Medical Bulletin 21/ June/ 2024

Stanford Medicine researchers and their colleagues have discovered that a class of drugs already on the market to lower blood pressure appears to reduce adults’ risk of developing epilepsy.

The study, published in JAMA Neurology, suggested that the drugs, called angiotensin receptor blockers, could prevent epilepsy in people at highest risk of the disease, including older adults who have had strokes.

Epilepsy, often diagnosed in childhood, also affects over 1% of people over 65, with seizures disrupting brain function and causing various symptoms. In older adults, stroke is the leading risk factor for epilepsy, with 10% of stroke survivors experiencing seizures within five years. Vascular disease and chronic high blood pressure further increase the risk.

While anti-seizure medications control epilepsy after diagnosis, no drugs currently prevent it in high-risk individuals. Recent studies, however, suggest that certain blood pressure medications might help prevent seizures by reducing inflammation, particularly in cases following stroke or traumatic brain injuries, which can trigger epilepsy.

In the study, researchers analysed data from 2.2 million adults diagnosed with high blood pressure who were prescribed at least one blood pressure medication and did not have epilepsy.

They found that individuals taking angiotensin receptor blockers had a 20% to 30% lower risk of developing epilepsy compared to those taking other blood pressure drugs. This reduced risk remained even when patients with strokes were excluded from the analysis, indicating that the lower epilepsy rates were not solely due to a decreased risk of stroke.

“All blood pressure medications likely reduce the risk of epilepsy since high blood pressure contributes to the disorder. Controlling blood pressure through medication and lifestyle changes can lower epilepsy risk. However, new research suggests that angiotensin receptor blockers might be more effective than other antihypertensives in reducing this risk. In the study, 14% of participants took angiotensin receptor blockers, while the majority used other blood pressure medications such as beta blockers, calcium channel blockers, and ACE inhibitors,” said the authors.

Reference: Wen X, Otoo MN, Tang J, et al. Angiotensin Receptor Blockers for Hypertension and Risk of Epilepsy. JAMA Neurol. Published online June 17, 2024. doi:10.1001/jamaneurol.2024.1714

A study published in Annals of Internal Medicine found that paternal use of metformin monotherapy was not associated with major congenital malformations (MCMs) in newborns. Associations between metformin in polytherapy and birth defects could potentially be explained by worse underlying parental cardiometabolic risk profile of those taking multiple diabetes medications.

Paternal use of metformin involves men taking the medication, often to manage type 2 diabetes, during the period of sperm production prior to conception. Metformin helps regulate blood sugar levels by reducing glucose production in the liver, improving insulin sensitivity, and decreasing sugar absorption in the intestines. While metformin is primarily used to treat diabetes, it has also been studied for other potential health benefits.

In the study, researchers analysed data from 400,000 live births between 1999 and 2020 to see if using metformin during the time sperm is produced before conception could cause problems in the next generation. They checked for major birth defects and parental heart and metabolic conditions by reviewing medical diagnoses, medication records, and lab test results.

The results indicated that metformin use by fathers was initially linked to a higher risk of major congenital malformations (MCM) in children (6.2% compared to 4.7% with no diabetic medication).

However, this association disappeared after adjusting for paternal cardiovascular and metabolic conditions and excluding children born to mothers with diabetes or hyperglycemia.

Fathers on metformin or other diabetic medications tended to be older, had cardiovascular and metabolic issues, were more likely to smoke, and had fertility problems. Similarly, when fathers used metformin, mothers were more likely to have cardiovascular co-morbidities and fertility issues.

“These findings underscore the importance of considering paternal health in the context of reproductive planning and prenatal care. Metformin is a safe and effective treatment option for type 2 diabetes for men and women trying to conceive as well as for managing hyperglycemia in pregnant women in the first trimester. As such, it may be time to reconsider current prenatal care guidelines that advocate switching to insulin therapy for those trying to conceive,” said the authors.

Reference: Sarah Martins da Silva. Paternal and Maternal Metformin Use and the Risk for Major Congenital Malformations. Ann Intern Med. [Epub 18 June 2024]. doi:10.7326/M24-0883

Early in the pandemic, many people who had SARS-Cov-2 infection or COVID-19 began to report that they couldn’t get rid off their symptoms even after a month or more—unusually long for a viral infection of the upper respiratory tract—or developed new, persistent symptoms soon after the infection cleared.

Although it’s still not clear what causes post-COVID-19 conditions or “long COVID”, a new study by researchers at Columbia University, published in JAMA Network Open, confirmed the high burden of long COVID and sheds light on who’s at greatest risk.

The study involved over 4,700 participants from the Collaborative Cohort of Cohorts for COVID 19 Research, who were asked to report their time to recovery after infection with SARS-CoV-2.

The study found that, between 2020 and early 2023, the median recovery time after SARS-CoV2-infection was 20 days, and more than one in five adults did not recover within three months.

Women and adults with pre-pandemic cardiovascular disease were less likely to recover within three months. Other pre-pandemic health conditions—including chronic kidney disease, diabetes, asthma, chronic lung disease, depressive symptoms, and a history of smoking—were linked to longer recovery times, but these associations were no longer significant after accounting for sex, cardiovascular disease, vaccination, and variant exposure.

The study also found that people with a milder infection—including those who were vaccinated against SARS-CoV-2 and those who were infected with an Omicron variant—were more likely to recover quickly. Recovery time was similar for subsequent infections.

“Although studies have suggested that many patients with long COVID experience mental health challenges, we did not find that depressive symptoms prior to SARS-CoV-2 infection were a major risk factor for long COVID. Our study clearly establishes that long COVID posed a substantial personal and societal burden,” says Oelsner. By identifying who was likely to have experienced a lengthy recovery, we have a better understanding of who should be involved in ongoing studies of how to lessen or prevent the long-term effects of SARS-CoV-2 infection,” said the authors.

Reference: Oelsner EC, Sun Y, Balte PP, et al. Epidemiologic Features of Recovery From SARS-CoV-2 Infection. JAMA Netw Open. 2024;7(6):e2417440. doi:10.1001/jamanetworkopen.2024.17440