Is it wise to lower cholesterol?
Ryan et al. (1) correctly mention that the risk factors with the lowest hazard ratios are obesity and the lipid profile. A relevant question is if high cholesterol (tC) or LDL-cholesterol (LDL-C) is a risk factor at all, because more than 20 cohort studies of elderly individuals from many countries have shown that tC is inversely associated with total mortality and either unassociated or inversely associated with cardiovascular mortality (2); and a systematic review of 19 studies including more than 68,000 individuals have shown that elderly people with the highest LDL-C values live longer than elderly people with low values (3). In the largest study those with the highest LDL-C lived even longer than those on statin treatment (4). The reason why most studies have shown that high tC is a risk factor for young and middle age people may be that working people are more stressed than senior citizens; that mental stress is able to raise cholesterol (5,6), and that stress may cause CVD by other ways (7-10). Furthermore, a recent study including more than 300,000 adult individuals of all ages from Asia, Australia and New Zealand found that high tC was not a risk factor for CVD among those who had no other risk factors (11).
It is well established that high LDL-cholesterol is a risk factor for CVD in familial hypercholesterolemia (FH). However, FH individuals may have inherited more important risk factors as well, because in five of six cohorts in four studies published before the introduction of statin treatment, LDL-cholesterol of those with and without CVD, none of whom had received any lipid-lowering treatment, did not differ with statistical significance (12-15). Furthermore, except from apheresis no randomized, controlled cholesterol-lowering trial including FH individuals only has succeeded with lowering the risk of CVD. Most of them have been very short, but in two trials with a duration of two years and in one with a duration of ten years, the number of CVD events increased in the groups whose LDL-C was lowered the most (16-18). The reason why apheresis is beneficial may be because apheresis removes not only blood lipids, but also various factors that promote coagulation (19,20).
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Competing interests: No competing interests