HDL Anti-Inflammatory Capacity Improves Cardiovascular Risk Forecast

Congzhuo Jia

High-density lipoprotein (HDL) anti-inflammatory capacity could be a new marker to help better predict the individual risk of developing a cardiovascular event or disease.

A team, led by Congzhuo Jia, Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet, examined whether HDL anti-inflammatory capacity is prospectively linked to first cardiovascular events in the general population.

Researchers have long believed high-density lipoprotein function in cardiovascular disease is an important concept that warrants future research.

In the study, the researchers determined HDL anti-inflammatory capacity as its ability to suppress tumor necrosis factor α (TNFα) –induced vascular cell adhesion molecule-1 (VCAM-1) mRNA expression in endothelial cells in vitro.

Parameters

The results were expressed as achieved percent reduction by individual HDL related to the maximum TNFα effect with no high-density lipoprotein present.

The nested case-control study, dubbed PREVEND (Prevention of Renal and Vascular End Stage Disease), included 369 individuals experiencing a first cardiovascular event, which included combined end point of death from cardiovascular causes, ischemic heart disease, nonfatal myocardial infarction, and coronary revascularization, during a median of 10.6 years of follow-up.

Each case was matched to a control case with respect to age, sex, smoking status, and HDL cholesterol. For the final analysis, there were baseline samples available for 340 cases in the study arm, as well as 340 matched control samples.

The researchers found high-density lipoprotein anti-inflammatory capacity was not associated with HDL cholesterol or high-sensitivity C-reactive protein (hsCRP).

HDL Anti-Inflammatory Capacity

In addition, HDL anti-inflammatory capacity was significantly lower in the case group when compared to the control group (31.6%; 95% CI, 15.7–44.2 versus 27.0%; 95% CI, 7.4–36.1; P <0.001). This was also inversely associated with incident cardiovascular disease after the team used a fully adjusted model (OR per 1 SD, 0.74; 95% CI, 0.61-0.90; P = 0.002).

This association was very similar with all individual components of the cardiovascular disease endpoint and the HDL anti-inflammatory was not correlated with cholesterol efflux capacity ((r = −0.02; P >0.05).

Next, the investigators combined 2 HDL function metrics into a singular model and found both were significantly and independently linked to incident cardiovascular disease in a fully adjusted model (efflux: OR per 1 SD, 0.74; P = 0.002; anti-inflammatory capacity: OR per 1 SD, 0.66; P <0.001).

By adding HDL anti-inflammatory capacity, the researchers found an improved risk prediction using the Framingham risk score, with a model likelihood-ration statistic increase from 10.50-20.40 (P = 0.002).

“The HDL anti-inflammatory capacity, reflecting vascular protection against key steps in atherogenesis, was inversely associated with incident cardiovascular events in a general population cohort, independent of HDL cholesterol and HDL cholesterol efflux capacity,” the authors wrote. “Adding HDL anti-inflammatory capacity to the Framingham risk score improves risk prediction.”

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