IMPORTANCE Although the benefit of reducing blood pressure for primary and secondary prevention of stroke has been established, the effect of antihypertensive treatment in patients with acute ischemic stroke is uncertain.OBJECTIVE To evaluate whether immediate blood pressure reduction in patients with acute ischemic stroke would reduce death and major disability at 14 days or hospital discharge. DESIGN, SETTING, AND PARTICIPANTS The China Antihypertensive Trial in Acute IschemicStroke, a single-blind, blinded end-points randomized clinical trial, conducted among 4071 patients with nonthrombolysed ischemic stroke within 48 hours of onset and elevated systolic blood pressure. Patients were recruited from 26 hospitals across China between August 2009 and May 2013.INTERVENTIONS Patients (n = 2038) were randomly assigned to receive antihypertensive treatment (aimed at lowering systolic blood pressure by 10% to 25% within the first 24 hours after randomization, achieving blood pressure less than 140/90 mm Hg within 7 days, and maintaining this level during hospitalization) or to discontinue all antihypertensive medications (control) during hospitalization (n = 2033). MAIN OUTCOMES AND MEASURESPrimary outcome was a combination of death and major disability (modified Rankin Scale score Ն3) at 14 days or hospital discharge.RESULTS Mean systolic blood pressure was reduced from 166.7 mm Hg to 144.7 mm Hg (−12.7%) within 24 hours in the antihypertensive treatment group and from 165.6 mm Hg to 152.9 mm Hg (−7.2%) in the control group within 24 hours after randomization (difference, −5.5% [95% CI, −4.9 to −6.1%]; absolute difference, −9.1 mm Hg [95% CI, −10.2 to −8.1]; P < .001). Mean systolic blood pressure was 137.3 mm Hg in the antihypertensive treatment group and 146.5 mm Hg in the control group at day 7 after randomization (difference, −9.3 mm Hg [95% CI, −10.1 to −8.4]; P < .001). The primary outcome did not differ between treatment groups (683 events [antihypertensive treatment] vs 681 events [control]; odds ratio, 1.00 [95% CI, 0.88 to 1.14]; P = .98) at 14 days or hospital discharge. The secondary composite outcome of death and major disability at 3-month posttreatment follow-up did not differ between treatment groups (500 events [antihypertensive treatment] vs 502 events [control]; odds ratio, 0.99 [95% CI, 0.86 to 1.15]; P = .93).CONCLUSION AND RELEVANCE Among patients with acute ischemic stroke, blood pressure reduction with antihypertensive medications, compared with the absence of hypertensive medication, did not reduce the likelihood of death and major disability at 14 days or hospital discharge.

We performed a meta-analysis of 2 genome-wide association studies of coronary artery disease comprising 1,515 cases with coronary artery disease and 5,019 controls, followed by de novo replication studies in 15,460 cases and 11,472 controls, all of Chinese Han descent. We successfully identified four new loci for coronary artery disease reaching genome-wide significance (P < 5 × 10−8), which mapped in or near TTC32-WDR35, GUCY1A3, C6orf10-BTNL2 and ATP2B1. We also replicated four loci previously identified in European populations (PHACTR1, TCF21, CDKN2A/B and C12orf51). These findings provide new insights into biological pathways for the susceptibility of coronary artery disease in Chinese Han population.

Renalase, a novel flavin adenine dinucleotide-dependent amine oxidase, is secreted by the kidney, degrades circulating catecholamines, and modulates cardiac function and systemic blood pressure (BP). Its discovery may provide novel insights into the mechanisms of BP regulation and the pathogenesis of essential hypertension (EH). We designed a two-stage case-control study to investigate whether the renalase gene harbored any genetic variants associated with EH in the northern Han Chinese population. From the International Collaborative Study of Cardiovascular Disease in Asia (InterASIA in China), 1,317 hypertensive cases and 1,269 normotensive controls were recruited. These total 2,586 subjects were taken as the main study population in this study. In stage 1, all the eight selected single nucleotide polymorphisms (SNPs) of the renalase gene were genotyped and tested within a subsample (503 cases and 490 controls) of the main study population. By single locus analyses, three SNPs, rs2576178, rs2296545, and rs2114406, showed significant associations with EH (P < 0.05). In stage 2, these three SNPs were genotyped on the remaining individuals and analyzed using all the individuals. After Bonferroni correction for multiple comparisons, the associations of rs2576178 and rs2296545 with EH were still significant in stage 2. The cases had higher frequencies of rs2576178 G allele and rs2296545 C allele than the controls (0.55 versus 0.49, P < 0.0001; 0.61 versus 0.55, P < 0.0001). Particularly, under the codominant model, the adjusted odds ratios for rs2576178 GG genotype and rs2296545 CC genotype were 1.58 (95% CI, 1.25 to 2.00; P = 0.0002) and 1.61 (95% CI, 1.26 to 2.04; P = 0.0002), respectively. We also found risk-associated haplotypes and diplotypes, which further confirmed the significant association between the renalase gene and EH. These findings may provide novel genetic susceptibility markers for EH and lead to a better understanding of EH pathophysiology. In addition, further replications in other populations and functional studies would be warranted.

Recent results have demonstrated that the spin trapping agent N-tert-butyl-a-phenylnitrone (PBN)

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The objective of this article is to amalgamate previous results into a speculative synthesis that sheds light on the causes of secondary brain damage following either global/forebrain or focal ischemia. The hypothesis is based on the well-founded assumption that the pathophysiology of the brain damage incurred by global or forebrain ischemia is different from that of focal ischemia. In the former, the ischemia is usually dense and of brief duration and, provided that reperfusion is adequate, cell damage is conspicuously delayed, mostly affecting selectively vulnerable neurons. In contrast, focal ischemia is either long-lasting or permanent, and it is usually less severe, particularly in the perifocal penumbral regions. The lesion is typically pan-necrotic ("infarction"), initially affecting the focus supplied by the occluded artery, later invading the penumbra zone. Available results allow a restatement of the calcium hypothesis of cell death. In global or forebrain ischemia, calcium influx through channels gated by voltage or glutamate receptors is envisaged to trigger reactions that limit the survival of neurons during reperfusion, leading to secondary neuronal death after hours or days of survival. It can be hypothesized that the initial insult leads to a sustained alteration of membrane calcium handling, resulting in slow, gradual calcium overload of mitochondria. Alternatively, a sustained perturbation of the intracellular signal transduction pathway leads to changes in transcription or translation, bereaving the cells of heat shock and stress proteins, of trophic factors, or of enzymes required for survival. However, with the possible exception of the gerbil, neither microvascular failure nor primary mitochondrial dysfunction is believed to be involved. In focal ischemia, similar reactions are probably triggered by calcium influx, whether this is sustained (the focus) or intermittent (the penumbra). However, these play a minor role in cell death since they are overridden by reactions producing mediators of rapidly developing secondary damage, affecting either microvessels or mitochondria. Very probably, some of these mediators are free radicals, or nitric oxide, or other reactive metabolites, emanating from lipid hydrolysis and arachidonic acid metabolism. During continuous ischemia, or during recirculation following 1-3 h of ischemia, these mediators activate adhesion molecules in endothelial cells or polymorphonuclear leucocytes, or oxidize key proteins. The result is either failure of microcirculation ("capillary plugging"), or sustained mitochondrial failure. Since calcium influx is an initial event, agents reducing presynaptic depolarization and calcium entry through glutamate receptor-gated and other calcium channels have predictably a narrow therapeutic window; however, since spin trapping agents of the nitrone class act many hours after the induction of focal ischemia, their therapeutic window is potentially very wide. This may be because expression of mRNAs for adhesion molecules and their synthesi...