Intensive Blood Pressure Management Preserves Functional Connectivity in Patients with Hypertension from the Systolic Blood Pressure Intervention Randomized Trial.

BACKGROUND AND PURPOSE: The Systolic Blood Pressure Intervention (SPRINT) randomized trial demonstrated that intensive blood pressure management resulted in slower progression of cerebral white matter hyperintensities, compared with standard therapy. We assessed longitudinal changes in brain functional connectivity to determine whether intensive treatment results in less decline in functional connectivity and how changes in brain functional connectivity relate to changes in brain structure. MATERIALS AND METHODS: Five hundred forty-eight participants completed longitudinal brain MR imaging, including resting-state fMRI, during a median follow-up of 3.84 years. Functional brain networks were identified using independent component analysis, and a mean connectivity score was calculated for each network. Longitudinal changes in mean connectivity score were compared between treatment groups using a 2-sample t test, followed by a voxelwise t test. In the full cohort, adjusted linear regression analysis was performed between changes in the mean connectivity score and changes in structural MR imaging metrics. RESULTS: Four hundred six participants had longitudinal imaging that passed quality control. The auditory-salience-language network demonstrated a significantly larger decline in the mean connectivity score in the standard treatment group relative to the intensive treatment group (P = .014), with regions of significant difference between treatment groups in the cingulate and right temporal/insular regions. There was no treatment group difference in other networks. Longitudinal changes in mean connectivity score of the default mode network but not the auditory-salience-language network demonstrated a significant correlation with longitudinal changes in white matter hyperintensities (P = .013). CONCLUSIONS: Intensive treatment was associated with preservation of functional connectivity of the auditory-salience-language network, while mean network connectivity in other networks was not significantly different between intensive and standard therapy. A longitudinal increase in the white matter hyperintensity burden is associated with a decline in mean connectivity of the default mode network.

Once-daily eprosartan mesylate in the treatment of elderly patients with isolated systolic hypertension: data from a 13-week double-blind, placebo-controlled, parallel, multicenter study.

This was a double-blind, randomized, placebo-controlled multicenter, titration-to-effect study of eprosartan in patients > or =60 years of age with isolated systolic hypertension. The study consisted of a 3 to 5-week placebo run-in period, a 13-week double-blind treatment period (6-week titration with eprosartan 600-1200 mg/day, 3-week maintenance, 4-week combination therapy with hydrochlorothiazide/HCTZ 12.5 mg), and a follow-up period within 5-7 days of last treatment dose. Overall, 283 patients (placebo/P: 135; eprosartan /E: 148) were randomized [female patients-P: 55.6%, E:54.7%; white-P:66.7%, E:67.6%). Mean sitting systolic blood pressure (SitSBP) at baseline was comparable (P: 170+/-0.8 mmHg; E: 171+/-0.8 mm Hg). At monotherapy end point, eprosartan produced a significant reduction in SitSBP (E: 16.1 mmHg vs P: 8.4 mmHg; P<0.0001). In all, 57.4% of patients responded to eprosartan monotherapy. Among nonresponders, the addition of HCTZ resulted in a decrease in SitSBP from baseline (E: 21.7 mmHg; P: 14.4 mmHg; P<0.002). Reductions were also noted in Standing SBP (monotherapy: P<0.001; combination therapy: P=0.03). No reductions in SitDBP >4 mmHg were found during the study. Age, gender, and race did not have any impact on the results. Post hoc analysis showed a reduction in pulse pressure from 87.3 to 78.2 mmHg with placebo and from 87.6 to 70.7 mmHg with eprosartan monotherapy. Treatment with eprosartan in once-daily doses up to 1200 mg alone or in combination with HCTZ was well tolerated, with dizziness and asthenia being the most common side effects.

Why ambulatory blood pressure monitoring?

Factors that affect the reliability and accuracy of blood pressure measurements are reviewed, and new technologies for measuring blood pressure are discussed. Blood pressure measurements obtained in an office, hospital, or clinic are subject to variation and error. Reasons for variations include the wrong cuff size, improper inflation or deflation technique, and patient apprehension ("white-coat syndrome"). Ambulatory blood pressure monitoring (ABPM) involves the use of a fully automated standard arm cuff that is inflated at predetermined intervals by a small battery-powered pump unit. The most reliable ABPM method is the oscillometric method, which detects subtle changes in air pressure within the cuff system caused by fluctuations of the brachial artery. The process for interpreting 24-hour ABPM data is still evolving. Twenty-four-hour ABPM has been shown to eliminate white-coat hypertension and is also useful for assessing patients whose blood pressure is inappropriately high in the absence of end organ damage, monitoring persons at risk of developing hypertension because of their race or family history, determining a medication's 24-hour effect on blood pressure, and assessing the early-morning rapid rise in blood pressure, which has been linked to an increased risk of nonembolic stroke and myocardial infarction. ABPM enables identification of patients whose blood pressure is elevated in the office but normal at home, allows more appropriate screening of patients for clinical trials, gives reproducible values, and enables evaluation of drug duration and action.

The treatment of severe hypertension with trandolapril, verapamil, and hydrochlorothiazide. Trandolapril/Verapamil Multicenter Study Group.

A multiple drug regimen consisting of trandolapril, verapamil and hydrochlorothiazide (HCTZ) were sequentially added in an open-label evaluation of patients with severe hypertension. Ninety patients (58 white and 32 black patients) were titrated on one or more drugs and followed for a 19-week maintenance period. Statistically significant (P = 0.001) mean (+/-s.d.) decreases in supine diastolic blood pressure (DBP) were 9.0 (+/-9.3) mm Hg for trandolapril, 13.9 (+/-11.0) mm Hg for the trandolapril + verapamil (TV) combination, and 19.0 (+/-12.3) mm Hg when hydrochlorothiazide was added to the combination. The decrease in BP observed on TV combination therapy plus HCTZ was significantly (P = 0.001) greater than the decrease observed for the TV combination, which was significantly (P = 0.001) greater than the decrease observed for trandolapril monotherapy. Clinical responder rates were 44.8%, 56% and 77.7% for trandolapril monotherapy, trandolapril + verapamil combination therapy and triple therapy, respectively. Black and white patients had similar response rates, but black patients appeared to benefit more from the addition of HCTZ; 20% of black patients achieved a post-treatment supine DBP <90 mm Hg compared to 12.8% of white patients. This study demonstrates that the addition of verapamil to trandolapril has an additive effect on BP that is maintained throughout the day.

Safety update: focus on cough.

Overall, angiotensin-converting enzyme (ACE) inhibitors have a very low side-effect profile. However, several reports in the literature cite cough as a possible complication of ACE inhibitor therapy. These reports have prompted speculation that the risk of cough may differ among ACE inhibitors and that the risk may be greater in patients with renal impairment, perhaps because of excessive drug accumulation. However, these hypotheses have not been tested in prospective, controlled studies. Fosinopril is a long-acting ACE inhibitor with a unique chemical structure and an elimination profile that is associated with stable clearance, regardless of the degree of renal impairment. Favorable clinical experience with fosinopril led to the evaluation of this agent's cough profile in a prospective, open-label study. This study focused on the frequency of cough in patients with mild-to-moderate hypertension who had previously experienced cough while taking another ACE inhibitor. Whereas most prior controlled studies and postmarketing surveillance trials measured the frequency of cough through spontaneous adverse-event reporting, in this study a methodology previously validated in antitussive and mucolytic studies was adapted to provide accurate and sensitive measure of fosinopril's cough profile. Twenty-four patients were switched from another ACE inhibitor to fosinopril, 10 mg once daily for 6 weeks. At study end, the mean occurrence of cough, frequency of cough, and cough severity significantly changed from baseline (p < or = 0.0002). Thus, fosinopril use was associated with a less frequent, less severe cough in patients who experienced cough while taking other ACE inhibitors.

A dose escalation trial comparing the combination of diltiazem SR and hydrochlorothiazide with the monotherapies in patients with essential hypertension.

A multicentre, randomised, placebo-controlled parallel group study comparing various doses of the combination diltiazem SR (DTZ SR)/hydrochlorothiazide (HCTZ) with the monotherapies was performed to delineate the optimal antihypertensive dosage of the two drug combinations. The study was carried out in 298 patients with mild to moderate essential hypertension (stable supine diastolic blood pressure, DBP, greater than or equal to 95 and less than or equal to 110 mmHg). After a single-blind placebo lead-in period lasting 4-6 weeks to establish stable baseline BP, the patients were randomised to receive either placebo (n = 75), HCTZ (n = 76), DTZ SR (n = 72), or the combination of DTZ SR/HCTZ (n = 75). There were three 4-week evaluation periods with forced escalation of therapy as follows: HCTZ (6.25, 6.25, 12.5 mg twice daily), DTZ SR (60, 90, 120 mg twice daily), and the combination of DTZ SR/HCTZ (60/6.25, 90/6.25, 120/12.5 mg twice daily). DTZ SR/HCTZ (120/12.5 mg) produced statistically significantly greater reductions in supine DBP compared with each monotherapy and placebo. The lower doses of DTZ SR/HCTZ (60/6.25 mg and 90/6.25 mg) produced statistically significantly greater supine DBP reductions compared with DTZ SR monotherapy and placebo, but not compared with HCTZ monotherapy. A comparison of reduction in supine DBP between evaluation periods demonstrated a dose-response relationship for the combination therapy in reducing BP over the dosage range studied. Adverse clinical and laboratory events were not significantly different between the therapies.(ABSTRACT TRUNCATED AT 250 WORDS)

Snuff-induced hypertension in pheochromocytoma.

The dipping of snuff provoked paroxysmal hypertension that induced myocardial ischemia in a 69-year-old woman with pheochromocytoma. The diagnosis of her tumor was delayed by a report of a falsely low urine metanephrine level, resulting from interference with the metanephrine assay by meglumine present in the urine because of contrast coronary angiography performed on the day of urine collection.