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Migraine, Predisposition To Blood Clots Can Increase Stroke Risk
Stroke prevention is a crucial area of preventative health measures. Because of the dangers of strokes, people must know if they are at risk and what they may be able to do to modify their risk.
While younger individuals typically have a lower stroke risk, it is still important to note what risk factors affect younger populations, particularly as the consequences of a stroke can be lifelong.
A study recently published in Circulation: Cardiovascular Quality and Outcomes examined how nontraditional and traditional risk factors for stroke contributed to stroke in younger adults.
Researchers examined data from over 2,600 stroke cases and over 7,800 controls and examined how traditional and nontraditional risk factors contributed to stroke risk in adults aged 55 and younger.
The study found that nontraditional risk factors contributed to strokes most in adults under 35, and the risks from these nontraditional factors declined with age. These results highlight the importance of identifying nontraditional stroke risk factors, particularly among younger adults.
Stroke is such a dangerous health event because it can lead to brain damage. There are two main types of strokes: ischemic and hemorrhagic. In an ischemic stroke, there is some kind of blockage of the brain's blood supply. In a hemorrhagic stroke, bleeding occurs in the brain, such as from a ruptured artery.
Multiple risk factors can increase someone's odds of experiencing a stroke, including having high blood pressure, diabetes, low levels of physical activity, and smoking.
Having a family history of stroke or an AB blood type can also increase risk. People can seek medical advice and guidance to help them determine their level of stroke risk.
The current researchers wanted to focus on some of the more nontraditional risk factors for stroke. They created the following breakdown for their research.
Traditional vascular risk factors included:
Nontraditional risk factors included:
This study was a retrospective case-control study, where researchers collected data from the Colorado All Payer Claims Database.
Researchers analyzed models stratified by age and biological sex to look at traditional and nontraditional stroke risk factors. This ultimately divided participants into three age group categories:
There were 2,628 stroke cases during the examined timeframe. Of this number, 73.3% were ischemic strokes, and 52% occurred in women. Researchers compared these stroke cases to 7,827 controls.
Researchers were more likely to see traditional risk factors linked to the stroke cases. The most common traditional risk factors they observed were high blood pressure, hyperlipidemia, and tobacco use.
Among men, the most common nontraditional risk factors were migraine, kidney failure, and thrombophilia. Among women, the most common nontraditional risk factors were migraine, thrombophilia, and malignancy — which refers to conditions where mutated cells invade healthy tissue.
Researchers further found that nontraditional risk factors contributed more to stroke risk in the youngest age group than traditional risk factors.
Among 18–34-year-olds, 31.4% of strokes among men and 42.7% of strokes among women were associated with nontraditional risk factors.
In contrast, traditional risk factors accounted for 25.3% of strokes among men and 33.3% of strokes among women. Researchers also found that the contributing risk from traditional factors peaked among participants in the 35–44-year-old category and that risk from nontraditional factors decreased with age.
Study author Michelle Hu Leppert, MD, MBA, assistant professor in the Department of Neurology at the University of Colorado School of Medicine, outlined the highlights of the research to Medical News Today:
"We wanted to better understand which risk factors were the most important contributors to stroke risk among young adults. We found that among adults 18 to 34 years of age, nontraditional risk factors were just as important as traditional risk factors. In fact, the younger the patient at the time of stroke, the more likely their stroke [was to occur] due to a nontraditional risk factor. We were surprised to find that migraine was the most important nontraditional stroke risk factor among adults [aged] 18 to 34 […] The association between migraine and strokes has been well established but this is the first study to show just how large this contribution could [be]."
The results do point to the importance of screening for nontraditional risk factors for stroke, particularly among younger individuals.
Adi Iyer, MD, neurosurgeon and interventional neuroradiologist at Pacific Neuroscience Institute at Providence Saint John's Health Center in Santa Monica, CA, not involved in the research, commented that, "[i]n addition to well known risk factors for stroke such as hypertension, this study elucidated the lesser-known risk factors in young patients such as migraines, autoimmune disorders and thrombophilia."
"This is an interesting study as it helps identify risk factors in young patients for stroke, which turn out to be just as important as already well understood risk factors such as hypertension and heart disease," he told us.
"Younger patients with nontraditional risk factors such as autoimmune disorders, migraine, and thrombophilia should be screened by physicians for their stroke risk," Iyer advised.
While this research brought some crucial information about stroke risk factors to light, the authors nevertheless outlined certain limitations to their study.
First of all, because of how researchers identified risk factors, they did not account for uncoded diagnoses or risk factors when participants did not seek care.
Secondly, there is some risk for unmeasured bias and residual confounding. It is possible that the risk from certain factors was not adequately captured because of how researchers conducted the study.
The research also did not focus on every potential stroke risk factor, and researchers noted that their assessment of nontraditional risk factors may actually be an underestimate.
The study authors further cautioned that the results may not be generalizable because the study was conducted in a claims database in Colorado, which has a higher altitude, which may have affected the study sample. For example, the altitude could trigger a sickle cell pain crisis. This might explain why there was a low number of participants with sickle cell disease.
Finally, the researchers acknowledged that they could not account for certain confounders and had some missing data on race and ethnicity.
Thus, researchers encouraged the replication of the study in different population-based cohorts to gather more data.
Leppert told MNT:
"We found that the potential contribution of migraine headaches to the development of strokes in young adults is large. However, we do not know why migraine [attacks] lead to strokes in the first place. There is currently no clinical treatment to prevent strokes in migraineurs. Developing a better understanding of the mechanisms of migraines which lead to strokes can help us to develop future clinical interventions."
Study: Air Pollution, Alcohol, Diabetes Are Top 3 Dementia Risk Factors
People who are exposed to air pollution, have diabetes or drink alcohol could be more likely to develop Alzheimer's disease, according to a new study.
The study, released Wednesday in the journal Nature Communications and conducted by researchers at the University of Oxford, was based on the brain scans of about 40,000 people between the ages of 44 and 82 in the U.K. Biobank.
For the study, researchers examined multiple different risk factors – blood pressure, diabetes, cholesterol, weight, alcohol, smoking, depression, hearing, inflammation, pollution, sleep, exercise, diet/supplementation, socialization and education.
Researchers determined that diabetes diagnoses, nitrogen air pollution and alcohol consumption were the top three biggest risk factors for dementia, based on their effects on the parts of the human brain associated with memory and thinking.
"What we're trying to do is say: What are the common risk factors for dementia that are affecting these regions?" study co-author and Oxford associate professor Gwenaëlle Douaud told The Washington Post.
Douaud told The Post that the three risk factors each have an effect that is double than the other three leading risk factors, sleep, weight, smoking and blood pressure.
Another similar study in 2020 found that other factors, such as hypertension, hearing impairment, smoking and obesity could contribute to up to 40% of dementia cases across the globe, according to the Post.
Paxlovid Fails To Shorten COVID In Standard-Risk And Vaccinated At-Risk Patients
Nirmatrelvir/ritonavir (Paxlovid) failed to shorten COVID-19 symptom duration among people at standard risk for severe COVID-19 and among vaccinated people with at least one risk factor for severe disease, according to final results of the phase II/III EPIC-SR trial.
In vaccinated and unvaccinated patients with COVID-19 at standard risk for severe disease and in fully vaccinated people with at least one risk factor who took nirmatrelvir/ritonavir, the median time to alleviation of COVID-19 symptoms was 12 days, compared with 13 days in patients who took a placebo (P=0.60), reported Jennifer Hammond, PhD, development head of antivirals at Pfizer in Collegeville, Pennsylvania, and colleagues in the New England Journal of Medicine.
"The usefulness of nirmatrelvir-ritonavir in patients who are not at high risk for severe COVID-19 has not been established," the authors wrote.
There was a trend toward fewer hospitalizations and death among participants who took nirmatrelvir/ritonavir, where five (0.8%) of these participants were hospitalized for COVID-19 or died from any cause, compared with 10 (1.6%) of those in the placebo group through day 28 (95% CI −2.0 to 0.4). However, the difference did not reach statistical significance.
In a subgroup analysis of at-risk participants only, three (0.9%) of the participants receiving nirmatrelvir/ritonavir were hospitalized or died versus seven (2.2%) in the placebo group (95% CI -3.3 to 0.7).
In 2022, the drug's manufacturer Pfizer announced an updated interim analysis of the EPIC-SR that reached similar conclusions to these final results. Because of low rates of hospitalization in the study population, Pfizer ended enrollment in EPIC-SR at that time.
In contrast to EPIC-SR, the EPIC-HR trial that enrolled high-risk unvaccinated participants found that nirmatrelvir/ritonavir reduced hospitalization or death by 88%.
"What can we conclude from these two trials about nirmatrelvir-ritonavir for the treatment of COVID-19?" wrote Rajesh Gandhi, MD, and Martin Hirsch, MD, of Massachusetts General Hospital and Harvard Medical School in Boston, in an accompanying editorial.
"Clearly, the benefit observed among unvaccinated high-risk persons does not extend to those at lower risk for severe COVID-19," they noted. The EPIC-SR results add support to current recommendations that nirmatrelvir/ritonavir is only indicated for treatment of mild-to-moderate COVID-19 in persons at high risk for disease progression, they said.
However, Gandhi and Hirsch also pointed out that although the EPIC-SR trial failed to show that nirmatrelvir/ritonavir shortened COVID-19 symptoms in vaccinated participants with at least one risk factor, the study enrolled only a small percentage of patients who were most likely to be hospitalized with COVID-19.
"Other than obesity, smoking, and hypertension, risk factors for severe COVID-19 were uncommon; for example, less than 2% of the participants had heart or lung disease," they wrote. Of note, only 5% of EPIC-SR enrollees were 65 years or older.
"As with many medical interventions, there is likely to be a gradient of benefit for nirmatrelvir–ritonavir, with the patients at highest risk for progression most likely to derive the greatest benefit," Gandhi and Hirsch commented.
About 26% of participants who received nirmatrelvir/ritonavir experienced an adverse event, similar to the 24.1% in the placebo group. The most commonly reported treatment-related adverse events among those who took nirmatrelvir/ritonavir were dysgeusia (5.8%) and diarrhea (2.1%). In participants receiving nirmatrelvir/ritonavir, 3.7% reported grade 3 or 4 adverse events versus 3.9% in the placebo group. No grade 5 adverse events occurred in the treatment group.
Of note, symptom rebound at day 14 occurred in 11.4% of participants treated with nirmatrelvir/ritonavir versus 16.1% in the placebo group. Viral load rebound at day 14 was similar between the 2 groups (4.3% in the nirmatrelvir/ritonavir group vs 4.1% in the placebo group).
The EPIC-SR trial included 1,296 participants who had confirmed COVID-19 and symptom onset within the previous 5 days. Participants were randomized 1:1 to receive either nirmatrelvir/ritonavir (n=654) or placebo (n=634). Participants recorded COVID-19 symptoms on a daily basis from day 1 through day 28.
The primary end point of the study was time to sustained alleviation of all targeted COVID-19 signs and symptoms. COVID-19-related hospitalization and death from any cause were also assessed through day 28. A total of 1,250 participants completed efficacy and safety follow-up assessments.
Of participants, 54% were women and the median age was 42 years. The majority of participants were white (78.5%) and 41.4% were Hispanic or Latino. Approximately 57% had been vaccinated for COVID-19, and about 50% had at least one risk factor for severe COVID-19. The most common comorbidity was hypertension (12.3%) and the most common risk factor was cigarette smoking (13.3%).
Most participants (72.5%) underwent randomization within 3 days after symptom onset. Adherence to nirmatrelvir/ritonavir -- defined as having taken at least 80% of the pills -- was nearly 95%.
Katherine Kahn is a staff writer at MedPage Today, covering the infectious diseases beat. She has been a medical writer for over 15 years.
Disclosures
The study was funded by Pfizer.
Hammond is an employee of Pfizer and reported holding stock options in Pfizer. Co-authors are employees of Pfizer or reported other ties to industry.
Gandhi and Hirsch reported no disclosures.
Primary Source
New England Journal of Medicine
Source Reference: Hammond J, et al "Nirmatrelvir for vaccinated or unvaccinated adult outpatients with COVID-19" New Engl J Med 2024; DOI: 10.1056/NEJMoa2309003.
Secondary Source
New England Journal of Medicine
Source Reference: Gandhi RT, Hirsch M "Treating acute COVID-19 -- final chapters still unwritten" New Engl J Med 2024; DOI: 10.1056/NEJMe2402224.
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