Patients with multiple sclerosis (MS) had a 3.5-fold increase in all-cause mortality and a 1.5-fold increase in cardiovascular disease mortality, compared with those without MS, even after controlling for traditional risk factors, and women were more at risk than men. Statins were linked with lowering the mortality risk.
Multiple sclerosis (MS) is associated with an increased risk of cardiovascular and cerebrovascular disease, according to a paper published recently in JAMA Neurology, and women were more severely affected than men.
Traditional vascular risk factors may not account for the higher risk, said the investigators, who examined UK data. The researchers conducted a population-based, retrospective matched cohort study involving 12,251 people diagnosed with MS between 1987 and 2018 in order to assess the risk of macrovascular events and mortality for patients. The information came from the UK Clinical Practice Research Datalink (CPRD), a large repository of anonymized longitudinal electronic medical records from primary care offices.
Each patient was matched to 6 people without MS by age, sex, and general practice. While the first MS diagnosis was considered the index date, the analysis included people with 3 or more diagnoses of MS recorded through their study period. The average follow-up time was about 10 years for people with MS and about 11 for their matched controls.
The researchers noted that people with MS have a higher prevalence of hypertension and hyperlipidemia, being overweight or obese, having ever smoked, and having lower levels of physical activity. Mortality among people with MS remains higher than the general population, but the evidence about the efficacy of tighter vascular risk factor controls that may benefit this population is lacking, they added.
Two-thirds of the patients with MS were women, compared with 69% in the control group, the study authors said. The mean age was 44 years in both groups. The proportion of individuals using cardiovascular medications in the MS and non-MS groups were similar, but there were more patients with MS who smoked compared with controls (37% vs. 29%, respectively).
The incidence of acute coronary syndrome in MS patients was 204.5 per 100,000 person-years, the study authors found. They said the incidence was 116.8 in the control group. Of cerebrovascular disease, the incidence was 159.6 per 100,000 person-years, compared with 81.4 in the controls.
Having MS was linked with a 28% increased hazard of acute coronary syndrome (hazard ratio [HR], 1.28; 95% CI, 1.09-1.51), 59% increased hazard of cerebrovascular disease (HR, 1.59; 95% CI, 1.32-1.92), 32% increased hazard of any macrovascular disease (HR, 1.32; 95% CI, 1.15-1.52), 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).
There were no observable differences between men with and without MS, but the study authors noted differences in women. Women with MS had an increased hazard of acute coronary syndrome, cerebrovascular disease, and any macrovascular disease compared to women without MS, the authors said.
The observed mortality rate was 2223.3 events per 100,000 person-years for people with MS but 619.5 events for the control groups. The investigators wrote that the people with MS had an increased risk of all-cause mortality and cardiovascular disease mortality.
Women, especially, were at risk, they said: 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) than men without MS.
These findings are consistent with prior studies that used matched cohort designs, the study authors wrote. This includes a Swedish study that found the risk for acute myocardial infarction was 85% higher and the risk of stroke was 71% higher in the MS population. The study also found a greater increased risk for women, the study authors added.
“This study suggests that MS is associated with an increased risk of cardiovascular and cerebrovascular disease that is not completely accounted for by traditional vascular risk factors,” the study authors concluded.
Palladino R, Marrie RA, Majeed A, Chataway J. Evaluating the risk of macrovascular events and mortality among people with multiple sclerosis in England [published online May 4, 2020]. JAMA Neurol. doi:10.1001/jamaneurol.2020.0664.