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“Of MS and Men” Morbidity & Mortality Outcomes. Mitchell T. Wallin, MD, MPH MS Clinic Director Department of Veterans Affairs Medical Center Washington, DC Assistant Professor of Neurology Georgetown University Medical School. “Of MS and Men” Morbidity & Mortality Outcomes. I. Definitions
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“Of MS and Men”Morbidity & Mortality Outcomes Mitchell T. Wallin, MD, MPH MS Clinic Director Department of Veterans Affairs Medical Center Washington, DC Assistant Professor of Neurology Georgetown University Medical School
“Of MS and Men”Morbidity & Mortality Outcomes I. Definitions II. Morbidity Data III. Mortality & Survival Data IV. Conclusions
Multiple Sclerosis Subtypes(Coyle P, 2002; adapted from Lublin F, et al Neurology 1996)
RR-SP MS PP MS Age at onset (mean) 30 yrs 40 yrs Sex ratio (M:F) 2:1 1:1 Race disability progression in AA disability progression in AA Onset symptoms Sensory, visual Paraparesis Secondary Progressive MSvs. Primary Progressive MS
“Of MS and Men”Morbidity & Mortality Outcomes I. Definitions II. Morbidity Data III. Mortality & Survival Data IV. Conclusions 2
Prevalence of Subtypes of MS Progressive- relapsing (PR) 5% (N = 3019) Primary- progressive (PP) 10% Relapsing-remitting (RR) 55% Secondary-progressive (SP) 30% Jacobs et al. Mult Scler. 1999;5:369-376.
Veteran Integrated Service Network (VISN)-5 MS Demographic Data
MS Morbidity in the US • Nationwide Prevalence • 58/100,000 population (Baum, 1981) • 102-139/100,000 population (Anderson, 1992) • 85/100,000 population (Noonan, 2002) • Olmsted County, MN (Mayr 2003) • Raw Incidence: 7.5/100,000 person-yrs • Raw Prevalence: 177/100,000 person-yrs
Estimated prevalence of MS per 100,000 by report in the US NHIS Survey, 1982-1996(Noonan, 2002)
Vietnam and later military service MS cohort Study Population Flow Chart (Wallin, et al 2004) Eligible MS patients 55345 Eligible Controls 10683 394 1305 MS Cases Analyzed 4951 Controls Analyzed 9378
WWII-KC Cohort Vietnam and later Cohort Race-sex category # of MS cases Case-control ratio (95% CI) # of MS cases Case-control ratio (95% CI) White female 182 1.86 (1.44 – 2.38) 604 2.85 (2.49-3.25) Black female 4 1.33 (0.23 – 9.10) 123 2.74 (2.00-3.52) Other race-female 2 ---- 16 3.37 (1.52-7.56) White male 4,923 1.04 (0.98 – 1.10) 3,758 0.96 (0.90-1.00) Black male 177 0.45 (0.38 – 0.54) 415 0.64 (0.57-0.43) Other race-male 17 0.23 (0.14 – 0.39) 35 0.29 (0.20-0.41) TOTAL 5,305 1.00 4,951 1.00 Adjusted case-control ratios for MS by race and sex at EAD
Vietnam & Later Service 129 111 116 169 143 116 160 152 55 180 141 138 230 113 216 141 108 126 86 101 147 103 107 110 115 73 67 67 144 83 80 79 94 83 81 74 56 81 92 59 81 63 62 54 54 62 46 75 Case Control Ratios x 100 < 60 61 to 90 91 to 120 121 to 149 >150 WWII-KC 167 200 131 183 161 211 131 198 172 127 117 145 118 118 203 133 118 105 92 116 85 138 78 121 101 132 74 95 131 72 109 86 64 61 66 44 59 61 67 61 52 64 56 41 48 52 61 50 Case Control Ratios x 100 < 60 61 to 90 91 to 120 121 to 149 >150
Risk of Bone Loss in MenWeinstock-Guttman, 2004 40 male MS patients, mean: EDSS 5.8; Age 51yrs • 32 (80%) with reduced bone loss of lumbar spine or femur • 17 (43%) had osteopenia • 15 (38%) had osteoporosis • 8/38 (21%) with fractures of ribs, vertebrae or extremities • Risk factors for low bone mineral density • Femoral neck: EDSS and BMI • Lumbar spine: EDSS
“Of MS and Men”Morbidity & Mortality Outcomes I. Definitions II. Morbidity Data III. Mortality & Survival Data IV. Conclusions 2
MS Survival • 10 years shorter than age-matched general population (Brønnum-Hansen, 2004) • US Veteran WWII Cohort (Wallin, 2000) • Men: median survival • Black males: 30 yrs • White males: 34 yrs • White women: median survival 43 yrs • Secular trend for improved survival over the past 50 years
Study Year of Study Region Total cases Age at onset Sex Clin course Leibowitz 1967 Israel 266 +/- + Visscher 1980 USA 941 + NS Phadke 1980 UK 1055 + NS + Riise 1986 Norway 598 + NS + Poser 1981 Germany 224/1429 + + Wynn 1984 USA 206 + + Brønnum-Hansen 1986 Denmark 6727 + + Midgard 1991 Norway 251 + NS + Wallin 1996 USA 2489 + + Risk Factors for MS Survival
MS Cause-specific mortality • MS as underlying or contributing cause of death in 47%-83% of cases (Sadovnick, 1991; Larsen, 1985) • Other causes (Brønnum-Hansen, 2004) • Cardiovascular disease: SMR 1.32 (1.22-1.43) • Cancer: SMR 0.85 (0.77-0.94) • Suicide/Accidents: 1.42 (1.22-1.64)
Conclusions • Despite a lower prevalence of MS, men are more likely to present with the PP subtype and generally have increased morbidity and mortality compared to women • Implications for clinical studies • Differential pathology by sex • Endocrine effects • More large longitudinal studies needed to evaluate sex differences in MS 9