Jean-Martin Boulanger

The 2009 Canadian Hypertension Education Program recommendations for the management of hypertension: Part 2 – therapy

OBJECTIVE To update the evidence-based recommendations for the prevention and management of hypertension in adults for 2009. OPTIONS AND OUTCOMES For lifestyle and pharmacological interventions, evidence from randomized controlled trials and systematic reviews of trials was preferentially reviewed. Changes in cardiovascular morbidity and mortality were the primary outcomes of interest. However, for lifestyle interventions, blood pressure lowering was accepted as a primary outcome given the lack of long-term morbidity and mortality data in this field. Progression of kidney dysfunction was also accepted as a clinically relevant primary outcome among patients with chronic kidney disease. EVIDENCE A Cochrane collaboration librarian conducted an independent MEDLINE search from 2007 to August 2008 to update the 2008 recommendations. To identify additional published studies, reference lists were reviewed and experts were contacted. All relevant articles were reviewed and appraised independently by both content and methodological experts using prespecified levels of evidence. RECOMMENDATIONS For lifestyle modifications to prevent and treat hypertension, restrict dietary sodium to less than 2300 mg (100 mmol)/day (and 1500 mg to 2300 mg [65 mmol to 100 mmol]/day in hypertensive patients); perform 30 min to 60 min of aerobic exercise four to seven days per week; maintain a healthy body weight (body mass index 18.5 kg/m(2) to 24.9 kg/m(2)) and waist circumference (smaller than 102 cm for men and smaller than 88 cm for women); limit alcohol consumption to no more than 14 units per week in men or nine units per week in women; follow a diet that is reduced in saturated fat and cholesterol, and that emphasizes fruits, vegetables and low-fat dairy products, dietary and soluble fibre, whole grains and protein from plant sources; and consider stress management in selected individuals with hypertension. For the pharmacological management of hypertension, treatment thresholds and targets should be predicated on by the patients global atherosclerotic risk, target organ damage and comorbid conditions. Blood pressure should be decreased to lower than 140/90 mmHg in all patients, and to lower than 130/80 mmHg in those with diabetes mellitus or chronic kidney disease. Most patients will require more than one agent to achieve these target blood pressures. Antihypertensive therapy should be considered in all adult patients regardless of age (caution should be exercised in elderly patients who are frail). For adults without compelling indications for other agents, initial therapy should include thiazide diuretics. Other agents appropriate for first-line therapy for diastolic and/or systolic hypertension include angiotensin- converting enzyme (ACE) inhibitors (in patients who are not black), long-acting calcium channel blockers (CCBs), angiotensin receptor antagonists (ARBs) or beta-blockers (in those younger than 60 years of age). A combination of two first-line agents may also be considered as the initial treatment of hypertension if the systolic blood pressure is 20 mmHg above the target or if the diastolic blood pressure is 10 mmHg above the target. The combination of ACE inhibitors and ARBs should not be used. Other agents appropriate for first-line therapy for isolated systolic hypertension include long- acting dihydropyridine CCBs or ARBs. In patients with angina, recent myocardial infarction or heart failure, beta-blockers and ACE inhibitors are recommended as first-line therapy; in patients with cerebrovascular disease, an ACE inhibitor/diuretic combination is preferred; in patients with proteinuric nondiabetic chronic kidney disease, ACE inhibitors or ARBs (if intolerant to ACE inhibitors) are recommended; and in patients with diabetes mellitus, ACE inhibitors or ARBs (or, in patients without albuminuria, thiazides or dihydropyridine CCBs) are appropriate first-line therapies. All hypertensive patients with dyslipidemia should be treated using the thresholds, targets and agents outlined in the Canadian Cardiovascular Society position statement (recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease). Selected high-risk patients with hypertension who do not achieve thresholds for statin therapy according to the position paper should nonetheless receive statin therapy. Once blood pressure is controlled, acetylsalicylic acid therapy should be considered. VALIDATION All recommendations were graded according to strength of the evidence and voted on by the 57 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. All recommendations reported here achieved at least 95% consensus. These guidelines will continue to be updated annually.

The 2013 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension.

We updated the evidence-based recommendations for the diagnosis, assessment, prevention, and treatment of hypertension in adults for 2013. This years update includes 2 new recommendations. First, among nonhypertensive or stage 1 hypertensive individuals, the use of resistance or weight training exercise does not adversely influence blood pressure (BP) (Grade D). Thus, such patients need not avoid this type of exercise for fear of increasing BP. Second, and separately, for very elderly patients with isolated systolic hypertension (age 80 years or older), the target for systolic BP should be < 150 mm Hg (Grade C) rather than < 140 mm Hg as recommended for younger patients. We also discuss 2 additional topics at length (the pharmacological treatment of mild hypertension and the possibility of a diastolic J curve in hypertensive patients with coronary artery disease). In light of several methodological limitations, a recent systematic review of 4 trials in patients with stage 1 uncomplicated hypertension did not lead to changes in management recommendations. In addition, because of a lack of prospective randomized data assessing diastolic BP thresholds in patients with coronary artery disease and hypertension, no recommendation to set a selective diastolic cut point for such patients could be affirmed. However, both of these issues will be examined on an ongoing basis, in particular as new evidence emerges.

Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign (PREDICT): a prospective observational study

BACKGROUND In patients with intracerebral haemorrhage (ICH), early haemorrhage expansion affects clinical outcome. Haemostatic treatment reduces haematoma expansion, but fails to improve clinical outcomes in many patients. Proper selection of patients at high risk for haematoma expansion seems crucial to improve outcomes. In this study, we aimed to prospectively validate the CT-angiography (CTA) spot sign for prediction of haematoma expansion. METHODS PREDICT (predicting haematoma growth and outcome in intracerebral haemorrhage using contrast bolus CT) was a multicentre prospective observational cohort study. We recruited patients aged 18 years or older, with ICH smaller than 100 mL, and presenting at less than 6 h from symptom onset. Using two independent core laboratories, one neuroradiologist determined CTA spot-sign status, whereas another neurologist masked for clinical outcomes and imaging measured haematoma volumes by computerised planimetry. The primary outcome was haematoma expansion defined as absolute growth greater than 6 mL or a relative growth of more than 33% from initial CT to follow-up CT. We reported data using standard descriptive statistics stratified by the CTA spot sign. Mortality was assessed with Kaplan-Meier survival analysis. FINDINGS We enrolled 268 patients. Median time from symptom onset to baseline CT was 135 min (range 22-470), and time from onset to CTA was 159 min (32-475). 81 (30%) patients were spot-sign positive. The primary analysis included 228 patients, who had a follow-up CT before surgery or death. Median baseline ICH volume was 19·9 mL (1·5-80·9) in spot-sign-positive patients versus 10·0 mL (0·1-102·7) in spot-sign negative patients (p<0·001). Median ICH expansion was 8·6 mL (-9·3 to 121·7) for spot-sign positive patients and 0·4 mL (-11·7 to 98·3) for spot-negative patients (p<0·001). In those with haematoma expansion, the positive predictive value for the spot sign was61% (95% CI 47–73) for the positive predictive value and 78% (71–84) for the negative predictive value, with 51% (39–63) sensitivity and 85% (78–90) specificity[corrected]. Median 3-month modified Rankin Scale (mRS) was 5 in CTA spot-sign-positive patients, and 3 in spot-sign-negative patients (p<0·001). Mortality at 3 months was 43·4% (23 of 53) in CTA spot-sign positive versus 19·6% (31 of 158) in CTA spot-sign-negative patients (HR 2·4, 95% CI 1·4-4·0, p=0·002). INTERPRETATION These findings confirm previous single-centre studies showing that the CTA spot sign is a predictor of haematoma expansion. The spot sign is recommended as an entry criterion for future trials of haemostatic therapy in patients with acute ICH. FUNDING Canadian Stroke Consortium and NovoNordisk Canada.

The 2011 Canadian Hypertension Education Program Recommendations for the Management of Hypertension: Blood Pressure Measurement, Diagnosis, Assessment of Risk, and Therapy

We updated the evidence-based recommendations for the diagnosis, assessment, prevention, and treatment of hypertension in adults for 2011. The major guideline changes this year are: (1) a recommendation was made for using comparative risk analogies when communicating a patients cardiovascular risk; (2) diagnostic testing issues for renal artery stenosis were discussed; (3) recommendations were added for the management of hypertension during the acute phase of stroke; (4) people with hypertension and diabetes are now considered high risk for cardiovascular events if they have elevated urinary albumin excretion, overt kidney disease, cardiovascular disease, or the presence of other cardiovascular risk factors; (5) the combination of an angiotensin-converting enzyme (ACE) inhibitor and a dihydropyridine calcium channel blocker (CCB) is preferred over the combination of an ACE inhibitor and a thiazide diuretic in persons with diabetes and hypertension; and (6) a recommendation was made to coordinate with pharmacists to improve antihypertensive medication adherence. We also discussed the recent analyses that examined the association between angiotensin II receptor blockers (ARBs) and cancer.

Bleeding Risk Analysis in Stroke Imaging Before ThromboLysis (BRASIL): Pooled Analysis of T2*-Weighted Magnetic Resonance Imaging Data From 570 Patients

Background and Purpose— There has been speculation that the risk of secondary symptomatic intracranial hemorrhage (SICH) may be increased after thrombolytic therapy in ischemic stroke patients who have cerebral microbleeds (CMBs) on T2*-weighted magnetic resonance imaging. Because of this concern, some centers withhold potentially beneficial thrombolytic therapy from these patients. Methods— We analyzed magnetic resonance imaging data acquired within 6 hours after symptom onset from 570 ischemic stroke patients treated with intravenous tissue plasminogen activator in 13 centers in Europe, North America, and Asia. Baseline T2*-weighted magnetic resonance images were evaluated for the presence of CMBs. The primary end point was SICH, defined as clinical deterioration with an increase in the National Institutes of Health Stroke Scale score by ≥4 points, temporally related to a parenchymal hematoma on follow-up-imaging. Results— A total of 242 CMBs were detected in 86 of 570 patients (15.1%). The number of CMBs ranged from 1 to 77 in the individual patient, with ≥5 CMBs in 6 of 570 patients (1.1%). Proportions of patients with SICH were 5.8% (95% CI, 1.9 to 13.0) in the presence of CMBs and 2.7% (95% CI, 1.4 to 4.5) in patients without CMBs (P=0.170, Fishers exact test), resulting in no significant absolute increase in the risk of SICH of 3.1% (95% CI, −2.0 to 8.3). Conclusions— The data suggest that if there is any increased risk of SICH attributable to CMBs, it is likely to be small and unlikely to exceed the benefits of thrombolytic therapy. No reliable conclusion regarding risk in the rare patient with multiple CMBs can be reached.

Leukoaraiosis and intracerebral hemorrhage after thrombolysis in acute stroke.

Objectives: To evaluate whether the presence of leukoaraiosis or multiple lacunes is associated with symptomatic intracerebral hemorrhage (ICH) and 90-day outcome after thrombolytic treatment with tissue plasminogen activator (tPA). Methods: Data were from a Canadian national registry of thrombolyzed patients with ischemic stroke. A total of 820 scans were assessed, blind to clinical features, for the presence of severe vs no/moderate leukoaraiosis, and of multiple (>2) vs no/single lacunar infarcts. Logistic regression was used to determine if an independent interaction existed between the presence and degree of leukoaraiosis/lacunes and risk of symptomatic ICH, and to evaluate the predictive role of leukoaraiosis and lacunes in relation to 90-day outcome. Results: An overall symptomatic ICH rate of 3.5% was observed. The rate of symptomatic ICH increased up to 10% in patients with severe leukoaraiosis and multiple lacunes. A significant association was observed between ICH risk and either severe leukoaraiosis (RR = 2.7 [95% CI 1.1 to 6.5]) or multiple lacunes (RR = 3.4 [95% CI 1.5 to 7.6]). Patients with multiple lacunes, but not leukoaraiosis, had higher mortality at 90 days compared to those with one or no lacunes (OR = 2.9, 95% CI 1.3 to 6.2, p = 0.008). No difference was observed in the good outcome rate among patients with and without leukoaraiosis or lacunes or both. Conclusion: The presence of small vessel disease on CT scan does not affect overall clinical outcome at 3 months in routine community use of tPA for ischemic stroke. A significant increase in the risk of symptomatic ICH is observed.

Cerebral Microhemorrhages Predict New Disabling or Fatal Strokes in Patients With Acute Ischemic Stroke or Transient Ischemic Attack

Background and Purpose— Cerebral microhemorrhages (MHs) are common among patients presenting with acute ischemic stroke and may predict both subsequent ischemic and hemorrhagic strokes. Methods— We prospectively studied patients with and without MHs presenting within 12 hours of their ischemic stroke or transient ischemic attack (TIA). A magnetic resonance (MR) scan was performed within 24 hours of symptom(s) onset. The primary outcome was disabling or fatal stroke at 18 months. Results— An MR scan was done in 236 patients with acute ischemic stroke or TIA. Forty-five (19.1%) patients had an MH on a baseline MR scan. Patients with MHs were 2.8× (10.8% versus 4.0%; P=0.036) more likely to have a subsequent disabling or fatal stroke than patients without an MH. The risk of symptomatic intracerebral hemorrhage was not statistically significant among MH and non-MH patients (3.3% versus 0.8%; P=0.31). Conclusions— The presence of cerebral MH(s) in patients with acute ischemic stroke or TIA predicts recurrent disabling and fatal strokes. This risk is mainly assumed by recurrent ischemic strokes.

Canadian Stroke Best Practice Recommendations: Hyperacute Stroke Care Guidelines, Update 2015

The 2015 update of the Canadian Stroke Best Practice Recommendations Hyperacute Stroke Care guideline highlights key elements involved in the initial assessment, stabilization, and treatment of patients with transient ischemic attack (TIA), ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and acute venous sinus thrombosis. The most notable change in this 5th edition is the addition of new recommendations for the use of endovascular therapy for patients with acute ischemic stroke and proximal intracranial arterial occlusion. This includes an overview of the infrastructure and resources required for stroke centers that will provide endovascular therapy as well as regional structures needed to ensure that all patients with acute ischemic stroke that are eligible for endovascular therapy will be able to access this newly approved therapy; recommendations for hyperacute brain and enhanced vascular imaging using computed tomography angiography and computed tomography perfusion; patient selection criteria based on the five trials of endovascular therapy published in early 2015, and performance metric targets for important time-points involved in endovascular therapy, including computed tomography-to-groin puncture and computed tomography-to-reperfusion times. Other updates in this guideline include recommendations for improved time efficiencies for all aspects of hyperacute stroke care with a movement toward a new median target door-to-needle time of 30 min, with the 90th percentile being 60 min. A stronger emphasis is placed on increasing public awareness of stroke with the recent launch of the Heart and Stroke Foundation of Canada FAST signs of stroke campaign; reinforcing the public need to seek immediate medical attention by calling 911; further engagement of paramedics in the prehospital phase with prehospital notification to the receiving emergency department, as well as the stroke team, including neuroradiology; updates to the triage and same-day assessment of patients with transient ischemic attack; updates to blood pressure recommendations for the hyperacute phase of care for ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. The goal of these recommendations and supporting materials is to improve efficiencies and minimize the absolute time lapse between stroke symptom onset and reperfusion therapy, which in turn leads to better outcomes and potentially shorter recovery times.

Spot Sign Number Is the Most Important Spot Sign Characteristic for Predicting Hematoma Expansion Using First-Pass Computed Tomography Angiography: Analysis From the PREDICT Study

Background and Purpose— The spot sign score (SSS) provides risk stratification for hematoma expansion in acute intracerebral hemorrhage; however, external validation is needed. We sought to validate the SSS and assess prognostic performance of individual spot characteristics associated with hematoma expansion from a prospective multicenter intracerebral hemorrhage study. Methods— Two hundred twenty-eight intracerebral hemorrhage patients within 6 hours after ictus were enrolled in the Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT (PREDICT) study, a multicenter prospective intracerebral hemorrhage cohort study. Patients were evaluated with baseline noncontrast computerized tomography, computerized tomography angiography, and 24-hour follow-up computerized tomography. Primary outcome was significant hematoma expansion (>6 mL or >33%) and secondary outcome was absolute and relative expansion. Blinded computerized tomography angiography spot sign characterization and SSS calculation were independently performed by 2 neuroradiologists and a radiology resident. Diagnostic performance of the SSS and individual spot characteristics were examined with multivariable regression, receiver operating characteristic analysis, and tests for trend. Results— SSS and spot number independently predicted significant, absolute, and relative hematoma expansion (P<0.05 each) and demonstrated near perfect interobserver agreement (&kgr;=0.82 and &kgr;=0.85, respectively). Incremental risk of hematoma expansion among spot-positive patients was not identified for SSS (P trend=0.720) but was demonstrated for spot number (P trend=0.050). Spot number and SSS demonstrated similar area under the curve (0.69 versus 0.68; P=0.306) for hematoma expansion. Conclusions— Multicenter external validation of the SSS demonstrates that the spot number alone provides similar prediction but improved risk stratification of hematoma expansion compared with the SSS.

Diffusion-weighted imaging-negative patients with transient ischemic attack are at risk of recurrent transient events.

Background and Purpose— Among patients presenting with a transient ischemic attack (TIA), some clinical features predispose to recurrent TIA, whereas others predispose to subsequent strokes. We assessed the implication of negative diffusion-weighted imaging on a baseline MRI in predicting subsequent TIA. Methods— We prospectively studied patients presenting in the emergency department within 12 hours of a TIA (motor or speech). All patients had a MRI within 24 hours of the index event. The primary outcome was TIA within 1 year of study entry. The 1-year risk of stroke was also evaluated. Results— A total of 85 patients had a MRI, among which 35 patients (41.2%) had a diffusion-weighted imaging lesion. The mean time from symptom onset to MRI was 12.1 hours. Patients without a diffusion-weighted imaging lesion on baseline MRI were 4.6 times (27.4% versus 5.9%; P<0.05) more likely to have a subsequent TIA at 1 year than patients with a diffusion-weighted imaging lesion, but 4.3 times (2.1% versus 9.1%; P=0.19) less likely to have a subsequent stroke. Conclusions— The absence of a diffusion-weighted imaging lesion on the baseline scan predicts recurrent transient events rather than stroke.