StrokeStroke
John C. StevensonEditor: Martin Birkhäuser
StrokeStroke
• Ischemic (thrombotic/embolic) – 86%
• Hemorrhagic– Intracerebral
10%– Subarachnoid 4%
Female stroke prevalenceFemale stroke prevalenceUSA females, 2004USA females, 2004
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100
200
300
400
500
20–39 40–59 60–79 80+
Age (years)
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www.americanheart.org
Copyright ©2006 American Heart Association
Ischemic stroke by raceIschemic stroke by race
Hendrix SL. et al. Circulation 2006;113:2425–34
0.04
0.03
0.02
0.01
0.00
0.04
0.03
0.02
0.01
0.00
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Time (years) Time (years)
0 1 2 3 4 5 6 7 8 0 1 2 3 4 5 6 7 8
CEECEE Placebo
CEECEE Placebo
Whites Blacks
Number at riskCEE Placebo 4075 4019 3963 3898 3835 3767 3401 2201 1111CEE 4007 3940 3898 3843 3786 3725 3348 2125 1037
835 821 812 801 784 773 687 472 242782 766 754 738 725 717 648 421 192
Female stroke mortalityFemale stroke mortalityUK females, 2004UK females, 2004
0
5
10
15
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25
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< 35 35–44 45–54 55–64 65–74 > 75
Age (years)
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www.heartstats.org
Female stroke mortality (USA)Female stroke mortality (USA)
• Third leading cause of death in USA
• Rates strongly age-related:– 50–59 years: 0.6–0.8/1000 women/year– 60–64 years: ~2/1000 women/year– 65–74 years: 4.2/1000 women/year– 75–87 years: 11.3/1000 women/year
Bushnell CD. Stroke 2006;37:2387–99Rothwell PM. Lancet 2004;363:1925–33
Increased stroke riskIncreased stroke risk
• Age
• History/family history– Prior stroke, TIA, MI– Atrial fibrillation
• Gender– Incidence greater in
males– Mortality greater in
females
• Hypertension
• Smoking
• Diabetes mellitus
• Arterial disease– Carotid,
peripheral, coronary
• Lifestyle– diet, exercise
HRT and stroke: current usersHRT and stroke: current users
0 1 2
Rosenberg
Pedersen
Pettiti
Paganini-Hill
Grodstein
Relative risk
Paganini-Hill A. Maturitas 2001;38:243–61
HRT and strokeHRT and strokeNurses Health StudyNurses Health Study
• Ischemic stroke RR 1.13 (CI 0.90–1.41)– (total 142) RR 1.26 (CI 1.00–1.61)
adjusted
• Hemorrhagic stroke RR 0.89 (CI 0.62–1.27)– (total 50) RR 0.93 (CI 0.64–1.34)
adjusted• Dose effect – significant increase with CEE
≥ 0.625 mg
• No duration effect over > 10 years
Grodstein, et al. Ann Intern Med 2000;133:933–41
HRT and strokeHRT and strokeRandomized clinical trialsRandomized clinical trials
• HERS RR 1.1 (CI 0.9–1.5)
• WEST RR 1.1 (CI 0.8–1.4)
• WHI (ischemic) RR 1.4 (CI 1.1–1.9)
• WHI (hemorrhagic) RR 0.8 (CI 0.4–1.6)
• WHI (E alone) RR 1.4 (CI 1.1–1.8)
Hulley, et al. J Am Med Assoc 1998;280:605–13; Viscoli, et al. N Eng J Med 2001;345:1243–49 Wassertheil-Smoller, et al. J Am Med Assoc 2003;289:2673–84
Women’s Health Initiative Steering Committee. J Am Med Assoc 2004;291:1701–12
Risk of stroke with HRT in the WHIRisk of stroke with HRT in the WHI
• No significant increase in risk of cerebral vascular accidents in WHI studies in the 50–59-year cohort
• E + P HR 1.46 (0.43–1.56)1
• E alone HR 1.09 (0.59–2.21)2
1Wassertheil-Smoller, et al. J Am Med Assoc 2003; 2Hendrix, et al. Circulation 2006
General population of women ages 50–59 years
First-year CHD and vascular events with HT use in First-year CHD and vascular events with HT use in 2 trials of 2 trials of younger postmenopausal womenyounger postmenopausal women and expected and expected
annual rates in women in the USA and Europeannual rates in women in the USA and Europe
Lobo R, Arch Intern Med 2004;164:482–4
1.9
3.01
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1
2
3
4
5
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0.80.56
0.84
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0.28
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General populationPlacebo groupHRT group
SERMs and strokeSERMs and strokeRandomized clinical trialsRandomized clinical trials
• Tamoxifen RR 1.82 (CI 1.41–2.36) (meta-analysis)
• Raloxifene RR 1.15 (CI 0.93–1.41) (RUTH)
Bushnell & Goldstein. Neurology 2004;63:1230–33 Barrett-Connor, et al. N Engl J Med 2006;355:125–37
Stroke preventionStroke prevention
• Low-dose aspirin
• Blood pressure control
• Lipid lowering– Diet ± statins, fibrates, etc.
• Lifestyle measures– Low saturated fat/low salt diet– Physical activity– Smoking cessation
• Avoid high-dose HRT– ? Use low-dose non-oral HRT if necessary
HRT and stroke:HRT and stroke: Misperceptions Misperceptions
• The risk of both venous and arterial thromboembolism is increased during HRT
• Stroke risk is substantially increased in women receiving HRT
IMS Global Summit 2008. Climacteric 2008;11:267–72
HRT and stroke:HRT and stroke:EvidenceEvidence
• It is unclear at present whether there is a statistical increase in ischemic stroke with standard HRT in healthy women aged 50–59
• The WHI data showed no statistically significant increase in risk; nevertheless, even if statistically increased, as found in the Nurses’ Health Study, the low prevalence of this occurrence in this age group makes the attributable risk extremely small
IMS Global Summit 2008. Climacteric 2008;11:267–72
• Safety data from studies of low-dose and ultra-low-dose regimens of estrogen and progestogen are encouraging
Climacteric 2007;10:181–96
HRT: cerebrovascular eventsHRT: cerebrovascular events