The Cardiorenal Anaemia Syndrome in Systolic HF
The Cardiorenal Anaemia Syndrome in Systolic HF
Aims We sought to assess the prevalence and clinical correlates of cardiorenal anaemia (CRA) syndrome in systolic heart failure and the relationship between renal dysfunction and anaemia on hard clinical outcomes.
Methods and results We studied 951 patients with chronic heart failure (CHF) and systolic dysfunction. The primary outcome was all-cause mortality and urgent heart transplantation (UHT). Cox's regression analyses were used to assess the relation of the variables to the primary outcome. Hazard ratios (HRs) with 95% confidence intervals (CI) were calculated.
The prevalence of CRA syndrome was 21.1%. Age (P < 0.001), body mass index (P< 0.001), diabetes (P =< 0.001), ischaemic aetiology (P< 0.006), left ventricular ejection fraction (P= 0.018), and treatment with renin–angiotensin system inhibitors (P< 0.001) were independently related to CRA syndrome. During a median follow-up of 3.7 years, the primary outcome occurred in 404 patients (42.5%). Compared with patients with preserved renal function and normal haemoglobin (Hb) levels, those with CRA syndrome had a significantly increased risk for the primary outcome; the univariate and multivariate-adjusted HRs were 4.04 (CI: 3.11–5.24; P< 0.0001) and 2.22 (CI: 1.64–2.98; P< 0.0001), respectively. Three-year UHT-free survival was 86 and 47%, respectively. Among patients with renal dysfunction, the adjusted HR for the primary outcome increased by 17% (CI: 8–26; P= 0.0001) for each 1g/dL decrease below an Hb value of 13.0 g/dL.
Conclusion Heart failure, renal dysfunction, and anaemia are a fatal combination. Despite a relatively low prevalence, the CRA syndrome contributes to considerable mortality due to CHF.
Renal dysfunction and anaemia are frequent complications of chronic heart failure (CHF) and may contribute to the progression of the disease by enhancing the level of activation of multiple pathophysiological pathways leading to myocardial tissue damage. Both renal dysfunction and anaemia are indeed associated with an increased activity of critical mechanisms of disease progression, e.g. sympathetic nervous system and renin–angiotensin–aldosterone axis activation, oxidative stress, and inflammation. Silverberg et al. called the association of CHF, renal dysfunction, and anaemia the 'cardiorenal anaemia syndrome', where CHF may cause progressive renal dysfunction and both may lead to anaemia, which in turn can worsen CHF and renal dysfunction. Therefore, regardless of the level of left ventricular dysfunction, the cardiorenal anaemia (CRA) syndrome might be viewed as a stage of HF where the progression rate of biochemical, cellular, and neurohormonal alterations leading to unfavourable outcomes is accelerated.
Both renal dysfunction and anaemia have been extensively studied in CHF and are known risk factors for increased mortality and morbidity. Despite this, almost half of the patients with renal dysfunction are unrecognized by hospital physicians and serum creatinine (SCr), an insensitive measure of glomerular filtration rate, is still widely used as a measure of renal function. In addition, less than 20% of anaemic HF patients are recognized, and even fewer are evaluated, by both cardiologists and internists. Moreover, owing to the lack of population-specific treatment effect data, current guidelines do not provide specific recommendations for the management of CHF patients with anaemia, renal dysfunction, or both, with consequent difficulties in clinical practice. The CRA syndrome, though of particular interest, has not been thoroughly characterized. In this study, we sought to assess the prevalence and clinical correlates of the CRA syndrome and the relationship between impaired kidney function and anaemia on hard clinical outcomes in patients with systolic HF.
Abstract and Introduction
Abstract
Aims We sought to assess the prevalence and clinical correlates of cardiorenal anaemia (CRA) syndrome in systolic heart failure and the relationship between renal dysfunction and anaemia on hard clinical outcomes.
Methods and results We studied 951 patients with chronic heart failure (CHF) and systolic dysfunction. The primary outcome was all-cause mortality and urgent heart transplantation (UHT). Cox's regression analyses were used to assess the relation of the variables to the primary outcome. Hazard ratios (HRs) with 95% confidence intervals (CI) were calculated.
The prevalence of CRA syndrome was 21.1%. Age (P < 0.001), body mass index (P< 0.001), diabetes (P =< 0.001), ischaemic aetiology (P< 0.006), left ventricular ejection fraction (P= 0.018), and treatment with renin–angiotensin system inhibitors (P< 0.001) were independently related to CRA syndrome. During a median follow-up of 3.7 years, the primary outcome occurred in 404 patients (42.5%). Compared with patients with preserved renal function and normal haemoglobin (Hb) levels, those with CRA syndrome had a significantly increased risk for the primary outcome; the univariate and multivariate-adjusted HRs were 4.04 (CI: 3.11–5.24; P< 0.0001) and 2.22 (CI: 1.64–2.98; P< 0.0001), respectively. Three-year UHT-free survival was 86 and 47%, respectively. Among patients with renal dysfunction, the adjusted HR for the primary outcome increased by 17% (CI: 8–26; P= 0.0001) for each 1g/dL decrease below an Hb value of 13.0 g/dL.
Conclusion Heart failure, renal dysfunction, and anaemia are a fatal combination. Despite a relatively low prevalence, the CRA syndrome contributes to considerable mortality due to CHF.
Introduction
Renal dysfunction and anaemia are frequent complications of chronic heart failure (CHF) and may contribute to the progression of the disease by enhancing the level of activation of multiple pathophysiological pathways leading to myocardial tissue damage. Both renal dysfunction and anaemia are indeed associated with an increased activity of critical mechanisms of disease progression, e.g. sympathetic nervous system and renin–angiotensin–aldosterone axis activation, oxidative stress, and inflammation. Silverberg et al. called the association of CHF, renal dysfunction, and anaemia the 'cardiorenal anaemia syndrome', where CHF may cause progressive renal dysfunction and both may lead to anaemia, which in turn can worsen CHF and renal dysfunction. Therefore, regardless of the level of left ventricular dysfunction, the cardiorenal anaemia (CRA) syndrome might be viewed as a stage of HF where the progression rate of biochemical, cellular, and neurohormonal alterations leading to unfavourable outcomes is accelerated.
Both renal dysfunction and anaemia have been extensively studied in CHF and are known risk factors for increased mortality and morbidity. Despite this, almost half of the patients with renal dysfunction are unrecognized by hospital physicians and serum creatinine (SCr), an insensitive measure of glomerular filtration rate, is still widely used as a measure of renal function. In addition, less than 20% of anaemic HF patients are recognized, and even fewer are evaluated, by both cardiologists and internists. Moreover, owing to the lack of population-specific treatment effect data, current guidelines do not provide specific recommendations for the management of CHF patients with anaemia, renal dysfunction, or both, with consequent difficulties in clinical practice. The CRA syndrome, though of particular interest, has not been thoroughly characterized. In this study, we sought to assess the prevalence and clinical correlates of the CRA syndrome and the relationship between impaired kidney function and anaemia on hard clinical outcomes in patients with systolic HF.