Plasma Cortisol, Aldosterone, and Ascorbic Acid Concentrations in Patients with Septic Shock Do Not Predict Treatment Effect of Hydrocortisone on Mortality A Nested Cohort Study
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Authors: Cohen, Jeremy; Bellomo, Rinaldo; Billot, Laurent; Burrell, Louise M.; Evans, David M.; Finfer, Simon; Hammond, Naomi E.; Li, Qiang; Liu, David; McArthur, Colin; McWhinney, Brett; Moore, John; Myburgh, John; Peake, Sandra; Pretorius, Carel; Rajbhandari, Dorrilyn; Rhodes, Andrew; Saxena, Manoj; Ungerer, Jacobus P. J.; Young, Morag J.; Venkatesh, Balasubramanian
Abstract
Rationale: Whether biomarkers can identify subgroups of patients with septic shock with differential treatment responses to hydrocortisone is unknown. Objectives: To determine if there is heterogeneity in effect for hydrocortisone on mortality, shock resolution, and other clinical outcomes based on baseline cortisol, aldosterone, and ascorbic acid concentrations. Methods: From May 2014 to April 2017, we obtained serum samples from 529 patients with septic shock from 22 ICUs in Australia and New Zealand. Measurements and Main Results: There were no significant interactions between the association with 90-day mortality and treatment with either hydrocortisone or placebo for total cortisol odds ratio [OR], 1.09; 95% confidence interval [CI], 1.02-1.16 vs. OR, 1.07; 95% CI, 1.00-1.13; P = 0.70), free cortisol (OR, 1.20; 95% CI, 1.04-1.38 vs. OR, 1.16; 95% CI, 1.02-1.32; P = 0.75), aldosterone (OR, 1.01; 95% CI, 0.97-1.05 vs. OR, 1.01; 95% CI, 0.98-1.04; P = 0.99), or ascorbic acid (OR, 1.11; 95% CI, 0.89-1.39 vs. OR, 1.05; 95% CI, 0.91-1.22; P = 0.70), respectively. Similar results were observed for the association with shock resolution. Elevated free cortisol was significantly associated with 90-day mortality (OR, 1.13; 95% CI, 1.00-1.27; P = 0.04), but total cortisol, aldosterone, and ascorbic acid were not. Conclusions: In patients with septic shock, there was no heterogeneity in effect of adjunctive hydrocortisone on mortality, shock resolution, or other clinical outcomes based on cortisol, aldosterone, and ascorbic acid concentrations. Plasma aldosterone and ascorbic acid concentrations are not associated with outcome.
Impact of spironolactone exposure on prostate cancer incidence amongst men with heart failure: A Pharmacoepidemiological study
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
Authors: Hiebert, Brett M.; Janzen, Bryan W.; Sanjanwala, Rohan M.; Ong, Aldrich D.; Feldman, Ross D.; Kim, Julian O.
Abstract
Aims Aldosterone has been found to influence cancer cell growth, cell cycle regulation and cell migration, including in prostate cancer cells. Spironolactone is an aldosterone antagonist used for managing chronic heart failure (HF) with known antiandrogenic effects. We examined the effect of spironolactone exposure amongst men with HF on the incidence of prostate cancer. Methods This retrospective cohort study utilized provincial clinical and administrative databases from the Manitoba Centre for Health Policy. Incident cases of prostate cancer were identified from the provincial cancer registry, and spironolactone exposure was quantified from pharmacare databases. A multivariable proportional hazards model was used to assess the time-dependent impact of spironolactone exposure on prostate cancer incidence. Results A total of 18 562 men with newly diagnosed HF from 2007 to 2015 with a median age of 72 years (interquartile range: 61-81) and a median follow-up from HF diagnosis to prostate cancer incidence of 2.7 years (interquartile range: 1.1-4.9) were included. A time-dependent multivariable analysis of spironolactone exposure following HF diagnosis found a reduced the risk of prostate cancer hazard ratio 0.55 (95% confidence interval 0.31-0.98, P = .043). Conclusion Spironolactone exposure significantly reduced the incidence of prostate cancer amongst men with HF. These findings support the plausibility of aldosterone as a promoter of prostate cancer growth and development. Prospective clinical trials are warranted to further assess the role of spironolactone or other mineralocorticoid receptor antagonists as a means to prevent prostate cancer development or as an adjunctive measure to prostate cancer treatments.