Pulmonary Hypertension Is Related to Peripheral Endothelial Dysfunction in Heart Failure With Preserved Ejection Fraction
Background—Pulmonary hypertension and collagen metabolism abnormalities are prevalent in patients with HFpEF. Peripheral endothelial dysfunction (PED) has been described in heart failure (HF), as well as in pulmonary arterial hypertension. Our aim is to determine whether pulmonary hypertension is associated with PED and impaired collagen metabolism in patients with heart failure and preserved ejection fraction (HFpEF).
Methods and Results—Flow-mediated dilation (FMD) of the brachial artery, matrix metalloproteinase-2 and -9 (MMP-2, -9), tissue metalloproteinase inhibitor 1 (TIMP-1), and C-terminal propeptide of type I procollagen (CICP) were determined in 28 patients with HFpEF and 42 hypertensive controls. Patients with systolic pulmonary artery pressure (PAP)>35 mmHg on echocardiogram underwent a right heart catheterization. HFpEF patients had more severe PED than controls: FMD 1.95%(-0.81-4.92) vs. 5.02%(3.90-10.12), p=0.002. Twenty patients with pulmonary hypertension (PH) underwent right heart catheterization: mean PAP 38(27-52)mmHg, wedge capillary pressure 18(16-22)mmHg, pulmonary vascular resistance (PVR) 362(235-603)dyn*s*cm-⁵. There was a significant inverse correlation between FMD and PVR in HFpEF patients with PH(r=-0.679, p=0.002). HFpEF patients showed higher MMP-2 and CICP values than hypertensive controls. HFpEF patients with higher CICP values also had higher mean PAP (r=0.553, p=0.014), transpulmonary gradient (r=0.560, p=0.013) and pulmonary vascular resistance (r=0.626, p=0.004).
Conclusions—In patients with HFpEF, there is a significant correlation between PED and PVR. Collagen metabolism was more impaired in patients with HFpEF and PH. PED and collagen metabolism assessment could be useful tools to identify HFpEF patients at risk of developing pulmonary hypertension.
- pulmonary vascular resistance
- heart failure and preserved ejection fraction
- endothelium dependent dilation
- collagen metabolism
- pulmonary circulation
- Received October 28, 2013.
- Accepted July 10, 2014.