Higher total blood cholesterol is associated with increased ischaemic heart disease (IHD) mortality in both middle and old age and at all blood pressure levels. However, the absence of an independent association of cholesterol with stroke mortality, especially at older ages or higher blood pressures, is unexplained and needs further research. These are the conclusions of authors of an Article published in this week's edition of The Lancet.
Dr Sarah Lewington, Oxford University Clinical Trial Service Unit (CTSU), UK and colleagues from The Prospective Studies Collaboration reanalysed information from 61 prospective observational studies, mostly in Western Europe and America, involving almost 900000 adults without previous IHD and with baseline measurements of total cholesterol and blood pressure. There were over 55000 vascular deaths in people aged between 40 and 89 years, including 34000 from IHD and 12000 from stroke. Information about high-density lipoprotein (HDL) cholesterol was available for 150000 participants, among whom there were 5000 deaths (3000 IHD, 1000 stoke, 1000 other).
The authors found that 1mmol/L lower cholesterol -- an easily achievable difference using cholesterol-lowering statin drugs - led to a more than halving (56% fall) in IHD mortality in the 40-49 age group. This mortality drop was a third (34%) in the 50-69 age group and a sixth (17%) in the 70-89 age group. These drops were seen throughout the main range of cholesterol concentrations in most developed countries. Further, they found the proportional risk reduction decreased with increasing blood pressure, since the absolute effects of cholesterol and blood pressure are approximately additive -- that is, the absolute gain from a given cholesterol difference is wholly independent of blood pressure.
The ratio of total cholesterol to HDL cholesterol was a very much stronger predictor of heart disease risk than total cholesterol alone, with no apparent threshold.
In relation to stroke, the authors found that total cholesterol was weakly positively related to ischaemic and total stroke mortality in early middle age (40-59 years), and that this finding could be largely or wholly accounted for by the association of cholesterol with blood pressure. Further, a positive relation was seen only in middle age and only in those with below-average blood pressure; at older ages, ie, 70-89 years, and, particularly for those with systolic blood pressure above around 145mm Hg, higher cholesterol was associated with lower stroke mortality -- a finding which the authors cannot explain. The authors say: "Irrespective of the explanation, however, treatment should be guided principally by the definitive 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."
In an accompanying Comment, Dr Pierre Amarenco and Dr Gabriel Steg, INSERM U-698 and Denis Diderot University and Medical School, Bichat-Claude Bernard University Hospital, Paris, France, say: "Cholesterol is a strong risk factor for ischaemic heart disease irrespective of age and blood pressure, and statins are associated with reductions in cholesterol and coronary event rates. A link between cholesterol and stroke risk probably exists (at least with atherothrombotic stroke), and there is good evidence that lowering blood cholesterol with statins reduces stroke risk and carotid atherosclerosis, independently of blood cholesterol, blood pressure, and age."
For the Prospective Studies Collaboration , please contact Dr Sarah Lewington (coordinator), Clinical Trial Service Unit (CSTU), University of Oxford T) +44 (0) 1865 743 824 E) psc@ctsu.ox.ac.uk
Dr Pierre Amarenco, INSERM U-698 and Bichat-Claude Bernard University Hospital, Denis Diderot University and Medical School, Paris, France T) +33 140 258 725 E) pierre.amarenco@bch.aphp.fr
The paper associated with this release can be found at http://multimedia.thelancet.com/pdf/press/Cholesterol.pdf
Journal
The Lancet