HDL Anti-Inflammatory Capacity Yields Greater Insight Into Heart-Disease Risk

For cardiovascular disease (CVD) risk prediction, the anti-inflammatory capacity of high-density lipoprotein (HDL) cholesterol may be more important than the HDL level, new research suggests.

In a nested case-control study among adults in the PREVEND study, HDL anti-inflammatory capacity was inversely associated with CVD events. "To the best of my knowledge, this has not been shown before," Dr. Uwe J.F. Tietge of the Karolinska Institutet, in Stockholm, told Reuters Health by email.

Writing in the journal Circulation, he and his colleagues say HDL anti-inflammatory capacity has the potential to provide "independent clinical information for cardiovascular disease risk assessment" and could represent "a novel pharmacological intervention target for improving cardiovascular disease risk."

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While high circulating levels of HDL cholesterol have been tied to reduced CVD risk in the general population, outcomes of drug trials aimed at boosting HDL cholesterol levels have been "disappointing and largely negative." The role of HDL function is "an important emerging concept," the researchers say.

Protection against inflammation is a key biological role of HDL, and given the inflammatory nature of the atherosclerotic process, anti-inflammatory properties of HDL might clinically relevant, they point out. Recently, a study of patients who suffered acute myocardial infarction showed that a lower anti-inflammatory capacity of HDL was associated with a higher incidence of new major cardiac events.

Using the PREVEND study cohort, Dr. Tietge and colleagues matched 369 case patients (mean age, 59 years; 70% men) who experienced a first CV event (combined endpoint of death from cardiovascular causes, ischemic heart disease, nonfatal myocardial infarction or coronary revascularization) to 369 controls of the same sex, smoking status, age and HDL level.

HDL anti-inflammatory capacity was determined as its ability to suppress tumor necrosis factor-alpha-induced vascular cell adhesion molecule-1 mRNA expression in endothelial cells in vitro. The results were expressed as achieved percent reduction by individual HDL related to the maximum TNF-alpha effect with no HDL present.

HDL anti-inflammatory capacity was significantly lower in cases than controls (27.0% vs. 31.6%; P<0.001), despite virtually no difference in HDL cholesterol levels, they report.

In the fully adjusted model, HDL anti-inflammatory capacity was inversely associated with incident CVD (odds ratio per 1 standard deviation, 0.74; P=0.002).

This association was roughly similar with all individual components of the CVD endpoint and "notably" was independent of a number of established cardiovascular biomarkers, including HDL cholesterol and high-sensitivity C-reactive protein, the researchers say.

The association of HDL anti-inflammatory capacity was also independent of HDL cholesterol efflux capacity.

"Adding 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=0.002)," the researchers report.

Dr. Tietge told Reuters Health, "It is too early for an immediate change in risk assessment. Our study should be more seen as conceptual; more research is required (e.g., PREVEND has white participants only) and an easier (i.e., more widely available) assay system would be needed."

This work was funded by the Netherlands Organization for Scientific Research and the Swedish Heart-Lung Foundation. The authors have indicated no relevant disclosures.

—Megan Brooks

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