Real-world study shows burden of heart, other complications in Fabry
Nearly half of all deaths over 20 years linked to cardiovascular problems
Serious complications like cardiovascular disease and other heart issues, kidney problems, and stroke are common among adults with Fabry disease and may be associated with factors such as sex, age at diagnosis, genetic profiles, and cardiometabolic risk factors like obesity, according to the findings of a 20-year U.K. study.
Slightly less than half of all reported deaths among these Fabry patients were related to cardiovascular problems like heart failure or heart attack, the data showed.
“This study provides real-world observational insights into the clinical trajectories of patients with FD [Fabry disease] over two decades,” the researchers wrote, noting that “a substantial proportion of patients experienced … outcomes” marked by heart and kidney complications.
The analysis, involving data from more than 400 people with Fabry in the U.K., helps to illustrate the disease burden experienced by patients, the researchers noted.
Moreover, the team wrote, “these findings support a comprehensive, individualised approach to care, including early diagnosis, [cardiovascular] risk assessment, and targeted multidisciplinary management to optimise outcomes.”
The study, “Real-world clinical outcomes in adult patients with Fabry disease: A 20-year retrospective observational cohort study from a single centre,” was published in the journal Molecular Genetics and Metabolism Reports.
A multisystemic condition, Fabry disease is caused by mutations in the GLA gene that result in the harmful accumulation of the fatty molecule globotriaosylceramide, called Gb3. This buildup, which occurs because there isn’t enough of the functional enzyme needed to break down Gb3, can happen throughout the body — and thus lead to a wide range of possible signs and symptoms.
Cardiovascular issues like heart attack or heart rhythm changes, known as arrhythmias, are the leading cause of death in Fabry. Kidney and cerebrovascular disease, in which blood flow to the brain is affected, also can be life-threatening.
Newer obesity, diabetes treatments may help Fabry patients
Emerging treatments for cardiometabolic risk factors such as obesity and diabetes may help in protecting against these complications, according to the researchers. Among newer medications are GLP-1 receptor agonists like the popular name brand Ozempic (semaglutide) or sodium-glucose cotransporter 2 (SGLT2) inhibitors like Jardiance (empagliflozin).
However, more research is needed to “better understand their potential in improving disease progression and clinical outcomes,” the scientists wrote.
To learn more, the team performed a retrospective analysis involving 20 years of clinical data from 405 adults with Fabry seen at a single center in the U.K. While the focus was particularly on cardiovascular disease, the researchers also looked at kidney, cerebrovascular, and mortality outcomes.
Overall, slightly less than half of the study population (47.9%) experienced one of the evaluated outcomes, most notably cardiovascular issues, as seen in 30%. Kidney problems were seen for 3%, cerebrovascular issues for 6.4%, and mortality events for 8.6%, per the data.
Relative to those who did not experience such complications, these patients were significantly more often men, obese, and with high blood pressure. Additionally, these individuals had a higher average disease severity score.
At the time of diagnosis, those who experienced any of these outcomes were also significantly older and had higher disease severity scores than those who did not.
Cardiometabolic risk factors like smoking, high blood pressure, and obesity were common in the study group; however, the use of cardiometabolic therapies like GLP-1 and SGLT2 medications was generally low. About a third of the entire study group had a GLA mutation called c.644A>G.
Men found to have more heart complications, higher burden
Among people who had cardiovascular outcomes, certain types of arrhythmias were most common, while stroke or mini-stroke were the recorded cerebrovascular events. The 12 people with serious kidney outcomes had kidney failure that required dialysis or a kidney transplant.
Overall, 35 people died. A total of 15 deaths were due to cardiovascular complications such as heart failure (60%), cardiac arrest (20%), or heart attack (13%). Other common causes of death included sepsis, which is a serious response to infection, and cancer.
There was a clear male predominance in the observed complications, including death, which is consistent with known sex differences in the disease. People who died also tended to have experienced a high burden of multiple health complications.
The c.644A>G mutation was the most commonly observed mutation in people who experienced cardiovascular events, cardiovascular-related death, or death due to other causes. According to the researchers, this “illustrates the importance of genetic characterisation in clinical evaluation.”
Moreover, risk factors like smoking, high blood pressure, and obesity were prevalent, which researchers believe “likely contributed” to the risk of life-threatening events, per the study. Thus, the team noted, there’s a need for a systemic approach to evaluate Fabry patients for these risk factors and to implement treatment strategies.
The typically late onset of symptoms … underscores the importance of heightened clinical awareness and early screening. … Even patients presenting with mild symptoms may be at risk of serious complications.
Given the little use of medications for obesity in this population, there was a limited ability to determine whether such treatments could help protect against serious cardiovascular problems or death. The scientists noted that this could represent “an underutilised opportunity for intervention,” and that “further studies are warranted to evaluate their role in [Fabry disease].”
Overall, the study showed the burden of disease complications, particularly heart-related issues, in people with Fabry.
“The typically late onset of symptoms, often accompanied by minimal noncardiac involvement at [the study’s start], underscores the importance of heightened clinical awareness and early screening,” the team wrote. “Even patients presenting with mild symptoms may be at risk of serious complications.”
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