Elsevier

American Heart Journal

Volume 153, Issue 6, June 2007, Pages 1088.e1-1088.e7
American Heart Journal

Clinical Investigation
Congestive Heart Disease
Impaired peripheral endothelial function in severe idiopathic pulmonary hypertension correlates with the pulmonary vascular response to inhaled iloprost

https://doi.org/10.1016/j.ahj.2007.03.005Get rights and content

Background

Pulmonary endothelial function is known to be impaired in subjects with idiopathic pulmonary arterial hypertension (IPAH), but peripheral endothelial dysfunction and its predictive value for pulmonary vasoreactivity have not been previously investigated.

Methods

Measurements of peripheral endothelium-dependent and endothelium-independent vasoreactivity using flow-mediated dilation (FMD) and nitroglycerin-mediated dilation of the brachial artery were performed in 18 patients with severe IPAH (15 women; mean age 50 years [95% confidence interval 46-55 years], mean pulmonary artery pressure [PAP] 51 mm Hg [43-59 mm Hg], pulmonary vascular resistance [PVR] 1239 dyn s cm−5 [861-1618 dyn s cm−5] at baseline) and in 36 age- and sex-matched controls. In patients with IPAH, acute pulmonary vasoreactivity was measured as pulmonary vascular response to inhaled iloprost (PVRII) during pulmonary catheterization.

Results

Compared to controls, patients with IPAH demonstrated impaired peripheral endothelial function (FMD, 0.19 [0.07-0.31] vs 0.38 [0.30-0.44] mm among controls; P =.002). No such impairment was observed for nitroglycerin-mediated dilation (0.34 [0.23-0.46] vs 0.36 [0.20-0.51] mm among controls; P = .679). Among patients with IPAH, iloprost lowered mean PAP by 8.2 mm Hg (2.0-14.5 mm Hg) (P = .001) and PVR by 395 dyn s cm−5 (109-680 dyn s cm−5) (P < .001). Subsequent analysis of the association between peripheral endothelial function and PVRII disclosed a correlation of FMD with the percent decrease in mean PAP (r = .65, P = .003) and PVR (r = 0.67, P = .002), in which patients with IPAH with the greatest PVRII also exhibited the highest FMD values.

Conclusions

Idiopathic pulmonary arterial hypertension is associated with peripheral endothelial dysfunction. Peripheral endothelium-dependent vasoreactivity correlates with the PVRII. It remains to be established if FMD has the potential as a clinical tool for noninvasive estimation of pulmonary vasoreactivity in IPAH.

Section snippets

Patient population

The study was conducted between February 2004 and June 2005. During this period, all patients with pulmonary arterial hypertension hospitalized for treatment of pulmonary hypertension were screened for inclusion. They were eligible if they met the following criteria: (1) a diagnosis of IPAH with exclusion of pulmonary arterial hypertension secondary to other causes; (2) chronically stable disease with New York Heart Association class II/III; (3) mean pulmonary artery pressure (PAP) ≥30 mm Hg at

Results

Characteristics of patients with IPAH and those in the control group are outlined in Table I. Patients in the IPAH group tended to have lower diastolic blood pressure values as well as lower high-density lipoprotein cholesterol levels. As to the distribution of all other characteristics, the 2 groups showed similar patterns. Patients with IPAH showed a mean baseline systolic PAP of 81 mm Hg (95% CI 70-93 mm Hg), a diastolic PAP of 32 mm Hg (95% CI 26-39 mm Hg), and a mean PAP of 51 mm Hg (95%

Discussion

The present study has 2 major findings. The first is an association of IPAH with endothelial dysfunction in peripheral, nonpulmonary conduit vessels. Compared to controls, patients with IPAH exhibited impaired endothelium-dependent vasoreactivity, whereas the level of endothelium-independent vasoreactivity was similar in both groups. Except for diastolic blood pressure and high-density lipoprotein cholesterol levels, controls exhibited a pattern of cardiovascular risk factors resembling that of

References (35)

  • S. Rich et al.

    High dose titration of calcium channel-blocking agents for primary pulmonary hypertension: guidelines for short-term drug testing

    J Am Coll Cardiol

    (1991)
  • H.H. Leuchte et al.

    Hemodynamic response to sildenafil, nitric oxide, and iloprost in primary pulmonary hypertension

    Chest

    (2004)
  • R. Budhiraja et al.

    Endothelial dysfunction in pulmonary hypertension

    Circulation

    (2004)
  • L.J. Rubin

    Primary pulmonary hypertension

    N Engl J Med

    (1997)
  • C.J. Cooper et al.

    Role of nitric oxide in the local regulation of pulmonary vascular resistance in humans

    Circulation

    (1996)
  • A. Giaid et al.

    Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension

    N Engl J Med

    (1995)
  • N. Galie et al.

    The endothelin system in pulmonary arterial hypertension

    Cardiovasc Res

    (2004)
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