Nutritional and anti-inflammatory interventions in chronic heart failure

Abstract

Currently, there are 5 million individuals with chronic heart failure (CHF) in the United States who have poor clinical outcomes, including high death rates. Observational studies have indicated a reverse epidemiology of traditional cardiovascular risk factors in CHF; in contrast to trends seen in the general population, obesity and hypercholesterolemia are associated with improved survival. The temporal discordance between the overnutrition (long-term killer) and undernutrition (short-term killer) not only can explain some of the observed paradoxes but also may indicate that malnutrition, inflammation, and oxidative stress may play a role that results in protein-energy wasting contributing to poor survival in CHF. Diminished appetite or anorexia and nutritional deficiencies may be both a cause and a consequence of this so-called malnutrition-inflammation-cachexia (MIC) or wasting syndrome in CHF. Neurohumoral activation, insulin resistance, cytokine activation, and survival selection-resultant genetic polymorphisms also may contribute to the prominent inflammatory and oxidative characteristics of this population. In patients with CHF and wasting, nutritional strategies including amino acid supplementation may represent a promising therapeutic approach, especially if the provision of additional amino acids, protein, and energy includes nutrients with anti-inflammatory and antioxidant properties. Regardless of the etiology of anorexia, appetite-stimulating agents, especially those with anti-inflammatory properties such as megesterol acetate or pentoxyphylline, may be appropriate adjuncts to dietary supplementation. Understanding the factors that modulate MIC and body wasting and their associations with clinical outcomes in CHF may lead to the development of nutritional strategies that alter the pathophysiology of CHF and improve outcomes.

Figure 1

Obesity paradox in CHF patients: Association of body mass index (BMI) as a continuous variable and unadjusted all-cause mortality using polynomial logistic regression. Data from 7767 patients with stable CHF enrolled in the Digitalis Investigation Group trial (adapted with permission from Curtis et al. Arch Intern Med 2005;165:55–61)

Figure 2

Schematic representation of the contributors and consequences of cardiac cachexia in CHF patients.

Figure 3

The Temporal Discordance Hypothesis: Competition between the short-term killer (undernutrition) and long-term killer (overnutrition) in CHF patients. (adapted with permission from Kalantar-Zadeh et al Seminars in Nephrology 2006;26:18–33)