[Cardiovascular risk factors in a community in Piedmont: changes after 11 years and a comparison with other regional and national data]. / Fattori di rischio cardiovascolare in una comunità del Piemonte: variazioni a distanza di undici anni e confronto con altri dati regionali e nazionali.

BACKGROUND: In 1986 the Cardiology Department, including an outpatient clinic, was established in the community hospital of Savigliano (Italy). In 1987, as a part of a cardiovascular community prevention program, an epidemiological survey on cardiovascular risk factors was carried out. Similar indicators have been object of the study held in 1998 by ANMCO-Istituto Superiore di Sanità: the Italian Cardiovascular Epidemiological Observatory. So, 11 years later, we have had the chance to compare the changes, in the same community, of three important risk factors: tobacco smoking, arterial blood pressure, and obesity. METHODS: The 1987 survey included 280 subjects, aged 20 to 59 years. The 1998 survey has examined 200 subjects, aged 35 to 74 years. In both cases the subjects have been randomly selected from the Electoral Registers; subjects were asked to answer a questionnaire on tobacco smoking; arterial blood pressure measured using a cuff manometer was registered and weight and height have been recorded. In order to have comparable data we have only considered subjects 35 to 59 years old. RESULTS: One hundred and fifty-seven subjects (84 males and 73 females) were included in the 1987 survey and 123 (60 males and 63 females) in the 1998 survey. In 1987, the percentage of smokers was 40.7% (61.4% of males and 17.8% of females), with an average of 23.4 cigarettes/day among males and 14.7 among females. In 1998, the percentage of smokers has dropped to 18.6%, without any differences between sexes, with an average of 11.9 cigarettes/day among males and 12.7 among females. The mean values of blood pressure were lower in 1998 than in 1987 both in males (129.4/85.7 vs 138.0/88.2 mmHg) and females (119.3/80.2 vs 138.4/86.5 mmHg). Although not statistically significant, the percentage of individuals with systolic blood pressure > or = 160 mmHg or diastolic blood pressure > or = 95 mmHg was lower in 1998 (15.9% among males and 14.2% among females) than in 1987 (25.6% among males and 22.8% among females). The mean values of body mass index were unchanged (from 25.4 to 25.2 kg/m2 in males and from 23.4 to 23.1 kg/m2 in females). CONCLUSIONS: The incidence of tobacco smoking and of hypertension has shown a significant reduction in the population of Savigliano between 1987 and 1998. No significant variation was found in body mass index or in the prevalence of obesity. The distribution of these three risk factors seems to be lesser than that reported in northern Italy.

Three-month treatment with metformin or dexfenfluramine does not modify the effects of diet on anthropometric and endocrine-metabolic parameters in abdominal obesity.

Abdominal obesity is connoted by hyperinsulinism and insulin insensitivity, a trend toward glucose intolerance, hypoactivity of GH/IGF-I axis and alterations of hypothalamo-pituitary-adrenal (HPA) axis. It has been hypothesized that treatment with metformin (MET) and dexfenfluramine (DEX) could counteract those endocrine-metabolic alterations. Thus, we studied the effects of 3-month treatment with MET or DEX on anthropometric (BMI, WHR, FM and FFM), metabolic (basal and OGTT-induced glucose) and hormonal variables (IGF-I, DHEA-S, androstendione, testosterone, fT3, fT4, TSH, basal and OGTT-induced insulin) as well as on blood pressure in 28 normotensive patients with abdominal obesity (OB, 3 M, 25 F; 47.5+/-1.5 yr [mean+/-SE], BMI 35.4+/-1.1 kg/m2, WHR 0.98+/-0.04 and 0.86+/-0.07, in M and F, respectively). All patients were on balanced hypocaloric diet (1400 Kcal/day). Patients were randomly assigned to treatment with MET (no.=10, 500 mg twice daily po) or DEX (no.=10, 15 mg thrice daily po) or placebo (no.=8). Before treatment all groups had similar anthropometric, metabolic and hormonal values. After 3-month treatment with MET, DEX or placebo, weight, BMI and WHR reductions were similar in all groups (p<0.05 vs baseline in either group). In each group FFM/FM ratio showed non significant trend toward increase. No significant variations in metabolic and endocrine variables were recorded in each group after 1 and 3-month treatment. However, glucose tolerance, OGTT-induced insulin response, glucose/insulin ratio showed a similar trend toward improvement in all groups, while IGF-I, 24 h urinary cortisol, DHEA-S, androstendione, testosterone, thyroid hormone and TSH levels did not show any variation. Significant (p<0.02) and similar reductions of DBP, but not of SBP, levels were found in all groups. In conclusion, our findings demonstrate that, at least after 3-month treatment, metformin and dexfenfluramine do not modify the effects of diet on anthropometric, metabolic and hormonal parameters as well as on blood pressure in patients with abdominal obesity.

Effects of 3-month nifedipine treatment on endocrine-metabolic parameters in patients with abdominal obesity and mild hypertension.

It is widely accepted that abdominal obesity presents with exaggerated insulin secretion, insulin resistance and a trend toward glucose intolerance. Hypertension is frequently associated to abdominal obesity, and hyperinsulinism could play a role in its pathogenesis. Some studies reported that Ca-antagonists positively influence insulin sensitivity and glucose tolerance in obese patients with normal or elevated blood pressure. However, other studies reported worsening of metabolic balance during treatment with Ca-antagonists in hypertensive non-insulin-dependent diabetes mellitus (NIDDM) patients and in normal subjects. We studied 19 patients with abdominal obesity, mild hypertension and insulin resistance on balanced, mild hypocaloric diet (1400 Kcal), to verify the effects of the Ca-antagonist nifedipine on both basal and oral glucose tolerance test (OGTT)-induced glucose and insulin levels as well as on IGF-I basal and DHEA-S levels and fat mass (FM). To achieve this goal, 10 hypertensive obese subjects (HOB-NIFE, 3 males, 7 females, mean age +/- SD 44.6 +/- 1.7 yr; body mass index (BMI) 37.1 +/- 2.5 Kg/m2, WHR 0.95 +/- 0.02) received 3-month treatment with nifedipine (Adalat Crono 30 Bayer, 1 tab daily) while other 9 hypertensive obese (HOB, 3 males, 6 females, 42 +/- 2.4 yr, BMI 35.8 +/- 1.8 Kg/m2, WHR 0.91 +/- 0.03) were studied during diet only. The same parameters were studied also in 8 normotensive obese patients (OB: 3 males, 5 females, 48.1 +/- 2.1 yr, BMI 35.8 +/- 2.4 Kg/m2, WHR 0.90 +/- 0.03) on the same balanced hypocaloric diet. Basal systolic (SBP) and diastolic (DBP) blood pressure levels in HOB-NIFE and HOB were similar. At baseline, all groups had similar basal and OGTT-induced glucose, insulin and glucose insulin ratio (GIR) levels as well as IGF-I and DHEA-S levels. After 3 months BMI fell to the same extent in all groups (p < 0.05 vs baseline) while WHR and FFM/FM ratio did not change. SBP and DBP decreased HOB-NIFE (p < 0.02) but also during diet alone in both HOB and OB, though to a lesser extent (p < 0.05). Both basal and OGTT-stimulated glucose and insulin levels as well as IGF-I and DHEA-S levels were not modified in HOB-NIFE as well as in HOB and OB. In conclusion, our data indicate that nifedipine treatment does not modify glucose tolerance as well as insulin secretion and sensitivity, IGF-I and DHEA-S levels in hypertensive abdominal obese patients. Thus, nifedipine treatment has no detrimental effects on endocrine-metabolic balance in hypertensive obese patients.

Comparison among the effects of arginine, a nitric oxide precursor, isosorbide dinitrate and molsidomine, two nitric oxide donors, on hormonal secretions and blood pressure in man.

Arginine has well-known stimulatory effects on GH, PRL and insulin secretion in man but the mechanisms underlying these effects are still unclear. More recently, it has been demonstrated that arginine is the precursor of nitric oxide (NO) which mediates its vasodilatatory effect. Thus, it has been hypothesized that NO could also mediate the hormonal effects of arginine. To clarify this point, in seven normal young volunteers (7 normal male subjects, age 26-35 yr) we compared the effects of arginine hydrochloride (ARG, 0.5 g/kg iv over 30 min) on GH, PRL, insulin and glucose levels as well as on blood pressure, with those of isosorbide dinitrate (ISDN, 5 mg po) and molsidomine (MOLS, 4 mg po), two NO donors which possess well-known vasodilatatory effects. ARG infusion elicited a clear-cut GH increase (peak vs baseline 17.6 +/- 4.7 vs 2.7 +/- 0.8 (g/L, p < 0.01), PRL (20.6 +/- 2.8 vs 6.9 +/- 0.5 (g/L, p < 0.01) and insulin levels (31.4 +/- 5.7 vs 4.5 +/- 2.1 (U/L, p < 0.01) while induced a biphasic variation of plasma glucose levels with early increase (p < 0.01), followed by late decrease below basal values (p < 0.01). On the other hand, blood pressure was decreased by ARG (nadir vs baseline; systolic: 103 +/- 6 vs 112 +/- 3, p < 0.02 and diastolic 61 +/- 4 vs 72 +/- 2 mmHg, p < 0.02, respectively). ISDN and MOLS did not modify basal GH, PRL and insulin as well as glucose levels while induced a clear reduction in blood pressure (ISDN: nadir vs baseline; systolic: 94 +/- 4 vs 112 +/- 2, p < 0.02; diastolic 69 +/- 3 vs 80 +/- 2, p < 0.02; MOLS: systolic: 94 +/- 3 vs 113 +/- 2 p < 0.02; diastolic 63 +/- 4 vs 72 +/- 2, p < 0.02). The lowering effect of both ISDN and MOLS on both systolic and diastolic blood pressure levels was higher than that induced by ARG. The effect of the latter was, in turn, significantly different from that of placebo on diastolic levels only. In conclusion, our present date are against the hypothesis that NO mediates the stimulatory effects of arginine on GH, PRL and insulin secretion. On the other hand, our findings agree with the hypothesis that ARG has NO-mediated vasodilatatory effect able to decrease blood pressure in man.

The inhibitory effect of glucose on growth hormone secretion is lost in obesity but not in hypertension.

In obesity there is a clear reduction of both spontaneous and stimulated GH secretion. Furthermore, in obese patients the somatotrope responsiveness to provocative stimulation is selectively refractory to the inhibitory effect of glucose load. It has been hypothesized that hyperinsulinism of obese patients could play a role in the pathogenesis of these alterations. Aim of the present study was to verify the GH response to GHRH and the ability of glucose load to inhibit it in patients with essential hypertension in whom hyperinsulinism and insulin resistance are frequently present. To this goal, 7 patients with essential hypertension (HP, age, mean +/- SE: 29.6 +/- 2.4 yr, 3 females and 4 males, BMI: 21.7 +/- 1.2 kg/m2), 7 obese (OB, 4 females and 3 males, 31.9 +/- 4.1 yr, 35.6 +/- 2.0 kg/m2) and 7 normal subjects (NS, 4 females and 3 males, 28.3 +/- 3.9 yr, 21.0 +/- 1.6 kg/m2) underwent the following tests: GHRH (1 microgram/kg i.v. at time 0) alone and preceded by oral glucose load (OGTT, 100 g po at -45 min). Basal insulin levels were similar in HP and OB (11.3 +/- 0.5 and 12.7 +/- 2.2 microU/ml, respectively); these, in turn, were higher (p < 0.005) than those in NS (6.8 +/- 0.8 microU/ml). Basal plasma glucose levels in HP were similar to those in OB and NS (80.3 +/- 3.6, 86.9 +/- 6.7 and 84.4 +/- 1.7 mg/dl, respectively). In HP and OB and NS basal GH (1.0 +/- 0.5, 1.0 +/- 0.6 and 0.3 +/- 0.1 micrograms/l, respectively) and IGF-I levels (132.6 +/- 14.8, 137.3 +/- 13.2 and 138.8 +/- 12.2 micrograms/l, respectively) were similar. In HP the GH response to GHRH (AUC: 1058.8 +/- 347.8 micrograms/l/min) was similar to that observed in NS (959.0 +/- 167.8 micrograms/l/min) and higher than that in OB (344.8 +/- 67.2 micrograms/l/min, p < 0.01). OGTT clearly blunted (p < 0.01) the GHRH-induced GH response in HP as well as in NS (401.8 +/- 104.4 and 521.6 +/- 76.6 (g/l/min, respectively) but not in OB (387.4 +/- 78.8 (g/l/min). The OGTT-induced insulin levels in HP did not differ from those of OB, both being higher (p < 0.05) than those recorded in NS. Glucose levels after OGTT were similar in the three groups. In conclusion, this study demonstrates that, like in normal subjects but differently from in obese patients the GH response to GHRH is normal in patients with essential hypertension and it is normally inhibited by oral glucose load even when these patients show high insulin levels. Thus, it is unlikely that the low somatotrope secretion and its refractoriness to inhibition by glucose load in obesity is due to hyperinsulinism.