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HDL Apolipoproteins May Identify Risk, Prognosis of CAD

Key findings

  • Using a new assay, the concentrations of proteins associated with HDL particles were measured in 943 patients undergoing coronary angiography
  • In a retrospective study, a high-density lipoprotein (HDL) apolipoproteomic score, comprised of five HDL-associated risk factors, distinguished those who had coronary artery disease (CAD) from those who did not, independent of conventional risk factors, including HDL cholesterol
  • The score was also associated with future risk of cardiovascular death among patients with CAD

Apolipoproteins, which are protein components of plasma lipoproteins, are known to influence the risk of developing coronary artery disease (CAD) in addition to their lipid components (cholesterol and triglycerides). ApoB is the primary determinant of low-density lipoprotein and other atherogenic lipoproteins, and apoA-1 is the primary determinant of high-density lipoprotein (HDL). Concentrations of these apolipoproteins in the bloodstream are predictive of cardiovascular disease risk.

Beyond that, whether quantifying the concentrations of the diverse apolipoproteins within lipoprotein particles has clinical relevance is not known. To explore, Pradeep Natarajan, MD, MMSc, director of the Cardiovascular Disease Prevention Center, and James L. Januzzi, Jr., MD, director of the Dennis and Marilyn Barry Fellowship in Cardiology Research at Massachusetts General Hospital, and colleagues recently characterized the HDL "apolipoproteome" in nearly 1,000 patients. They calculated an HDL apolipoproteomic score (pCAD), comprised of five protein concentrations within HDL, for each individual.

In the Journal of the American College of Cardiology, the team reports that the pCAD score distinguishes patients with CAD from controls, independent of conventional risk factors, and may also be able to identify patients at higher risk of cardiovascular death.

Calculating pCAD

The researchers obtained blood samples provided by 943 subjects in the previously reported CASABLANCA study, who underwent angiography with or without subsequent intervention.

Using mass spectrometry, the team assessed the samples for plasma lipids and five HDL-associated apolipoproteins: apoA-1, apoC-1, apoC-2, apoC-3 and apoC-4. The pCAD was calculated as a weighted sum of the individual apo measurements.

pCAD and CAD

At the time of angiography, 587 subjects (62.2%) had been diagnosed with CAD, defined in this study as ≥70% stenosis of ≥1 vessel. pCAD was significantly associated with the presence of CAD (OR, 1.39; 95% CI, 1.14–1.69; P = .001). When the HDL apolipoproteins were assessed individually, apoC-1 was significantly associated with 36% reduced odds of CAD.

pCAD was similar to or better than all clinical CAD risk factors assessed (age, sex, smoking status, systolic blood pressure, hypertension, diabetes, statin prescription) and plasma apoB and apoA-1 at distinguishing between controls and subjects who had CAD. The C-statistic for pCAD and CAD was 0.63 (95% CI, 0.59–0.67).

pCAD was useful even in subjects who did not have diabetes and in those whose CAD was nonobstructive (as little as 30% stenosis in ≥1 vessel). Thus, an elevated pCAD score might be used to alert primary care clinicians that more aggressive patient management is necessary.

pCAD and Cardiovascular Mortality

In the entire cohort, there was no significant association between pCAD and cardiovascular death. However, pCAD was associated with cardiovascular death among subjects with CAD (HR, 1.48; 95% CI, 1.07–2.05; P = .02).

When HDL apolipoproteins were evaluated individually, apoC-3 was significantly associated with about a doubled risk of cardiovascular mortality among subjects with and without CAD. ApoC-2 was significantly associated with about a 90% reduced risk of cardiovascular mortality among subjects without CAD.

These findings require confirmation in larger prospective datasets, but they suggest that even after conventional cardiovascular risk factors are adequately addressed, HDL apolipoproteome abnormalities identify patients with CAD who have residual cardiovascular risk.

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