title: The high-density lipoprotein-adjusted SCORE model worsens SCORE-based risk classification in a contemporary population of 30,824 Europeans: the Copenhagen General Population Study.
abstract: OBJECTIVE
  Recent European guidelines recommend to include high-density lipoprotein (HDL) cholesterol in risk assessment for primary prevention of cardiovascular disease (CVD), using a SCORE-based risk model (SCORE-HDL). We compared the predictive performance of SCORE-HDL with SCORE in an independent, contemporary, 'low-risk' European population, focusing on ability to identify those in need of intensified CVD prevention.
  
  
  RESULTS
  Between 2003 and 2008, 46,092 individuals without CVD, diabetes, or statin use were enrolled in the Copenhagen General Population Study (CGPS). During a mean of 6.8 years of follow-up, 339 individuals died of CVD. In the SCORE target population (age 40-65; n = 30,824), fewer individuals were at baseline categorized as high risk (≥5% 10-year risk of fatal CVD) using SCORE-HDL compared with SCORE (10 vs. 17% in men, 1 vs. 3% in women). SCORE-HDL did not improve discrimination of future fatal CVD, compared with SCORE, but decreased the detection rate (sensitivity) of the 5% high-risk threshold from 42 to 26%, yielding a negative net reclassification index (NRI) of -12%. Importantly, using SCORE-HDL, the sensitivity was zero among women. Both SCORE and SCORE-HDL overestimated risk of fatal CVD. In well-calibrated models developed from the CGPS, HDL did not improve discrimination or NRI. Lowering the decision threshold from 5 to 1% led to progressive gain in NRI for both CVD mortality and morbidity.
  
  
  CONCLUSIONS
  SCORE-HDL did not improve discrimination compared with SCORE, but deteriorated risk classification based on NRI. Future guidelines should consider lower decision thresholds and prioritize CVD morbidity and people above age 65.
authors.affiliation: Atherosclerosis Research Unit, Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Martin B
authors.initials: MB
authors.lastname: Mortensen
authors.affiliation: The Department of Clinical Biochemistry and The Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Shoaib
authors.initials: S
authors.lastname: Afzal
authors.affiliation: The Department of Clinical Biochemistry and The Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark boerge.nordestgaard@regionh.dk.
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
authors.affiliation: Atherosclerosis Research Unit, Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Erling
authors.initials: E
authors.lastname: Falk
mesh_terms: D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control*; D008076:Cholesterol, HDL / Q000097:blood*; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000401:mortality; D011446:Prospective Studies; D018570:Risk Assessment / Q000379:methods; D012680:Sensitivity and Specificity; D017678:Sex Distribution; D020521:Stroke / Q000401:mortality
chemical_list: D008076:Cholesterol, HDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
keywords: Copenhagen General Population Study; HDL; SCORE; risk assessment