Canadian study highlights stroke danger for young adults with Fabry
Men younger than 40 have significantly higher risk than the general population
Young adults with Fabry disease in Canada are at a significantly higher risk of experiencing a first-time stroke or transient ischemic attack (temporary blockages sometimes referred to as “mini-strokes”) than the general population, a new study reveals.
Despite this elevated risk, very few Fabry patients who experienced a first stroke or transient ischemic attack (TIA) had a history of atherosclerotic cardiovascular disease (CVD). In the general population, CVD is the leading cause of stroke, typically driven by the buildup of fatty plaques on artery walls.
In addition, the prescribing rates of low-dose aspirin to prevent stroke in Fabry patients have only slightly declined, even though multiple clinical trials have recently shown no benefits to this treatment strategy among the general population without CVD.
High stroke incidence in younger patients
“There was a high incidence of stroke/TIA in the younger [Canadian Fabry patients] compared to the general Canadian population, despite low levels of traditional vascular risk factors,” researchers wrote.
The study, “Risk factors, stroke rates and aspirin prescribing trends in the Canadian Fabry disease initiative cohort,” was published in the Orphanet Journal of Rare Diseases.
Fabry disease is caused by mutations in the GLA gene, leading to a deficiency of the alpha-galactosidase A (alpha-Gal A) enzyme. This deficiency results in the accumulation of fatty molecules, primarily globotriaosylceramide (Gb3), within cells. In turn, this accumulation can cause progressive organ damage, affecting the heart, blood vessels, kidneys, and nervous system.
Gb3 deposits can accumulate in blood vessel walls, narrowing them and restricting blood flow to the brain, which can lead to a stroke. Strokes and TIAs occur in Fabry patients at a significantly younger age than in the general population.
To determine the incidence of the first stroke or TIA in Canadian Fabry patients, a team led by researchers at The University of British Columbia, in Canada, examined data from 641 Fabry patients who participated in the Canadian Fabry Disease Initiative (CFDI) from 2007 to 2023. Two-thirds of the participants were women (65%).
During the study period, 57 patients (27 women, 30 men) experienced a new stroke or TIA. Approximately 60% of them were younger than 60 years old at the time. Most (72%) were on enzyme replacement therapy or chaperone therapy, while about one-fourth (28%) were receiving anticoagulant therapy.
Overall, the incidence of stroke/TIA was 0.016 events per patient-year. A patient-year is calculated by multiplying the number of people in the study by the time each person spends in the study.
The stroke/TIA rate in men was 2.65 times higher than in women (0.026 vs. 0.0098 events per patient-year). Men with severe GLA mutations accounted for the majority of these cases, with a rate of 0.031 events per patient-year. In contrast, men with less-severe mutations had overall stroke rates similar to women with severe mutations (0.011 vs. 0.0096 events per patient-year).
Traditional risk factors are missing
When compared to the Canadian population younger than 40, the incident stroke/TIA rate was markedly higher in Fabry patients: nine times higher in women and 30 times higher in men at this age.
In the general population, strokes are caused mainly by atherosclerotic CVD, marked by the buildup of fatty plaques on the artery walls, which narrows blood vessels and restricts blood flow to the brain. Therefore, the team assessed the risk of atherosclerotic CVD in Fabry patients who experienced a stroke/TIA.
In this analysis, none of the Fabry patients younger than 60 at the time of their first stroke/TIA met the criteria for a moderate-to-high 10-year atherosclerotic CVD risk. Of those 60 years or older, half (52%) had moderate-to-high risk. Overall, very few (8.8%) had experienced a cardiovascular event before their first stroke/TIA.
Based on these findings, the researchers suggested that atherosclerotic CVD may not be the predominant cause of stroke/TIA in these early-presenting Fabry patients.
Aspirin, or acetylsalicylic acid (ASA), is a common pain reliever that also helps prevent blood clots by inhibiting platelets, the cell fragments that help blood clot. The benefits of low-dose aspirin in preventing cardiovascular events are well-established among those with CVD. However, three large clinical trials conducted in 2018 demonstrated that these benefits did not necessarily extend to those without CVD in the general population. Instead, they showed an increased risk of bleeding.
Therefore, the team investigated whether prescribing practices for ASA or other antiplatelet (AP) therapies changed after 2018 among the 193 Fabry patients (73% women, 27% men) who had never experienced a cardiovascular event.
Data showed that after 2018, there was a “relatively small” but significant decrease of 8% in the proportion of patients on ASA/AP for primary CVD prevention, “suggesting ongoing physician belief it may be beneficial in this population,” the team noted.
“Although the stroke/TIA burden is higher in CFDI [Fabry] patients compared to the Canadian general population, there is conflicting evidence supporting the relevance of using traditional [atherosclerotic CVD] risk calculators to stratify this population for primary prevention of stroke/TIA, and uncertain benefits of ASA for primary prevention,” the team concluded.
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