Association between plasma phosphate/pyrophosphate ratio and CT derived aortic valve calcification score in an unselected cohort of cardiovascular patients

Juhász, Dénes and Várhegyi, Martin and Rakovics, Márton and Szilveszter, Bálint and Jermendy, Ádám Levente and Dósa, Edit and Straub, Éva and Merkely, Béla and Arányi, Tamás and Apor, Astrid and Szüts, Dávid and Manouras, Aristomenis and Bäck, Magnus and Szeri, Flóra and Nagy, Anikó Ilona (2025) Association between plasma phosphate/pyrophosphate ratio and CT derived aortic valve calcification score in an unselected cohort of cardiovascular patients. European Heart Journal - Cardiovascular Imaging. ISSN 2047-2404 (In Press)

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Abstract

Aims: Inorganic pyrophosphate (PPi) is an endogenous inhibitor of soft-tissue calcification. A disturbed equilibrium between pro- and anti-mineralization agents, like extracellular phosphate (Pi) and PPi, have been implicated in the mechanism of aortic valve calcification (AVC). We aimed to investigate the association of the plasma PPi concentration and Pi/PPi ratio with the degree AVC in cardiovascular patients. Methods and results: 154 patients referred for cardiac CT, including 43 individuals with severe aortic stenosis, were prospectively enrolled. The aortic valve calcium score (AVCS) was measured on non-contrast CT images. Plasma PPi level was determined enzymatically. Of the entire population (age: 67±12 years, 42.5% female), 42% had some degree of AVC (range 9-6641 AU). Plasma PPi showed a significant positive association with plasma Pi and low density lipoprotein cholesterol (LDL-C) concentration and was inversely related to alkaline phosphatase activity. When controlled for age, female patients had higher PPi levels. In univariate analysis, plasma PPi level did not show an association with AVCS, however, the Pi/PPi ratio was significantly positively associated with the degree of AVC (estimate: 1508.1; SE 616.0, p=0.015), along with age, hypertension, plasma lipoprotein(a) concentration and statin treatment, whereas eGFR and LDL-C level showed significant negative associations. In multivariate analysis only age and Pi/PPi ratio remained significant determinant of the AVCS (estimate: 1128.6; SE 562.5, p=0.047). Conclusion: This is the first study to investigate the association between PPi homeostasis and AVC in humans. The plasma Pi/PPi ratio was significantly positively associated with the AVC load even after adjustment for traditional risk factors.

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