HDL Cholesterol Particles Linked to Reduced Inflammation, Lower CVD Risk

April 14, 2021
Patrick Campbell

A case-controlled study of patients in the PREVEND study indicates HDL anti-inflammatory capacity could help identify patients at a greater risk of cardiovascular disease.

While HDL has long been referred to as the “good” cholesterol, new research from European investigators suggests assessments of HDL particles could be more useful than previously thought.

Results of the study suggest HDL anti-inflammatory capacity was not correlated with HDL-C or hsCRP and also revealed HDL anti-inflammatory capacity was inversely associated with incident cardiovascular disease events.

"The HDL cholesterol level is a good, established, simple and cost-efficient CVD risk biomarker. Our results, however, demonstrate that the anti-inflammatory capacity or assays looking at HDL function in general have the potential to provide clinically relevant information beyond the static HDL cholesterol measurements that are currently used," said study investigator Uwe Tietge, MD, PhD, a Professor in the Department of Laboratory Medicine at Karolinska Institutet, in a statement from the American Heart Association.

Spurred by an interest in the utility of HDL function on risk of cardiovascular disease, Tietge and a team of colleagues designed the current study to assess whether HDL anti-inflammatory capacity is prospectively associated with first cardiovascular events in the general population. To do so, they designed their study with a case-control design using data from the Prevention of Renal and Vascular End Stage Disease (PREVEND) study.

HDL anti-inflammatory capacity was considered its ability to suppress TNFa-induced VCAM-1 mRNA expression ini endothelial cells, which is expressed as an achieved percent reduction by individual HDL relative to the maximum TNFa effect without the presence of HDL.

From the PREVEND study, investigators identified 369 first cardiovascular events during a median of 10.5 years of follow-up. Using these patients, investigators identified 369 controls matched based on age, sex, smoking status, and HDL cholesterol. Of these, 340 patients in each group had baseline samples related to HDL available.

For the purpose of analysis, incident cardiovascular disease was defined as a combined endpoint of death from cardiovascular causes, ischemic heart disease, nonfatal myocardial infarction, and coronary revascularization.

After analysis, investigators found HDL anti-inflammatory capacity was significantly lower in cases compared with controls. In a fully adjusted model, results indicated HDL anti-inflammatory capacity was inversely associated with incident cardiovascular disease (OR per 1 SD, 0.74; 95% CI, 0.61-0.90; P=.002). Additionally, results suggested this association was approximately similar with all individual components of the cardiovascular disease endpoint used for the study.

HDL anti-inflammatory capacity was not correlated with cholesterol efflux capacity. When combining HDL anti-inflammatory capacity and cholesterol efflux capacity into a single model, both were significantly and independently associated with incident cardiovascular disease after adjustment (efflux: OR per 1 SD, 0.74; P=.002; anti-inflammatory capacity: OR per 1 SD, 0.66; P <.001). Investigators also pointed out the addition of HDL anti-inflammatory capacity improved risk prediction by the Framingham risk score, with a model likelihood-ratio statistic increase from 10.50 to 20.40 (P=.002).

"Our results point to new opportunities for improved cardiovascular risk assessment by using a biologically meaningful functional biomarker for HDL instead of its cholesterol content," added Tietge, in a statement. “However, the method for analyzing the anti-inflammatory activity of HDLs is currently rather complex and difficult. Our next goal is therefore to make the method simpler and more clinically implementable."

This study, “High-Density Lipoprotein Anti-Inflammatory Capacity and Incident Cardiovascular Events,” was published in Circulation.