so1o42019 ‘Overview of secondary prevention of ischemic stoke - UpToDate Upto Date’ Official reprint from UpToDate® \www.uptadate.com ©2019 UpToDate, Inc. and/or its affiliates. All Rights Reserved. 2d. Wolters Kluwer Overview of secondary prevention of ischemic stroke Authors: Karen L Furie, MD, MPH, Natalia S Rost, MD, MPH Section Editor: Scott E Kasner, MD Deputy Editor: John F Dashe, MD, PhD All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Mar 2019. | This topic last updated: Nov 22, 2017. INTRODUCTION The management of treatable risk factors and common mechanisms of brain ischemia is important for reducing the risk of ischemic stroke. This topic will review the risk factors for stroke, with a focus on secondary prevention in patients who have a history of transient ischemic attack or ischemic stroke, or are considered to have a high risk of ischemic stroke due to the presence of coronary heart disease or diabetes. Risk factors for hemorrhagic stroke are reviewed elsewhere. (See "Spontaneous intracerebral hemorrhage: Pathogenesis. cinical features, and diagnosis". section on Risk factors’ and ‘Risk factors) The role of primary prevention for cardiovascular disease, including stroke, is discussed ‘separately. (See “Overview of primary prevention of coronary heart disease and stroke") RISK FACTORS AND MECHANISMS The major modifiable risk factors for stroke are the following [1-4] Hypertension Diabetes mellitus Smoking Dyslipidemia Physical inactivity ‘Two important mechanisms of ischemic stroke are amenable to effective secondary prevention: Iitpsslwwnsuptodate.comicontents/overview-of-secondary-prevertion-oFischemicstoke/prin’?search=acidente vascular cerebral8topicRef=111.... 1/22toos2019 COvarviw of saondary prevarton of ichemi Hoke -UsTeDae * Atrial fibrillation + Carotid artery stenosis Important but unmodifiable risk factors for stroke include age, ethnicity, sex, family history, and genetics [3,5-8]: + Older age, particularly age >80 years [3] + Race and ethnicity, with risk higher for blacks than for whites [8] * Sex, with risk higher at most ages for men compared with women, except for ages 35 to 44 years and >85 years, where women have a similar or higher risk than men [9,10] + Family history and genetic disorders, with a higher risk for monozygotic twins and those with genetic disorders (see "Pathophysiology of ischemic stroke", section on ‘Monogenic disorder such as sickle cell disease or cerebral autosomal dominant arteriopathy with subcortical infarctions and leukoencephalopathy [5-71 The risk of stroke is particularly increased in patients with two or more risk factors, as suggested by calculators (calculator 1 and calculator 2) derived from the Framingham Study [11]. These risk factor assessment tools incorporate atrial fibrillation, a common cause of ischemic stroke, and the presence of coronary heart disease and other types of cardiovascular disease (table 1), which are markers of increased risk for subsequent cardiovascular and cerebrovascular events. When all of these risk factors and stroke mechanisms are considered together, they account for 60 to 80 percent of the population-attributable risk of ischemic stroke [2] Control of atherosclerotic risk factors is important for the primary and secondary prevention of stroke. Control of risk factors also reduces the risk of coronary events, a common comorbidity in patients with cerebrovascular disease, (See "Overview of primary prevention of coronary heart disease and stroke" and "Overview of the prevention of cardiovascular di vents in th Hypertension — Hypertension, which promotes the formation of atherosclerotic lesions, is the single most important treatable risk factor for stroke [4]. + Epidemiologic studies of treated and untreated patients reveal that there is a gradually increasing incidence of cardiovascular mortality as the blood pressure rises above 110/75 mmHg (figure 1A-B) [12,13]. + Hypertension is associated with an increased likelihood of subclinical or silent stroke, which in turn has been linked with an elevated risk of vascular dementia and recurrent stroke [14-16] * In addition to hypertension defined by systolic and diastolic blood pressure, stroke risk may be associated with other blood pressure variables including mean blood pressure, pulse hips slwwn.uptodate.comicontents/overview-of-secondary-prevertion-oFischemic-stoke/prin?search=acidente vascular cerebral8topicRef=111..._ 2/22toos2019 COvarviw of saondary prevarton of ichemi Hoke -UsTeDae pressure, blood pressure variability, blood pressure instability, and nocturnal nondipping (17,18) However, these observations alone do not prove a causal relationship, since increasing blood pressure could be a marker for other risk factors such as increasing body weight, dyslipidemia, glucose intolerance, and the metabolic syndrome. The best evidence supporting a causal role of increasing blood pressure in cardiovascular complications comes from studies that show outcome reduction in the risk of recurrent stroke with antihypertensive therapy. This evidence is reviewed elsewhere. (See "Antihypertensive therapy to prevent recurrent stroke or transient ischemic attack.) Smoking — Cigarette smoking is associated with an increased risk for all stroke subtypes and has a strong, dose-response relationship for both ischemic stroke and subarachnoid hemorrhage 19-25]. + Inthe Nurses’ Health Study, smokers had a relative risk of stroke of 2.58 compared with never ‘smokers [20]. Evaluation of former smokers found that the excess risk disappeared within two to four years after the cessation of smoking + In the Framingham Heart Study, the odds ratio for moderate carotid stenosis was 1.08 for each five pack-years of smoking [22] + Among 10,938 normotensive subjects in a prospective Swedish cohort study, about 39 percent of strokes were attributable to smoking [23]. There are no randomized controlled trials of smoking cessation for stroke prevention. However, observational studies have shown that the elevated risk of stroke due to smoking declines after quitting and is eliminated by five years later [20,24,26]. Therefore, American Heart Association/American Stroke Association (AHA/ASA) guidelines recommend smoking cessation for patients with stroke or transient ischemic attack who have smoked in the year prior to the event and suggest avoidance of environmental tobacco smoke [27]. (See "Overview of smoking ) cessation management in adults’, Diabetes mellitus — Patients with diabetes mellitus have approximately twice the risk of ischemic stroke compared with those without diabetes [28-32]. In addition, the risk of stroke associated with diabetes is higher in women than in men [32]. Dyslipidemia, endothelial dysfunction, and platelet and coagulation abnormalities are among the risk factors that may promote the development of carotid atherosclerosis in diabetics. (See "Prevalence of and risk factors for coronary heart disease in diabetes meliitus".) Impaired glucose tolerance may be a risk factor for ischemic stroke in patients with a history of transient ischemic attack (TIA) or minor ischemic stroke [33]. It may also be a risk factor for carotid Iitpsslwwn.uptodate.comicontents/overview-of-secondary-prevertion-oFischemic-stoke/prin!?search=acidente vascular cerebral8topicRef=111.... 3/22so1o42019 ‘Overview of secondary prevention of ischemic stoke - UpToDate atherosclerosis, as illustrated by studies in nondiabetics showing that elevated serum hemoglobin, AIC is associated with an increased risk of carotid plaque development [34,35] Dyslipidemia — Hyperlipidemia is a major risk factor for coronary heart disease (see "Overview of established risk factors for cardiovascular disease"). However, the relationship between the serum cholesterol concentration and stroke incidence appears to be more complex, in that cholesterol is an established risk factor for atherosclerosis, but the degree of risk varies for stroke subtypes [36]. Studies that have examined ischemic and hemorrhagic stroke types have generally found a weak but positive association of elevated cholesterol with ischemic stroke, particularly for large artery atherosclerotic and lacunar stroke subtypes, and an inverse association of cholesterol levels with hemorrhagic stroke. The strong association between cholesterol and carotid atherosclerosis also supports the role of cholesterol in the pathogenesis of large artery ischemic stroke [37] The association of dyslipidemia and ischemic stroke risk is illustrated by the following observations: * Most [38-41] but not all [42,43] large observational studies have found that elevated cholesterol and LDL levels are associated with an increased risk of ischemic stroke [36] + Ina prospective study that compared cases of ischemic stroke (n = 1242) and hemorrhagic stroke (n = 313) with controls (n = 6455), elevated total cholesterol and lower high-density lipoprotein (HDL) levels were associated with an increased risk of ischemic stroke, especially for large artery atherosclerotic and lacunar stroke subtypes [44]. The study excluded nonhypertensive males, limiting the strength of the findings + Ameta-analysis of lipid-lowering therapy found that dietary or drug intervention (fibrates and resins) other than statins did not significantly reduce the risk of stroke in subjects with elevated cholesterol levels [45]. * Some [46-48], but not all [42, hypertriglyceridemia is a risk factor for ischemic stroke. 9,50], observational studies suggested that The relationship of cholesterol levels and statin therapy with intracerebral hemorrhage is discussed in greater detail separately. (See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis", section on ‘Risk factors.) While treatment with statins decreases the risk of recurrent ischemic stroke in patients with hyperlipidemia, the available evidence suggests that lipid lowering by other means (eg, fibrates, bile acid sequestrants, niacin, diet) has no significant impact on the secondary prevention of stroke or prevention of other cardiovascular events. (See "Low density lipoprotein cholesterol lowering with drugs other than statins and PCSK9 inhibitors" and “Lipid lowering with diet or Iitpsslwwnsuptodate.comicontents/overview-of-secondary-prevertion-oFischemic-stoke/prin?search=acidente vascular cerebral8topicRef=111... 4/2201042019 ‘Overview of secondary prevetion of scheme stoke - UpToDate dietary supplements" and "Management of low density lipoprotein cholesterol (LDL-C) in the secondary prevention of cardiovascular disease”.) Physical inactivity — Increasing evidence suggests that low physical activity and prolonged sitting increases the risk of cardiovascular disease, including stroke [4,51,52]. Additional support that physical inactivity is a risk factor for stroke comes from studies showing the benefit of increased physical activity and exercise for reducing the risk of cardiovascular events [53]. Atrial fibrillation — Atrial fibrillation is the most common cause of cardioembolic ischemic stroke and is amenable to effective secondary prevention with anticoagulation. (See “Atrial fibrillation ) Risk of embolization" and "Stroke in patients with atrial fibrillation". Large and small vessel disease — The risk of ischemic stroke due to symptomatic carotid artery stenosis can be effectively treated with revascularization combined with intensive medical management. (See "Management of symptomatic carotid atherosclerotic disease".) The mainstay of secondary prevention of ischemic stroke or TIA caused by large vessel (other than carotid artery stenosis) and small vessel cerebrovascular disease is intensive medical management, including treatment with antiplatelet agents, antihypertensive drugs, statins, and lifestyle modification as discussed below. (See ‘Interventions’ below.) Others — In addition to the traditional stroke risk factors, myriad other risk factors and pathologic mechanisms are associated with ischemic stroke [54]. * Alcohol intake — Alcohol affects the risk of stroke in different directions depending upon level of consumption, type of stroke, and possibly ethnicity. Light drinking (one to two drinks per day) is associated with a reduced risk of ischemic stroke, while heavy drinking is associated with an increased risk. (See "Cardiovascular benefits and risks of moderate alcohol consumption", section on 'Stroke risk’,) + Cardiac disease — While atrial fibrillation is the most common cause of cardioembolic stroke (see ‘Atrial fibrilla stroke risk include a history of myocardial infarction, left ventricular dysfunction, valvular bove), additional conditions potentially associated with an increased disease, left ventricular thrombus, atrial septal defects, and complex atheroma in the ascending aorta or proximal arch. (See "Etiology, classification, and epidemiology of stroke" cerebral emboli in adults".) + Fibrinogen — Plasma fibrinogen is associated with the risk of stroke and cardiovascular disease and may act by several possible mechanisms, including promotion of atherogenesis and inflammation, elevation of blood and plasma viscosity, increased platelet aggregability, and increased tendency to form fibrin within thrombus. Elevated fibrinogen levels appear to correlate with vulnerable atherosclerotic plaque characteristics, including thinning of the hitpsslwwnsuptodate.comicontents/overview-of-secondary-prevertion-oFischemic-stoke/prin!?search=acidente vascular cerebral&topicRef=111..._ 5/2201042019 ‘Overview of secondary prevetion of scheme stoke - UpToDate fibrous cap of atheroma predisposing to rupture, and to increased plaque inflammation [55] (see "Pathophysiology of symptoms from carotid atherosclerosis"). However, it is not established that elevated fibrinogen is an independent risk factor for carotid atherosclerosis progression, as some evidence suggests it is rather a nonspecific marker of inflammatory activity [56] + Hypercoagulability - Hypercoagulable states can increase the risk of transient ischemic attack and stroke (see “Overview of the evaluation of stroke", section on ‘Hypercoagulable studies’). + The antiphospholipid syndrome is a known cause of venous and arterial thrombosis or thromboembolism, including ischemic stroke, as reviewed elsewhere. (See "Clinical ndrome" and "Treatment of anti jospholipid syndrome”.) + Inherited thrombophilias are hypercoagulable states that include a number of disorders: Protein C deficiency ~ Protein S deficiency ~ Antithrombin deficiency ~ Activated protein C resistance ~ Factor V Leiden as a cause of activated protein C resistance + Prothrombin G20210A mutation + Methylenetetrahydrofolate reductase (MTHFR) mutations associated with hyperhomocysteinemia Although inherited thrombophilias are clearly linked to venous thrombosis, it remains unclear if they predispose to arterial thromboembolism and stroke in adults; the evidence linking them to ischemic stroke in children is somewhat stronger. (See “Overview of the evaluation of stroke", section on 'Hypercoagulable studies’ and "Ischemic stroke in children and young adults: Etiology and clinical features”, section on ‘Hematologic’.) + Hyperhomocysteinemia — Increased serum homocysteine concentrations are associated with an increased risk of coronary and cerebrovascular disease, as discussed separately (see "Overview of homocysteine"). Elevated homocysteine appears to be associated with an increased risk of the large artery subtype of ischemic stroke, and possibly to the small artery subtype; it does not appear to be associated with cardioembolic or other stroke subtypes [57,58]. Unfortunately, there is evidence from several clinical trials that treatment with homocysteine-reducing vitamins is not beneficial for secondary prevention of cardiovascular disease or stroke [27]. * Infection — Although not established as stroke risk factors, some reports have found an increased risk of stroke associated with certain infectious agents and conditions, including hitpsslwwn.uptodate.comicontents/overview-of-secondary-prevertion-oFischemic-stoke/prin!?search=acidente vascular cerebral&topicRef=111..._ 6/22so1o42019 ‘Overview of secondary prevention of ischemic stoke - UpToDate cytomegalovirus, herpes simplex virus, chlamydia pneumonia, helicobacter pylori, legionella species, and periodontal disease [2]. + Inflammation — Mounting data suggest that inflammation plays a role in atherosclerosis and contributes to stroke risk. C-reactive protein (CRP) concentration is associated with the long- term risk of cardiovascular events, including ischemic stroke, as confirmed by a meta-analysis of 54 prospective studies and individual records from over 160,000 subjects without a history of vascular disease [59]. While elevated CRP levels could be used as an additional marker of increased stroke risk, there are no randomized clinical trial data to support the hypothesis that lowering CRP levels will lead to reduced stroke risk, Furthermore, appropriate critical thresholds of CRP elevation and optimal timing of CRP measurements in the setting of acute cerebral ischemia have not been established [60]. Therefore, we do not recommend routinely checking CRP levels for primary or secondary ischemic stroke prevention. Leukocyte counts and neutrophil counts were associated with ischemic events including stroke, myocardial infarction, and vascular death in a high-risk population [64]. In the week before the recurrent event, the leukocyte count was significantly increased over baseline levels. However, treatment with aspirin or clopidogrel did not modify the predictive effects of elevated leukocyte counts. An independent association of leukocyte count elevation with increased ischemic stroke risk was also found among stroke-free participants in a prospective, longitudinal, cohort study (the Northern Manhattan Study) [62]. (See "C-reactive protein in cardiovascular disease" and "Acute phase reactants".) + Lipid-related factors — Lipoprotein (a) [Lp(a)] is a modest independent risk factor for atherosclerotic cardiovascular disease and cerebrovascular events. In addition, several reports have found an association between lipoprotein-associated phospholipase A2 activity and ischemic stroke [63-65]. The treatment of excess Lp(a) is speculative, as discussed separately. (See "! .oprotein ).and cardiovascular disease".) + Metabolic syndrome — The metabolic syndrome, defined as the presence of three or more components that include high fasting glucose, hypertension, low serum HDL, elevated serum triglycerides, and abdominal obesity, is considered to be a prediabetic condition linked to increased risk of cardiovascular disease. (See "The metabolic syndrome (insulin resistance syndrome or syndrome X)".) However, itis unclear if the metabolic syndrome is an independent risk factor for ischemic stroke beyond the sum of its individual components, and the available evidence is conflicting [66-74]. Furthermore, the utility of the metabolic syndrome to predict stroke risk does not appear to improve upon more conventional assessments such as the Framingham Risk Score [69]. (See "Cardiovascular disease risk assessment for primary prevention: Risk calculators".) Although the metabolic syndrome is not clearly established as an independent stroke risk factor, it is important to treat the underlying causes such as obesity and physical inactivity. hitpsslwwn.uptodate.comicontents/overview-of-secondary-prevertion-oFischemic-stoke/prin!?search=acidente vascular cerebral8topicRef=111.... 7/22sonos2019 Overview of secondary prevention of ischemic stroke - UpToDate Management should include counseling for lifestyle modification (diet, exercise, and weight loss) and appropriate treatment for individual components of the metabolic syndrome, particularly hypertension and dyslipidemia, which are also stroke risk factors [27]. (See ‘Hypertension’ above and ‘Dyslipidemia’ above and "The metabolic syndrome (insulin resistance syndrome or syndrome X)", section on ‘Therapy'.) + Obesity — Obesity is associated with an increased risk of stroke, as discussed separately. (See “Overweight and obesity in adults: Health consequences”, section on ‘Stroke’ and “Comorbidities and complications of obesity in children and adolescents", section on ‘Cardiovascular’.) + Sleep-related breathing disorders — Patients with obstructive sleep apnea (OSA) appear to be at increased risk of having a stroke. It is unknown whether patients with central sleep apnea syndrome, including Cheyne-Stokes breathing, also have an increased risk. Limited data suggest that the presence of sleep-related breathing disorders following a stroke may be a marker of a poorer long-term outcome. Positive airway pressure (PAP) therapy and behavioral modifications are the mainstays of treatment for patients diagnosed with sleep-related breathing disorders, This is reviewed elsewhere. (See "Sleep-related breathing disorders and stroke".) + Radiotherapy — Head and neck radiotherapy for cancer treatment may lead to a delayed vasculopathy of large and small vessels mediated by endothelial damage, fibrosis, and accelerated atherosclerosis [75-77]. Radiotherapy-related occlusive disease is often diffuse and occurs in uncommon locations, in contrast to the typical focal lesions that develop at vessel bifurcations from atherosclerosis in the absence of radiation. Depending on the site and dose of radiation, the involved vessels may include the extracranial carotid and vertebral arteries and the intracranial circle of Willis vessels [75,78]. This process may lead to symptomatic carotid disease, moyamoya syndrome, and ischemic stroke. (See "Moyamoya disease: Etiology, clinical features, and diagnosis", section on ‘Associated conditions’ and "Management of late complications of head and neck cancer and its treatment", section on ‘Carotid artery injury’) INTERVENTIONS Most patients with an ischemic stroke or transient ischemic attack (TIA) should be treated with all available risk reduction strategies. Currently viable strategies include blood pressure reduction, statin therapy, antithrombotic therapy, and lifestyle modification [27]; select patients with symptomatic carotid disease may benefit from revascularization. By some estimates, treatment of all major stroke risk factors, compared with no treatment, would reduce the risk of recurrent stroke by 80 percent [79]. hitpsslwwn.uptodate.comicontents/overview-of-secondary-prevertion-oFischemic-stoke/prin!?search=acidente vascular cerebral&topicRef=111..._ 8/22sonos2019 Overview of secondary prevention of ischemic stroke - UpToDate Antihypertensive therapy — In accordance with American Heart Association/American Stroke Association (AHA/ASA) guidelines, we recommend resumption of antihypertensive therapy for previously treated patients with known hypertension for both prevention of recurrent stroke and prevention of other vascular events [27]. In addition, we recommend initiation of antihypertensive therapy for patients with any type of ischemic stroke or TIA who have an established blood pressure 2140 mmHg systolic or 290 mmHg diastolic. Unlike the 2014 AHA/ASA guidelines, we suggest (a weaker recommendation) initiation of antihypertensive therapy for previously untreated patients with ischemic stroke or TIA of atherothrombotic, lacunar (small vessel occlusive), or cryptogenic type, whose baseline blood pressure is >120 mmHg systolic or >70 mmHg diastolic. However, we do not suggest antihypertensive therapy for nonhypertensive patients (ie, blood pressure <130/80 mmHg) who have had an ischemic stroke or TIA due to a cardioembolic phenomenon (eg, atrial fibrillation). The role of antihypertensive therapy in secondary stroke prevention is discussed in detail separately. (See "Antihypertensive therapy to prevent recurrent stroke or transient ischemic attack") In patients with acute ischemic stroke (je, the first hours and days after onset), it is important not to lower the blood pressure too quickly. The management of blood pressure in the setting of acute stroke is reviewed elsewhere. (See “Initial ment and management of acute stroke", section on ‘Blood pressure management’,) Lifestyle modifications that have been associated with blood pressure reductions should be included as part of the antihypertensive regimen [27]. Important modifications include weight loss, salt restriction, a diet rich in fruits, vegetables, and low-fat dairy products, regular aerobic physical activity, and limited alcohol consumption. (See ‘Lifestyle modification’ below.) Antithrombotic therapy — With the major exception of patients with atrial fibrillation, where anticoagulation is superior to aspirin, randomized clinical trials have found no statistically significant difference between aspirin and anticoagulant therapy for reducing the risk of recurrent ischemic stroke [80]. However, the risk of major hemorrhage is higher with warfarin than with aspirin + Since antiplatelet agents are effective for the prevention of recurrent ischemic stroke in patients with a history of noncardioembolic ischemic stroke or TIA of atherothrombotic, lacunar (small vessel occlusive), or cryptogenic type, nearly all such patients should be treated with an antiplatelet agent. Aspirin (50 to 100 mg daily), clopidogrel (75 mg daily), and the combination of aspirin-extended-release dipyridamole (25 mg/200 mg twice a day) are all acceptable options for preventing recurrent noncardioembolic ischemic stroke, (See hitpsslwwn.uptodate.comicontents/overview-of-secondary-prevertion-oFischemicstoke/prin!?search=acidente vascular cerebral8topicRef=111..._ 9/2201042019 Overview of secondary prevention of ischemic stroke - UpToDate + Long-term anticoagulation with warfarin, dabigatran, apixaban, or rivaroxaban should be considered as prevention for patients with chronic nonvalvular atrial fibrillation who have had an ischemic stroke or transient ischemic attack. However, the use of anticoagulant therapy is also associated with an increased risk of major bleeding. While the benefit outweighs the risk in most patients, careful consideration of the risk to benefit ratio is necessary in those at relatively low risk. These issues are discussed elsewhere. (See “Atrial fibrillation: event thromboemb¢ Anticoagulant therapy to | + Antithrombotic therapy is the main treatment for patients with ischemic neurologic symptoms caused by cervical artery dissection, The choice between aspirin and anticoagulation in this setting remains somewhat controversial. (See "Spontaneous cerebral and cervical artery, dissection: Treatment and prognosis", section on ‘Antithrombotic therapy’. * In addition to atrial fibrillation, other potential cardiac sources of embolism for which anticoagulation therapy may be indicated for select patients include the following (see "Secondary prevention for specific causes of ischemic stroke and transient ischemic attack", section on ‘Cardiogenic embolism’): Mechanical heart valves and a subpopulation of high-risk patients with bioprosthetic valves (see "Antithrombotic therapy for prosthetic heart valves: Indications") + Left ventricular thrombus (see “Antithrombotic therapy in patients with heart failure", section on ‘Left ventricular thrombus’ and "Left ventricular thrombus after acute myocardial infarction", section on ‘Prevention of embolic events') + Dilated cardiomyopathy (see “Antithrombotic therapy in patients with heart failure") + Rheumatic valve disease (see "Management and prevention of rheumatic heart disease", section on ‘Management of carditis in acute rheumatic fever’) + Recent myocardial infarction in high-risk patients (see "Anticoagulant therapy in non-ST and "Anticoagulant therapy in acute ST elevation elevation acute coronary syndrome: infarction" and "Chronic anticoagulation after acute coronary syndromes’ Statin therapy — In patients with hyperlipidemia, treatment with HMG CoA reductase inhibitors (statins) decreases the risk of stroke, while lipid lowering by other means (eg, fibrates, resins, diet) has no significant impact on stroke incidence [45,81]. Therefore, it seems plausible that the protective effects of statins are not mediated by cholesterol lowering (82), but by anti- atherothrombotic properties [83]. Long-term treatment with statins reduces the risk of ischemic stroke, even though hypercholesterolemia is not a strong risk factor for stroke. An explanation for this apparent paradox is becoming clear as we continue to learn more about the mechanism of benefit of statins. In addition to their cholesterol lowering properties, statins also have a role in plaque hitpsslwwnsuptodate.comicontents/overview-of-secondary-prevertion-oFischemic-stoke/prin?search=acidente vascular cerebral8topicRef=11..._ 10/22sonos2019 Overview of secondary proventon of ischamic stroke - UpToDate stabilization, reducing inflammation, slowing carotid arterial disease progression [84-86] improving endothelial function, and reducing embolic stroke by prevention of myocardial infarction and left ventricular dysfunction. (See "Mechanisms of benefit of lipid-lowering drugs in patients with coronary heart disease") For patients with TIA or ischemic stroke of atherosclerotic origin who are able to tolerate statins, we suggest high-intensity statin therapy, independent of the baseline low-density lipoprotein cholesterol (LDL-C), to reduce the risk of stroke and cardiovascular events [87]. We suggest treating with atorvastatin 80 mg/day, since this was the agent and dose used in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial that showed a benefit for secondary ischemic stroke prevention, (See ‘Randomized trials’ below and "Statins: Actions, side effects, and administration’.) A similar approach is recommended for patients with coronary heart disease and other types of cardiovascular disease (table 1). (See "Overview of the prevention of cardiovascular disease section on prevention of cardiovascular disease".) For patients who are intolerant of high-intensity statin therapy, alternatives are moderate-intensity statin therapy (eg, atorvastatin 10 to 20 mg daily, rosuvastatin 5 to 10 mg daily, simvastatin 20 to 40 mg daily, pravastatin 40 to 80 mg daily, lovastatin 40 mg daily, or fluvastatin 40 mg daily in two divided doses) or low-intensity statin therapy (eg, pravastatin 10 to 20 mg daily or lovastatin 20 mg daily) if tolerated [87]. For patients with ischemic stroke or TIA who are intolerant of even low-intensity statin therapy, we suggest treatment with another class of lipid lowering agent. (See "Management of low density lipoprotein cholesterol (LDL-C) in the secondary prevention of cardiovascular disease" and "Low poprotein cholesterol lowering with drugs other than statins and PCSK9 inhibitors".) den: Randomized trials — Statins reduce the risk of both initial and recurrent stroke. This conclusion is supported by the following observations: + Ameta-analysis of randomized controlled trials with more than 165,000 participants published through December 2008 evaluated statin treatment in combination with other preventive strategies for all stroke (ischemic and hemorrhagic), including both primary and secondary prevention [88]. Compared with control assignment, statin treatment reduced the risk of all stroke by 18 percent (95% Cl 13-23 percent). In the only trial (SPARCL) designed to evaluate statins for secondary stroke prevention, atorvastatin significantly reduced the risk of noncardioembolic recurrent stroke, as discussed below. + A subsequent meta-analysis reviewed the literature through January 2011 and found that statins significantly reduced the risk of major cerebrovascular events (ie, fatal and nonfatal hitpsslwwn.uptodate.comicontents/overview-of-secondary-prevertion-oFischemic-stoke/prin!?search=acidente vascular cerebral&topicRef=11.... 11/22sonos2019 Overview of secondary proventon of ischamic stroke - UpToDate strokes and transient ischemic attacks) compared with controls, both in patients with established cerebrovascular disease (odds ratio [OR] 0.83, 95% Cl 0.75-0.91) and in those without prior cerebrovascular disease (OR 0.80, 95% Cl 0.71-0.91) [89] + The SPARCL trial was the first to show that statin treatment decreased the risk of recurrent ischemic stroke among patients with a history of stroke or TIA [20]. The trial randomly assigned 4731 ambulatory patients with no known coronary heart disease (CHD) who had a stroke or TIA within one to six months to treatment with either atorvastatin 80 mg/day or placebo. Patients were required to have a baseline LDL-C of 100 to 190 mg/dL (2.6 to 4.9 mmol/L). The mean baseline LDL-C and total cholesterol levels were about 133 and 212 mg/dL (3.4 and 5.5 mmol/L), Patients with hemorrhagic stroke were included if they were deemed to be at risk for ischemic stroke or CHD. Patients were excluded if they had atrial fibrillation, other cardiac sources of embolism, or subarachnoid hemorrhage. At a median follow-up of 4.9 years, the following observations were noted for atorvastatin treatment compared with placebo [20]: + Atorvastatin led to a mean reduction in LDL-C of 56 mg/dL (1.4 mmol/L). + Atorvastatin reduced fatal or nonfatal stroke, the primary endpoint (11.2 versus 13.1 percent, adjusted hazard ratio [HR] 0.84, 95% C! 0.71-0.99, absolute risk reduction at five years 2.2 percent, 95% Cl 0.2-4.2 percent). + Atorvastatin led to a reduction in all coronary events (5.2 versus 8.6 percent, HR 0.58, 95% Cl 0.46-0.73) and all cardiovascular events (22.4 versus 29 percent, HR 0.74, 95% CI 0.66-0.83). + There was no difference between the atorvastatin and placebo groups in overall mortality. Taken together, these and other findings showed that statin therapy substantially reduced ischemic stroke risk, regardless of age, gender, or pretreatment blood lipid concentration (see ‘UU vascular events among people who had a previous stroke. despite normal cholestero!' below). Furthermore, statin therapy reduced the risk of major Utility despite normal cholesterol — Even patients with "average" serum cholesterol concentrations appear to benefit from statin therapy in terms of stroke reduction. This was demonstrated in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial [20], where the mean baseline LDL-C and total cholesterol levels were 133 and 212 mg/dL. (3.4 and 5.5 mmol/L), respectively, and in the Heart Protection Study (HPS) trial [91], where the mean baseline LDL-C and total cholesterol levels were 131 and 224 mg/dL (3.4 and 5.8 mmol/L), respectively. Benefit with statin treatment was also seen in the CARE trial, which included 4159 patients with a history of a myocardial infarction in the previous two years who had mean LDL-C and total hitps ww. uptodate.comlcontents/overview-of-secondary-prevention-ofschemic-strokelprint?search=acidente vascular cerebral8topicRef=11.... 12122sonos2019 Overview of secondary proventon of ischamic stroke - UpToDate cholesterol serum concentrations of 139 and 209 mg/dL (3.6 and 5.4 mmol/L), respectively [22). In addition to a reduction in coronary events, therapy with pravastatin led to significant reductions in the frequency of stroke (2.6 versus 3.8 percent) and of stroke plus transient ischemic attacks (4.4 versus 6.0 percent) A similar reduction in stroke was noted with atorvastatin (10 mg) in the ASCOT-LLA trial that looked at high-risk patients with hypertension but relatively normal cholesterol levels who did not have coronary heart disease [93]. The rate of fatal and nonfatal stroke was significantly lower with atorvastatin than placebo (5.4 versus 7.4 events per 1000 patient-years). It should be noted that the mechanism of stroke was poorly characterized in several of these trials. Itis possible that reducing the risk of myocardial infarction reduced the risk of cardioembolic. stroke. The investigators did not prove that statins had an impact upon the rate of large vessel atherothrombotic or lacunar infarcts. Glycemic control — For patients with ischemic stroke or TIA, the 2014 AHA/ASA guidelines recommend screening for diabetes mellitus with testing of fasting plasma glucose, hemoglobin AIC, or an oral glucose tolerance test [27]. For patients with diabetes and ischemic stroke or TIA, the AHAJASA recommends the use of guidelines from the American Diabetes Association for glycemic control and blood pressure targets [27]. (See "Glycemic control and vascular complications in type 1 diabetes mellitus" and "Glycemic control and vascular complications in type 2 diabetes mellitus", section on ‘Glycemic targets'.) For patients with diabetes who have had an ischemic stroke or TIA, we suggest glucose control to near normoglycemic levels. This recommendation is based on evidence that tight glucose control reduces microvascular complications. Diet, exercise, oral hypoglycemic drugs, and insulin are proven methods to achieve glycemic control. A reasonable goal of therapy is an A1C value of <7 percent for most patients. However, the available evidence has not demonstrated a consistent beneficial effect of intensive glucose-lowering therapy or lifestyle modification for macrovascular outcomes (eg, stroke and death) in patients with type 2 diabetes. These issues are discussed in detail elsewhere: (Se (See "Glycemic control and vascular complications in type 2 diabetes mellitus", section on ") /cemic control and vascular complications in type 1 diabetes mellitus", ‘Microvascular disease'.) (See "Glycemic control and vascular complications in type 2 diabetes mellitus", ‘!Macrovascular disease’.) (See “Initial management of blood glucose in adults with type 2 diabetes mellitus.) ection on Treatment of insulin resistance — Although data are limited, disordered glucose metabolism appears to be common among nondiabetic patients with ischemic stroke or TIA [94]; one small study found a prevalence of 50 percent on the basis of an abnormal oral glucose tolerance test hitpsslwwn.uptodate.comicontents/overview-of-secondary-prevertion-oFischemic-stoke/prin?search=acidente vascular cerebral8topicRef=11.... 19/22sonos2019 Overview of secondary prevention of ischemic stroke - UpToDate [25]. Pioglitazone treatment appears to reduce the risk of recurrent stroke and myocardial infarction in nondiabetic patients who have insulin resistance, though this benefit is partially offset by an increased risk of adverse effects such as bone fracture. These points are illustrated by the findings of the multicenter IRIS trial, which randomly assigned over 3800 subjects with recent ischemic stroke or TIA and insulin resistance to treatment with pioglitazone (target dose 45 mg daily) or placebo [96]. The trial defined insulin resistance as a value of >3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index, calculated as the level of fasting glucose (measured in mmoles/L) times the level of fasting insulin (measured in microU/mL) divided by 22.5. Patients with diabetes, heart failure, or active liver disease were excluded. The following outcomes were reported [96]: + At 4.8 years, the primary composite outcome of stroke or myocardial infarction was significantly reduced in the pioglitazone group compared with the placebo group (9.0 versus 11.8 percent, hazard ratio [HR] 0.76, 95% Cl 0.62-0.93); the absolute risk reduction with pioglitazone for the composite outcome was 2.8 percent. + Several adverse effects were significantly more common with pioglitazone compared with placebo, including bone fracture requiring surgery or hospitalization (5.1 versus 3.2 percent), edema (36 versus 25 percent), and weight gain exceeding 4.5 kg (52 versus 34 percent). + There was no difference between groups in the incidence of heart failure (the pioglitazone dose was adjusted for symptoms such as new or worsening edema, shortness of breath, or excessive weight gain during the trial). However, there is good evidence from other studies that thiazolidinediones increase the risk of heart failure. (See "Heart failure in diabetes mellitus", section on 'Thiazolidinediones' and "Thiazolidinediones in the treatment of diabetes mellitus", section on ‘Fluid retention/heart failure’ Based upon the results of the IRIS trial [96], the number needed to treat (NNT) with pi prevent one patient from developing stroke or myocardial infarction is 36, while the number needed to harm (NNH) to cause one patient to develop bone fracture requiring hospitalization is 53. Given the benefit of pioglitazone in this setting, it is an option for carefully selected nondiabetic patients with insulin resistance who are willing to accept the risk of adverse events such as bone fracture and heart failure. Since there is no validated test for measuring insulin resistance in clinical practice, clinicians should emulate the IRIS methodology as closely as possible by calculating the HOMA-IR index using laboratories that adapt the IRIS trial assays for plasma insulin level. Lifestyle modification — A number of behavioral and lifestyle modifications may be beneficial for reducing the risk of ischemic stroke and cardiovascular disease [27,97]. These include smoking cessation, limited alcohol consumption, weight control, regular aerobic physical activity, salt hitpsslwwn.uptodate.comicontents/overview-of-secondary-prevertion-oFischemic-stoke/prin?search=acidente vascular cerebral&topicRef=11.... 14/22toos2019 COvarviw of saondary prevarton of ichemi Hoke -UsTeDae restriction, and a Mediterranean diet (see ‘Diet’ below). Our recommendations are in concordance with the national guidelines [27] Smoking cessation — All patients who are recent or current tobacco smokers should be counseled routinely to quit smoking. (See ‘Smoking’ above and "Overview of smoking cessation management in adults".) Alcohol consumption — All patients with ischemic stroke or TIA who are heavy drinkers should eliminate or reduce their alcohol consumption because of the increased risk of stroke and high morbidity associated with alcoholism, despite the lack of clear evidence from clinical trials that reduction of alcohol intake decreases the risk of recurrent stroke [27]. (See "Cardiovascular benefits and risks of moderate alcohol consumption”, section on ‘Stroke risk’ and 'sychosocial treatment of alcohol use disorder" and "Pharmacotherapy for alcohol use disorder" and "Screening rief intervention for unhealthy aleohol and other drug use: Efficacy, adverse effects, and administration’.) Physical activity and exercise — For patients with ischemic stroke or TIA who are capable of regular exercise, we suggest moderate to vigorous intensity physical exercise most days of the week for at least 40 minutes, Moderate intensity exercise is defined as activity sufficient to break a sweat or noticeably raise the heart rate (eg, walking briskly, using an exercise bicycle) [27]. (See “The benefits and risks of aerobic exercise", section on ‘Benefits of exercise'.) Diet — Emerging evidence suggests that dietary interventions, and in particular a Mediterranean diet (see "Healthy diet in adults", section on ‘Mediterranean diet), improves ‘outcomes in patients with established cardiovascular disease. Until further studies evaluate the magnitude of benefit of a Mediterranean diet, it is reasonable to advise all patients to adhere to its components. Our recommendations are consistent with the 2013 American Heart Association/American College of Cardiology (AHA/ACC) guideline on lifestyle management to reduce cardiovascular risk (see "Overview of the prevention of cardiovascular di vents in those with (secondary prevention) or at high risk", section on ‘Diet’) [98] and the 2014 AHA/ASA guideline for stroke prevention in patients with stroke or TIA [27]: + For patients with a history of stroke or TIA, we suggest encouraging patients to follow a Mediterranean-type diet that emphasizes the intake of vegetables, fruits, whole grains, low-fat dairy products, poultry, fish, legumes, nontropical vegetable oils, and nuts. It limits the intake of sweets, sugar-sweetened beverages, and red meats. Calories from saturated fat should be limited to 5 to 6 percent and calories from trans fat should be reduced. + For patients who would benefit from blood pressure lowering, a reduction in sodium (no more than 2400 mg per day) is also suggested. hitpsslwwn.uptodate.comicontents/overview-of-secondary-prevertion-oFischemic-stoke/prin'?search=acidente vascular cerebral8topicRef=11.... 15/22sonos2019 Overview of secondary prevention of ischemic stroke - UpToDate Supplementation with beta-carotene, vitamin E, and vitamin C, either alone or in combination with each other or other antioxidant vitamins does not appear to be effective in the primary or secondary prevention of cardiovascular disease. The data supporting these conclusions are reviewed elsewhere. (See "Nutritional antioxidants in atherosclerotic cardiovascular disease". ) Fish oil (omega-3 fatty acids) consumption lowers serum triglyceride concentrations and appears to decrease the proportions of small dense LDL particles while increasing HDL-C levels. Observational evidence suggests that fish consumption may reduce the risk of ischemic stroke, but there is no convincing evidence from randomized trials that fish consumption or fish oil supplementation either increases or decreases the risk of stroke, The evidence regarding fish oil intake and ischemic stroke risk is discussed in detail separately. (See "Fish oil and marine omega- 3 fatty acids", section on 'Stroke'.) Weight reduction — As with glycemic control, the available data do not show that weight reduction reduces the risk of recurrent stroke [27]. However, weight reduction for obese patients is potentially beneficial for improved control of other important parameters, including blood pressure, blood glucose, and serum lipid levels. Thus, the 2014 AHA/ASA guidelines for stroke prevention recommend screening all patients with stroke or TIA for obesity with measurement of body mass index [27]. (See "Obesity in adults: Overview of management’.) Revascularization — Revascularization of the cervical internal carotid artery with endarterectomy or stenting is beneficial for patients with recently symptomatic internal carotid artery atherosclerotic disease, as reviewed elsewhere. (See "Management of symptomatic carotid atherosclerotic disease".) There is no proven benefit of revascularization for patients with large vessel atherothrombotic disease in anterior and posterior cerebral circulation sites other than the cervical internal carotid artery. (See "Secondary prevention for specific causes of ischemic stroke and transient ischemic attack", section on ‘Large artery disease’ and "Intracranial large artery atherosclerosi ) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately, (See "Society guideline links: Stroke in adults".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5"" to 6" grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to- hitpsslwwnsuptodate.comicontents/overview-of-secondary-prevertion-oFischemic-stoke/prin?search=acidente vascular cerebral8topicRef=11.... 16/22sonos2019 Overview of secondary prevention of ischemic stroke - UpToDate read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10" to 12"" grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients, (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) * Basics topics (see "Patient education: Stroke (The Basics)" and "Patient education: Medicines after an ischemic stroke (The Basics)" and "Patient education: Lowering the risk of having another stroke (The Basics)") the Basics)") SUMMARY AND RECOMMENDATIONS. + The major treatable atherosclerotic stroke risk factors are hypertension, diabetes, smoking, and dyslipidemia. Common causes of ischemic stroke amenable to treatment include atrial fibrillation and carotid artery stenosis. Myriad additional factors may influence the risk of stroke. (See ‘Risk factors and mechanisms’ above.) + Most patients with an ischemic stroke or transient ischemic attack (TIA) should be treated with all available risk reduction strategies. Currently viable strategies include blood pressure reduction, antithrombotic therapy, statin therapy, and lifestyle modification; select patients with symptomatic cervical internal carotid artery disease may benefit from revascularization. (See ‘Interventions’ above.) + For previously treated patients with known hypertension who are beyond the first few days after stroke onset, we recommend resumption of antihypertensive therapy. For patients previously untreated with antihypertensive therapy who are beyond the first few days after stroke onset, we make the following recommendations (see ‘Antihypertensive theraj above): + For patients with ischemic stroke or TIA of any type who have an established blood pressure 2140 mmHg systolic or 290 mmHg diastolic, we recommend initiation of antihypertensive therapy (Grade 1A). + For patients with ischemic stroke or TIA of atherothrombotic, lacunar (small vessel occlusive), or cryptogenic type, and an established blood pressure >120 mmHg systolic or >70 mmHg diastolic, we suggest initiation of antihypertensive therapy (Grade 2C), hitpsslwwn.uptodate.comicontents/overview-of-secondary-prevertion-oFischemic-stoke/prin!?search=acidente vascular cerebral8topicRef=11.... 17/22toos2019 COverviw of secondary prevention ofischemic stoke - UpToDate + We do not suggest antihypertensive therapy for nonhypertensive patients (ie, blood pressure <130/80 mmHg) who have had a stroke or TIA due to a cardioembolic phenomenon (eg, atrial fibrillation). + Nearly all patients with TIA or ischemic stroke of atherosclerotic origin should be treated with an antiplatelet agent. The combination of aspirin-extended-release dipyridamole, clopidogrel alone, or aspirin alone are all acceptable options for initial therapy. Long-term anticoagulation should be considered as prevention for patients with chronic nonvalvular atrial fibrillation who have had an ischemic stroke or transient ischemic attack. While the benefit outweighs the risk in most patients, careful consideration of the risk to benefit ratio is necessary in those at relatively low risk, (See ‘Antithrombotic therapy’ above.) + For patients with TIA or ischemic stroke of atherosclerotic origin who are able to tolerate statins, we suggest high-intensity statin therapy, independent of the baseline low-density lipoprotein cholesterol (LDL-C), to reduce the risk of stroke and cardiovascular events (Grade 2B), We suggest treating with atorvastatin 80 mg/day, since this was the agent and dose used in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial that showed a benefit for secondary ischemic stroke prevention, For patients who are intolerant of high-intensity statin therapy, altematives are moderate-intensity statin therapy (eg, atorvastatin 10 to 20 mg daily, rosuvastatin 5 to 10 mg daily, simvastatin 20 to 40 mg daily, pravastatin 40 to 80 mg daily, lovastatin 40 mg daily, or fluvastatin 40 mg daily in two divided doses) or low-intensity statin therapy (eg, pravastatin 10 to 20 mg daily or lovastatin 20 mg daily). For patients with ischemic stroke or TIA who are intolerant of even low-intensity statin therapy, we suggest treatment with another class of lipid lowering agent. (See ‘Statin therapy" above.) + For patients with diabetes who have had an ischemic stroke or TIA, we suggest glucose control to near normoglycemic levels (Grade 2C), * Anumber of behavioral and lifestyle modifications may be beneficial for reducing the risk of ischemic stroke and cardiovascular disease (see ‘Lifestyle modification’ above): + Allpatients who are recent or current tobacco smokers should be counseled routinely to quit smoking. + Patients who are heavy drinkers should eliminate or reduce alcohol consumption. + For patients with ischemic stroke or TIA who are capable of regular exercise, we suggest moderate to vigorous intensity physical exercise for at least 40 minutes most days of the week + For patients with ischemic stroke or TIA, we suggest a Mediterranean diet that emphasizes intake of vegetables, fruits, and whole grains. In addition, for patients who hitpsslwwn.uptodate.comicontents/overview-of-secondary-prevertion-oFischemic-stoke/prin!?search=acidente vascular cerebral8topicRef=11..._ 18/22so1o42019 ‘Overview of secondary prevention of ischemic stoke - UpToDate would benefit from blood pressure lowering, we suggest restricting sodium intake to no more than 2400 mg per day. + Weight reduction for obese patients is potentially beneficial for improved control of blood pressure, blood glucose, and serum lipid levels. Use of UpToDate is subject to the Subscription and License Agreement. Topic 1120 Version 53.0 hitpsslwwn.uptodate.comicontents/overview-of-secondary-prevertion-oFischemicstoke/prin!?search=acidente vascular cerebral8topicRef=11..._ 19/22so1o42019 ‘Overview of secondary prevention of ischemic stoke - UpToDate GRAPHICS Known cardiovascular ease and similar risk Patients with the following are at high risk for a second (or first) cardiovascular disease event Coronary heart disease Myocardial infarction Angina Coronary revascularzation Cerebrovascular disease Stroke Transient Ischemic attack Peripheral arterial disease Multiple risk factors that confer a 10-year risk of CVD >20% Chronic kidney disease with estimates GFR <45 mL/min per 1.73 m2* CVD: cardiovascular disease; GFR: glomerular filtration rate. * Statin doses may require adjustment in patients with chronic kidney disease. Graphic 91576 Version 3.0 hitpsslwwnsuptodate.comicontents/overview-of-secondary-prevertion-oFischemic-stoke/prin!?search=acidente vascular cerebral&topicRef=11.... 20/22so1o42019 ‘Overview of secondary prevention of ischemic stoke - UpToDate Stroke mortality related to blood pressure and age Systolic blood pressure Diastolic blood pressure ‘Age at risk: ‘Age at risk: 256 20.89 20-09 8 years years 5 n-79 70-79 8 years % years a 64 60-69 - 60-69 8 vears years z + 50-59 50-59 Bult ve u ve 7 b i ea ' i g 1 ty bo 160 7 90 110 Usual systolic blood Usual diastolic blood Pressure, mmo Dressure, mmg Stroke mortality rate, pictured on a log scale with 95% confidence intervals (CI), in each decade of age in relation to the estimated usual systolic and diastolic blood pressure at the start of that decade, Stroke mortality increases with both higher pressures and older ages. Inores the left-hand point (ie, at slightly less than 75 mmHg), for which the risk lies significantly above the fitted regression For diastolic pressure, each age-specific regression lin line (as indicated by the broken line below 75 mmHg). Data from Prospective Studies Collaboration, Lancet 2002; 360:1903. Graphic 66793 Version 4.0 hitpsslwwn.uptodate.comicontents/overview-of-secondary-prevention-oFischemi-stoke/print?search=acidente vascul cerebral&topioRef=11, 2122so1o42019 ‘Overview of secondary aravention of ischemic stroke - UpTaDate Coronary heart disease mortality related to blood pressure and age Systolic blood pressure Diastolic blood prescure Age at risk: Age at risk: 3 256 80-89 80-89 ¢ years: years, 8 70.79 70-79 a years years » 60-69 0-69 32 years years aa 50-59 50-59 S% 16 years years Ee 40-49 40-49 9 ears pears 3s ¥ . y Bo, s * z 3 Boa L oA oo 120 150 70 90 110 Usual systolic blood Usual diastolic blood Dressure (mmiig) Dressure (mmHg) Coronary heart disease (CHD) mortality rate, pictured on a log scale with 95% confidence intervals, (CD), in each decade of age in relation to the estimated usual systolic and diastolic blood pressure at the stert of that decade, CHD mortality increases with both higher pressures and older ages. For diastolic pressure, each age-specific regression line ignores the left-hand point (ie, at slightly less than 75 mmHg) for which the risk lies significantly above the fitted regression line (as indicated by the broken line below 75 mmHg) IHD: Ischemic heart disease. Reproduced from: Lewington S, Clarke R, Qizilbash N, et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of Individual data for one milion adults in 61 prospective studles. Lancet 2002; 360:1903. Illustration used with the permission of Elsevier. All rights reserved. Graphic 75106 Version 9.0 hitps:lwwn-uptodate.comlcontents/overview-of-secondary-prevertion-ofschemic-strokelpint?search-acidente vascular cerebral8topicRef=11 2aree