Flow-mediated Dilation In Women Research Articles

Effects Of A Randomized Placebo-Controlled Oral Salsalate Intervention On Flow-Mediated Dilation In Women With Endometriosis

Effects Of A Randomized Placebo-Controlled Oral Salsalate Intervention On Flow-Mediated Dilation In Women With Endometriosis

Shear rate patterns during flow-mediated dilation in women with endometriosis: preliminary findings

Purpose: Endometriosis is an estrogen-dependent gynecological disorder associated with systemic inflammation and arterial stiffness, which may negatively modulate shear stress patterns to promote a pro-atherogenic state, and thus contribute to the elevated cardiovascular disease risk observed in women with the disease. However, shear stress patterns have not previously been examined in this population. Therefore, the purpose of this study was to investigate whether arterial blood flow patterns are altered in women with endometriosis. We hypothesized that women with endometriosis would exhibit disturbed blood flow patterns, characterized by high retrograde shear rates and oscillatory flow as well as reduced anterograde shear rates, as compared with women without the disease. Methods: We examined anterograde and retrograde shear rates, and oscillatory shear index (OSI; |retrograde shear rate|÷[|antegrade shear rate|+|retrograde shear rate|]) in four women with surgically confirmed endometriosis and eight without (mean (SD), 28 (5) years, BMI 24.7 (4.2) kg·m -2 ) at rest, during hyperemia (60 s post-forearm occlusion at 220 mmHg) and recovery (120-180 s post-occlusion) from flow-mediated dilation using duplex Doppler ultrasound. Shear rates were compared using two-factor (group x phase) linear mixed-effects models with post-hoc corrections for multiple comparisons of three time-points. Results: Endometriosis patients exhibited greater OSI (interaction: p=0.001) at rest (mean difference [95%CI]; 0.095 [0.001, 0.188], p=0.033) and recovery (0.126 [0.034, 0.226], p=0.005), though not during hyperemia ( p>0.999) compared to controls. This was driven by greater retrograde shear (interaction: p=0.013) during recovery (15 sec -1 [2, 28], p=0.002), though retrograde shear did not differ between groups at rest ( p=0.155) or during hyperemia ( p>0.999). Anterograde shear (interaction: p=0.049) was greater in controls than in endometriosis patients during hyperemia (276 sec -1 [61, 613], p=0.026), but not during rest or recovery (both p>0.999). Conclusions: Women with endometriosis exhibited greater oscillatory shear at rest and greater oscillatory and retrograde shear during recovery from flow-mediated dilation, as compared to controls. However, anterograde shear was diminished in endometriosis patients during hyperemia. These data indicate that shear stress patterns are negatively altered in women with endometriosis, which provides novel mechanistic insight into the pathophysiology underlying the associated elevated cardiovascular disease risk. National Institutes of Health Grant R01 HL161000 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Decline in endothelial function across the menopause transition in healthy women is related to decreased estradiol and increased oxidative stress.

Endothelial function declines progressively across stages of the menopause transition; however, the mechanisms contributing to this decline are unknown. We hypothesized that differences in endothelial function among pre-, peri, and postmenopausal women are related to differences in estradiol and oxidative stress. Brachial artery flow-mediated dilation (FMD) was measured in 87 healthy women categorized by menopause stage (24 premenopausal, 17 early and 21 late perimenopausal, and 25 postmenopausal) before and after 3 days of ovarian hormone suppression (gonadotropin releasing hormone antagonist [GnRHant]) alone, and an additional 3 days of GnRHant with concurrent transdermal estradiol or placebo add-back treatment. In 82 women, FMD during acute vitamin C (antioxidant) infusion was measured before and after GnRHant + add-back. Before GnRHant, FMD was different among groups (p < 0.005; reduced across stages of menopause). Vitamin C increased FMD in late peri- and post- (p < 0.005) but not pre- or early perimenopausal women (p > 0.54). After GnRHant alone, FMD decreased in pre- and peri- (p < 0.01), but not postmenopausal women, and was restored to premenopausal levels by estradiol add-back in the pre- and perimenopausal groups. Vitamin C improved FMD in pre-, peri-, and postmenopausal women on GnRHant + placebo. There was no effect of vitamin C on FMD in women on GnRHant + estradiol. These observations support the concept that the decline in endothelial function across the menopause transition is related to the loss of ovarian estradiol. The decline in estradiol may alter redox balance, thereby increasing oxidative stress and impairing endothelial function.

Endogenous Sex Hormones and Endothelial Function in Postmenopausal Women and Men: The Multi-Ethnic Study of Atherosclerosis.

Background: The relationship of endogenous sex hormones (SH) with vascular endothelial function and with cardiovascular disease (CVD) is incompletely understood. We examined the associations between SH and endothelial function measured by brachial artery flow-mediated dilation (FMD). Materials and Methods: We included 1368 postmenopausal women and 1707 men, free of clinical CVD, participating in MESA Visit 1 (2000-2002). Serum SH [total testosterone, SH binding globulin (SHBG), dehydroepiandrosterone (DHEA), estradiol] were measured; free testosterone was calculated. The percent FMD difference (%FMD) was measured by high-resolution ultrasound. Using multivariable-adjusted linear regression, we tested the cross-sectional associations of SH (log transformed, compared per one SD increment) with %FMD. Results: The mean age of women and men were 64.2 and 61.4 years, respectively. Among women, after adjusting for demographics, CVD risk factors, and hormone therapy, higher SHBG was associated with greater %FMD [β = 0.215% (95% CI 0.026-0.405)], whereas higher free testosterone was associated with a smaller %FMD [-0.209% (-0.402, -0.017)]. Estradiol and DHEA were not associated with %FMD in women after multivariable adjustment. There was an age interaction, with higher free testosterone and lower SHBG associated with worse FMD in women <65 years of age, but not in those ≥65 years (p = 0.04). We did not see similar associations in men. Conclusions: A more androgenic SH profile of higher free testosterone and lower SHBG was associated with worse %FMD in postmenopausal women. Changes in SH with aging and menopause may result in vascular changes in women. Further studies are needed to assess longitudinal changes in SH levels and their association with vascular function.

The impact of acute mental stress on brachial artery flow-mediated dilation in women diagnosed with depression.

Endothelial function, assessed by flow-mediated dilation (FMD), may be transiently attenuated in healthy adults following acute mental stress. However, the impact of acute mental stress on endothelial function in the context of clinical depression is unknown. This study examined the impact of acute mental stress on FMD in women with a diagnosis of a depressive disorder. Forty-three otherwise healthy women (33 ± 14 years) participated. Brachial artery diameter and blood velocity were assessed with ultrasound. FMD was assessed immediately prior to and 15 min following the Trier Social Stress Test (TSST). The FMD protocol included 5 min of forearm cuff occlusion (pressure = 250 mm Hg), followed by release. Shear stress was estimated by calculating shear rate (SR = brachial artery blood velocity/diameter). Stress reactivity was assessed via changes in mean arterial pressure (MAP), heart rate (HR) and salivary cortisol. Results are mean ± SD. A significant stress response was elicited by the TSST [MAP, HR and salivary cortisol increased (p < 0.05)]. Neither the SR stimulus nor FMD response differed pre-versus post-stress (p = 0.124 and p = 0.641, respectively). There was a modest negative correlation between cortisol reactivity and change in FMD from pre- to post-stress (R = -0.392, p = 0.011). To conclude, acute mental stress did not consistently impair endothelial function in women diagnosed with a depressive disorder; however, higher cortisol reactivity may increase the likelihood of post-stress endothelial dysfunction. Further research is required to better understand the factors influencing the relationship between acute mental stress, cortisol and endothelial function in women with depression.

Blood pressure predicts endothelial function and the effects of ethinyl estradiol exposure in young women.

Hypertension, obesity, and endothelial function predict cardiovascular disease in women, and these factors are interrelated. We hypothesized that hypertension and obesity are associated with endothelial dysfunction in young women and that short-term ethinyl estradiol exposure mitigates this dysfunction. We examined flow-mediated dilation (FMD) responses before and during 7 days of oral ethinyl estradiol (30 µg/day) in 19 women (25 ± 5, 18-35 yr). We divided our sample into two groups based on two criteria: blood pressure and obesity. Women were divided into normal blood pressure (NBP; mean arterial pressure range: 78-91 mmHg, n = 7) and high blood pressure (HBP; mean arterial pressure range: 95-113 mmHg, n = 9) groups. We also stratified our subjects by body composition (lean: 18-31%, n = 8; obese: 38-59%, n = 9). We evaluated brachial FMD after two distinct shear stress stimuli: occlusion alone and occlusion with ischemic handgrip exercise. Obesity was unrelated to both FMD responses. Before ethinyl estradiol administration, the HBP group had blunted ischemic exercise responses relative to the NBP group (8.0 ± 3.5 vs. 12.3 ± 3.2%, respectively, P = 0.05). However, during ethinyl estradiol administration, ischemic exercise responses increased in the HBP group (12.8 ± 6.1%, P = 0.04) but decreased in the NBP group (5.6 ± 2.4%, P = 0.01). Standard FMD did not reveal differences between groups. In summary, 1) moderate HBP predicted endothelial impairment, 2) ethinyl estradiol administration had divergent effects on FMD in women with NBP versus HBP, and 3) enhanced FMD (ischemic handgrip exercise) revealed differences in endothelial function, whereas standard FMD (occlusion alone) did not. NEW & NOTEWORTHY We are the first to show that mild hypertension is a stronger predictor of endothelial dysfunction than obesity in healthy women without overt cardiovascular dysfunction. Importantly, the standard 5-min flow-mediated vasodilation stimulus did not detect endothelial dysfunction in our healthy population; only an enhanced ischemic handgrip exercise shear stress stimulus detected endothelial impairment. Estradiol administration increased flow-mediated dilation in women with high blood pressure, so it may be a therapeutic intervention to improve endothelial function.

Substantial Variability Across Individuals in the Vascular and Nutrigenomic Response to an Acute Intake of Curcumin: A Randomized Controlled Trial

Curcumin exerts biological activities of interest in cardiovascular prevention. However, its vascular protective effect is still poorly investigated in humans. The present study aims to assess vascular effect of an acute intake of curcumin and its nutrigenomic impact in circulating immune cells. In a randomized, double-blind, crossover design, 18 healthy smokers consume a placebo or a 5-g curcumin. Before and 2 h after the intake, vascular function measurements are performed by using flow-mediated dilation (FMD). In addition, endothelial function in the microcirculation and blood pressure are evaluated. Plasma curcumin concentrations and changes in gene expression in peripheral blood mononuclear cells (PBMC) are analyzed. No significant effect of curcumin on FMD is observed when considering the entire study population, mainly due to a high interindividual variability. A subgroup analysis according to the gender or the cardiovascular-risk score reveals a significant effect of curcumin on FMD in women and in subjects presenting lower cardiovascular risk. No change in gene expression is observed when data are analyzed for all volunteers but changes in expression are observed when analyzed according to gender. This clinical trial highlights that a substantial variability in efficacy of curcumin exists across individuals.

Effect of a continuous aerobic exercise session on flow-mediated dilation in women with prehypertension.

Introduction : Hypertension is defined by a chronic elevation of arterial pressure above a certain threshold value (140/90 mmhg). Pre-hypertension is the harbinger of systemic hypertension. Brachial artery flow-mediated dilation (FMD) that messured by high resolution ultrasound is used to assess endothelial dysfunction in humans. the purpose of this study was to investigate the acute effects of a continuous aerobic session on Flow-Mediated Dilation and blood pressure in women with prehypertension (SBP=120-139 mmhg and DBP=80-89 mmhg). Methods : The study method was laboratorial and crossover design. Subjects included 12 women with prehypertension (age: 29/4±3/6 yrs), without exercise activities or any cardiovascular disease, were participated in two control and aerobic exercise trials. Continuous aerobic exercise concluded 45 minutes with 65 to 70 percent of maximum heart rate running on the treadmill. Flow mediated dilation was measured before and 1 hour after the exercise session. Also blood pressure was measured pre exercise, immediately post exercise and every ten minutes to 60 minutes after exercise. For data analysis independent t-test and paired t-test were used. Results : Flow-Mediated Dilation increased significantly 1 hour after exercise ( P=0.000 ). Also blood pressure levels decreased significantly from 30 to 60 minutes after the exercise. Conclusion : Performing continuous aerobic exercise, with improving in Flow-Mediated Dilation and blood pressure in women with prehypertension, can be helpful for these patients.

Effect of gender and adiposity on in vivo vascular function in young African Americans

The relationship between obesity and high blood pressure is not as strong among African Americans (AA) as compared to Caucasians. We designed the current study to determine the effect of adiposity on vascular endothelial function (a harbinger of hypertension) among young healthy AA without additional cardiovascular disease risk factors. A total of 108 AA subjects (46 women) between the ages of 18 and 45 years were recruited. All the subjects were normotensive, nonsmokers, and normoglycemic. Anthropometric and cardiovascular disease risk factor measurements (lipid, insulin resistance, and inflammatory markers) were obtained. Vascular endothelial function was measured by brachial artery flow-mediated dilation (FMD). Adiposity distribution was measured by using magnetic resonance imaging scan. There were no gender differences in age and levels of blood pressure, lipids, insulin resistance, and inflammatory markers. Women had higher total body fat percentage and higher peripheral adiposity compared to men. We observed that total and central adiposity did not correlate significantly with brachial artery FMD in women (r = −0.12 and r = 0.23, respectively; P = NS). However, in men, waist circumference was positively associated with FMD (r = 0.3, P ≤ .05). Hyperemic flow was negatively correlated significantly with total and central adiposity in men (r = −0.34 and r = −0.48, respectively; P < .05), but not in women (r = −0.26 and r = 0.03, respectively; P = NS). Our study suggests that increased adiposity may pose greater risk to AA men compared to AA women by adversely affecting resistance vessel function (as measured by hyperemic flow). Larger studies are necessary to validate these findings.

Short-term tibolone does not interfere with endothelial function: a double-blinded, randomized, controlled trial

ABSTRACTObjective To evaluate the effect of short-term hormone replacement therapy with tibolone 2.5 mg daily on endothelial function of healthy postmenopausal women, using flow-mediated dilation (FMD) of the brachial artery.Methods We performed a randomized, double-blinded, placebo-controlled study. A total of 100 healthy postmenopausal women were randomly allocated to receive tibolone (n = 50) or placebo (n = 50) for 28 days. Measurement of the FMD of the brachial artery was performed before and after the use of tibolone and placebo.Results A total of 31 women completed the study in the tibolone group, and 32 women completed the study in the control group. The results of the FMD measurements obtained from the women in the two groups before treatment were similar (0.018 and 0.091, for tibolone and placebo, p = 0.57). The values of the FMD in women who used tibolone and placebo, before and after the treatment, were similar in both groups. The numbers of women who presented an increase in the values of the FMD in both groups were also similar.Conclusion Our results demonstrate that the administration of 2.5 mg tibolone to healthy postmenopausal women for 28 days does not promote endothelial-dependent vasodilation, measured by FMD of the brachial artery.

Plasma norepinephrine is an independent predictor of vascular endothelial function with aging in healthy women

We tested the hypothesis that reductions in vascular endothelial function (endothelium-dependent dilation, EDD) with age are related to increases in sympathetic activity. Among 314 healthy men and women, age was inversely related to brachial artery flow-mediated dilation (FMD) (r = -0.30, P < 0.001), a measure of EDD, and positively related to plasma norepinephrine concentrations (PNE), a marker of sympathetic activity (r = 0.49, P < 0.001). Brachial FMD was inversely related to PNE in all subjects (r = -0.25, P < 0.001) and in men (n = 187, r = -0.17, P = 0.02) and women (n = 127, r = -0.37, P < 0.001) separately. After controlling for PNE (multiple regression analysis), brachial FMD remained significantly related to age in all subjects (r = -0.20, P < 0.001) and in men (r = -0.23, P < 0.01), but not women (r = -0.16, P = 0.06). Consistent with this, brachial FMD remained significantly related to PNE when controlling for age (r = -0.24, P < 0.01) and menopause status (r = -0.24, P < 0.01) in women. Indeed, PNE was the strongest independent correlate of brachial FMD in women after controlling for conventional cardiovascular disease risk factors (r = -0.22, P = 0.01). This relation persisted in a subset of women (n = 113) after further accounting for the effects of plasma oxidized low-density lipoprotein (P < 0.05), a circulating marker of oxidative stress. Endothelium-independent dilation was not related to age in either men or women (P > 0.05). These results provide the first evidence that EDD is inversely related to sympathetic activity, as assessed by PNE, among healthy adults varying in age. In particular, our findings suggest that sympathetic nervous system activity may be a key factor involved in the modulation of vascular endothelial function with aging in women.

Association between glycosylated haemoglobin A 1c and endothelial function in an adult non-diabetic population

Objective Endothelial dysfunction precedes apparent atherosclerosis in humans and is associated with a number of cardiovascular risk factors, including Type 2 diabetes. To investigate the impact of long-term glucose homeostasis on endothelial function in an adult non-diabetic population, we analysed the association of serum HbA 1c levels with endothelial function. Methods We studied cross-sectional data from 1384 subjects (696 women), aged 25–85, without diabetes, from the population-based Study of Health in Pomerania (SHIP-1). Flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) measurements of the brachial artery were performed using standardised ultrasound techniques. Linear regression models were carried out to assess the association between serum HbA 1c levels and FMD/NMD. Results Multivariable analyses disclosed an inverse association between serum HbA 1c levels and FMD in women, but not in men. In women without current use of antihypertensive medication, increasing serum HbA 1c levels were associated with decreasing FMD levels after adjustment for age, body mass index, smoking status, hypertension, low-density lipoprotein cholesterol, and sex-hormone medication ( β = −1.17; 95% CI −2.03; −0.30, p = 0.009). There was an inverse association between serum HbA 1c levels and NMD in men ( β = −1.68; 95% CI −2.83; −0.52, p = 0.005), but not in women. Conclusion We conclude that higher serum HbA 1c levels in non-diabetic subjects are inversely associated with FMD in women without antihypertensive medication, but not in men. The gender-specific aspects concerning the association of HbA 1c levels and NMD in this population should be investigated in further studies. Our results support current considerations that subclinical disorders of glucose metabolism measured by serum HbA 1c are associated with subclinical cardiovascular diseases detected by FMD, especially in women.

Relation of omega-3 fatty acid and dietary fish intake with brachial artery flow-mediated vasodilation in the Multi-Ethnic Study of Atherosclerosis

The relation between dietary fish intake and brachial artery measures, including brachial artery flow-mediated dilation (FMD), has not been well established across sex and racial-ethnic groups. We hypothesized that consumption of nonfried fish and plasma phospholipid measures of long-chain omega-3 (n-3) fatty acids would be positively associated with larger FMD in men and women across racial-ethnic groups. We investigated cross-sectional associations of brachial artery measures with fish intake (ascertained with a food-frequency questionnaire) and plasma phospholipid omega-3 concentrations in 3045 adults, aged 45-84 y, who were free of clinical cardiovascular disease. In overall multivariate-adjusted analyses, there were no significant associations between fish intake or any brachial artery measures. However, when stratified by sex, there was an association between the highest quartile of nonfried fish consumption and a 0.10-mm lower (1 SD) brachial artery diameter in men (P = 0.01) and a 0.27% smaller FMD in women (P = 0.02) compared with the lowest quartile of nonfried fish intake in each respective sex strata. When stratified by race-ethnicity and race-ethnicity by sex, additional heterogeneity was noted, but results were difficult to interpret because of small sample sizes. Plasma phospholipid omega-3 concentrations showed a similar directionality of association with brachial artery measures observed for nonfried fish consumption, although statistical significance was not achieved in fully adjusted models. This study indicates that the association between nonfried fish intake and baseline brachial artery size varies by sex, with suggestive evidence of sex differences in the association between nonfried fish intake and FMD.

Cortisol patterns and brachial artery reactivity in a high stress environment

Chronic stress can result in frequent or persistent challenges of the hypothalamic-pituitary-adrenal (HPA) axis resulting in abnormal cortisol patterns and increased risk for cardiovascular disease (CVD). Police work is an environment replete with stress. The present article describes associations between cortisol, a biomarker of stress, and brachial artery flow mediated dilation (FMD) in police officers. A random sample stratified on gender ( n = 100, 33% women) was generated from officers in a mid-sized urban department. Four salivary cortisol parameters were derived: after awakening, following a standardized high protein meal challenge, during the entire day, and after a dexamethasone suppression test. Continuous scan B-Mode ultrasound was used to measure percent change in brachial artery FMD following occlusion and release. Elevated cortisol secretion after awakening was significantly associated with impaired FMD in women, reflected by an inverse trend. Adjustment for age, smoking, and alcohol consumption did not appreciably alter this trend. A similar result was not evident among male officers. Responses of other cortisol challenges to the HPA axis were not associated with FMD. In conclusion, increased cortisol secretion after awakening was independently associated with impaired FMD in female police officers only, indicating a possible link between HPA axis stress response and subclinical CVD. However, because associations were not found with other cortisol parameters and were not evident in male officers, replication of these findings with a prospective study design may be warranted.

Characteristics And Determinants Of Age-related Changes In Brachial And Popliteal Artery Flow-mediated Dilation In Women

Flow-mediated dilation (FMD) declines in the brachial artery (BA) with healthy aging in women. However, the physiological determinants of this decline are not welled fined, particularly after the BA FMD response has been normalized to the shear stress stimulus. Furthermore, it is not known whether this diminished FMD is seen in the leg vasculature (popliteal artery, PA), a more hemodynamically significant vascular bed utilized during ambulatory activities. PURPOSE To determine the characteristics and determinants of age-related changes in BA and PA FMD in healthy women. METHODS 41 normally active, healthy women (ages 20–79) were measured for variables including cycle VO2peak, body mass index (BMI) and regional muscle mass (forearm and calf). Resting PA and BA diameters and BA shear rate (SR= blood velocity/diameter, an estimate of shear stress) were measured prior to infiation of an upper arm or leg cuff to suprasystolic pressure for 10 min; post-occlusion diameter measurements and peak BA shear rate were used to calculate BA and PA dilation (% D = % change from baseline to peak diameter) and BA % D normalized to shear stimulus (% D/% change in SR from resting to peak). Simple linear regression was used to determine the age-associated changes in BA and PA FMD; forward/reverse stepwise linear regression was then used to determine the predictors of these age-related changes. RESULTS Resting BA and PA diameters did not differ with age (p>0.05). BA FMD normalized to shear stimulus declined 11.6% /decade with age (p <0.01); the strongest predictors of this decline were age, VO2peak, and forearm muscle mass (cumulative r2=.41; p=0.01). PA % D was not related to age (p>0.05). The only significant predictors of PA FMD were calf muscle mass (p=0.03, r2=.112) and BMI (p=0.03; r2=.121). CONCLUSION These results suggest that agerelated changes in the intrinsic dilator capacity of a conduit artery are limb-specific; additionally, the strong predictive ability of forearm flow-mediated dilation does not exist in the calf with predictors such as regional muscle mass and VO2peak. Supported by College of Health and Human Development Seed Grant #423-22

Characteristics And Determinants Of Age-related Changes In Brachial And Popliteal Artery Flow-mediated Dilation In Women

Characteristics And Determinants Of Age-related Changes In Brachial And Popliteal Artery Flow-mediated Dilation In Women