Should the Framingham Risk Score Include HDL Anti-Inflammatory Capacity?

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This nested case-control study included more than 300 patients from the PREVEND study who experienced a first CV event.

In the general population, the anti-inflammatory capacity of high-density lipoprotein (HDL) is inversely associated with incident cardiovascular (CV) events, according to a study published in Circulation. The incorporation of the HDL anti-inflammatory capacity into the Framingham risk score may improve risk prediction regarding CV events.

The investigators performed a nested case-control study that included 369 patients from PREVEND (the Prevention of Renal and Vascular Endstage Disease study) who experienced a first CV event—which the authors defined as a combined endpoint of death from CV causes, ischemic heart disease, nonfatal myocardial infarction, and coronary revascularization. All events were reported during a median follow-up period of 10.5 years.

Patients who experienced incident CV events were matched to 369 controls for age, sex, smoking status, and HDL cholesterol. The reported analysis is based on findings from 340 matched case-control pairs for whom blood samples for HDL anti-inflammatory capacity determinations were available.

There was no association found between the HDL anti-inflammatory capacity and HDL cholesterol or high-sensitivity C-reactive protein (hsCRP). Despite this finding, the investigators saw significantly lower HDL anti-inflammatory capacity in cases vs controls (31.6% [95% CI, 15.7-44.2] vs 27.0% [95% CI, 7.4-36.1], respectively; P <.001).

There was an inverse association between the HDL anti-inflammatory capacity and incident CV events after an adjusted analysis (odds ratio [OR] per 1 SD, 0.74; 95% CI, 0.61-0.90; P =.002). This association was similar for the individual components of the CV disease (CVD) endpoint.

The researchers found no correlation between the HDL anti-inflammatory capacity and cholesterol efflux capacity (r = −0.02; P >.05). The combination of the cholesterol efflux capacity and the anti-inflammatory capacity in a single model demonstrated a significant and independent association with both HDL function metrics and incident CVD events in a fully adjusted analysis (OR per 1 SD, 0.74; P =.002 and OR per 1 SD, 0.66; P <.001).

Also, the addition of the anti-inflammatory capacity to the Framingham risk score improved the score’s risk prediction capability, demonstrated by a significant increase in the model likelihood-ratio statistic from 10.50 to 20.40 (P =.002).

Limitations of this study noted by the authors include its case-control design, which may limit the ability to make inferences regarding the association between the HDL anti-inflammatory capacity and other CVD risk factors; the inclusion of mostly White participants; the lack of standardization of HDL function assays currently, so interpretations can only be made in the context of the assay conditions applied; and the fact that stroke was not included as an endpoint.

The investigators concluded that “the HDL anti-inflammatory capacity could represent a novel pharmacological intervention target for improving cardiovascular disease risk.”


Jia C, Anderson JLC, Gruppen EG, et al. High-density lipoprotein anti-inflammatory capacity and incident cardiovascular events. Published online April 12, 2021. Circulation. doi:10.1161/CIRCULATIONAHA.120.050808