Novel Lipid Biomarker HDL3-C Predicts Severity of Coronary Artery Disease

low density lipid particle and receptor
low density lipid particle and receptor
Investigators sought to determine the effect HDL-C subparticles HDL2-C and HDL3-C have on assessing CAD severity in patients who receive statin therapy.

In patients who use statins, severe coronary artery disease (CAD) was associated with low levels of the high-density lipoprotein cholesterol subparticle 3 (HDL3-C) and with high levels of lipoprotein(a) cholesterol (Lp[a]-C), according to study results published in Cardiovascular Revascularization Medicine.

The investigators of this cross-sectional study sought to identify the association of high-density lipoprotein cholesterol (HDL-C) subparticles with severe CAD and the relationship of HDL-C subparticles with inflammation in patients who receive statin therapy.

The study cohort included 304 consecutive adults with suspected CAD treated with statin and aspirin 325 mg/d. Participants were enrolled in the Multi-Analyte, thrombogenic, and Genetic Markers of Atherosclerosis study and underwent elective cardiac catheterization. Blood samples were collected before catheterization and analyzed for detailed lipid profiles (including HDL-C subclasses HDL₂-C and HDL₃-C) and oxidized low-density lipoprotein cholesterol levels.

Disease severity was based on angiographically defined stenosis of any major coronary vessel: Severe CAD was defined as >75% luminal diameter stenosis, and nonsevere CAD was defined as ≤75% luminal diameter stenosis. Receiver-operated curve analysis was used to determine the association between HDL-C subparticles with severe CAD, and multiregression analysis was used to test statistical significance of these associations.

Of the 304 participants, 203 had severe CAD and 101 had minor to moderate CAD. Analysis of blood samples showed that patients with severe CAD were associated with a significantly lower total HDL-C and HDL₃-C and significantly higher Lp[a]-C. Only the association between severe CAD and HDL₃-C and Lp(a)-C remained significant in multivariate analysis.

To predict severe CAD, receiver-operated CURVE analysis determined a cut point of ≤33 mg/dL for HDL₃-C with an area under the curve of 0.6 (P =.003) and a cut point of >7 mg/dL for Lp(a)-C with an area under the curve of 0.61 (P =.0007). In addition, participants with HDL₃-C ≤33 mg/dL and Lp(a)-C >7 mg/dL were associated with significantly elevated oxidized low-density lipoprotein cholesterol levels or markers of inflammation.

Limitations included the inability to infer causality because of the cross-sectional study design and small sample size. The study included patients both with and without any clinical manifestations, potentially affecting the predictive value of certain variables. Finally, the severity of CAD was measured angiographically and did not use other quantitative scoring criteria.

Related Articles

The study investigators found that HDL₃-C and Lp(a)-C were novel biomarkers to predict severe CAD in patients who use statin therapy. In addition, low HDL₃-C levels and high Lp(a)-C correlated with elevated markers of inflammation. Future studies should determine the use of these biomarkers to predict the severity of CAD.


Chaudhary R, Kinderytė M, Chaudhary R, et al. HDL3-C is a marker of coronary artery disease severity and inflammation in patients on statin therapy [published online December 27, 2018]. Cardiovasc Revasc Med. doi: 10.1016/j.carrev.2018.12.019