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. 2018 Jun 28;51(6):1800467.
doi: 10.1183/13993003.00467-2018. Print 2018 Jun.

Lower DHEA-S levels predict disease and worse outcomes in post-menopausal women with idiopathic, connective tissue disease- and congenital heart disease-associated pulmonary arterial hypertension

Grayson L Baird  1 , Christine Archer-Chicko  2 , R Graham Barr  3 , David A Bluemke  4 , Andrew E Foderaro  1 , Jason S Fritz  2 , Nicholas S Hill  5 , Steven M Kawut  2   6   7 , James R Klinger  1 , Joao A C Lima  8 , Christopher J Mullin  1 , Pamela Ouyang  8 , Harold I Palevsky  2 , Amy J Palmisicano  1 , Diane Pinder  2 , Ioana R Preston  5 , Kari E Roberts  5 , K Akaya Smith  2   7 , Thomas Walsh  1 , Mary Whittenhall  1 , Corey E Ventetuolo  1   9
Affiliations

Lower DHEA-S levels predict disease and worse outcomes in post-menopausal women with idiopathic, connective tissue disease- and congenital heart disease-associated pulmonary arterial hypertension

Grayson L Baird et al. Eur Respir J. .

Abstract

High oestradiol (E2) and low dehydroepiandrosterone-sulfate (DHEA-S) levels are risk factors for pulmonary arterial hypertension (PAH) in men, but whether sex hormones are related to PAH in women is unknown.Post-menopausal women aged ≥55 years with PAH were matched by age and body mass index to women without cardiovascular disease. Plasma sex hormone levels were measured by immunoassay.Lower levels of DHEA-S (p<0.001) and higher levels of E2 (p=0.02) were associated with PAH. In PAH cases (n=112), lower DHEA-S levels were associated with worse haemodynamics (all p<0.01) and more right ventricular dilatation and dysfunction (both p=0.001). Lower DHEA-S levels were associated with shorter 6-min walking distance (6MWD) (p=0.01) and worse functional class (p=0.004). Each Ln(1 µg·dL-1) decrease in DHEA-S was associated with a doubling in the risk of death (hazard ratio 2.0, 95% CI 1.5-2.7; p<0.001). Higher levels of E2 were associated with shorter 6MWD (p=0.03) and worse functional class (p=0.01).High E2 and low DHEA-S levels are associated with the risk and severity of PAH in post-menopausal women. Hormonal modulation should be studied as a treatment strategy in PAH.

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Conflict of interest statement

Conflict of interest: S.M. Kawut reports grants (for research and CME) from Actelion, United Therapeutics, Gilead, Lung Biotech, Bayer and the Cardiovascular Medical Research and Education Fund, and personal fees (for travel) from the American Thoracic Society, outside the submitted work. Conflict of interest: J.R. Klinger reports grants from Actelion, United Therapeutics, Gilead, Eiger and Bayer, outside the submitted work. Conflict of interest: H.I. Palevsky reports personal fees from Actelion, Janssen, Bayer, GSK and United Therapeutics, outside the submitted work. Conflict of interest: I.R. Preston reports grants and personal fees from Actelion, grants from Bayer and Gilead, and personal fees from Arena, United Therapeutics and Pfizer, outside the submitted work. Conflict of interest: A. Smith reports grants from Actelion, Gilead and United Therapeutics, outside the submitted work. Conflict of interest: M. Whittenhall reports personal fees from Actelion, Bayer, Gilead and United Therapeutics, outside the submitted work. Conflict of interest: C.E. Ventetuolo reports personal fees from Bayer, Acceleron and United Therapeutics and grants from the CHEST Foundation (Actelion sponsored) and Eiger paid to her institution, outside the submitted work. Conflict of interest: C. Archer-Chicko reports personal fees from Actelion, outside the submitted work.

Figures

FIGURE 1
FIGURE 1
Adjusted parameter estimates for hormone levels by case status after matching for age and body mass index. a) Oestradiol; b) dehydroepiandrosterone-sulfate (DHEA-S). Data are presented as median (95% CI). PAH: pulmonary arterial hypertension.
FIGURE 2
FIGURE 2
Adjusted parameter estimates for hormone levels by functional class in pulmonary arterial hypertension (PAH) cases. a) Oestradiol; b) dehydroepiandrosterone-sulfate (DHEA-S). Data are presented as median (95% CI). p-value: test for trend across category.
FIGURE 3
FIGURE 3
Adjusted parameter estimates for hormone levels by degree of right ventricular (RV) dilatation (a, c) and dysfunction (b, d) on echocardiogram in pulmonary arterial hypertension (PAH) cases. a, b) Oestradiol; c, d) dehydroepiandrosterone-sulfate (DHEA-S). Data are presented as median (95% CI). p-value: test for trend across category.
FIGURE 4
FIGURE 4
Kaplan–Meier survival estimates and 95% confidence limits in pulmonary arterial hypertension cases. Numbers of subjects at risk as indicated over the follow-up period. DHEA-S: dehydroepiandrosterone-sulfate.
See this image and copyright information in PMC

Comment in

References

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