The BIGuanides and Prevention of Risks in Obesity (BIGPRO1) results suggest that metformin would be a suitable candidate for long-term intervention for the prevention of diabetes but that its use in a trial of primary prevention of cardiovascular diseases requires either a reevaluation of its properties toward the most potentially atherogenic anomalies of the IRS or a better definition of the target population.

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Background In the BIGPRO 1 trial, one year of treatment with metformin in non‐diabetic obese subjects with a central fat distribution had no significant effect on fasting plasma triglyceride concentration or on blood pressure despite a decrease in weight, fasting plasma insulin and glucose concentrations. To re‐evaluate the effect of metformin on fasting triglyceride concentration and on blood pressure, the BIGPRO 1.2 trial included non‐diabetic men (n=168) with a fasting plasma triglyceride concentration ≥1.7 and ≤6.5 mmol/l, high blood pressure (systolic ≥140 and ≤180 and/or diastolic ≥90 and ≤105 mmHg, or treatment for hypertension) and a waist‐to‐hip ratio ≥0.95. Methods A randomised double‐blind trial comparing metformin treatment (850 mg bid) with placebo. Results Metformin had no significant effect either on blood pressure or plasma triglyceride concentration. In comparison with the placebo group, fasting plasma insulin (p<0.04), total cholesterol (p<0.05) and Apo B (p<0.008) concentrations decreased more in the metformin group in the BIGPRO 1.2 trial, confirming most of the previous results of the BIGPRO 1 trial. Tissue plasminogen activator antigen concentration decreased significantly (p<0.01) only in the metformin group, but this was not significantly different from the placebo group (p<0.12); further, there were no significant differences in the change in plasminogen activator inhibitor 1. Conclusions The consistency of the two BIGPRO trials supports the conclusion that metformin affects several cardiovascular risk factors favourably in non‐diabetic subjects with a central fat distribution. Copyright © 2000 John Wiley & Sons, Ltd.

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The incidence of hypertension was evaluated in 359 patients with primary chronic glomerulonephritis who underwent renal biopsy. It was compared to a control group of 7,468 subjects who were obtained from an epidemiologic study performed in the same area at the same period. The prevalence of hypertension was 42%. On the basis of multiple regression analysis, the level of blood pressure was shown to be positively correlated to four independent variables: age, body mass index, degree of renal insufficiency and presence of proliferative glomerulonephritis. It was concluded that, although renal insufficiency increases the incidence of hypertension, proliferative lesions play an important contributive role in the development of hypertension.

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Acute converting enzyme inhibition relaxes arterial smooth muscle and increases arterial complicance in several models of animal and human hypertension. However, it is unknown whether the doses needed for the relaxation of large arteries are similar to those inducing arteriolar relaxation and blood pressure (BP) decrease. To answer this question, we used a previously described model of the in situ carotid artery to determine the pressure-volume relationship over a range of transmural pressures from 25 to 200 mm Hg in normotensive rats (WKY) and spontaneously hypertensive rats (SHR). The pressure-volume relation was determined after an acute single oral administration of either a placebo or the converting enzyme inhibitor quinapril given at two different doses (0.3 or 3 mg/kg). At the end of each experiment, the total relaxation of arterial smooth muscle was achieved after a local administration of potassium cyanide (KCN). In the WKY placebo group, from 25 to 100-125 mm Hg transmural pressure, carotid compliance increased and reached a maximum value at 100-125 mm Hg (i.e. close to the operating range of systemic mean BP of the animals), and decreased thereafter. In the SHR placebo group, carotid compliance was significantly lower than in the WKY placebo group for transmural pressure up to 125 mm Hg, and thereafter was equal or even higher; the maximum value of compliance was reached at 125-150 mm Hg transmural pressure, i.e. substantially less than the operating range of the systemic mean BP of the SHR placebo (180 mm Hg). For transmural pressure steps up to 100 mm Hg in WKY and 125 mm Hg in SHR, both doses of quinapril produced an identical relaxation of arterial smooth muscle which approximated 80-90% of the maximum relaxation produced by KCN. For higher transmural pressure levels, neither quinapril nor KCN were able to change compliance values. Although the two doses caused the same degree of arterial smooth muscle relaxation in SHR, operating carotid compliance was substantially increased only with the higher dose, i.e. the dose which significantly shifted the operating systemic BP towards normotensive levels. The study provides evidence that, although low, nonhypertensive doses of quinapril are able to induce maximal relaxation of the carotid artery, operating compliance is substantially increased only if blood pressure is significantly decreased.

SummaryIncreased free erythrocyte protoporphyrin concentrations and depressed motor nerve conduction velocities (MNCV) were observed in 45 patients on maintenance haemodialysis. Neither of these findings could be correlated with age, duration or frequency of dialysis, or the degree of uraemia present. A strong negative correlation (r =-053; P