Cholesterol in the bloodstream is transported in two main forms: ‘low-density lipoprotein-cholesterol’ (LDL-cholesterol) and ‘high-density lipoprotein-cholesterol’ (HDL-cholesterol). Conventional wisdom tells us that LDL-cholesterol is responsible for the fatty build-up on the inside of arteries known as ‘atherosclerotic plaque’, but that HDL-cholesterol clears this plaque. Because of this, HDL- and LDL-cholesterols are dubbed ‘good’ and ‘bad’ cholesterol respectively.
A paper was published recently which attempted to explore further the relationship between HDL-cholesterol and risk of cardiovascular disease. Low levels of HDL-cholesterol have been associated with enhanced risk. But just because two things are associated with each other, does not mean one is causing the other.
Low HDL-cholesterol levels often go hand-in-hand with other metabolic ‘abnormalities’ including raised triglyceride (a form of blood fat) levels, raised blood pressure, raised blood sugar levels and abdominal obesity. Could it be one or more of these associated factors or other factors entirely that account for the relationship between low HDL-cholesterol levels and heightened risk of cardiovascular disease.
To answer this question, Danish scientists isolated individuals with low HDL-cholesterol levels as a result of a genetic glitch . In these individuals, HDL-cholesterol levels are low, but this is usually in isolation and not in combination with other metabolic abnormalities (such as raised triglycerides, blood pressure, blood sugar and abdominal obesity).
It turns out that in these individuals with genetically determined low HDL-cholesterol levels, risk of heart attack is no higher than in the general population. The logical conclusion here is that low HDL-cholesterol does not cause heart attacks (which means that higher levels do not protect against it either). In other words, this evidence strongly suggests the link between HDL-cholesterol levels and cardiovascular disease risk is only an association and not causal.
But if this is the case, could the same not be true for LDL-cholesterol too?
Many doctors and scientists will not hear of such a thing, of course, and will quote studies which show cholesterol-reduction with statin drugs reduces risk of cardiovascular disease as evidence of the fact LDL-cholesterol causes heart disease. However, as is well-recognised now, statins have many actions in the body which might reduce cardiovascular disease risk in a way which has nothing to do with cholesterol (including anti-inflammatory and blood-thinning properties).
Also, we have evidence that statins substantially reduce the risk of stroke, even though cholesterol is a weak or non-existent risk factor for stroke. And we have evidence that statins reduce the risk of cardiovascular disease in individuals with normal or even low levels of cholesterol. These lines of evidence suggest that statins actually work through mechanisms that are distinct from their cholesterol-reducing properties.
I know that some will tell us that cholesterol is to be found in atherosclerotic plaque and that ‘proves’ that cholesterol causes cardiovascular disease. Actually, though, it does nothing of the sort. If I graze my knee and form a scab there, chemical analysis of the scab will reveal something called fibrin (a clotting agent). Has fibrin caused my scab? Of course not.
1. Haase CL, et al. LCAT, HDL Cholesterol and Ischemic Cardiovascular Disease: A Mendelian Randomization Study of HDL Cholesterol in 54,500 Individuals. The Journal of Clinical Endocrinology & Metabolism November 16, 2011