Apolipoprotein C-III Levels and Incident Coronary Artery Disease Risk

Abstract

Objective Apolipoprotein C-III (apoC-III) is a key regulator of triglyceride (TG) metabolism. Elevated TG rich lipoproteins and apoC-III levels are causally linked to coronary artery disease (CAD) risk. The mechanism(s) through which apoC-III increases CAD risk remains largely unknown. The aim was to confirm the association between apoC-III plasma levels and CAD risk and to explore which lipoprotein subfractions contribute to this relationship between apoC-III and CAD risk. Approach and Results Plasma apoC-III levels were measured in baseline samples from a nested case-control study in the prospective EPIC-Norfolk study. The study comprised 2,711 apparently healthy study participants, of whom 832 subsequently developed CAD. We studied the association of baseline apoC-III levels with incident CAD risk, lipoprotein subfractions measured by nuclear magnetic resonance spectroscopy (NMR) and inflammatory biomarkers. ApoC-III levels were significantly associated with CAD risk (odds ratio 1.91 95% CI 1.48–2.48 for highest compared to lowest quintile), retaining significance after adjustment for traditional CAD risk factors (odds ratio 1.47, 95% CI 1.11–1.94). ApoC-III levels were positively correlated with TG levels, (r=0.39), particle numbers of very-low density lipoprotein (VLDL; r=0.25), intermediate-density lipoprotein (IDL; r=0.23), small dense LDL (r=0.26), and high-sensitivity C-reactive protein (hsCRP) (r=0.15), whereas an inverse correlation was observed with large LDL particle number (r=−0.11), p<0.001 for each. Mediation analysis indicated that the association between apoC-III and CAD risk could be explained by TG-elevation (TG, VLDL and IDL particles), small LDL particle size and hsCRP. Conclusions ApoC-III levels are significantly associated with incident CAD risk. Elevated levels of remnant lipoproteins, small dense LDL and low-grade inflammation may explain this association.

Comparing the effects of sucrose and high-fructose corn syrup on lipid metabolism and the risk of cardiovascular disease in male rats [pdf]

“…In this study, food intake per 100 g of body weight was lower in animals consuming added sugars compared to the control group, but only the effect of sucrose was statistically significant. Similar results were obtained by Tsanzi et al (2008) and Light et al (2009) who found that food intake in animals on a sucrose diet was lower compared to those on HFCS-55 diet. The glycemic index (GI) is regarded as one of the most significant factors affecting food consumption.…”

“…It has been found that the amount of added sugars had a significant effect on body weight gains in the tested animals, regardless of sugar type. Similar results were obtained by Light et al (2009) and Tsanzi et al (2008). In contrast, Bocarsly et al (2010) observed higher weight gains in animals on an HFCS diet than animals on a sucrose diet.…”

“…However, such an effect was not observed in this study. Due to higher VLDL levels, in quantitative terms, there is also more apoC-III and apoC-I formed in the liver (Cooper, 1987;van Capelleveen et al, 2017). The apoproteins inhibit the activity of lipoprotein lipase (C-III) and decrease binding of lipoprotein particles to hepatic receptors (C-I), which in turn delays VLDL clearance from plasma.…”

Apolipoproteins A1, B, and apoB/apoA1 ratio are associated with first ST-segment elevation myocardial infarction but not with recurrent events during long-term follow-up

“…These apos were found to be strong predictors of CVD [ 17 ]. The association of apoCIII with incident CVD was further corroborated by Van Capelleveen et al [ 18 ] in a nested case–control study of the EPIC-Norfolk cohort. As residual cardiovascular risk remains high [ 8 ] even after successful treatment of traditional risk factors, a case–control study with long-term follow-up of patients with STEMI was executed to evaluate the value of extensive serum apo profiling for (1) prediction of STEMI and for (2) prediction of recurrent major adverse cardiac events (MACE) in patients with STEMI.…”

“…The VLDL-associated apos apoCII, apoE and—to a large extent—apoCIII have recently been identified as potentially important new risk factors [ 17 , 18 ]. These apos are abundant on TG-rich lipoproteins, strongly modulate their metabolism [ 39 ], and might play an important role in the development of atherosclerosis and subsequent CVD.…”