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Treatment with omega-3 polyunsaturated fatty acids does not improve endothelial function in patients with type 2 diabetes and very high cardiovascular risk: A randomized, double-blind, placebo-controlled study (Omega-FMD).
Siniarski, A, Haberka, M, Mostowik, M, Gołębiowska-Wiatrak, R, Poręba, M, Malinowski, KP, Gąsior, Z, Konduracka, E, Nessler, J, Gajos, G
Atherosclerosis. 2018;:148-155
Abstract
BACKGROUND AND AIMS Numerous recent studies conducted in different clinical settings have focused on the benefits of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in the prevention of cardiovascular diseases. There is limited evidence that patients with type 2 diabetes (T2D) and very high cardiovascular risk can also benefit from a high dose of n-3PUFAs, especially those on optimal medical therapy as recommended by the guidelines. The aim of the present study was to assess the impact of high-dose n-3 PUFA treatment on endothelial function in patients with T2D and established atherosclerotic cardiovascular disease (ASCVD). METHODS We conducted a prospective randomized double-blind, placebo-controlled, 2-center study, in which endothelial function was measured using flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD). Serum fatty acids composition was measured by gas chromatography. All measurements were done at baseline and after 3 months of treatment with PUFAs at a dose of 2 g/d (n = 36) or placebo (n = 38). RESULTS The majority of the study population was treated with optimal medical therapy. Despite significantly higher concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid in the n-3 PUFA group after 3-month treatment, we did not observe significant changes in endothelial function indices (FMD and NMD). However, in regression analysis, only baseline FMD was associated with EPA concentration before 3 months of n-3 PUFA treatment. CONCLUSIONS Three months of high-dose n-3 PUFA treatment in very high-risk patients with ASCVD and T2D did not improve the endothelial function indices.
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Differential effects of aliskiren/amlodipine combination and high-dose amlodipine monotherapy on endothelial function in elderly hypertensive patients.
Fukutomi, M, Hoshide, S, Mizuno, H, Kario, K
American journal of hypertension. 2014;(1):14-20
Abstract
BACKGROUND The aim of this study was to compare the effects of direct renin inhibitor, aliskiren, and amlodipine combination therapy with those of high-dose amlodipine monotherapy on endothelial function in elderly hypertensive patients. METHODS Participants included 105 patients (mean age 77 years) who had receive 5mg amlodipine for 4 weeks. Patients were allocated to the aliskiren/amlodipine group (AL/AM) or the high-dose amlodipine (AM) group. The AL/AM group received 150mg aliskiren in addition to 5mg amlodipine for 8 weeks; then the dose of aliskiren was doubled to 300mg for another 8 weeks. The AM group received 10mg amlodipine for 16 weeks. Of the 105 patients, 87 who underwent measurements of brachial flow-mediated vasodilation (FMD) and nitroglycerin-mediated vasodilation (NMD) before and after the study were included in the analysis. RESULTS Blood pressure-lowering effects were similar in the 2 groups. Plasma renin activity significantly decreased in the AL/AM group (P < 0.001) but increased in the AM group (P < 0.001). Improvement of FMD was found in the AL/AM group (2.6% to 3.7%, P = 0.001) but not in the AM group, while NMD did not change in either group. The changes in 24-hour systolic blood pressure (r = -0.60, P < 0.001) and diastolic blood pressure (r = -0.46, P = 0.004) were significantly correlated with improvement of FMD in the AL/AM group but not in the AM group. CONCLUSION Addition of aliskiren improved endothelial function in elderly hypertensive patients treated with amlodipine. CLINICAL TRIAL REGISTRY NUMBER UMIN000010163.
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Open-label, randomized, placebo-controlled evaluation of intracoronary adenosine or nitroprusside after thrombus aspiration during primary percutaneous coronary intervention for the prevention of microvascular obstruction in acute myocardial infarction: the REOPEN-AMI study (Intracoronary Nitroprusside Versus Adenosine in Acute Myocardial Infarction).
Niccoli, G, Rigattieri, S, De Vita, MR, Valgimigli, M, Corvo, P, Fabbiocchi, F, Romagnoli, E, De Caterina, AR, La Torre, G, Lo Schiavo, P, et al
JACC. Cardiovascular interventions. 2013;(6):580-9
Abstract
OBJECTIVES This study sought to assess whether intracoronary adenosine or nitroprusside following thrombus aspiration (TA) is superior to TA alone for the prevention of microvascular obstruction (MVO) in ST-segment elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI). BACKGROUND MVO, due to its multifactorial pathogenesis, still occurs after TA in a sizeable portion of patients. METHODS We performed a placebo-controlled, randomized, open-label, blind-examination, multicenter trial. A total of 240 STEMI patients with Thrombolysis In Myocardial Infarction (TIMI) flow grade 0/1 were randomly allocated 1:1:1 to receive adenosine (n = 80), nitroprusside (n = 80), or saline (n = 80) given distal to the occluded site after TA. The primary endpoint was the incidence of ST-segment resolution (STR) >70% on surface electrocardiogram at 90 min after PCI. Secondary endpoints were angiographic MVO incidence (TIMI flow grade ≤2 or 3 with a myocardial blush grade <2) and major adverse cardiac event (MACE) rate at 30 days as a composite of cardiac death, myocardial infarction, target lesion revascularization, and heart failure requiring hospitalization. RESULTS STR >70% occurred in in 71% of adenosine-treated patients, in 54% of nitroprusside-treated patients, and in 51% of saline-treated patients (p = 0.009 and p = 0.75, respectively, vs. saline). Angiographic MVO occurred in 18% of adenosine-treated patients, in 24% of nitroprusside-treated patients, and in 30% of saline-treated patients (p = 0.06 and p = 0.37, respectively, vs. saline). MACE occurred in 10%, 14%, and 20% of patients, respectively (p = 0.08 and p = 0.29 vs. saline). CONCLUSIONS In STEMI patients treated by PCI and TA, the additional intracoronary administration of adenosine, but not that of nitroprusside, results in a significant improvement of MVO, as assessed by STR.
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Effect of angiotensin receptor blockade on insulin sensitivity and endothelial function in abdominally obese hypertensive patients with impaired fasting glucose.
Perlstein, TS, Henry, RR, Mather, KJ, Rickels, MR, Abate, NI, Grundy, SM, Mai, Y, Albu, JB, Marks, JB, Pool, JL, et al
Clinical science (London, England : 1979). 2012;(4):193-202
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Abstract
AngII (angiotensin II) may contribute to cardiovascular risk in obesity via adverse effects on insulin sensitivity and endothelial function. In the present study, we examined the effects of ARB (angiotensin receptor blocker) therapy (losartan, 100 mg/day) on insulin sensitivity and endothelial function in 53 subjects with stage I hypertension, abdominal obesity and impaired fasting glucose. The study design was a randomized double-blinded parallel design placebo-controlled multi-centre trial of 8 weeks duration. We used the hyperinsulinaemic-euglycaemic clamp technique to measure insulin sensitivity (expressed as the 'M/I' value) and RH-PAT (reactive hyperaemia-peripheral arterial tonometry) to measure endothelial function. Additional measures included HOMA (homoeostasis model assessment)-B, an index of pancreatic β-cell function, and markers of inflammation [e.g. CRP (C-reactive protein)] and oxidative stress (e.g. F2-isoprostanes). ARB therapy did not alter insulin sensitivity [5.2 (2.7) pre-treatment and 4.6 (1.6) post-treatment] compared with placebo therapy [6.1 (2.9) pre-treatment and 5.3 (2.7) post-treatment; P value not significant], but did improve the HOMA-B compared with placebo therapy (P=0.05). ARB therapy also did not change endothelial function [RH-PAT, 2.15 (0.7) pre-treatment and 2.11 (0.7) post-treatment] compared with placebo therapy [RH-PAT, 1.81 (0.5) pre-treatment and 1.76 (0.7) post-treatment; P value not significant]. Markers of inflammation and oxidative stress were not significantly changed by ARB therapy. In conclusion, ARB therapy did not alter peripheral insulin sensitivity or endothelial function in this cohort of patients with essential hypertension, abdominal obesity and impaired fasting glucose, but did improve pancreatic β-cell function.
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Influence of rosiglitazone on flow-mediated dilation and other markers of cardiovascular risk in HIV-infected patients with lipoatrophy.
Kovacic, JC, Martin, A, Carey, D, Wand, H, Mallon, PW, Feneley, MP, Emery, S, Cooper, DA, Carr, A, ,
Antiviral therapy. 2005;(1):135-43
Abstract
BACKGROUND Antiretroviral therapy for HIV infection is commonly complicated by lipoatrophy, insulin resistance and dyslipidaemia. In HIV-uninfected adults with insulin resistance or type 2 diabetes, thiazolidinediones can lower blood pressure and improve both insulin sensitivity and endothelial function. This study sought to investigate the effects of rosiglitazone on endothelial function and other markers of cardiovascular risk in patients with HIV-related lipoatrophy. METHODS HIV-infected, lipoatrophic adults receiving antiretroviral therapy were randomized to receive either rosiglitazone 4 mg or matched placebo, twice daily. Percentage flow-mediated forearm arterial dilation (FMD%) was measured at weeks 0, 12, 24 and 48, together with other markers of vascular risk (blood pressure, lipids, glycaemic parameters, adiponectin and leptin). RESULTS Out of 64 enrolled adults, 44 (69%) attended all visits (23 rosiglitazone, 21 placebo). Relative to placebo, at week 48, rosiglitazone decreased systolic blood pressure (8 mmHg, P=0.03), insulin (3 microIU/ml, P=0.02), insulin resistance (P=0.03) and leptin (0.6 ng/ml, P=0.02), whilst adiponectin was increased (3.3 microg/lml, P<0.0001). However, rosiglitazone increased total cholesterol (49.1 mg/dl, P=0.001), low-density lipoprotein cholesterol (23.5 mg/dl, P=0.01) and triglycerides (146 mg/dl, P=0.06). Mean baseline FMD% for the entire cohort was moderately impaired (4.5%). Compared with baseline, mean on-treatment FMD% increased by 0.8% with rosiglitazone and decreased by 0.3% with placebo, (mean difference 1.1%, 95% CI -0.2 to 2.5, P=0.09). CONCLUSIONS Rosiglitazone has minimal effect on flow-mediated dilation in HIV-infected lipoatrophic adults. However, despite worsening of the lipid profile, the overall effect of rosiglitazone on the cardiovascular risk profile in these subjects was positive.
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Effect of rosuvastatin on plasma levels of asymmetric dimethylarginine in patients with hypercholesterolemia.
Lu, TM, Ding, YA, Leu, HB, Yin, WH, Sheu, WH, Chu, KM
The American journal of cardiology. 2004;(2):157-61
Abstract
Elevated plasma levels of asymmetric dimethylarginine (ADMA) have been associated with attenuated endothelium-dependent vasodilation in hypercholesterolemic patients. However, whether lowering of plasma cholesterol concentration by hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) can reduce plasma ADMA levels is still not clear. This study was a multicenter, randomized, double-blind, placebo-controlled design including 46 patients with elevated low-density lipoprotein cholesterol levels. Patients were randomized into 2 groups: rosuvastatin 10 mg/day and placebo for 6 weeks. Plasma levels of ADMA, 8-isoprostane (as a marker of oxidative stress), homocysteine, and high-sensitivity C-reactive protein were measured at baseline and 6 weeks later. Endothelial function assessed by flow-mediated vasodilation of the brachial artery was performed in 11 patients in the rosuvastatin group and in 12 in the placebo group. Baseline characteristics of both groups were similar, and the plasma ADMA levels were significantly correlated with 8-isoprostane (r = 0.388, p = 0.008). After 6 weeks of treatment, plasma ADMA levels were significantly reduced in the rosuvastatin group (from 0.60 +/- 0.19 to 0.49 +/- 0.10 micromol/L, p <0.001). Increases in flow-mediated vasodilation were positively correlated with reductions in plasma levels of ADMA (p = 0.017) and low-density lipoprotein cholesterol (p <0.001). Thus, our findings suggest that treatment with rosuvastatin in patients with hypercholesterolemia may lead to a significant reduction in plasma ADMA levels, which appear to be related to the improvement in endothelial function by rosuvastatin.
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A comparison of angiotensin-converting enzyme inhibitors, calcium antagonists, beta-blockers and diuretic agents on reactive hyperemia in patients with essential hypertension: a multicenter study.
Higashi, Y, Sasaki, S, Nakagawa, K, Ueda, T, Yoshimizu, A, Kurisu, S, Matsuura, H, Kajiyama, G, Oshima, T
Journal of the American College of Cardiology. 2000;(2):284-91
Abstract
OBJECTIVES The purpose of this study was to compare the effect of different antihypertensive agents, calcium antagonists, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers and diuretic agents on endothelial function. BACKGROUND Endothelial dysfunction is a component of essential hypertension, and various antihypertensive drugs may be able to restore normal function. METHODS Forearm blood flow (FBF) was measured in 296 patients with essential hypertension, including 46 untreated subjects using strain-gauge plethysmography during reactive hyperemia and after sublingual administration of nitroglycerin (NTG). Forty-seven normotensive subjects were similarly evaluated as control subjects. RESULTS The FBF during reactive hyperemia in the 296 hypertensive patients was significantly less than that in age-matched normotensive subjects. The increase in FBF after administration of sublingual NTG was similar in both groups. Systolic and diastolic blood pressures and forearm vascular resistance were greater in the untreated group than in the four treated groups and did not differ with respect to the antihypertensive agent used. The maximal FBF response from reactive hyperemia was significantly greater in the ACE inhibitor-treated group than in the group treated with calcium antagonists, beta-blockers, diuretic agents, or nothing (40.5 +/- 5.2 vs. 32.9 +/- 5.8, 34.0 +/- 5.6, 32.1 +/- 5.9, and 31.9 +/- 5.8 ml/min per 100 ml tissue, p < 0.05, respectively). Reactive hyperemia was similar in the calcium antagonist, beta-blocker, diuretic and untreated groups, and changes in FBF after sublingual NTG administration were similar in all groups. The infusion of NG-monomethyl-L-arginine, a nitric oxide (NO) synthase inhibitor, abolished the enhancement of reactive hyperemia in hypertensive patients treated with ACE inhibitors. CONCLUSIONS These findings suggest that ACE inhibitors augment reactive hyperemia, an index of endothelium-dependent vasorelaxation, in patients with essential hypertension. This augmentation may be due to increases in NO.