No abstract

A study was carried out in 1988 in Verona, Italy, to examine the relation of body fat and its localization to several risk factors for atherosclerosis in young men. Total body fat (bioelectrical impedance), waist and hip circumferences, and waist/hip circumference ratio were measured in 1,293 18-year-old men. Fasting serum levels of total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglycerides, and insulin, as well as systolic and diastolic blood pressure, were also measured. Significant differences were found in all metabolic and hemodynamic variables among quartiles of total body fat. Most of these differences remained significant after the authors controlled for the independent effect of fat localization and behavioral factors such as smoking, alcohol intake, and physical activity. Triglycerides, insulin, and blood pressure were significantly different among quartiles of waist/hip ratio, but these differences disappeared after the authors controlled for the independent effect of total body fat. These results indicate that in young men, irrespective of its regional localization, an excess of body fat is associated with a poor profile of risk for atherosclerosis. On the other hand, the prevalent localization of fat in the central part of the body is not independently associated with any risk factor.

The associations between fasting plasma insulin concentration and risk factors for cardiovascular diseases were examined in 979 18-year-old men participating in the Verona Young Men Atherosclerosis Risk Factors Study, a cross-sectional population-based study. Body mass index (BMI), waist-to-hip ratio (WHR), plasma triglycerides and uric acid concentrations, and blood pressure values significantly increased, and the high-density lipoprotein (HDL)-total cholesterol ratio decreased, across quartiles of fasting insulin. Total and low-density lipoprotein cholesterol concentrations did not change significantly with the increase in fasting insulin levels. After adjustment for BMI, WHR, smoking, alcohol intake and physical activity, only plasma triglycerides significantly increased across insulin quartiles (F ¼ 7 : 1; P < 0 : 001). However, systolic blood pressure and uric acid were close to statistical significance (P ¼ 0 : 06-0 . 07). Multiple linear regression analysis confirmed that plasma insulin was independently correlated with plasma triglycerides and, to a lesser extent, with blood pressure and uric acid concentration. This analysis pointed out that BMI was a stronger independent predictor of all cardiovascular disease risk factors than fasting insulin. When subjects were categorized according to the number of metabolic and haemodynamic disorders occurring within the same individual, subjects with multiple disorders (i.e. three or four) had higher plasma insulin levels than those with none or few disorders, even after adjusting for BMI, WHR and behavioural variables (F ¼ 4 : 0; P < 0 : 01). These results indicate that hyperinsulinaemia is already associated with a cluster of cardiovascular disease risk factors in young adulthood, the strongest independent association being with plasma triglycerides.

Objective. To investigate whether human obesity is characterized by a worse cardiovascular risk profile (than no obesity) even in the absence of hyperinsulinaemia. Subjects and design. A total of 367 healthy subjects (247 nonobese and 120 obese) with normal glucose tolerance and without family history of diabetes mellitus. Interventions. A 75-g oral glucose tolerance test was performed in all participants. Main outcome measures. Anthropometry, blood pressure, fasting plasma lipids and urate, plasma glucose and insulin concentrations at fasting, 1 h and 2 h after oral glucose load. Results. In a multivariate linear regression analysis, body mass index was strongly related to all cardiovascular risk factors, independently of sex, age and plasma insulin. When risk factors were compared in 37 normoinsulinaemic obese subjects (plasma insulin within one standard deviation of the mean values observed in the 247 nonobese subjects), and in 3 7 sex-and age-matched normoinsulinaemic nonobese subjects, we found that plasma glucose levels were similar in the two groups, whereas plasma triglyceride (1.50+0.13 vs. 1.13f0.08 mmol L-': mean 4 SE). lowdensity lipoprotein cholesterol (3.4240.25 vs. 2.77f0.18 mmolL-') and urate (290f12 vs. 2 5 5 f 1 2 pmolL-') levels were significantly higher, and plasma highdensity lipoprotein cholesterol concentrations were lower (1.27k0.04 vs. 1.46f0.06 mmol L-' ) in obese than in nonobese subjects with normal plasma insulin levels (P c 0.01). Also systolic (132 f 2 vs. 2 4 f 2 mmHg)and diastolic ( 8 6 f l vs. 81 f 1 mmHg) blood pressure values were significantly higher in normoinsulinaemic obese subjects than in normoinsulinaemic nonobese individuals (P c 0.001).Conclusions. These results suggest that in human obesity a worse cardiovascular risk profile is found (than in the nonobese) independently of the presence of hyperinsulinaemia.

SummaryPatients with primary hypercholesterolaemia (30 with familial hypercholesterolaemia and 17 with polygenic hypercholesterolaemia), were randomly treated with either simvastatin or pravastatin 40 mg/day or gemfibrozil 1200 mg/day for up to 18 months. Efficacy and safety parameters were measured every 3 months. To date, out of the initial 47 subjects who entered the study, 38 have been treated for 12 months and 34 for 18 months.Both simvastatin and pravastatin lowered total and low density lipoprotein (LDL) cholesterol (by about 30%). This effect was already maximal by the third month of therapy and the decrease was maintained for up to 18 months. The effect of gemfibrozil on these lipid parameters was slower (maximum lowering effect at the sixth month) and less marked during the first 6 months of therapy. However, after the sixth month the differences between the 3 drugs were no longer statistically significant, possibly because of large interindividual variability in the response to treatment. All 3 treatment groups had similar reductions in apolipoprotein-(Apo) Al and Apo-B levels. High density lipoprotein (HDL) cholesterol levels were increased significantly during treatment with gemfibrozil, but not during therapy with either of the statins. However, intergroup analysis did not reveal consistent differences in HDL-cholesterol during treatment. Gemfibrozil markedly decreased triglyceride levels, and this effect was maintained throughout the study. Neither simvastatin nor pravastatin affected triglyceride levels. The statins therefore did not show different influences on any lipid parameter studied. All 3 drugs were well tolerated. Simvastatin was, however, associated with significant increases in GGT and CPK activities at the 6-month evaluation.In conclusion, there were no significant differences between simvastatin, pravastatin or gemfibrozil in long term effects on total, LDL-and HDL-cholesterollevels in patients with primary hypercholesterolaemia, although this finding may have been due to large interindividual variations in the response to therapy. It would therefore appear that gemfibrozil is an effective Iipidlowering agent which is suitable for long term treatment.