Treatment of severe hypertension during pregnancy: we still do not know what the best option is.

Intracranial hemorrhage and stroke are primary causes of maternal mortality in pregnancies affected by hypertensive disorders. As such antihypertensive therapy plays a crucial role in the management of severe hypertension. However, the target level to achieve the best outcome for both - mother and fetus - is still unclear. Moreover, given the lack of well-designed randomized controlled trials with standardized key outcomes, the current choice of antihypertensive medications depends rather on clinicians' preference. Furthermore, data on long-term outcomes of offspring is not available. Therefore, there is an urgent need for randomized trials comparing different anti-hypertensive options to address efficacy and safety questions.

Intensive blood pressure control reduces the risk of progressive hemorrhage in patients with acute hypertensive intracerebral hemorrhage: A retrospective observational study.

OBJECTIVE: To investigate the impact of intensive blood pressure control on progressive intracerebral hemorrhage and outcome in patients with high blood pressure and intracerebral hemorrhage. PATIENTS AND METHODS: A retrospective study was conducted recruiting 659 patients with acute hemorrhagic stroke between Jan. 2012 and May 2018. Patients recruited before May 2015 were treated with a target systolic level of <180 mm Hg, while those recruited after May 2015 received intensive blood pressure control treatment with a target systolic level of <140 mm Hg within 1 h. Uni- and multi-variate analysis were conducted to illustrate the association between intensive blood pressure control and progressive intracerebral hemorrhage. Mortality, rates of operation, length of ICU stay, modified Rankin scores at 90 days, and the rate of serious adverse events were also compared between the two groups. RESULTS: A total of 351 and 308 patients with acute hypertensive intracerebral hemorrhage were recruited before and after May 2015, respectively. Progressive intracerebral hemorrhage was identified among 111 out of 659 patients. Patients who received intensive blood pressure control showed a statistically lower rate of hematoma enlarging (43 of 308, 13.9% vs. 74 of 351, 21.1%, p = 0.018). The rates of operation and modified Rankin scores at 90 days were statistically lower with intensive blood control, while the mortality, length of ICU stay and rate of serious adverse events were similar between the two groups. Intensive BP control is an independent factor in predicting hematoma growing, with a more favorable discrimination (AUC = 0.889; 95%CI, 0.859-0.917) than other two models (AUC = 0.821; 95%CI, 0.791-0.852; and AUC = 0.635; 95%CI, 0.588-0.682). CONCLUSION: Intensive blood pressure control reduce the risk of progressive intracerebral hemorrhage and improved functional outcomes in patients with acute hemorrhagic stroke.

Overexpression of LH3 reduces the incidence of hypertensive intracerebral hemorrhage in mice.

Hypertensive intracerebral hemorrhage (ICH) is a devastating cerebrovascular disease with no effective treatment. Lysyl hydroxylase 3 (LH3) is essential for collagen IV intermolecular crosslinking and stabilization. Deficiency in LH3 affects the assembly and secretion of collagen IV and basement membrane (BM) integrity of vessels. Here, we investigated whether LH3 has significant implications for disease progression and therapeutic intervention. Spontaneous hypertensive ICH of mice was induced by angiotensin II and L-NAME treatment. The adeno-associated virus was delivered into brain by stereotactic injection to knockdown or overexpress LH3. We found LH3 levels were reduced in human patients with ICH and gradually decreased in mice before ICH. LH3 knockdown increased the incidence of hypertensive ICH in mice. The incidence, number, and size of ICHs in mice were markedly reduced by LH3 overexpression. RNA-seq revealed that LH3 overexpression significantly reversed the profound alterations in gene transcriptional profiles of cerebral vessels. LH3 overexpression was sufficient to enhance BM integrity, inhibit matrix metalloproteinase activity, attenuate microglial activation and leukocyte infiltration, and reduce VSMC apoptosis before ICH. These results indicate that LH3 overexpression attenuates susceptibility to hypertensive ICH. We emphasize that LH3 modulation may serve as a viable approach for future investigations of ICH prevention.

Adherence to Antihypertensive Medications and Stroke Risk: A Dose-Response Meta-Analysis.

BACKGROUND: Inconsistent findings have been obtained for previous studies evaluating the association between antihypertensive medication (AHM) adherence and the risk of stroke. This dose-response meta-analysis was designed to investigate the association between AHM adherence and stroke risk. METHODS AND RESULTS: MEDLINE and Embase databases were systematically searched to identify relevant studies. The quantification of adherence to AHM was calculated as the percentage of the sum of days with AHM actually taken divided by the total number of days in a specific period. Summary relative risks (RR) and 95% CIs were estimated using a random-effects model. Stratified and dose-response analyses were also performed. A total of 18 studies with 1 356 188 participants were included. The summary RR of stroke for the highest compared with the lowest AHM adherence level was 0.73 (95% CI, 0.67-0.79). Stratified by stroke subtype, a higher AHM adherence was associated with lower risks of ischemic stroke (RR, 0.74; 95% CI, 0.69-0.79) and hemorrhagic stroke (RR, 0.55; 95% CI, 0.42-0.72). Moreover, both fatal (RR, 0.51; 95% CI, 0.36-0.73) and nonfatal stroke (RR, 0.52; 95% CI, 0.28-0.94) were lower in participants with higher AHM adherence. The results of a dose-response analysis indicated that a 20% increment in AHM adherence level was associated with a 9% lower risk of stroke (RR, 0.91; 95% CI, 0.86-0.96). CONCLUSIONS: Higher AHM adherence is dose-dependently associated with a lower risk of stroke in patients with hypertension.

Clinical analysis and treatment of symptomatic intracranial hemorrhage after deep brain stimulation surgery.

BACKGROUND: Symptomatic intracranial hemorrhage (ICH) may lead to permanent neurological disability of patients and has impeded the extensive clinical application of deep brain stimulation (DBS). The present study was conducted to discuss the incidence, prevention, and treatment of symptomatic ICH after DBS surgery. METHODS: From January 2009 to December 2014, 396 patients underwent DBS with a total of 691 implanted leads. In all, 10 patients had symptomatic ICH. We analyzed these cases' clinical characteristics, including comorbid diagnoses and coagulation profile. We described the onset of ICH, imaging features, clinical manifestations, treatment, neurological impairment, and outcome of DBS. RESULTS: Of the 10 patients with symptomatic ICH, 2 had hypertension. Three cases of ICH occurred within 12 h of the procedure; four cases within 24 h. Five experienced grand mal seizures concurrently with hemorrhage. Unilateral frontal lobe hemorrhage occurred in all cases. In seven cases, hematomas occurred around the electrodes. Some hematomas were not well-circumscribed and had perihematomal edema. Conservative therapy was administered to 8 patients, and 2 patients underwent craniotomy and hematoma evacuation. All electrodes were successfully preserved. Neurological dysfunction in all patients gradually improved. Nine patients ultimately experienced effective symptom relief of Parkinson's disease with DBS. CONCLUSIONS: Symptomatic ICH should be identified as soon as possible after implantation surgery and treated effectively to limit neurological deficit and preserve DBS leads.

Effects of platelet infusion, anticoagulant and other risk factors on the rehaemorrhagia after surgery of hypertensive cerebral hemorrhage.

OBJECTIVE: Our objective is to explore the effect of platelet infusion, anticoagulant and other risk factors on the rehaemorrhagia after surgery of hypertensive cerebral hemorrhage (HCH), and to provide a reference for the prevention and treatment of rehaemorrhagia in patients with HCH. PATIENTS AND METHODS: The patients with HCH admitted during April, 2007-June, 2012 in our hospital were selected. The general data such as age and gender, disease course, past pathogenic characters, past and present medical history such as treatment, personal history, family history and son on, were collected. The data were analyzed by t test, ANOVA, Chi-squared test and logistic regression analysis. RESULTS: The application of aspirin and platelets has significant effect on rehaemorrhagia after surgery of HCH: 72 patients received aspirin, of which 14 cases had rehaemorrhagia while 197 patients did not receive aspirin, of which 20 cases had rehaemorrhagia. The difference between these two groups was statistically significant (p < 0.05). 186 patients received platelet infusions, of which 18 cases had rehaemorrhagia whereas among other 83 patients not receiving platelet infusions, 16 cases had rehaemorrhagia. Statistical analysis showed a significant difference between these two groups (p < 0.05). In the univariate logistic regression analysis of related data in patients with rehaemorrhagia after surgery of HCH, diastolic or systolic blood pressure at admission, the time from onset to surgery, coagulation disorder, surgical method, hematoma volume, cerebral hemia, effect of hematoma clearance and GCS at admission were the potential risk factors for rehaemorrhagia after surgery of HCH (p < 0.05). In the multivariate logistic regression analysis of related data in the same patients, diastolic blood pressure at admission (> 120 mmHg), systolic blood pressure at admission (> 200 mmHg), the time from onset to surgery and coagulation disorder were screened out (p < 0.05) to be associated with rehaemorrhagia. CONCLUSIONS: Aspirin increased the risk of rehaemorrhagia after surgery of HCH. On the contrary, infusion of platelets decreased the risk of rehaemorrhagia and improved the prognosis of patients. High diastolic and/or high systolic blood pressure at admission, ultra-early surgery after onset of HCH and coagulation disorder were related with rehaemorrhagia after operation of HCH. Our results indicate that rehaemorrhagia rate can be decreased by controlling related risk factors.

The China Stroke Secondary Prevention Trial (CSSPT) protocol: a double-blinded, randomized, controlled trial of combined folic acid and B vitamins for secondary prevention of stroke.

RATIONALE: Epidemiological studies suggest that elevated homocysteine is linked to stroke and heart disease. However, the results of lowering homocysteine levels in reducing the risk of stroke recurrence are controversial. AIMS: The study aims to evaluate whether homocysteine-lowering therapy with folic acid and vitamins B6 and B12 reduces recurrent stroke events and other combined incidence of recurrent vascular events and vascular death in ischemic stroke patients of low folate regions. DESIGN: This is a multicenter, randomized, double-blinded, placebo-controlled trial. Patients (n = 8000, α = 0.05, ß = 0.10) within one-month of ischemic stroke (large-artery atherosclerosis or small-vessel occlusion) or hypertensive intracerebral haemorrhage with plasma homocysteine level ≥ 15 µmol/l will be enrolled. Eligible patients will be randomized by a web-based, random allocation system to receive multivitamins (folic acid 0.8 mg, vitamin B6 10 mg, and vitamin B12 500 µg) or matching placebo daily with a median follow-up of three-years. STUDY OUTCOMES: Patients will be evaluated at six monthly intervals. The primary outcome event is the composite event 'stroke, myocardial infarction, or death from any vascular cause', whichever occurs first. Secondary outcome measures include nonvascular death, transient ischemic attack, depression, dementia, unstable angina, revascularization procedures of the coronary, and cerebral and peripheral circulations. DISCUSSION: This is the first multicenter randomized trial of secondary prevention for ischemic stroke in a Chinese population with a higher homocysteine level but without folate food fortification.

Effects of heparin on synaptic activity in the hemorrhagic stroke model in vitro.

We studied the ability of heparin to modify synaptic activity on the original stroke model in vitro. Cultured slices of the brain slices from hypertensive rats were treated with the autoblood clot. Administration of heparin (2 mg/ml) before autoblood treatment had a protective effect on ionotropic glutamatergic and GABAergic receptors, whose activity was inhibited by the blood.

Intracranial hemorrhage as a complication of dobutamine stress echocardiography: case report and review of the literature.

Dobutamine stress echocardiography is a generally well-tolerated study to evaluate patients with suspected coronary artery disease. Rare but life-threatening complications of this study have been well described. Severe hypertensive responses are a known but uncommon adverse reaction to dobutamine infusion. The authors report a case of intracranial hemorrhage in the setting of severe hypertension as a complication of dobutamine stress echocardiography. The patient was on systemic anticoagulation with warfarin for a prosthetic mitral valve and had an international normalized ratio (INR) of 3.8 that was slightly over the therapeutic goal INR of 2.5-3.5. He had no predisposing intracranial lesions such as tumor, vascular malformation, or aneurysm. He suffered an intraparenchymal hemorrhage in three distinct areas of his brain. Intracranial hemorrhage related to dobutamine infusion has not been reported previously, but given the known risk of hypertension, life-threatening sequelae including intracranial hemorrhage are possible.

Hypertension in the elderly: what is the goal blood pressure target and how can this be attained?

For the aging populations of Europe, many emerging health problems in addition to myocardial infarction and stroke are associated with hypertension. Recently, the role of hypertension in the risk of vascular cognitive impairment and dementia has been highlighted, and there are studies to show that control of hypertension may slow this process. Furthermore, as many elderly individuals will also develop type 2 diabetes or impaired renal function, the risk of hypertension in these patients is more pronounced. New guidelines have tried to provide evidence-based treatment algorithms in which control of hypertension is just one aspect of general risk factor control, with the aim of decreasing the total risk.

Postcarotid endarterectomy cerebral hyperperfusion can be prevented by minimizing intraoperative cerebral ischemia and strict postoperative blood pressure control under continuous sedation.

OBJECTIVE: Cerebral hyperperfusion syndrome is a major complication after carotid endarterectomy (CEA). We investigated whether our strategy of minimizing intraoperative cerebral ischemia and strict postoperative blood pressure control under continuous sedation prevented postoperative hyperperfusion. METHODS: Eighty consecutive patients undergoing CEA were studied. A shunt was used in all patients during CEA. All patients were managed postoperatively under continuous sedation for as long as 48 hours on the basis of the regional cerebral blood flow (rCBF) measured immediately after CEA. Postoperative hyperperfusion was assessed, on the basis of the cerebral blood flow study under sedation (propofol) after CEA, either as a greater than 30% increase in rCBF compared with the contralateral side, or a greater than 100% increase in the corrected rCBF (calculated from percentage reduction of the contralateral rCBF induced by propofol) compared with preoperative values. RESULTS: No patient developed cerebral hyperperfusion syndrome. Postoperative hyperperfusion was found at very low rates (2.5% in the middle cerebral artery territory and 1.3% in the anterior cerebral artery territory by definition 1, and 0% in both territories by definition 2). Ratios of regional oxygen saturation after internal carotid artery clamping to preclamp baseline values were greater than 0.9 in 78 of 80 patients, indicating very mild intraoperative cerebral ischemia. Parameters related to cerebral ischemia during CEA, such as regional oxygen saturation, internal carotid artery cross-clamping duration, and stump pressure (index), did not affect the incidence of postoperative hyperperfusion. CONCLUSION: The present study suggests that minimizing intraoperative cerebral ischemia using a shunt, followed by strict postoperative blood pressure control under continuous sedation, can prevent post-CEA hyperperfusion.

Intracranial hemorrhage associated with cerebral hyperperfusion syndrome following carotid endarterectomy and carotid artery stenting: retrospective review of 4494 patients.

OBJECT: Intracranial hemorrhage associated with cerebral hyperperfusion syndrome (CHS) following carotid endarterectomy (CEA) or carotid artery stenting (CAS) is a rare but potentially devastating complication. In the present study the authors evaluated 4494 patients with carotid artery stenosis who had undergone CEA or CAS to clarify the clinicopathological features and outcomes of those with CHS and associated intracranial hemorrhage. METHODS: Patients with postoperative CHS were retrospectively selected, and clinicopathological features and outcomes were studied. RESULTS: Sixty-one patients with CHS (1.4%) were identified, and intracranial hemorrhage developed in 27 of them (0.6%). The onset of CHS peaked on the 6th postoperative day in those who had undergone CEA and within 12 hours in those who had undergone CAS. Results of logistic regression analysis demonstrated that poor postoperative control of blood pressure was significantly associated with the development of intracranial hemorrhage in patients with CHS after CEA (p = 0.0164). Note, however, that none of the tested variables were significantly associated with the development of intracranial hemorrhage in patients with CHS after CAS. Mortality (p = 0.0010) and morbidity (p = 0.0172) rates were significantly higher in patients with intracranial hemorrhage than in those without. CONCLUSIONS: Cerebral hyperperfusion syndrome after CEA and CAS occurs with delayed classic and acute presentations, respectively. Although strict control of postoperative blood pressure prevents intracranial hemorrhage in patients with CHS after CEA, there appears to be no relationship between blood pressure control and intracranial hemorrhage in those with CHS after CAS. Finally, the prognosis of CHS in patients with associated intracerebral hemorrhage is poor.

Acidosis of severe falciparum malaria: heading for a shock?

Severe Plasmodium falciparum malaria encompasses a complex syndrome affecting many organs and causing physiological perturbations that have many features in common with children with sepsis. Among these, metabolic acidosis has emerged as a central feature of severe malaria and is the best independent predictor of a fatal outcome in both adults and children. There is now clear evidence that intravascular hypovolaemia (shock) is common in children with malarial acidosis. How it should be treated presents a therapeutic dilemma because acidosis often coexists with impaired consciousness (cerebral malaria). We summarize the results of recent clinical trials examining the safety and efficacy of volume expansion in children with 'cerebral malaria' complicated by acidosis.

Digoxin antibody prevents cerebral hemorrhage-induced hypertension.

BACKGROUND: Brain injury may induce hypertension. Because serum ouabain-like compound (OLC) has vasoconstrictor activity, digoxin antibody antihypertensive effects were evaluated using an intracerebroventricular (ICV) hemorrhage rat model. METHODS: Four ICV infused Wistar rat groups were studied: control; blood; blood plus digoxin antibody, and cerebrospinal fluid-like solution. Tail-cuff blood pressure, cumulative sodium balance, and serum OLC were measured. RESULTS: The ICV blood infusion increased blood pressure (BP) and OLC without sodium balance change. Digoxin antibody prevented BP and OLC rise. Blood pressure was positively correlated with OLC in blood and blood plus digoxin antibody rats (R = 0.63; P <.05). CONCLUSIONS: Cerebral hemorrhage increased OLC and BP, which were reversed by digoxin antibody administration.