The Paris Prospective Study is a long-term investigation of the incidence of coronary heart disease in a large population of working men. The first follow-up examination involved 7,038 men, aged 43-54 years. Subjects with impaired glucose tolerance or diabetes (n = 943) were selected from the total population for a separate analysis of coronary heart disease mortality risk factors. During a mean follow-up of 11 years, 26 of these 943 subjects with abnormal glucose tolerance died from coronary heart disease. Univariate analysis showed that plasma triglyceride level (p less than 0.006), plasma cholesterol level (p less than 0.02), and plasma insulin level both fasting and 2-h post-glucose load (p less than 0.02), were significantly higher in subjects who died from coronary heart disease compared to those who did not. In multivariate regression analysis using the Cox model, plasma triglyceride level was the only factor positively and significantly associated with coronary death. The distribution of plasma triglyceride levels was clearly higher for the subjects who died from coronary heart disease compared to those who did not die from this cause or were alive at the end of the follow-up. This new epidemiological evidence that hypertriglyceridaemia is an important predictor of coronary heart disease mortality in subjects with impaired glucose tolerance or diabetes suggests a possible role of dyslipidaemia in the excessive occurrence of atherosclerotic vascular disease in this category of subjects.
The Paris Prospective Study is a long-term, large-scale study of the factors predicting coronary heart disease. The first follow-up examination included, for subjects not known as having diabetes mellitus, a 75 g oral glucose tolerance test with measurement of plasma insulin and glucose levels, fasting and 2 h post-load. Between 1968 and 1973, 6903 men aged 43-54 years were thus examined. Causes of death were ascertained within this group after 15 years of mean follow-up. The baseline variables were tested as predictors of death from coronary heart disease by a Cox regression analysis. Significant independent predictors of coronary heart disease death were: systolic blood pressure, number of cigarettes per day, plasma cholesterol level, and 2 h post-load plasma insulin level when entered as a categorical variable (below or above 452 pmol/l. i.e. the lower limit of the fifth quintile of the distribution). This dichotomization was performed to account for the non-linear univariate distribution of deaths with increasing post-load insulin values. Fasting plasma insulin level was not an independent predictor of death by coronary heart disease over this long-term follow-up. Levels of blood glucose were not significant independent predictors of death by coronary heart disease when plasma insulin levels were included in the model. The same applied to abnormalities of glucose tolerance when the 125 men with known non-insulin-treated diabetes at baseline were added to the group. Under the assumption that hyperinsulinaemia is a marker of insulin resistance, the results are consistent with the hypothesis that insulin resistance is associated with a higher risk of coronary heart disease mortality. However, it is doubtful that circulating insulin per se is a direct cause of arterial complications.
Since the relation between serum triglyceride level and coronary heart disease after adjustment for cholesterol and other risk factors remains controversial, the authors have tested the hypothesis that it could be different according to the level of serum cholesterol, i.e., that there may be an interaction between cholesterol and triglyceride level in prediction of coronary heart disease risk. The data of the Paris Prospective Study were used to carry out a survival analysis, by using the Cox model, with coronary heart disease death as the end point and triglyceride and different risk factors as the predictor variables. In this study, during a mean follow-up of 11.4 +/- 2.2 years, 157 coronary heart disease deaths occurred. Serum triglyceride level is not an independent predictor of coronary heart disease death after adjustment for serum cholesterol. However, when cholesterol, triglyceride, and their interaction term are introduced in the regression equation, all variables contribute significantly to the risk. This is also true when other risk factors are taken into account. As a consequence of this interaction, among the 3,585 subjects with a serum cholesterol level lower than 220 mg/100 ml, serum triglyceride level is an independent predictor of risk, even after adjustment for all other risk factors.
Obesity, hypertension, a high plasma level of glucose, and some llpid abnormalities (high plasma levels of cholesterol and triglycerides) often occur in the same individuals. Some authors have postulated that the elevated levels of plasma insulin in obese individuals may explain this association. To explore this hypothesis further, the relationships between body mass index, fasting plasma glucose and insulin, blood pressure, serum lipids, and apoproteins were Investigated in a group of 2144 healthy middle-aged men. Analysis of the data show that the associations between body mass index and blood pressure or lipid variables are largely independent of plasma glucose and Insulin. Plasma glucose is strongly related to blood pressure in nonobese subjects. Plasma Insulin is not associated with blood pressure independently of body mass index and plasma glucose; however, the simultaneous elevation of body mass index, plasma glucose, and insulin is strongly associated with blood pressure. The results also confirm that plasma insulin is positively related to triglycerides and negatively related to high density Iipoprotein cholesterol independently of plasma glucose and body mass index. (Arteriosclerosis 7:197-202, March/April 1987) I n a previous work using the data of the Paris Prospective Study I (PPS I), 1 we studied the relationship between blood pressure, heart rate, and plasma glucose and insulin levels obtained after an oral load of glucose. Analysis of the results demonstrated that in an active population of middle-aged men, glucose level was independently associated with blood pressure, whereas insulin was not. From that analysis, we concluded that insulin is unlikely to affect the blood pressure level. However, the results of recent clinical 2 ' 3 and epidemiologic 4 studies have emphasized the possible role of insulin as a determinant of blood pressure level and these observations are supported by physiopathological hypotheses stressing the effect of insulin on sodium transports. 5 On the other hand, other investigators have demonstrated an independent relationship between plasma insulin and some plasma lipids and lipoproteins 6 " 9 which could be explained by the effect of insulin on lipopro- Received July 7,1986; revision accepted November 24,1986. tein lipase and on VLDL synthesis. These observations are of clinical importance because if insulin is a determinant of either blood pressure or lipoproteins levels, it might at least partly explain the frequent association of obesity, hypertension, elevated plasma glucose, and lipids or Iipoprotein abnormalities in many individuals, particularly those from industrialized countries and would point to insulin's role in the determinism of coronary heart disease and suggest preventive measures. 1011The purpose of this analysis is to investigate the independent and interactive "effects" of body mass index (BMI), plasma glucose, and insulin on systolic (SBP) and diastolic (DBP) blood pressure and on some lipid parameters, after adjustment for the possibly confounding...
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