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

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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.

Reference List

  1. 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.
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