Relationship Between Endothelial Function and the Eliciting Shear Stress Stimulus in Women: Changes Across the Lifespan Differ to Men

Sophie M. Holder, Aine Brislane, Ellen A. Dawson, Nicola D. Hopkins, Maria T. E. Hopman, N. Timothy Cable, Helen Jones, Tim H. A. Schreuder, Victoria S. Sprung, Louise Naylor, Andrew Maiorana, Andrew Thompson, Dick H. J. Thijssen, Daniel J. Green

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Abstract

Background-Premenopausal women have a lower incidence of cardiovascular disease, which may partly be due to a protective effect of estrogen on endothelial function. Animal studies suggest that estrogen may also improve the relationship between shear rate (SR) and endothelial function. We aimed to explore the relationship between endothelial function (ie, flow-mediated dilation [FMD]) and SR (ie, SR area under the curve [SRAUC]) in women versus men, and between pre-versus postmenopausal women.

Methods and Results-Brachial artery FMD and SRAUC were measured in accordance with expert-consensus guidelines in 932 healthy participants who were stratified into young adults (18-40 years, 389 men, 144 women) and older adults (>40 years, 260 men, 139 women). Second, we compared premenopausal (n=173) and postmenopausal women (n=110). There was evidence of a weak correlation between SRAUC and FMD in all groups but older men, although there was variation in strength of outcomes. Further exploration using interaction terms (age-sex9SRAUC) in linear regression revealed differential relationships with FMD (young women versus young men [beta=-5.8(-4), P=0.017] and older women [beta=-5.9(-4), P=0.049]). The correlation between SRAUC and FMD in premenopausal women (r(2)=0.097) was not statistically different from that in postmenopausal women (r(2)=0.025; Fisher P=0.30). Subgroup analysis using stringent inclusion criteria for health markers (n=505) confirmed a stronger FMD-SRAUC correlation in young women compared with young men and older women.

Conclusions-Evidence for a stronger relationship between endothelial function and the eliciting SR stimulus is present in young women compared with men. Estrogen may contribute to this finding, but larger healthy cohorts are required for conclusive outcomes.

Original languageEnglish
Article number010994
Number of pages8
JournalJournal of the American Heart Association
Volume8
Issue number4
DOIs
Publication statusPublished - 19 Feb 2019

Cite this

Holder, Sophie M. ; Brislane, Aine ; Dawson, Ellen A. ; Hopkins, Nicola D. ; Hopman, Maria T. E. ; Cable, N. Timothy ; Jones, Helen ; Schreuder, Tim H. A. ; Sprung, Victoria S. ; Naylor, Louise ; Maiorana, Andrew ; Thompson, Andrew ; Thijssen, Dick H. J. ; Green, Daniel J. / Relationship Between Endothelial Function and the Eliciting Shear Stress Stimulus in Women : Changes Across the Lifespan Differ to Men. In: Journal of the American Heart Association. 2019 ; Vol. 8, No. 4.
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abstract = "Background-Premenopausal women have a lower incidence of cardiovascular disease, which may partly be due to a protective effect of estrogen on endothelial function. Animal studies suggest that estrogen may also improve the relationship between shear rate (SR) and endothelial function. We aimed to explore the relationship between endothelial function (ie, flow-mediated dilation [FMD]) and SR (ie, SR area under the curve [SRAUC]) in women versus men, and between pre-versus postmenopausal women.Methods and Results-Brachial artery FMD and SRAUC were measured in accordance with expert-consensus guidelines in 932 healthy participants who were stratified into young adults (18-40 years, 389 men, 144 women) and older adults (>40 years, 260 men, 139 women). Second, we compared premenopausal (n=173) and postmenopausal women (n=110). There was evidence of a weak correlation between SRAUC and FMD in all groups but older men, although there was variation in strength of outcomes. Further exploration using interaction terms (age-sex9SRAUC) in linear regression revealed differential relationships with FMD (young women versus young men [beta=-5.8(-4), P=0.017] and older women [beta=-5.9(-4), P=0.049]). The correlation between SRAUC and FMD in premenopausal women (r(2)=0.097) was not statistically different from that in postmenopausal women (r(2)=0.025; Fisher P=0.30). Subgroup analysis using stringent inclusion criteria for health markers (n=505) confirmed a stronger FMD-SRAUC correlation in young women compared with young men and older women.Conclusions-Evidence for a stronger relationship between endothelial function and the eliciting SR stimulus is present in young women compared with men. Estrogen may contribute to this finding, but larger healthy cohorts are required for conclusive outcomes.",
keywords = "endothelial function, estrogen, sex-specific, shear stress, FLOW-MEDIATED DILATION, ESTROGEN-RECEPTOR-ALPHA, NITRIC-OXIDE SYNTHASE, BRACHIAL-ARTERY, BLOOD-FLOW, GENDER-DIFFERENCE, VASCULAR FUNCTION, MENSTRUAL-CYCLE, SEX-DIFFERENCES, AGE",
author = "Holder, {Sophie M.} and Aine Brislane and Dawson, {Ellen A.} and Hopkins, {Nicola D.} and Hopman, {Maria T. E.} and Cable, {N. Timothy} and Helen Jones and Schreuder, {Tim H. A.} and Sprung, {Victoria S.} and Louise Naylor and Andrew Maiorana and Andrew Thompson and Thijssen, {Dick H. J.} and Green, {Daniel J.}",
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Holder, SM, Brislane, A, Dawson, EA, Hopkins, ND, Hopman, MTE, Cable, NT, Jones, H, Schreuder, THA, Sprung, VS, Naylor, L, Maiorana, A, Thompson, A, Thijssen, DHJ & Green, DJ 2019, 'Relationship Between Endothelial Function and the Eliciting Shear Stress Stimulus in Women: Changes Across the Lifespan Differ to Men' Journal of the American Heart Association, vol. 8, no. 4, 010994. https://doi.org/10.1161/JAHA.118.010994

Relationship Between Endothelial Function and the Eliciting Shear Stress Stimulus in Women : Changes Across the Lifespan Differ to Men. / Holder, Sophie M.; Brislane, Aine; Dawson, Ellen A.; Hopkins, Nicola D.; Hopman, Maria T. E.; Cable, N. Timothy; Jones, Helen; Schreuder, Tim H. A.; Sprung, Victoria S.; Naylor, Louise; Maiorana, Andrew; Thompson, Andrew; Thijssen, Dick H. J.; Green, Daniel J.

In: Journal of the American Heart Association, Vol. 8, No. 4, 010994, 19.02.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Relationship Between Endothelial Function and the Eliciting Shear Stress Stimulus in Women

T2 - Changes Across the Lifespan Differ to Men

AU - Holder, Sophie M.

AU - Brislane, Aine

AU - Dawson, Ellen A.

AU - Hopkins, Nicola D.

AU - Hopman, Maria T. E.

AU - Cable, N. Timothy

AU - Jones, Helen

AU - Schreuder, Tim H. A.

AU - Sprung, Victoria S.

AU - Naylor, Louise

AU - Maiorana, Andrew

AU - Thompson, Andrew

AU - Thijssen, Dick H. J.

AU - Green, Daniel J.

PY - 2019/2/19

Y1 - 2019/2/19

N2 - Background-Premenopausal women have a lower incidence of cardiovascular disease, which may partly be due to a protective effect of estrogen on endothelial function. Animal studies suggest that estrogen may also improve the relationship between shear rate (SR) and endothelial function. We aimed to explore the relationship between endothelial function (ie, flow-mediated dilation [FMD]) and SR (ie, SR area under the curve [SRAUC]) in women versus men, and between pre-versus postmenopausal women.Methods and Results-Brachial artery FMD and SRAUC were measured in accordance with expert-consensus guidelines in 932 healthy participants who were stratified into young adults (18-40 years, 389 men, 144 women) and older adults (>40 years, 260 men, 139 women). Second, we compared premenopausal (n=173) and postmenopausal women (n=110). There was evidence of a weak correlation between SRAUC and FMD in all groups but older men, although there was variation in strength of outcomes. Further exploration using interaction terms (age-sex9SRAUC) in linear regression revealed differential relationships with FMD (young women versus young men [beta=-5.8(-4), P=0.017] and older women [beta=-5.9(-4), P=0.049]). The correlation between SRAUC and FMD in premenopausal women (r(2)=0.097) was not statistically different from that in postmenopausal women (r(2)=0.025; Fisher P=0.30). Subgroup analysis using stringent inclusion criteria for health markers (n=505) confirmed a stronger FMD-SRAUC correlation in young women compared with young men and older women.Conclusions-Evidence for a stronger relationship between endothelial function and the eliciting SR stimulus is present in young women compared with men. Estrogen may contribute to this finding, but larger healthy cohorts are required for conclusive outcomes.

AB - Background-Premenopausal women have a lower incidence of cardiovascular disease, which may partly be due to a protective effect of estrogen on endothelial function. Animal studies suggest that estrogen may also improve the relationship between shear rate (SR) and endothelial function. We aimed to explore the relationship between endothelial function (ie, flow-mediated dilation [FMD]) and SR (ie, SR area under the curve [SRAUC]) in women versus men, and between pre-versus postmenopausal women.Methods and Results-Brachial artery FMD and SRAUC were measured in accordance with expert-consensus guidelines in 932 healthy participants who were stratified into young adults (18-40 years, 389 men, 144 women) and older adults (>40 years, 260 men, 139 women). Second, we compared premenopausal (n=173) and postmenopausal women (n=110). There was evidence of a weak correlation between SRAUC and FMD in all groups but older men, although there was variation in strength of outcomes. Further exploration using interaction terms (age-sex9SRAUC) in linear regression revealed differential relationships with FMD (young women versus young men [beta=-5.8(-4), P=0.017] and older women [beta=-5.9(-4), P=0.049]). The correlation between SRAUC and FMD in premenopausal women (r(2)=0.097) was not statistically different from that in postmenopausal women (r(2)=0.025; Fisher P=0.30). Subgroup analysis using stringent inclusion criteria for health markers (n=505) confirmed a stronger FMD-SRAUC correlation in young women compared with young men and older women.Conclusions-Evidence for a stronger relationship between endothelial function and the eliciting SR stimulus is present in young women compared with men. Estrogen may contribute to this finding, but larger healthy cohorts are required for conclusive outcomes.

KW - endothelial function

KW - estrogen

KW - sex-specific

KW - shear stress

KW - FLOW-MEDIATED DILATION

KW - ESTROGEN-RECEPTOR-ALPHA

KW - NITRIC-OXIDE SYNTHASE

KW - BRACHIAL-ARTERY

KW - BLOOD-FLOW

KW - GENDER-DIFFERENCE

KW - VASCULAR FUNCTION

KW - MENSTRUAL-CYCLE

KW - SEX-DIFFERENCES

KW - AGE

U2 - 10.1161/JAHA.118.010994

DO - 10.1161/JAHA.118.010994

M3 - Article

VL - 8

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

SN - 2047-9980

IS - 4

M1 - 010994

ER -