Publication Date

3-11-2022

Journal

European Journal of Preventive Cardiology

DOI

10.1093/eurjpc/zwaa152

PMID

33580780

PMCID

PMC8277878

PubMedCentral® Posted Date

3-11-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Aged, Aged, 80 and over, Angiopoietin-Like Protein 3, Angiopoietin-like Proteins, Apolipoprotein C-III, Atherosclerosis, Brain Ischemia, Humans, Lipoproteins, Middle Aged, Stroke, Triglycerides, Triglyceride-rich lipoprotein, Atherosclerotic cardiovascular disease, Low-density lipoprotein triglyceride, Remnant-like particle cholesterol, Apolipoprotein C-III, Angiopoietin-like 3

Abstract

AIMS: Despite statin and antihypertensive therapies, older Americans have high atherosclerotic cardiovascular disease (ASCVD) risk. Novel measures of triglyceride-rich lipoproteins, low-density lipoprotein triglycerides (LDL-TG), and remnant-like particle cholesterol (RLP-C), are associated with ASCVD in middle-aged adults. Polymorphisms in genes encoding angiopoietin-related protein 3 (ANGPTL3) and apolipoprotein C-III (apoC-III), two proteins involved in triglyceride catabolism, are associated with increased risk for hypertriglyceridaemia and ASCVD and are potential therapeutic targets. We examined associations of LDL-TG, RLP-C, apoC-III, and ANGPTL3 levels with ASCVD events in older adults in the Atherosclerosis Risk in Communities (ARIC) study.

METHODS AND RESULTS: In 6359 participants (mean age 75.8 ± 5.3 years) followed for ASCVD events [coronary heart disease (CHD) or ischaemic stroke] up to 6 years, associations between LDL-TG, RLP-C, apoC-III, and ANGPTL3 and ASCVD events were assessed using Cox regression. With adjustment for age, sex, and race, RLP-C, LDL-TG, apoC-III, and ANGPTL3 (as continuous variables) were significantly associated with CHD. However, after adjustment for traditional risk factors and lipid-lowering medications, only LDL-TG and ANGPTL3 were significantly associated with ASCVD events [hazard ratio (HR) 1.72, 95% confidence interval (CI) 1.25-2.37 per log unit increase in LDL-TG; HR 1.63, 95% CI 1.17-2.28 per log unit increase in ANGPTL3].

CONCLUSIONS: In older adults, LDL-TG, RLP-C, apoC-III, and ANGPTL3 were associated with CHD events in minimally adjusted models; LDL-TG and ANGPTL3 remained independent predictors of ASCVD events with further adjustment. Future studies should assess potential benefit of lowering hepatic apoC-III or ANGPTL3 expression in patients with elevated triglyceride-rich lipoproteins.

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