While the health risks of hypercholesterolemia are well recognized (i.e. increased risk of coronary heart disease, stroke, Alzheimer’s disease, and all-cause mortality),2-5 the nature and implications of low blood cholesterol are less well understood. Low concentrations of total cholesterol and LDL cholesterol have been associated with an increased risk of cancer (gastrointestinal cancer, hematological cancer, urological cancer, and female-specific cancer), infectious disease, sepsis, and heart failure.6-10
In this study, researchers from university hospitals throughout South Korea analyzed a group of 2,797 heart failure patients recruited from the Korean Heart Failure Registry to investigate the causal relationships and associations between total cholesterol level and clinical outcome of patients with heart failure. Patients were divided into quartiles (Q) of total cholesterol (Q1 <133 mg/dl, Q2 133-158 mg/dl, Q3 159-190 mg/dl, and Q4 >190 mg/dl). Mean total cholesterol for all patients within the study was 163.2 ± 46.6 mg/dl, with total cholesterol ranging from 30 to 474 mg/dl.
Many studies suggest that low cholesterol values develop in the course of chronic disease as a result of enhanced utilization, diminished biosynthesis or malnutrition and may precede clinically overt symptoms.11-13 Thus, a cause-effect relationship between low cholesterol level and a more severe illness with poorer prognosis in patients with heart failure is difficult to confirm because of the effect of the many confounding factors (variables whose association independently affects the results of a study) on heart failure outcome. Some examples of confounding factors in the current study include: age, sex, NYHA functional class, heart rate, blood pressure, hypertension history, diabetes mellitus history and serum sodium.
The results of this study show that patients with lower serum total cholesterol had lower blood pressure, lower hemoglobin, lower serum sodium, and higher natriuretic peptide levels (all known to be surrogate markers predicting poor prognosis in patients with heart failure) than patients with higher total cholesterol levels. In order to minimize the effect of confounding factors, the investigators used a statistical tool known as propensity score matching to further analyze their results. Such an analysis led the researchers to conclude that a low cholesterol level was probably a consequence of poor cardiac function or comorbidity, rather than a causative factor leading to poor prognosis in patients with heart failure.
A previous study by Horwich et al.14 demonstrated that a serum total cholesterol level <190 mg/dl was a strong, independent predictor of mortality in patients with heart failure. Furthermore, a more recent study by Horwich et al.10 showed that heart failure patients with lower serum total cholesterol levels not only experienced a longer hospital length of stay and worse symptoms of heart failure, but also had significantly increased in-hospital mortality.
The results of this study and other related studies suggest that the further evaluation of optimal cholesterol levels and the use of cholesterol-lowering medications in patients with heart failure is warranted.
- Yoon CH, Youn TJ, Ahn S et al. Low Serum Total Cholesterol Level is a Surrogate Marker, But Not a Risk Factor, for Poor Outcome in Patients Hospitalized With Acute Heart Failure: A Report From the Korean Heart Failure Registry. J Card Fail 2012;18:194-201.
- Schaefer EJ. Lipoproteins, nutrition, and heart disease. Am J Clin Nutr 2002;75:191-212.
- Ankolekar S, Rewell S, Howells DW, Bath PMW. The influence of stroke risk factors and comorbidities on assessment of stroke therapies in humans and animals. Int J Stroke 2012;7:386-397.
- Ferraz Alves TCadT, Ferreira LK, Wajngarten M, Busatto GF. Cardiac Disorders as Risk Factors for Alzheimer’s Disease. Journal of Alzheimer’s Disease 2010;20:749-763.
- Okamura T, Tanaka H, Miyamatsu N et al. The relationship between serum total cholesterol and all-cause or cause-specific mortality in a 17.3-year study of a Japanese cohort. Atherosclerosis 2007;190:216-223.
- Benn M, Tybj+ªrg-Hansen A, Stender S, Frikke-Schmidt R, Nordestgaard BG. Low-Density Lipoprotein Cholesterol and the Risk of Cancer: A Mendelian Randomization Study. Journal of the National Cancer Institute 2011;103:508-519.
- Iribarren C, Jacobs DR, Jr., Sidney S, Claxton AJ, Feingold KR. Cohort Study of Serum Total Cholesterol and In-Hospital Incidence of Infectious Diseases. Epidemiology and Infection 1998;121:335-347.
- Shor R, Wainstein J, Oz D et al. Low Serum LDL Cholesterol Levels and the Risk of Fever, Sepsis, and Malignancy. Ann Clin Lab Sci 2007;37:343-348.
- Afsarmanesh N, Horwich TB, Fonarow GC. Total cholesterol levels and mortality risk in nonischemic systolic heart failure. American Heart Journal 2006;152:1077-1083.
- Horwich TB, Hernandez AF, Dai D, Yancy CW, Fonarow GC. Cholesterol levels and in-hospital mortality in patients with acute decompensated heart failure. American Heart Journal 2008;156:1170-1176.
- Windler E, Ewers-Grabow U, Thiery J et al. The prognostic value of hypocholesterolemia in hospitalized patients. The Clinical Investigatior 1994;72:939-943.
- Gordon BR, Parker TS, Levine DM et al. Low lipid concentrations in critical illness: Implications for preventing and treating endotoxemia. Critical Care Medicine 1996;24:584-589.
- Giovannini I, Boldrini G, Chiarla C et al. Pathophysiologic correlates of hypocholesterolemia in critically ill surgical patients. Intensive Care Medicine 1999;25:748-751.
- Horwich TB, Hamilton MA, MacLellan WR, Fonarow GC. Low serum total cholesterol is associated with marked increase in mortality in advanced heart failure. J Card Fail 2002;8:216-224.