Association of TNF-R1 with Exercise Capacity in Asymptomatic Hypertensive Heart Disease-Mediating Role of Left Ventricular Diastolic Function Deterioration.

TNF receptor 1 (TNF-R1) mediates the proinflammatory and proapoptotic effects of TNF-alpha, with its soluble form predicting incident heart failure (HF). While there is evidence linking TNF pathway activation to cardiac dysfunction, the mechanisms involved remain unclear. This study aimed to investigate the association between TNF-R1, exercise capacity, and cardiac function in asymptomatic patients with hypertensive heart disease (HHD). We enrolled 80 patients (mean age 55 ± 12 years) with HHD and no clinical symptoms of HF (stages A and B). Echocardiography, including tissue Doppler and left atrial and left ventricular (LV) strain assessment, was performed at rest. Peripheral venous blood samples were collected to measure serum TNF-R1 concentration. The study population was divided into two subsets based on the median exercise capacity (peak VO) value. Patients with higher VO had lower serum TNF-R1 concentration and higher early peak mitral annular velocity (e') and peak atrial longitudinal strain (PALS). After adjusting for other covariates, multivariable regression analysis identified TNF-R1 as an independent determinant of peak VO. Mediation analysis revealed that the relationship between TNF-R1 and peak VO was mediated by LV diastolic function (PALS or e'), with a decrease in the beta coefficient after including mediator variables from 0.37 ( < 0.001) to 0.30 ( < 0.006) and 0.31 ( = 0.004), respectively. In patients with HHD, higher TNF-R1 levels are associated with lower exercise capacity, which may be mediated by impaired LV diastolic function. These findings might suggest a role of TNF signalling in early HF development, justifying further studies to evaluate TNF-R1 as a biomarker for risk of HF progression.