Does Chronic Kidney Disease Facilitate Malignant Myocardial Fibrosis in Heart Failure with Preserved Ejection Fraction of Hypertensive Origin?
Eiros R (1), Romero-González G (2), Gavira JJ (1,3), Beloqui O (3,4), Colina I (3,4), Fortún Landecho M (3,4), López B (3,5,6), González A (3,5,6), Díez J (1,2,3,5,6), Ravassa S (3,5,6).
(1) Department of Cardiology and Cardiac Surgery, Clínica Universidad de Navarra, 31008 Pamplona, Spain.
(2) Department of Nephrology, Clínica Universidad de Navarra, 31008 Pamplona, Spain.
(3) Program of Cardiovascular and Renal Diseases, Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain.
(4) Department of Internal Medicine, Clínica Universidad de Navarra, 31008 Pamplona, Spain.
(5) Program of Cardiovascular Diseases, CIMA Universidad de Navarra, 31008 Pamplona, Spain.
(6) Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain.
In hypertensive patients with heart failure (HF) a serum biomarker combination of high carboxy-terminal propeptide of procollagen type-I (PICP) and low carboxy-terminal telopeptide of collagen type-I to matrix metalloproteinase-1 (CITP:MMP-1) ratio identifies a histomolecular phenotype of malignant myocardial fibrosis (mMF) associated with severe diastolic dysfunction (DD) and poor outcomes.
As chronic kidney disease (CKD) facilitates MF and DD, we investigated the influence of CKD on the mMF biomarker combination in HF patients with preserved ejection fraction (HFpEF). Hypertensives (n = 365), 232 non-HF and 133 HFpEF, were studied, and 35% non-HF and 46% HFpEF patients had CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m2 or urine albumin-to-creatinine ratio ≥ 30 mg/g). Specific immunoassays were performed to determine biomarkers. Medians were used to establish the high PICP and low CITP:MMP-1 combination.
A comparison with non-HF showed that the biomarker combination presence was increased in HFpEF patients, being associated with CKD in all patients. CKD influenced the association of the biomarker combination and HFpEF (p for interaction ≤ 0.019).
The E:e' ratio was associated with the biomarker combination in CKD patients. Among CKD patients with HFpEF, those with the biomarker combination exhibited higher (p = 0.016) E:e' ratio than those without the pattern. These findings suggest that CKD facilitates the development of biomarker-assessed mMF and DD in hypertensive HFpEF patients.
CITATION J Clin Med. 2020 Feb 3;9(2). pii: E404. doi: 10.3390/jcm9020404