Leukotriene modifiers in the treatment of cardiovascular diseases

Cysteinyl-leukotrienes (Cys-LTs) and LTB4 are potent proinflammatory mediators derived from arachidonic acid through the 5-lipoxygenase (5-LO) pathway, which exerts important pharmacological effects through their interaction with specific receptors: Cys-LT receptors (CysLT1 and CysLT2) and LTB4 receptors (BLT1 and BLT2). Published evidence justifies a broader role for LT receptor antagonists (LTRAs), in particular, montelukast, in the treatment of bronchial asthma, allergic rhinitis, and recently, in cardiocerebrovascular disease. The actions of Cys-LTs on the cardiovascular (CV) system are well-documented and include a broad array of activities with promising therapeutic targets in animal models exploring the use of selective 5-LO (or 5-LO-activating protein) inhibitors or dual LO-cycloxygenase-blocking agents in experimentally induced acute myocardial infarction. The picture that emerges from studies with LTRAs is more controversial at the moment, and some findings suggest a role for Cys-LTs in the extension of ischemic damage and in cardiac dysfunction during reperfusion; others do not. The aim of this short review is to summarize the state of present research about LT modifier treatment in CV diseas

Acute hypertension: A systematic review and appraisal of guidelines

Background: Few clinical practice guidelines provide management recommendations for acute hypertensive episodes except in the context of specific conditions such as pregnancy and stroke.Methods: We performed a systematic search to identify guidelines addressing acute hypertension and appraised the guidelines using the Appraisal of Guidelines for Research and Evaluation (AGREE II) validated quality assessment tool. Two reviewers independently appraised and one extracted key recommendations. Literature on secondary hypertension, hypertension in pregnancy, preeclampsia/eclampsia, stroke, aortic dissection, and pheochromocytoma was excluded.Results: Three guidelines were identified, sponsored by the American College of Emergency Physicians (ACEP), the National Heart, Lung, and Blood Institute (NHLBI), and the European Society of Hypertension (ESH) in conjunction with the European Society of Cardiology (ESC). AGREE II yielded mean domain (%) and overall assessment scores (1-7) as follows: NHLBI: 73%, 5.5; ACEP: 67%, 5.5; and ESH/ESC: 56%, 4.5. In hypertensive emergencies, the NHLBI guideline recommends reducing mean arterial pressure by_25% for the first hour, and then to 160/100-110 mmHg by 2-6 hours with subsequent gradual normalization in 24-48 hours. The ESH/ESC has similar recommendations. The ACEP does not address guidelines for hypertensive emergency but focuses on whether screening for target organ damage or medical intervention in patients with asymptomatic elevated blood pressure in emergency departments reduces the rate of adverse outcomes, concluding that routine screening does not reduce adverse outcomes, but patients with poor follow-up may benefit from routine screening.Conclusion: NHLBI and ESH/ESC guidelines are high quality and provide similar recommendations for management of asymptomatic acute hypertensive episodes and hypertensive emergencies. Additional research is needed to inform clinical practice guidelines for this common condition

Supplementary Material for: Early Blood Pressure Reduction in Acute Ischemic Stroke with Various Severities: A Subgroup Analysis of the CATIS Trial

<b><i>Background:</i></b> Clinical trials have generally showed a neutral effect of blood pressure (BP) reduction on clinical outcomes among acute ischemic stroke patients. We conducted a prespecified subgroup analysis to assess whether disease severity modifies the effect of early antihypertensive treatment on death and disability among patients with acute ischemic stroke. <b><i>Methods:</i></b> In the China Antihypertensive Trial in Acute Ischemic Stroke, 4,071 patients with acute ischemic stroke and elevated BP were randomly assigned to receive antihypertensive treatment or to discontinue all hypertension medications within 48 h of symptom onset. The primary outcome was a combination of death and major disability at 14 days or hospital discharge. In this subgroup analysis, participants were categorized into 3 groups according to their baseline NIH Stroke Scale (NIHSS) scores (0-4, 5-15, or ≥16). <b><i>Results:</i></b> At 24 h after randomization, mean systolic BP differences (95% CIs) were -8.5 (-10.0 to -7.1), -9.8 (-11.4 to -8.3), and -9.1 (-14.4 to -3.8) mm Hg between the treatment and control groups (all p values <0.001) for patients with a baseline NIHSS score of 0-4, 5-15, and ≥16, respectively. At day 7 after randomization, the corresponding mean systolic BP differences were -9.3 (-10.5 to -8.2), -9.1 (-10.3 to -7.8), and -10.1 (-15.1 to -5.1) mm Hg between the treatment and control groups (all p values <0.001). The primary outcome was not significantly different between the treatment and control groups at day 14 or hospital discharge among all NIHSS subgroups (p value for homogeneity = 0.66). ORs (95% CI) associated with treatment were 1.14 (0.87-1.49, p = 0.33), 1.04 (0.86-1.25, p = 0.70), and 0.67 (0.18-2.44, p = 0.54) for patients with a baseline NIHSS score of 0-4, 5-15, and ≥16, respectively. The composite outcome of death and major disability at 3-month follow-up did not differ between the 2 comparison groups for all NIHSS subgroups. In addition, vascular events and recurrent stroke were not significantly different between the 2 comparison groups at the 3-month follow-up visit among all NIHSS subgroups except that there was a suggestive risk reduction for recurrent stroke among those with an NIHSS score of 5-15 (OR 0.45, 95% CI 0.20-0.99, p = 0.05). <b><i>Conclusion:</i></b> Early BP reduction with antihypertensive medications did not reduce or increase the risk of death, major disabilities, recurrent instances of stroke, and vascular events in acute ischemic stroke patients with a variety of disease severities