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High-normal levels of bilirubin linked to lower rates of heart disease

Pank Jit Sin
23 May 2018

Persons with blood bilirubin levels in the higher range of normal have lower rates of heart failure, myocardial infarction and stroke in patients with or without HIV infection, reveals a new large-scale study.

The study, which was published in the Journal of the American Heart Association, looked at health data from close to 100,000 veterans (with or without HIV infection), where it was revealed that higher levels of bilirubin in the blood, within the normal ranges, was associated with lower rates of heart failure, heart attack and stroke. The researchers specifically looked at people living with HIV because an anti-HIV drug, atazanavir, is known to cause elevations in bilirubin level.

According to Dr Vincent C. Marconi, lead author of the study, HIV infection has negative effects in cardiovascular health even if the disease is well-controlled by antiretroviral drugs. He said: "We initially wanted to see if bilirubin and cardiovascular disease had a different relationship in people who were HIV positive, compared to HIV negative.” Marconi is a professor of medicine and global health at Emory University School of Medicine and Rollins School of Public Health, US. He is also the director of infectious disease research at the Atlanta Veterans Affairs Medical Center.

Marconi and his team of researchers examined data from the Veterans Aging Cohort Study (VACS), a nationwide look at HIV infection, supported by the National Institutes of Health. VACS data included 31,418 HIV-positive and 66,987 HIV-negative veterans, almost all men and 48 percent African American. Their age was an average of 48 years. They divided the study subjects into four groups based on their bilirubin levels and arrived at the conclusion that higher levels of bilirubin meant lower risk of heart attack, heart failure or stroke. The group with the highest level of bilirubin had 76 percent of the risk for combined cardiovascular events as the group with the lowest level, with effects seen even in people without liver disease.

"Large increases in bilirubin were not required to see an effect on CVD risk reduction," Marconi says. "Most of the change happened well within the normal physiologic range and specifically from the first to the second quartile."

The researchers concluded that their work provides the epidemiologic rationale for future studies to investigate how the antioxidant effect of bilirubin could be harnessed to reduce chronic disease morbidity risk. Future studies should explore the use of bilirubin as a biomarker for other inflammation-mediated conditions and all-cause mortality.

About bilirubin and atazanavir
Bilirubin’s apparent cardiovascular benefit may be due to an antioxidant effect or possibly interference with atherosclerosis, as alluded by several existing studies. The data from this study adds to this evidence.
Bilirubin is formed by the breakdown of red blood cells and is eliminated by the liver. It is a yellow-orange pigment and is responsible for the colouration of bruises.

Atazanavir is a HIV protease inhibitor, and is designed to stop HIV from processing itself. It has a side effect on an enzyme in human cells that is necessary for the recycling of bilirubin. There are some indications that the drug itself has negative effects, balancing out the benefits of bilirubin, Marconi added.

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