High uric acid levels linked to future risk for heart failure, researchers say

- By Tracie White

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Eswar Krishnan

A simple $2-blood test may allow doctors to predict whether a patient is at risk of developing heart failure sometime in their future, according to new research from the Stanford University School of Medicine.

“Our study shows that high levels of uric acid significantly increase your risk of developing heart failure later in life,” said Eswar Krishnan, MD, assistant professor of immunology and rheumatology. “The novelty is that the test for measuring this is very cheap and easily available.”

The study appears online in August in the journal Circulation: Heart Failure.

Uric acid naturally occurs in the body as a byproduct of many different foods. High levels are best known as a cause for a type of arthritis known as gout. Krishnan, who authored the study, became interested in the relationship between uric acid levels and heart failure while researching gout and heart attacks. “This was a detour of sorts for me,” he said.

While high levels of uric acid are also known to be a marker for adverse prognosis for people already diagnosed with heart failure, no previous study had convincingly linked high levels of uric acid and future cases of the disease.

Nearly 5 million Americans suffer from heart failure, a disease that weakens the ability of the heart to pump blood through the body. It reduces life expectancy, affects quality of life and can eventually be fatal. While medications sometimes help, currently the only known cure is a heart transplant.

Krishnan analyzed the relationship between high uric acid levels — above 6 mg per one-tenth liter — and subsequent heart failure among the participants of the Framingham Offspring cohort study from data obtained from the National Heart, Lung and Blood Institute. Of the 4,989 participants in the cohort study, 4,912 were eligible for this study. There were 196 cases of heart failure recorded. Participants in the Framingham Offspring cohort study, which began in 1971, were followed and observed for cardiovascular events for 25 years.

After adjusting for a long list of variables including smoking, weight, kidney dysfunction, valvular heart disease, diabetes, alcohol use and use of anti-hypertensive medications, Krishnan found the incidence of heart failure rates was significantly higher among those with high uric acid levels.

The median age at which participants began the Framingham Offspring study was 36. Those with high uric acid levels on average developed heart disease about 20 years later in life.

Using a simple blood test that is already available to physicians to determine a patient’s chances of developing heart failure could be an effective screening tool, Krishnan said. It could help doctors target younger patients who should aggressively reduce other treatable risk factors for heart failure, such as hypertension or obesity. However, he noted that it’s not known whether medications that reduce uric acid levels could help reduce future heart failure cases. Future studies could explore this, Krishnan said.

Just why uric acid is a predictor of heart failure isn’t clear, according to the study. Uric acid is known to contribute to endothelial dysfunction by impairing nitric oxide production, which could lead to damage to the heart. Another possibility is that high uric acid levels cause inflammation that eventually result in heart failure.

Krishnan has received grant support from Takeda Pharmaceuticals of North America Inc. of Deerfield, Ill., (formerly TAP Pharmaceutical Products, Inc.) and previously held stock in Savient Pharmaceuticals. He has served as an advisor/consultant for both these companies. Products manufactured by these companies are not discussed in the study.

About Stanford Medicine

Stanford Medicine is an integrated academic health system comprising the Stanford School of Medicine and adult and pediatric health care delivery systems. Together, they harness the full potential of biomedicine through collaborative research, education and clinical care for patients. For more information, please visit med.stanford.edu.

2023 ISSUE 3

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