ESPE Yearbook of Paediatric Endocrinology

In Brief: In this US cohort study of 30,239 Black and White individuals aged >=45 years followed up for a median of 10 years, low baseline levels of HDL-Cholesterol (HDL-C) were associated with increased risk of coronary heart disease (CHD) in White (HR: 1.22; 95% CI: 1.05–1.43) but not in Black (HR: 0.94; 95% CI: 0.78–1.14) adults (P-interaction by race =0.08).

Comment: The established clinical risk factors for coronary heart disease (CHD) were originally based on data from the famous Framingham Heart Study in the 1970s. While weightings of the contributing factors have been updated with extended data, the original Framingham Heart Score has stood the test of time, encompassing age, sex, LDL cholesterol, HDL cholesterol, blood pressure (and hypertension treatment), diabetes, and smoking. However the original Framingham Heart Study was universally of white European origin. Although the town of Framingham and surrounding community has since increased in racial diversity, large sample sizes are needed to robustly detect population group differences.

These notable findings highlight the need to check the validity of so-called ‘established’ risk markers for disease in different populations. In contrast to the new findings with HDL-C, the authors observed the expected associations between LDL-cholesterol and triglycerides with increased risk of CHD in both races, which supports the validity of the study design. The authors comment that the findings are consistent with those in other studies of racially diverse cohorts, which have reported weaker or null heart disease associations with HDL-C. Black Americans have a lower overall risk of CHD compared with White Americans, but higher risk of fatal CHD events. Further work is needed to calibrate new heart disease prediction scores based on robust data in non-white populations.

Of note, high HDL-C was not associated with CHD risk in either White or Black Americans, suggesting that in White Americans the relationship between HDL-C and CHD is non-linear (low levels are harmful but high levels are not protective). Indeed, beyond its role as a predictor, the causal effect of HDL-C on CHD remains unestablished.