Association of anemia and long-term survival in patients with pulmonary hypertension
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].
References (41)
- et al.
Anemia, allogenic blood transfusion, and immunomodulation in the critically ill
Chest
(2005 Jan) - et al.
Hemoglobin levels and 30-day mortality in patients after myocardial infarction
Int J Cardiol
(2005 Apr 20) - et al.
Impact of anemia in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: analysis from the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial
J Am Coll Cardiol
(2004 Aug 4) - et al.
Impact of anemia on outcomes of patients undergoing percutaneous coronary interventions
Am J Cardiol
(2004 Oct 15) - et al.
Anemia and mortality in heart failure patients a systematic review and meta-analysis
J Am Coll Cardiol
(2008) - et al.
Anaemia is an independent predictor of poor outcome in patients with chronic heart failure
Int J Cardiol
(2003) - et al.
Anemia in chronic heart failure: pathogenetic mechanisms
J Card Fail
(2004 Feb) - et al.
Updated clinical classification of pulmonary hypertension
J Am Coll Cardiol
(2009) - et al.
Inflammation and resistance to treatment with recombinant human erythropoietin
J Ren Nutr
(2005 Jan) Hematological management of the cyanotic adult with congenital heart disease
Int J Cardiol
(2004)
Hypoxia, red blood cells, and nitrite regulate NO-dependent hypoxic vasodilation
Blood
The biochemistry of nitric oxide, nitrite, and hemoglobin: role in blood flow regulation
Free Radic Biol Med
Effect of darbepoetin alfa on exercise tolerance in anemic patients with symptomatic chronic heart failure: a randomized, double-blind, placebo-controlled trial
J Am Coll Cardiol
Ethical authorship and publishing
Int J Cardiol
Japanese haemodialysis anaemia management practices and outcomes (1999–2006): results from the DOPPS
Nephrol Dial Transplant
Prevalence and outcomes of anemia in cancer: a systematic review of the literature
Am J Med
Reducing Bleeding in Cardiac Surgery (RBC) Investigators. Risk associated with preoperative anemia in cardiac surgery: a multicenter cohort study
Circulation
Nutritional anemias: report of a WHO Scientific Group
Anemia in older adults
Curr Opin Hematol
Association of mild anemia with cognitive, functional, mood and quality of life outcomes in the elderly: the “Health and Anemia” study
PLoS ONE
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