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HDL Apolipoproteomic Score and CAD, CV Death
Study Questions:
What is the performance of the high-density lipoprotein (HDL) apolipoproteomic score for the detection of angiographic coronary artery disease (CAD) and outcomes?
Methods:
HDL-associated apolipoprotein (apo) A-1, apoC-1, apoC-2, apoC-3, and apoC-4 were measured by targeted mass spectrometry in 943 participants referred for coronary angiography in the CASABLANCA (Catheter Sampled Blood Archive in Cardiovascular Diseases) study. Primary endpoints were the association of composite HDL apolipoproteomic score (pCAD) with obstructive CAD (≥70% lesion in ≥1 vessel) and with incident cardiovascular (CV) outcomes over 4-year follow-up.
Results:
Mean age was 66.6 years, 72% were male, about 50% had a clinical diagnosis of CAD at presentation, and 70% were on statins. Overall, 553 (58.6%) had clinical atherosclerosis in ≥1 of coronary, peripheral, or cerebrovascular beds. There were 587 (62.2%) patients with coronary stenosis. The pCAD score was associated with the presence of obstructive CAD (odds ratio, 1.39; 95% confidence interval [CI], 1.14-1.69; p < 0.001), independently of conventional CV risk factors including circulating plasma apoA-1 and apoB. The C-index for pCAD was 0.63 (95% CI, 0.59-0.67) for the presence of obstructive CAD. Although pCAD was not associated with CV mortality among all individuals (hazard ratio, 1.24; 95% CI, 0.93-1.66; p = 0.15), there was evidence of association for individuals with obstructive CAD (hazard ratio, 1.48; 95% CI, 1.07-2.05; p = 0.019).
Conclusions:
An HDL apolipoproteomic score is associated with the presence of CAD, independent of circulating apoA-1 and apoB concentrations and other conventional CV risk factors. Among individuals with CAD, this score may be independently associated CV death.
Perspective:
The protein apoC-III is on the surface of HDL and apoB triglyceride-rich particles and is an independent risk factor for CV disease (CVD) when present on lipoproteins containing apoB. It is an endogenous inhibitor of lipoprotein lipase and hepatic lipase, which results in an increase in triglyceride-rich atherogenic very low-density lipoprotein (VLDL) remnant particles and decrease in hepatic clearance, and genetic deficiency is associated with a reduced risk of CAD. Volanesorsen, an antisense to apoC-III, has been shown to reduce apoC-III and triglycerides by about 75% and to increase HDL cholesterol by 40%. It has not been approved for the familial chylomicronemia syndrome and familial partial lipodystrophy each of which have frequent bouts of pancreatitis despite approval by the FDA advisory committee because of the risk of thrombocytopenia. The clinical relevance of an apoC-III inhibitor on atherosclerotic plaque and atherosclerotic CVD will need to be assessed in placebo-controlled trials.
Clinical Topics: Arrhythmias and Clinical EP, Diabetes and Cardiometabolic Disease, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Atherosclerotic Disease (CAD/PAD), Hypertriglyceridemia, Lipid Metabolism, Nonstatins, Novel Agents, Primary Hyperlipidemia, Statins, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Nuclear Imaging
Keywords: Atherosclerosis, Apolipoprotein A-I, Apolipoprotein C-I, Apolipoprotein C-II, Apolipoprotein C-III, Apolipoproteins B, Cholesterol, HDL, Coronary Angiography, Coronary Artery Disease, Coronary Stenosis, Dyslipidemias, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hyperlipoproteinemia Type I, Lipids, Mass Spectrometry, Plaque, Atherosclerotic, Primary Prevention, Proteomics, Risk Factors, Triglycerides
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