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.