Reserpine Substantially Lowers Blood Pressure in Patients with Refractory Hypertension: A Proof of Concept Study.
- 作者列表："Siddiqui M","Bhatt H","Judd EK","Oparil S","Calhoun DA
BACKGROUND:Refractory hypertension (RfHTN), a phenotype of antihypertensive treatment failure, is defined as uncontrolled automated office BP [AOBP] ≥130/80 mmHg and awake ambulatory BP [ABP] ≥130/80 mmHg on ≥5 antihypertensive medications, including chlorthalidone and a mineralocorticoid receptor antagonist. Previous studies suggest that RfHTN is attributable to heightened sympathetic tone. The current study tested whether reserpine, a potent sympatholytic agent, lowers BP in patients with RfHTN. METHODS:Twenty-one out of 45 consecutive patients with suspected RfHTN were determined to be fully adherent with their antihypertensive regimen. Seven patients agreed to participate in the current clinical trial with reserpine and six patients completed the study. Other sympatholytic medications, such as clonidine or guanfacine were tapered and discontinued before starting reserpine. Reserpine 0.1 mg daily was administered in an open-label fashion for 4 weeks. All patients were evaluated by AOBP and 24-hour ABP at baseline and after 4 weeks of treatment. RESULTS:Reserpine lowered mean systolic and diastolic AOBP by 29.3±22.2 and 22.0±15.8 mmHg, respectively. Mean 24-hr systolic and diastolic ABP was reduced by 21.8±13.4 and 15.3±9.6 mmHg, mean awake systolic diastolic ABP by 23.8±11.8 and 17.8±9.2 mmHg, and mean asleep systolic and diastolic ABP by 21.5±11.4 and 13.7±6.4 mmHg, respectively. CONCLUSIONS:Reserpine, a potent sympatholytic agent, lowers BP in patients whose BP remained uncontrolled on maximal antihypertensive therapy, lending support to the hypothesis that excess sympathetic output contributes importantly to the development of RfHTN.
背景: 难治性高血压 (RfHTN)，一种降压治疗失败的表型,定义为在 ≥ 5 种抗高血压药物 (包括氯噻酮和一种盐皮质激素受体拮抗剂) 下，不受控制的自动化 office BP [AOBP] ≥ 130/80 mmHg 和清醒的非卧床 BP [ABP] ≥ 130/80 mmHg。既往研究表明，RfHTN 可归因于交感神经张力增强。目前的研究测试了利血平，一种有效的交感神经溶解剂，是否能降低 RfHTN 患者的血压。 方法: 在 45 例疑似 RfHTN 的连续患者中，有 21 例被确定为完全符合其降压方案。7 名患者同意参加利血平目前的临床试验，6 名患者完成了研究。其他交感神经药物，如可乐定或胍法辛，在开始利血平前逐渐减量并停药。利血平 0.1 mg 每日以开放标签方式给药 4 周。所有患者在基线和治疗 4 周后通过 AOBP 和 24 小时 ABP 进行评价。 结果: 利血平使平均收缩期和舒张期 AOBP 分别降低 29.3 ± 22.2 和 22.0 ± 15.8 mmHg。平均 24 h 收缩期和舒张期 ABP 分别降低 21.8 ± 13.4 和 15.3 ± 9.6 mmHg，平均清醒收缩期舒张期 ABP 分别降低 23.8 ± 11.8 和 17.8 ± 9.2 mmHg,平均睡眠收缩和舒张 ABP 分别为 21.5 ± 11.4 和 13.7 ± 6.4 mmHg。 结论: 利血平是一种有效的交感神经溶解剂，在最大限度降压治疗时，利血平可降低血压仍然不受控制的患者的血压，支持交感神经输出过多对 RfHTN 发生有重要影响的假设。
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.