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BackgroundPosttraumatic stress disorder (PTSD) has been associated with increased cardiovascular risk, however, underlying mechanisms have not been fully specified. PTSD is associated with stress-related hormones, including dysregulated glucocorticoid activity. Dysregulation of aldosterone, a mineralocorticoid activated by psychological stress and implicated in cardiovascular damage, may be a relevant pathway linking PTSD and cardiovascular risk. Few studies to date have evaluated the association between PTSD and aldosterone, none with repeated measures of aldosterone. We examined if trauma and PTSD were associated with altered aldosterone levels relative to women unexposed to trauma.MethodsThe association of trauma exposure and chronic PTSD with plasma aldosterone levels was investigated in 521 middle-aged women in the Nurses' Health Study II. Aldosterone was assessed at two time points, 10-16 years apart, and trauma exposure and PTSD were also ascertained for both time points. Regarding exposure assessment, women were characterized based on a structured diagnostic interview as: having chronic PTSD (PTSD at both time points; n = 174); being trauma-exposed (trauma exposure at first time point but no PTSD; n = 174); and being unexposed (no trauma exposure at either time point; reference group for all analyses; n = 173). Linear mixed models examined associations of trauma and PTSD status with log-transformed aldosterone levels, adjusting for covariates and health-related variables that may confound or lie on the pathway between PTSD and altered aldosterone levels.ResultsAcross the sample, mean aldosterone concentration decreased over time. Adjusting for covariates, women with chronic PTSD had significantly lower aldosterone levels averaged over time, compared to women unexposed to trauma (β = - 0.08, p = 0.04). Interactions between trauma/PTSD group and time were not significant, indicating change in aldosterone over time did not differ by trauma/PTSD status. Post-hoc exploratory analyses suggested that menopausal status partially mediated the relationship between chronic PTSD status and aldosterone level, such that postmenopausal status explained 7% of the effect of PTSD on aldosterone.ConclusionsThese findings indicate that PTSD is associated with lower levels of aldosterone. Further work is needed to understand implications of this type of dysregulation in a key biological stress system for cardiovascular and other health outcomes previously linked with PTSD.

Context and objectiveWe examined whether a prevalent caveolin-1 gene (CAV1) variant, previously related to insulin resistance, is associated with metabolic syndrome (MetS).Patients and methodsWe included subjects genotyped for the CAV1 variant rs926198 from two cohorts: 735 Caucasians from the HyperPATH multicenter study, and 810 Hispanic participants from the HTN-IR cohort.ResultsMinor allele carriers from HyperPATH cohort (57% of subjects) had higher Framingham risk scores, higher odds of diabetes (10.7% vs 5.7%, p=0.016), insulin resistance (44.3% vs 35.1%, p=0.022), low HDL (49.3% vs 39.6%, p=0.018) and MetS (33% vs 20.5%, p

BACKGROUND: Salt sensitivity of blood pressure (SSBP) is a substantial risk factor for cardiovascular morbidity and mortality. Striatin (STRN) is critical for estrogen and aldosterone nongenomic signaling. However, the role of biological sex on the SSBP phenotype associated with STRN gene variants remains unexplored. METHOD: Data from 1306 subjects participating in the Hypertensive Pathotype (HyperPATH) Consortium were used to identify STRN gene single-nucleotide variants associated with SSBP. Haploblock analysis revealed a novel diplotype in the upstream regulatory region of STRN (rs888083 and rs6744560), with 31% of subjects being homozygous for the risk diplotype. RESULTS: Individuals homozygous for the risk diplotype had significantly greater SSBP than nonrisk diplotypes (P<0.009). While a significant genotype/SSBP association was present in both sexes, their potential mechanisms differed. Women, but not men homozygous risk diplotypes, had significantly greater aldosterone levels than nonrisk diplotypes (5.8±0.4 versus 3.2±0.7 ng/dl; P=0.01; liberal Na+ diet, adjusted). Men, but not women, homozygous risk diplotypes, had significantly reduced renal plasma flow response to Angiotensin II than nonrisk diplotypes (delta 95.2±5.2 versus 122.9±10.2 mL/min per 1.73 m²; P=0.01; liberal Na+ diet, adjusted). The single-nucleotide variants composing the risk diplotype were associated with lower STRN mRNA expression in human tissues (in silico). CONCLUSION: In women, the primary driver of SSBP is increased aldosterone, while in men, it is reduced renal plasma flow responses. Thus, despite a common hypertensive phenotype (SSBP) in both sexes, the specific treatment approaches might differ to increase therapeutic gain and mitigate adverse effects. These genetic- and sex-based observational results require confirmation in a prospective clinical study. [ABSTRACT FROM AUTHOR]

Context Black women have a higher prevalence of hypertension as compared to White women. Differences in dietary sodium intake have been implicated as a contributing factor for the disparities in hypertension. Objective Our objective was to understand whether young Black women would have higher systolic blood pressure (SBP) than White women even on controlled sodium diets and to determine whether SBP differences were due to differences in dietary sodium intake and/or aldosterone regulation. Design The analyses included 525 hypertensive and normotensive women (ages 18-71) from the International Hypertensive Pathotype consortium, who were maintained on liberal sodium (LIB; >200 mEq sodium/day) and restricted sodium (RES; 10 mEq sodium/day) diets. Results Multivariate regression analyses (adjusted for age, race, study site, body mass index) found that Black women (ages 18-50) had significantly higher SBP than White women on both sodium diets: +8.7 ± 2.7 mmHg (P -value =.002) on a LIB diet and +8.5 ± 2.5 mmHg (P -value =.001) on a RES diet. Even among 18- to 35-year-olds—who were normotensive and nonobese—Black women had higher SBP: +7.9 ± 2.4 mmHg (P -value =.001) on a LIB diet and +7.6 ± 2.7 mmHg (P -value =.005) on a RES diet. Younger Black women also had higher plasma aldosterone concentration to plasma renin activity ratio (ARR) on both LIB and RES diets as well as a higher sodium-modulated aldosterone suppression-stimulation index—an indicator of aldosterone dysregulation. In younger Black women—but not in White women—there was a significant association between SBP and ARR on both LIB and RES diets. Conclusion Young Black women had increased SBP and ARR as compared to White women on LIB and RES diets, which offers insights into the possible mechanisms for the increased hypertension and cardiovascular disease risk in an at-risk and understudied population. [ABSTRACT FROM AUTHOR]

Background Increased renin angiotensin aldosterone system (RAAS) activity may contribute to excess cardiovascular disease in people with HIV (PWH). We investigated how RAAS blockade may improve myocardial perfusion, injury, and function among well-treated PWH. Methods Forty PWH, on stable ART, without known heart disease were randomized to eplerenone 50 mg PO BID (n = 20) or identical placebo (n = 20) for 12 months. The primary endpoints were (1) myocardial perfusion assessed by coronary flow reserve (CFR) on cardiac PET or stress myocardial blood flow (sMBF) on cardiac MRI or (2) myocardial inflammation by extracellular mass index (ECM i) on cardiac MRI. Results Beneficial effects on myocardial perfusion were seen for sMBF by cardiac MRI (mean [SD]: 0.09 [0.56] vs −0.53 [0.68] mL/min/g; P =.03) but not CFR by cardiac PET (0.01 [0.64] vs −0.07 [0.48]; P =.72, eplerenone vs placebo). Eplerenone improved parameters of myocardial function on cardiac MRI including left ventricular end diastolic volume (−13 [28] vs 10 [26] mL; P =.03) and global circumferential strain (GCS; median [interquartile range 25th–75th]: −1.3% [−2.9%–1.0%] vs 2.3% [−0.4%–4.1%]; P =.03), eplerenone versus placebo respectively. On cardiac MRI, improvement in sMBF related to improvement in global circumferential strain (ρ = −0.65, P =.057) among those treated with eplerenone. Selecting for those with impaired myocardial perfusion (CFR <2.5 and/or sMBF <1.8), there was a treatment effect of eplerenone versus placebo to improve CFR (0.28 [0.27] vs −0.05 [0.36]; P =.04). Eplerenone prevented a small increase in troponin (0.00 [−0.13–0.00] vs 0.00 [0.00–0.74] ng/L; P =.03) without effects on ECM i (0.9 [−2.3–4.3] vs −0.7 [−2.2–−0.1] g/m2; P =.38). CD4+ T-cell count (127 [−38–286] vs −6 [−168–53] cells/μL; P =.02) increased in the eplerenone- versus placebo-treated groups. Conclusions RAAS blockade with eplerenone benefitted key indices and prevented worsening of myocardial perfusion, injury, and function among PWH with subclinical cardiac disease when compared with placebo. Clinical Trials Registration NCT02740179 (https://clinicaltrials.gov/ct2/show/NCT02740179?term=NCT02740179&draw=2&rank=1). [ABSTRACT FROM AUTHOR]