Low Serum Glutathione Peroxidase Activity Increases Risk of Cardiovascular Disease in Individuals with Low HDL-cholesterol

A retrospective study of stored serum samples has found that individuals with low HDL-cholesterol (cholesterol associated with high-density lipoproteins) and low levels of the enzyme glutathione peroxidase (GPx3) suffered significantly more incidence of fatal cardiovascular disease than did those with low HDL-cholesterol but elevated levels of GPx3.

GPx3 is a natural antioxidant that contains a selenocysteine (Sec) residue at its active site. One of its activities in the body is to reduce oxidized lipids, such as LDL (low-density lipoproteins), which have been linked to the development of atherosclerosis. This relationship to cardiovascular disease was the basis for a study conducted by investigators at the University of Minnesota (Minneapolis, USA) to determine whether high GPx3 activity could reduce cardiovascular disease (CVD) mortality.

The investigators evaluated 130 stored serum samples obtained during the Minnesota Heart Survey from participants aged 26-85 years who had died of cardiovascular disease after five to 12 years of follow-up care. Odds ratios (OR) were calculated after adjustment for age, sex, baseline year, body mass index, smoking, alcohol intake, physical activity, total and HDL-cholesterols, systolic blood pressure, serum glucose, and gamma glutamyltransferase (GTT) activity. Data was compared to that from 240 control samples from individuals without cardiovascular disease.

Results published in the June 15, 2012, online edition of the journal PLoS One revealed that individuals with low levels of HDL-cholesterol and GPx3 were six times more likely to die from cardiovascular disease, including heart attack or stroke, than those with low levels of HDL-cholesterol and high levels of GPx3. GPx3 levels were not linked significantly to risk of cardiovascular disease in individuals with high levels of HDL-cholesterol.

“In our study, we found that people with high levels of the GPx3 enzyme and low levels of good cholesterol were six times less likely to develop cardiovascular disease than people with low levels of both,” said senior author Dr. Jordan L. Holtzman, professor of pharmacology and medicine at the University of Minnesota. “This GPx3 enzyme gives us a good reason to believe that natural antioxidants like GPx3 are good for heart health. This is an important enzyme for people with low HDL-cholesterol. We think further research will be important in determining the future role of GPx3 and what drugs may serve to increase its activity in the blood.”

"It is important to point out that people should not rush out to their doctors and demand testing for the GPx3 enzyme,” said Dr. Holtzman. “But in time, we hope that measuring this enzyme will be a common blood test when determining whether a patient is at risk for cardiovascular disease, including heart attacks and strokes.”

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