01 March 2017 by Wassim Fares

Prognostic value of the baseline serum sodium level in two independent cohorts of pulmonary arterial hypertension

Introduction

Hyponatremia has prognostic value in heart failure and liver disease, so we studied the potential prognostic value of hyponatremia in pulmonary arterial hypertension (PAH).

Methods

We performed secondary analyses of 2 PAH cohorts: 1) United Therapeutics’ randomized clinical trials (including P0:03, P0:04, P0:05, & P0:06), and 2) A long-term PAH registry at the Cleveland Clinic.  We included adult WHO group 1 PH patients.  Our hypothesis was that baseline hyponatremia is associated with worse 1-year survival.

Results

Baseline Na level is negatively correlated with baseline mean right atrial pressure (r= -0.09; p=0.018; r=-0.089 p=0.015 in cohorts #1 and 2 respectively).  In unadjusted analyses of cohort #1, sodium level (as a continuous variable) is associated with 1-year mortality (Hazard ratio=0.94; p=0.035).  Hyponatremia (Na <137) status loses its significance (p=0.12) in the multivariable regression Cox model when adjusted for functional class (after applying a stepwise model selection procedure to identify the confounding variable whose presence turns the effect of baseline sodium level into insignificant).  Secondary analyses using a cut-off value of < 135 mmol/liter to define hyponatremia and looking at 2-, 3-, and 4-year mortality showed overall similar results. 

These results were validated in cohort #2, which suggested the association between hyponatremia and survival is driven by poor outcomes among patients below a very low sodium cutoff of <130.  Although the sample size for patients with severe hyponatremia (Na <130) was small (31 patients), severe hyponatremia in the validation cohort was associated with poorer overall survival (53% versus 77%; p=0.01), and that the statistical significance of the association at this cutoff holds up under covariate adjustment for age, functional class, and baseline 6-minute walk distance (p<0.001).

Conclusion

Although baseline hyponatremia is associated with 1-year mortality, it loses its significance when adjusted for functional class in the multivariable regression Cox model.

 

Acknowledgement

We thank United Therapeutics Corporation for making its database available for our secondary analyses.

References

  • Hyponatremia predicts right heart failure and poor survival in pulmonary arterial hypertension.  Forfia PR, et al.  Am J Respir Crit Care Med. 2008 Jun 15;177(12):1364-9.
  • Association of hyponatremia and outcomes in pulmonary hypertension.  Rabinovitz A, et al.  J Card Fail. 2013;19(8):550-6.
  • Outcomes of hospitalisation for right heart failure in pulmonary arterial hypertension.  Campo A, et al.  Eur Respir J. 2011;38(2):359-67.
  • Characteristics and outcome after hospitalization for acute right heart failure in patients with pulmonary arterial hypertension.  Haddad F, et al.  Circ Heart Fail. 2011;4(6):692-9.
  • Hyponatraemia: A strong predictor of mortality in adults with congenital heart disease.  Dimopoulos K, et al.  Eur Heart J. 2010;31(5):595-601.
  • Hyponatremia and mortality: moving beyond associations.  Hoorn EJ, Zietse R.  Am J Kidney Dis. 2013; 62(1): 139-49.

Key Contributors

Anastasiia A. Rudkovskaiia MD1, Adriano R. Tonelli MD2, Youlan Rao PhD3, Raed A. Dweik MD2, Wassim H. Fares MD, MSc4 1: Bridgeport Hospital, Yale New Haven Health, Department of Internal Medicine, Bridgeport, Connecticut, USA 2: Cleveland Clinic, Respiratory Institute, Cleveland, Ohio 3: United Therapeutics Inc., Research Triangle Park, North Carolina 4: Yale University, Pulmonary Critical Care & Sleep Medicine, New Haven, CT


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