Causes that Contribute to the Excess Mortality Risk in Multiple Sclerosis: A Population-Based Study

Abstract

<b><i>Background:</i></b> Lifespan is 6–10 years shorter in multiple sclerosis (MS), but the reasons remain unclear. Using linked clinical- and population-based administrative health databases, we compared cause-specific mortality in an MS cohort to the general population. <b><i>Methods:</i></b> MS patients in British Columbia (BC), Canada, were followed from the later of first MS clinic visit or January 1, 1986, to the earlier of death, emigration, or December 31, 2013. Comprehensive mortality information was obtained by linkage to BC’s multiple-cause-of-death mortality data. Causes were grouped using International Classification of Disease codes. Standardized mortality ratios (SMRs) were calculated for underlying cause, and relative mortality ratios (RMRs) for any mention cause, by comparison to mortality rates in the age-, sex-, and calendar year-matched general population. Cause-specific relative mortality was explored by sex and disease course (relapsing onset and primary progressive). <b><i>Results:</i></b> Among 6,629 MS patients with 104,236 patient-years of follow-up, 1,416 died. The all-cause mortality risk was increased relative to the general population (SMR 2.71; 95% CI 2.55–2.87). MS was the underlying cause in 50.4%, and a mentioned cause in 77.9%, of deaths. Mortality by underlying cause was higher than expected for genitourinary disorders/infections (SMR 3.55; 95% CI 2.25–5.32), respiratory diseases/infections (SMR 2.69; 95% CI 2.17–3.28), suicide (SMR 2.40; 95% CI 1.61–3.45), cardiovascular disease (SMR 1.57; 95% CI 1.36–1.81), and other infections/septicemia (SMR 1.83; 95% CI 1.15–2.78). Risks of death due to overall cancer, accidents, digestive system disorders, and endocrine/nutritional diseases as underlying causes were similar to the general population. However, mortality with any mention of accidents (RMR 2.71; 95% CI 2.22–3.29) or endocrine/nutritional diseases (RMR 1.75; 95% CI 1.46–2.09) was greater. Bladder cancer mortality was increased in women (SMR 3.87; 95% CI 1.42–8.42) but not men. No notable differences were observed by disease course. <b><i>Conclusions:</i></b> MS itself was the most frequent underlying cause of death. Infections (genitourinary, respiratory, and septicemia), suicides, cardiovascular disease, and accidents contributed significantly to the increased risk of death. Some findings differed by sex, but not disease course. Multiple-cause death data offer advantages over “traditional” use of underlying cause only.

Standardized mortality ratios in multiple sclerosis: Systematic review with meta‐analysis

“…A total of 10 studies reported SMR for cardiovascular disease. Of these 10 studies, four were in addition to the previous publication 4,6,8,9 . The SMR for cardiovascular disease was 1.74 (95% CI 1.67 to 1.81, I 2 = 94%, p < .01).…”

“…Of these eight studies, three were new to the cohort of the previous meta-analysis. 6,8,9 The SMR for respiratory illness and infection was…”

“…Two studies reported on accident only, 6,8 whereas four studies reported on both accident and suicide. 9,15,17,18 The remaining five studies commented on suicide only.…”

“…In 2015, a meta‐analysis of the SMR in MS by Manouchehrinia et al (2015) found a 2.8 times greater risk of mortality in MS patients with no temporal trend over time from 1949–2012 2 . Consensus regarding the increased mortality compared to the general population was confirmed in later studies which showed an SMR for patients with MS between 2.45–2.92 3–9 . The lack of a temporal trend in the meta‐analysis by Manouchehrinia et al was in contrast to the improved survival over time demonstrated by the study by Koch‐Henriksen et al, who found over fifty percent improvement in SMR in a 1990–1999 cohort compared to a 1950–1959 cohort 7 .…”

The Canadian Women’s Heart Health Alliance ATLAS on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women—Chapter 2: Scope of the Problem

“…84 Cardiovascular morbidity results are similar to those reported in a recent Canadian population-based study, although CVD mortality was reported to be higher in men (n ¼ 515) compared to women (n ¼ 901) with multiple sclerosis. 85 Adults with disabilities are 4 times more likely to report their health to be fair or poor compared to people with no disabilities (40% vs 10%), 78 and women with disabilities are particularly vulnerable due to having fewer resources and protective factors. 74 Adjusted for age, women with physical disabilities have 6.6 (95% CI, 5.2-8.4) times higher odds of having CAD, 5.9 (95% CI, 4.3-8.1) times higher odds of having cardiac symptoms, 86 and are less likely to receive preventive or urgent care compared to women without disabilities.…”