Re: Cholesterol and stroke: A paradox

The Lancet 2007; 370:1829-1839

Blood cholesterol and vascular mortality by age, sex, and blood
pressure: a meta-analysis of individual data from 61 prospective
studies with 55 000 vascular deaths
Prospective Studies Collaboration

‡Collaborators listed in full at end of paper

Summary
Background
Age, sex, and blood pressure could modify the associations of total
cholesterol (and its main two fractions, HDL and LDL cholesterol) with
vascular mortality. This meta-analysis combined prospective studies of
vascular mortality that recorded both blood pressure and total
cholesterol at baseline, to determine the joint relevance of these two
risk factors.

Methods
Information was obtained from 61 prospective observational studies,
mostly in western Europe or North America, consisting of almost 900
000 adults without previous disease and with baseline measurements of
total cholesterol and blood pressure. During nearly 12 million person
years at risk between the ages of 40 and 89 years, there were more
than 55 000 vascular deaths (34 000 ischaemic heart disease [IHD], 12
000 stroke, 10 000 other). Information about HDL cholesterol was
available for 150 000 participants, among whom there were 5000
vascular deaths (3000 IHD, 1000 stroke, 1000 other). Reported
associations are with usual cholesterol levels (ie, corrected for the
regression dilution bias).

Findings
1 mmol/L lower total cholesterol was associated with about a half
(hazard ratio 0·44 [95% CI 0·42–0·48]), a third (0·66 [0·65–0·68]),
and a sixth (0·83 [0·81–0·85]) lower IHD mortality in both sexes at
ages 40–49, 50–69, and 70–89 years, respectively, throughout the main
range of cholesterol in most developed countries, with no apparent
threshold. The proportional risk reduction decreased with increasing
blood pressure, since the absolute effects of cholesterol and blood
pressure were approximately additive. Of various simple indices
involving HDL cholesterol, the ratio total/HDL cholesterol was the
strongest predictor of IHD mortality (40% more informative than non-
HDL cholesterol and more than twice as informative as total
cholesterol). Total cholesterol was weakly positively related to
ischaemic and total stroke mortality in early middle age (40–59
years), but this finding could be largely or wholly accounted for by
the association of cholesterol with blood pressure. Moreover, a
positive relation was seen only in middle age and only in those with
below-average blood pressure; at older ages (70–89 years) and,
particularly, for those with systolic blood pressure over about 145 mm
Hg, total cholesterol was negatively related to haemorrhagic and total
stroke mortality. The results for other vascular mortality were
intermediate between those for IHD and stroke.

Interpretation
Total cholesterol was positively associated with IHD mortality in both
middle and old age and at all blood pressure levels. The absence of an
independent positive association of cholesterol with stroke mortality,
especially at older ages or higher blood pressures, is unexplained,
and invites further research. Nevertheless, there is conclusive
evidence from randomised trials that statins substantially reduce not
only coronary event rates but also total stroke rates in patients with
a wide range of ages and blood pressures.


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