Although higher levels of HDL-cholesterol (HDL-C) are associated with reduced cardiovascular disease (CVD) risk, the relationship is not linear and after an intermediate range of 50–70 mg/dL, very high HDL-C is not always associated with lower CV risk. [Pagidipati P, AHA 2017, abstract 779]

In a study of data from 22,569 adults without prior CVD followed for a median of 19.5 years, 6,539 died, 31 percent of which were CV deaths. Comparing to a reference point of 50 mg/dL and adjusting for factors including age, race and systolic blood pressure, lower HDL-C was associated with higher CVD composite events (CV death, MI, angina or stroke), but higher HDL-C was not, suggesting a U-shaped relationship between HDL-C and CV risk.

“Higher HDL-C is not always better,” said lead researcher Dr Neha Pagidipati of the Duke Clinical Research Institute in Durham, North Carolina, US. “This may help us understand why many cholesteryl ester transfer protein [CETP] inhibitor trials and niacin trials didn’t necessarily result in lower CVD with higher HDL-C.”

“The benefit of high HDL-C was also not fully balanced by the risk of high LDL-C, especially in women,” Pagidipati added.