Therapeutic Relevance of Elevated Blood Pressure After Ischemic Stroke in the Hypertensive Rats.
- 作者列表："Thakkar PC","McGregor AL","Barber PA","Paton JFR","Barrett CJ","McBryde FD
Over 80% of patients exhibit an acute increase in blood pressure (BP) following stroke. Current clinical guidelines make no distinction in BP management between patients with or without prior hypertension. Spontaneously hypertensive (SH) rats were preinstrumented with telemeters to record BP, intracranial pressure, and brain tissue oxygen in the predicted ischemic penumbra for 3 days before and 10 days after transient middle cerebral artery occlusion (n=8 per group) or sham (n=5). Before stroke, BP was either left untreated or chronically treated to a normotensive level (enalapril 10 mg/kg per day). Poststroke elevations in BP were either left uncontrolled, controlled (to the prestroke baseline level), or overcontrolled (to a normotensive level) via subcutaneous infusion of labetalol. Baseline values of intracranial pressure and brain tissue oxygen were similar between all groups, whereas BP was lower in treated SH rats (144±3 versus 115±5 mm Hg; <0.001). Following middle cerebral artery occlusion, a similar rise in BP was observed in untreated (+16±2 mm Hg; =0.005) and treated SH rats (+13±5 mm Hg; =0.021). Intervening to prevent BP from increasing after stroke did not worsen outcome. However, reducing BP below prestroke baseline levels was associated with higher intracranial pressure (days 1-3; <0.001), reduced cerebral perfusion pressure (days 2-4; <0.001), higher mortality, slower functional recovery and larger infarct volumes. Although treating to maintain BP at the prestroke baseline level was not detrimental, our results suggest that when setting BP targets after stroke, consideration must be given to the potential negative impact of inadvertent excessive BP lowering in subjects with undiagnosed or poorly controlled hypertension.
超过 80% 的患者在卒中后表现出血压 (BP) 的急性升高。目前的临床指南对既往有或无高血压患者的 BP 管理没有区别。自发性高血压 (SH) 大鼠用遥测仪预先记录血压、颅内压、和脑组织氧在预测缺血半暗带前 3 天和短暂大脑中动脉闭塞后 10 天 (每组 n = 8) 或假 (n = 5)。卒中前，BP 要么未经治疗，要么长期治疗至正常血压水平 (依那普利 10 mg/kg/天)。卒中后 BP 升高要么不受控制，要么通过皮下输注拉贝洛尔控制 (至卒中前基线水平)，要么过度控制 (至正常血压水平)。各组间颅内压和脑组织氧的基线值相似，而治疗 SH 大鼠的 BP 较低 (144 ± 3 vs 115 ± 5毫米 hg; <0.001)。大脑中动脉闭塞后，未治疗 (+ 16 ± 2毫米 hg; = 0.005) 和治疗 SH 大鼠 (+ 13 ± 5毫米 hg; = 0.021) 的 BP 升高相似。干预以防止卒中后血压升高并没有使结局恶化。然而，降低血压低于卒中前基线水平与较高的颅内压 (第 1-3 天; <0.001) 、脑灌注压降低 (第 2-4 天; <0.001) 相关, 死亡率较高，功能恢复较慢，梗死体积较大。尽管治疗将血压维持在卒中前基线水平并无不利，但我们的结果表明，在卒中后设定血压目标时, 必须考虑在未确诊或控制不佳的高血压受试者中无意地过度降低血压的潜在负面影响。
METHODS:BACKGROUND:Hypertensive disorders of pregnancy (HDP) increase cardiovascular disease (CVD) risk. Pregnancy morbidities, including preeclampsia, and CVD are common in systemic lupus erythematosus (SLE). Possible connections are important to explore. In a population-based cohort, we investigated whether HDP is associated with a higher risk of cardiovascular outcomes separately in SLE and non-SLE to examine the role of SLE. METHODS:We identified first singleton births in the Medical Birth Register (1987-2012) among mothers with SLE and a large general population comparison group. Discharge diagnoses for HDP, cardiovascular outcomes, and hypertension in the Patient Register were identified using ICD codes. We estimated adjusted hazard ratios and 95% confidence intervals (HR, 95% CI) of the association between HDP and outcomes, in separate models in women with and without SLE. We then evaluated additive and multiplicative effect modification using relative excess risk due to interaction and Cox models jointly accounting for SLE and HDP, respectively. Mediation analysis estimated the proportion of the association between SLE and outcome explained by HDP. RESULTS:HDP were more common in SLE pregnancies (20% vs 7%). In SLE, HDP were associated with a two-fold higher rate of cardiovascular outcomes and three-fold higher rate of incident hypertension. HDP mediated 20% of the latter association. In women without SLE, HDP was associated with higher hypertension incidence later in life. CONCLUSION:In women with and without SLE, HDP were associated with a three-fold higher rate of hypertension. In SLE, women with HDP developed cardiovascular outcomes twice as often as women without HDP.
METHODS:BACKGROUND:'Neuronal precursor cell expressed developmentally down-regulated 4-like' (NEDD4L) is considered a candidate gene for hypertension-both functionally and genetically-through the regulation of the ubiquitination of the epithelial sodium channel (ENaC). This study explores the relationship between genetic variation in NEDD4L and hypertension with chronic kidney disease (CKD) in the southeastern Han Chinese population. METHODS:We recruited 623 CKD patients and measured ambulatory blood pressure monitoring (ABPM), and the rs4149601 and rs2288774 polymorphisms in NEDD4L were genotyped using qPCR. RESULTS:For rs4149601, significant differences in genotype frequencies in an additive model (GG vs GA vs AA) were observed between normotensive patients and hypertensive patients when hypertension was classified into ambulatory hypertension, clinical hypertension and ambulatory systolic hypertension (P = 0.038, 0.005 and 0.006, respectively). In a recessive model (GG+GA vs AA), the frequency of the AA genotype of rs4149601 in the hypertension groups were all higher than that in the normotensive groups. The genotype distribution of rs2288774 did not differ significantly between the normotensive and hypertensive patients. In both the full cohort and the propensity score matching (PSM) cohort, the AA genotype of rs4149601 (compared to the GG+GA genotype group) was independently correlated with ambulatory hypertension, clinical hypertension and ambulatory systolic hypertension by multivariate logistic regression analysis. CONCLUSIONS:The present study indicates that the AA genotype of rs4149601 associates with hypertension in CKD. Consequently, the rs4149601 A allele might be a risk factor for hypertension with CKD.
METHODS:BACKGROUND:The burden of hypertension in many low-and middle-income countries is alarming and requires effective evidence-based preventative strategies that is carefully appraised and accepted by key stakeholders to ensure successful implementation and sustainability. We assessed nurses' perceptions of a recently completed Task Shifting Strategy for Hypertension control (TASSH) trial in Ghana, and facilitators and challenges to TASSH implementation. METHODS:Focus group sessions and in-depth interviews were conducted with 27 community health nurses from participating health centers and district hospitals involved in the TASSH trial implemented in the Ashanti Region, Ghana, West Africa from 2012 to 2017. TASSH evaluated the comparative effectiveness of the WHO-PEN program versus provision of health insurance for blood pressure reduction in hypertensive adults. Qualitative data were analyzed using open and axial coding techniques with emerging themes mapped onto the Consolidated Framework for Implementation Research (CFIR). RESULTS:Three themes emerged following deductive analysis using CFIR, including: (1) Patient health goal setting- relative priority and positive feedback from nurses, which motivated patients to make healthy behavior changes as a result of their health being a priority; (2) Leadership engagement (i.e., medical directors) which influenced the extent to which nurses were able to successfully implement TASSH in their various facilities, with most directors being very supportive; and (3) Availability of resources making it possible to implement the TASSH protocol, with limited space and personnel time to carry out TASSH duties, limited blood pressure (BP) monitoring equipment, and transportation, listed as barriers to effective implementation. CONCLUSION:Assessing stakeholders' perception of the TASSH implementation process guided by CFIR is crucial as it provides a platform for the nurses to thoroughly evaluate the task shifting program, while considering the local context in which the program is implemented. The feedback from the nurses informed barriers and facilitators to implementation of TASSH within the current healthcare system, and suggested system level changes needed prior to scale-up of TASSH to other regions in Ghana with potential for long-term sustainment of the task shifting intervention. TRIAL REGISTRATION:Trial registration for parent TASSH study: NCT01802372. Registered February 27, 2013.