Biomarker could prevent sudden cardiac death in men

Plasma 4β-hydroxycholesterol (4βHC) measurement could help to predict and prevent sudden cardiac death in men with coronary artery disease, according to Finnish researchers. 4βHC is a cholesterol derivative that activates the liver X receptor (LXR), which is expressed in the liver as well as in the heart.

Most often, sudden cardiac death related to coronary artery disease occurs completely unexpectedly, and there are no effective ways to anticipate it. With this in mind, researchers at the University of Oulu set out to investigate whether plasma 4βHC could act as a prognostic factor in coronary artery disease and its adverse cardiac events. The research group had previously studied the role of the compound — which is secreted into the bloodstream from the liver — in obesity-induced hypertension, but the significance of 4βHC levels had not been previously studied in patients with coronary artery disease.

The team’s study was based on the ARTEMIS cohort of nearly 2000 patients with coronary artery disease treated at Oulu University Hospital; the average follow-up time for patients participating in the study was almost nine years. The results of the study, published in the Journal of the American Heart Association (JAHA), found that high levels of 4βHC were associated with total mortality, cardiac mortality and especially sudden cardiac death in men. Indeed, men with the highest level of 4βHC had a four-fold risk of sudden death.

This result was surprising for two reasons. First, both women and men who were the healthiest had the highest levels of 4βHC; they had the lowest body mass index, the least diabetes and the best physical performance. Second, high levels of 4βHC predicted sudden deaths only in men but not in women, who on the contrary were protected from cardiac mortality and sudden cardiac death by high levels of 4βHC.

“In this study, fit men died of sudden cardiac death if they had a high level of 4βHC, whereas fit women with a high level of 4βHC were not harmed; rather, they seemed to benefit,” said Professor of Internal Medicine Janne Hukkanen, the leader of the study. And while some previous studies have suggested that LXR’s function differs between women and men with coronary artery disease, which may go some way to explaining the results, Hukkanen nevertheless claimed that the difference between the sexes was “a very surprising and significant finding”.

According to the researchers, the results must be confirmed by a sufficiently long follow-up in other research datasets of patients with coronary artery disease. “If the finding can be confirmed,” Hukkanen said, “we may be able to prevent sudden cardiac deaths better in the future.”

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