Addition of HDL-c to SCORE model does not improve risk prediction

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

Literature - Mortensen MB et al., Eur Heart J 2015

Mortensen MB, Afzal S, Nordestgaard BG, and Falk E.
Eur Heart J 2015 36: 2446-2453


A new SCORE (Systematic COronary Risk Evaluation)-based model was provided in the most recent European guidelines for the management of dyslipidaemias [1] and prevention of CVD [2], which incorporates HDL-c as an independent predictor for primary CVD prevention (SCORE-HDL). This prediction model received a Class I recommendation [1].
This new SCORE-HDL model has, however, not been compared head-to-head with the original SCORE model, nor has it been validated in an independent cohort. This study (n=46092, mean follow-up of 6.8 years) therefore compared the two risk assessment models and evaluated the incremental predictive value of HDL-c in the ongoing contemporary Copenhagen General Population Study (CGPS) [3-5].

Main results

  • Adding HDL-c to a Cox regression model including sex, age, smoking, total cholesterol and systolic blood pressure, did not improve discrimination between cases of fatal CVD and non-cases (Harrell’s c-statistic: 0.887 vs. 0.888, p=0.49).
  • Although predicted 10-year fatal CVD risk calculated by SCORE and SCORE-HDL correlated strongly (Spearman’s rho: 093, P<0.0001), median predicted risk was lower with SCORE-HDL than with SCORE for men and women. According to SCORE-HDL, 10% of men and 1% of women were considered high-risk, as opposed to 17% and 3% respectively with SCORE.
  • A 7-year risk for fatal CVD was calculated by slightly modifying the baseline survival function, to assess calibration of SCORE and SCORE-HDL. Both models overestimated risk as compared with observed events; SCORE 4.9-fold in men and 5.5-fold in women.
  • Using SCORE-HDL instead of SCORE decreased the sensitivity of the 5% high-risk threshold for detecting fatal CVD events (26% vs. 42%) and increased specificity for detecting non-events by 4%, yielding a negative net reclassification index (NRI) of -12%.
  • For the combined endpoint of fatal CVD+non-fatal MI or stroke, SCORE-HDL did not improve the discriminative performance as compare with SCORE (c-statistics: 0.714 vs. 0.712, P=0.75). Sensitivity of the 5% high-risk threshold decreased from 26 to 16% yielding an NRI of -5%.  
  • In a SCORE-like risk model based on predictors and outcomes of the CGPS cohort, inclusion of HDL-c did not provide incremental predictive value.
  • Stepwise lowering of the decision threshold from 5 to 1% increased NRI progressively.


In this first direct comparison of the clinical performance of the SCORE and SCORE-HDL risk prediction models in a contemporary population-based cohort in a ‘low-risk’ European country, the newly recommended SCORE-HDL model did not improve discrimination. Relative to the SCORE model, addition of HDL-c lowered the sensitivity of the 5% high-risk threshold, yielding a negative NRI.
Both models strongly overestimated risk of fatal CVD in this ‘low-risk’ European population. In this type of population, the SCORE model may be preferable, particularly among women. European guidelines may consider lower thresholds to initiate intensified primary prevention and to include CVD morbidity in the predicted endpoint, to better reflect the current situation in such countries.

Find this article online at Eur Heart J


1. Reiner Z, Catapano AL, De Backer G et al. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J 2011;32:1769–1818.
2. Perk J, De Backer G, Gohlke H, et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). (Constituted by representatives of nine societies and by invited experts). Eur Heart J 2012;33:1635–1701.
3. Thomsen M, Nordestgaard BG. Myocardial infarction and ischemic heart disease in overweight and obesity with and without metabolic syndrome. JAMA Intern Med 2014;174:15–22.
4. Nordestgaard BG, Palmer TM, Benn M, et al. The effect of elevated body mass index on ischemic heart
disease risk: causal estimates from a Mendelian randomisation approach. PLoS Med 2012;9:e1001212.
5. Jørgensen AB, Frikke-Schmidt R, Nordestgaard BG et al.Loss-of-function mutations in APOC3 and risk of ischemic vascular disease. N Engl J Med 2014;371:32–41.

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