Liberato Aldo Ferrara

Long-Term Magnesium Supplementation in Essential Hypertension

The main objective of this clinical trial was to evaluate the effects of magnesium pidolate (15 mmol/day) on blood pressure at rest and during sympathetic stimulation induced by cold, isometric and tilt test; peripheral blood flow has been evaluated by strain-gauge plethysmography. Fourteen mild to moderate hypertensives (8 males, 6 females, age range 40-60 years) were randomly given magnesium or placebo in a double-blind parallel clinical trial for 6 months. In the actively treated group magnesium urinary excretion increased from 5.3 +/- 2 to 7.7 +/- 2 mmol/24 h, and serum magnesium changed from 0.9 +/- 0.1 to 1.0 +/- 0.2 mmol/l. On magnesium, BP changed at rest from 156/97 +/- 12/4 to 149/90 +/- 8/3 mm Hg, during cold pressor test from 169/105 +/- 9/6 to 174/105 +/- 15/4, during isometric exercise from 170/107 +/- 13/9 to 170/105 +/- 20/6, and during tilt test from 149/96 +/- 11/6 to 153/96 +/- 17/7 mm Hg. Similar changes were observed in the placebo group. Peripheral resistances were 14.7 +/- 4 and 9.8 +/- 2 PRU before and after magnesium, respectively. These data indicate that long-term magnesium pidolate supplementation does not affect blood pressure at rest and during sympathetic stimulation, despite a slight, nonsignificant reduction in forearm peripheral resistance.

Controlled study of the effect of angiotensin converting enzyme inhibition versus calcium-entry blockade on insulin sensitivity in overweight hypertensive patients : Trandolapril Italian Study (TRIS)

OBJECTIVE The aim of this study was to evaluate the effect of trandolapril, an angiotensin converting enzyme inhibitor, on blood pressure, forearm blood flow and insulin sensitivity in comparison with nifedipine gastrointestinal therapeutic system. PATIENTS AND METHODS This is a multicentre, two-way parallel-group, open-label comparative study in 90 overweight hypertensive patients, who were randomly assigned to treatment for 8 weeks with either trandolapril or nifedipine. At baseline and after treatment, all patients underwent an oral glucose tolerance test, an evaluation of their metabolic profiles and a euglycaemic hyperinsulinaemic clamp test. In a subgroup of 18 patients, a forearm study was carried out. RESULTS Blood pressure fell by the second week of treatment and remained significantly reduced compared with baseline in both treatment groups. Plasma triglyceride levels were also significantly reduced after trandolapril therapy, but no significant changes occurred in the other metabolic parameters during treatment with either drug. During the euglycaemic hyperinsulinaemic clamp, whole-body glucose use was similar in the two treatment groups at baseline, and a moderate but statistically significant increase in insulin sensitivity was observed after trandolapril treatment (trandolapril: 5.0 +/- 0.2 versus 4.5 +/- 0.2 mg/kg per min; nifedipine: 4.1 +/- 0.3 versus 4.2 +/- 0.3 mg/kg per min; P < 0.05, versus baseline and trandolapril versus nifedipine treatment). Skeletal muscle glucose uptake was significantly higher after trandolapril than after nifedipine therapy (5.0 +/- 0.7 and 3.0 +/- 0.4 mg/min, respectively; P < 0.01). As forearm blood flow was similar in the two treatment groups at baseline and was unchanged after 8 weeks of therapy, skeletal muscle glucose extraction was significantly greater in the ACE inhibitor treated-group than in the nifedipine comparative group (trandolapril: baseline 21 +/- 2, treatment 24 +/- 3 mg/dl; nifedipine: baseline 18 +/- 3, treatment 16 +/- 2 mg/dl; P < 0.05, trandolapril versus nifedipine treatment). CONCLUSIONS During short-term treatment, ACE inhibition with trandolapril was able to moderately improve insulin sensitivity, in comparison with calcium blockade, and this effect appeared to be independent of the haemodynamic action of the drug.

Cardiovascular risk factors, angiotensin-converting enzyme gene I/D polymorphism, and left ventricular mass in systemic hypertension

We investigated the influence of major cardiovascular risk factors (smoking, hypercholesterolemia, diabetes mellitus) on the association between angiotensin-converting enzyme (ACE) gene insertion (I)/deletion (D) polymorphism and echocardiographic left ventricular mass in 225 patients with sustained hypertension, assessed by ambulatory blood pressure monitoring. When the study population was analyzed as a whole, the 3 ACE genotypes did not differ in left ventricular mass (II, 47 g/m2.7; ID, 49 g/m2.7; DD, 51 g/m2.7; p = NS). No difference was found in subjects (n = 135) in whom at least 1 major cardiovascular risk factor was present (II, 51 g/m2.7; ID, 51 g/m2.7; DD: 52 g/m2.7; p = NS). In contrast, in the absence of cardiovascular risk factors, DD subjects (n = 32) exhibited left ventricular mass index higher than non-DD (ID/II) subjects (n = 75; p <0.05). After controlling for age and sex, in the absence of cardiovascular risk factors, the risk of left ventricular hypertrophy was 3.8-fold higher in DD than in non-DD patients (odds ratio 3.8; 95% confidence interval 1.2 to 12.1, p <0.02). We conclude that in the present setting of patients with established sustained systemic hypertension, the absence of risk factors potentially affecting cardiovascular adaptation allows for the detection of a positive association between homozygosity for the D allele of the ACE gene and left ventricular hypertrophy.

Metabolic syndrome and left ventricular hypertrophy in a general population. Results from the Gubbio Study.

Aims of this study were to investigate the prevalence of metabolic syndrome (MS), diagnosed according to the International Diabetes Federation (IDF) criteria and its relationship with echocardiographic parameters of cardiac structure and function. The study was performed in 707 subjects, age 45–54 years, of the Gubbio Population Study who underwent a comprehensive examination including measurement of body size, blood pressure (BP) and heart rate, 12-lead electrocardiogram, Doppler echocardiography, standardized blood and urine laboratory tests. One hundred and fifty-three subjects were found to have MS, which was more frequent among hypertensive patients than normotensive controls (36.2 vs 13.7%, P<0.001). Apart from visceral obesity present in all subjects by definition according to the IDF criteria, high levels of BP (>130/85 mm Hg) and triglycerides (⩾150 mg/dl) were the most frequently observed components of the syndrome, since their prevalence averaged 75% of those with the syndrome. Left ventricular mass (95.6±22 vs 86.4±22 g/m2; P<0.001) and prevalence of left ventricular hypertrophy were increased in the subgroup with MS. Waist circumference, BP and blood glucose were the components of the syndrome with stronger impact on cardiac mass. An early impairment of the diastolic function was detected in this subgroup with a reduction of the early-to-late diastolic filling (0.91±0.17 vs 0.99±0.23, P<0.001). The results of the present study indicate that MS is frequent in middle-aged general population, particularly in subjects with arterial hypertension. The syndrome is associated to the increase in ventricular mass and the early impairment of diastolic function.

Antihypertensive and cardiovascular effects of nitrendipine: a controlled study vs. placebo.

The antihypertensive and cardiovascular effects of nitrendipine, a calcium entry blocker similar to nifedipine, have been evaluated in a double‐blind, placebo‐controlled study in 20 patients with hypertension. At baseline and at the end of the 8‐week period (nitrendipine, 20 mg once a day, or placebo, 1 tablet once a day) the following parameters were measured: systolic and diastolic blood pressure (BP) and heart rate (HR) at rest by an automatic recorder; BP, HR, and cardiac workload (systolic BP × HR) during exercise testing on a bicycle; left ventricular mass (LVMe according to the method of Devereux) and cross‐sectional area (CSA), and main parameters of systolic function (end diastolic volume, end systolic volume [ESV], and ejection fraction [EF]) by M mode echocardiography. There was a significant decrease in BP at rest (163/108 vs. 144/92 mm Hg; P < 0.001) and during exercise in subjects receiving nitrendipine, while placebo did not modify these parameters. LVMe (from 195 to 188 gm; P < 0.01) and CSA (from 20.2 to 19.8 cm2; P < 0.05) were reduced by nitrendipine, which also improved cardiac performance (ESV fell from 44 to 38 ml [P < 0.001] and EF fell from 62% to 66% [P < 0.01]). No effect was observed in the placebo group. Our results indicate that nitrendipine is a powerful antihypertensive agent that also improves cardiac performance and slightly but significantly reduces left ventricular mass.

Age related antihypertensive effect of nitrendipine, a new calcium entry blocking agent

SummaryThe effect of nitrendipine 20 mg o.d., a new calcium entry blocker similar in structure to nifedipine, on blood pressure has been evaluated in 14 patients (aged 24–62 years) with uncomplicated mild or moderate arterial hypertension. A significant decrease both in systolic (160±12 at baseline vs 141±8 mm Hg, p<0.001) and diastolic (106±8 vs 93±3 mm Hg, p<0.001) blood pressure was observed at the end of 8 weeks of nitrendipine treatment. An inverse correlation was found between age and the reduction in diastolic blood pressure (r=0.772, p<0.001 as absolute reduction; r=0.791, p<0.001 as percentage reduction versus baseline). This peculiar characteristic differentiates the effect of nitrendipine from that of other calcium entry blockers, which appear to be more effective in older patients.

Effect of oral ketanserin administration on intraocular pressure in glaucomatous patients

We evaluated the effect of the antihypertensive drug ketanserin, a 5-HT antagonist, on intraocular pressure (IOP) in 20 patients with ocular hypertension. IOP, pupil diameter, systolic arterial pressure (SBP), diastolic arterial pressure (DBP) and heart rate (HR) were recorded at baseline and at 1-hr intervals for 3 hr after oral administration of 20 mg ketanserin or placebo, given in a randomized, double masked, cross-over fashion. The alternative treatment was given a week later. In all patients, ketanserin significantly lowered IOP and SBP, while no variations in pupil diameter, DBP and HR were found. Moreover, after drug administration, total outflow facility, measured by conventional tonography, increased significantly. These findings indicate that oral ketanserin could represent a new antiglaucomatous drug.

Serum uric acid does not predict incident metabolic syndrome in a population with high prevalence of obesity

AIM To evaluate whether uric acid (UA) predicts 4-yr incidence of metabolic syndrome (MetS) in non-diabetic participants of the Strong Heart Study (SHS) cohort. METHODS AND RESULTS In this population-based prospective study we analyzed 1499 American Indians (890 women), without diabetes or MetS, controlled during the 4th SHS exam and re-examined 4 years later during the 5th SHS exam. Participants were divided into sex-specific tertiles of UA and the first two tertiles (group N) were compared with the third tertile (group H). Body mass index (BMI = 28.3 ± 7 vs. 31.1 ± 7 kg/m(2)), fat-free mass (FFM = 52.0 ± 14 vs. 54.9 ± 11 kg), waist-to-hip ratio, HOMA-IR (3.66 vs. 4.26), BP and indices of inflammation were significantly higher in group H than in group N (all p < 0.001). Incident MetS at the time of the 5th exam was more frequent in group H than group N (35 vs. 28%, OR 1.44 (95% CI = 1.10-1.91; p < 0.01). This association was still significant (OR = 1.13, p = 0.04) independently of family relatedness, sex, history of hypertension, HOMA-IR, central adiposity and renal function, but disappeared when fat-free mass was included in the model. CONCLUSIONS In the SHS, UA levels are associated to parameters of insulin resistance and to indices of inflammation. UA levels, however, do not predict incident MetS independently of the initial obesity-related increased FFM.

Effects of different dietary protein intakes on body composition and vascular reactivity.

Objective:To assess the effects of a diet rich in protein of animal origin in comparison to one with a protein intake of about 15% of the total daily calories on body composition and arterial function.Design:Randomized prospective study with parallel groups. Body weight (BW), blood pressure (BP), main parameters of carbohydrate and lipid metabolism, body mass composition by bioelectrical impedance analysis, forearm blood flow at rest and in the postischaemic phase by strain gauge plethysmography and flow-mediated dilation of the brachial artery by echography were measured at baseline and after 6 months of the dietary intervention.Subjects:In total, 15 clinically healthy male volunteers, regularly performing a mixed training three times weekly for 90 min.Intervention:The participants were randomly prescribed a diet with high (1.9 g/kg BW) or normal (1.3 g/kg BW) protein content.Statistical analysis:Differences between means were evaluated by the t-tests for paired or unpaired data and by one way analysis of variance. The strength of correlation between variables was investigated by bivariate Pearson correlation.Results:Serum cholesterol significantly decreased with both diets in comparison to baseline values, whereas BW was slightly but significantly reduced only by the high-protein (HP) diet. No change was detected in BP and the other metabolic parameters. Body mass composition was not significantly modified by either diet. On the other hand, postischaemic flow-mediated dilation of the brachial artery was enhanced by the sole normal protein (NP) diet, whereas no change in the forearm blood flow, both at rest and in the postischaemic phase, was detected.Conclusions:These preliminary results indicate that HP diet was found to be not useful in increasing the muscle mass in comparison to a NP intake. In contrast to this, the latter diet seems to enhance the endothelial function of the arterial vessels with a more pronounced dilatation of the lumen in response to the increase in blood flow.

Doxazosin and captopril in mildly hypercholesterolemic hypertensive patients. The Doxazosin-Captopril in Hypercholesterolemic Hypertensives Study.

The evidence linking hypertension and hypercholesterolemia is strong and has fueled research into possible adverse effects of some antihypertensive agents on serum lipid profile. This multicenter, open, parallel study compares the effects of doxazosin and captopril on blood pressure, serum lipid levels, and quality of life in 224 hypercholesterolemic hypertensive patients. Blood pressure was significantly reduced in both treatment groups (p < 0.001) and was normalized (standing diastolic pressure < or = 90 mm Hg) in 73% of the doxazosin patients and 67% of the captopril group. Serum total cholesterol level was favorably reduced by both doxazosin (from 238 to 223 mg/dl, p < 0.001) and captopril (from 245 to 233 mg/dl, p < 0.001), whereas high density lipoprotein cholesterol concentration increased only in the doxazosin group (from 33 to 36 mg/dl, p < 0.001). The calculated 10-year risk for the development of coronary heart disease was reduced significantly (p < 0.001) by 28% in the doxazosin group and by 19% in the captopril group. The quality of life evaluation showed beneficial changes in both treatment groups. As a result of proven antihypertensive efficacy and a lack of unfavorable effects on lipid parameters and health status measures, these findings support the use of both doxazosin and captopril as agents of first choice in the treatment of hypertensive patients with associated lipid abnormalities.