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Misleading associations between cholesterol and vascular outcomes in dialysis patients: the need for randomized
Colin Baigent1, Martin J Landray, David C Wheeler
1Clinical Trial Service Unit & Epidemiological Studies Unit, Oxford, UK. colin.baigent@ctsu.ox.ac.uk
Insights
Higher cholesterol levels do not increase mortality risk in dialysis patients, unlike in the general population. Studies show a negative association at low cholesterol and a flat or weak positive association at high cholesterol levels.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Epidemiology
Background:
- Elevated cholesterol is a known risk factor for coronary heart disease (CHD) in the general population.
- The association between cholesterol and mortality in dialysis patients is unexpectedly unclear.
- Dialysis patients face a high burden of cardiovascular disease and mortality.
Purpose of the Study:
- To review prospective studies examining the relationship between total cholesterol and mortality in dialysis patients.
- To understand the paradoxical association between cholesterol and mortality in this specific population.
- To identify factors that may explain the lack of a clear positive association.
Main Methods:
- Systematic review of prospective cohort studies.
- Analysis of the association between total cholesterol levels and all-cause mortality.
- Examination of associations stratified by cholesterol levels (below average, above average).
Main Results:
- A negative association between total cholesterol and mortality was observed at below-average cholesterol levels.
- A flat or weakly positive association was found at above-average cholesterol levels.
- The lack of a strong positive association may be due to a high proportion of non-CHD vascular deaths.
Conclusions:
- The cholesterol-mortality paradox in dialysis patients may be influenced by reverse causality and confounding factors.
- Randomized controlled trials are necessary to definitively assess cholesterol's role in vascular disease risk for dialysis patients.
- Ongoing trials of cholesterol-lowering therapies are expected to provide crucial insights.
Abstract:
Higher cholesterol is strongly associated with an increased risk of coronary heart disease (CHD) in nonrenal populations, so the lack of a clear positive association between total cholesterol and mortality among dialysis patients is unexpected. This review of prospective studies of the association between total cholesterol and mortality among dialysis patients suggests that there is a negative association at below average cholesterol levels and a flat or weakly positive association at higher levels. In nonrenal populations total cholesterol is not positively associated with vascular causes of death other than CHD, so the lack of a strongly positive association at above average cholesterol concentrations in dialysis patients may be explained by the high proportion of deaths due to non-CHD vascular causes. The observation of a negative association between total cholesterol and mortality at below average cholesterol concentrations in some studies is consistent with confounding by both vascular and nonvascular morbidity (i.e., reverse causality). We argue that evaluating the importance of cholesterol for vascular disease risk in dialysis patients can only be achieved through the eradication of confounding by randomization, and that ongoing trials of cholesterol-lowering therapy will provide a definitive answer to this question.
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