Increasing evidence has shown that loss-of-function mutations in APOC3 is associated with reduction in plasma triglycerides levels and will confer a benefit in patients at high risk for cardiovascular disease.
Conclusions HDL particles of larger size and higher concentrations of large HDL and of HDL without apolipoprotein C-III were associated with lower CVD risk, with risk estimates seemingly stronger among participants with lower eGFR.
Therefore, there appears to be a need for effective TG-lowering agents.<b>Areas covered</b>: This review presents the most recent advances in hypertriglyceridemia treatment; specifically, it discusses the results of clinical trials and critically comments on apolipoprotein C-III inhibitors, angiopoietin-like 3 inhibitors, alipogene tiparvovec, pradigastat, pemafibrate and novel formulations of omega-3 fatty acids.<b>Expert opinion</b>: In the era of extreme lowering of LDL-C levels with several agents, there seems to be space for novel therapeutic options to combat parameters responsible for residual CVD risk, among which are elevated TGs.
To explore the potential usefulness of screening for genetic predictors of cardiovascular disease, we surveyed BioVU, the Vanderbilt University Medical Center's biorepository linked to de-identified electronic health records (EHRs), for APOC3 19X mutations among adult European American patients (> 45 and > 55 years of age for men and women, respectively) with the lowest percentile of TG levels.
When put in the context of studies demonstrating significant protection from cardiovascular events in individuals with loss of function variants in the APOC3 gene, our results provide strong evidence that therapies which increase the efficiency of conversion of VLDL to LDL, thereby reducing remnant concentrations, should reduce the risk of cardiovascular disease.
ApoC-III is a critical cardiovascular risk factor, and humans expressing null mutations in apoC-III are robustly protected from cardiovascular disease.
Variation within and around the apolipoprotein C-III (APOC3) gene has been associated with elevated triglyceride (Tg) levels and cardiovascular disease.
Rs45456595 (CDKN2A, Gly63Arg), rs5128 (APOC3, 3'UTR), and rs72650673 (SH2B3, rs72650673;rs1285539239;s72650673;rs370155845" genes_norm="10019;1124;1284">Glu400Lys) were nominally associated with history of CVD, subclinical CVD, or CVD risk factors (p < 0.010).
We examined the association of LpPLA2 activity and ApoC3 LOF mutations and incident cardiovascular disease (CVD) (defined as coronary heart disease [CHD] plus ischemic stroke) and all-cause mortality in the biracial longitudinal Atherosclerosis Risk In Communities (ARIC) study.
Here, we review the pathophysiological role of apoC-III in TG metabolism and the evidence supporting this apolipoprotein as an emerging target for hypertriglyceridemia (HTG) and associated cardiovascular disorders.
Antisense inhibition of apoC-III in preclinical models and in a phase I clinical trial with healthy subjects produced potent, selective reductions in plasma apoC-III and triglyceride, 2 known risk factors for cardiovascular disease.
Furthermore, apoC-III and ANGPTL3, both of which are now known to associate with increased atherosclerotic cardiovascular diseases, were enriched in patients with CETP-D compared with normolipidemic subjects (35.9 ± 5.3 vs 27.1 ± 3.7, 2.3 ± 1.1 vs 0.4 ± 1.1, respectively; P < .01).
Apolipoprotein C-III has been referred to as an important participant in the metabolism of triglyceride-rich lipoproteins, leading to hypertriglyceridemia and thereafter cardiovascular disease.
ApoCIII and triglyceride (TG)-rich lipoproteins (TRL), particularly, large TG-rich lipoproteins particles, have been described as important mediators of cardiovascular disease (CVD) risk.
This favourable lipid profile in patients with genetically low apoCIII levels holds promise for current studies investigating the potential of apoCIII inhibition as a novel therapeutic in cardiovascular disease prevention.
Serum apoCIII concentration was highly correlated with multiple changes in lipids and lipoproteins that resulted in an adverse cardiovascular disease risk profile.
Mixed dyslipidemia, characterized by elevated triglyceride and apoC-III levels and low HDL cholesterol level, with or without elevated LDL cholesterol, increases cardiovascular disease risk and is commonly treated with combined statin and fibrate therapy.