Effect of Hypoglycemia on QT Interval in Individuals with and without Type 2 Diabetes: A Randomized Crossover Trial.

Background: Our goal was to determine in healthy individuals and individuals with type 2 diabetes the impact of repeated episodes of hypoglycemia on the corrected QT (QTc) interval and the time course for QTc recovery. Further, since hypoglycemia increases aldosterone and patients with primary aldosteronism have prolonged QTc, we also determined whether mineralocorticoid receptor blockade prevents hypoglycemia-induced QTc alterations.

Methods: Twenty-seven healthy participants completed a double-blinded crossover trial contrasting 3 experimental conditions: 1) euglycemia, 2) hypoglycemia, and 3) hypoglycemia with mineralocorticoid receptor blockade pretreatment.

Increased Salt Sensitive Blood Pressure in Women Versus men: Is Relative Hyperaldosteronism the Mechanism?

Context: Women versus men have more Salt sensitive blood pressure (SSBP) and higher stimulated aldosterone (ALDO) levels, suggesting that their increased SSBP is secondary to a relative hyper-ALDO state. Contrariwise, men versus women have higher sedentary ALDO levels.

Objective: Thus, the present project was designed to address the question are women versus men in a relatively hyper-ALDO state?

Methods: 363 women, and 483 men were selected from HyperPATH cohort to assess the potential underlying mechanism for observed sex differences.

Coronary Microvascular Dysfunction Is Present Among Well-Treated Asymptomatic Persons With HIV and Similar to Those With Diabetes.

Background: Coronary microvascular dysfunction (CMD) could be a potential underlying mechanism for myocardial disease in HIV.

Methods: Comparisons of coronary flow reserve corrected for heart rate-blood pressure product (CFR) were made among people with HIV (PWH) with no known history of cardiovascular disease (CVD) or diabetes mellitus, persons without HIV (PWOH), and persons with diabetes (PWDM) and no known history of CVD or HIV.

Results: PWH (n = 39, 74% male, age 55 [7] years, body mass index [BMI] 32.

Protocol for a randomized placebo-controlled clinical trial using pure palmitoleic acid to ameliorate insulin resistance and lipogenesis in overweight and obese subjects with prediabetes.

Palmitoleic acid (POA), a nonessential, monounsaturated omega-7 fatty acid (C16:1n7), is a lipid hormone secreted from adipose tissue and has beneficial effects on distant organs, such as the liver and muscle. Interestingly, POA decreases lipogenesis in toxic storage sites such as the liver and muscle, and paradoxically increases lipogenesis in safe storage sites, such as adipose tissue. Furthermore, higher POA levels in humans are correlated with better insulin sensitivity, an improved lipid profile, and a lower incidence of type-2 diabetes and cardiovascular pathologies, such as myocardial infarction.

Mineralocorticoid Receptor Antagonism by Eplerenone and Arterial Inflammation in HIV: The MIRABELLA HIV Study.

Importance: The risk for atherosclerotic disease is increased 1.5- to 2.0-fold among persons with HIV (PWH).

Striatin Gene Variants Are Associated With Salt Sensitivity of Blood Pressure by Mechanisms That Differ in Women and Men.

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.

Gene Polymorphisms Associate With Increased Blood Pressure and Salt Sensitivity of Blood Pressure in White Individuals.

Background: Disease-causing mutations in gene occur in aldosterone-producing adenomas and familial hyperaldosteronism. We determined whether single nucleotide polymorphisms in gene associate with higher aldosterone resulting in salt sensitivity of blood pressure (BP) and increased BP in men and women.

Methods: Data were obtained from the HyperPATH (International Hypertension Pathotypes) cohort, where participants completed a cross-over intervention of liberal and restricted sodium diets.

Effect of hypoglycemia on baroreflex sensitivity in individuals with type 2 diabetes: implications for autonomic control of cardiovascular function in diabetes.

Purpose: Hypoglycemia is associated with increased mortality, though the mechanisms underlying this association are not established. Hypoglycemia impairs the counterregulatory hormonal and autonomic responses to subsequent hypoglycemia. It is unknown whether hypoglycemia elicits a generalized impairment in autonomic control of cardiovascular function in individuals with type 2 diabetes.

Elevated Blood Pressure and Aldosterone Dysregulation in Young Black Women Versus White Women on Controlled Sodium Diets.

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.

Visceral Adiposity Index as a Measure of Cardiovascular Disease in Persons With Human Immunodeficiency Virus.

Background: Persons with well-treated human immunodeficiency virus (HIV) demonstrate a 2-fold higher risk of cardiovascular disease (CVD), which may be related to excess visceral adipose tissue (VAT). The visceral adiposity index (VAI) is a score to approximate VAT by combining biochemical measures with anthropometrics without quantification by imaging. We evaluated VAI in association with cardiometabolic factors among persons with HIV (PWH).

Randomized Placebo-Controlled Trial to Evaluate Effects of Eplerenone on Myocardial Perfusion and Function Among Persons With Human Immunodeficiency Virus (HIV)-Results From the MIRACLE HIV Study.

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.

Association Between Life's Simple 7 and Biomarkers of Cardiovascular Disease: Aldosterone, Interleukin-6, C-Reactive Protein.

Background To promote ideal cardiovascular health, the American Heart Association recommends adhering to Life's Simple 7 (LS7)-achieving healthy targets for body mass index, physical activity, dietary intake, blood pressure, fasting plasma glucose, and cholesterol, along with smoking abstinence. Poorer achievement of LS7 (lower score) has been associated with the development of hypertension and cardiovascular disease. However, less is known about the associations between LS7 and specific biomarkers linked to cardiovascular health: aldosterone, CRP (C-reactive protein), and IL-6 (interleukin-6).

Effects of Mineralocorticoid Receptor Blockade and Statins on Kidney Injury Marker 1 (KIM-1) in Female Rats Receiving L-NAME and Angiotensin II.

Kidney injury molecule-1 (KIM-1) is a biomarker of renal injury and a predictor of cardiovascular disease. Aldosterone, via activation of the mineralocorticoid receptor, is linked to cardiac and renal injury. However, the impact of mineralocorticoid receptor activation and blockade on KIM-1 is uncertain.

Role of renin-angiotensin-aldosterone system activation and other metabolic variables in relation to arterial inflammation in HIV.

Background: Arterial inflammation remains increased among persons with HIV (PWH) compared with persons without HIV (PWOH) even when controlling for traditional risk factors. We sought to understand whether increased renin-angiotensin-aldosterone system (RAAS) activation may be related to arterial inflammation in PWH and when compared with PWOH.

Design: Twenty PWH and 9 PWOH followed a controlled, standardized low and liberal sodium diet to simulate a RAAS-activated and RAAS-suppressed state, respectively.

Evaluation of Mineralocorticoid Receptor Antagonism on Changes in NT-proBNP Among Persons With HIV.

Unlabelled: Subclinical myocardial dysfunction is prevalent among well-treated persons with HIV (PWH). We have previously demonstrated unique renin-angiotensin-aldosterone system physiology among PWH with metabolic dysregulation. Mineralocorticoid receptor blockade may be a targeted treatment strategy for subclinical heart disease in PWH.

Effect of adrenocorticotropic hormone infusion on circulating sclerostin levels.

Glucocorticoid use is the most common cause of secondary osteoporosis. Poor skeletal health related to glucocorticoid use is thought to involve inhibition of the Wnt/β-catenin signaling pathway, a key pathway in osteoblastogenesis. Sclerostin, a peptide produced primarily by osteocytes, is an antagonist of the Wnt/β-catenin signaling pathway, raising the possibility that sclerostin is involved in glucocorticoids' adverse effects on bone.

Genetic Predictors of Salt Sensitivity of Blood Pressure: The Additive Impact of 2 Hits in the Same Biological Pathway.

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Biological sex modifies aldosterone's secretion at a cellular level.

Inconsistencies have been reported on the effect of sex on aldosterone (ALDO) levels leading to clinical confusion. The reasons for these inconsistencies are uncertain but include estrogen and/or its receptor modulating target gene responses to mineralocorticoid receptor activation and ALDO secretagogues' levels. This study's goal was to determine whether ALDO's biosynthesis also differed by sex.

Myeloid Mineralocorticoid Receptor Transcriptionally Regulates P-Selectin Glycoprotein Ligand-1 and Promotes Monocyte Trafficking and Atherosclerosis.

Objective: MR (mineralocorticoid receptor) activation associates with increased risk of cardiovascular ischemia while MR inhibition reduces cardiovascular-related mortality and plaque inflammation in mouse atherosclerosis. MR in myeloid cells (My-MR) promotes inflammatory cell infiltration into injured tissues and atherosclerotic plaque inflammation by unclear mechanisms. Here, we examined the role of My-MR in leukocyte trafficking and the impact of sex.

Acute effects of the food preservative propionic acid on glucose metabolism in humans.

Introduction: Propionic acid (PA) is a common food preservative generally recognized as safe by the US Food and Drug Administration; however, exogenous PA has effects on glucose metabolism that are not fully understood. Our preclinical studies demonstrated exogenous PA increases glucagon, norepinephrine, and endogenous glucose production (EGP).

Research Design And Methods: We performed a randomized, placebo-controlled, crossover study in 28 healthy men and women to determine the effect of PA (1500 mg calcium propionate) on these factors.

Associations of trauma and posttraumatic stress disorder with aldosterone in women.

Background: Posttraumatic 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.

The Role of Thyroid in Renovascular Function: Independent Association of Serum TSH With Renal Plasma Flow.

Context: There are well-established interactions between the thyroid and the kidney. Thyroid hypofunction is associated with reduced renal plasma flow (RPF), and hypothyroidism is highly prevalent in chronic kidney disease; however, less is known about the thyroid-kidney axis in the euthyroid state.

Objective: This work aimed to study the association of thyroid function with renovascular parameters in a well-phenotyped cohort of euthyroid normotensive and hypertensive individuals.

Striatin genotype-based, mineralocorticoid receptor antagonist-driven clinical trial: study rationale and design.

Objectives: In human studies and genetically altered mouse studies, variants in the striatin gene (STRN) are associated with increased blood pressure (BP) and aldosterone on a liberal salt diet. This clinical trial is based on the presumed mechanism for striatin-associated HTN - increased aldosterone. It is designed to determine if participants with the STRN risk alleles will have a greater BP reduction on a liberal salt diet with a specific, mechanism-based therapy - a mineralocorticoid receptor antagonist, eplerenone - as compared with a nonspecific anti-hypertensive therapy - amlodipine.