In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 35, No. 8 ( 2015-08), p. 1880-1888
Abstract:
Triglyceride-rich lipoproteins have emerged as causal risk factors for developing coronary heart disease independent of low-density lipoprotein cholesterol levels. Apolipoprotein C-III (ApoC-III) modulates triglyceride-rich lipoprotein metabolism through inhibition of lipoprotein lipase and hepatic uptake of triglyceride-rich lipoproteins. Mutations causing loss-of-function of ApoC-III lower triglycerides and reduce coronary heart disease risk, suggestive of a causal role for ApoC-III. Little data exist about the relationship of ApoC-III, triglycerides, and atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Here, we examined the relationships between plasma ApoC-III, triglycerides, and coronary artery calcification in patients with T2DM. Approach and Results— Plasma ApoC-III levels were measured in a cross-sectional study of 1422 subjects with T2DM but without clinically manifest coronary heart disease. ApoC-III levels were positively associated with total cholesterol (Spearman r =0.36), triglycerides ( r =0.59), low-density lipoprotein cholesterol ( r =0.16), fasting glucose ( r =0.16), and glycosylated hemoglobin ( r =0.12; P 〈 0.0001 for all). In age, sex, and race-adjusted analysis, ApoC-III levels were positively associated with coronary artery calcification (Tobit regression ratio, 1.78; 95% confidence interval, 1.27–2.50 per SD increase in ApoC-III; P 〈 0.001). As expected for an intermediate mediator, these findings were attenuated when adjusted for both triglycerides (Tobit regression ratio, 1.43; 95% confidence interval, 0.94–2.18; P =0.086) and separately for very low–density lipoprotein cholesterol (Tobit regression ratio, 1.14; 95% confidence interval, 0.75–1.71; P =0.53). Conclusions— In persons with T2DM, increased plasma ApoC-III is associated with higher triglycerides, less favorable cardiometabolic phenotypes, and higher coronary artery calcification, a measure of subclinical atherosclerosis. Therapeutic inhibition of ApoC-III may thus be a novel strategy for reducing plasma triglyceride-rich lipoproteins and cardiovascular risk in T2DM.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/ATVBAHA.115.305415
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2015
detail.hit.zdb_id:
1494427-3
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