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Diabetes confers greater cardiovascular risk to women than to men. Whether insulin-resistance-mediated risk extends to the healthy population is unknown. Measures of insulin resistance (fasting insulin, homeostatic model assessment, hemoglobin A1c, quantitative insulin sensitivity check index, glucose) were determined in 48 (56% female) healthy subjects. Heart rate variability (HRV) was calculated by spectral power analysis and arterial stiffness was determined using noninvasive applanation tonometry. Both were measured at baseline and in response to angiotensin II infusion. In women, there was a non-statistically significant trend towards increasing insulin resistance being associated with an overall unfavourable HRV response and increased arterial stiffness to the stressor, while men demonstrated the opposite response. Significant differences in the associations between insulin resistance and cardiovascular physiological profile exist between healthy women and men. Further studies investigating the sex differences in the pathophysiology of insulin resistance in cardiovascular disease are warranted. Key words: insulin resistance, cardiac autonomic tone, human, women, heart rate variability, arterial stiffness, cardiovascular, angiotensin II. Le diabete expose les femmes a un risque cardiovasculaire plus eleve que chez les hommes. On ne sait pas si le risque qu'entraine la resistance a l'insuline s'applique aussi a la population en bonne sante. Chez 48 sujets en bonne sante (56% de femmes), nous avons effectue les mesures de resistance a l'insuline suivantes : taux d'insuline a jeun, indice HOMA (pour <>), taux d'hemoglobine glyquee, indice QUICKI (pour <>), glycemie. Nous avons calcule la variabilite de la frequence cardiaque (VFC) a l'aide de l'analyse spectrale de puissance et etabli la rigidite arterielle a l'aide de la tonometrie d'aplanation, une technique non effractive. Les deux mesures ont ete effectuees au debut de l'etude et en reaction a une perfusion d'angiotensine II. Chez la femme, nous avons observe une tendance non significative sur le plan statistique vers une augmentation de la resistance a l'insuline associee a une reaction en matiere de VFC (non favorable dans l'ensemble), ainsi qu'a une augmentation de la rigidite arterielle en reaction a l'agent stressant, tandis que nous avons observe des reactions opposees chez l'homme. L'association de la resistance a l'insuline avec le profil cardiovasculaire physiologique est tres differente entre les hommes et les femmes en bonne sante. Il serait judicieux d'effectuer plus d'etudes portant sur les differences entre les sexes en matiere de physiopathologie de la resistance a l'insuline dans les maladies cardiovasculaires. [Traduit par la Redaction] Mots-cles : resistance a l'insuline, tonus cardiaque autonome, humain, femmes, variabilite de la frequence cardiaque, rigidite arterielle, systeme cardiovasculaire, angiotensine II., Introduction Insulin resistance is a stronger cardiovascular risk in women than in men (Oterdoom et al. 2009). The risk factors for early cardiac autonomic impairment differ among diabetic women and [...]

Obstructive sleep apnea (OSA) is common in heart and kidney disease, both conditions prone to fluid retention. Nocturnal rostral fluid shift contributes to the pathogenesis of OSA in men more than women, suggesting a potential role for sex differences in body fluid composition in the pathogenesis of OSA, with men having a predisposition to more severe OSA due to an underlying volume expanded state. Continuous positive airway pressure (CPAP) increases intraluminal pressure in the upper airway and mitigates the rostral fluid shift; this, in turn, may prevent fluid redistribution from other parts of the body to the upper airway. We sought to determine the impact of CPAP on sex differences in body fluid composition. Twenty‐nine (10 women, 19 men) incident, sodium replete, otherwise healthy participants who were referred with symptomatic OSA (oxygen desaturation index >15/h) were studied pre‐ and post‐CPAP (>4 h/night × 4 weeks) using bioimpedance analysis. Bioimpedance parameters including fat‐free mass (FFM, %body mass), total body water (TBW, %FFM), extracellular and intracellular water (ECW and ICW, %TBW), and phase angle (°) were measured and evaluated for sex differences before and after CPAP. Pre‐CPAP, despite TBW being similar between sexes (74.6 ± 0.4 vs. 74.3 ± 0.2%FFM, p = 0.14; all values women vs. men), ECW (49.7 ± 0.7 vs. 44.0 ± 0.9%TBW, p < 0.001) was increased, while ICW (49.7 ± 0.5 vs. 55.8 ± 0.9%TBW, p < 0.001) and phase angle (6.7 ± 0.3 vs. 8.0 ± 0.3°, p = 0.005) were reduced in women compared to men. There were no sex differences in response to CPAP (∆TBW –1.0 ± 0.8 vs. 0.7 ± 0.7%FFM, p = 0.14; ∆ECW –0.1 ± 0.8 vs. −0.3 ± 1.0%TBW, p = 0.3; ∆ICW 0.7 ± 0.4 vs. 0.5 ± 1.0%TBW, p = 0.2; ∆Phase Angle 0.2 ± 0.3 vs. 0.0 ± 0.1°, p = 0.7). Women with OSA had baseline parameters favoring volume expansion (increased ECW, reduced phase angle) compared to men. Changes in body fluid composition parameters in response to CPAP did not differ by sex. We utilized bio‐electrical impedance analysis to assess sex differences in body composition in 10 women and 19 men with obstructive sleep apnea (OSA) before and after treatment with continuous positive airway pressure (CPAP) therapy. We observed that despite similar total body water (% fat‐free mass), women with OSA had increased extracellular water and reduced intracellular water compared to men, suggestive of a volume expanded state, though the response of these body composition parameters to 1 month of CPAP therapy did not differ by sex. Our findings support that there are underlying sex differences in body composition in OSA, though contrary to our expectations, women with OSA in our study had body composition parameters which favored volume expansion compared to men. Importantly, the impact of CPAP therapy on body composition did not differ by sex. [ABSTRACT FROM AUTHOR]

Introduction: Despite the availability of various pressure injury (PI) prevention strategies (e.g., risk identification, use of pressure re-distribution surfaces, frequent repositioning), they persist as a significant issue for healthcare systems worldwide. Continuous pressure imaging (CPI) is a novel technology that could be integrated within a comprehensive approach to the prevention of PIs. We studied the perceptions of healthcare providers and patients/families to identify facilitators and barriers to the use of this technology. Methods: Hospitalized patients/family members from a randomized controlled trial assessing the efficacy of CPI in preventing PIs completed a survey after 72 hours (or upon discharge from hospital) of CPI monitoring. They were asked questions about prior and current experience with CPI technology. For healthcare providers, perceptions on the use of the device and its impact on care were explored through a survey distributed by email or hard copies. Results: A total of 125 healthcare providers and 525 patients/family members completed the surveys. Of the healthcare providers, 95% either agreed/strongly agreed that the CPI technology was easy to use and 65% stated that the device improved how they provided pressure relief for patients. Identified issues with the device were cost, the fitting of the mattress cover, and the fixation of the patients/families on the device. Over a quarter of the patient/family respondents agreed/strongly agreed that the device influenced how pressure relief was provided. This response was statistically associated with whether the monitor was turned on (intervention arm; 52.7%) or off (control arm; 4.2%). Discussion and conclusion: CPI technology was positively perceived by healthcare providers. Most patients/families felt it influenced care when the CPI monitor was turned on. Concerns raised around cost and the ease of use of these devices by healthcare providers may affect the decisions of healthcare system administrators to adopt and implement this technology. [ABSTRACT FROM AUTHOR]

Transgender women (individuals assigned male sex at birth who identify as women) and nonbinary and gender-diverse individuals receiving gender-affirming estrogen therapy (GAET) are at increased cardiovascular risk. Nonoral (i.e., patch, injectable) compared with oral estrogen exposure in cisgender women (individuals assigned female sex at birth who identify as women) may be associated with lower cardiovascular risk, though whether this applies to transgender women and/or gender-diverse individuals is unknown. We sought to determine the association between the route of estrogen exposure (nonoral compared with oral) and cardiovascular risk in transgender women and gender diverse individuals. Bibliographic databases (MEDLINE, Embase, PsycINFO) and supporting relevant literature were searched from inception to January 2022. Randomized controlled trials and observational studies reporting cardiovascular outcomes, such as all-cause and cardiovascular mortality, adverse cardiovascular events, and cardiovascular risk factors in individuals using nonoral compared with oral gender-affirming estrogen therapy were included. The search strategy identified 3,113 studies, 5 of which met inclusion criteria (3 prospective cohort studies, 1 retrospective cohort study, and 1 cross-sectional study; n = 259 participants, range of duration of exposure of 2 to 60 mo). One out of five studies reported on all-cause and cardiovascular mortality or adverse cardiovascular events. All five studies reported lipid levels [low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), and total cholesterol (TC)], whereas only two studies reported systolic blood pressure (SBP) and diastolic blood pressure (DBP). Limited studies have examined the effect of the route of GAET on all-cause cardiovascular mortality, morbidity, and risk factors. In addition, there is significant heterogeneity in studies examining the cardiovascular effects of GAET. NEW & NOTEWORTHY This study is the first to summarize the potential effect of nonoral versus oral gender-affirming estrogen therapy use on cardiovascular risk factors in transgender women or nonbinary or gender-diverse individuals. Heterogeneity of studies in reporting gender-affirming estrogen therapy formulation, dose, and duration of exposure limits quantification of the effect of gender-affirming estrogen therapy on all-cause and cardiovascular mortality, adverse cardiovascular events, and cardiovascular risk factors. This systematic review highlights the needs for large prospective cohort studies with appropriate stratification of gender-affirming estrogen therapy by dose, formulation, administration route, and sufficient follow-up and analyses to limit selection bias to optimize the cardiovascular care of transgender, nonbinary, and gender-diverse individuals. [ABSTRACT FROM AUTHOR]

Low estradiol status is associated with increased cardiovascular risk. We sought to determine the association between heart rate variability (HRV), a marker of cardiovascular risk, at baseline and in response to stressor as a function of menopausal status, menstrual cycle phase and estradiol level. Forty‐one healthy women (13 postmenopausal, 28 premenopausal) were studied. Eleven premenopausal women were additionally studied in the high and low estradiol phases of the menstrual cycle. HRV was calculated by spectral power analysis (low Frequency (LF), high frequency (HF) and LF:HF) at baseline and in response to graded Angiotensin II (AngII) infusion. The primary outcomes were differences in HRV at baseline and in response to AngII. Compared to premenopausal women in the low estradiol phase, postmenopausal women demonstrated lower baseline LF (p = 0.01) and HF (p < 0.001) measures, which were not significant after adjustment for age and BMI. In response to AngII, a decrease in cardioprotective HRV (ΔHF = −0.43 ± 0.46 ln ms2, p = 0.005 vs. baseline) was observed in postmenopausal women versus premenopausal women. Baseline HRV parameters did not differ by menstrual phase in premenopausal women. During the low estradiol phase, no differences were observed in the HRV response to AngII challenge. In contrast, women in the high estradiol phase were unable to maintain HRV (ΔLF = −0.07 ± 0.46 ln ms2, p = 0.048 response vs. baseline, ΔHF = −0.33 ± 0.74 ln ms2, p = 0.048 response vs. baseline). No association was observed between any measure of HRV and estradiol level. Menopausal status and the high estradiol phase in premenopausal women were associated with reduced HRV, a marker of cardiovascular risk. Understanding the role of estradiol in the modulation of cardiac autonomic tone may help guide risk reduction strategies in women. [ABSTRACT FROM AUTHOR]

Introduction: Sex influences the cardiovascular risk associated with body mass index (BMI) in older adults. Whether this risk differs by sex in younger adults is unknown. We aimed to evaluate the association between measures of adiposity and arterial stiffness and reninangiotensin‐aldosterone system (RAAS) activity in younger adults, stratified by sex. Methods: Body mass index (BMI), waist circumference (WC), hip circumference (HC), waist‐to‐hip ratio (WHR), waist‐to‐height ratio (WHtR) and fat mass% (FM%) were measured in healthy participants in a fasting, high‐salt state. Arterial stiffness [pulse wave velocity (PWV) and aortic augmentation index (AIx)] were measured at baseline and in response to angiotensin II challenge, a validated marker of RAAS activity. Associations were evaluated using linear regression analysis and stratified by sex. Results: Ninety‐five healthy, normotensive, non‐diabetic females (n = 67, 37 ± 2 y, BMI 25 ± 1 kg/m2) and males (n = 28, 39 ± 3 y, BMI 27 ± 1 kg/m2) participated in the study. No association was observed between any measure of adiposity and PWV, either at baseline or in response to angiotensin II challenge in premenopausal females. In contrast, all measures of adiposity except HC were associated with PWV at baseline (BMI r = 0.32; WC r = 0.18; WHtR r = 0.34; FM r = 0.21; all values p <.05) and in response to AngII (BMI r = −0.39; WC r = −0.42; WHR r = −0.39; and WHtR r = −0.55) in males. Most adiposity measures were positively associated with baseline AIx (BMI r = 0.33; WC r = 0.27; WHtR r = 0.35; FM% r = 0.25; p <.05) in females, while only WHtR was associated with baseline AIx (r = 0.39; p =.04) in males. All measures of adiposity were positively associated with a blunted Aix response to Ang II (all values p <.001) in females. BMI, WC, WHR and WHtR were associated with a blunted AIx response to Ang II (ΔAIx: BMI r = −0.37; WC r = −0.31; WHR r = −0.16; and WHtR r = −0.22; all values p <.05) in males. Conclusion: The associations between adiposity measures and cardiovascular risk differ by sex in a young population. These factors should be considered when managing cardiovascular risk. [ABSTRACT FROM AUTHOR]

Men have faster loss of kidney function and greater renal renin-angiotensin system (RAS) activity compared with women. Obstructive sleep apnea (OSA) is common in chronic kidney disease; the vascular effects of OSA differ by sex, and OSA-associated glomerular hyperfiltration can be reversed by continuous positive airway pressure (CPAP) therapy. We evaluated sex differences in the effect of CPAP on renal hemodynamics and the renal RAS in OSA. Twenty-nine Na-replete, otherwise healthy study participants with OSA (10 women and 19 men) with nocturnal hypoxemia were studied pre- and post-CPAP (-4 h/night for 4 wk). Renal hemodynamics [renal plasma flow (RPF), glomerular filtration rate (GFR), and filtration fraction(FF)] were measured at baseline and in response to ANG II challenge, as a marker of renal RAS activity, pre- and post-CPAP therapy for 1 mo. In women, CPAP was associated with increased RPF (626 ± 22 vs. 718 ± 43 mL/min, P = 0.007, pre- vs. post- CPAP), maintained GFR (108 ± 2 vs. 105 ± 3 mL/min, P = 0.8), and reduced FF (17.4 ± 0.8% vs. 15.0 ± 0.7%, P = 0.017). In men, CPAP was associated with maintained RPF (710 ± 37 vs. 756 ± 38 mL/min, P = 0.1), maintained GFR (124 ± 8 vs. 113 ± 6 mL/min, P = 0.055), and reduced FF (18.6 ± 1.7% vs. 15.5 ± 1.1%, P = 0.035). Pre-CPAP, there were no sex differences in renal hemodynamic responses to ANG II. CPAP use was associated with a greater renovasoconstrictive response to ANG II in women (RPF at 30 min: -100 ± 27 vs. -161 ± 25 mL/min, P = 0.007, and RPF at 60 min: -138 ± 27 vs. -206 ± 32 mL/min, P = 0.007) but not men. CPAP use was associated with improved renal hemodynamics in both sexes and downregulated renal RAS activity in women but not men. [ABSTRACT FROM AUTHOR]

Compared to other cyclooxygenase-2 inhibitors, celecoxib is associated with a lower cardiovascular risk, though the mechanism remains unclear. Angiotensin II is an important mediator of oxidative stress in the pathophysiology of vascular disease. Cyclooxygenase-2 may modify the effects of angiotensin II though this has never been studied in humans. The purpose of the study was to test the effects of selective cyclooxygenase-2 inhibition on plasma measures of oxidative stress, the vasoconstrictor endothelin-1, and nitric oxide metabolites, both at baseline and in respose to Angiotensin II challenge in healthy humans. Measures of 8-hydroxydeoxyguanosine, advanced oxidation protein products, nitrotyrosine, endothelin-1, and nitric oxide metabolites were assessed from plasma samples drawn at baseline and in response to graded angiotensin II infusion (3 ng/kg/min × 30min, 6 ng/kg/min × 30min) before and after 14 days of cyclooxygenase-2 inhibition in 14 healthy subjects (eight male, six female) in high salt balance, a state of maximal renin angiotensin system suppression. Angiotensin II infusion significantly increased plasma oxidative stress compared to baseline (8-hydroxydeoxyguanosine; +17%; advanced oxidation protein products; +16%), nitrotyrosine (+76%). Furthermore, levels of endothelin-1 levels were significantly increased (+115%) and nitric oxide metabolites were significantly decreased (-20%). Cycloxygenase-2 inhibition significantly limited the increase in 8- hydroxydeoxyguanosine, nitrotyrosine and the decrease in nitric oxide metabolites induced by angiotensin II infusion, though no changes in advanced oxidation protein products and endothelin-1 concentrations were observed. Cyclooxygenase-2 inhibition with celecoxib partially limited the angiotensin II-mediated increases in markers of oxidative stress in humans, offering a potential physiological pathway for the improved cardiovascular risk profile of this drug. [ABSTRACT FROM AUTHOR]

End-stage kidney disease (ESKD) patients are at increased cardiovascular risk. Vitamin D deficiency is associated with depressed heart rate variability (HRV), a risk factor depicting poor cardiac autonomic tone and risk of cardiovascular death. Vitamin D deficiency and depressed HRV are highly prevalent in the ESKD population. We aimed to determine the effects of oral vitamin D supplementation on HRV ((low frequency (LF) to high frequency (HF) spectral ratio (LF:HF)) in ESKD patients on hemodialysis. Fifty-six subjects with ESKD requiring hemodialysis were recruited from January 2013-March 2015 and randomized 1:1 to either conventional (0.25 mcg alfacalcidol plus placebo 3x/week) or intensive (0.25 mcg alfacalcidol 3x/week plus 50,000 international units (IU) ergocalciferol 1x/week) vitamin D for six weeks. The primary outcome was the change in LF:HF. There was no difference in LF:HF from baseline to six weeks for either vitamin D treatment (conventional: p = 0.9 vs. baseline; intensive: p = 0.07 vs. baseline). However, participants who remained vitamin D-deficient (25-hydroxyvitamin D < 20 ng/mL) after treatment demonstrated an increase in LF:HF (conventional: n = 13, DLF:HF: 0.20 - 0.06, p < 0.001 vs. insufficient and sufficient vitamin D groups; intensive: n = 8: DLF:HF: 0.15 - 0.06, p < 0.001 vs. sufficient vitamin D group). Overall, six weeks of conventional or intensive vitamin D only augmented LF:HF in ESKD subjects who remained vitamin D-deficient after treatment. Our findings potentially suggest that while activated vitamin D, with or without additional nutritional vitamin D, does not appear to improve cardiac autonomic tone in hemodialysis patients with insufficient or sufficient baseline vitamin D levels, supplementation in patients with severe vitamin D deficiency may improve cardiac autonomic tone in this higher risk sub-population of ESKD. Trial Registration: ClinicalTrials.gov, NCT01774812. [ABSTRACT FROM AUTHOR]

Objective: Men have high cardiovascular risk and unfavourable cardiac autonomic tone compared to premenopausal women. The role of sex hormones in control of autonomic tone is unclear. We sought to determine the association between sex hormones and cardiosympathovagal tone at baseline and in response to a physiological stressor. Methods: Forty-eight healthy subjects (21 men, 27 premenopausal women) were studied in high-salt balance. Cardiac autonomic tone was assessed by heart rate variability, calculated by spectral power analysis (low frequency (LF, a measure of sympathetic modulation), high frequency (HF, a measure of vagal modulation) and LF:HF (a measure of cardiosympathovagal balance)) at baseline and in response to graded Angiotensin II (AngII) infusion (3 ng/kg/min × 30 min, 6 ng/kg/min ×30 min) were measured. The primary outcome was association between endogenous sex hormone levels and measures of cardiac autonomic tone. Results: All subjects had sex hormone levels in the normal range. No associations were observed between sex hormones and baseline cardiac autonomic tone in men or women. Men with lower testosterone levels, however, were unable to maintain both cardiosympathetic ( p = 0.045) and cardiovagal tone ( p = 0.035) in response to AngII even after adjustments for covariates. No association was observed between estradiol and progesterone and cardiac autonomic response to AngII in either sex. Conclusion: An unfavourable shift in the cardiac autonomic tone in men with lower testosterone levels was observed in response to a stressor. Understanding the role of sex hormones in modulation of cardiac autonomic tone may help guide risk reduction strategies in men. [ABSTRACT FROM AUTHOR]

Uric acid is associated with hypertension and increased renin-angiotensin system activity, although this relationship diminishes after chronic exposure to high levels. Uric acid is more strongly associated with poor outcomes in women compared to men, although whether this is due to a sex-specific uric acid-mediated pathophysiology or reflects sex differences in baseline uric acid levels remains unknown. We examined the association between uric acid and vascular measures at baseline and in response to angiotensin- II challenge in young healthy humans. Fifty-two subjects (17 men, 35 premenopausal women) were studied in high-salt balance. Serum uric acid levels were significantly higher in men compared to women (328 ± 14 μmol/L vs. 248 ± 10 μmol/L, P < 0.001), although all values were within normal sex-specific range. Men demonstrated no association between uric acid and blood pressure, either at baseline or in response to angiotensin- II. In stark contrast, a significant association was observed between uric acid and blood pressure at baseline (systolic blood pressure, P = 0.005; diastolic blood pressure, P = 0.02) and in response to angiotensin- II (systolic blood pressure, P = 0.035; diastolic blood pressure, P = 0.056) in women. However, this sex difference lost significance after adjustment for baseline uric acid. When all subjects were stratified according to high (>300 μmol/L) or low (≤300 μmol/L) uric acid levels, only the low uric acid group showed a positive association between uric acid and measures of vascular tone at baseline and in response to angiotensin- II. Differences in uric acid-mediated outcomes between men and women likely reflect differences in exposure to increased uric acid levels, rather than a sex-specific uric acid-mediated pathophysiology. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency is associated with increased arterial stiffness. We sought to clarify the influence of vitamin D in modulating angiotensin II-dependent arterial stiffness. Thirty-six healthy subjects (33 ± 2 years, 67% female, mean 25-hydroxyvitamin D 69 ± 4 nmol/L) were studied in high salt balance. Arterial stiffness, expressed as brachial pulse wave velocity (bPWV) and aortic augmentation index (AIx), was measured by tonometry at baseline and in response to angiotensin II infusion (3 ng/kg/min × 30 min then 6 ng/kg/min × 30 min). The primary outcome was change in bPWV after an angiotensin II challenge. Results were analyzed according to plasma 25-hydroxyvitamin D status: deficient (<50 nmol/L) and sufficient (≥50 nmol/L). There were no differences in baseline arterial stiffness between vitamin D deficient (25-hydroxyvitamin D 40 ± 2 nmol/L) and sufficient (25-hydroxyvitamin D 80 ± 4 nmol/L) groups. Compared with sufficient vitamin D status, vitamin D deficiency was associated with a decreased arterial response to angiotensin II challenge (Δbrachial pulse wave velocity: 0.48 ± 0.44 m/s versus 1.95 ± 0.22 m/s, p = 0.004; Δaortic augmentation index: 9.4 ± 3.4% versus 14.2 ± 2.7%, p = 0.3), which persisted for brachial pulse wave velocity response after adjustment for covariates ( p = 0.03). Vitamin D deficiency is associated with increased arterial stiffness in healthy humans, possibly through an angiotensin II-dependent mechanism. [ABSTRACT FROM AUTHOR]

Increased levels of albuminuria and proteinuria, both linked to augmented renin-angiotensin system (RAS) activity, are associated with adverse kidney and cardiovascular events. However, the relationship between variations in urinary albumin excretion (UAE) and total protein excretion (UTPE) in the normal range and RAS activity is unclear. We examined the association between UAE and UTPE and the hemodynamic response to angiotensin II (ANG II) challenge, a well-accepted indirect measure of RAS activity, in healthy individuals with normal UAE and UTPE. Forty subjects (15 men, 25 women; age 38 ± 2 yr; UAE, 3.32 ± 0.55 mg/day; UTPE, 56.8 ± 3.6 mg/day) were studied in high-salt balance. Blood pressure (BP), arterial stiffness determined by applanation tonometry, and circulating RAS components were measured at baseline and in response to graded ANG II infusion. The primary outcome was the BP response to ANG II challenge at 30 and 60 min. UAE was associated with a blunted diastolic BP response to ANG II infusion (30 min, P < 0.005; 60 min, P = 0.17), a relationship which remained even after adjustment (30 min, P < 0.001; 60 min, P = 0.035). Similar results were observed with UTPE (30 min, P = 0.031; 60 min, P = 0.001), even after multivariate analysis (30 min, P = 0.008; 60 min, P = 0.001). Neither UAE nor UTPE was associated with systolic BP, circulating RAS components, or arterial stiffness responses to ANG II challenge. Among healthy individuals with UAE and UTPE in the normal range, increased levels of these measures were independently associated with a blunted diastolic BP response to ANG II, indicating increased vascular RAS activity, which is known to be deleterious to both renal and cardiac function. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Declining Kidney Function Increases the Prevalence of Sleep Apnea and Nocturnal Hypoxia," by D. D. M. Nicholl and colleagues in the June 2012 issue of the periodical.

Background: Hypertension is the most important modifiable cardiovascular risk factor among women. Chronic kidney disease (CKD), which affects 1 in 10 reproductive-aged women, increases the risk of hypertension; however, awareness of hypertension in this population is unknown. This study aimed to determine hypertension awareness among reproductive-aged women living with chronic kidney disease., Methods: Women aged 18 to 50 years with CKD were recruited from nephrology clinics in Calgary, Alberta, Canada. Participants completed a semistructured interview and focused chart review, serum and urine laboratory assessment, and a physical examination that included anthropomorphic measurements and 2 automated office blood pressure readings. Hypertension was defined according to the use of ≥ 1 antihypertensive medications and/or an automated office blood pressure reading of ≥ 135/85 mm Hg. Data were stratified by hypertension status, as well as by awareness, and descriptively presented as mean ± standard deviation, numerical values, and percentages., Results: Sixty-three participants with CKD were included. Thirty-eight (60%) participants had hypertension according to study definitions. Of those with hypertension, 30 participants (79%) were aware of their hypertension status., Conclusions: Hypertension awareness is relatively high in reproductive-aged women living with CKD. However, hypertension awareness is the critical component for hypertension management, and further work is necessary to optimize reduction of cardiovascular risk in this important population., (© 2023 The Authors.)

Cardiovascular disease is the leading cause of death in women, and women with chronic kidney disease (CKD) experience especially elevated risk. This study examined the association between testosterone and vascular function in 61 reproductive-aged females with CKD. Testosterone levels and measures of vascular function were assessed, including pulse wave velocity, aortic augmentation, flow-mediated dilation (FMD), and velocity time integral. Multivariable linear regression analyses assessed the relationship between testosterone and each measure of vascular function. No associations were observed between testosterone and vascular function outcomes, although a significant positive association between testosterone-to-estradiol ratio and FMD was demonstrated. Although testosterone levels were not independently predictive of vascular function, the level of testosterone relative to estradiol was associated with FMD and may therefore influence endothelial function in the high-risk population of reproductive-aged female patients with CKD., (© 2023 The Authors.)

Background: Cardiovascular disease is the leading cause of death globally. Cyclooxygenase (COX)-derived prostaglandins play an important role in cardiovascular health regulation. Animal studies suggest a greater vascular dependence on prostaglandins in female subjects, but whether this extends to humans is unknown. We aimed to assess the effect of COX-2 inhibition on blood pressure and arterial stiffness, validated markers of cardiovascular risk, in human adults., Methods: Healthy premenopausal females and males were studied in high-salt balance before and after 14 days of daily oral celecoxib, 200 mg ingestion, on 2 identical study days. Blood pressure (BP) and pulse-wave velocity (PWV) were measured at baseline and in response to an Angiotensin II (AngII) challenge, a validated marker of renin-angiotensin-aldosterone system activity., Results: Thirteen females (age [mean ± standard deviation], 38 ± 13 years) and 11 males (age, 34 ± 9 years) were studied. Pre-COX-2 inhibition, resting measures of systolic (S)BP ( P  = 0.2) and diastolic (D)BP ( P  = 0.1) were similar between sexes. Post-COX-2 inhibition, resting SBP ( P < 0.001) and DBP ( P  = 0.02) were significantly lower in females than in males. COX-2 inhibition was not associated with changes in arterial parameters by sex (change in DBP: P  = 0.54; change in PWV: P  = 0.55; females vs males). COX-2 inhibition was associated with increased SBP ( P  = 0.039 vs pre-COX-2 inhibition), but no change in DBP ( P  = 0.16) or PWV ( P  = 0.52) response to AngII challenge in females. Measures did not differ in response to AngII pre- vs post-COX-2 inhibition in males (SBP: P  = 0.88; DBP: P  = 0.93; PWV: P  = 0.97)., Conclusions: The effects of COX-2 inhibition on arterial function may differ by sex, but further studies are needed. Given the association between nonsteroidal anti-inflammatory drugs (NSAIDs) and cardiovascular risk, increased attention regarding sex-specific pathophysiology is warranted., (© 2022 The Authors.)

Transgender women (individuals assigned male sex at birth who identify as women) and nonbinary and gender-diverse individuals receiving gender-affirming estrogen therapy (GAET) are at increased cardiovascular risk. Nonoral (i.e., patch, injectable) compared with oral estrogen exposure in cisgender women (individuals assigned female sex at birth who identify as women) may be associated with lower cardiovascular risk, though whether this applies to transgender women and/or gender-diverse individuals is unknown. We sought to determine the association between the route of estrogen exposure (nonoral compared with oral) and cardiovascular risk in transgender women and gender diverse individuals. Bibliographic databases (MEDLINE, Embase, PsycINFO) and supporting relevant literature were searched from inception to January 2022. Randomized controlled trials and observational studies reporting cardiovascular outcomes, such as all-cause and cardiovascular mortality, adverse cardiovascular events, and cardiovascular risk factors in individuals using nonoral compared with oral gender-affirming estrogen therapy were included. The search strategy identified 3,113 studies, 5 of which met inclusion criteria (3 prospective cohort studies, 1 retrospective cohort study, and 1 cross-sectional study; n = 259 participants, range of duration of exposure of 2 to 60 mo). One out of five studies reported on all-cause and cardiovascular mortality or adverse cardiovascular events. All five studies reported lipid levels [low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), and total cholesterol (TC)], whereas only two studies reported systolic blood pressure (SBP) and diastolic blood pressure (DBP). Limited studies have examined the effect of the route of GAET on all-cause cardiovascular mortality, morbidity, and risk factors. In addition, there is significant heterogeneity in studies examining the cardiovascular effects of GAET. NEW & NOTEWORTHY This study is the first to summarize the potential effect of nonoral versus oral gender-affirming estrogen therapy use on cardiovascular risk factors in transgender women or nonbinary or gender-diverse individuals. Heterogeneity of studies in reporting gender-affirming estrogen therapy formulation, dose, and duration of exposure limits quantification of the effect of gender-affirming estrogen therapy on all-cause and cardiovascular mortality, adverse cardiovascular events, and cardiovascular risk factors. This systematic review highlights the needs for large prospective cohort studies with appropriate stratification of gender-affirming estrogen therapy by dose, formulation, administration route, and sufficient follow-up and analyses to limit selection bias to optimize the cardiovascular care of transgender, nonbinary, and gender-diverse individuals.

Men have faster loss of kidney function and greater renal renin-angiotensin system (RAS) activity compared with women. Obstructive sleep apnea (OSA) is common in chronic kidney disease; the vascular effects of OSA differ by sex, and OSA-associated glomerular hyperfiltration can be reversed by continuous positive airway pressure (CPAP) therapy. We evaluated sex differences in the effect of CPAP on renal hemodynamics and the renal RAS in OSA. Twenty-nine Na + -replete, otherwise healthy study participants with OSA (10 women and 19 men) with nocturnal hypoxemia were studied pre- and post-CPAP (>4 h/night for 4 wk). Renal hemodynamics [renal plasma flow (RPF), glomerular filtration rate (GFR), and filtration fraction(FF)] were measured at baseline and in response to ANG II challenge, as a marker of renal RAS activity, pre- and post-CPAP therapy for 1 mo. In women, CPAP was associated with increased RPF (626 ± 22 vs. 718 ± 43 mL/min, P = 0.007, pre- vs. post-CPAP), maintained GFR (108 ± 2 vs. 105 ± 3 mL/min, P = 0.8), and reduced FF (17.4 ± 0.8% vs. 15.0 ± 0.7%, P = 0.017). In men, CPAP was associated with maintained RPF (710 ± 37 vs. 756 ± 38 mL/min, P = 0.1), maintained GFR (124 ± 8 vs. 113 ± 6 mL/min, P = 0.055), and reduced FF (18.6 ± 1.7% vs. 15.5 ± 1.1%, P = 0.035). Pre-CPAP, there were no sex differences in renal hemodynamic responses to ANG II. CPAP use was associated with a greater renovasoconstrictive response to ANG II in women (RPF at Δ30 min: -100 ± 27 vs. -161 ± 25 mL/min, P = 0.007, and RPF at Δ60 min: -138 ± 27 vs. -206 ± 32 mL/min, P = 0.007) but not men. CPAP use was associated with improved renal hemodynamics in both sexes and downregulated renal RAS activity in women but not men.

Study Objectives: Obstructive sleep apnea (OSA) is associated with increased cardiovascular risk. The effect of OSA treatment with continuous positive airway pressure (CPAP) on the cardiovascular response to a stressor is unknown. We sought to determine the effect of CPAP therapy on heart rate variability (HRV) and arterial stiffness, at baseline, in response to, and recovery from a physiological stressor, Angiotensin II (AngII), in humans with OSA., Methods: Twenty-five incident healthy subjects (32% female; 49 ± 2 years) with moderate-severe OSA and nocturnal hypoxia were studied in high-salt balance, a state of maximal renin-angiotensin system (RAS) suppression, before CPAP, and after 4 weeks of effective CPAP therapy (usage > 4 h/night) in a second identical study day. HRV was calculated by spectral power and time domain analysis. Aortic augmentation index (AIx) and carotid-femoral pulse-wave velocity (PWV cf ) were measured by applanation tonometry. HRV and arterial stiffness were measured at baseline and in response to AngII challenge (3 ng/ kg/min·30 minutes, 6 ng/kg/min·30 minutes, recovery·30 minutes). The primary outcome was the association between CPAP treatment and HRV and arterial stiffness responses to, and recovery from, AngII challenge. In an exploratory analysis subjects were stratified by sex., Results: CPAP corrected OSA and nocturnal hypoxemia. CPAP treatment was associated with increased sensitivity and delayed recovery from AngII (Δln HF [high frequency; recovery: -0.09 ± 0.19 versus -0.59 ± 0.17 ms 2 , P = .042; ΔrMSSD [root mean successive differences; recovery: -0.4 ± 2.0 versus -7.2 ± 1.9 ms, P = .001], ΔpNN50 [percentage of normal waves differing ≥ 50 ms compared to the preceding wave; AngII: 1.3 ± 2.3 versus -3.0 ± 2.4%, P = .043; recovery: -0.4 ± 1.4 versus -6.0 ± 1.9%, P = .001], all values pre-CPAP versus post-CPAP treatment). No differences were observed by sex. There was increased AIx sensitivity to AngII after CPAP among men (8.2 ± 1.7 versus 11.9 ± 2.2%, P = .046), but not women (11.4 ± 1.5 versus 11.6 ± 2.1%, P = .4). No change in PWV cf sensitivity was observed in either sex., Conclusions: CPAP therapy was associated with delayed cardiovagal reactivation after a stressor and down-regulation of the arterial RAS. These findings may have important implications in mitigating cardiovascular risk in both men and women with OSA., (© 2018 American Academy of Sleep Medicine.)

Background: Patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) have a high prevalence of obstructive sleep apnea (OSA) that can have significant clinical implications. An accurate clinical screening tool for OSA that identifies patients for further diagnostic testing would assist in the identification of this comorbidity. The Berlin Questionnaire (BQ), Adjusted Neck Circumference (ANC), and STOP-BANG questionnaire are 3 such instruments that have been validated in patients with normal kidney function., Objective: The objective of this study was to determine the validity of these screening instruments in patients with CKD and ESRD, using overnight cardiopulmonary monitoring to diagnose OSA., Methods: One hundred seventy-two patients were recruited from nephrology clinics and hemodialysis units (CKD: n = 109; ESRD: n = 63). All patients completed the BQ, ANC, STOP-BANG, and overnight cardiopulmonary monitoring to diagnose OSA (respiratory disturbance index [RDI] ≥ 15). Sensitivity, specificity, positive and negative predictive values, and accuracy were calculated for the BQ, ANC, and STOP-BANG., Results: Obstructive sleep apnea was present in 41 CKD patients (38%) and 32 ESRD patients (51%). All screening instruments had satisfactory sensitivity (56% to 94%) but poor specificity (29% to 77%) and low accuracy (51% to 69%) in both CKD and ESRD patients with RDI ≥ 15. Using an RDI ≥ 30 yielded similar results., Conclusions: Current screening questionnaires do not accurately identify patients at high risk for OSA or rule out the presence of OSA in patients with CKD and ESRD. Consequently, objective monitoring during sleep is required to reliably identify sleep apnea in these patient populations.

Background: Obstructive sleep apnea (OSA) is an important and common comorbidity in patients with chronic kidney disease (CKD). However, few studies have addressed how OSA presents in this patient population and whether it is clinically apparent., Objective: The objectives of this study were to determine if the prevalence and severity of sleep related symptoms distinguished CKD patients with OSA from those without apnea, and whether the clinical presentation of OSA in CKD patients differed from the general OSA population., Methods: One hundred nineteen patients were recruited from outpatient nephrology clinics. All patients completed a sleep history questionnaire, the Epworth Sleepiness Scale (daytime sleepiness, ESS > 10), the Pittsburgh Sleep Quality Index (poor sleep quality, PSQI > 5), and underwent overnight cardiopulmonary monitoring for determination of sleep apnea (respiratory disturbance index ≥ 15). CKD patients with OSA (n = 46) were compared to (1) CKD patients without OSA (n = 73) and (2) OSA patients without CKD (n = 230) who were referred to the sleep centre., Results: The prevalence of OSA symptoms and PSQI scores did not differ between CKD patients with OSA and CKD patients without apnea. Although the prevalence of daytime sleepiness was higher in CKD patients with OSA compared to CKD patients without apnea (39% vs. 19%, p = 0.033), both daytime sleepiness and other symptoms of sleep apnea were considerably less frequent than in OSA patients without a history of kidney disease., Conclusions: The presence of OSA in patients with CKD is unlikely to be clinically apparent. Consequently, objective cardiopulmonary monitoring during sleep is required to reliably identify this comorbidity.