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Objective: The Gubbio Study is an Italian population study measuring risk factors for and incidence of major cardiovascular diseases. This analysis investigates the association of serum uric acid with the incidence of coronary and cardiovascular events., Methods: A population sample of 2469 men and women aged 35-74 years, free from major cardiovascular diseases and in whom serum uric acid was measured in 1983 along with other standard risk factors, were followed up for 6 years and the incidence of coronary heart disease (CHD) and all cardiovascular atherosclerotic (CVD) events, both fatal and non-fatal, was computed. Proportional hazards models were used for the prediction of these events., Results: In six years 61 CHD hard criteria, 109 CHD any criterion and 149 CVD events were recorded. Age-adjusted rates per 1000 of the 3 event categories were computed in sex-specific quintiles (Q) of serum uric acid with 428 +/- 76 (Q5) and 198 +/- 42 (Q1) micromol/l, respectively. Although higher rates were seen in Q5 as compared to Q1 for all three first event categories considered (relative risks 6.2, 3.6 and 3.7, respectively), a statistically significant trend was seen only for CVD all criteria (t = 3.63, p < 0.036). These trends were borderline significant for CHD any criterion (t = 2.92, p < 0.06) and not significant for CHD hard criteria (t = 2.23, p < 0.11). In multivariate models, adjusted for 8 other risk factors, serum uric acid showed a statistically significant contribution to predict CVD incidence [relative risk (RR) for 92 micromol/l difference of 1.24 with 95% confidence intervals (CI) 1.05-1.45], whereas the statistical contribution to predict CHD any criterion (RR = 1.19 with CI 0.98-1.45) and CHD hard criteria (RR = 1.20 with CI 0.93-1.55) was not significant. Diuretic treatment and blood urea, as further confounders, were positively and significantly related to event incidence (RR ranging from 1.21 to 2.00) but serum uric acid maintained its independent and statistically significant role in the prediction of CVD events (RR = 1.18 with CI 1.00-1.39). Presence of specific treatments to lower serum uric acid levels (in 1.13% of the population), tested as final confounders, was not statistically contributory., Conclusions: Increased serum uric acid levels are independently and significantly associated with risk of CVD events in the 6-year follow-up of the Gubbio Study. Longer follow-up is needed before the contributory role of serum uric acid can be properly assessed to explain CHD incidence.

Objective: To study the time-related association of a single measurement of serum cholesterol and systolic blood pressure with the occurrence of a first coronary event in a population sample of middle-aged men., Methods and Results: A single measurement of serum total cholesterol and systolic blood pressure (along with age, cigarette consumption, physical activity at work and body mass index as possible confounders) was made in 1,605 coronary disease-free men aged 40-59 belonging to the Italian rural cohorts of the Seven Countries Study. During 25 years of follow-up 353 men developed a first event, that is a coronary death (sudden or not), and definite or possible myocardial infarction. Twenty-five partitioned proportional hazards models were solved, one for each independent year of follow-up, to predict the risk of incident events. Single-year hazard functions, separately for serum cholesterol and systolic blood pressure, were cumulated and smoothed. The resulting curves showed a regularly increasing risk for coronary events. They fit straight lines, with large correlation coefficients for both serum total cholesterol (r = 0.99) and systolic blood pressure (r = 0.99). These slopes were similar to the coefficients estimated by a single proportional hazards model solved for all events during 25 years., Conclusion: A single measurement of serum total cholesterol and systolic blood pressure in middle aged-men maintains a regular and monotonic relationship with occurrence of a first coronary event during 25 years of follow-up.