Acute stroke, hematocrit, and blood pressure.

Marc Fisher MD Kennedy Lees MD Section Editors: Hypertension is the most important modifiable risk factor for stroke.1,2 It is estimated that 25% or more of strokes may be attributable to hypertension. Because many patients with stroke have mild hypertension or prehypertension, we have shifted our focus and now think of stroke on a continuum of risk based on blood pressure (BP) level rather than on a threshold effect.3 Because high BP may not exist in isolation, a wider definition of hypertension has been proposed that also takes into account the absolute risk of cardiovascular events and associated metabolic factors or early disease markers.3 Lowering BP reduces the risk of stroke. Epidemiological studies have shown that for each 10 mm Hg lower systolic blood pressure (SBP), there is a decrease in risk of stroke of approximately one third in persons aged 60 to 79 years. This association is continuous down to levels of at least 115/75 mm Hg and is consistent across sexes, regions, stroke subtypes, and for fatal and nonfatal events.4 Lowering diastolic blood pressure (DBP) was once the main target to achieve stroke and other cardiovascular event reduction, but SBP has now become the target.3 As recently shown, even the elderly with sustained SBP elevation may gain from BP reduction in relation to less fatal or nonfatal stroke, death, and heart failure.5 Although the role of longer-term BP control to improve outcomes in patients with stroke is undisputed, BP management immediately after a stroke remains controversial. In an effort to resolve this controversy, several pilot clinical trials have been initiated. In this review, we discuss the results of some of these trials and available evidence-based guidelines for BP control in the settings of acute ischemic and hemorrhagic stroke (excluding subarachnoid hemorrhage) and …

The increasing use of ambulatory blood pressure monitoring (ABPM) devices in the investigation of hypertension has allowed detailed study of the circadian rhythm of blood pressure variability, the assessment of resistant hypertension, and the syndrome of “white coat” hypertension. The relevance of ABPM to target-organ damage and the complications of hypertension, such as heart attacks and strokes, has only recently gained prominence. There are more than 30 cross-sectional studies that have linked ABPM to hypertensive target-organ damage, including left ventricular hypertrophy (LVH),1 2 microalbuminuria,3 hypertensive retinal changes, and cerebrovascular disease.4 The majority of these studies have consistently reported that patients with an absent or reduced fall in blood pressure at night (referred to as “nondippers”) have more severe target-organ damage, including LVH5 and cerebrovascular disease,4 6 when compared with patients who demonstrate a normal nocturnal fall in blood pressure. For example, Verdecchia et al,7 in a prospective cohort of over 1100 hypertensive patients, reported higher mortality rates both in nondippers and “reverse dippers” and higher cardiovascular morbidity rates in female nondippers compared with dippers.8 In addition, Yamamoto et al9 recently reported that progressive cerebrovascular disease, including silent ischemic lesions and symptomatic stroke, was associated with a reduced nocturnal blood pressure fall in patients with a history of lacunar infarction. In a cross-sectional study of patients admitted with acute stroke (ictus <12 hours), Lip at al10 reported that such patients could generally be classed as nondippers, with higher blood pressures recorded using ABPM (but not using casual manual measurements) in black/Afro-Caribbean patients and also in patients with hemorrhagic stroke. These studies therefore suggest the potential usefulness of ABPM in epidemiological, cohort, or cross-sectional studies and the assessment of ethnic differences, stroke subtypes, and prognosis. A nondipper status …

BackgroundElevated blood pressure is frequently seen in acute stroke, and patients with lacunar and nonlacunar infarcts may have different underlying mechanisms for increase in blood pressure. The impact of hypertension as a risk factor may also vary. The aims of the present study were to investigate blood pressure in patients presenting with lacunar syndromes but with different anatomical subtypes of stroke, to explore the impact of subtype on blood pressure, and to identify stroke-related factors associated with hypertension.MethodsConsecutive patients presenting with an acute lacunar syndrome were enrolled. Patients were classified into a lacunar or nonlacunar group based on radiological verified infarcts. Blood pressure was measured. Between-group differences were analyzed by χ2-test, t-test, and Mann–Whitney U test, as appropriate. We performed linear regression to analyze the association between blood pressure and lacunar infarct, and multiple linear regression to adjust for other covariates.ResultsOne hundred thirteen patients were included. Seventy five percent had lacunar and 25% nonlacunar infarcts. There was no significant difference in clinical severity between the two groups. In the linear regression model, we found a significant association between blood pressure and lacunar infarct. No other factor was significantly associated with blood pressure in the two groups.ConclusionsLacunar infarcts may be independently associated with higher blood pressure compared to nonlacunar infarcts with the same clinical severity. Blood pressure differences between different subtypes of stroke may not be related to clinical severity but to the underlying cause of stroke.

d’Esterre, CD1, 3 Qazi, E1, 3 Patil, S1, 3 Almekhlafi, M3, 1 Lee, T2, 3 Demchuk, A1, 3 Goyal, M1, 3 Menon, B1, 3; 1. University of Calgary, Calgary, AB; 2. University of Western Ontario, London, ON; 3. Calgary Stroke Program, Calgary, AB Background : For ischemic stroke, CT Perfusion (CTP) may change thrombolytic/endovascular treatment decisions when compared to NCCT/CTA alone. Two distinct thresholds may be useful in this regard: separation of 1) non-salvageable tissue (infarct core) from salvageable electrically silent tissue (penumbra), and 2) penumbra from benign oligemia (hypoperfused, but will survive if clot persists). Methods : CTP (120s,8cm) was performed on 180 patients within 12hrs of ischemic stroke. Two patient cohorts were analyzed: (1) recanalization (TICI 2b,3) 6s. For group (2) CBF, CBV, and Tmax values were obtained from within the final infarct region, and total ipsilateral hemisphere, excluding infarction. CBF, CBV and Tmax were used in univariate regression models. Results : For group (1)[n=11], mean time from CTP to recanalization was 60±19min. CBF parameter (thresholds for gray and white matter 7.2 and 5.2 ml•min-1•(100g)-1) had the highest sensitivity (90.9%) and specificity (81.8%) for infarction. For group (2)[n=15], the Tmax parameter (thresholds for gray and white matter 11.3s and 11.8s) had the highest sensitivity (86.6%) and specificity (80.0%) for penumbra. Conclusion : Knowing the status of recanalization within 90mins of CTP allows for accurate delineation of infarct core, as …

### Case A 68-year-old right-hand-dominant man was brought to the hospital because of a speech disturbance and right arm and leg weakness. He awoke with these deficits and was last known to be symptom-free when retiring to bed the previous evening 8 hours earlier. His past medical history was notable for coronary heart disease, the patient having underwent coronary artery bypass surgery 7 years previously for unstable angina, but he had no known history of myocardial infarction. He also had hypertension and hyperlipidemia, and smoked 1 pack of cigarettes daily for more than 40 years. He had no history of calf claudication. His hypertension was being treated with a diuretic and β-adrenergic receptor blocker. He was also prescribed 325 mg of aspirin daily and an HMG CoA-reductase inhibitor (statin); however, his wife remarked that he often forgot to take his medications. His last total cholesterol was 240 mg/dL, with LDL cholesterol of 130 mg/dL. He had a strong family history of coronary heart disease after the age of 50. He had no known drug allergies. #### Physical Examination The patient’s blood pressure was 195/100 mm Hg in both arms, with a regular pulse of 90 bpm. His weight was 225 lb (body mass index: 31.4 kg/m2). His lungs were clear to auscultation. Cardiac examination showed a laterally displaced point of maximum impulse with an S4 gallop and a soft nonradiating systolic murmur at the base. His abdomen was obese without organomegaly and no abdominal bruits were detected. He had no rashes and no joint deformities. The left superficial temporal artery pulse was stronger than the right. There were soft bilateral anterior cervical bruits, left louder than right, but no supraclavicular bruits. There were bilateral femoral bruits. Radial pulses were 2+ and symmetric. Dorsalis pedis and posterior tibial pulses were 1+. …

Hypertension is highly prevalent in the United States and worldwide. In the United States, 1 in 3 adults (≈73 million people) have hypertension. The financial and human costs of hypertension are substantial. The estimated costs attributable to hypertension in the United States alone in 2010 were $70 billion direct costs for medical treatments and $24 billion indirect costs because of lost productivity.1 Awareness and treatment of hypertension have improved considerably during the past several decades: >80% of all people with hypertension are aware of the condition and 75% are using antihypertensive medications.2,3 However, despite enormous effort and treatment-related expenditures, only 53% of those with documented hypertension have their blood pressure controlled.3 Older age (Figure 1), left ventricular hypertrophy, and obesity are important risk factors for uncontrolled or drug-resistant hypertension.4 Importantly, the foregoing are also risk factors for increased aortic stiffness.5 Figure 1. Hypertension prevalence and control rates as a function of age in the National Health and Nutrition Examination Survey 2003 to 2004. Data derived from Wong et al.44 During the past 2 decades, measures of aortic stiffness have emerged as important risk factors for progression of blood pressure and incident cardiovascular disease. Carotid femoral pulse wave velocity (CFPWV), a measure of aortic wall stiffness, increases markedly with age, particularly after midlife. For example, Framingham Heart Study investigators have shown that the prevalence of CFPWV ≥12 m/s increases from a few percentage before 50 years of age to ≥60% after 70 years of age (Figure 2A). Importantly, elevated CFPWV is associated with high risk for incident hypertension (Figure 2B) and cardiovascular disease (Figure 2C). Figure 2C should be interpreted within the context that a normal value (<95th percentile) for CFPWV in a healthy Framingham Heart Study reference sample <50 years of age was 8.1 …

In hypertensive populations, increasing blood pressure (BP) levels and BP variability (BPV) are associated with a greater incidence of target organ damage. After stroke, elevated 24-hour BP levels predict a poor outcome, although it is uncertain whether shorter-length BP recordings assessing mean BP levels and BPV have a similar predictive role. The objectives of this study were to compare the different measures of beat-to-beat BP and BPV on outcome after acute ischemic stroke and assess whether these parameters were affected by stroke subtype. Ninety-two consecutive admissions with a CT-confirmed diagnosis of acute ischemic stroke were recruited, of whom 54 had cortical infarction, 29 subcortical, and 9 posterior circulation infarction. Casual and two 5-minute recordings of beat-to-beat BP (Finapres, Ohmeda) were made under standardized conditions within 72 hours of ictus, with mean BP levels taken as the average of this 10-minute recording and BPV as the standard deviation. Outcome was assessed at 30 days as dead/dependent or independent (Rankin </=2). The effects of BP, BPV, and stroke subtype on outcome were studied with the use of logistic regression. Stroke subjects were subsequently divided by BP quartiles and within each quartile into low- and high-variability groups; the influence of high BPV on outcome was also assessed. The odds ratio for death/dependency was significantly higher in cortical strokes compared with subcortical and posterior circulation strokes even after controlling for differences in BP and BPV (OR 4.19, P=0.002). Beat-to-beat systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP +/- SD) levels were higher in the dead/dependent group compared with the independent group (MAP 106+/-20.4 mm Hg vs 97+/-19.1 mm Hg, P<0.02), as was MAP variability: 6.1 (interquartile range 4.5 to 7.4 mm Hg) versus 4.9 (3.8 to 6.4 mm Hg, P=0.02). The odds ratio for a poor outcome was 1. 38 (P=0.014) for every 10-mm Hg increase in MAP and 1.32 (P=0.02) for every 1-mm Hg increase in MAP variability. Casual BP measurements had no prognostic significance. For the group as a whole when separated into BP quartiles, those with a high MAP and DBP but not SBP variability within each quartile had a worse prognosis compared with those with a low BPV. A poor outcome at 30 days after ischemic stroke was dependent on stroke subtype, beat-to-beat DBP, and MAP levels and variability. Important prognostic information can be readily obtained from a short period of noninvasive BP monitoring in the acute stroke patient. These findings have important implications, particularly regarding the use of hypotensive agents in the acute stroke period.

P133 Background and Purpose: Isolated systolic hypertension (ISH) is frequently observed in elderly persons. The effect of ISH on the long-term risk for stroke and stroke subtypes is unclear. We performed this study to evaluate the long-term risk of stroke in persons with ISH. METHODS: We evaluated the incidence of stroke and stroke subtypes(ischemic and hemorrhagic) in a nationally representative cohort of 14,047 adults who participated in the First National Health and Nutrition Examination Survey during the 20-year follow-up. ISH was defined as a systolic blood pressure(BP)&gt;160mmHg and diastolic BP&lt;90mmHg. RESULTS: A total of 376 persons with ISH, 8985 persons with normotension, and 4686 persons with classic hypertension were followed. During the follow-up period, the annual incidences of ischemic stroke and intracerebral hemorrhage for patients with ISH were 1.7% and .05% respectively. After adjusting for differences in age, race,and gender, the risk for ischemic stroke was increased in persons with ISH compared to persons with normotension (odds ratio [OR]=1.6, 95% confidence interval [CI]=1.1 to 2.2). The increased risk was similar to persons with classic hypertension (OR=1.3, 95% CI=1.03 to 1.6). The risk of intracerebral hemorrhage was increased in persons with classic hypertension (OR=3.0, 95% CI=1.5 to 7.1) but not in persons with ISH (OR=0.7, 95% CI=0.1 to 2.3). CONCLUSION: Persons with ISH are at increased risk for ischemic stroke, similar to those with classic hypertension.

The aim of this prospective observational study was to determine the association of acute blood pressure values with independent factors (demographic, clinical characteristics, early complications) in stroke subgroups of different aetiology. We evaluated data of 346 first-ever acute (<24 h) stroke patients treated in our stroke unit. Casual and 24-h blood pressure (BP) values were measured. Stroke risk factors and stroke severity on admission were documented. Strokes were divided into subgroups of different aetiopathogenic mechanism. Patients were imaged with CT-scan on admission and 5 days later to determine the presence of brain oedema and haemorrhagic transformation. The relationship of different factors to 24-h BP values (24-h BP) was evaluated separately in each stroke subgroup. In large artery atherosclerotic stroke (n=59), history of hypertension and stroke severity correlated with higher 24-h BP respectively. In cardioembolic stroke (n=87), history of hypertension, stroke severity, haemorrhagic transformation and brain oedema were associated with higher 24-h BP, while heart failure with lower 24-h BP. History of hypertension and coronary artery disease was related to higher and lower 24-h BP, respectively, in lacunar stroke (n=75). In patients with infarct of undetermined (n=57) cause 24-h BP were mainly influenced by stroke severity and history of hypertension. An independent association between higher 24-h BP and history of hypertension and cerebral oedema was documented in intracerebral haemorrhage (n=68). In conclusion, different factors influence acute BP values in stroke subtypes of different aetiology. If the clinical significance of these observations is verified, a differentiated approach in acute BP management based on stroke aetiology may be considered.

Several issues regarding ethnic-cultural factors, sex-related variation, and risk factors for stroke have been described in the literature. However, there have been no prospective studies comparing ethnic differences and stroke subtypes between populations from South America and North America. It has been suggested that natives from Buenos Aires, Argentina, may have higher frequency of hemorrhagic strokes and penetrating artery disease than North American subjects. The aim of this study was to validate this hypothesis. We studied the database of all consecutive acute stroke patients admitted to the Ramos Mejia Hospital (RMH) in Buenos Aires and to the Beth Israel Deaconess Medical Center (BIMC) in Boston, Massachusetts, from July 1997 to March 1999. Stroke subtypes were classified according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. All information on patients (demographic, clinical, and radiographic) was recorded prospective to the assessment of the stroke subtype. Three hundred sixty-one and 479 stroke patients were included at RMH and BIMC stroke data banks, respectively. Coronary artery disease was significantly more frequent in BIMC (P:<0.001), whereas tobacco and alcohol intake were significantly more frequent in RMH (P:<0.001). Intracerebral hemorrhage (P:<0.001) and penetrating artery disease (P:<0.001) were significantly more frequent in the RMH registry, whereas large-artery disease (P:<0.02) and cardioembolism (P:<0.001) were more common in the BIMC data bank. Penetrating artery disease and intracerebral hemorrhage were the most frequent stroke subtypes in natives from Buenos Aires. Lacunar strokes and intracerebral hemorrhage were more frequent among Caucasians from Buenos Aires than Caucasians from Boston. Poor risk factor control and dietary habits could explain these differences.

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Objective: We aimed to evaluate the differences in biomarker levels and brachial and central blood pressure estimates during the acute and subacute phase of stroke, between lacunar infarcts and other ischemic stroke subtypes. Design and method: Patients > 18 years old, with a first episode of ischemic stroke, admitted to our institution between July 2015 and July 2017 were consecutively included. Subjects with Rankin > 2 and patients with history of previous heart failure were excluded. Blood pressure (BP) was measured at admission and during the acute phase of stroke. Determination of proBNP, urinary albumin excretion (UAE) and an echocardiographic study were performed in all subjects. The aortic pulse wave velocity (aPWV) and 24 h brachial and central BP (24h-ABPM) were measured by means of Mobil-O-Graph device during the subacute phase of stroke. Results: 71 subjects with a first episode of ischemic stroke were included, mean age: 64.7 ± 13.9 years, 62% men: 22 lacunar stroke (31%), and 49 cases (69%) with non lacunar ischemic stroke. The levels of proBNP were significantly lower in patients with lacunar stroke as compared as atherothrombotic and cardioembolic stroke (median: 36, 277 and 274 pg/mL, respectively; p = 0.009). After adjusting for age, patients with lacunar stroke had significantly higher levels of BP in the emergency department: systolic BP 173 ± 37 vs 153 ± 28 mm Hg respectively; p = 0.006, diastolic BP: 97 ± 21 vs 86 ± 16 mm Hg; p = 0.035, and during the acute phase of stroke: systolic BP 142 ± 19 vs 128 ± 16 mm Hg; p = 0.002; diastolic BP: 79 ± 12 and 73 ± 12 mm Hg respectively; p = 0.025. Regarding 24h-ABPM, patients with lacunar stroke showed higher values of daytime pulse pressure, daytime brachial systolic BP, daytime brachial diastolic BP and central BP estimates, after adjusting for age. No significant differences were observed in target organ damage between the different ischemic stroke subtypes. Conclusions: Patients with a first episode of lacunar stroke had lower levels of proBNP and higher BP levels during acute and subacute phase of stroke, suggesting a closer relationship with hypertension.

Establishing new approaches for the prevention and treatment of stroke relies on identifying modifiable risk factors that contribute to the development of this complex disease. Mendelian randomization (MR) studies, analogous to naturally occurring randomized trials, can assess causality of potentially modifiable biomarkers and offer new insights into biological pathways. Stroke is the second leading cause of death worldwide and the chief determinant of long-term disability. Stroke is a heterogeneous disease arising from several distinct underlying pathologies and is typically classified as ischemic or hemorrhagic, and further subclassified using imaging data. Ischemic stroke (IS), including its 3 main subtypes: small vessel disease, large vessel disease, and cardioembolic stroke, accounts for ≈80% of stroke and is the result of an interrupted blood supply, leading to localized areas of ischemia in the brain. Small vessel disease may be a consequence of nonatherosclerotic, as well as atherosclerotic, mechanisms that result in an occlusion of the small perforating arteries, whereas large vessel disease results from occlusions or emboli from plaque rupture in larger vessels, such as a carotid artery. Cardioembolic stroke arises typically from emboli from the heart. By contrast, hemorrhagic stroke is a consequence of intracerebral hemorrhage (bleeding into the brain) or subarachnoid hemorrhage (bleeding into the subarachnoid space). These diverse stroke subtypes have distinct underlying pathologies reflecting different risk factor distributions. MR studies, using genetic variants as instrumental variables, afford a powerful approach to assessing causality of risk factors and avoid biases inherent in observational studies, including confounding and reverse causation. This review considers the contribution of MR studies to stroke epidemiology and their relevance to understanding risk factors and new therapeutic targets for stroke. Meta-analyses of large prospective studies have enhanced our knowledge of classical and emerging risk factors for stroke.1–4 Classical risk factors for stroke include nonmodifiable characteristics, …

Discharge ICD-9-CM (International Classification of Diseases, 9th Revision, Clinical Modification) codes have been used to identify patients with acute stroke for epidemiological, quality of care, and cost studies. The aim of this study was to determine if the accuracy of the primary ICD-9-CM codes for ischemic stroke is improved by modifier codes and how specific codes reflect stroke subtype diagnoses. Available hospital charts for all patients discharged from a single hospital between May 1995 and June 1997 with ICD-9-CM codes 433 (occlusion and stenosis of precerebral arteries), 434 (occlusion of cerebral arteries), or 436 (acute but ill-defined cerebrovascular disease) listed in the first position were reviewed. The primary discharge diagnosis was verified, and a presumed stroke subtype was assigned on the basis of information provided in the medical record. Charts were available for 175 of the 198 identified patients (88%). Of these, 61% had an acute ischemic stroke (code 433, 4%; 434, 82%; 436, 79%) with the remaining patients having other conditions. Of the 130 patients with a modifier code indicating cerebral infarction, 79% had an acute stroke; of the 45 patients with a modifier code indicating an absence of cerebral infarction, 7% had acute stroke (sensitivity, 0.97; specificity, 0.60). The codes with the highest proportions of ischemic stroke cases were 434.11 (embolic occlusion of cerebral arteries with infarction, 85%), 434.91 (unspecified occlusion of precerebral arteries with infarction, 82%), and 436 (79%), with a combined sensitivity of 0.81 and specificity of 0.90. On review, 73% of patients with code 434.11 had embolic strokes, and 47% of those with code 436 had an identified stroke cause. Of patients with code 434.91, 39% had stroke of uncertain cause, 25% "lacunar," 17% atherothrombosis, and 15% embolism. Despite the use of modifier codes, 15% to 20% of patients with the indicated primary ICD-9-CM codes have conditions other than acute ischemic stroke. Although the proportion of patients with acute stroke increased from 61% to 79% with the use of modifier codes, the inclusion of modifier codes did not have an appreciable effect on the accuracy of the coding if patients with code 433 are excluded. Assignment of presumed ischemic stroke subtype is particularly inaccurate.

Blood pressure as a prognostic factor after acute stroke