ramipril and Metabolic-Syndrome

Hypertension in combination with clinically overt diabetes mellitus is recognized as a particularly powerful combination of risk factors that greatly increases cardiovascular vulnerability. There is also evidence that presumed pre-diabetic conditions such as insulin resistance, hyperinsulinaemia and compensatory hyperglycaemia may amplify overall cardiovascular risk in patients with hypertension, especially when encountered as part of the condition known as metabolic syndrome X (Reaven's syndrome). The long-term benefits of antihypertensive therapy may be compromised if these drugs exert adverse effects on metabolic parameters such as insulin sensitivity, or if they promote a transition from pre-diabetes to overt diabetes. Class differences in the effects of antihypertensives on metabolic indices may therefore be an important consideration when choosing treatment for patients who exhibit these characteristics. Experience from clinical trials suggests that drugs that target the renin-angiotensin system may have metabolic advantages over drugs such as beta-blockers and diuretics, but this conclusion has not been proved definitively. Moxonidine, which selectively targets imidazoline type-1 receptors in the sympathetic vasomotor centres of the rostral-ventrolateral medulla, is an effective antihypertensive and has been reported to exert favourable metabolic effects in preclinical and clinical studies. The MARRIAGE study (Moxonidine And Ramipril Regarding Insulin And Glucose Evaluation) will extend these preliminary observations by comparing the effects of moxonidine and the ACE inhibitor ramipril--and the combination of both drugs--on metabolic and haemodynamic parameters in patients with hypertension and impaired fasting glycaemia. A description is provided of the design and conduct of MARRIAGE.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Glucose; Cardiovascular Diseases; Clinical Trials as Topic; Humans; Hypertension; Imidazoles; Imidazoline Receptors; Insulin Resistance; Metabolic Syndrome; Ramipril; Receptors, Drug; Risk

This study evaluated the effect of telmisartan, ramipril, and amlodipine on atrial fibrillation (AF) recurrence and severity in hypertensive patients with metabolic syndrome. A total of 391 hypertensive outpatients with metabolic syndrome, in sinus rhythm but with at least 2 episodes of AF in the previous 6 months were randomized to telmisartan, ramipril, or amlodipine for 1 year. At the first AF, ventricular rate (VR) and plasma cardiac troponin I (TnI) were evaluated. P-wave dispersion (PWD) and procollagen type I carboxy-terminal peptide (PIP) were evaluated before and after 12 months of treatment. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were similarly and significantly reduced by all treatments (P < .001). In all, 49% of patients treated with amlodipine had a recurrence of AF as did 25.5% of patients with ramipril and 12.9% of patients with telmisartan (P < .01 vs amlodipine and P < .05 vs ramipril). Ventricular rate and TnI at the first AF recurrence were significantly lower with telmisartan and ramipril than with amlodipine. P-wave dispersion was reduced by ramipril (-5.1 ms, P < .05) and even more by telmisartan (-11 ms, P < .01). Telmisartan and ramipril induced a similar PIP reduction (-52.8 and -49.8 µg/L, respectively, P < .01). These findings suggested that in these patients telmisartan was more effective than ramipril in reducing AF recurrence and severity as well as in improving PWD, despite a similar BP reduction and a similar improvement in cardiac fibrosis. This could be related to a specific effect of telmisartan on atrial electric remodeling.

Topics: Aged; Atrial Fibrillation; Benzimidazoles; Benzoates; Double-Blind Method; Female; Follow-Up Studies; Humans; Hypertension; Male; Metabolic Syndrome; Prospective Studies; Ramipril; Secondary Prevention; Severity of Illness Index; Telmisartan; Treatment Outcome

Two recent identically designed trials (one Italian and one European multinational) have compared the head-to-head efficacy and safety of the angiotensin II receptor blocker olmesartan medoxomil and the angiotensin converting enzyme inhibitor ramipril, in elderly patients with essential hypertension.. The aim of the present study was to assess the antihypertensive efficacy of olmesartan and ramipril in elderly patients with hypertension, with or without metabolic syndrome, by performing a pooled analysis of data from the two head-to-head trials.. After a 2-week, placebo wash-out, 1,453 treated or untreated elderly hypertensive patients aged 65-89 years [with sitting office diastolic blood pressure (DBP) 90-109 mmHg and/or sitting office systolic BP (SBP) 140-179 mmHg] were randomized to 12-weeks of double-blind treatment with olmesartan 10 mg or ramipril 2.5 mg once daily. Treatment could be up-titrated to 20 and 40 mg for olmesartan, and 5 and 10 mg for ramipril, after the first 2 and 6 weeks, respectively, in patients with inadequately controlled BP (BP ≥ 140/90 mmHg for non-diabetics and ≥ 130/80 mmHg for diabetics). Office BP was measured at randomization and after 2, 6 and 12 weeks of treatment. 24-h ambulatory BP recordings were obtained at randomization and after 12 weeks.. Of the 1,426 patients in the intent-to-treat analysis, 735 (51.5 %) had metabolic syndrome (olmesartan, n = 372; ramipril, n = 363). After 12 weeks of treatment, baseline-adjusted office BP reductions were greater (p < 0.05) with olmesartan (SBP 17.0 mmHg; 95% CI 18.4, 15.6; DBP 9.6 mmHg; 95% CI 10.4, 8.8) than with ramipril (SBP 14.7 mmHg; 95% CI 16.1, 13.2; DBP 8.4 mmHg; 95% CI 9.2, 7.6) in patients with metabolic syndrome. In these patients, BP normalization rates were also greater with olmesartan than with ramipril (46.0 vs. 35.8%, p < 0.01). Similarly, in patients without metabolic syndrome, the antihypertensive efficacy of olmesartan was also significantly (p < 0.05) better than that of ramipril. In the subgroup of patients with valid ambulatory BP (ABP) recordings and metabolic syndrome (olmesartan, n = 182; ramipril, n = 170), the reduction in mean 24-h ABP was greater with olmesartan (SBP 10.2 mmHg; 95% CI 11.8, 8.6; DBP 6.6 mmHg; 95% CI 7.5, 5.6) than with ramipril (SBP 8.5 mmHg; 95% CI 10.2, 6.9; DBP 4.7 mmHg; 95% CI 5.7, 3.7), with a statistically significant (p < 0.01) difference for the DBP comparison. The proportion of patients experiencing drug-related adverse events was comparable in patients with (olmesartan 2.4 % vs. ramipril 2.8 %) and without (3.5 vs. 3.7 %) metabolic syndrome.. Olmesartan provides more effective BP control than ramipril in elderly hypertensive patients with and without metabolic syndrome.

Topics: Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Female; Humans; Hypertension; Imidazoles; Male; Metabolic Syndrome; Monitoring, Physiologic; Olmesartan Medoxomil; Ramipril; Safety; Tetrazoles

We investigated benefits of Pycnogenol(R) as an adjunct to hypotensive medication in metabolic syndrome patients with micro-albuminurea.. Fifty eight patients were treated with Ramipril and a subgroup received Pycnogenol in addition for six months. Colour Doppler duplex ultrasound was employed for cortical flow measurements.. Blood pressure decreased with Ramipril from 188.8/95.2 to 128.2/90.2, with additional Pycnogenol from 189.3/97.2 to 122.2/85.3 (P<0.05). Kidney function improved in both groups, with 24 hour urinary albumin decreasing from 88.8 to 68.9 mg with Ramipril and from 89.3 to 42.2 mg with additional Pycnogenol (P<0.05). In both groups treatment lowered serum creatinine, with combination treatment being significantly more effective. Cortical flow velocities significantly increased with Ramipril from systolic 17.2 +/- 3.1 to 23.8 +/- 2.0 cms-1 and diastolic 4.2+/-2.8 to 2.0+/-3.1 cms-1. The addition of Pycnogenol was more effective, improving cortical flow from systolic 18.2+/-2.2 to 27.2+/-2.9 cms-1 and diastolic 4.1+/-2.2 to 9.8+/-2.1 cms-1 (P>0.05). C-reactive protein (CRP) levels decreased marginally with Ramipril, but significantly with Pycnogenol from 2.17 to 1.62 mg/dL. Pycnogenol significantly lowered fasting blood glucose to 102.3 +/- 11.2 mg/mL and HbA1c to 6.9 +/- 0.3 %. The Pycnogenol group showed a significantly lowered BMI, from baseline 26.5+/-0.9 to 25.0+/-1.2 kgm-2, without reaching statistical significance versus control. Only a limited improvement of blood lipid profile was found in both groups.. Pycnogenol should be further investigated for kidney function.

Topics: Adjuvants, Immunologic; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Flow Velocity; Creatinine; Female; Flavonoids; Humans; Kidney; Male; Metabolic Syndrome; Middle Aged; Plant Extracts; Ramipril; Treatment Outcome; Ultrasonography, Doppler, Color

This study tested the hypothesis that phosphodiesterase 5 inhibition alone or in combination with ACE inhibition improves glucose homeostasis and fibrinolysis in individuals with metabolic syndrome.. Insulin sensitivity, beta-cell function, and fibrinolytic parameters were measured in 18 adults with metabolic syndrome on 4 separate days after a randomized, crossover, double-blind, 3-week treatment with placebo, ramipril (10 mg/day), tadalafil (10 mg o.d.), and ramipril plus tadalafil.. Ramipril decreased systolic and diastolic blood pressure, ACE activity, and angiotensin II and increased plasma renin activity. Ramipril did not affect insulin sensitivity or beta-cell function. In contrast, tadalafil improved beta-cell function (P = 0.01). This effect was observed in women (331.9 +/- 209.3 vs. 154.4 +/- 48.0 32 micro x mmol(-1) x l(-1), respectively, for tadalafil treatment vs. placebo; P = 0.01) but not in men. There was no effect of any treatment on fibrinolysis. CONCLUSIONS Phosphodiesterase 5 inhibition may represent a novel strategy for improving beta-cell function in metabolic syndrome.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Carbolines; Cross-Over Studies; Double-Blind Method; Female; Humans; Insulin-Secreting Cells; Male; Metabolic Syndrome; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Ramipril; Renin; Tadalafil

Plasma adiponectin levels are well associated with metabolic syndrome. However, the relationship between hypertension and plasma adiponectin levels is not clear. Also, there is not enough data about the effects of different antihypertensive regimens on plasma adiponectin levels.. Ninety-six hypertensive patients (48 male, 48 female) who fulfil the diagnostic criteria of metabolic syndrome were enrolled. Patients were treated for 3 months with metoprolol (n = 18, 100 mg/day), amlodipine (n = 20, 10 mg/day), doxazosin (n = 18, 4 mg/day), ramipril (n = 20, 5 mg/day) and valsartan (n = 20, 80 mg/day). Blood biochemistry and plasma adiponectin concentrations were measured both before and after the study. Insulin resistance was measured by homeostasis assessment index (HOMA).. Plasma adiponectin levels were correlated with the total cholesterol (r = -0.244, P = 0.017), triglyceride (r = -0.306, P = 0.002), high-density lipoprotein-cholesterol (r = 0.286, P = 0.005), body mass index (r = -374, P < 0.001), systolic (r = -502, P < 0.001) and diastolic blood pressures (r = -235, P = 0.021). The independent predictors of plasma adiponectin levels were HOMA (beta = -0.199, P = 0.02), body mass index (beta = -0.313, P < 0.001) and systolic blood pressures (beta = -0.483, P < 0.001). Ramipril and valsartan increased the plasma adiponectin levels significantly higher than the other regimens (P < 0.05 for both) while metoprolol did not make a significant effect.. According to the results, plasma adiponectin levels are associated with the arterial blood pressures, body fat content and the lipid parameters in hypertensive patients with metabolic syndrome. The effects of antihypertensive drugs on plasma adiponectin levels are parallel to their effects on blood pressures and insulin sensitivities. The different effects of several regimens on plasma adiponectin levels and insulin sensitivities may account for the diversity of the cardiovascular outcomes in patients with hypertension.

Topics: Adiponectin; Adrenergic beta-Antagonists; Adult; Amlodipine; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Body Mass Index; Calcium Channel Blockers; Doxazosin; Female; Humans; Hypertension; Insulin Resistance; Lipids; Male; Metabolic Syndrome; Metoprolol; Middle Aged; Predictive Value of Tests; Prospective Studies; Ramipril; Tetrazoles; Time Factors; Treatment Outcome; Valine; Valsartan

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Body Size; Cardiovascular Diseases; Humans; Life Style; Metabolic Syndrome; Obesity; Ramipril; Renin-Angiotensin System; Risk Assessment; Risk Factors; Telmisartan

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzimidazoles; Benzoates; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hypertension; Metabolic Syndrome; Ramipril; Randomized Controlled Trials as Topic; Risk Factors; Telmisartan; Time Factors

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Anti-Obesity Agents; Female; Humans; Hypoglycemic Agents; Lactones; Metabolic Syndrome; Orlistat; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Ramipril; Sulfonylurea Compounds

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diuretics; Drug Therapy, Combination; Enalapril; Glomerular Filtration Rate; Humans; Hypertension; Male; Metabolic Syndrome; Ramipril; Tetrazoles; Valine; Valsartan