title: Causes of death in patients with multiple sclerosis and matched referent subjects: a population-based cohort study.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Lalmohamed
authors.forename: M T
authors.initials: MT
authors.lastname: Bazelier
authors.forename: T P
authors.initials: TP
authors.lastname: Van Staa
authors.forename: B M J
authors.initials: BM
authors.lastname: Uitdehaag
authors.forename: H G M
authors.initials: HG
authors.lastname: Leufkens
authors.forename: A
authors.initials: A
authors.lastname: De Boer
authors.forename: F
authors.initials: F
authors.lastname: De Vries
mesh_terms: D000293:Adolescent; D000328:Adult; D015992:Body Mass Index; D002423:Cause of Death / Q000639:trends; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000453:epidemiology / Q000401:mortality*; D011159:Population Surveillance / Q000379:methods*; D012189:Retrospective Studies; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology / Q000401:mortality; D055815:Young Adult