Science Update

Anti-Inflammatory Capacity of HDL Correlated with Reduced Cardiovascular Events

High-density lipoproteins (HDL) are complex particles with anti-atherosclerotic functions, as they absorb excess cholesterol from the atherosclerotic plaque in the arteries and carry it back to the liver where it can be excreted. The ratio of triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) levels has emerged as a key indicator and standard test to predict risk for cardiovascular disease (CVD). An HDL level <40 mg/dL is considered a risk factor for a stroke or heart attack. However, according to researchers, merely measuring the cholesterol quantity is not an accurate reflection of HDL-C levels of anti-atherosclerotic functions; therefore, the researchers sought another clinically useful test to help determine CVD risk prediction.

According to a recent study published this month in the American Heart Association’s journal, Circulation, tests on the anti-inflammatory function of HDL may help predict who is at an increased risk to develop CVD caused by ischemic heart disease or narrowed arteries. The HDL anti-inflammatory capacity reflects vascular protection against key phases in atherogenesis and was determined as its ability to decrease the inflammatory response by suppressing tumor necrosis factor (TNF)-α-induced vascular cell adhesion molecule-1 messenger RNA (mRNA) expression in endothelial cells lining blood vessels in vitro.

Of the 680 adults (average age of 59 years; 70% male) in this large population study that began in 1997, researchers identified and analyzed HDL particles in 340 participants who experienced a first cardiovascular (CV) event before the end of the 10.5-year follow-up period. These participants were matched to a control group who had no cardiovascular events during follow-up. Researchers found HDL anti-inflammatory capacity was significantly higher in healthy participants than in those who had a CV event, and that for every 22% increase in the HDL particles was the ability to suppress endothelial inflammation, and the likelihood of having a CV event in the next decade dropped by 23%. Furthermore, the protection from increased HDL anti-inflammatory capacity was higher in women than in men.     

The results demonstrated that independent of HDL-C levels, C-reactive protein levels, and HDL-C efflux capacity, HDL anti-inflammatory capacity was inversely correlated with incident CV events in the cohort population, suggesting that adding this test to the Framingham Risk Score or replacing HDL-C levels with this new measure of HDL function may improve risk prediction. It is important to note that researchers did not analyze stroke incidence; therefore, no conclusions can be drawn about HDL-C and stroke. Additionally, the results are not generalizable to other races and ethnicities as the study participants were all white and genetically similar.

Fortunately, there are several supportive dietary and lifestyle modifications that patients can begin to implement to help increase their HDL-C levels naturally. Encourage patients to increase moderate-intensity exercise, quit smoking (if they do), lose excess weight, and consume more heart-healthy foods like olive oil, fatty fish and/or fish oil, and non-starchy vegetables to support optimal HDL-C levels. Previous articles discuss how adopting a very low-carbohydrate or ketogenic diet can improve metabolic health parameters, including lowering TG levels and increasing HDL-C levels, in individuals with metabolic syndrome, diabetes, and/or obesity. By restricting carbohydrate intake (or increasing fat intake), ketogenic diets reduce insulin levels, which redirect lipid metabolism, resulting in a shift to ketone utilization as an alternative energy source instead of glucose. Supplemental exogenous ketones and MCT oil, in combination with a low-carbohydrate diet, may help accelerate this process.

A previous study found that curcumin supplementation significantly increased HDL-C in type 2 diabetes patients. Probiotic supplementation and L-carnitine supplementation have also been shown to increase HDL-C levels in patients with metabolic syndrome and type 2 diabetes. Niacin supplementation has been shown to increase HDL-C levels up to 35%. Anthocyanin supplementation (such as grape seed, bilberry, and wild blueberry extracts) significantly improved HDL-C levels compared to a placebo.

By Caitlin Higgins, MS, CNS, LDN