Leptin levels predict survival in pulmonary arterial hypertension - PubMed (original) (raw)

Leptin levels predict survival in pulmonary arterial hypertension

Adriano R Tonelli et al. Pulm Circ. 2012 Apr-Jun.

Abstract

Evidence suggests that leptin is involved in relevant processes in the cardiovascular system. Low serum leptin levels have been associated with increased cardiovascular events and mortality in patients with coronary artery, diabetes, or chronic kidney disease. We hypothesized that leptin is increased in pulmonary arterial hypertension (PAH) and provides prognostic information. We correlated leptin levels with clinical data and assessed its association with survival. Sixty-seven patients with PAH and 29 healthy controls were studied. Plasma leptin levels were nonlinearly associated with BMI. Leptin level <15 μg/l was associated with higher mortality in PAH patients, with an adjusted (age, gender, BMI, and smoking status) hazard ratio of 3.8 (95% CI: 1.3-11.2), P=0.016. Similarly, PAH patients with leptin/BMI ratio <0.5 μg * m(2)/kg * l had worse survival than those with a level >0.5 μg * m(2)/ kg * l (P=0.046 by log-rank test). Two-year mortality in PAH patients was 24%. A receiver operating characteristic curve using leptin/BMI ratio as the test variable and 2-year mortality as the state variable showed an area under the curve of 0.74 (95% CI: 0.62-0.86). A leptin/BMI ratio cut-off of 0.6 had a high sensitivity (94%) and negative predictive value (96%) for predicting death of any cause at 2 years. In PAH, plasma leptin levels are directly associated with BMI. Lower leptin levels, when adjusted by BMI, are associated with an increased overall mortality and leptin/BMI ratio has high negative predictive value for mortality at 2 years.

Keywords: leptin; mortality; obesity; pulmonary hypertension.

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Conflict of interest statement

Conflict of Interest: None declared.

Figures

Figure 1

Figure 1

Scatterplot of leptin level and BMI. Both axes in the plot are logged. Restrictive cubic spline (black, solid) and Lowess (gray, dash) lines are displayed.

Figure 2

Figure 2

ROC curve of leptin/BMI and dot chart of log leptin/BMI with mortality at 2 years as the classification variable. (A) leptin/BMI measurements are in μg * m2/ kg * l. Area under the curve: 0.74 (95% CI: 0.62-0.86). (B) Dot chart of log leptin/BMI with line placed at a leptin/BMI ratio of 0.6. All but one of PAH patients who died at 2 years had a leptin/BMI ratio <0.6.

Figure 3

Figure 3

Survival analysis. Kaplan–Meier survival analysis with log-rank test comparing the ratio of leptin/BMI <0.5 and ≥ 0.5 μg * m2/ kg * l (A) and Cox regression analysis using the same cut-off of leptin/BMI adjusted for age, gender, BMI, and smoking status (B).

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