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1.
Background
The “Mediterranean” diet and statin treatment have both independently been shown to improve survival and reduce the risk of cardiovascular events in patients with ischemic heart disease (IHD), but no studies have evaluated the effect of this combination on endothelial function. We therefore sought to evaluate the effect of the combination dietary intervention and lipid-lowering treatment on brachial vasoreactivity.Methods
A total of 131 consecutive patients with documented IHD and a serum cholesterol level ≥5 mmol/L (193 mg/dL) were randomized to receive Mediterranean dietary advice (n = 68) or no specific dietary advice (n = 63). Endothelial function was assessed at baseline and after 12 months with noninvasive ultrasound scanning vessel-wall tracking of brachial artery flow-mediated vasodilatation (FMD). All patients started statin treatment with Fluvastatin (40 mg once daily) at baseline.Results
A total of 115 patients completed the study. At baseline, FMD was 4.30% ± 4.89% in the control group versus 4.32% ± 6.15% in the intervention group (P = not significant). After 12 months of follow-up, FMD was significantly higher in the intervention group (control group 5.72% ± 4.87% vs intervention group 8.62% ± 6.60%, P < .01). This was accompanied by a larger intake of fatty fish and a significant decrease in triglyceride levels. In multivariate analysis, randomization status was a significant predictor of FMD after adjustment for classic cardiovascular risk factors and vessel size (P = .02; β = −2.66 [−4.91; −0.41]).Conclusion
Dietary intervention with the Mediterranean diet and statin treatment improve FMD in the brachial artery in patients with IHD and hypercholesterolemia to a greater degree than statin treatment alone. 相似文献2.
Papamichael C Karatzis E Karatzi K Aznaouridis K Papaioannou T Protogerou A Stamatelopoulos K Zampelas A Lekakis J Mavrikakis M 《American heart journal》2004,147(2):274
Background
Long-term smoking is believed to cause endothelial dysfunction via increased oxidative stress, whereas short-term smoking impairs vasodilatation through an as yet undefined mechanism. However, red wine and its constituents have a powerful antioxidant effect both in long-term and acute consumption. The aim of the current study was to investigate whether red wine, with or without alcohol, influences endothelial dysfunction induced by acute cigarette smoking.Methods
Sixteen healthy volunteers (8 males and 8 females) were recruited for a double-blind, crossover study, comprising 3 study days. Each subject smoked 1 cigarette, or smoked and drank 250 mL of red wine, or smoked and drank 250 mL of dealcoholized red wine. Flow-mediated dilatation (FMD) was measured after fasting and 15, 30, 60, and 90 minutes after each trial (smoke or smoke and drink either beverage).Results
Acute smoking of 1 cigarette caused a reduction in FMD (P < .001), which was statistically significant 15, 30, and 60 minutes after the inhalation of smoke compared to baseline levels (P < .001, P < .001, P = .043, respectively). However, simultaneous ingestion of either red wine or dealcoholized red wine with smoking did not lead to a change in FMD.Conclusions
Acute smoking caused a significant impairment in endothelial function. Simultaneous consumption of red wine or dealcoholized red wine with smoking decreased smoke's harmful effect on endothelium. 相似文献3.
Tamis-Holland JE Palazzo A Stebbins AL Slater JN Boland J Ellis SG Hochman JS;GUSTO II-B Angioplasty Substudy Investigators 《American heart journal》2004,147(1):133-139
Background
Direct angioplasty (PTCA) and thrombolytic therapy are the chief therapies for treating an ST-segment elevation myocardial infarction (MI).Objective
This study was designed to evaluate sex differences in the relative benefit of direct PTCA versus thrombolytic therapy among patients enrolled in the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes Angioplasty (GUSTO II-B PTCA) Substudy.Methods
Women and men presenting with an acute ST-segment elevation MI were randomized to receive either direct PTCA or accelerated tissue plasminogen activator (t-PA). Patients were then randomized to treatment with either heparin or bivalirudin. A gender analysis of outcome was performed.Results
Women were older than men (68.6 ± 11.5 vs 59.5 ± 12.0 years, P < .001) and were more likely to have diabetes (22.5% vs 13.5%, P <.0001) and hypertension (53.3% vs 34.8%, P = .001). After adjusting for differences in baseline variables, the odds ratio (OR) for reaching a 30-day clinical end point (death, nonfatal infarction, or nonfatal disabling stroke) was similar for women and men (1.35, 95% CI 0.88-2.08). The OR for reaching a clinical end point at 30 days for the PTCA-treated women compared with the t-PA-treated women was 0.685 (95% CI 0.36-1.32) and similar to the OR in men, 0.565 (95% CI 0.35-0.91), P for interaction = .535. Because women had a higher event rate than men, the absolute number of major events prevented when treating women with direct PTCA was higher than men (56 events/1000 women treated with PTCA vs 42 events per 1000 men treated with PTCA).Conclusions
Although the relative benefit of direct PTCA to t-PA for the treatment of an acute MI appears to be similar in women and men, women may derive a larger absolute benefit from direct PTCA. 相似文献4.
Impact of physical training and detraining on endothelium-dependent vasodilation in patients with recent acute myocardial infarction 总被引:1,自引:0,他引:1
Vona M Rossi A Capodaglio P Rizzo S Servi P De Marchi M Cobelli F 《American heart journal》2004,147(6):1039-1046
Background
There is evidence that aerobic exercise improves endothelial function in healthy subjects as well as in patients with chronic heart failure. However, it is unknown whether this effect occurs in patients with recent myocardial infarction (AMI).Methods
Fifty-two patients with a recent first uncomplicated AMI underwent endothelial function evaluation before and after 3 months of moderate aerobic exercise training. We measured brachial artery vasomotor reactivity using flow-mediated dilation (FMD), a cold pressor (CP) test, and sublingual nitroglycerin. Patients were randomized into 2 groups: 28 patients (G1) underwent training, while 24 patients (G2) served as controls. Brachial artery vasomotor reactivity was reassessed after 1 month of detraining (DT).Results
At baseline the FMD was 1.66% ± 4.11% in G1 and 2.04% ± 3.4% in G2 (P = NS) and vasoconstriction was evident after a CP test. The diameter reduction was −4.1% ± 3.89% in G1 and −4.39% ± 5.67% in G2 (P = NS). At follow-up the FMD had increased to 9.39% ± 4.87% in G1 (P < .01) and to 4.4% ± 3.9% in G2 (P < .01 vs G1). Vasoconstriction during a CP test was observed only in G2. Endothelium-independent vasodilation was unchanged in both groups. Effort tolerance increased by 32% in G1 patients (P < .01 versus G2) and was correlated with FMD change (R = 0.51, P < .01). After detraining the FMD was significantly reduced in G1 (P < .01) and a further vasoconstriction was evident after CP testing.Conclusions
Exercise training improves endothelium-dependent vasodilation in post-AMI patients. This improvement is associated with a significant increase in exercise tolerance. These benefits disappeared after detraining. 相似文献5.
Cutuli B De Lafontan B Vitali E Costa L Aristei C Marchal C Quetin P Fay R 《Critical reviews in oncology/hematology》2009,71(1):79-88
Introduction
Few breast conserving treatment (BCT) data include women older than 70.Material
910 women older than 70 were treated by BCT for stage I-II BC, with 670 pT1 (72.3%), 245 pT2 (26.4%) and 12 pTx (1.3%). Axillary nodal involvement occurred in 30.7% of cases. ER and PgR were positive in 85% and 71% of cases. Radiotherapy (RT) was delivered in all patients, tamoxifen in 55.8% and chemotherapy in 4.8%.Results
With a 65-month median follow-up, 28 (3%) local recurrences (LR) and 83 (9.1%) metastases occurred. Second cancer occurred in 51 (5.6%) patients. The 8-year overall survival (OS) and disease-specific survival (DSS) rates were 74% and 90%. The 8-year OS and DSS rates were 77% and 92% versus 65% and 84% in pT1 versus pT2 patients (p = 0.01). 676 patients were in complete remission (74.3%); 22 were evolutive (2.4%). 206 patients died (22.6%).Conclusion
Our study confirms the excellent local control in elderly patients treated by BCT with RT and identifies subgroups at high risk of distant relapse that should be treated more aggressively. 相似文献6.
Momesso DP Bussade I Epifanio MA Schettino CD Russo LA Kupfer R 《Diabetes research and clinical practice》2011,91(1):47-53
Aims
The present study evaluated the relationship between metabolic syndrome (MS), body fat composition and epicardial adipose tissue (EAT) in type 1 diabetes. Epicardial adipose tissue is a new independent marker of coronary artery disease (CAD).Methods
Forty-five type 1 diabetic women were evaluated (age 36 ± 9 years; body mass index 24.6 ± 4.4 kg/m2). Metabolic syndrome was defined by the World Health Organization criteria. Body fat composition and EAT were analyzed by dual-energy-X-ray absorptiometry and echocardiogram, respectively.Results
Twenty patients (45%) had MS. Patients with MS had greater android (central) fat deposition than patients without MS (41.9 ± 2.0% vs. 33.7 ± 1.8%, p = 0.004). Total body fat and gynoid (peripheric) fat distribution were similar between the groups. Mean EAT was higher in patients with MS (6.15 ± 0.34 mm vs. 4.96 ± 0.25 mm; p = 0.006) and EAT was positively correlated with android (central) fat distribution (r = 0.44; p = 0.002), however no correlation was found with gynoid (peripheric) fat distribution.Conclusions
There was a high incidence of MS in type 1 diabetes related to increased central adiposity, despite the absence of obesity. Metabolic syndrome and central obesity were associated with increased EAT. Thus, young non-obese type 1 diabetic women with central adiposity and/or MS may have increased EAT, what may predict CAD risk. 相似文献7.
Fabricatore AN Wadden TA Ebbeling CB Thomas JG Stallings VA Schwartz S Ludwig DS 《Diabetes research and clinical practice》2011,92(1):37-45
Aims
To compare the effects of lifestyle modification programs that prescribe low-glycemic load (GL) vs. low-fat diets in a randomized trial.Methods
Seventy-nine obese adults with type 2 diabetes received low-fat or low-GL dietary instruction, delivered in 40-week lifestyle modification programs with identical goals for calorie intake and physical activity. Changes in weight, HbA1c, and other metabolic parameters were compared at weeks 20 and 40.Results
Weight loss did not differ between groups at week 20 (low-fat: −5.7 ± 3.7%; low-GL: −6.7 ± 4.4%, p = .26) or week 40 (low-fat: −4.5 ± 7.5%; low-GL: −6.4 ± 8.2%, p = .28). Adjusting for changes in antidiabetic medications, subjects on the low-GL diet had larger reductions in HbA1c than those on the low-fat diet at week 20 (low-fat: −0.3 ± 0.6%; low-GL: −0.7 ± 0.6%, p = .01), and week 40 (low-fat: −0.1 ± 1.2%; low-GL: −0.8 ± 1.3%; p = .01). Groups did not differ significantly on any other metabolic outcomes (p ≥ .06).Conclusions
Results suggest that targeting GL, rather than dietary fat, in a low-calorie diet can significantly enhance the effect of weight loss on HbA1c in patients with type 2 diabetes. 相似文献8.
Stamatelopoulos KS Lekakis JP Poulakaki NA Papamichael CM Venetsanou K Aznaouridis K Protogerou AD Papaioannou TG Kumar S Stamatelopoulos SF 《American heart journal》2004,147(6):1093-1099
Background
Tamoxifen is a selective estrogen-receptor modulator shown to improve several cardiovascular risk factors in postmenopausal women with breast cancer. In animal studies tamoxifen inhibits the progression of atherosclerosis. Although the presence of a history with tamoxifen treatment is related to a lower intima-media thickness (IMT) of the common carotid artery, data from controlled follow-up studies are lacking to support this observation.Methods
We examined 14 postmenopausal women with early stage breast cancer with indication for tamoxifen treatment (20 mg/d) and 13 healthy postmenopausal women. Flow-mediated dilatation (FMD) of the brachial artery, combined carotid IMT, and aortic pulse wave were measured before and 6 months after treatment in the tamoxifen group and at the same times in the control group.Results
FMD and IMT were significantly increased and decreased, respectively, in the treatment group compared to the control group (FMD: +2.2% ± 0.9% vs +0.085% ± 1%, P = .012; IMT: −0.088 ± 0.03 mm vs +0.04 ± 0.03 mm, P = .018, mean ± standard error of the mean, treatment vs control group). These differences remained significant even when adjusted for age, duration of menopause, and cardiovascular risk factors. Low-density lipoprotein cholesterol was also significantly reduced after tamoxifen treatment.Conclusions
Tamoxifen treatment slows the progression of atherosclerosis in postmenopausal women with breast cancer as assessed by changes in carotid IMT. An improvement in endothelial function and blood lipid profile may be the reason for this beneficial effect. 相似文献9.
Background
This study sought to determine whether adding an anti-histaminic medication, loratidine, to anti-ischemic treatment would ameliorate or improve ischemic parameters induced by exercise stress test in patients who suffered an acute myocardial infarction.Methods
Twenty stable patients with acute inferior myocardial infarction who had a positive EST were randomly allocated into 2 groups, A and B. Patients in group A and B received a 10 mg loratidine tablet added daily to their anti-ischemic regimen for 7 days during the second and third week post-event, respectively. At the end of each period they underwent an exercise stress test (EST). Exercise parameters in each group were then compared before and after loratidine therapy.Results
Both groups showed improvements in exercise parameters after loratidine therapy compared to basal EST results. STmax ( group A: 1.9 ± 0.74 vs 0.9 ± 1.29 mm, P = .046; group B: 2.5 ± 0.71 vs 1.4 ± 1.17 mm, P = .041), STlead ( group A: 3.4 ± 1.08 vs 1.5 ± 2.12, P = .027; group B: 4.6 ± 1.71 vs 2.22 ± 2.25, P = .011), STtotal ( group A: 4.7 ± 2.18 vs 2.1 ± 3.11 mm, P = .024; group B: 7.9 ± 2.92 vs 3.33 ± 3.81 mm, P = .005).Conclusion
Our study revealed that loratidine, a histamine-1 receptor blocker, improves ischemic parameters of EST when given as additive therapy to a routine anti-ischemic regimen during the sub-acute phase of myocardial infarction. 相似文献10.
Gyöngyösi M Glogar D Weidinger F Domanovits H Laggner A Wojta J Zorn G Iordanova N Huber K 《American heart journal》2004,147(1):158-164
Background
The association between intravascular ultrasound (IVUS) signs of plaque instability and plasma levels of biomarkers was determined in patients with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI).Methods
Fifty-two patients underwent coronary angiography and IVUS 8 ± 5 hours after the onset of chest pain. IVUS analysis included plaque morphology, disruption, thrombi and eccentricity, lumen, external elastic membrane, and plaque plus media areas of culprit lesion and reference segments and arterial remodeling. Plasma levels of the thrombin activation system (thrombin-antithrombin complex [TAT], tissue factor pathway inhibitor [TFPI], and prothrombin fragments 1+2 [F1+2]) and plasmin activation system (tissue and urokinase-type plasminogen activator [t-PA and u-PA], plasminogen activator inhibitor-1 [PAI-1], and D-dimer) were measured with enzyme-linked immunosorbent assay kits before angiography.Results
Elevated levels of TAT (7.2 ± 6.0 μg/L), F1+2 (1.8 ± 1.0 nmol/L), TFPI (179.1 ± 131.0 ng/mL), PAI-1 (95.4 ± 54.6 ng/mL), t-PA (10.6 ± 8.8 ng/mL), and u-PA (2.6 ± 0.9 ng/mL) were found in patients with UA/NSTEMI. The serum levels of D-dimer (40.0 ± 39.5 ng/mL) remained in reference range. Expansive and constrictive remodeling were found in 18 (35%) and 12 (23%) patients, respectively. Expansive remodeling of the culprit lesion was associated with significantly higher plasma levels of PAI-1 (121.6 ± 55.0 vs 87.7 ± 61.5 and 77.4 ± 42.8 ng/ml, P = .039), and u-PA (3.0 ± 1.2 vs 2.2 ± 0.5 and 2.5 ± 0.7 ng/mL, P = .026) as compared with constrictive and neutral remodeling. Increased plasma levels of u-PA were associated with plaque rupture (3.0 ± 0.7 vs 2.5 ± 0.9 ng/mL, P = .062). Plasma levels of PAI-1 and u-PA correlated positively with plaque plus media (P = .0297 and P = .0093) and external elastic membrane areas (P = .010 and P = .0002).Conclusions
Elevated levels of biomarkers of plasmin activation system are associated with signs of plaque instability of culprit lesion in UA/NSTEMI and might therefore serve as non-invasive determinants of the population that is at high risk for subsequent adverse events. 相似文献11.
Caroline M. Apovian Richard M. Bergenstal Robert M. Cuddihy Yongming Qu Sheila Lenox Michelle S. Lewis Leonard C. Glass 《The American journal of medicine》2010,123(5):1717
Objective
To determine the effect of a lifestyle modification program plus exenatide versus lifestyle modification program plus placebo on weight loss in overweight or obese participants with type 2 diabetes treated with metformin and/or sulfonylurea.Methods
In this 24-week, multicenter, randomized, double-blind, placebo-controlled study, 194 patients participated in a lifestyle modification program, consisting of goals of 600 kcal/day deficit and physical activity of at least 2.5 hours/week. Participants were randomized to 5 μg exenatide twice daily injection + lifestyle modification program (n = 96) or placebo + lifestyle modification program (n = 98), and after 4 weeks increased their exenatide dose to 10 μg twice daily or volume equivalent of placebo.Results
Baseline characteristics: (mean ± standard deviation) age, 54.8 ± 9.5 years; weight, 95.5 ± 16.0 kg; hemoglobin A1c, 7.6 ± 0.8%. At 24 weeks (least squares mean ± standard error), treatments showed similar decreases in caloric intake (−378 ± 58 vs −295 ± 58 kcal/day, exenatide + lifestyle modification program vs placebo + lifestyle modification program, P = .27) and increases in exercise-derived energy expenditure. Exenatide + lifestyle modification program showed greater change in weight (−6.16 ± 0.54 kg vs −3.97 ± 0.52 kg, P = .003), hemoglobin A1c (−1.21 ± 0.09% vs −0.73 ± 0.09%, P <.0001), systolic (−9.44 ± 1.40 vs −1.97 ± 1.40 mm Hg, P <.001) and diastolic blood pressure (−2.22 ± 1.00 vs 0.47 ± 0.99 mm Hg, P = .04). Nausea was reported more for exenatide + lifestyle modification program than placebo + lifestyle modification program (44.8% vs 19.4%, respectively, P <.001), with no difference in withdrawal rates due to adverse events (4.2% vs 5.1%, respectively, P = 1.0) or rates of hypoglycemia.Conclusions
When combined with lifestyle modification, exenatide treatment led to significant weight loss, improved glycemic control, and decreased blood pressure compared with lifestyle modification alone in overweight or obese participants with type 2 diabetes on metformin and/or sulfonylurea treatment. 相似文献12.
Clarke B Howlett J Sapp J Andreou P Parkash R 《The Canadian journal of cardiology》2011,27(2):254-261
Background
Sudden death (SD) and non-sudden cardiac death are responsible for the majority of deaths in patients with heart failure. We sought to identify the influence of comorbid illness (Charlson Comorbidity Index [CCI]) on competing modes of death in heart failure.Methods
A retrospective analysis of 824 patients followed in a tertiary care heart failure clinic was performed. We analyzed the cumulative incidence of sudden and nonsudden death. Competing risk regression was used to examine the association between medical comorbidities and mode of death. The outcomes of interest were overall mortality, SD, SD and/or appropriate implantable cardioverter-defibrillator therapy (ICD), and non-SD.Results
Mean age of the study population was 64.1 ± 14.7 years, 68.6% were male, and mean ejection fraction was 32.8% ± 13.5%. Over a mean follow-up of 4.4 years, 229 patients (27.8%) died. SD accounted for 33 deaths (14.4%), whereas SD/appropriate ICD therapy occurred in 56 patients (24.5%). The risk of non-SD and total mortality increased (P < .0001) as the CCI increased, whereas the risk of SD decreased (P = .03). The cumulative incidence of SD, SD and/or ventricular tachycardia/fibrillation, and non-SD at 5 years was 5.6%, 9.1%, and 27.8%, respectively. In multivariate competing risk analysis, advancing age, New York Heart Association class, and a CCI >4 were significantly associated with non-SD.Conclusion
Patients with heart failure with significant comorbidities are much more likely to sustain non-SD. These findings may have implications in optimal selection of patients with heart failure for interventions such as prophylactic ICD therapy. 相似文献13.
Carmina E Orio F Palomba S Longo RA Cascella T Colao A Lombardi G Rini GB Lobo RA 《The American journal of medicine》2006,119(4):356-356.e6
Purpose
Polycystic ovary syndrome (PCOS) is an extremely prevalent disorder in which elevated blood markers of cardiovascular risk and altered endothelial function have been found. This study was designed to determine if abnormal carotid intima-media thickness (IMT) and brachial flow-mediated dilation (FMD) in young women with PCOS may be explained by insulin resistance and elevated adipocytokines.Methods
A prospective study in 50 young women with PCOS (age: 25.2 ± 1 years; body mass index [BMI]: 28.7 ± 0.8) and 50 matched ovulatory controls (age: 25.1 ± 0.7 years; BMI: 28.5 ± 0.5) was performed. Carotid IMT, brachial FMD, and blood for fasting glucose, insulin, leptin, adiponectin and resistin were measured.Results
PCOS, IMT was increased (P <.01), FMD was decreased (P <.01), fasting insulin was increased (P <.01), QUICKI (a marker of insulin resistance) was decreased (P <.01), and adiponectin was lower (P <.05), whereas leptin and resistin were not different compared with matched controls. Whereas BMI or waist/hip ratios did not correlate with IMT or FMD, insulin and QUICKI correlated positively and negatively with IMT (P <.01). There was a significant negative correlation between adiponectin and IMT (P <.05). These correlations were unchanged when adjusting for BMI and the correlation between IMT and adiponectin was unaffected by insulin resistance parameters.Conclusions
These data suggest that young women with PCOS have evidence for altered endothelial function. Adverse endothelial parameters were correlated with insulin resistance and lower adiponectin. Both insulin resistance and adiponectin appear to be important parameters. It is hypothesized that the type of fat distribution may influence these factors. © 2006 Elsevier Inc. All rights reserved. 相似文献14.
Stein JH Merwood MA Bellehumeur JL Aeschlimann SE Korcarz CE Underbakke GL Mays ME Sosman JM 《American heart journal》2004,147(4):713
Background
Although recommended as initial therapy for patients with dyslipidemia who are taking human immunodeficiency virus protease inhibitors (HIV PIs), the effects of pravastatin on lipoproteins and arterial reactivity have not been elucidated. The purpose of this study was to determine the effects of pravastatin on lipoprotein subfractions and endothelial function in patients with dyslipidemia who are receiving HIV PIs.Methods
This was a placebo-controlled, double-blind, crossover study comparing pravastatin (40 mg) to placebo in 20 patients who were taking HIV PIs. Lipoprotein subfractions were measured with nuclear magnetic resonance spectroscopic analysis. Flow-mediated vasodilation (FMD) of the brachial artery was evaluated with high-resolution ultrasound scanning.Results
At baseline, subjects had an increased concentration of low-density lipoprotein (LDL) particles (1756 ± 180 nmol/L), which tended to be small (19.9 ± 0.2 nm), a low concentration of large high-density lipoproteins (HDL; 0.94 ± 0.07 mmol/L), and an increased concentration of large very low-density lipoproteins (VLDL; 1.90 ± 0.58 mmol/L). FMD was impaired (4.5% ± 1.1%). Compared with placebo, pravastatin resulted in a 20.8% reduction in LDL particles (P = .030), a 26.7% reduction in small LDL (P = .100), and a 44.9% reduction in small VLDL (P = .023). Total and non-HDL cholesterol levels decreased by 18.3% (P <.001) and 21.7% (P <.001), respectively. FMD tended to increase in patients receiving pravastatin (0.7% ± 0.6%); however, the difference between treatment phases was not statistically significant (P = .080).Conclusions
This is the first double-blind, placebo-controlled study of the effects of statin therapy on lipids, lipoprotein subfractions, and endothelial function in patients taking HIV PIs. Pravastatin reduced concentrations of atherogenic lipoproteins, particularly those most associated with future coronary events. 相似文献15.
Rozenfeld PA Fritz M Blanco P Gonzalez P Rinaldi GJ 《The Canadian journal of cardiology》2011,27(3):339-345
Background
Fabry disease results from deficiency of alpha-galactosidase A (AGA), causing lysosomal storage of globotriaosylceramide in heart and other tissues. Since 2003, enzymatic replacement therapy with recombinant AGA agalsidase alfa (R-AGA) was approved for clinical use.Methods
We evaluated whether, in mice knocked out for AGA (FM, n = 31), the myocardium was altered with respect to the wild-type mice (WT, n = 25) and whether alterations were reversed in FM treated with intravenous R-AGA, 0.5 mg/kg every other week during 2 months (FM-AGA, n = 12).Results
Left ventricular (LV) contractility was depressed in FM, evaluated by LV ΔP/Δt (FM = 2832 ± 85 mm Hg/s, WT = 3179 ± 119 mm Hg/s; P < 0.05), papillary muscle contraction (FM = 39.8 ± 17.3 mg, WT = 67.5 ± 15.7 mg; P < 0.05), or shortening fraction measured by M-mode echocardiography (FM = 30% ± 6%, WT = 47% ± 2%; P < 0.05). LV stiffness (arrested hearts) decreased in FM (FM = 35.57 ± 3.5 mm Hg/20 μl; WT = 68.86 ± 6.12 mm Hg/20 μl; P < 0.05). FM myocytes showed augmented size, disorganized architecture, and intracytoplasmic vacuolization. Alterations reverted in FM-AGA: LV ΔP/Δt = 3281 ± 456 mm Hg/s and LV stiffness = 58.83 ± 2.15 mm Hg/20 μl, with normalization of myocyte architecture. No reversion was detected with AGA solvent.Conclusions
The FM represent a mild, early stage of the disease, since myocardial alterations are not prominent and appear in nonhypertrophic hearts. Reversion of alterations in the FM-AGA suggests that enzymatic replacement therapy can be useful when administered in early stages of this disease. 相似文献16.
Liran Hirsch Alon Shechter Micha S. Feinberg Nira Koren-MoragMichael Shechter 《International journal of cardiology》2011,151(3):342-347
Background
Adverse cardiovascular events (CVE) tend to peak during early morning post-waking hours. Our objective was to explore a possible correlation between early and late morning hours and flow-mediated dilation (FMD), and whether early morning FMD reduction contributes to a circadian pattern of cardiac and vascular vulnerability.Methods
Brachial FMD was prospectively assessed in 268 consecutive healthy subjects, 169 (63%) men, mean age 53 ± 11 years, without any concomitant medications. Following an overnight fast, FMD and endothelium-independent nitroglycerin-mediated vasodilation were assessed using high-resolution ultrasound. All subjects were followed up by phone every 6 months for combined CVE, which included all-cause mortality, myocardial infarction, hospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting and percutaneous coronary interventions.Results
The cohort was divided into Group A with FMD performed immediately post-waking, between 6:00 and 10:00 am [n = 151 (56%) subjects], and Group B after 10:00 am [n = 117 (46%) subjects]. Although both groups were comparable regarding baseline brachial artery diameter and the prevalence of risk factors, FMD was significantly lower in Group A compared with Group B subjects (10.4 ± 3.4% vs. 13.5 ± 3.5%, p = 0.007, respectively). In a mean follow-up of 45 ± 21 months, the composite CVEs were significantly more common in subjects with ≤(n = 128) vs. >(n = 140) the median FMD of 11.3% [18/128 (14.1%) vs. 1/140 (0.7%), p = 0.007, respectively]. Furthermore, FMD independently predicted long-term adverse CVE.Conclusions
FMD is blunted in early compared to late morning post-waking hours, and independently predicts long-term adverse CVE in healthy subjects with no apparent heart disease. 相似文献17.
Purpose
The paradox of obesity in patients with heart failure (HF) also has been observed in non-HF veteran patients. Veterans had to have met military fitness requirements at the time of their enlistment. Therefore, we assessed the relation of body mass index (BMI) to mortality in a clinical cohort of non-HF veterans, adjusting for fitness.Methods
After excluding HF patients (n = 580), the study population comprised 6876 consecutive patients (mean age 58 [±11] years) referred for exercise testing. Patients were classified by BMI category: normal weight (BMI 18.5-24.9 kg/m2), overweight (BMI 25.0-29.9 kg/m2), or obese (BMI ≥30.0 kg/m2). The association between BMI, fitness, other clinical variables, and all-cause mortality was assessed by Cox proportional hazards analysis.Results
During a mean (±SD) follow-up of 7.5 ± 4.5 years, a total of 1571 (23%) patients died. In a multivariate analysis including clinical, risk factor, and exercise test data, higher BMI was associated with better survival. Expressing the data by BMI category, obese patients were 22% less likely to die (relative risk [RR] = 0.78, 95% confidence interval [CI], 0.69-0.90, P <.001) than patients of normal weight. After further adjustment for cardiorespiratory fitness (CRF), this relationship strengthened such that mortality risk for the obese category was 35% lower (RR = 0.65, 95% CI, 0.57-0.76, P <.001), versus the normal weight category.Conclusions
As has been observed in HF patients, obesity was associated with a substantially lower mortality risk in a clinical population of non-HF veterans. Higher CRF and obesity in later life may account for an obesity paradox in this population. 相似文献18.
Fabrice Extramiana Pierre Maison-Blanche Fabio Badilini Anne Messali Isabelle Denjoy Antoine Leenhardt 《Journal of electrocardiology》2010,43(5):408
Background
Spontaneous type 1 electrocardiographic (ECG) is a risk factor for arrhythmic events in Brugada patients but the importance of the proportion of time with a type 1 ECG is unknown.Patients and Methods
Thirty-four Brugada patients (15 symptomatic) underwent a 24-hour 12-lead ECG recording. One-minute averaged waveforms displaying ST-segment elevation above 200 μV, with descending ST-segment and negative T-wave polarity on leads V1-V3 were considered as type 1 Brugada ECG. The burden was defined as the percentage of type 1 Brugada waveforms.Results
Type 1 ECG on lead V2 was more frequent in symptomatic patients (median 80.6% [15.7-96.7] vs 12.4% [0.0-69.7], P = .05). Patients with a permanent type 1 pattern on lead V2 were more likely to be symptomatic (5/6) than patients without type 1 ECG during a 24-hour period (2/9) (P < .05).Conclusion
Type 1 pattern is more prevalent across a 24-hour period in symptomatic Brugada patients. 相似文献19.
Background
Intermittent intravenous dobutamine therapy is used to treat patients with decompensated end-stage chronic heart failure (CHF), in whom the vascular endothelium is usually impaired. Although it has been suggested that modification or reversal of endothelial dysfunction may be of significant therapeutic benefit, the impact of short-term intermittent intravenous dobutamine therapy on flow-mediated dilation (FMD) in patients with severe decompensated end-stage chronic CHF has not been assessed.Methods
We prospectively assessed the impact of intermittent intravenous low-dose dobutamine therapy on endothelium-dependent brachial artery FMD and endothelium-independent nitroglycerin (NTG)-mediated vasodilation using high resolution ultrasound scanning in 20 consecutive male patients with severe CHF and ischemic cardiomyopathy (New York Heart Association functional class IV), at baseline and after 4 months, and compared them to 20 age- and sex-matched control subjects. The cardiac index (CI), stroke index (SI), and systemic vascular resistance (SVR) were assessed non-invasively with a thoracic electrical bioimpedance device before and after intravenous dobutamine therapy.Results
Intermittent intravenous dobutamine therapy resulted in significant improvement in post-intervention FMD compared with baseline (7.7% ± 2.4% vs 1.1% ± 2.6%; P = .001), a finding not evident in control subjects (1.3% ± 2.6% vs 1.2% ± 2.1%; P = .78). There was no significant effect of dobutamine treatment compared with control subjects on NTG-induced vasodilation (7.6% ± 5.5% vs 7.5% ± 8.8%, P = .979). Short-term dobutamine therapy also significantly improved SVR (1797 ± 926 dyne sec/cm5 vs 2172 ± 1133 dyne sec/cm5, P = .05), CI (2. 4± 0.6 L/min/m2 vs 1.9 ± 0.6 L/min/m2, P = .01), and SI (33.5 ± 11.7 mL/m2 vs 27.2 ± 12.4 mL/m2, P = .02).Conclusions
Short-term intermittent intravenous low-dose dobutamine therapy significantly improved vascular endothelial function, perhaps demonstrating an additional mechanism for improved SVR, CI, and SI in patients with severe CHF. 相似文献20.
Grossmann G Hoffmeister A Imhof A Giesler M Hombach V Spiess J 《American heart journal》2004,147(4):721-728