Background and purpose: Multiple sclerosis (MS) has been associated with increased mortality rates. However, influence of lifestyle parameters remains unknown, and inconsistencies exist regarding findings for causes of death.

Methods: We conducted a population-based cohort study using the General Practice Research Database, Hospital Episode Statistics, and national death certificates (January 2001 through March 2008). To each patient with MS (n = 1270), up to six referent subjects without MS were matched by age, gender, and practice. Cox proportional hazards models were used to estimate mortality rate ratios (HRs).

Results: Patients with MS had a 3.5-fold increased mortality rate for all-cause mortality, compared with referent subjects (HR 3.51, 95% CI 2.63-4.69). The rate further increased amongst current smokers (HR 6.72, 95% CI 4.16-10.87) (but not in ex-smokers) and subjects with a body mass index of <20 kg/m(2) (HR 6.67, 95% CI 3.50-12.73). The HR was highest for infectious/respiratory-related deaths (HR 7.69, 95% CI 4.92-12.02) and was significantly increased for deaths related to cardiovascular diseases (2.4-fold) and cancer (1.9-fold), but not for accidents and suicide related deaths.

Conclusion: British patients with MS have a 3.5-fold increased mortality rate compared with the general population. Smoking and respiratory diseases are major (potentially preventable) factors related to increased mortality rate amongst patients with MS.