Telmisartan and irbesartan therapy in type 2 diabetic patients treated with rosiglitazone: effects on insulin-resistance, leptin and tumor necrosis factor-alpha.

The aim of our study was to investigate the metabolic effect of telmisartan and irbesartan in subjects treated with rosiglitazone, a well-known insulin-sensitizing drug, in order to clarify the direct metabolic effects of the two former drugs. Patients were enrolled, evaluated, and followed at 3 Italian centers. We evaluated 188 type 2 diabetic patients with metabolic syndrome (94 males and 94 females in total; 49 males and 46 females, aged 56+/-5, treated with telmisartan; and 45 males and 48 females, aged 55+/-4, treated with irbesartan). All had been diabetic for at least 6 months, and glycemic control by the maximum tolerated dietary changes and maximum tolerated dose of oral hypoglycemic agents had been attempted and failed in all cases. All patients took a fixed dose of rosiglitazone, 4 mg/day. We administered telmisartan (40 mg/day) or irbesartan (150 mg/day) in a randomized, controlled, double-blind clinical manner. We evaluated body mass index (BMI), glycemic control (HbA1c fasting plasma glucose and insulin levels [FPG, and FPI, respectively], and homeostasis model assessment [HOMA] index), lipid profile (total cholesterol [TC], low density lipoprotein-cholesterol [LDL-C], high density lipoprotein-cholesterol [HDL-C], and triglycerides [TG]), systolic and diastolic blood pressure (SBP and DBP), tumor necrosis factor-alpha (TNF-alpha), and leptin during the 12 months of this treatment. No BMI change was observed after 6 or 12 months in either group. Significant decreases in HbAlc and FPG were observed after 6 months in the telmisartan group, and after 12 months in both groups. The decrease in HbA1c and FPG at 12 months was statistically significant only in the telmisartan group. A significant decrease in FPI was observed at 12 months in both groups, and this decrease was significantly greater in the telmisartan group. Significant decreases in the HOMA index were observed at 6 and 12 months in both groups, and the decrease in the HOMA index after 12 months was significantly greater in the telmisartan group than in the irbesartan group. Significant changes in SBP, DBP, TC, and LDL-C were observed after 6 and 12 months in both groups. Significant decreases in TNF-alpha and leptin levels were observed after 6 months in the telmisartan group, and after 12 months in both groups. In conclusion, in this study of patients with type 2 diabetes mellitus and metabolic syndrome, telmisartan seemed to result in a greater improvement in glycemic and lipid control and metabolic parameters related to metabolic syndrome compared to irbesartan. These observed metabolic effects of different angiotensin type 1 receptor blockers could be relevant when choosing a therapy to correct metabolic derangement of patients affected by metabolic syndrome and diabetes.     

Effects of nifedipine and indomethacin on cough induced by angiotensin-converting enzyme inhibitors: a double-blind, randomized, cross-over study.

Prostaglandins (PG) have been suggested to play a role in the genesis of cough induced by angiotensin-converting enzyme inhibitors (ACE-I) and that inhibition of PG synthesis can reduce or abolish the incidence of this side effect. Moreover, experimental and clinical data suggest that nifedipine, a dihydropyridine Ca antagonist, can inhibit PG synthesis. Therefore, we wished to determine whether nifedipine can reduce cough induced by ACE-I as compared with indomethacin, a known inhibitor of PG synthesis. Fourteen hypertensive patients who developed cough during captopril chronic therapy randomly received slow-release nifedipine 20 mg twice daily (b.i.d.), indomethacin 50 mg b.i.d., and placebo b.i.d. for 1 week in a double-blind, cross-over design. At the end of each treatment phase, cough was evaluated by a self-administered questionnaire containing an ordinal scale for daily cough intensity and frequency. Indomethacin abolished or markedly reduced cough induced by ACE-I, whereas nifedipine reduced it but to a lesser degree. These findings suggest that PG can play a role in cough caused by ACE-I, and a dihydropyridine Ca antagonist can reduce the occurrence of this side effect.     

Antihypertensive activity and duration of action of dilevalol in hypertensive patients at rest and during exercise. A comparison with captopril

The aim of this study was to compare the effect of dilevalol and captopril on blood pressure and heart rate in hypertensive subjects, both at rest and during bicycle exercise. Thirty mild hypertensive patients (24 men, 6 women), aged 34-55, were studied in a randomized, double-blind, parallel group trial. After a 3-week placebo run-in, patients were randomized to receive either dilevalol (200 mg once daily) or captopril (50 mg twice daily) for 4 weeks. Dilevalol-treated patients whose diastolic blood pressure had not decreased by more than 8 mmHg from baseline (or to less than 95 mmHg) were given 400 mg once daily for a further 2 weeks. Treatment was stopped for all other patients. Blood pressure and heart rate were measured at rest and during bicycle exercise tests 4 ("peak") and 24 hours ("trough") after dosing in the dilevalol group and 4 ("peak") and 12 hours ("trough") after dosing in the captopril group. At the end of the placebo run-in, mean resting blood pressure was 156/102 mmHg in the dilevalol group and 157/103 in the captopril group. Six patients had blood pressure normalization with captopril and 9 with dilevalol 200 mg; a further 2 patients achieved normalized blood pressure levels with dilevalol 400 mg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum testosterone levels and arterial blood pressure in the elderly.

The aim of this study was to evaluate the relationship between serum testosterone levels and arterial blood pressure (BP) in the elderly. We studied 356 non-diabetic, non-smoking, non-obese men aged 60 to 80 years and untreated for hypertension. All subjects were evaluated in the morning after an overnight fast. Evaluation included measurements of the following: BP (by mercury sphygmomanometer, Korotkoff I and V), body weight, height and free testosterone (T) plasma levels (by radioimmunoassay). According to the BP values, the subjects were classified as normotensives (NT; n=112; SBP/DBP<140/90 mmHg), systolic and diastolic hypertensives (HT; n=127; SBP/DBP>140/90 mmHg), and isolated systolic hypertensives (ISH; n=117; SBP>140 mmHg and DBP<90 mmHg). T values decreased with increasing age in all 3 groups and was significantly lower in HT (-15%) and ISH men (-21%) than in NT men (p<0.05). In each group, the T levels showed a highly significant negative correlation with BMI (p<0.001). A significant negative correlation was also found between T levels and SBP in NT (r=-0.35, p<0.001), ISH (r=-0.67, p<0.001), and HT (r=-0.19, p<0.05) men, whereas a negative correlation with DBP was observed only in the NT men (r=-0.19, p<0.05). Adjusting for the BMI confirmed a significant difference in plasma T levels between ISH and NT men, but not between HT and NT men. Multiple regression analysis employing BP as a dependent variable confirmed a strong relationship between T levels and SBP in all 3 groups, whereas a significant relationship between T levels and DBP was found only in NT men. In conclusion, although further studies are needed to clarify the relationship between plasma T levels and BP, our findings suggest that in elderly men with ISH, the reduced plasma levels of testosterone might contribute to the increased arterial stiffness typical of these subjects.     

Effects of aliskiren on QT duration and dispersion in hypertensive patients with type 2 diabetes mellitus

Aim: To evaluate the effect of aliskiren compared to amlodipine on QT duration and dispersion in hypertensive patients with type 2 diabetes. Methods: A total of 170 outpatients aged 50–75 years with mild to moderate hypertension (SBP >130 and <180 mmHg and DBP >80 and <100 mmHg) and type 2 diabetes were randomly treated with aliskiren 300 mg or amlodipine 10 mg, both given once daily for 24 weeks, according to a prospective, open label, blinded‐end point, parallel group design. At the end of the placebo run‐in, and after 12, and 24 weeks of treatment blood pressure (BP) measurements (by mercury sphygmomanometer, Korotkoff I and V), plasma biochemistry and a standard 12‐lead surface ECG were evaluated. Results: Both aliskiren and amlodipine significantly reduced systolic blood pressure (SBP)/diastolic blood pressure (DBP) values (?27.2/?14.3 mmHg, p < 0.001 vs. placebo and ?27.8/?14.2 mmHg, p < 0.001 vs. placebo, respectively), with no statistical difference between the two drugs. Aliskiren, but not amlodipine, significantly reduced maximum QT interval (QTmax) (?14 ms at 12 weeks and ?17 ms at 24 weeks, both p < 0.05 vs. placebo) and corrected QT max (QTc max) (?26 ms and ?31 ms, p < 0.01) as well as the dispersion of both QT (?11 ms and ?13 ms, p < 0.01) and QTc (?18 ms and ?19 ms, p < 0.01). Conclusions: Despite similar BP lowering effect, aliskiren, but not amlodipine, reduced QT duration and dispersion, which might be related to the ability of aliskiren to interfere with mechanisms underlying myocardial electrical instability in the heart of diabetic hypertensive patients.     

Effect on the development of ankle edema of adding delapril to manidipine in patients with mild to moderate essential hypertension: a three-way crossover study

BACKGROUND: Use of the combination of an angiotensin-converting enzyme inhibitor (ACEI) and a calcium channel blocker (CCB) is considered a rational approach in patients whose hypertension is not controlled by monotherapy, providing better blood pressure (BP) control than the individual components with a lower incidence of adverse effects. In particular, such combinations have been found to reduce the incidence of ankle edema, the most common adverse effect of dihydropyridine annhypertensives. OBJECTIVE: The present study was undertaken to evaluate the effect on the development of ankle edema of adding the ACEI delapril to the CCB manidipine in patients with mild to moderate essential hypertension. METHODS: Patients between the ages of 30 and 70 years who had mild to moderate hypertension (diastolic BP [DBP] >90 and <110 mm Hg) were included in the study. After a 4-week placebo run-in period, eligible patients were randomized to receive 6 weeks each of manidipine 10 mg/d, delapril 30 mg/d, and both in a crossover fashion. There was a 2-week washout period between treatments. Ankle edema was assessed based on ankle-foot volume (AFV) and pretibial subcutaneous tissue pressure (PSTP). Sitting BP, AFV, and PSTP were measured at the end of the placebo run-in period and the end of each active-treatment period. RESULTS: The study enrolled 40 patients with previously untreated hypertension (21 women, 19 men). Both manidipine and delapril monotherapy were associated with significant reductions from baseline in systolic BP (SBP) (mean [SD], -17.3 [4] and -14.8 [4] mm Hg, respectively; both, P<0.01) and DBP (-14.6 [3] and -12.9 [3] mm Hg; both, P<0.01). Compared with monotherapy, the combination of manidipine and delapril was associated with greater reductions from baseline in SBP (-21.8 [5] mm Hg; P<0.001) and DBP (-18.6 [4] mm Hg; P<0.001). Manidipme monotherapy was associated with significant increases from baseline in both AFV (7.9%; P<0.001) and PSTP (36.6%; P<0.01). Compared with manidipine alone, the combination of manidipine and delapril was associated with less pronounced increases in AFV (3.3%; P<0.05) and PSTP (10.4%; P<0.05). Ankle edema was clinically evident in 3 patients after receipt of manidipine monotherapy and in 1 patient after receipt of combination treatment. CONCLUSION: In these patients with mild to moderate essential hypertension, the addition of delapril to manidipine partially counteracted the manidipine-induced microcirculatory changes responsible for ankle edema.     

Different Aspects of Sartan + Calcium Antagonist Association Compared to the Single Therapy on Inflammation and Metabolic Parameters in Hypertensive Patients

This study aims to evaluate the effects of an angiotensin receptor blocker (ARB)/calcium channel blocker combination on blood pressure control, lipid profile, insulin sensitivity, and inflammation markers. We randomized 276 hypertensive patients to olmesartan 20 mg, amlodipine 10 mg, or a single pill containing an olmesartan/amlodipine combination 20/5 mg for 12 months. We evaluated the following: body weight, systolic and diastolic blood pressure, fasting plasma glucose, fasting plasma insulin (FPI), M value, lipid profile, adiponectin (ADN), high sensitivity C-reactive protein (Hs-CRP), monocyte chemoattractant protein-1 (MCP-1), and macrophage migration inhibitory factor-1β (MIP-1β). Olmesartan/amlodipine combination better reduced blood pressure, FPI, homeostasis model assessment index, and increased M value and ADN compared to olmesartan and amlodipine monotherapies. Olmesartan/amlodipine significantly decreased Hs-CRP, MCP-1, and MIP-1β. In this multicenter, randomized, double-blind, clinical study, ARB/calcium antagonist combination resulted to be more effective than single monotherapies in reducing blood pressure, in improving insulin sensitivity, and in reducing inflammation parameters in patients with stage I essential hypertension.     

Repeated office blood pressure controls reduce the prevalence of white-coat hypertension and detect a group of white-coat normotensive patients

BACKGROUND: The aim of this study was to evaluate whether repeated office blood pressure controls may change the prevalence of white-coat hypertension among hypertensive patients. METHODS: We studied 221 newly diagnosed, never-treated hypertensive patients, all men, aged 31-60 years. On the first visit, they underwent sitting blood pressure measurements (two readings were taken by mercury sphygmomanometer and averaged) and non-invasive 24 h ambulatory blood pressure monitoring (ABPM) every 15 min. Thereafter, each patient made four further visits over an 8-week period. On each visit, three sitting readings were taken and averaged. On the last visit, ABPM was performed again. Subjects who had hypertension in the clinic but whose daytime ambulatory blood pressure was less than 134/90 mmHg were considered to have white-coat hypertension. RESULTS: On the first visit, all patients were, by definition, clinically hypertensive and ABPM detected a prevalence of white-coat hypertension of 25.8%. On the following visits, the prevalence of clinical hypertensive patients progressively declined; on the last visit, the 82.3% of all patients resulted yet clinical hypertensive: on ambulatory blood pressure 71.9% were sustained hypertensives, whereas 10.4 had white-coat hypertension. Of the patients originally labelled as hypertensive, 17.7% proved to be clinically normotensive: 13.6% had also daytime ambulatory blood pressure in the normal range, whereas 4.1% showed elevated blood pressure during daytime ABPM (white-coat normotensives). CONCLUSION: These data suggest that repeated office blood pressure controls in newly diagnosed hypertensives reduce the number of office hypertensive patients, reduce the number of white-coat hypertensive patients and detect a small group of white-coat normotensive patients.     

Comparison between orlistat plus l-carnitine and orlistat alone on inflammation parameters in obese diabetic patients

To evaluate the effects of 1-year treatment with orlistat plus L-carnitine compared to orlistat alone on body weight, glycemic and lipid control, and inflammatory parameters in obese type 2 diabetic patients. Two hundred and fifty-eight patients with uncontrolled type 2 diabetes mellitus (T2DM) [glycated hemoglobin (HbA(1c)) > 8.0%] in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomized to take orlistat 120 mg three times a day plus L-carnitine 2 g one time a day or orlistat 120 mg three times a day. We evaluated the following parameters at baseline and after 3, 6, 9, and 12 months: body weight, body mass index (BMI), glycated hemoglobin (HbA(1c) ), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (Tg), adiponectin (ADN), leptin, tumor necrosis factor-α (TNF-α), vaspin, and high-sensitivity C-reactive protein (Hs-CRP). We observed a better decrease in body weight, glycemic profile, HOMA-IR, LDL-C, and ADN and a faster improvement in FPI, TC, Tg, leptin, TNF-α, Hs-CRP with orlistat plus L-carnitine compared to orlistat alone. We also recorded an improvement in vaspin with orlistat plus l-carnitine not reached with orlistat alone. Orlistat plus L-carnitine gave a better improvement in body weight, glycemic and lipid profile compared to orlistat alone; furthermore, a faster and better improvement in inflammatory parameters was observed with orlistat plus L-carnitine compared to orlistat alone.