A recent review highlighted the importance of managing cardiovascular risk factors in patients with Fabry disease versus the general population.
Fabry disease (FD) is a rare, X-linked multisystem lysosomal storage disorder caused by a deficiency in the enzyme α-galactosidase A. This causes accumulation of sphingolipids and ultimately leads to life-threatening renal, cardiac, and cerebrovascular events. Currently, cardiovascular disease is the most common cause of FD-related morbidity and mortality, according to the most recent surveys and registries.
A recent review examined atherosclerosis and angina in Fabry patients and highlighted the importance of managing cardiovascular risk factors in these patients.
The current review examines post-mortem findings from a 69-year old male FD patient treated with enzyme replacement therapy (ERT), which is thought to be disease-modifying. The average life expectancy in FD patients is 58 years for males and 75 years for females.
The patient in this case died suddenly, and medical examination found evidence of prior myocardial infarction as a result of an occlusive blood clot complicating atherosclerotic coronary artery disease (CAD). “This case illustrates the point that, as Fabry patients live longer, they are susceptible to acquired heart disease in the same way as the general population,” the authors wrote. Therefore, physicians treating these patients should be aware of their susceptibility and the same symptoms of cardiovascular morbidity and mortality as other patients.
Cardiovascular symptoms are relatively frequent in FD, with angina, dyspnoea, and palpitations being the most common. Between 22% to 23% of patients experience angina, and it is more common in those undergoing treatment than in untreated patients. For the majority of these patients, angina is severe enough to affect quality of life. The authors suspect this is due to more advanced disease and left ventricular hypertrophy (LVH), which is caused by the buildup of sphingolipids in cardiac cells.
The patient in the case was found to have both CAD that was treated and LVH due to FD. And while overall, angina is about as common in FD as it is in chronic coronary syndromes in the general population, it affects women more often, impacts quality of life earlier than in the general population, and a higher proportion of FD patients with angina are limited by more severe symptoms.
“The diagnostic approach in patients with FD and angina should follow conventional methods of assessing patients with chest pain of suspected cardiac origin with the aim to exclude conventional coronary artery disease as a cause of symptoms,” the authors wrote. They recommend assessing the nature of the pain (typical, atypical, or non-anginal), considering CAD likelihood, and using non-invasive CT coronary angiography with calcium scoring.
Atherosclerosis is more common in older age in the general population, and coronary events are most often explained by factors other than age that can exacerbate atherosclerosis, such ahypertension, high cholesterol, smoking, diabetes, renal impairment, and obesity. These conventional risk factors are also common in FD patients, and study authors argue that although atherosclerosis in FD patients may be driven by different pathological processes, it “seems logical for aggressive risk factor modification though lifestyle and pharmacological therapy to be promoted to minimize cardiovascular risk.”
The review points to past studies showing ischemia—slow and inadequate blood flow—in patients with FD more often than in the general population. This is consistent with the effects of microvascular disease seen in FD, according to the authors. They also cite other mechanisms such as altered coronary vasoreactivity, perfusion mismatch caused by LVH, and accelerated atherosclerosis as potential causes of FD-related ischemia and resulting angina.
While management of conventional atherosclerosis risk factors is encouraged in FD patients to minimize end-organ damage, more research is needed to confirm the effects of atherosclerosis in these patients.
“The effect of FD and atherosclerosis is still not completely understood and further research is therefore needed in this area in order to better understand the disease mechanisms involved with the aim of reducing cardiovascular mortality in FD,” the authors concluded. “In patients with FD that have chest pain, while this may be due to microvascular dysfunction, it is important to ensure macrovascular CAD is excluded, in particular in the older, male cohort.”
Roy A, Umar H Ochoa-Ferraro A, et al. Atherosclerosis in Fabry disease—a contemporary review. J Clin Med. Published online September 27, 2021. doi:10.3390/jcm10194422