Age-related white matter hyperintensities and overactive bladder: A systematic review.

INTRODUCTION: Age-related white matter hyperintensities (ARWMHs) on brain magnetic resonance imaging have been associated with lower urinary tract symptoms/dysfunction (LUTS/LUTD), namely overactive bladder (OAB) and detrusor overactivity. We aimed to systematically review existing data on the association between ARWMH and LUTS and which clinical tools have been used for this assessment. MATERIALS AND METHODS: We searched PubMed/MEDLINE, Cochrane Library, and clinicaltrials.gov (from 1980 to November 2021) and considered original studies reporting data on ARWMH and LUTS/LUTD in patients of both sexes aged 50 or above. The primary outcome was OAB. We calculated the unadjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for the outcomes of interest using random-effects models. RESULTS: Fourteen studies were included. LUTS assessment was heterogeneous and mainly based on the use of nonvalidated questionnaires. Urodynamics assessment was reported in five studies. ARWMHs were graded using visual scales in eight studies. Patients with moderate-to-severe ARWMHs were more likely to present with OAB and urgency urinary incontinence (UUI; OR = 1.61; 95% CI: 1.05-2.49, p = 0.03), I2 = 21.3%) when compared to patients with similar age and absent or mild ARWMH. DISCUSSION AND CONCLUSIONS: High-quality data on the association between ARWMH and OAB is scarce. Patients with moderate to severe ARWMH showed higher levels of OAB symptoms, including UUI, when compared to patients with absent or mild ARWMH. The use of standardized tools to assess both ARWMH and OAB in these patients should be encouraged in future research.

Effectiveness of low-dose diuretics for blood pressure reduction to optimal values in prehypertension: a randomized clinical trial.

BACKGROUND: To determine the effectiveness of low-dose diuretic therapy to achieve an optimal level of blood pressure (BP) in adults with prehypertension. METHODS: The PREVER-prevention trial was a randomized, parallel, double-blinded, placebo-controlled trial, with 18 months of follow-up, conducted at 21 academic medical centers in Brazil. Of 1772 individuals evaluated for eligibility, 730 volunteers with prehypertension who were aged 30-70 years, and who did not reach optimal blood pressure after 3 months of lifestyle intervention, were randomized to a fixed association of chlorthalidone 12.5 mg and amiloride 2.5 mg or placebo once a day. The main outcomes were the percentage of participants who achieved an optimal level of BP. RESULTS: A total of 372 participants were randomly allocated to diuretics and 358 to placebo. After 18 months of treatment, optimal BP was noted in 25.6% of the diuretic group and 19.3% in the placebo group (P < 0.05). The mean net reduction in SBP and DBP for the diuretic group compared with placebo was 2.8 mmHg (95% CI 1.1 to 4.5) and 1.1 mmHg (95% CI -0.09 to 2.4), respectively. Most participants in the active treatment group (74.5%) and in the placebo group (80.7%) continued to have BP in the prehypertension range or progressed to hypertension. CONCLUSION: Low-dose diuretic therapy increased the probability of individuals with prehypertension to achieve optimal BP but most of those treated continued to have a BP in the prehypertension range or progressed to having overt hypertension.

Effectiveness of Chlorthalidone Plus Amiloride for the Prevention of Hypertension: The PREVER-Prevention Randomized Clinical Trial.

BACKGROUND: Prehypertension is associated with higher cardiovascular risk, target organ damage, and incidence of hypertension. The Prevention of Hypertension in Patients with PreHypertension (PREVER-Prevention) trial aimed to evaluate the efficacy and safety of a low-dose diuretic for the prevention of hypertension and end-organ damage. METHODS AND RESULTS: This randomized, parallel, double-blind, placebo-controlled trial was conducted in 21 Brazilian academic medical centers. Participants with prehypertension who were aged 30 to 70 years and who did not reach optimal blood pressure after 3 months of lifestyle intervention were randomized to a chlorthalidone/amiloride combination pill or placebo and were evaluated every 3 months during 18 months of treatment. The primary outcome was incidence of hypertension. Development or worsening of microalbuminuria, new-onset diabetes mellitus, and reduction of left ventricular mass were secondary outcomes. Participant characteristics were evenly distributed by trial arms. The incidence of hypertension was significantly lower in 372 study participants allocated to diuretics compared with 358 allocated to placebo (hazard ratio 0.56, 95% CI 0.38-0.82), resulting in a cumulative incidence of 11.7% in the diuretic arm versus 19.5% in the placebo arm (P=0.004). Adverse events; levels of blood glucose, glycosylated hemoglobin, creatinine, and microalbuminuria; and incidence of diabetes mellitus were no different between the 2 arms. Left ventricular mass assessed through Sokolow-Lyon voltage and voltage-duration product decreased to a greater extent in participants allocated to diuretic therapy compared with placebo (P=0.02). CONCLUSIONS: A combination of low-dose chlorthalidone and amiloride effectively reduces the risk of incident hypertension and beneficially affects left ventricular mass in patients with prehypertension. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov, www.ensaiosclinicos.gov. Unique identifiers: NCT00970931, RBR-74rr6s.