Association of anemia and long-term survival in patients with pulmonary hypertension

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Abstract

Background

Anemia is a marker of worsened clinical outcome in patients with heart failure from left ventricular dysfunction. Pulmonary hypertension often results in right ventricular dysfunction. Accordingly we sought to examine the association of hemoglobin levels and long-term all-cause mortality in a cohort of patients with pulmonary hypertension.

Methods

Baseline demographic information, clinical characteristics and fasting blood work were obtained in a cohort of 145 patients with pulmonary hypertension referred for pulmonary vasodilator testing. Data was retrospectively analyzed with Cox-proportional hazards analysis.

Results

Baseline characteristics of the cohort included age (mean ± SD) 55.8 ± 14.6 years, 75% women, 50% with idiopathic pulmonary hypertension, mean pulmonary artery pressure 46.1 ± 14.2 mm Hg and arterial O2 saturation 91 ± 6%. The most commonly utilized pulmonary hypertension specific therapeutic agents in descending order of frequency were epoprostenol (27%), sildenafil (21%), bosentan (17%), and treprostinil (6%). Over a median follow-up of 2.1 years, there were 39 deaths (26.9%). Patients who died had significantly lower hemoglobin levels than those survived (12.2 ± 2.3 vs. 13.7 ± 2.0, p < 0.001). After adjustment for known predictors of death and pulmonary hypertension etiology, anemic patients were 3.3 times more likely to die than non-anemic patients (95% CI [1.43–7.51], p = 0.005).

Conclusions

Hemoglobin levels closely parallel survival in pulmonary hypertension. Modification of anemia in this disorder could alter the clinical course and calls for further research in this area.

Introduction

Anemia is a strong, independent risk factor for morbidity and mortality in a number of chronic conditions including kidney disease [1] and cancer [2]. It also negatively influences the course of acute illnesses [3] including myocardial infarction [4], [5] and increases periprocedural and perioperative morbidity and mortality [6], [7]. By the classic World Health Organization definition [8], anemia is present in only ∼ 9% of the United States population, but becomes significantly more common in older adults and in patients with comorbid illness [9], [10]. In certain conditions such as cancer and chronic kidney disease, anemia has a well-described pathophysiological basis and is nearly ubiquitous; while in other conditions the mechanism is less clear and attributed to the so-called “anemia of chronic disease” [11]. A number of studies have described an increased prevalence of anemia in patients with heart failure (HF) resulting from left ventricular (LV) dysfunction [12], [13]. Anemia occurs in up to 20% of outpatients and 30% of hospitalized patients with HF. In HF patients anemia is associated with an increased risk of cardiovascular events and is an independent predictor of mortality [14], [15], [16].

Pulmonary hypertension (PH) is a devastating clinical disorder associated with progressive right ventricular (RV) dysfunction and high rates of mortality. Patients with PH and RV dysfunction appear to have significantly worse clinical outcomes despite several new therapies [17], [18]. The range of hemoglobin levels in patients with PH has not been previously established. Furthermore, the effect of PH on erythropoiesis appears more complex than in left ventricular (LV) dysfunction. Low cardiac output, one of the postulated mechanisms of anemia in patients with LV dysfunction [19], is also prevalent in PH owing to RV dysfunction. On the other hand, hypoxia is also quite common, particularly in patients with idiopathic pulmonary hypertension, and PH from interstitial lung disease, collagen-vascular disease, and cyanotic congenital heart disease. Hypoxia stimulates erythropoiesis and may therefore counteract the effect of RV failure. This study was designed to retrospectively investigate the prevalence of anemia in a cohort of patients with PH referred for vasodilator testing, and to examine its association with long-term all-cause mortality.

Section snippets

Patients

Consecutive patients with pulmonary hypertension were entered into a database between November 1998 and December 2007 at two tertiary care academic affiliated medical centers. Complete blood counts were collected from a fasting blood-draw on either the morning of or the evening prior to cardiac catheterization. Abnormal values were repeated for validation purposes and only stable hemoglobin measurements were used for analysis. The World Health Organization classification of anemia (< 12 g/dL for

Patient characteristics

One hundred sixty nine patients were entered into the database between November 1998 and December 2007 and underwent invasive hemodynamic assessment including vasodilator challenge with iNO. Two patients with moderate or worse renal insufficiency (serum creatinine ≥ 2.5), 1 patient with sickle cell anemia, 13 patients with cyanotic congenital heart disease, and 7 patients with Dana Point Class 2 pulmonary hypertension were excluded. Blood counts for one patient were not complete. Of the 145

Discussion

This study shows for the first time that anemia is common in patients with advanced pulmonary hypertension. More importantly, the presence of anemia appears to have a powerful association with clinical outcome in PH patients and its prognostic significance is independent of previously described risks for morbidity and mortality and PH etiology. Anemia, as defined by the WHO, increases the hazard of death by more than 3 fold. Since dichotomization of continuous variables (such as hemoglobin

Funding

No outside funding was obtained for this study.

Acknowledgement

The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [41].

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