NMR Lipoprotein Profiling Identifies HDL Subclasses Associated With Obstructive CAD: Insights From the PROMISE Clinical Trial

Introduction: In patients at high CV risk, the molar sum of concentrations of small and medium HDL subclasses (HMSP) has significant protective associations with CV outcomes, and outperforms HDL cholesterol for risk prediction. The association of HMSP with CV risk has not been studied in lower risk populations.Methods: The PROMISE clinical trial randomized 10,003 outpatients with chest pain to one of two diagnostic strategies, usual care (most often exercise stress testing) vs. CT-angiography (CTA) based anatomic assessment. NMR-based lipoprotein profiling was performed on individuals with available frozen plasma samples (N=4071); this study focused on individuals randomized to the CTA arm who had available lipoprotein data (N=1832). A multivariable logistic regression model was used to assess the association between obstructive CAD (>=50% left main or >=70 other vessel stenosis) and HMSP, adjusting for age, race, sex, diabetes, systolic blood pressure, and Framingham Risk Score.Results: The mean HMSP level was 22.4 μmol/liter (SD 3.4). Among patients with available HMSP measurements (n=1,832), the median age was 59.3 years (IQR 54.0-65.3), 53.1% were female, and 20.4% had history of diabetes. In the multivariable model, HMSP, age and sex were independently associated with CTA-defined obstructive CAD. In particular, every unit increase in HMSP was associated with decreased CAD (adjusted odds ratio 0.92 [95% confidence interval 0.88-0.96], p=0.0003). This finding is consistent with the association of HMSP with angiographically-defined obstructive CAD (OR 0.838 [95% CI 0.792,0.886], p<0.0001) from prior studies in high CV risk populations.Conclusions: Using a large cohort of low-risk patients referred for noninvasive evaluation of chest pain in the PROMISE clinical trial, HDL particle size parameters are associated with CTA-defined obstructive CAD, even after adjustment for relevant clinical variables. HMSP may help to identify patients at higher risk of CAD for more intensive prevention.Author Disclosures: R.W. McGarrah: None. A.M. Navar: Research Grant; Significant; Amgen, Sanofi, and Regeneron. Consultant/Advisory Board; Modest; Amgen and Sanofi. S. Giamberardino: None. A. Coles: None. L.C. Kwee: None. U. Hoffmann: None. G.S. Ginsburg: Research Grant; Significant; Singulex, Abbott, 23andMe. Consultant/Advisory Board; Modest; CardioDx, Interleukin Genetics, Pappas Ventures, Fabric Genomics, Genome Magazine. Other; Modest; Alere, CardioDx, Fabric Genomics, Origin Commercial Advisors, Elsevier. W.E. Kraus: None. P.S. Douglas: Research Grant; Significant; GE, HeartFlow. S.H. Shah: None.

Duke Scholars

Author William Erle Kraus Medicine, Cardiology

Author Robert W. McGarrah III Medicine, Cardiology

Author Geoffrey Steven Ginsburg Medicine, Cardiology

Author Pamela Susan Douglas Medicine, Cardiology