Cerebrovascular, cardiovascular disease risk seen higher in SSc

Meta-analysis has implications for prognosis and prevention, researchers sayby Andrea Lobo, PhD | April 23, 2024

​Having scleroderma increases the risk of developing diseases affecting blood vessels of the brain or heart, known as cerebrovascular and cardiovascular diseases, a review study found.

Relative to controls, the risk of stroke — caused by poor blood flow to the brain — in scleroderma patients was 64% higher, whereas that of cardiovascular disease was 112% higher.
“Our findings support increased clinical surveillance and consideration of preventative strategies in this high-risk population,” researchers in Taiwan wrote.

Their study, “Association between systemic sclerosis and risk of cerebrovascular and cardiovascular disease: a meta-analysis,” was published in Scientific Reports.

Scleroderma, also known as systemic sclerosis (SSc), is characterized by the excessive production of collagen that leads to the accumulation of scar tissue, affecting the skin and potentially internal organs, such as the digestive tract and lungs. The disease may also damage blood vessels, both small and large, leading to complications such as pulmonary arterial hypertension and scleroderma renal crisis.
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Evidence has suggested that people with scleroderma may have an increased risk of stroke, heart attack, and peripheral vascular disease, which is reduced circulation in blood vessels outside the brain and heart. However, “the risk of cerebrovascular and cardiovascular complications attributed to SSc remains debated,” the researchers wrote.

​The study and its findings
To explore this topic further, the scientists conducted a systematic review of published research and a meta-analysis, which pools data from multiple studies. More details can be found in PROSPERO (CRD42023471039), an international prospective register of systematic reviews.

The analysis included 17 studies with 6,642,297 participants from different geographical regions (U.S., Europe, and Taiwan). The mean age of the participants ranged from 35 to 60.9 years; they were mostly female and were followed up for periods between one and 14 years.

Overall, 11 studies with 1,157,175 participants reported an association between scleroderma and stroke; compared to controls, SSc patients were at a 64% higher risk of having a stroke. Subgroup analysis revealed that the risk was increased by 55% in non-Asians; in Asians (from Taiwan) the risk also was higher, but the difference was not statistically different.

Seven studies involving 5,524,044 participants identified a more than two times greater risk for cardiovascular disease in scleroderma patients.

People with SSc were also over two times more likely to have a heart attack and venous thromboembolism, when a blood clot forms in a vein. Their risk of peripheral vascular disease was more than five times higher.

Regarding other heart disease manifestations, heart failure and atrial fibrillation — an irregular and often very fast heart rhythm — were more common in scleroderma patients, as was the need to have a pacemaker.

A sensitivity analysis showed that the findings were consistent, as the omission of any study from the analysis did not affect the overall results, the scientists stated.

Overall, they said this meta-analysis demonstrates that SSc is associated with an increased cerebrovascular and cardiovascular risk across a broad range of complications, emphasizing bodywide blood vessel disease as a feature of underlying scleroderma processes.
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According to the researchers, “elucidating the relationship between SSc and cerebrovascular/[cardiovascular diseases] has significant implications for prognosis, screening, prevention, and management.”
Therefore, “future studies should delve deeper into the mechanistic underpinnings of these associations, explore potential interventions, and assess the efficacy of preventative strategies tailored for this high-risk population,” they added.