Risk of Cardiovascular Disease Increased in Those With Multiple Sclerosis

Data from a population-based, retrospective-matched cohort study revealed patients with multiple sclerosis (MS) are at an increased risk of cardiovascular and cerebrovascular disease that is not completely accounted for by traditional vascular risk factors.

The MS cohort was associated with a 28% increased hazard of acute coronary syndrome (hazard ratio [HR], 1.28; 95% CI, 1.09—1.51), a 59% increased hazard of cerebrovascular disease (HR, 1.59; 95% CI, 1.32–1.92), and a 32% increased hazard of any macrovascular disease (HR, 1.32; 95% CI, 1.15–1.52) compared with the cohort without MS.

The research, conducted by Raffaele Palladino, PhD, research associate, Imperial College London, and colleagues, found that compared to people without MS, people with MS had a 3.5-fold increased hazard of all-cause mortality (HR, 3.46; 95% CI, 3.28—3.65) and 1.5-fold increased hazard in cardiovascular disease mortality (HR, 1.47; 95% CI, 1.27–1.71).

Results also showed that differences in macrovascular events were more pronounced among women than men. Additionally, women showed higher rates of mortality risk, while treatment with lipid-lowering medications—mainly statins—was associated with lower mortality rates among patients with MS.

When stratifying by sex, compared with women without MS, women with MS had a 3.5-fold increase in all-cause mortality (HR, 3.52; 95% CI, 3.28—3.77) and a 1.3-fold increase in cardiovascular disease mortality (subhazard ratio [SHR], 1.30; 95% CI, 1.04–1.62). Men with MS had a 2.7-fold increased risk of all-cause mortality (HR, 2.74; 95% CI, 2.35–3.18) and a 1.5-fold increased risk of cardiovascular disease mortality (SHR, 1.54; 95% CI, 1.06–2.23) compared with men without MS.

Differences in rates of macrovascular disease were also observed in men. Men with MS has an increased hazard of acute coronary syndrome (HR, 1.81; 95% CU, 1.22—2.69) and any macrovascular disease (HR, 1.67; 95% CI, 1.15–2.43) compared with men without MS.

Almost 3% of the study population was taking lipid-lowering medications during the index year. Compared with the controls not taking lipid-lowering medications, those with MS not taking lipid-lowering medications had 3.6-fold increased mortality rates (HR, 3.62; 95% CI, 3.43—3.83), while those with MS taking lipid-lowering medications had 2-fold increased mortality rates (HR, 1.95; 95% CI, 1.58–2.42).

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“Treatment with lipid-lowering medications (approximately 95% of which were statins) seemed to have a protective association with all-cause mortality in people with MS,” Palladino and colleagues concluded. “The role of statins in neuroprotection in MS has been investigated during the last 2 decades, with numerous mechanisms postulated, such as direct vasculoprotection and enhanced perfusion and reduction in free radical damage either by improved blood flow and reducing hypoxia-mediated reactive oxygen species production or through direct inhibition of cytotoxic pathways; also, statins may exert a neuroprotective effect by preventing glutamate-mediated excitotoxic effects.”

A total of 12,251 people with MS (66.9% women; mean age, 44.9 [standard deviation (SD), 13.3] years) were matched with 72,572 people without MS (69.8% women; mean age, 44.9 [SD, 13.3]) in the retrospective matched cohort study. Each patient had general practices registered with the Clinical Practice Research Datalink in England between January 1, 1987, and September 30, 2018, with a mean follow-up of 11.3 (SD, 6.5) years.

Patients with 3 or more diagnoses of MS recorded during the study period were included, with the index date defined as the first MS diagnosis. Researchers used cox proportional hazards regression and Fine and Gray proportional subhazard regression models to assess differences in rates of main outcomes such as acute coronary syndrome, cerebrovascular disease, any macrovascular disease (including peripheral arterial disease), and all-cause mortality and cardiovascular disease-specific mortality.

Palladino and colleagues concluded that although the study suggests that MS is associated with an increased risk of cardiovascular and cerebrovascular disease, further investigation is needed to assess the adverse effects of these comorbidities in patients with MS.

REFERENCE

Palladino R, Marrie RA, Majeed A, Chataway J. Evaluating the risk of macrovascular events and mortality among people with multiple sclerosis in England. JAMA Neurol. Published online May 4, 2020. doi: 10.1001/jamaneurol.2020.0664.