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.

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Abstract 530: Impact of a Single Mixed Mediterranean-Type Meal Compared with a High-Saturated Fat Meal on Postprandial Endothelial Function and Metabolic Markers

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.32.suppl_1.a530 ◽

2012 ◽

Vol 32 (suppl_1) ◽

Author(s):

Sebastien Lacroix ◽

Christine Des Rosiers ◽

Mathieu Gayda ◽

Anil Nigam

Keyword(s):

Endothelial Dysfunction ◽

Endothelial Function ◽

Saturated Fat ◽

Random Order ◽

Flow Mediated Dilation ◽

Omega 3 ◽

Metabolic Markers ◽

Endothelial Impairment ◽

Artery Flow ◽

Fat Meal

Background: Endothelial dysfunction is considered a precursor of atherosclerosis and is an independent predictor of cardiovascular events. A high-saturated fat meal (HFM) has been shown to induce postprandial endothelial dysfunction. However, no studies have evaluated the acute endothelial effect of a single mixed Mediterranean-type meal (MMM). Our objective was to evaluate postprandial endothelial and metabolic function in response to a MMM in comparison to an isocaloric HFM. Methods: In this ongoing crossover study, 26 of 28 healthy non-smoking males have completed the research protocol. In random order on two separate days during a 1-week interval, subjects were fed two isocaloric meals after an overnight fast. The MMM (885 kcal) consisted of fresh salmon, almonds and vegetables baked in olive oil providing 51% of total calories from fat (7.87g SFA and 2.29g of omega-3, 2:1 DHA:EPA). The HFM consisted of a McDonald’s sausage, egg and cheese McMuffin and three hashbrowns (858 kcal) providing 58% of total energy from fat (14.78g SFA and no omega-3). Endothelial function was evaluated by measuring brachial artery flow-mediated dilation (%FMD) at baseline and at two (T2) and four (T4) hours postprandial. Results: Mean postprandial %FMD tends to be less impaired following the MMM than the HFM (variation at T4 -0.15±3.6% vs -2.83±3.3% respectively, p<0.1). Postprandial variations of TG and TG/HDL at T4 were also less severe with the MMM than the HFM (p≤0.05) and did not correlate to %FMD variations. When subdividing the population on the basis of the median fasting TG levels (0.90 mmol/L), the HFM led to significant endothelial impairment in the subjects with higher-TG while it had no effect in the low-TG group. Conclusion: Our data suggest that a single MMM exerts less of a deleterious effect on postprandial endothelial function and metabolic markers than does a HFM. A single MMM could thus be less atherogenic than a HFM. Moreover, subjects with higher fasting TG levels (avg. 1.54±0.59 mmol/L, well bellow hypertriglyceridemia threshold) could be at higher risk of endothelial injury following a single HFM. Data on all 28 subjects will be available in April 2012.

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Abstract 3519: Modest Fat Gain Causes Endothelial Dysfunction In Lean Healthy Humans: A Randomized Blinded Controlled Trial

Circulation ◽

10.1161/circ.116.suppl_16.ii_797 ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Abel Romero Corral ◽

Justo Sierra-Johnson ◽

Marek Orban ◽

Apoor S Gami ◽

Fatima H Sert Kuniyoshi ◽

...

Keyword(s):

Blood Pressure ◽

Weight Loss ◽

Body Composition ◽

Weight Gain ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Brachial Artery ◽

Controlled Trial ◽

Subcutaneous Fat ◽

Flow Mediated Dilation

Background: Endothelial dysfunction assessed by flow mediated dilation (FMD) of the brachial artery has been identified as an independent predictor of cardiovascular events. However, whether weight gain impairs endothelial function is unknown. Methods: A randomized blinded controlled-trial to assess the effects of weight gain on endothelial function. After a weight maintenance period supervised by an experience dietitian, volunteers were randomized to gain weight (4 kg) or maintain weight. We recruited lean (BMI 18.5–24.9 kg/m 2 ) healthy volunteers (no diseases, medications and non-smokers) from the community. Using ultrasound, endothelial function was measured by FMD and non-flow mediated dilation (NFMD) of the brachial artery in the early morning (6:30 a.m.). Endothelial function was measured at baseline, after fat gain at 8 weeks and after weight loss at 16 weeks for fat-gainers and at baseline and follow-up (8 weeks) for weight maintainers. Body composition techniques to measure body fat %, such as dual x-ray absorptiometry and abdominal CT scans were performed. Results: We recruited 35 fat-gainers and 8 weight maintainers. Mean age was 29 ± 6 years and 18 (42 %) were women. There were no differences in age, anthropometric and body composition measurements, blood pressure, heart rate or apnea hypopnea index at baseline between both groups. After an average gain of 4 kg, the fat-gainer group significantly increased their total, visceral and subcutaneous fat. Brachial artery FMD and NFMD remained unchanged in weight maintainers. However, it decreaed in fat-gainers (FMD=9.1 ± 3 vs. 7.6 ± 3.2, p=0.003 and NFMD=12.0 ± 4.9 vs. 10.1 ± 6.0, p=0.01), but recovered to baseline after subjects shed the gained weight (basleline vs. recovery: FMD=9.1 ± 3 vs. 9.0 ± 3, p=NS and NFMD =12.0 ± 4.9 vs.12.6 ± 5.0, p=NS). Visceral fat gain, but not subcutaneous fat gain was significantly correlated with the decrease in brachial artery FMD (rho =−0.42, p=0.004 and rho =−0.22, p=0.15, respectively). Conclusions: In lean healthy young subjects, modest weight gain results in impaired endothelial function, even in the absence of changes in blood pressure. Endothelial funcion recovers after weight loss. Viscerar rather than subcutaneous fat predicts endothelial dysfunction.

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Assessment of endothelial function by flow-mediated dilation of the brachial artery in adolescents with a history of preeclampsia or a normotensive pregnancy

Revista Brasileira de Saúde Materno Infantil ◽

10.1590/s1519-38292014000100008 ◽

2014 ◽

Vol 14 (1) ◽

pp. 81-90 ◽

Cited By ~ 1

Author(s):

Joana Adalgisa Furtado Magalhães Andrade ◽

Francisco Herlânio Costa Carvalho ◽

Rosa Maria Salani Mota ◽

Guilherme Augusto Magalhães Andrade ◽

Helvécio Neves Feitosa ◽

...

Keyword(s):

Blood Pressure ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Systolic Blood Pressure ◽

Brachial Artery ◽

Cross Sectional Study ◽

Flow Mediated Dilation ◽

Cross Sectional ◽

History Of ◽

Normotensive Pregnancy

Objectives: to determine the prevalence of endothelial dysfunction and its association with a history of mild and severe preeclampsia in adolescents. Methods: a cross-sectional study was carried out at the MEAC-UFC with 103 primiparous adolescents postpartum. The assessment of endothelial function was performed by way of flow-mediated dilatation of the brachial artery. Variables (age, body mass index, gestational age at delivery, systolic and diastolic blood pressure and flow-mediated dilation) were compared between groups. p<0.05 was considered to be statistically significant. Results: twenty-four (23.3%) patients had preeclampsia (PE): 11 mild and 13 severe. The overall prevalence of endothelial dysfunction was 23.3% (21.5% of patients with normotensive pregnancies and 29.2% of the PE patients: 18.2% of those with mild PE and 38.5% of those with severe PE). The figures were statistically significant for systolic blood pressure, p=0.007. Conclusions: patients with a history of PE have higher systolic blood pressure than patients with a history of normotensive pregnancy, but did not have more endothelial dysfunction.

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Isometric handgrip training does not improve flow-mediated dilation in subjects with normal blood pressure

Clinical Science ◽

10.1042/cs20060195 ◽

2007 ◽

Vol 112 (7) ◽

pp. 403-409 ◽

Cited By ~ 37

Author(s):

Cheri L. Mcgowan ◽

Andrew S. Levy ◽

Neil Mccartney ◽

Maureen J. Macdonald

Keyword(s):

Blood Pressure ◽

Endothelial Function ◽

Internal Control ◽

Repeated Measures ◽

Flow Mediated Dilation ◽

Normal Blood Pressure ◽

Isometric Handgrip ◽

Repeated Measures Design ◽

Artery Flow ◽

Maximal Effort

Isometric HG (handgrip) training lowers resting arterial BP (blood pressure), yet the mechanisms are elusive. In the present study, we investigated improved systemic endothelial function as a mechanism of arterial BP modification following isometric HG training in normotensive individuals. This study employed a within-subject repeated measures design primarily to assess improvements in BA FMD (brachial artery flow-mediated dilation; an index of endothelium-dependent vasodilation), with the non-exercising limb acting as an internal control. Eleven subjects performed four 2-min unilateral isometric HG contractions at 30% of maximal effort, three times per week for 8 weeks. Pre-, mid- and post-training resting ABP and BA FMD (exercised arm and non-exercised arm) were measured via automated brachial oscillometry and ultrasound respectively. BA FMD (normalized to the peak shear rate experienced in response to the reactive hyperaemic stimulus) remained unchanged [exercised arm, 0.029±0.003 to 0.026±0.003 to 0.029±0.004%/s−1 (pre- to mid- to post-training respectively); non-exercised arm, 0.023±0.003 to 0.023±0.003 to 0.024±0.003%/s−1 (pre- to mid- to post-training respectively); P=0.22]. In conclusion, improved systemic endothelial function is unlikely to be responsible for lowering arterial BP in this population.

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Dietary Approaches to Stop Hypertension Dietary Intervention Improves Blood Pressure and Vascular Health in Youth With Elevated Blood Pressure

Hypertension ◽

10.1161/hypertensionaha.120.16156 ◽

2021 ◽

Vol 77 (1) ◽

pp. 241-251

Author(s):

Sarah C. Couch ◽

Brian E. Saelens ◽

Philip R. Khoury ◽

Katherine B. Dart ◽

Kelli Hinn ◽

...

Keyword(s):

Blood Pressure ◽

Endothelial Function ◽

Dietary Intervention ◽

Routine Care ◽

Dash Score ◽

Flow Mediated Dilation ◽

Post Intervention ◽

Program Outcomes ◽

National High Blood Pressure

This randomized control trial assessed the post-intervention and 18-month follow-up effects of a 6-month dietary approaches to stop hypertension (DASH)-focused behavioral nutrition intervention, initiated in clinic with subsequent telephone and mail contact, on blood pressure (BP) and endothelial function in adolescents with elevated BP. Adolescents (n=159) 11 to 18 years of age with newly diagnosed elevated BP or stage 1 hypertension treated at a hospital-based clinic were randomized. DASH participants received a take-home manual plus 2 face-to-face counseling sessions at baseline and 3 months with a dietitian regarding the DASH diet, 6 monthly mailings, and 8 weekly and then 7 biweekly telephone calls focused on behavioral strategies to promote DASH adherence. Routine care participants received nutrition counseling with a dietitian consistent with pediatric guidelines established by the National High Blood Pressure Education Program. Outcomes, measured pre- and post-intervention and at 18-months follow-up, included change in BP, change in brachial artery flow-mediated dilation, and change in DASH score based on 3-day diet recalls. Adolescents in DASH versus routine care had a greater improvement in systolic BP (–2.7 mm Hg, P = 0.03, –0.3 z-score, P =0.03), flow-mediated dilation (2.5%, P =0.05), and DASH score (13.3 points, P <0.0001) from baseline to post-treatment and a greater improvement in flow-mediated dilation (3.1%, P =0.03) and DASH score (7.4 points, P =0.01) to 18 months. The DASH intervention proved more effective than routine care in initial systolic BP improvement and longer term improvement in endothelial function and diet quality in adolescents with elevated BP and hypertension. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00585832.

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Supplementation with Hydroxytyrosol and Punicalagin Improves Early Atherosclerosis Markers Involved in the Asymptomatic Phase of Atherosclerosis in the Adult Population: A Randomized, Placebo-Controlled, Crossover Trial

Nutrients ◽

10.3390/nu11030640 ◽

2019 ◽

Vol 11 (3) ◽

pp. 640 ◽

Cited By ~ 5

Author(s):

Rebeca Quirós-Fernández ◽

Bricia López-Plaza ◽

Laura Bermejo ◽

Samara Palma-Milla ◽

Carmen Gómez-Candela

Keyword(s):

Blood Pressure ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Crossover Trial ◽

Adult Population ◽

Oral Supplementation ◽

Flow Mediated Dilatation ◽

Asymptomatic Phase ◽

Double Blinded ◽

Early Atherosclerosis

Hydroxytyrosol (HT) and Punicalagin (PC) exert cardioprotective and anti-atherosclerotic effects. This study evaluates the effect of oral supplementation with HT and PC (SAx) on early atherosclerosis markers in middle-aged, seemingly healthy adults. A randomized, double-blinded, placebo-controlled, crossover trial was performed for 20 weeks. There were two treatment sequences (Placebo/SAx, n = 41; SAx/Placebo, n = 43) for which the intervention periods (Placebo and SAx) were 8 weeks long, followed by a 4-week wash out period. The supplement was composed of 9.9 mg of HT and 195 mg of PC, and the placebo was composed of maltodextrin. SAx increased endothelial function (Flow-mediated dilatation [FMD]: 2.36%; p < 0.001) in the endothelial dysfunction subgroup compared to the placebo (2.36 ± 3.9 vs. 0.76 ± 3.5%, p < 0.05). SAx also reduced oxLDL by −28.74 ng/mL (p < 0.05) in subjects with higher levels of oxLDL, which was an improvement compared with the placebo (−28.74 ± 40.2 vs. 25.64 ± 93.8 ng/mL, p < 0.001). The prehypertension and hypertension subgroups exhibited decreased systolic (−15.75 ± 9.9 mmHg; p < 0.001) and diastolic (−6.36 ± 8.7 mmHg; p < 0.001) blood pressure after SAx consumption. Moreover, the systolic prehypertension and hypertension subgroups presented significant differences in systolic blood pressure compared to the placebo (−15.75 ± 9.9 vs. −2.67 ± 12.0 mmHg, p < 0.05). In conclusion, the supplement exerted anti-atherosclerotic effects by improving endothelial function, blood pressure, and levels of circulating oxLDL, especially for persons in whom these parameters were altered.

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Association of APOL1 Genotypes With Measures of Microvascular and Endothelial Function, and Blood Pressure in MESA

Journal of the American Heart Association ◽

10.1161/jaha.120.017039 ◽

2020 ◽

Vol 9 (17) ◽

Author(s):

Teresa K. Chen ◽

Ronit Katz ◽

Michelle M. Estrella ◽

Wendy S. Post ◽

Holly Kramer ◽

...

Keyword(s):

Blood Pressure ◽

High Risk ◽

Kidney Disease ◽

Endothelial Function ◽

Aortic Distensibility ◽

The United States ◽

Flow Mediated Dilation ◽

Arterial Elasticity ◽

Increased Risk ◽

Significant Difference

Background APOL1 high‐risk genotypes are associated with increased risk for hypertension‐attributed kidney disease among Black adults in the United States. Biopsy studies show differences in kidney vasculature by APOL1 status; less is known about the variants' associations with systemic vascular and endothelial function. Whether APOL1 risk variants are associated with blood pressure (BP) is also uncertain. Methods and Results Using linear regression, we examined cross‐sectional associations of APOL1 risk genotypes (high=2 risk alleles, low=0 or 1 risk allele) with subclinical measures of vascular function (small arterial elasticity, n=1586; large arterial elasticity, n=1586; ascending aortic distensibility, n=985) and endothelial function (flow‐mediated dilation, n=777). Using linear mixed‐effects models, we studied longitudinal associations of APOL1 risk genotypes with BP (n=1619), adjusting for age, sex, and African ancestry. Among 1619 (12% APOL1 high‐risk) Black participants in MESA (Multi‐Ethnic Study of Atherosclerosis), mean age was 62 years old, 58% had hypertension, and mean systolic BP was 131 mm Hg at baseline. At examination 1 (2000–2002), there was no significant difference in small arterial elasticity, large arterial elasticity, ascending aortic distensibility, or flow‐mediated dilation in participants with APOL1 high‐ versus low‐risk genotypes ( P >0.05 for all). Over a mean follow‐up of 7.8 years, relative annual changes in systolic and diastolic BP and pulse pressure did not differ significantly by APOL1 risk status (between‐group differences of −0.20, −0.14, and −0.25, respectively; P >0.05 for all). Conclusions Among Black participants in MESA, APOL1 high‐risk genotypes were not associated with subclinical vascular and endothelial function or BP trajectories. The relationship of APOL1 with kidney disease may be intrinsic to the kidney rather than through peripheral effects on systemic vasculature or BP.

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Endothelial dysfunction following prolonged sitting is mediated by a reduction in shear stress

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00943.2015 ◽

2016 ◽

Vol 310 (5) ◽

pp. H648-H653 ◽

Cited By ~ 61

Author(s):

Robert M. Restaino ◽

Lauren K. Walsh ◽

Takuma Morishima ◽

Jennifer R. Vranish ◽

Luis A. Martinez-Lemus ◽

...

Keyword(s):

Shear Stress ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Internal Control ◽

Popliteal Artery ◽

Local Heating ◽

Underlying Mechanism ◽

Flow Mediated Dilation ◽

Prolonged Sitting ◽

Artery Flow

We and others have recently reported that prolonged sitting impairs endothelial function in the leg vasculature; however, the mechanism(s) remain unknown. Herein, we tested the hypothesis that a sustained reduction in flow-induced shear stress is the underlying mechanism by which sitting induces leg endothelial dysfunction. Specifically, we examined whether preventing the reduction in shear stress during sitting would abolish the detrimental effects of sitting on popliteal artery endothelial function. In 10 young healthy men, bilateral measurements of popliteal artery flow-mediated dilation were performed before and after a 3-h sitting period during which one foot was submerged in 42°C water (i.e., heated) to increase blood flow and thus shear stress, whereas the contralateral leg remained dry and served as internal control (i.e., nonheated). During sitting, popliteal artery mean shear rate was reduced in the nonheated leg (pre-sit, 42.9 ± 4.5 s−1; and 3-h sit, 23.6 ± 3.3 s−1; P < 0.05) but not in the heated leg (pre-sit, 38.9 ± 3.4 s−1; and 3-h sit, 63.9 ± 16.9 s−1; P > 0.05). Popliteal artery flow-mediated dilation was impaired after 3 h of sitting in the nonheated leg (pre-sit, 7.1 ± 1.4% vs. post-sit, 2.8 ± 0.9%; P < 0.05) but not in the heated leg (pre-sit: 7.3 ± 1.5% vs. post-sit, 10.9 ± 1.8%; P > 0.05). Collectively, these data suggest that preventing the reduction of flow-induced shear stress during prolonged sitting with local heating abolishes the impairment in popliteal artery endothelial function. Thus these findings are consistent with the hypothesis that sitting-induced leg endothelial dysfunction is mediated by a reduction in shear stress.

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Olive Oil Polyphenols Decrease Blood Pressure and Improve Endothelial Function in Young Women with Mild Hypertension

American Journal of Hypertension ◽

10.1038/ajh.2012.128 ◽

2012 ◽

Cited By ~ 42

Author(s):

Rafael Moreno-Luna ◽

Rocio Muñoz-Hernandez ◽

Maria L. Miranda ◽

Alzenira F. Costa ◽

Luis Jimenez-Jimenez ◽

...

Keyword(s):

Blood Pressure ◽

Endothelial Function ◽

Olive Oil ◽

Young Women ◽

Mild Hypertension ◽

Decrease Blood Pressure

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Correlation between masked hypertension and endothelial dysfunction measured by flow-mediated dilation: a protocol of systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2020-047564 ◽

2021 ◽

Vol 11 (11) ◽

pp. e047564

Author(s):

Xiaohua Zhang ◽

Yong Li ◽

Ling Gao ◽

Qian Yu ◽

Congliang Zhou ◽

...

Keyword(s):

Blood Pressure ◽

Endothelial Dysfunction ◽

Meta Analysis ◽

Surrogate Marker ◽

Sensitivity Analyses ◽

Cochrane Library ◽

Control Group ◽

Pool Data ◽

Masked Hypertension ◽

Flow Mediated Dilation

IntroductionA surrogate marker to evaluate artery endothelial response when stimulated by reactive hyperaemia, known as brachial flow-mediated dilation (FMD), has prognostic value in predicting hypertensive organ damage and cardiovascular disease events. However, the degree of correlation between brachial FMD and masked hypertension (MH) outcomes is still unclear. Therefore, the purpose of this study is to pool data regarding FMD with respect to MH.Methods and analysisElectronic databases MEDLINE, EMBASE, China National Knowledge Infrastructure and Cochrane Library will be searched for the following keywords: endothelial dysfunction, flow-mediated dilation, and masked hypertension, masked uncontrolled hypertension (MUCH) and prehypertension. The following are the eligibility criteria: population—adults (18 years old or older) without hypertension at baseline, with suspected endothelial dysfunction, or from MH/MUCH populations (office blood pressure <140/90 mm Hg and home blood pressure ≥135 mm Hg and/or 85 mm Hg) and from controlled clinical trials, cohort studies, or randomised and controlled trials; exposures—any metrics for FMD; comparisons—participants without MH or MUCH; and outcome—change in FMD between the case group and the control group. Two authors will be engaged in screening and collecting data independently; disagreements will be resolved through discussion. Data extraction will include primary data designated as HR, OR, correlations and regression coefficients. Comprehensive Meta-Analysis V.2.0 will be used to conduct related subgroup and sensitivity analyses and publication bias.Ethics and disseminationThis study does not require ethics approval. It will be submitted to a peer-reviewed journal.PROSPERO registration numberCRD42020208362.

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