Re-assessing the contribution of serum total cholesterol, blood pressure and cigarette smoking to the aetiology of coronary heart disease: impact of regression dilution bias

AIMS: To estimate the combined contribution of serum total cholesterol, blood pressure and cigarette smoking to coronary heart disease (CHD) risk after adjustment for regression dilution bias. METHODS AND RESULTS: Six thousand, five hundred and thirteen middle-aged British men without CHD were followed for major CHD events over 10 years. The population attributable risk fraction (PARF) was predicted for a range of risk factor thresholds before and after adjustment for regression dilution of serum total cholesterol and blood pressure. Defining 'low-risk' individuals as being in the bottom tenth of the population distributions of serum total cholesterol (<5.2 mmol/l) and diastolic blood pressure (<70 mmHg) and a non-cigarette smoker, the PARF was 75%, increasing to 86% after adjustment for regression dilution. Regardless of the threshold criteria chosen, the PARF was substantially greater than 65% before adjustment for regression dilution and greater than 75% after adjustment. Exclusion of ex-smokers and passive smokers from the low-risk group increased estimates further. Adjustment for other coronary risk factors had little effect on the results. CONCLUSIONS: At least 80% of major CHD events in middle-aged men can be attributed to the three strongest risk factors. Population-wide control of these factors is crucial for effective CHD prevention.