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.
N1 - Funding Information:
The Jackson Heart Study is supported by contracts HHSN268-201300046C, HHSN268201300047C, HHSN26820130004-8C, HHSN268201300049C, and HHSN268201300050C from the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute on Minority Health and Health Disparities, with additional support from the National Institute on Biomedical Imaging and Bioengineering. The Framingham Heart Study (FHS) is supported by the National Institutes of Health/NHLBI (Contract N01-HC-25195-06). The FHS is conducted and supported by the NHLBI in collaboration with Boston University.
Funding Information:
Drs Joshi and Martin have received support from the Pollin Cardiovascular Prevention Fellowship and NIH Training Grants T32HL007227 and T32HL07024, respectively. Dr Martin has also received support from the Marie-Josée and Henry R. Kravis fellowship. Drs Martin and Jones are coinventors on a pending patent filed by Johns Hopkins University for a method of LDL-C estimation. Drs Massaro and D’Agostino were funded by Atherotech Research for this work. Dr Blaha served on the advisory board for Pfizer. Dr Kulkarni is Atherotech research director and receives royalty from the University of Alabama at Birmingham. Dr Toth is consultant for Amgen, AstraZeneca, Kowa, Merck, and Novartis and on the speaker’s bureau for Amarin, AstraZeneca, Genzyme GlaxoSmithKline, Kowa, and Merck. There are no disclosures for Mr Khokhar, Mr Lirette, Dr Griswold, and Dr Correa.
Publisher Copyright:
© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
PY - 2016/5
Y1 - 2016/5
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.
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.
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
SN - 2047-9980
VL - 5
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 5
M1 - e002765
ER -