Relationships between sodium levels, haemodynamics and metalloproteinases in heart failure patients

Heart Vessels. 2022 Jun;37(6):986-993. doi: 10.1007/s00380-021-02004-9. Epub 2022 Jan 15.

Abstract

To estimate the associations between dysnatraemia and inflammatory marker [including interleukin-6 (IL-6)], and tissue remodelling marker [matrix metalloproteinase (MMP)-9 and tissue inhibitor of MMP (TIMP)-1], the pulmonary capillary wedge pressure (PCWP), mean pulmonary artery pressure (PAP), and left ventricular end-diastolic pressure (EDP), and the prognostic relevance in patients with heart failure. The serum sodium level and circulating levels of IL-6, MMP-9, and TIMP-1 were measured in 173 heart failure patients. Dual heart catheterisation was performed to measure PCWP, mean PAP, and EDP. All-cause mortality was assessed during the follow-up period (mean 88 ± 49 months). Restricted cubic spline (RCS) regression showed a U-shaped association of serum sodium level with TIMP-1, with the lowest values in the 138-140 mmol/L range (P for effect = 0.042, P for non-linearity = 0.017). IL-6 and MMP-9 levels showed non-significant associations with serum sodium level. U-shaped associations of serum sodium level with PCWP (P for effect = 0.004, P for non-linearity = 0.001) and mean PAP (P for effect = 0.042, P for non-linearity = 0.017) were found with the RCS regression model. The random forest model revealed that TIMP-1, MMP-9, and IL-6 were important predictors for serum sodium levels. Restricted cubic spline Cox regressions demonstrated that TIMP-1 levels indicated a U-shaped, concaved, non-linear association with all-cause mortality (P for effect = 0.011, P for non-linearity = 0.022). Dysnatraemia is an index of TIMP-1 aggravation and elevated PCWP, mean PAP; hence, it is associated with worsening all-cause mortality.Clinical Trial Registration: UMIN000023840.

Keywords: All-cause mortality; Chronic heart failure; Hyponatraemia; Interleukin-6; Matrix metalloproteinase-9; Tissue inhibitors of matrix metalloproteinase-1.

MeSH terms

  • Heart Failure* / blood
  • Hemodynamics
  • Humans
  • Interleukin-6 / blood
  • Matrix Metalloproteinase 9 / blood
  • Sodium* / blood
  • Tissue Inhibitor of Metalloproteinase-1*

Substances

  • Interleukin-6
  • Tissue Inhibitor of Metalloproteinase-1
  • Sodium
  • Matrix Metalloproteinase 9