Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2016 Apr 29;5(5):e002765.
doi: 10.1161/JAHA.115.002765.

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

Parag H Joshi  1 , Arif A Khokhar  2 , Joseph M Massaro  3 , Seth T Lirette  4 , Michael E Griswold  4 , Seth S Martin  5 , Michael J Blaha  5 , Krishnaji R Kulkarni  6 , Adolfo Correa  7 , Ralph B D'Agostino Sr  3 , Steven R Jones  5 , Peter P Toth  8 ; Lipoprotein Investigators Collaborative (LIC) Study Group
Affiliations
Observational Study

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

Parag H Joshi et al. J Am Heart Assoc. .

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Forest plot of hazard ratios for CHD events in a combined population from the Jackson Heart and Framingham Offspring Cohort Studies. Hazard ratios are for a 1‐SD increase in remnant lipoprotein cholesterol (RLP‐C) and its components, IDL‐C and VLDL 3‐C, in unadjusted models, risk factor–adjusted models (model 1), and models inclusive of HDL‐C and real LDL‐C [LDL‐R; excludes IDL and Lp(a)]. Model 1 variables were age, sex, body mass index (BMI), current smoking, systolic and diastolic blood pressures (SBP and DBP, respectively), lipid‐altering medications, and diabetes. HDL‐C indicates high‐density lipoprotein cholesterol; IDL‐C, intermediate‐density lipoprotein cholesterol; LDL‐C, low‐density lipoprotein cholesterol; Lp(a)‐C, lipoprotein(a) cholesterol; real LDL‐C, XXX; VLDL‐C, very low density lipoprotein cholesterol.
Figure 2
Figure 2
Three‐dimensional plot of modeled risk for coronary heart disease (CHD) by high‐density lipoprotein cholesterol (HDL‐C) and remnant lipoprotein cholesterol (RLP‐C) levels showing a trend toward the highest risk in those with the lowest HDL‐C and highest RLP‐C levels (P for interaction 0.066).
See this image and copyright information in PMC

References

    1. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, De Ferranti S, Despres J, Fullerton HJ, Howard VJ, Huffman MD, Judd SE, Kissela BM, Lackland DT, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Matchar DB, Mcguire DK, Mohler ER III, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Willey JZ, Woo D, Yeh RW, Turner MB. Heart disease and stroke statistics‐2015 update: a report from the American Heart Association. Circulation. 2015;131:E29–E322. - PubMed
    1. Miller M, Stone NJ, Ballantyne C, Bittner V, Criqui MH, Ginsberg HN, Goldberg AC, Howard WJ, Jacobson MS, Kris‐Etherton PM, Lennie TA, Levi M, Mazzone T, Pennathur S; American Heart Association Clinical Lipidology T, Prevention Committee Of The Council On Nutrition Pa, Metabolism, Council On Arteriosclerosis T, Vascular B, Council On Cardiovascular N And Council On The Kidney In Cardiovascular D . Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2011;123:2292–2333. - PubMed
    1. Sniderman AD, Williams K, Contois JH, Monroe HM, Mcqueen MJ, De Graaf J, Furberg CD. A meta‐analysis of low‐density lipoprotein cholesterol, non‐high‐density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk. Circ Cardiovasc Qual Outcomes. 2011;4:337–345. - PubMed
    1. Fujioka Y, Ishikawa Y. Remnant lipoproteins as strong key particles to atherogenesis. J Atheroscler Thromb. 2009;16:145–154. - PubMed
    1. Moyer MP, Tracy RP, Tracy PB, Van't Veer C, Sparks CE, Mann KG. Plasma lipoproteins support prothrombinase and other procoagulant enzymatic complexes. Arterioscler Thromb Vasc Biol. 1998;18:458–465. - PubMed

Publication types

MeSH terms

Associated data