Vitamin D Status and Outcomes in Heart Failure Patients
Vitamin D Status and Outcomes in Heart Failure Patients
Aims Vitamin D status has been implicated in the pathophysiology of heart failure (HF). The aims of this study were to determine whether a low vitamin D status is associated with prognosis in HF and whether activation of the renin–angiotensin system (RAS) and inflammatory markers could explain this potential association.
Methods and results We measured 25-hydroxy-vitamin D (25(OH)D), plasma renin activity (PRA), interleukin-6 (IL-6), C-reactive protein (CRP), and the incidence of death or HF rehospitalization in 548 patients with HF. Median age was 74 (64–80) years, left ventricular ejection fraction was 30% (23–42), and mean follow-up was 18 months. Low 25(OH)D levels were associated with female gender (P< 0.001), higher age (P= 0.002), and higher N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (P< 0.001). Multivariable linear regression analysis showed that PRA (P= 0.048), and CRP levels (P= 0.006) were independent predictors of 25(OH)D levels. During follow-up, 155 patients died and 142 patients were rehospitalized. Kaplan–Meier analysis showed that lower 25(OH)D concentration was associated with an increased risk for the combined endpoint (all-cause mortality and HF rehospitalization; log rank test P= 0.045) and increased risk for all-cause mortality (log rank test P= 0.014). After adjustment in a multivariable Cox regression analysis, low 25(OH)D concentration remained independently associated with an increased risk for the combined endpoint [hazard ratio (HR) 1.09 per 10 nmol/L decrease; 95% confidence interval (CI) 1.00–1.16; P= 0.040] and all-cause mortality (HR 1.10 per 10 nmol/L decrease; 95% CI 1.00–1.22; P= 0.049).
Conclusion A low 25(OH)D concentration is associated with a poor prognosis in HF patients. Activation of the RAS and inflammation may confer the adverse effects of low vitamin D levels.
Heart failure (HF) remains a major cause of morbidity and mortality in Western society. There is growing evidence to suggest that vitamin D status is associated with the development and progression of HF. Smaller clinical studies have shown that a low vitamin D status is prevalent in HF patients and is associated with a poor outcome.
The precise mechanisms explaining the association between low vitamin D status and outcome in HF patients remain unclear. However, two important potential mechanisms have been proposed as an explanation of the association between low vitamin D and HF. First, low vitamin D levels have been shown to be inversely related to plasma renin activity (PRA). The vitamin D receptor (VDR) has emerged as a negative regulator of renin transcription. Vitamin D receptor knockout mice have high levels of renin, resulting in an activated renin–angiotensin system (RAS), accompanied by typical signs of HF, such as cardiac hypertrophy, hypertension, and increased levels of atrial natriuretic peptide. Second, several studies have shown that vitamin D supplementation suppresses the release of inflammatory markers. These findings suggest that low vitamin D levels may contribute to the pro-inflammatory status present in HF, and may therefore play an important role in the development and progression of HF. In addition, vitamin D supplementation improves the cytokine profile in HF patients, providing further proof that vitamin D modulates the inflammatory process that occurs in HF.
So far there are no data available that relate vitamin D status to these potential mechanisms in HF patients. Therefore, the aims of this study were to determine whether a low plasma vitamin D level is associated with a poor prognosis in a large cohort of patients with HF, and to evaluate whether RAS activation and inflammation could explain this potential association.
Abstract and Introduction
Abstract
Aims Vitamin D status has been implicated in the pathophysiology of heart failure (HF). The aims of this study were to determine whether a low vitamin D status is associated with prognosis in HF and whether activation of the renin–angiotensin system (RAS) and inflammatory markers could explain this potential association.
Methods and results We measured 25-hydroxy-vitamin D (25(OH)D), plasma renin activity (PRA), interleukin-6 (IL-6), C-reactive protein (CRP), and the incidence of death or HF rehospitalization in 548 patients with HF. Median age was 74 (64–80) years, left ventricular ejection fraction was 30% (23–42), and mean follow-up was 18 months. Low 25(OH)D levels were associated with female gender (P< 0.001), higher age (P= 0.002), and higher N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (P< 0.001). Multivariable linear regression analysis showed that PRA (P= 0.048), and CRP levels (P= 0.006) were independent predictors of 25(OH)D levels. During follow-up, 155 patients died and 142 patients were rehospitalized. Kaplan–Meier analysis showed that lower 25(OH)D concentration was associated with an increased risk for the combined endpoint (all-cause mortality and HF rehospitalization; log rank test P= 0.045) and increased risk for all-cause mortality (log rank test P= 0.014). After adjustment in a multivariable Cox regression analysis, low 25(OH)D concentration remained independently associated with an increased risk for the combined endpoint [hazard ratio (HR) 1.09 per 10 nmol/L decrease; 95% confidence interval (CI) 1.00–1.16; P= 0.040] and all-cause mortality (HR 1.10 per 10 nmol/L decrease; 95% CI 1.00–1.22; P= 0.049).
Conclusion A low 25(OH)D concentration is associated with a poor prognosis in HF patients. Activation of the RAS and inflammation may confer the adverse effects of low vitamin D levels.
Introduction
Heart failure (HF) remains a major cause of morbidity and mortality in Western society. There is growing evidence to suggest that vitamin D status is associated with the development and progression of HF. Smaller clinical studies have shown that a low vitamin D status is prevalent in HF patients and is associated with a poor outcome.
The precise mechanisms explaining the association between low vitamin D status and outcome in HF patients remain unclear. However, two important potential mechanisms have been proposed as an explanation of the association between low vitamin D and HF. First, low vitamin D levels have been shown to be inversely related to plasma renin activity (PRA). The vitamin D receptor (VDR) has emerged as a negative regulator of renin transcription. Vitamin D receptor knockout mice have high levels of renin, resulting in an activated renin–angiotensin system (RAS), accompanied by typical signs of HF, such as cardiac hypertrophy, hypertension, and increased levels of atrial natriuretic peptide. Second, several studies have shown that vitamin D supplementation suppresses the release of inflammatory markers. These findings suggest that low vitamin D levels may contribute to the pro-inflammatory status present in HF, and may therefore play an important role in the development and progression of HF. In addition, vitamin D supplementation improves the cytokine profile in HF patients, providing further proof that vitamin D modulates the inflammatory process that occurs in HF.
So far there are no data available that relate vitamin D status to these potential mechanisms in HF patients. Therefore, the aims of this study were to determine whether a low plasma vitamin D level is associated with a poor prognosis in a large cohort of patients with HF, and to evaluate whether RAS activation and inflammation could explain this potential association.