Posttraumatic stress disorder and incident heart failure among a community-based sample of US veterans.

OBJECTIVES: We investigated the association between posttraumatic stress disorder (PTSD) and incident heart failure in a community-based sample of veterans. METHODS: We examined Veterans Affairs Pacific Islands Health Care System outpatient medical records for 8248 veterans between 2005 and 2012. We used multivariable Cox regression to estimate hazard ratios and 95% confidence intervals for the development of heart failure by PTSD status. RESULTS: Over a mean follow-up of 7.2 years, veterans with PTSD were at increased risk for developing heart failure (hazard ratio [HR] = 1.47; 95% confidence interval [CI] = 1.13, 1.92) compared with veterans without PTSD after adjustment for age, gender, diabetes, hyperlipidemia, hypertension, body mass index, combat service, and military service period. Additional predictors for heart failure included age (HR = 1.05; 95% CI = 1.03, 1.07), diabetes (HR = 2.54; 95% CI = 2.02, 3.20), hypertension (HR = 1.87; 95% CI = 1.42, 2.46), overweight (HR = 1.72; 95% CI = 1.25, 2.36), obesity (HR = 3.43; 95% CI = 2.50, 4.70), and combat service (HR = 4.99; 95% CI = 1.29, 19.38). CONCLUSIONS: Ours is the first large-scale longitudinal study to report an association between PTSD and incident heart failure in an outpatient sample of US veterans. Prevention and treatment efforts for heart failure and its associated risk factors should be expanded among US veterans with PTSD.

Clusterin protects renal tubular epithelial cells from gentamicin-mediated cytotoxicity.

Clusterin is a heterodimeric secreted glycoprotein that is upregulated after acute renal injury. In aminoglycoside nephrotoxicity, clusterin is induced in the tubular epithelium and increased levels are found in the urine. In this study, we developed an in vitro model of gentamicin-induced cytotoxicity in renal proximal tubule cells and tested whether clusterin protected these cells from injury. LLC-PK(1) cells were incubated with varying concentrations of gentamicin in serum-free media, and cytotoxicity was quantified by lactate dehydrogenase release and confirmed by vital dye exclusion. A dose-dependent increase in cytotoxicity occurred with gentamicin concentrations up to 27 mg/ml. Clusterin decreased cytotoxicity in a dose- and time-dependent manner at 6, 12, and 24 h, whereas albumin, used as a control protein, had no effect. In contrast to the aminoglycoside model, when cells were injured by depletion of ATP, clusterin had only a minimally protective effect. LLC-PK(1) cells did not express megalin, a receptor that can mediate the uptake of both clusterin and aminoglycosides into proximal tubule cells. Uptake of gentamicin into LLC-PK(1) cells was observed despite the absence of megalin. In conclusion, clusterin specifically protects against gentamicin-induced renal tubular cell injury by a megalin-independent mechanism.