A clinical trial to evaluate the effect of statin use on lowering aldosterone levels.

BACKGROUND: Statins are the first-line pharmaceutical agent in the management of hypercholesterolemia and cardiovascular (CV) risk reduction, and the most commonly prescribed class of drugs worldwide. Studies describing CV risk reduction independent of LDL-cholesterol lowering have evoked an interest in the pleiotropic mechanisms of statins' benefits. We recently demonstrated that administration of statins in animal models lowers aldosterone levels and observed an association between statin use and reduced aldosterone levels in two human cohorts, with lipophilic statins displaying a greater effect than hydrophilic statins. Therefore, we designed a randomized, placebo-controlled, double-blinded intervention study to assess whether statin treatment lowers aldosterone in a type-dependent manner in humans, with simvastatin (lipophilic) showing a greater effect than pravastatin (hydrophilic). METHODS/DESIGN: One hundred five healthy participants will be recruited from the general population to enroll in a 12-week, randomized, placebo-controlled, double-blinded, 3-arm clinical trial. Ninety participants are anticipated to complete the protocol. After baseline assessment of aldosterone levels, participants will be randomized to daily simvastatin, pravastatin, or placebo. Aldosterone levels will be assessed after 2 days on study drug and again after 6 weeks and 12 weeks on study drug. Prior to each aldosterone assessment, participants will consume an isocaloric sodium and potassium-controlled run-in diet for 5 days. Assessments will occur on an inpatient research unit to control for diurnal, fasting, and posture conditions. The primary outcome will compare 12-week angiotensin II-stimulated serum aldosterone by study drug. Secondary outcomes will compare baseline and 12-week 24-h urine aldosterone by study drug. DISCUSSION: Results from this rigorous study design should provide strong support that statins lower aldosterone levels in humans. These results may explain some of the beneficial effects of statins that are not attributed to the LDL-lowering effect of this important class of medications. Results would demonstrate that statin lipophilicity is an important attribute in lowering aldosterone levels. The outcomes of this program will have implications for the design of studies involving statin medications, as well as for the differential use of classes of statins. TRIAL REGISTRATION: ClinicalTrials.gov; NCT02871687 ; First Posted August 18, 2016.

Pediatric pneumomediastinum: Symptom-based management.

BACKGROUND: Pediatric spontaneous pneumomediastinum is known to have a benign course. Despite this, there is no consensus or standardization for the workup and management. There are often a variety of imaging studies performed for patients with similar presentations. METHODS: This is a retrospective chart review evaluating the presentation, workup, and management of all pediatric patients with a primary diagnosis of spontaneous pneumomediastinum over a 5-year period at a children's hospital. RESULTS: Of the 62 patients, the initial workup consisted of either a chest x-ray (CXR) only (n = 31, 50%), a chest computed tomography scan only (n = 11, 18%) or both (n = 14, 23%); additionally, some patients came with 'other' imaging only (n = 3, 5%) or no imaging (n = 3, 5%). Twenty-seven patients (44%) underwent an additional CXR and 19 (31%) underwent an esophagram. All esophagrams were negative for an esophageal leak. A presenting symptom of pain was associated with a hospital stay of less than 24 h (p = 0.008) while shortness of breath (p = 0.0005) and emesis (p = 0.0006) were associated with a hospital stay of greater than 24 h. Associated diagnoses of respiratory infections (p = 0.02) and gastrointestinal issues (p = 0.006), such as hyperemesis, were associated with inpatient admission. CONCLUSION: Pediatric patients with spontaneous pneumomediastinum benefit from evaluation, management, and treatment based on their presenting symptoms. There is an opportunity to decrease unnecessary radiation exposure in this patient population with fewer CXRs and avoidance of esophagrams, neither of which alter management. LEVEL OF EVIDENCE: Level III.

Physical Activity and the Acute Hemodynamic Response to ACE Inhibition in Hypertension.

Introduction. Physical activity (PA) can reduce blood pressure (BP) in hypertensives through possibly interacting with the renin-angiotensin-aldosterone system (RAAS). We conducted a nested-cohort analysis to determine if self-reported PA was associated with BP responsiveness to acute angiotensin converting enzyme inhibition (ACEi). Methods. Data were extracted from the HyperPATH dataset, a cohort designed to identify mechanisms of cardiometabolic risk. Hypertensives that completed a self-assessed PA questionnaire, hormonal assessments (aldosterone [ALDO]), and BP to a single dose of an ACEi (captopril, 25 mg) were included. All participants (n = 144) were studied on a controlled diet for 7 days. PA was recorded as no PA, or little, moderate, or high amounts of exercise. Analyses were adjusted for age, sex, race, and body mass index. Results. Individuals who reported high amounts of PA displayed a greater BP lowering effect from ACEi compared to those who reported moderate (-14.8 ± 8.1 vs -8.4 ± 9.9 mm Hg, P < .01) or no additional PA (-14.8 ± 8.1 vs -2.6 ± 9.9 mm Hg, P < .001). Exploratory analyses indicated high amounts of PA were associated with a reduced heart rate (54 ± 8 vs 66 ± 10 bpm, P < .001) and blunted ALDO (ß = 0.44, 95% confidence interval = 0.19-0.70). Conclusions. Higher self-reported PA was associated with an augmented BP lowering effect to acute ACEi in hypertensive patients.