Two new studies reveal potential mechanisms behind alcohol-induced heart arrhythmias and the impact of estrogen on alcohol-related heart dysfunction.


Summary: Two new studies presented at the American Heart Association’s Basic Cardiovascular Sciences Scientific Sessions 2024 shed light on alcohol’s effects on the heart. The first study explores why binge drinking can cause irregular heartbeats and suggests that the molecule Alda-1 might prevent these arrhythmias. The second study examines how alcohol affects heart function in women undergoing estrogen replacement therapy, finding that alcohol worsens cardiovascular health in these women despite estrogen’s protective effects.

Key Takeaways:

  • Binge Drinking and Arrhythmias: The first study found that binge drinking significantly increases the risk of atrial fibrillation (AFib) by activating the stress-induced protein JNK2. The molecule Alda-1 may prevent this activation, potentially offering a future treatment to prevent alcohol-induced arrhythmias.
  • Alcohol and Estrogen: The second study discovered that regular alcohol consumption in menopausal rats receiving estrogen replacement therapy leads to both positive and negative heart health changes, including increased blood pressure and heart rate, and a reduction in the heart’s ability to pump blood effectively.
  • Impact on Heart Function: Both studies highlight the complex and detrimental effects of alcohol on heart function, especially in vulnerable populations such as habitual binge drinkers and women on estrogen replacement therapy, emphasizing the need for cautious alcohol consumption and further research into protective treatments.

Two new, basic animal research studies shed light on alcohol consumption and the heart. 

The first study may help explain why binge drinking sometimes causes an irregular heartbeat and a possible way to prevent it. The second study investigated why alcohol may have a negative impact on heart function in women taking estrogen replacement therapy. 

Both studies are preliminary research on posters presented at the American Heart Association’s Basic Cardiovascular Sciences Scientific Sessions 2024. The meeting is in Chicago, July 22–25, and offers the latest research on innovations and discovery in cardiovascular science.

An Anti-arrhythmic Action and Novel Mechanisms of Alda-1 in Holiday Heart Syndrome

Binge drinking (five drinks within two hours for men and four drinks within two hours for women) is common around the world. Recent research has also found the incidence of atrial fibrillation (AFib), the most common type of irregular heart rhythm or arrhythmia, continues to rise, according to the study.

“Around the holidays, opportunities for celebration—often accompanied by heavy drinking— occur during a brief period of time. Unfortunately, this sometimes sends revelers, even those with no previous heart condition, to the hospital with a racing or abnormally beating heart,” says Saugat Khanal, PhD, lead author of the study and a post-doctoral scholar in the department of physiology and cell biology at The Ohio State University College of Medicine, in a release. “Our study in mice explored the mechanism of alcohol-induced arrhythmia and a possible way to prevent it in the future.

“Repeated binge drinking can lead to serious arrhythmias. This includes AFib, which is the most common type of arrhythmia. AFib can raise the risk of stroke and heart failure. About one-third of new AFib diagnoses are related to alcohol use. Recurrence of AFib is common in habitual binge drinkers. The link between repeated binge drinking and arrhythmia at times of celebration is so well-known that medical professionals call it holiday heart syndrome which is caused by repeated binge drinking over the holidays.”

Previous animal research by this research team found binge-drinking-related arrhythmias are induced by elevations in a stress-induced protein called JNK2. This can cause heart cells to mishandle calcium and misfire, resulting in the heart beating too fast or irregularly. The new study suggests  that the molecule Alda-1 may prevent the activation of JNK2 that leads to AFib.

The study found:

  • In this study, more than 70% of the mice that were given alcohol-mimicking binge drinking developed AFib, compared with none of those who also received the investigational cardiac protective agent Alda-1.
  • Exposure to binge drinking levels of alcohol doubled levels of JNK2 activity compared to a control group that did not mimic binge drinking. This activated JNK2 increased the AFib susceptibility in the mouse models mimicking binge drinking.
  • Both JNK2 enzyme activity and calcium handling remained normal in the heart cells of the mice treated with Alda-1.

“Abstinence from alcohol can prevent most alcohol-associated AFib risks. Unfortunately, despite nationwide education efforts, binge drinking among all age groups continues to rise. Our findings suggest that developing new drugs, including Alda-1 and other JNK2-specific inhibitors, may be an effective anti-AFib strategy for people with holiday heart syndrome,” Khanal says in a release.

The study was limited because researchers used a mouse model to replicate human holiday heart syndrome. Although the mouse model showed promising results, it may not have fully captured the complexities of binge drinking in humans and related cardiovascular consequences.

“Studies using larger animals will be a future direction to translate our exciting findings into clinical applications,” Khanal says in a release.

Estrogen Modulation of Ethanol-evoked Cardiac Oxidative Stress and Dysfunction

The hormone estrogen helps keep blood vessels open and flexible and is generally thought to help protect women from heart disease. These higher estrogen levels may lead to fewer heart attacks and strokes in premenopausal women than in men of the same age. 

However, alcohol exposure worsens cardiovascular function more in women than men, researchers said. Also, in previous animal studies, alcohol has been confirmed to worsen heart function more in those animals with the highest estrogen levels.

This study explored whether several measures of heart function and the proteins that regulate it differed with regular alcohol exposure in female rats that received hormones to replenish their estrogen supply and those that did not.

The eight-week study included female rats with ovaries removed to simulate menopause (when the ovaries make virtually no estrogen). Researchers compared the menopausal rats who received regular alcohol exposure (delivered as 5% ethanol in a liquid diet) to those who were given alcohol and estrogen replacement.

The study found that, compared to those receiving alcohol alone, the menopausal rats treated with estrogen replacement plus alcohol had:

  • both positive (lower weight gain and fat mass) and negative (higher blood pressure and heart rate) changes in measures related to heart health;
  • a reduction in the heart’s ejection fraction, the heart’s ability to pump oxygen-rich blood to the rest of the body, as well as two other indicators of poorer pumping that may eventually result in heart failure; and
  • disruption in circadian clock proteins, which are known to regulate heart function and other body processes, increased both oxidative stress (which can trigger plaque build-up in the arteries) and ferroptosis (a type of cell death that is a result of too much iron) in the heart’s cells.

“It was surprising to see the significant impact estrogen had on alcohol-induced heart dysfunction, despite its known cardioprotective effects. Premenopausal and menopausal women taking hormone replacement therapy should be cautious about alcohol consumption because it may be a factor in heart dysfunction,” says Syed Anees Ahmed, PhD, lead author of the study and a postdoctoral researcher in pharmacology and toxicology at the Brody School of Medicine at East Carolina University, in a release.

The study findings are limited by the short duration and the use of an animal model. Because the study was conducted in rats, the results may not fully represent the longer-term impact of taking estrogen and regularly consuming alcohol in menopausal women as they age.

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