Objective-To estimate the size of the association between serum concentration of low density lipoprotein cholesterol and mortality from ischaemic heart disease.Design-Prospective study of total serum cholesterol concentration and mortality from ischaemic heart disease in 21515 men (538 deaths) and study of total cholesterol concentration measured on two occasions an average of three years apart in 5696 men in whom low density lipoprotein cholesterol concentration was also measured on the second occasion.Subjects-Men who attended the medical centre of the British United Provident Association (BUPA) in London between 1975 and1982. Main outcome measure-The difference in mortality from ischaemic heart disease for a 06 mmol/I difference in concentration oflow density lipoprotein cholesterol after adjustment for, firstly, regression dilution bias, which arises from the random fluctuation of serum cholesterol concentration in people over time, and, secondly, the surrogate dilution effect, which arises because differences in total cholesterol concentration between people reflect smaller differences in low density lipoprotein cholesterol concentration.Results-The observed difference in mortality from ischaemic heart disease associated with a difference of 0-6 mmoIl in total serum cholesterol concentration was 17% but increased to 24% after correction for the regression dilution bias and to 27% (95% confidence interval 21% to 330/%) after adjustment for both sources of underestimation, which provides an estimate of the difference in mortality for a true difference of 0-6 mmoVI in low density lipoprotein cholesterol concentration. The association was greater at younger ages. The estimated decrease in mortality from all causes was 6% before and 100/0 (1% to 17%) after adjustment for the two sources of underestimation. There was no excess mortality from any cause associated with low cholesterol concentration.
Carboxyhaemoglobin (COHb) levels were studied in 11 249 men. The distribution among the 2613 men who smoked cigarettes was well separated from that in 6641 non-smokers (including ex-smokers The level of carboxyhaemoglobin (COHb) in the blood has been shown to be a useful marker of tobacco smoke absorption, 1-6 and for this reason there are epidemiological and clinical reasons for performing COHb measurements. The precise distributions of COHb levels in smokers and nonsmokers, and the extent to which they overlap, are not well known. We therefore investigated this in over 11 000 men. We also investigated the measurement of carbon monoxide (CO) in alveolar breath using a portable analyser, as an indirect measure of the COHb level which avoids the inconvenience of taking blood samples.
Methods
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