Evaluation of newer risk markers for coronary heart disease risk classification: a cohort study.

BACKGROUND

Whether newer risk markers for coronary heart disease (CHD) improve CHD risk prediction remains unclear.

OBJECTIVE

To assess whether newer risk markers for CHD risk prediction and stratification improve Framingham risk score (FRS) predictions.

DESIGN

Prospective population-based study.

SETTING

The Rotterdam Study, Rotterdam, the Netherlands.

PARTICIPANTS

5933 asymptomatic, community-dwelling participants (mean age, 69.1 years [SD, 8.5]).

MEASUREMENTS: Traditional CHD risk factors used in the FRS (age, sex, systolic blood pressure, treatment of hypertension, total and high-density lipoprotein cholesterol levels, smoking, and diabetes) and newer CHD risk factors (N-terminal fragment of prohormone B-type natriuretic peptide levels, von Willebrand factor antigen levels, fibrinogen levels, chronic kidney disease, leukocyte count, C-reactive protein levels, homocysteine levels, uric acid levels, coronary artery calcium [CAC] scores, carotid intima-media thickness, peripheral arterial disease, and pulse wave velocity).

RESULTS

Adding CAC scores to the FRS improved the accuracy of risk predictions (c-statistic increase, 0.05 [95% CI, 0.02 to 0.06]; net reclassification index, 19.3% overall [39.3% in those at intermediate risk, by FRS]). Levels of N-terminal fragment of prohormone B-type natriuretic peptide also improved risk predictions but to a lesser extent (c-statistic increase, 0.02 [CI, 0.01 to 0.04]; net reclassification index, 7.6% overall [33.0% in those at intermediate risk, by FRS]). Improvements in predictions with other newer markers were marginal.

LIMITATION: The findings may not be generalizable to younger or nonwhite populations.

CONCLUSION

Among 12 CHD risk markers, improvements in FRS predictions were most statistically and clinically significant with the addition of CAC scores. Further investigation is needed to assess whether risk refinements using CAC scores lead to a meaningful change in clinical outcome. Whether to use CAC score screening as a more routine test for risk prediction requires full consideration of the financial and clinical costs of performing versus not performing the test for both persons and health systems.

PRIMARY FUNDING SOURCE: Netherlands Organization for Health Research and Development (ZonMw).