Association of the metabolic syndrome with pulmonary venous hypertension

Abstract

Background: Pulmonary venous hypertension (PVH) is a well-described cause of pulmonary hypertension (PH) in patients with left heart disease associated with elevated left heart filling pressure. PVH results from a number of processes, including left-sided valvular disease, constrictive pericardial disease, restrictive cardiomyopathies, and left ventricular (LV) systolic dysfunction. PVH in patients with normal LV systolic function, commonly referred to as diastolic dysfunction, is not well characterized. We observed that many patients with PH due to PVH have obesity, hypertension, diabetes mellitus, and hypercholesterolemia, which are clinical features of the metabolic syndrome (MS), a previously identified cause for systemic vascular disease.

Methods: We evaluated 122 consecutive patients referred for diagnosis and treatment of PH and compared the prevalence of features of the MS between patients with PVH and those with pulmonary arterial hypertension (PAH). We also compared clinical and hemodynamic characteristics between these two groups.

Results: Compared to patients with PAH, patients with PVH had a higher frequency of hypertension, obesity, diabetes mellitus, and hyperlipidemia. Two or more features of the MS were found in 16 of 17 patients with PVH (94.1%) compared with 34.3% of patients with PAH (p < 0.001; odds ratio, 30.7; 95% confidence interval, 3.6 to 260.0). PH was substantial, but less severe overall, in patients with PVH compared to those with PAH (mean pulmonary artery pressure, 45 +/- 17 mm Hg [range, 26 to 71 mm Hg] vs 53 +/- 10 [range, 33 to 72 mm Hg], respectively [p = 0.041]; and pulmonary vascular resistance, 4.4 +/- 2.9 units [range, 1.2 to 10.8 units] vs 10.8 +/- 4.7 units [range, 4.8 to 21.9 units], respectively [p < 0.001]).

Conclusion: PVH is highly associated with the MS. Our results suggest that the MS may predispose patients to develop pulmonary vascular disease.

Conflict of interest statement

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Figures

Figure 1

Flow diagram showing the final diagnoses of the 122 patients included in the study. CHD = congenital heart disease; CTD = connective tissue disease; CTEPH = chronic thromboembolic pulmonary hypertension; IPAH = idiopathic PAH; ME = mixed etiology, patients with more than one potential etiology for pulmonary hypertension; PLD = parenchymal lung disease; POPH = portopulmonary hypertension; Sarcoid = sarcoidosis; Valve = mitral or aortic valve disease.

Figure 2

Bar graph demonstrating the percentage of patients with PAH and PVH with each of the four clinical features of the MS, p = 0.004 for hypertension, p = 0.002 for obesity, p = 0.005 for diabetes mellitus, and p = 0.023 for hyperlipidemia. The odds ratio with 95% CI for PVH with each factor is presented below the graph. DM = diabetes mellitus; HL = hyperlipidemia; HTN = hypertension.

Figure 3

The MS may contribute to pulmonary hypertension through mechanisms similar to those in systemic vascular disease. Systemic hypertension leading to left ventricular end-diastolic hypertension raises pulmonary vascular pressure and may result in reactive vasoconstriction. Obesity is associated with inflammatory cytokines that cause vasomotor abnormalities and perhaps proliferation. Although hyperglycemia is not yet proven to affect pulmonary vessels directly, hyperglycemic vasculopathy is suggested by peroxisome proliferator-activated receptor gamma abnormalities. Atherosclerosis occurs only in large pulmonary arteries and is less likely to be involved directly in pulmonary manifestations of the MS.