TY - JOUR
T1 - The association between markers of type I collagen synthesis and echocardiographic response to spironolactone in patients at risk of heart failure: findings from the HOMAGE trial
AU - Kobayashi, M.
AU - Girerd, N.
AU - Ferreira, J.P.
AU - Kevin, D.
AU - Huttin, O.
AU - Gonzalez, A.
AU - Bozec, E.
AU - Clark, A.L.
AU - Cosmi, F.
AU - Cuthbert, J.
AU - Diez, J.
AU - Edelmann, F.
AU - Hazebroek, M.
AU - Heymans, S.
AU - Mariottoni, B.
AU - Pellicori, P.
AU - Petutschnigg, J.
AU - Pieske, B.
AU - Staessen, J.A.
AU - Verdonschot, J.A.J.
AU - Rossignol, P.
AU - Cleland, J.G.F.
AU - Zannad, F.
AU - HOMAGE Trial Committees
PY - 2022/9
Y1 - 2022/9
N2 - Aims Procollagen type I C-terminal propeptide (PICP) and procollagen type III N-terminal propeptide (PIIINP) are markers reflecting collagen synthesis in cardiac fibrosis. However, they may be influenced by the presence of non-cardiac comorbidities (e.g. ageing, obesity, renal impairment). Understanding the associations between markers of collagen synthesis and abnormalities of cardiac structure and function is important to screen for myocardial fibrosis and monitor the antifibrotic effect of medications. Methods and results The HOMAGE (Heart 'OMics' in AGEing) trial showed that spironolactone decreased serum PICP concentrations and improved cardiac remodelling over 9 months in a population at risk of developing heart failure (HF). We evaluated the associations between echocardiographic variables, PICP, PIIINP and galectin-3 at baseline and during the course of the trial. Among 527 individuals (74 +/- 7 years, 26% women), median serum concentrations of PICP, PIIINP and galectin-3 were 80.6 mu g/L (65.1-97.0), 3.9 mu g/L (3.1-5.0), and 16.1 mu g/L (13.5-19.7), respectively. After adjustment for potential confounders, higher serum PICP was significantly associated with left ventricular hypertrophy, left atrial enlargement, and greater ventricular stiffness (all p < 0.05), whereas serum PIIINP and galectin-3 were not (all p > 0.05). In patients treated with spironolactone, a reduction in serum PICP during the trial was associated with a decrease in E/e ' (adjusted-beta = 0.93, 95% confidence interval 0.14-1.73; p = 0.022). Conclusions In individuals at high risk of developing HF, serum PICP was associated with cardiac structural and functional abnormalities, and a decrease in PICP with spironolactone was correlated with improved diastolic dysfunction as assessed by E/e '. In contrast, no such associations were present for serum PIIINP and galectin-3.
AB - Aims Procollagen type I C-terminal propeptide (PICP) and procollagen type III N-terminal propeptide (PIIINP) are markers reflecting collagen synthesis in cardiac fibrosis. However, they may be influenced by the presence of non-cardiac comorbidities (e.g. ageing, obesity, renal impairment). Understanding the associations between markers of collagen synthesis and abnormalities of cardiac structure and function is important to screen for myocardial fibrosis and monitor the antifibrotic effect of medications. Methods and results The HOMAGE (Heart 'OMics' in AGEing) trial showed that spironolactone decreased serum PICP concentrations and improved cardiac remodelling over 9 months in a population at risk of developing heart failure (HF). We evaluated the associations between echocardiographic variables, PICP, PIIINP and galectin-3 at baseline and during the course of the trial. Among 527 individuals (74 +/- 7 years, 26% women), median serum concentrations of PICP, PIIINP and galectin-3 were 80.6 mu g/L (65.1-97.0), 3.9 mu g/L (3.1-5.0), and 16.1 mu g/L (13.5-19.7), respectively. After adjustment for potential confounders, higher serum PICP was significantly associated with left ventricular hypertrophy, left atrial enlargement, and greater ventricular stiffness (all p < 0.05), whereas serum PIIINP and galectin-3 were not (all p > 0.05). In patients treated with spironolactone, a reduction in serum PICP during the trial was associated with a decrease in E/e ' (adjusted-beta = 0.93, 95% confidence interval 0.14-1.73; p = 0.022). Conclusions In individuals at high risk of developing HF, serum PICP was associated with cardiac structural and functional abnormalities, and a decrease in PICP with spironolactone was correlated with improved diastolic dysfunction as assessed by E/e '. In contrast, no such associations were present for serum PIIINP and galectin-3.
KW - Collagen markers
KW - Myocardial fibrosis
KW - Spironolactone
KW - Diastolic function
KW - Cardiac structural remodelling
KW - Heart failure
KW - VENTRICULAR DIASTOLIC FUNCTION
KW - CARBOXY-TERMINAL PROPEPTIDE
KW - PROCOLLAGEN TYPE-I
KW - EUROPEAN ASSOCIATION
KW - MYOCARDIAL FIBROSIS
KW - AMERICAN SOCIETY
KW - CIRCULATING BIOMARKERS
KW - GALECTIN-3
KW - DISEASE
KW - ADULTS
U2 - 10.1002/ejhf.2579
DO - 10.1002/ejhf.2579
M3 - Article
C2 - 35703355
SN - 1388-9842
VL - 24
SP - 1559
EP - 1568
JO - European journal of heart failure
JF - European journal of heart failure
IS - 9
ER -