Author + information
- Received December 19, 2017
- Revision received April 2, 2018
- Accepted April 16, 2018
- Published online July 2, 2018.
- Anum Saeed, MDa,b,
- Elena V. Feofanova, MSc,
- Bing Yu, PhDc,
- Wensheng Sun, MPH, MSa,b,
- Salim S. Virani, MD, PhDa,b,d,e,
- Vijay Nambi, MD, PhDa,b,e,
- Josef Coresh, MD, PhDf,
- Cameron S. Guild, MDg,
- Eric Boerwinkle, PhDc,
- Christie M. Ballantyne, MDa,b,h and
- Ron C. Hoogeveen, PhDa,b,∗ (, )@bcmhouston
- aSection of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, Texas
- bCenter for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston, Texas
- cHuman Genetics Center, The University of Texas School of Public Health, Houston, Texas
- dSection of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, Texas
- eSection of Cardiology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
- fDepartment of Epidemiology, Biostatistics, and Medicine, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
- gDepartment of Medicine, University of Mississippi School of Medicine, Jackson, Mississippi
- hSection of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, Texas
- ↵∗Address for correspondence:
Dr. Ron C. Hoogeveen, Section of Cardiovascular Research, Baylor College of Medicine, 6565 Fannin Street, MS F701, Houston, Texas 77030.
Background Hypertriglyceridemia is associated with increased remnant-like particle cholesterol (RLP-C) and triglycerides in low-density lipoprotein (LDL-TG). Recent studies have focused on atherogenicity of RLP-C, with few data on LDL-TG.
Objectives The aim of this study was to examine associations of RLP-C and LDL-TG with incident cardiovascular disease (CVD) events and genetic variants in the ARIC (Atherosclerosis Risk In Communities) study.
Methods Fasting plasma RLP-C and LDL-TG levels were measured in 9,334 men and women without prevalent CVD. Participants were followed for incident CVD events (coronary heart disease and ischemic stroke) for up to 16 years. Associations between LDL-TG and RLP-C levels and genetic variants were assessed by whole-exome sequencing using single-variant analysis for common variants and gene-based burden tests for rare variants; both an unbiased and a candidate gene approach were explored.
Results RLP-C and LDL-TG levels were correlated with triglyceride levels (r = 0.85 and r = 0.64, p < 0.0001). In minimally adjusted analyses, RLP-C and LDL-TG were associated with CVD risk, but in models adjusted for traditional risk factors including lipids, only LDL-TG was associated with incident CHD (hazard ratio: 1.28; 95% confidence interval: 1.10 to 1.50) and stroke (hazard ratio: 1.47; 95% confidence interval: 1.13 to 1.92). A common APOE variant, rs7412, had the strongest association with LDL-TG and RLP-C (p < 5 × 10−8).
Conclusions RLP-C and LDL-TG levels were predictive of CVD and associated with APOE variants. LDL-TG may represent a marker of dysfunctional remnant lipoprotein metabolism associated with increased CVD risk. Further research is needed to determine whether LDL-TG plays a causal role in CVD and may be a target for therapy.
The ARIC study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). Funding support for “Building on GWAS for NHLBI-Diseases: The U.S. CHARGE Consortium” was provided by the National Institutes of Health through the American Recovery and Reinvestment Act of 2009 (5RC2HL102419). Sequencing was carried out at the Baylor College of Medicine Human Genome Sequencing Center (U54 HG003273). Dr. Hoogeveen has received a research grant from Denka Seiken; Denka Seiken had no role in the design, analysis, or data interpretation of this study. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received December 19, 2017.
- Revision received April 2, 2018.
- Accepted April 16, 2018.
- 2018 American College of Cardiology Foundation
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