Awareness of Hypertension in Reproductive-Aged Women Living With Chronic Kidney Disease.

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.

Contexte: L'hypertension est le principal facteur de risque cardiovasculaire modifiable chez les femmes. La néphropathie chronique, qui touche une femme en âge de procréer sur 10, augmente le risque d'hypertension, mais le niveau de sensibilisation de cette population à ce sujet est inconnu. La présente étude visait à déterminer le niveau de sensibilisation à l'hypertension chez les femmes en âge de procréer atteintes de néphropathie chronique. Méthodologie: Des femmes âgées de 18 à 50 ans atteintes de néphropathie chronique ont été recrutées dans les cliniques de néphrologie de Calgary, en Alberta (Canada). Les participantes ont été soumises à des entrevues semi-structurées, un examen ciblé du dossier médical, des analyses de laboratoire du sérum et de l'urine et un examen physique incluant des mesures anthropométriques et deux lectures automatisées de la pression artérielle réalisées en cabinet. L'hypertension a été définie de la façon suivante : (1) l'utilisation de ≥ 1 agent antihypertenseur, et/ou (2) une lecture automatisée de la pression artérielle en cabinet ≥ 135/85 mmHg. Les données ont été stratifiées selon le statut d'hypertension et le niveau de sensibilisation, et elles sont présentées de façon descriptive par la moyenne ± l'écart-type, les valeurs numériques et les pourcentages. Résultats: Soixante-trois participantes atteintes de néphropathie chronique ont été incluses dans l'étude. Trente-huit (60 %) participantes étaient atteintes d'hypertension selon la définition utilisée dans l'étude. Parmi les participantes hypertendues, 30 (79 %) étaient conscientes de leur statut d'hypertension. Conclusions: Le niveau de sensibilisation à l'hypertension est relativement élevé parmi les femmes en âge de procréer atteintes de néphropathie chronique. Toutefois, la sensibilisation à l'hypertension est un élément clé pour sa prise en charge, et d'autres travaux sont nécessaires pour optimiser la réduction du risque cardiovasculaire dans cette population importante.

Association Between the Route of Administration and Formulation of Estrogen Therapy and Hypertension Risk in Postmenopausal Women: A Prospective Population-Based Study.

BACKGROUND: Hypertension is the leading global cause of cardiovascular disease and premature mortality in women. The effects of postmenopausal hormone therapy (HT) on blood pressure are uncertain but may be related to route of estrogen administration and formulation of estrogen. We sought to determine the association between route of administration and formulation of estrogen HT and hypertension risk in postmenopausal women. METHODS: Population-based cohort study with women aged ≥45 years who filled ≥2 consecutive prescriptions for estrogen-only HT, identified from linked provincial health administrative data from Alberta, Canada, between 2008 and 2019. The primary outcome, incident hypertension, was identified using standardized International Classification of Diseases, Ninth and Tenth Revision. Cox proportional hazard models were used to calculate hazard ratios (HRs) for hypertension in women using oral HT compared with nonoral HT (transdermal, vaginal, or intramuscular). RESULTS: In total, 112 240 women used an estrogen-only form of HT. Oral estrogen was associated with a higher risk of hypertension compared with both transdermal (HR, 1.14 [95% CI, 1.08-1.20]) and vaginal (HR, 1.19 [95% CI, 1.13-1.25]) estrogens. Conjugated equine estrogen was associated with an increased risk of hypertension compared with estradiol (HR, 1.08 [95% CI, 1.04-1.14]) but not estrone (HR, 1.00 [95% CI, 0.93-1.10]). Duration of estrogen exposure and cumulative dose of estrogen was positively associated with risk of hypertension. CONCLUSIONS: Oral estrogen-only HT use was associated with an increased risk of hypertension in women. In women using estrogen-only HT, nonoral estradiol at the lowest dose and for the shortest time-period is associated with the lowest risk of hypertension.

Gender-affirming estrogen therapy route of administration and cardiovascular risk: a systematic review and narrative synthesis.

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.

The Association Between Route of Post-menopausal Estrogen Administration and Blood Pressure and Arterial Stiffness in Community-Dwelling Women.

Background: Postmenopausal hormone therapy (HT) is associated with increased cardiovascular risk. Although the route of estrogen administration may play a role in mediating risk, previous studies have not controlled for concomitant progestin use. Objective: To investigate the association between the route of estrogen therapy (oral or non-oral) HT use, without concomitant progestin, and blood pressure and arterial stiffness in postmenopausal women. Methods: Systolic blood pressure [SBP], diastolic blood pressure [DBP]), arterial stiffness (aortic pulse wave velocity [aPWV] and augmentation index at 75 beats per minute [AIx]) were measured using a validated automated brachial cuff-based oscillometric approach (Mobil-O-Graph) in a community-dwelling sample of 328 women. Results: Fifty-five participants (16.8%) were ever users (current and past use) of estrogen-only HT (oral [n = 16], transdermal [n = 20], vaginal [n = 19]), and 223 were never HT users (control). Ever use of oral estrogen was associated with increased SBP and DBP (Oral: SBP: 137 ± 4 mmHg, DBP: 79 ± 2 mmHg) compared to use of non-oral estrogen (transdermal: SBP: 118 ± 2 mmHg, DBP: 73 ± 1 mmHg; p < 0.01 & p = 0.012, respectively; vaginal: SBP: 123 ± 2 mmHg DBP: 73 ± 2 mmHg; p = 0.02 & p = 0.01, respectively.) and controls (SBP: 124 ± 1 mmHg, DBP: 74 ± 1 mmHg, p = 0.03, p = 0.02, respectively) after adjustment for covariates. aPWV was higher in oral estrogen ever users (9.9 ± 1 m/s) compared to non-oral estrogen (transdermal: 8.6 ± 0.3 m/s, p < 0.01; vaginal: 8.8 ± 0.7 m/s, p = 0.03) and controls (8.9 ± 0.5 m/s, p = 0.03) but these associations were no longer significant after adjustment for covariates. AIx was higher in oral estrogen (29 ± 2 %) compared to non-oral estrogen (transdermal: 16 ± 2 %; vaginal: 22 ± 1.7 %) but this association was no longer significant after adjustment for covariates (p = 0.92 vs. non-oral; p = 0.74 vs. control). Conclusion: Ever use of oral estrogen was associated with increased SBP and DBP compared to non-oral estrogen use and no use. Given the cardiovascular risk associated with both menopause and increased blood pressure, further studies are required exploring the potential benefits of non-oral estrogen in postmenopausal women.

The effect of non-oral hormonal contraceptives on hypertension and blood pressure: A systematic review and meta-analysis.

Oral contraceptives (OC) are associated with increased risk of hypertension and elevated blood pressure (BP). Whether non-oral hormonal contraceptives have similar associations is unknown. We sought to investigate the effect of non-oral hormonal contraceptive (NOHC) use on the risk of hypertension and changes in BP, compared to non-hormonal contraceptive and OC use. We searched bibliographic databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials) until August 2020. Studies reporting risk of hypertension or changes in systolic and diastolic BP with NOHC use compared with either non-hormonal contraceptive or OC use. Abstract screening, full-text review, data extraction, and quality assessment were completed in duplicate. For studies reporting dichotomous outcomes, we reported results as relative risk with 95% confidence intervals (CI). A random-effects model was used to estimate pooled weighted mean difference and 95% CI of change in BP. Twenty-five studies were included. A lower incidence of hypertension was observed with injectable contraceptive use compared to non-hormonal contraceptive and OC use, although it was unclear if this was statistically significant. Compared to non-hormonal contraceptive use, injectable contraceptive use was associated with increased BP (SBP: 3.24 mmHg, 95%CI 2.49 to 3.98 mmHg; DBP: 3.15 mmHg, 95%CI 0.09 to 6.20 mmHg), the hormonal intra-uterine device use was associated with reduced BP (SBP: -4.50 mmHg, 95%CI -8.44 to -0.57 mmHg; DBP: -7.48 mmHg, 95% -14.90 to -0.05 mmHg), and the vaginal ring was associated with reduced diastolic BP (-3.90 mmHg, 95%CI -6.67 to -1.13 mmHg). Compared to OC use, the injectable contraceptive use was associated with increased diastolic BP (2.38 mmHg, 95%CI 0.39 to 4.38 mmHg). NOHC use is associated with changes in BP which differ by type and route of administration. Given the strong association between incremental increases in BP and cardiovascular risk, prospective studies are required.

Anti-Müllerian hormone and vascular dysfunction in women with chronic kidney disease.

Young women with chronic kidney disease (CKD) have disproportionately increased risk of cardiovascular mortality. Reduced anti-Müllerian hormone (AMH) is linked to poor cardiovascular outcomes in the general population, but whether AMH is associated with increased cardiovascular risk in the high-risk CKD population is unknown. This study examined the association between AMH and vascular function, validated markers of cardiovascular risk, in women with CKD. An exploratory cross-sectional study was performed in 47 young women with CKD. Laboratory measurements of AMH were collected. Using standardized protocols, endothelial function was measured with brachial artery flow-mediated dilation and hyperemic velocity time integral. Arterial stiffness was measured with aortic augmentation index and pulse wave velocity. Multivariate linear regression analyses were utilized to evaluate the association between AMH levels and each measure of vascular health. Forty women (36 ± 7 years) with non-dialysis-dependent CKD and 7 women (38 ± 6 years) with dialysis-dependent CKD participated. AMH levels were inversely associated with age (p = 0.01) but not associated with eGFR (p = 0.59) or dialysis status (p = 0.97). AMH was associated with brachial artery flow-mediated dilation (R2  = 0.21 [p = 0.03]) and aortic augmentation index (R2  = 0.20 [p = 0.04]) in the non-dialysis-dependent participants, and with aortic augmentation index in all participants (R2  = 0.18 [p = 0.03]). No association between AMH and any measure of vascular function was demonstrated in the dialysis-dependent participants. AMH levels are associated with impaired vascular function in young women with CKD and may be an important marker of future cardiovascular risk. Further investigation into this female-specific cardiovascular risk factor is warranted in this high-risk population.

Sex influences the effect of adiposity on arterial stiffness and renin-angiotensin aldosterone system activity in young adults.

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.