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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www.americanheart.org

Copyright ©2006 American Heart Association

Ischemic stroke by raceIschemic stroke by race

Hendrix SL. et al. Circulation 2006;113:2425–34

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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

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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

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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

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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