American Heart Assn and American Stroke Assn just published 44-page, highly referenced guideline for stroke prevention in women, noting that there are both unique female risk factors (eg preeclampsia, oral contraceptives, menopause and hormone replacement) as well as other risk factors that are more common in women (obesity/metabolic syndrome, atrial fibrillation, migraine with aura). see DOI: 10.1161/01.str.0000442009.06663.48. they note:
–stroke more common in women (53.5% occur in women, with 3.8 million women and 3 million men now living after having had a stroke), and is the 3rd leading cause of death (fifth for men)
–the increased incidence in women is likely to get worse, with an aging population and increased longevity of women
–the types of stroke differ some: overall 87% of strokes are ischemic, and men have more ischemic strokes than women (the exception being in those >85yo); women have more hemorrhagic strokes (though subarach hemorrhages more often in men <55yo). women have more cerebral aneurysms, esp in the posterior communicating artery. hemorrhagic strokes highest in Asian-Americans.
–women fare worse than men, having poorer recovery after a stroke. in 2010, 60% of stroke deaths occurred in women. some of the reason for this is that women tend to be older when they have strokes
–no clear difference in delay to getting to hospital after stroke.
–hypertension is the most common modifiable risk factor, and there are epidemiologic data suggesting that women may be more likely to have htn (esp >55yo), and that for similar self-reported levels of blood pressure (eg 160/90), women are more likely to have a first stroke (OR 4.89 vs 3.88 in men). not known if women respond to specific meds differently from men, though most studies suggest that women are more likely to be treated than men, may have more adverse effects of meds and may be less likely to achieve BP control. But studies in general clearly show benefit of therapy (38% reduction in cerebrovasc disease, 25% reduction in cardiovasc). particular benefit of BP reduction in younger and black women. why the gender differences?? part may be that ovarian hormones affect blood pressure (diff sympathetic activity, vascular reactivity, water regulation through arginine vasopressin, autonomic control). there are also hormone-independent vascular differences (eg, women have smaller caliber internal carotids and typically shorter stenotic segments than men)
–prepregnancy hypertension increases risk of pre-eclampsia and stroke. in fact the strongest predictor of developing pregnancy-induced htn (PIH) is pre-existing htn, other risk factors include obesity, age>40, diabetes, renal dz, and migraine with aura. also, women with PIH are at increased risk of future htn and stroke up to 30 years after delivery. women who develop PIH should have different meds (avoid ACE-I/ARB for teratogenicity, atenolol for fetal growth restriction). women with either pre-pregnancy htn or PIH should take low-dose aspirin by 12th week gestation and calcium supplementation (through foods or pills) to achieve >1 gm/day
–central venous thrombosis (typically presents with headache, with or without neurological signs/symptoms). much more common in women (though still rarest form of stroke), esp in those 31-50yo. risk factors include hormones (oral contraceptives, pregnancy), thrombophilia
–oral contraceptives (OCs) –ischemic stroke is increased with OCs and increases with ethinyl estradiol concentration (no increase assoc with progestins). also increases with age (3.4/100K women aged 15-19 on OCs, increasing to 64.4 /100K aged 45-49), cigarette smoking, htn and migraine headaches (esp with aura, though the studies are mixed and low-dose OCs are not strictly contraindicated). also with thrombophilia (esp Factor V Leiden, but data do not support routine check for hypercoag state prior to starting OCs). OCs can increase the risk of hypertension, though get significant hypertension rarely (2% of women). in sum, risk of stroke with OCs increases in older women, and those with htn, obesity, high cholesterol, prothrombotic mutations, possibly with migraine with aura
–hormone replacement therapy (HRT) — there are a few epidemiologic studies suggesting that women with early natural menopause have increased risk of stroke, as do women with surgical menopause and not on HRT, though data mixed. the studies of HRT and stroke are mostly negative, though in the WHI (women’s health initiative) study, only women who started HRT >20 yrs after menopause had increased stroke risk. not surprisingly, transdermal estrogens seem to do better than oral (avoids first-pass hepatic metabolism and inducement of hepatic vitamin-K dependent clotting factors). bottom line: not use HRT in primary or secondary stroke prevention
–risk factors more common in women:
–migraine with aura: prevalence 4.4%, 4x higher in women. risk of stroke, though low (4/10K women with migraine), is higher in women than men with migraine with aura. esp in women who also smoke.
–obesity, metabolic syndrome, lifestyle: obesity/metabolic syndrome more common in women (35.2 vs 32%), with highest freq in non-hispanic black women (49.6% in 2008). NHANES data even worse: 61.8% vs 43.7%. up to 58.9% of premenopausal women have abdominal obesity. women (and men) with obesity have a graded increased stroke risk with increasing BMI or with increasing waist circumference, even after adjusting for other risk factors. metab syndrome in NHANES data found in 36.1% of men and 32.4% of women, but there is a higher stroke risk in women than men (??why). studies of lifestyle change have often found that women are less likely to maintain the intervention than men (?if lifestyle changes suggested in the studies should more tailored to women)
–atrial fibrillation (AF). common. assoc with 4-5x risk of ischemic stroke. similar incidence of AF in men and women, but since AF increases with age, 60% of people with AF and stroke who are older than 75yo are women. but female sex in AF is an independent predictor of stroke risk (eg Swedish study of >65yo: stroke in 6.2%/yr in women and 4.2% in men), and is incorporated into several of the risk stratification tools (eg CHA2DS2-VASc). warfarin may be more protective in women than men. also, women may be more prone to bleeding with dabigatran than men: women have 30% higher blood levels for a given dose. the AHA does not recommend anticoag in women <65yo with AF alone, just antiplatelet therapy
–depression and psychosocial stress: antecedant depression or psychosocial stress assoc with increased stroke incidence, and both conditions more common in women
–there needs to be lots more research on women and stroke, including developing an accurate tool to assess stroke risk in women
so, this guideline is the first one specific to women and stroke. some of the increased stroke risks in women are directly hormone-related (endogenous or exogenous), and some to differing physiology from men. it is clear from other literature that there are often differences between men and women, as noted above with size of carotid arteries, and that assumptions that the physiology, pathophysiology or therapy (nonpharmacologic or meds) are the same in men and women is not necessarily true. for example, in terms of cardiovascular disease, women are more likely to have silent MIs, more likely to have a false-positive stress test, not have chest pain as a presenting symptom for MI (more often presenting with shortness of breath or weakness, for example), and are more likely to have microvascular cardiac disease (which can manifest itself as acute coronary syndrome or even MI, but with normal coronary arteries). also, in terms of primary prevention of vascular disease with ASA, men have fewer cardiac events and women (esp >65yo) have fewer strokes. so, perhaps the most striking thing about this guideline is the remarkable deficiency in systematic studies assessing the specific pathophysiology and therapy for women, esp in terms of risk factors, and is a call-to-action for more studies.
geoff