title: Beyond Coronary Calcification, Family History, and C-Reactive Protein: Cholesterol Efflux Capacity and Cardiovascular Risk Prediction.
abstract: Cholesterol efflux capacity (CEC), which is a key step in the reverse cholesterol transport pathway, is independently associated with atherosclerotic cardiovascular disease (ASCVD). However, whether it predicts ASCVD beyond validated novel risk markers is unknown.
  
  
  
  This study assessed if CEC improved ACSVD risk prediction beyond using coronary artery calcium (CAC), family history (FH), and high-sensitivity C-reactive protein (hs-CRP).
  
  
  
  CEC, CAC, self-reported FH, and hs-CRP were assessed among participants without baseline ASCVD who were enrolled in the Dallas Heart Study (DHS). ASCVD was defined as a first nonfatal myocardial infarction (MI) or stroke, coronary revascularization, or cardiovascular death, assessed over a median 9.4 years. Risk prediction was assessed using various modeling techniques and improvements in the c-statistic, the integrated discrimination index (IDI), and the net reclassification index (NRI).
  
  
  
  The mean age of the population (N = 1,972) was 45 years, 52% had CAC (>0), 31% had FH, and 58% had elevated hs-CRP (≥2 mg/l). CEC greater than the median was associated with a 50% reduced incidence of ASCVD in those with CAC (5.4% vs. 10.5%; p = 0.003), FH (5.8% vs. 10%; p = 0.05), and elevated hs-CRP (3.8% vs. 7.9%; p = 0.004). CEC improved all metrics of discrimination and reclassification when added to CAC (c-statistic, p = 0.004; IDI, p = 0.02; NRI: 0.38; 95% confidence interval [CI]: 0.13 to 0.53), FH (c-statistic, p = 0.006; IDI, p = 0.008; NRI: 0.38; 95% CI: 0.13 to 0.55), or elevated hs-CRP (c-statistic p = 0.008; IDI p = 0.02; NRI: 0.36; 95% CI 0.12 to 0.52).
  
  
  
  CEC improves ASCVD risk prediction beyond using CAC, FH, and hs-CRP and warrants consideration as a novel ASCVD risk marker.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas.
authors.forename: Purav
authors.initials: P
authors.lastname: Mody
authors.affiliation: Division of Cardiology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas; Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland.
authors.forename: Parag H
authors.initials: PH
authors.lastname: Joshi
authors.affiliation: Division of Cardiology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas.
authors.forename: Amit
authors.initials: A
authors.lastname: Khera
authors.affiliation: Division of Cardiology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas; Department of Clinical Sciences, UT Southwestern Medical Center, Dallas, Texas.
authors.forename: Colby R
authors.initials: CR
authors.lastname: Ayers
authors.affiliation: Division of Cardiology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas. Electronic address: Anand.Rohatgi@utsouthwestern.edu.
authors.forename: Anand
authors.initials: A
authors.lastname: Rohatgi
mesh_terms: D001692:Biological Transport; D002097:C-Reactive Protein / Q000032:analysis*; D002784:Cholesterol / Q000378:metabolism*; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000453:epidemiology; D003331:Coronary Vessels / Q000000981:diagnostic imaging*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D009204:Myocardial Revascularization; D018570:Risk Assessment; D020521:Stroke / Q000453:epidemiology; D013781:Texas / Q000453:epidemiology; D061205:Vascular Calcification
chemical_list: D002097:C-Reactive Protein; D002784:Cholesterol
keywords: cholesterol efflux capacity; coronary artery calcium; family history; high-density lipoprotein; risk prediction