- Seven Countries Study, 25 yr Follow-up
- Modified LDL, Low Density Lipoprotein
- Brown and Goldstein, Nobel Laureates
Cholesterol is an insoluble, waxy substance, essential for proper functioning of cell membranes and various hormones, that must be carried in the blood by packages, called lipoproteins, known as HDL, high density lipoprotein, and LDL, low density lipoprotein.
The Seven Countries Study, while usually thought to have shown the relation between cholesterol and coronary mortality, actually showed the opposite. In the above graph the y-axis is death rate from heart attacks (CHD mortality). The relation is highly dependent upon the population observed. Only in Northern Europe and North America is there any relation. Around the world there are huge differences in mortality for the same cholesterol level. The problem is that blood cholesterol has almost no connection with events in the vascular wall where plaque is present. We hypothesize that these differences between cultures are mostly diet related and have something to do with the production of modified LDL in the vascular wall, a crucial step in the accretion of lipids in plaque. Without modification in the arterial wall LDL is harmless. Cholesterol carried by LDL is not the proximate cause of atherosclerosis. It only causes a problem because its package is damaged, like radioactive waste in a sealed, shielded package will not harm unless the package is disrupted. Brown and Goldstein, the winners of a Nobel Prize for their work on cholesterol metabolism have said so explicitly. What exactly damages cholesterol’s LDL package is not known but it has something to do with diet. Blood cholesterol is only a very crude marker for atherogenic lifestyles.
There is an alternative explanation for the above graph. It might be that the response of the body to some sort of nutritional “stress” associated with northern European lifestyle is to raise total and LDL, “bad” cholesterol, and reduce HDL, “good” cholesterol” as a protective mechanism and that changing blood levels of these cholesterol packages with drugs could be harmful. Some evidence for this is now appearing. Drugs whose only effect is to lower LDL (ezetimibe) or raise HDL (torcetrapib) tend to worsen atherosclerosis.
One can attempt to reduce mortality with Panaceia (Drugs), blue arrow, but to achieve the same CHD mortality as Japan would require industrial quantities of expensive drugs with no evidence that total mortaltity would be reduced. But the major side effect of drugs is moral hazard, red arrow. If one is led to believe that a pill will protect one, one has no incentive to be vigilant in lifestyle choices.
By simple lifestyle change, Hygeia, CHD mortality can be almost eliminated, green arrow.
By far the best way of reducing mortality is to change lifestyle to something similar to the Southern Europeans, Cubans or the Japanese. Cubans have a longer life expectancy than Americans in spite of having no access to statins and spending per capita on “health care” only 4% of the Americans.
Drugs to reduce cholesterol will have a minor effect on coronary mortality (but no effect on total mortality) and will inevitably lead to a deterioration in lifestyle by those who believe a pill will protect them, an effect known as moral hazard. If blood cholesterol is lowered but there is more production of modified LDL in the vascular wall plaque will progress.
So, why the pressure to measure blood cholesterol in the general population, why a cholesterol neurosis, why measure blood cholesterol at all unless there is an obvious congenital lipid problem with visible xanthomas? See who is promoting the cholesterol myth in the USA and Canada.
See our slide show on the cholesterol myth.