Is total:HDL cholesterol a reliable predictor of risk?
The use of total:HDL cholesterol implies that diet-induced
decreases in HDL cholesterol increase CAD risk. Such a causal
role for diet-induced changes in HDL cholesterol has not been
proven in controlled clinical trials. However, results of prospective
observational studies, controlled clinical trials with drugs, mechanistic
studies, and genetic “experiments of nature” all strongly
suggest that high concentrations of HDL cholesterol in the circulation
help to prevent CAD and other cardiovascular diseases
(3–7). Given these observations, it appears imprudent to ignore
the marked effects of diet on HDL cholesterol. An additional justification
for using total:HDL cholesterol might be that it includes
the amount of cholesterol in the triacylglycerol-rich VLDL fraction,
which also positively correlates with CAD risk (85). However,
our analysis also underlines the fact that effects of diet on
biomarkers such as blood lipids can never replace studies that
employ disease or death as outcomes. Total:HDL cholesterol is
more sensitive and specific than is total cholesterol as a risk predictor
(8–10), but the favorable effects on this ratio by such factors
as coconut fat, which is rich in lauric acid, do not exclude the
possibility that coconut fat may promote CAD through other pathways,
known or as yet unknown. Similarly, the unfavorable effect
of carbohydrates on the ratio does not rule out a favorable effect
of high-carbohydrate diets on health outcomes.