Aldosterone, inactive matrix gla-protein, and large artery stiffness in hypertension

Julio A. Chirinos, Mayank Sardana, Amer Ahmed Syed, Maheshwara R. Koppula, Swapna Varakantam, Izzah Vasim, Harold G. Oldland, Timothy S. Phan, Nadja E.A. Drummen, Cees Vermeer, Raymond R. Townsend, Scott R. Akers, Wen Wei, Edward Lakatta, Olga V. Fedorova

Research output: Contribution to journalArticle

Abstract

Vascular calcification leads to increased large artery stiffness. Matrix gla-protein (MGP) is a vitamin K–dependent protein that inhibits arterial calcification. Aldosterone promotes vascular calcification and stiffness, but the relationships between aldosterone, MGP, and arterial stiffness are unknown. We studied 199 adults (predominantly older men) with hypertension. We assessed the relationship between levels of dephospho-uncarboxylated MGP (dp-ucMGP), aldosterone, and carotid-femoral pulse wave velocity (CF-PWV) using standard regression and mediation analyses. Plasma aldosterone was measured in a subgroup of subjects (n = 106). Aldosterone was strongly associated with dp-ucMGP (standardized β = 0.50, P <.001), which was independent of potential confounders (β = 0.37, P <.001). Levels of dp-ucMGP were significantly associated with CF-PWV (β = 0.30; P <.001), which persisted after adjustment for potential confounders (β = 0.25; P =.004). Plasma aldosterone was also significantly associated with CF-PWV (standardized β = 0.21; P =.035). However, in a model that included aldosterone and dp-ucMGP, only the latter was associated with CF-PWV. Mediation analyses demonstrated a significant dp-ucMGP–mediated effect of aldosterone on CF-PWV, without a significant direct (dp-ucMGP independent) effect. Our study demonstrates a novel independent association between high aldosterone levels and dp-ucMGP, suggesting that aldosterone may influence the MGP pathway. This relationship appears to underlie the previously documented relationship between aldosterone and increased arterial stiffness.

Original languageEnglish (US)
JournalJournal of the American Society of Hypertension
DOIs
StateAccepted/In press - Jan 1 2018
Externally publishedYes

Fingerprint

Aldosterone
Arteries
Hypertension
Pulse Wave Analysis
Thigh
Vascular Stiffness
Vascular Calcification
matrix Gla protein
Vitamins
Regression Analysis

Keywords

  • Aldosterone
  • arterial stiffness
  • matrix gla-protein
  • vitamin K

ASJC Scopus subject areas

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Chirinos, J. A., Sardana, M., Syed, A. A., Koppula, M. R., Varakantam, S., Vasim, I., ... Fedorova, O. V. (Accepted/In press). Aldosterone, inactive matrix gla-protein, and large artery stiffness in hypertension. Journal of the American Society of Hypertension. https://doi.org/10.1016/j.jash.2018.06.018

Aldosterone, inactive matrix gla-protein, and large artery stiffness in hypertension. / Chirinos, Julio A.; Sardana, Mayank; Syed, Amer Ahmed; Koppula, Maheshwara R.; Varakantam, Swapna; Vasim, Izzah; Oldland, Harold G.; Phan, Timothy S.; Drummen, Nadja E.A.; Vermeer, Cees; Townsend, Raymond R.; Akers, Scott R.; Wei, Wen; Lakatta, Edward; Fedorova, Olga V.

In: Journal of the American Society of Hypertension, 01.01.2018.

Research output: Contribution to journalArticle

Chirinos, JA, Sardana, M, Syed, AA, Koppula, MR, Varakantam, S, Vasim, I, Oldland, HG, Phan, TS, Drummen, NEA, Vermeer, C, Townsend, RR, Akers, SR, Wei, W, Lakatta, E & Fedorova, OV 2018, 'Aldosterone, inactive matrix gla-protein, and large artery stiffness in hypertension', Journal of the American Society of Hypertension. https://doi.org/10.1016/j.jash.2018.06.018
Chirinos, Julio A. ; Sardana, Mayank ; Syed, Amer Ahmed ; Koppula, Maheshwara R. ; Varakantam, Swapna ; Vasim, Izzah ; Oldland, Harold G. ; Phan, Timothy S. ; Drummen, Nadja E.A. ; Vermeer, Cees ; Townsend, Raymond R. ; Akers, Scott R. ; Wei, Wen ; Lakatta, Edward ; Fedorova, Olga V. / Aldosterone, inactive matrix gla-protein, and large artery stiffness in hypertension. In: Journal of the American Society of Hypertension. 2018.
@article{673a1e5e01a540ab8d59eccf0d866164,
title = "Aldosterone, inactive matrix gla-protein, and large artery stiffness in hypertension",
abstract = "Vascular calcification leads to increased large artery stiffness. Matrix gla-protein (MGP) is a vitamin K–dependent protein that inhibits arterial calcification. Aldosterone promotes vascular calcification and stiffness, but the relationships between aldosterone, MGP, and arterial stiffness are unknown. We studied 199 adults (predominantly older men) with hypertension. We assessed the relationship between levels of dephospho-uncarboxylated MGP (dp-ucMGP), aldosterone, and carotid-femoral pulse wave velocity (CF-PWV) using standard regression and mediation analyses. Plasma aldosterone was measured in a subgroup of subjects (n = 106). Aldosterone was strongly associated with dp-ucMGP (standardized β = 0.50, P <.001), which was independent of potential confounders (β = 0.37, P <.001). Levels of dp-ucMGP were significantly associated with CF-PWV (β = 0.30; P <.001), which persisted after adjustment for potential confounders (β = 0.25; P =.004). Plasma aldosterone was also significantly associated with CF-PWV (standardized β = 0.21; P =.035). However, in a model that included aldosterone and dp-ucMGP, only the latter was associated with CF-PWV. Mediation analyses demonstrated a significant dp-ucMGP–mediated effect of aldosterone on CF-PWV, without a significant direct (dp-ucMGP independent) effect. Our study demonstrates a novel independent association between high aldosterone levels and dp-ucMGP, suggesting that aldosterone may influence the MGP pathway. This relationship appears to underlie the previously documented relationship between aldosterone and increased arterial stiffness.",
keywords = "Aldosterone, arterial stiffness, matrix gla-protein, vitamin K",
author = "Chirinos, {Julio A.} and Mayank Sardana and Syed, {Amer Ahmed} and Koppula, {Maheshwara R.} and Swapna Varakantam and Izzah Vasim and Oldland, {Harold G.} and Phan, {Timothy S.} and Drummen, {Nadja E.A.} and Cees Vermeer and Townsend, {Raymond R.} and Akers, {Scott R.} and Wen Wei and Edward Lakatta and Fedorova, {Olga V.}",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.jash.2018.06.018",
language = "English (US)",
journal = "Journal of the American Society of Hypertension",
issn = "1933-1711",
publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - Aldosterone, inactive matrix gla-protein, and large artery stiffness in hypertension

AU - Chirinos, Julio A.

AU - Sardana, Mayank

AU - Syed, Amer Ahmed

AU - Koppula, Maheshwara R.

AU - Varakantam, Swapna

AU - Vasim, Izzah

AU - Oldland, Harold G.

AU - Phan, Timothy S.

AU - Drummen, Nadja E.A.

AU - Vermeer, Cees

AU - Townsend, Raymond R.

AU - Akers, Scott R.

AU - Wei, Wen

AU - Lakatta, Edward

AU - Fedorova, Olga V.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Vascular calcification leads to increased large artery stiffness. Matrix gla-protein (MGP) is a vitamin K–dependent protein that inhibits arterial calcification. Aldosterone promotes vascular calcification and stiffness, but the relationships between aldosterone, MGP, and arterial stiffness are unknown. We studied 199 adults (predominantly older men) with hypertension. We assessed the relationship between levels of dephospho-uncarboxylated MGP (dp-ucMGP), aldosterone, and carotid-femoral pulse wave velocity (CF-PWV) using standard regression and mediation analyses. Plasma aldosterone was measured in a subgroup of subjects (n = 106). Aldosterone was strongly associated with dp-ucMGP (standardized β = 0.50, P <.001), which was independent of potential confounders (β = 0.37, P <.001). Levels of dp-ucMGP were significantly associated with CF-PWV (β = 0.30; P <.001), which persisted after adjustment for potential confounders (β = 0.25; P =.004). Plasma aldosterone was also significantly associated with CF-PWV (standardized β = 0.21; P =.035). However, in a model that included aldosterone and dp-ucMGP, only the latter was associated with CF-PWV. Mediation analyses demonstrated a significant dp-ucMGP–mediated effect of aldosterone on CF-PWV, without a significant direct (dp-ucMGP independent) effect. Our study demonstrates a novel independent association between high aldosterone levels and dp-ucMGP, suggesting that aldosterone may influence the MGP pathway. This relationship appears to underlie the previously documented relationship between aldosterone and increased arterial stiffness.

AB - Vascular calcification leads to increased large artery stiffness. Matrix gla-protein (MGP) is a vitamin K–dependent protein that inhibits arterial calcification. Aldosterone promotes vascular calcification and stiffness, but the relationships between aldosterone, MGP, and arterial stiffness are unknown. We studied 199 adults (predominantly older men) with hypertension. We assessed the relationship between levels of dephospho-uncarboxylated MGP (dp-ucMGP), aldosterone, and carotid-femoral pulse wave velocity (CF-PWV) using standard regression and mediation analyses. Plasma aldosterone was measured in a subgroup of subjects (n = 106). Aldosterone was strongly associated with dp-ucMGP (standardized β = 0.50, P <.001), which was independent of potential confounders (β = 0.37, P <.001). Levels of dp-ucMGP were significantly associated with CF-PWV (β = 0.30; P <.001), which persisted after adjustment for potential confounders (β = 0.25; P =.004). Plasma aldosterone was also significantly associated with CF-PWV (standardized β = 0.21; P =.035). However, in a model that included aldosterone and dp-ucMGP, only the latter was associated with CF-PWV. Mediation analyses demonstrated a significant dp-ucMGP–mediated effect of aldosterone on CF-PWV, without a significant direct (dp-ucMGP independent) effect. Our study demonstrates a novel independent association between high aldosterone levels and dp-ucMGP, suggesting that aldosterone may influence the MGP pathway. This relationship appears to underlie the previously documented relationship between aldosterone and increased arterial stiffness.

KW - Aldosterone

KW - arterial stiffness

KW - matrix gla-protein

KW - vitamin K

UR - http://www.scopus.com/inward/record.url?scp=85050097406&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85050097406&partnerID=8YFLogxK

U2 - 10.1016/j.jash.2018.06.018

DO - 10.1016/j.jash.2018.06.018

M3 - Article

C2 - 30033123

AN - SCOPUS:85050097406

JO - Journal of the American Society of Hypertension

JF - Journal of the American Society of Hypertension

SN - 1933-1711

ER -