerprint

Coronary Disease
Cohort Studies
Lipoproteins
Cholesterol
Population
lipoprotein cholesterol
Ultracentrifugation
Primary Prevention
LDL Lipoproteins
LDL Cholesterol
HDL Cholesterol
Body Mass Index
Smoking
Myocardial Infarction
Clinical Trials
Blood Pressure
Lipids
Serum

Keywords

  • coronary heart disease
  • lipids
  • primary prevention
  • remnant lipoprotein cholesterol
  • triglycerides

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Remnant Lipoprotein Cholesterol and Incident Coronary Heart Disease : The Jackson Heart and Framingham Offspring Cohort Studies. / Lipoprotein Investigators Collaborative (LIC) Study Group.

In: Journal of the American Heart Association, Vol. 5, No. 5, 29.04.2016.

Research output: Contribution to journalArticle

@article{4dce00dee2254f3b823b6f8bf7fa4f7a,
title = "Remnant Lipoprotein Cholesterol and Incident Coronary Heart Disease: The Jackson Heart and Framingham Offspring Cohort Studies",
abstract = "BACKGROUND: Remnant lipoproteins (RLPs), the triglyceride-enriched precursors to low-density lipoprotein, are an emerging risk factor for coronary heart disease (CHD). We sought to determine the association of RLP cholesterol (RLP-C) levels with incident CHD in 2 diverse, prospective, longitudinal observational US cohorts.METHODS AND RESULTS: We analyzed cholesterol levels from serum lipoprotein samples separated via density gradient ultracentrifugation in 4114 US black participants (mean age 53.8 years, 64{\%} women) from the Jackson Heart Study and a random sample of 818 predominantly white participants (mean age 57.3 years, 52{\%} women) from the Framingham Offspring Cohort Study. Multivariable-adjusted hazard ratios (HRs) for RLP-C (the sum of very low-density lipoprotein3 cholesterol and intermediate-density lipoprotein cholesterol) were derived to estimate associations with incident CHD events consisting of myocardial infarction, CHD death, and revascularizations for each cohort separately and as a combined population. There were 146 CHD events in the combined population. After adjustments for age, sex, body mass index, smoking, blood pressure, diabetes, and lipid-lowering therapy for the combined population, RLP-C (HR 1.23 per 1-SD increase, 95{\%} CI 1.06-1.42, P<0.01) and intermediate-density lipoprotein cholesterol (HR 1.26 per 1-SD increase, 95{\%} CI 1.08-1.47, P<0.01) predicted CHD during an 8-year follow-up. Associations were attenuated by high-density lipoprotein cholesterol and ultimately lost significance with inclusion of real low-density lipoprotein cholesterol, which excludes Lp(a) and IDL cholesterol fractions. Similar associations were seen in multivariable analyses within each cohort.CONCLUSION: RLP-C levels are predictive of incident CHD in this diverse group of primary prevention subjects. Interventions aimed at reducing RLP-C to prevent CHD warrant further intensive investigation.CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00415415.",
keywords = "coronary heart disease, lipids, primary prevention, remnant lipoprotein cholesterol, triglycerides",
author = "{Lipoprotein Investigators Collaborative (LIC) Study Group} and Joshi, {Parag H.} and Khokhar, {Arif A.} and Massaro, {Joseph M.} and Lirette, {Seth T.} and Griswold, {Michael E.} and Martin, {Seth S.} and Blaha, {Michael J.} and Kulkarni, {Krishnaji R.} and Adolfo Correa and D'Agostino, {Ralph B.} and Jones, {Steven R.} and Toth, {Peter P.}",
year = "2016",
month = "4",
day = "29",
doi = "10.1161/JAHA.115.002765",
language = "English (US)",
volume = "5",
journal = "Journal of the American Heart Association",
issn = "2047-9980",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - Remnant Lipoprotein Cholesterol and Incident Coronary Heart Disease

T2 - The Jackson Heart and Framingham Offspring Cohort Studies

AU - Lipoprotein Investigators Collaborative (LIC) Study Group

AU - Joshi, Parag H.

AU - Khokhar, Arif A.

AU - Massaro, Joseph M.

AU - Lirette, Seth T.

AU - Griswold, Michael E.

AU - Martin, Seth S.

AU - Blaha, Michael J.

AU - Kulkarni, Krishnaji R.

AU - Correa, Adolfo

AU - D'Agostino, Ralph B.

AU - Jones, Steven R.

AU - Toth, Peter P.

PY - 2016/4/29

Y1 - 2016/4/29

N2 - BACKGROUND: Remnant lipoproteins (RLPs), the triglyceride-enriched precursors to low-density lipoprotein, are an emerging risk factor for coronary heart disease (CHD). We sought to determine the association of RLP cholesterol (RLP-C) levels with incident CHD in 2 diverse, prospective, longitudinal observational US cohorts.METHODS AND RESULTS: We analyzed cholesterol levels from serum lipoprotein samples separated via density gradient ultracentrifugation in 4114 US black participants (mean age 53.8 years, 64% women) from the Jackson Heart Study and a random sample of 818 predominantly white participants (mean age 57.3 years, 52% women) from the Framingham Offspring Cohort Study. Multivariable-adjusted hazard ratios (HRs) for RLP-C (the sum of very low-density lipoprotein3 cholesterol and intermediate-density lipoprotein cholesterol) were derived to estimate associations with incident CHD events consisting of myocardial infarction, CHD death, and revascularizations for each cohort separately and as a combined population. There were 146 CHD events in the combined population. After adjustments for age, sex, body mass index, smoking, blood pressure, diabetes, and lipid-lowering therapy for the combined population, RLP-C (HR 1.23 per 1-SD increase, 95% CI 1.06-1.42, P<0.01) and intermediate-density lipoprotein cholesterol (HR 1.26 per 1-SD increase, 95% CI 1.08-1.47, P<0.01) predicted CHD during an 8-year follow-up. Associations were attenuated by high-density lipoprotein cholesterol and ultimately lost significance with inclusion of real low-density lipoprotein cholesterol, which excludes Lp(a) and IDL cholesterol fractions. Similar associations were seen in multivariable analyses within each cohort.CONCLUSION: RLP-C levels are predictive of incident CHD in this diverse group of primary prevention subjects. Interventions aimed at reducing RLP-C to prevent CHD warrant further intensive investigation.CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00415415.

AB - BACKGROUND: Remnant lipoproteins (RLPs), the triglyceride-enriched precursors to low-density lipoprotein, are an emerging risk factor for coronary heart disease (CHD). We sought to determine the association of RLP cholesterol (RLP-C) levels with incident CHD in 2 diverse, prospective, longitudinal observational US cohorts.METHODS AND RESULTS: We analyzed cholesterol levels from serum lipoprotein samples separated via density gradient ultracentrifugation in 4114 US black participants (mean age 53.8 years, 64% women) from the Jackson Heart Study and a random sample of 818 predominantly white participants (mean age 57.3 years, 52% women) from the Framingham Offspring Cohort Study. Multivariable-adjusted hazard ratios (HRs) for RLP-C (the sum of very low-density lipoprotein3 cholesterol and intermediate-density lipoprotein cholesterol) were derived to estimate associations with incident CHD events consisting of myocardial infarction, CHD death, and revascularizations for each cohort separately and as a combined population. There were 146 CHD events in the combined population. After adjustments for age, sex, body mass index, smoking, blood pressure, diabetes, and lipid-lowering therapy for the combined population, RLP-C (HR 1.23 per 1-SD increase, 95% CI 1.06-1.42, P<0.01) and intermediate-density lipoprotein cholesterol (HR 1.26 per 1-SD increase, 95% CI 1.08-1.47, P<0.01) predicted CHD during an 8-year follow-up. Associations were attenuated by high-density lipoprotein cholesterol and ultimately lost significance with inclusion of real low-density lipoprotein cholesterol, which excludes Lp(a) and IDL cholesterol fractions. Similar associations were seen in multivariable analyses within each cohort.CONCLUSION: RLP-C levels are predictive of incident CHD in this diverse group of primary prevention subjects. Interventions aimed at reducing RLP-C to prevent CHD warrant further intensive investigation.CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00415415.

KW - coronary heart disease

KW - lipids

KW - primary prevention

KW - remnant lipoprotein cholesterol

KW - triglycerides

UR - http://www.scopus.com/inward/record.url?scp=84984837342&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84984837342&partnerID=8YFLogxK

U2 - 10.1161/JAHA.115.002765

DO - 10.1161/JAHA.115.002765

M3 - Article

C2 - 27130348

AN - SCOPUS:84984837342

VL - 5

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

SN - 2047-9980

IS - 5

ER -