AIMS: 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.

METHODS AND 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.

CONCLUSION: 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.