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Stroke: Risk Factors and Prevention William Hewitt, M.D. Neurologist Diagnostic & Medical Clinic.

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Presentation on theme: "Stroke: Risk Factors and Prevention William Hewitt, M.D. Neurologist Diagnostic & Medical Clinic."— Presentation transcript:

1 Stroke: Risk Factors and Prevention William Hewitt, M.D. Neurologist Diagnostic & Medical Clinic

2 Risk Factors for Stroke ●90 % of strokes are attributable to modifiable risk factors. 1 ●80 % of recurrent strokes can be prevented by optimal management of risk factors 2 1.Gorelick. Stroke Prevention. Arch Neurol 1995. 2.O’Donnell et al. Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case control study. Lancet 2010

3 Modifiable and Non-modifiable risk factors Modifiable ●Hypertension ●Diabetes Mellitus ●Smoking ●Dyslipidemia ●Alcohol use ●Diet ●Physical Activity Non-modifiable ●Advanced age (>80) ●Race o Higher risk for African- Americans ●Sex o (depending on age) o Higher risk for men from ages 45-85 ●Family History ●Genetic disorders o Sickle-cell, CADASIL

4 Modifiable Risk Factors for Stroke Medical ●Hypertension ●Diabetes ●Dyslipidemia ●Obesity ●OSA Behavioral ●Smoking ●Alcohol ●Physical activity ●Diet ●Medication compliance

5 Hypertension Normal ●SBP < 120 mm Hg and ●DBP < 80 mm Hg Pre-hypertension ●SBP 120-139 mm Hg or ●DBP 80-89 mm Hg Stage I Hypertension ●SBP 140-159 mm Hg or ●DBP 90-99 mm Hg Stage II Hypertension ●SBP ≥ 160 mm Hg or ●DBP ≥ 100 mm Hg

6 Hypertension ●Most important risk factor for both ischemic and hemorrhagic stroke ●⅓ of US Adults have hypertension  (30 % may have pre-hypertension) ●Continuous linear increase in stroke risk for BP >115/75 o Also linked to increased risk of subclinical stroke & vascular dementia. ●In primary prevention, every 10-mm Hg of BP reduction is associated with a roughly ⅓ reduction in stroke risk. 1 1.Lawes et al. Stroke 2004; 35(3):776-785

7 Figure 1. Usual SBP and risk of stroke by age, with data from prospective cohort study overviews. Carlene M.M. Lawes et al. Stroke. 2004;35:776-785 Copyright © American Heart Association, Inc. All rights reserved.

8 Hypertension after stroke o Antihypertensive therapy is associated with a significant reduction of recurrent stroke risk whether the patient had hypertension or not. 1,2 o Even in patients with symptomatic intracranial stenosis, hypertension in the postacute phase is associated with increased risk of recurrent stroke. 3 o However, SBP < 120 may be associated with an increased risk of recurrent stroke vs. 120-140. 4 1.Rashid et al. Stroke 2003; 34 (11):2741-2748 2.Thompson et al. JAMA 2011;305 (9):913-922 3.Turan et al. Circulation 2007; 115(23):2969-2975 4.Ovbiagele et al. JAMA 2011; 306 (19):2137-2144

9 Blood Pressure Reduction for Secondary Stroke Prevention ●< 140/90 mm Hg in hypertensive patients ●<130/80 in patients with CKD or DM ●< 130/80 in non-hypertensive patients ●Reduce SBP by 10 mm Hg and DBP by 5 mm Hg from baseline even in non-hypertensive patients ●Ideal Goal BP may be SBP = 120-140 and DBP = 80- 90 ●Actual reduction in blood pressure is far more important than which antihypertensive agent is used.  Compliance is the key  Thiazide diuretic and ACE-I/ARB alone or in combination are reasonable first-line options. Refer to published hypertension management guidelines  JNC8 guidelines have liberalized BP reduction targets in primary prevention.

10 Blood Pressure in Acute Ischemic Stroke - (Preserve the Penumbra!) ●Low blood pressure or aggressive lowering of high blood pressure may be associated with worsening of stroke deficits in the acute setting. IV fluid boluses or pressors may needed if blood pressure is low. ●In patients not receiving thrombolysis, permissive hypertension (up to 220/120 if tolerated) is recommended in the first 24 hours ●BP should be maintained below 180/105 during and after IV thrombolysis ●Gradual lowering of blood pressure (10-15% per 24 hours) is recommended.

11 Blood Pressure in Spontaneous Intracerebral Hemorrhage ●Balance risks of elevated BP (hematoma expansion, re- bleeding, vasogenic edema) with potential loss of cerebral perfusion o CPP = MAP - ICPNormal ICP = 5 to 15 mm Hg ●Ischemic penumbra hypothesis - lacks empirical support ●Consider monitoring intracranial pressure if: o GCS ≤8 o Clinical evidence of transtentorial herniation o Significant intraventricular hemorrhage o Hydrocephalus

12 Blood Pressure in Spontaneous Intracerebral Hemorrhage Guidelines (limited data) 1 If no evidence of elevated ICP  Target MAP < 110 or BP <160/90 ● For SBP> 200 or MAP > 150 - continuous IV infusion & monitor closely (q5 minute BP checks) ● For SBP> 180 or MAP > 130 - Intermittent vs. continuous IV medication with frequent (q15 minute) clinical assessments If possible elevated ICP and SBP > 180 or MAP > 130 ●Consider monitoring ICP and titrating IV infusion to target CPP 60 - 80 1.Guidelines for Management of Spontaneous Intracerebral Hemorrhage. Stroke. 2010; 41 (9): 2108

13 Diabetes Mellitus ●Doubles the risk of ischemic stroke o 19 million diabetic adults in USA (HgbA 1c >6.5%) - 8% of adults o 90 million with pre-diabetes ●Strong risk factor for first stroke and for recurrent lacunar stroke 1 ●Intensive glycemic control (HgbA 1c < 6.5%) failed to show benefit for secondary stroke prevention. 2 1 Mast et al. Hypertension and diabetes mellitus as determinants of multiple lacunar infarcts. Stroke. 1995; 26(1):30-33 2 Skyler at al. Circulation 2009; 119(2):351-357

14 Diabetes Mellitus ●Target HgbA 1c < 7% 1 o diet o exercise o oral hypoglycemic drugs o insulin o less stringent A 1c goals may be appropriate in certain patients ●Agressive treatment of BP (<130/80) and lipids (LDL<70) associated with reduced stroke risk in diabetics 2 1 Executive summary: standards of medical care in diabetes–2009. Diabetes Care. 2009;32(suppl 1):S6–S12. 2 UKPDS (BMJ 1998) and CARDS (Lancet 2004)

15 ●Risk factor for stroke in general and strong risk factor for atherothrombotic stroke with a dose-response relationship, i.e. heavier smoking = higher risk 1 o After 5 years of cessation, stroke risk returns to level of nonsmokers ●Passive smoking may increase stroke risk 2 ●Goal: Complete cessation of smoking and avoidance of environmental smoke exposure 1 Wolf et al. Cigarette smoking as a risk factor for stroke. The Framingham Study. JAMA 1988: 259 (7):1025-1029 2 He at al. Passive smoking and risk of peripheral artery disease and ischemic stroke in Chinese women who never smoked. Circulation 2008; 118(15):1535-1540. (Risk of ischemic stroke in women exposed to 20+ passive cigarettes per day was nearly double that of non-smokers.) Cigarette Smoking

16 Dyslipidemia ●About ¼ of adults in USA have elevated serum cholesterol ●Elevated LDL levels have been associated with increased ischemic stroke risk ●HDL and triglyceride levels have not been associated with stroke risk. ●Associations with stroke are not as clear as for CAD or PAD. (probably due to heterogeneity of stroke)

17 Dyslipidemia ●LDL lowering has been shown to reduce risk of stroke o Every 39 points of LDL lowering reduced relative risk of stroke by 21% in meta-analysis of primary and secondary prevention trials 1 ●SPARCL randomized patients with recent (within 6 months) stroke or TIA, LDL of 100-190, and no CAD to 80 mg of atorvastatin vs. placebo o 2.2 % absolute risk reduction (16% RRR) for stroke over 5 years o 3.4 % absolute risk reduction for coronary events o No difference in mortality 1 Amarenco et al. Lipid management in the prevention of stroke: Lancet Neurol 2009 2 Amarenco et al. HIgh-dose atorvastatin after stroke or transient ischemic attack. NEJM 2006

18 Dyslipidemia ●Initiate statin therapy in stroke patients with atherosclerosis, history of CAD (or equivalent), or LDL >100 o Target 50 % reduction in LDL or LDL < 70 o Recheck every 6 weeks until target is reached, then every 6-12 months  High-dose statin therapy may be preferred for those < 75 and those who tolerate it. ●Non-statin lipid lowering drugs have not shown the same benefits for secondary stroke prevention ●Niacin may have benefit in patients with low HDL ●Fibrates are of unclear benefit in stroke prevention

19 Alcohol ●Heavy drinking is a risk factor for all types of stroke. Alcohol causes dependence and is associated with a host of health problems. ●Risk of ischemic stroke is lower for light to moderate drinkers than for abstainers, but rises sharply beyond moderate use. 1,2 ●Lowest risk group for ischemic stroke:(<2 drinks per day in men and <1 drink per day in women.) ●All-cause mortality rises sharply (J-curve) 3 1 Sacco et al. The protective effect of moderate alcohol consumption on ischemic stroke. JAMA 1999 2 Reynolds et al. Alcohol consumption and risk of stroke: a meta-analysis. JAMA 2003 3 Di Castelnuovo et al. Meta-analysis of wine and beer consumption in relation to vascular risk. Circulation. 2002 Jun 18;105(24):2836-44

20 The J-curve

21 Alcohol - What to do? ●Encourage heavy drinkers to moderate their alcohol intake. ●Counsel about increased risks of stroke with heavy drinking and educate about what constitutes heavy drinking. ●Recommendations: o Men: Reduce to two or fewer drinks per day o Nonpregnant women: Reduce to one or fewer drinks per day. o Drinkers who are not able to conform to these guidelines should be encouraged to abstain. o Non-drinkers should not be encouraged to start.

22 Physical Activity ●Beneficial effects on multiple stroke risk factors ●Although beneficial effects have been demonstrated in primary prevention, good data are lacking on therapeutic exercise for secondary prevention of stroke. ●Structured programs of therapeutic exercise after stroke have been shown to improve function and not to cause harm. Recommendation: At least 30 minutes moderate intensity exercise 3 times per week (breaking a sweat) - preferably most days of the week.

23 Diet - Dietary Approaches to Stop Hypertension (DASH) ●Modification of dietary components to reduce blood pressure o salt restriction o increased consumption of fresh fruit, vegetables, and low-fat dairy o reduced animal protein ●Higher DASH adherence has been associated with lower risk for stroke. 1 1 Fung et al. Adherence to a DASH-style diet and risk of coronary heart disease and stroke in women. Arch Intern Med 2008

24 Mediterranean Diet ●Several studies have suggested benefit for cardiovascular health and better outcomes in patients with cardiovascular disease. 1 Emphasizes:  Vegetables and fruits  Whole grains  Low-fat dairy  poultry, fish, legumes  olive oil, nuts  Red wine 1 Estruch et al. Primary prevention of cardiovascular disease with a Mediterranean diet. NEJM 2013. (Compared Mediterranean diet with low-fat diet for primary prevention in patients with diabetes or multiple other vascular risk factors and showed significant risk reduction in composite vascular outcome and even greater risk reduction for stroke alone.) Limits:  Red meat  Sweets  Sugary drinks

25 Obstructive Sleep Apnea ●OSA is associated with several conditions which increase stroke risk (elevated BP, cardiomyopathy, atrial fib.) ●Sleep-disordered breathing is an independent risk factor for stroke and may increase the risk of post-stroke morbidity and mortality ●Stroke may also cause sleep apnea ●Treatment of OSA with CPAP has not been evaluated for reduction in recurrent stroke risk or post-stroke mortality. ●Screening for OSA among stroke survivors is suggested.

26 Obesity ●Obesity (BMI > 30kg/m 2 ) associated with premature death and vascular disease ●Weight loss not shown to reduce risk of recurrent stroke ●However weight loss may improve BP, blood glucose, and lipids Recommendation: Goal BMI 18.5-25 kg/m 2

27 Antithrombotic Therapy Antiplatelet agents ●Aspirin (ASA) ●Clopidogrel ●Aspirin/dipyridamole Anticoagulants ●Warfarin ●Heparin ●Novel oral anticoagulants (rivaroxaban, dabigatran, apixaban)

28 Antithrombotic Therapy in Ischemic Stroke and TIA (short term) Aspirin should be given within 48 hours ●1% reduction in stroke over first 2 weeks 1, 2 ●ASA (160-325 mg) should be given as early as possible, i.e. in the ED if not receiving thrombolysis. ●In patients who receive thrombolytic therapy, aspirin is begun after 24 hours if brain imaging shows no hemorrhagic transformation. ●For TIA or minor stroke (NIHSS ≤ 3), ASA plus clopidogrel may be superior. 3 1 CAST - Lancet 1997 (20k patients in 400+ Chinese stroke centers) 2 IST - Lancet 1997 (20k patients in 36 countries) 3 Wang et al. Clopidogrel with Aspirin in Acute Minor Stroke or Transient Ischemic Attack. NEJM 2013. (5k patients in 100+ Chinese stroke centers)

29 Antithrombotic Therapy in Ischemic Stroke and TIA Atrial fibrillation (AF) ●Oral anticoagulation is clearly more effective than antiplatelet therapy for secondary stroke prevention o Warfarin with target INR 2-3 o Novel oral anticoagulants ●Anticoagulation may delayed a few weeks in patients at high risk for hemorrhagic transformation (large infarcts or imaging evidence of hemorrhage). ●In patients with clear contraindications to anticoagulation, antiplatelet therapy may be used but is significantly less effective than warfarin. LAA closure or occlusion may also be an option.

30 Other Sources of Cardioembolic Stroke Valvular disease ●Infective endocarditis ●Nonbacterial thrombotic endocarditis o Marantic endocarditis, Libman-Sacks endocarditis ●Prosthetic valves Cardiomyopathy (EF<30%) ●Antiplatelet agents vs. Warfarin ●Benefit of warfarin not established Myocardial infarction with left ventricular thrombus Atrial tumors Aortic arch atherosclerosis

31 Carotid Artery Disease Symptomatic ●Highest risk in first month after stroke or TIA ●Benefit of revascularization declines over time ●Revascularization within 2 weeks of stroke or TIA Asymptomatic ●Intensive medical therapy can achieve very low stroke rates (<1% per year) ●Consider revascularization for men < 75, only if complication rates are very low

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