Low serum albumin: A neglected predictor in patients with cardiovascular disease

Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved.

Abstract Hypoalbuminemia is associated with inflammation. Despite being addressed repeatedly in the literature, there is still confusion regarding its pathogenesis and clinical significance. Inflammation increases capillary permeability and escape of serum albumin, leading to expansion of interstitial space and increasing the distribution volume of albumin. The half‐life of albumin has been shown to shorten, decreasing total albumin mass. These 2 factors lead to hypoalbuminemia despite increased fractional synthesis rates in plasma. Hypoalbuminemia, therefore, results from and reflects the inflammatory state, which interferes with adequate responses to events like surgery or chemotherapy, and is associated with poor quality of life and reduced longevity. Increasing or decreasing serum albumin levels are adequate indicators, respectively, of improvement or deterioration of the clinical state. In the interstitium, albumin acts as the main extracellular scavenger, antioxidative agent, and as supplier of amino acids for cell and matrix synthesis. Albumin infusion has not been shown to diminish fluid requirements, infection rates, and mortality in the intensive care unit, which may imply that there is no body deficit or that the quality of albumin “from the shelf” is unsuitable to play scavenging and antioxidative roles. Management of hypoalbuminaemia should be based on correcting the causes of ongoing inflammation rather than infusion of albumin. After the age of 30 years, muscle mass and function slowly decrease, but this loss is accelerated by comorbidity and associated with decreasing serum albumin levels. Nutrition support cannot fully prevent, but slows down, this chain of events, especially when combined with physical exercise.

Among patients with end-stage renal disease who are treated with hemodialysis, solute clearance during dialysis and nutritional adequacy are determinants of mortality. We determined the effects of reductions in blood urea nitrogen concentrations during dialysis and changes in serum albumin concentrations, as an indicator of nutritional status, on mortality in a large group of patients treated with hemodialysis. We analyzed retrospectively the demographic characteristics, mortality rate, duration of hemodialysis, serum albumin concentration, and urea reduction ratio (defined as the percent reduction in blood urea nitrogen concentration during a single dialysis treatment) in 13,473 patients treated from October 1, 1990, through March 31, 1991. The risk of death was determined as a function of the urea reduction ratio and serum albumin concentration. As compared with patients with urea reduction ratios of 65 to 69 percent, patients with values below 60 percent had a higher risk of death during follow-up (odds ratio, 1.28 for urea reduction ratios of 55 to 59 percent and 1.39 for ratios below 55 percent). Fifty-five percent of the patients had urea reduction ratios below 60 percent. The duration of dialysis was not predictive of mortality. The serum albumin concentration was a more powerful (21 times greater) predictor of death than the urea reduction ratio, and 60 percent of the patients had serum albumin concentrations predictive of an increased risk of death (values below 4.0 g per deciliter). The odds ratio for death was 1.48 for serum albumin concentrations of 3.5 to 3.9 g per deciliter and 3.13 for concentrations of 3.0 to 3.4 g per deciliter. Diabetic patients had lower serum albumin concentrations and urea reduction ratios than nondiabetic patients. Low urea reduction ratios during dialysis are associated with increased odds ratios for death. These risks are worsened by inadequate nutrition.