Serum concentration of lipoprotein(a) decreases on treatment with hydrosoluble coenzyme Q10 in patients with coronary artery disease: discovery of a new role

OBJECTIVE: To examine the effect of coenzyme Q10 supplementation on serum lipoprotein(a) in patients with acute coronary disease. STUDY DESIGN: Randomized double blind placebo controlled trial. SUBJECTS AND METHODS: Subjects with clinical diagnosis of acute myocardial infarction, unstable angina, angina pectoris (based on WHO criteria) with moderately raised lipoprotein(a) were randomized to either coenzyme Q10 as Q-Gel (60 mg twice daily) (coenzyme Q10 group, n=25) or placebo (placebo group, n=22) for a period of 28 days. RESULTS: Serum lipoprotein(a) showed significant reduction in the coenzyme Q10 group compared with the placebo group (31.0% vs 8.2% P<0.001) with a net reduction of 22.6% attributed to coenzyme Q10. HDL cholesterol showed a significant increase in the intervention group without affecting total cholesterol, LDL cholesterol, and blood glucose showed a significant reduction in the coenzyme Q10 group. Coenzyme Q10 supplementation was also associated with significant reductions in thiobarbituric acid reactive substances, malon/dialdehyde and diene conjugates, indicating an overall decrease in oxidative stress. CONCLUSION: Supplementation with hydrosoluble coenzyme Q10 (Q-Gel) decreases lipoprotein(a) concentration in patients with acute coronary disease.     

Natural history of the first non-Q wave myocardial infarction in the placebo arm of the Beta-Blocker Heart Attack Trial

Despite extensive investigation, the prognostic significance of the first non-Q wave acute myocardial infarction (AMI), when compared with Q wave AMI, remains controversial. The placebo arm of the Beta-Blocker Heart Attack Trial (BHAT) provides a unique opportunity to compare the long-term cardiac events in patients suffering from their first and uncomplicated Q wave or non-Q wave AMI. Of a total 3837 patients enrolled in the BHAT, 3375 were classifiable in terms of appearance or absence of Q waves during the prerandomization period. Of these, 1444 patients with their first AMI were randomized to placebo. Of these, 1186 experienced a Q wave AMI; the remaining 258 suffered a non-Q wave AMI. At 36 months of follow-up, the mortality was 8.4% in the Q wave AMI group and 7.4% in the non-Q wave AMI group. Sudden death was 5.4% in the Q wave AMI group and 4.7% in the non-Q wave AMI group. The reinfarction rate was 5.5% in the Q wave AMI patients and 7.4% in the non-Q wave AMI patients. More patients developed angina (44.6%) in the non-Q wave AMI group compared with 35.2% in the Q wave AMI group. Despite similar long-term cardiac event rates within the two groups, the 1-year mortality rate for patients with Q wave AMI appeared higher than in the non-Q wave AMI group, 5.2% versus 3.1%, respectively. In contrast, the rate of reinfarction appeared higher at the 12-month follow-up period in the non-Q wave AMI group, 4.7% versus 3.4%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)c     

Randomized, Double-Blind, Placebo-Controlled Trial of Fish Oil and Mustard Oil in Patients with Suspected Acute Myocardial Infarction: The Indian Experiment of Infarct Survival—4

In a randomized, placebo-controlled trial, the effects of treatment with fish oil (eicosapentaenoic acid, 1.08 g/day) and mustard oil (alpha-linolenic acid, 2.9 g/day) were compared for 1 year in the management of 122 patients (fish oil, group A), 120 patients (mustard oil, group B), and 118 patients (placebo, group C) with suspected acute myocardial infarction (AMI). Treatments were administered about (mean) 18 hours after the symptoms of AMI in all three groups. The extent of cardiac disease, rise in cardiac enzymes, and lipid peroxides were comparable among the groups at entry into the study. After 1 year total cardiac events were significantly less in the fish oil and mustard oil groups compared with the placebo group (24.5% and 28% vs. 34.7%, p > 0.01). Nonfatal infarctions were also significantly less in the fish oil and mustard oil groups compared with the placebo group (13.0% and 15.0% vs. 25.4%, p > 0.05). Total cardiac deaths showed no significant reduction in the mustard oil group; however, the fish oil group had significantly less cardiac deaths compared with the placebo group (11.4% vs. 22.0%, p > 0.05). Apart from the decrease in the cardiac event rate, the fish oil and mustard oil groups also showed a significant reduction in total cardiac arrhythmias, left ventricular enlargement, and angina pectoris compared with the placebo group. Reductions in blood lipoproteins in the two intervention groups were modest and do not appear to be the cause of the benefit in the two groups. Diene conjugates showed a significant reduction in the fish oil and mustard oil groups, indicating that a part of the benefit may be caused by the reduction in oxidative stress. The findings of this study suggest that fish oil and mustard oil, possibly due to the presence of n-3 fatty acids, may provide rapid protective effects in patients with AMI. However, a large study is necessary to confirm this suggestion.     

Comparison of urinary biopyrrin levels in acute myocardial infarction (after reperfusion therapy) versus stable angina pectoris and their usefulness in predicting subsequent cardiac events

We examined the relation between oxidative stress and cardiac events in patients with acute myocardial infarction (AMI). There is now increasing evidence that reactive oxygen species cause reperfusion injury to the previously ischemic myocardium after reperfusion. We measured urinary biopyrrin/creatinine levels, an oxidative stress marker, in 41 patients with AMI, 34 patients with stable angina pectoris (SAP), and 29 control subjects. In the patients with AMI, urine samples were taken before, at 4 and 24 hours, and at 1 and 2 weeks after reperfusion therapy. Of these 41 patients with AMI, 38 received reperfusion therapy, and the urinary biopyrrin/creatinine levels (micromol/g.creatinine) before reperfusion were significantly higher than those of the other 2 groups (AMI 4.24 +/- 0.49, SAP 2.45 +/- 0.15, control subjects 2.31 +/- 0.16; p = 0.0003 vs AMI). The onset of reperfusion significantly increased the levels of urinary biopyrrins/creatinine, and this time course was mapped out, peaking at 4 hours (8.21 +/- 0.96 vs 4.24 +/- 0.49 before, p = 0.0001), and decreasing to control levels between 24 hours and 7 days. The peak levels of urinary biopyrrins/creatinine were higher in the positive cardiac event group than in the negative cardiac event group (11.89 +/- 1.77 vs 7.57 +/- 1.00 micromol/g.creatinine, p = 0.029). These findings add further evidence that oxidative stress contributes to the complications of reperfusion injury, and suggest that urinary assessment of biopyrrins may be useful in predicting subsequent cardiac events after reperfusion in AMI.     

Lack of effect of coenzyme Q on left ventricular function in patients with congestive heart failure.

OBJECTIVES: This study evaluated the effects of oral therapy with coenzyme Q on echocardiographic and hemodynamic indexes of left ventricular function and on quality of life in patients with chronic left ventricular dysfunction. BACKGROUND: Coenzyme Q is a coenzyme for oxidative phosphorylation and an antioxidant and free radical scavenger. It has been claimed to improve symptoms, quality of life, left ventricular ejection fraction and prognosis in patients with cardiac failure. METHODS: Thirty patients with ischemic or idiopathic dilated cardiomyopathy and chronic left ventricular dysfunction (ejection fraction 26 +/- 6%) were randomized to a double-blind crossover trial of oral coenzyme Q versus placebo, each for 3 months. Right heart pressures, cardiac output and echocardiographic left ventricular volumes were measured at baseline and after each treatment phase, and quality of life was assessed using the Minnesota "Living With Heart Failure" questionnaire. It was calculated that to demonstrate an increase in left ventricular ejection fraction from 25% to 30% with a standard deviation of 5% using 95% confidence intervals with a power of 80% we would require 17 patients. RESULTS: Twenty-seven completed both treatment phases. There was no significant difference in left ventricular ejection fraction, cardiac volumes or hemodynamic and quality of life indices after treatment with coenzyme Q or placebo, although plasma coenzyme Q levels increased from 903 +/- 345 nmol/l(-1) to 2,029 +/- 856 nmol/l(-1). CONCLUSIONS: In patients with left ventricular dysfunction, treatment for three months with oral coenzyme Q failed to improve resting left ventricular systolic function or quality of life despite an increase in plasma levels of coenzyme Q to more than twice basal values.     

Cardiovascular mortality and N-terminal-proBNP reduced after combined selenium and coenzyme Q10 supplementation: A 5-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens

Background

Selenium and coenzyme Q10 are essential for the cell. Low cardiac contents of selenium and coenzyme Q10 have been shown in patients with cardiomyopathy, but inconsistent results are published on the effect of supplementation of the two components separately. A vital relationship exists between the two substances to obtain optimal function of the cell. However, reports on combined supplements are lacking.

Methods

A 5-year prospective randomized double-blind placebo-controlled trial among Swedish citizens aged 70 to 88 was performed in 443 participants given combined supplementation of selenium and coenzyme Q10 or a placebo. Clinical examinations, echocardiography and biomarker measurements were performed. Participants were monitored every 6th month throughout the intervention.The cardiac biomarker N-terminal proBNP (NT-proBNP) and echocardiographic changes were monitored and mortalities were registered. End-points of mortality were evaluated by Kaplan–Meier plots and Cox proportional hazard ratios were adjusted for potential confounding factors. Intention-to-treat and per-protocol analyses were applied.

Results

During a follow up time of 5.2 years a significant reduction of cardiovascular mortality was found in the active treatment group vs. the placebo group (5.9% vs. 12.6%; P = 0.015). NT-proBNP levels were significantly lower in the active group compared with the placebo group (mean values: 214 ng/L vs. 302 ng/L at 48 months; P = 0.014). In echocardiography a significant better cardiac function score was found in the active supplementation compared to the placebo group (P = 0.03).

Conclusion

Long-term supplementation of selenium/coenzyme Q10 reduces cardiovascular mortality. The positive effects could also be seen in NT-proBNP levels and on echocardiography.     

Effect of coenzyme Q(10) supplementation on simvastatin-induced myalgia

Myalgia is the most frequently reported adverse side effect associated with statin therapy and often necessitates reduction in dose, or the cessation of therapy, compromising cardiovascular risk management. One postulated mechanism for statin-related myalgia is mitochondrial dysfunction through the depletion of coenzyme Q(10), a key component of the mitochondrial electron transport chain. This pilot study evaluated the effect of coenzyme Q(10) supplementation on statin tolerance and myalgia in patients with previous statin-related myalgia. Forty-four patients were randomized to coenzyme Q(10) (200 mg/day) or placebo for 12 weeks in combination with upward dose titration of simvastatin from 10 mg/day, doubling every 4 weeks if tolerated to a maximum of 40 mg/day. Patients experiencing significant myalgia reduced their statin dose or discontinued treatment. Myalgia was assessed using a visual analogue scale. There was no difference between combined therapy and statin alone in the myalgia score change (median 6.0 [interquartile range 2.1 to 8.8] vs 2.3 [0 to 12.8], p = 0.63), in the number of patients tolerating simvastatin 40 mg/day (16 of 22 [73%] with coenzyme Q(10) vs 13 of 22 [59%] with placebo, p = 0.34), or in the number of patients remaining on therapy (16 of 22 [73%] with coenzyme Q(10) vs 18 of 22 [82%] with placebo, p = 0.47). In conclusion, coenzyme Q(10) supplementation did not improve statin tolerance or myalgia, although further studies are warranted.     

急性心肌梗死并发心脏破裂危险因素分析

目的分析急性心肌梗死(AMI)并发心脏破裂的临床特点、危险因素及预后,并探讨临床防治措施。方法回顾性收集AMI患者1561例,其中发生心脏破裂患者21例为心脏破裂组,随机选取未发生心脏破裂的AMI患者105例为对照组,采集2组患者临床资料及治疗方案,分析AMI并发心脏破裂的危险因素。结果与对照组比较,心脏破裂组年龄、入院心率、女性、肌钙蛋白、N末端B型钠尿肽前体、尿素明显升高(P<0.05,P<0.01),急诊PCI、血红蛋白、红细胞计数、使用β受体阻滞剂及血管紧张素转换酶抑制剂(ACEI)/血管紧张素受体阻滞剂(ARB)比例明显降低,差异有统计学意义[42.86%vs 72.38%,P=0.011;(119.33±19.37)g/L vs (139.29±17.65)g/L,P=0.001;(4.13±0.62)×10^12/L vs (4.60±0.69)×10^12/L,P=0.010;47.62%vs 73.33%,P=0.020;23.81%vs 52.38%,P=0.017]。结论女性、高龄、再灌注时间延迟、入院心率快、高NT-ProBNP、高肌钙蛋白、低血红蛋白、低红细胞计数是AMI患者心脏破裂的危险因素,早期的再灌注治疗、ACEI/ARB、β受体阻滞剂的使用是预防AMI后发生心脏破裂的重要措施。     

Nuclear magnetic resonance and radionuclide angiographic assessment of acute myocardial infarction in a randomized trial of intravenous streptokinase

Sixty-six patients presenting with their first evolving transmural acute myocardial infarction (AMI) were randomized to receive either streptokinase (n = 41) or placebo therapies (n = 25) within 6 hours of the onset of chest pain. These patients then underwent supine rest, exercise and after-nitroglycerin radionuclide angiography 3 weeks after AMI. Nuclear magnetic resonance (NMR) imaging was performed at 3 weeks as a more direct estimate of AMI size. Although peak creatine kinase values were comparably elevated between groups (2,367 +/- 1,486 IU/liter for streptokinase vs 2,637 +/- 1,305 IU/liter for placebo), there was a significant reduction in NMR-measured AMI size in the streptokinase group (3 +/- 2% of left ventricular volume vs 10 +/- 4% in the placebo group, p less than 0.05). This occurred despite comparable resting (54 +/- 11 vs 47 +/- 10% and exercise (53 +/- 12 vs 49 +/- 11%) global ejection fractions. However, following nitroglycerin, there was an improvement in global ejection fraction in the streptokinase-treated group that was not observed with placebo (61 +/- 13 vs 48 +/- 10%, p less than 0.05). A similar pattern was also observed with regional functional analysis. Thus, streptokinase therapy leads to a significant reduction in NMR-measured AMI size and to a greater degree of reversible left ventricular dysfunction.     

Effect of coenzyme Q10 on experimental atherosclerosis and chemical composition and quality of atheroma in rabbits

The effects of the administration of coenzyme Q10 (3 mg/kg per day) (group A, n=10) and placebo (aluminum hydroxide, 3 mg/kg per day) (group B, n=10) were compared over 24 weeks in a randomized, single-blind, controlled trial. There were two groups of rabbits receiving a trans fatty acid (TFA)-rich diet (5-8 g/day) for 36 weeks. Oxidized rabbit chow with vitamin C plus ferric chloride was administered for 4 weeks in all rabbits. Intervention with coenzyme Q10 after feeding of TFA-rich diet was associated with a significant decline in thiobarbituric acid reactive substances (TBARS), diene conjugates and malondialdehyde, and an increase in plasma levels of vitamin E in the coenzyme Q group compared to placebo group. These changes, which were indicators of a decrease in oxidative damage, were independent of lipid lowering. The aortic and coronary artery plaque sizes, coronary atherosclerosis index, aortic and coronary atherosclerosis scores were significantly lower in the coenzyme Q group than placebo group. Aortic and coronary plaque frequencies, as well as frequencies of ulceration, thrombosis or hemorrhage, and cracks and fissures, were also significantly lower in the coenzyme Q group, indicating a better quality of atheroma compared to those in the control group. Aortic cholesterol, triglycerides and sudanophilia were significantly lower and vitamin E significantly higher in the coenzyme Q group in comparison to the placebo group indicating that coenzyme Q10 can have beneficial effect on the chemical composition of atheroma. The findings suggest that antioxidant therapy with coenzyme Q10 may be used as an adjunct to lipid lowering for additional beneficial effects related to chemical composition and quality of atheroma independent of hypolipidemic agents.     

Frequency and significance of late evolution of Q waves in patients with initial non-Q-wave acute myocardial infarction. Diltiazem Reinfarction Study Group

Serial 12-lead electrocardiogram and plasma creatine kinase (CK)-MB values from 544 patients with confirmed non-Q-wave acute myocardial infarction (AMI) were analyzed to define the rate of progression of non-Q-wave AMI to Q-wave AMI and to examine its relation to CK-MB evidence of extension. The baseline electrocardiogram was obtained 50 +/- 10 hours after AMI and compared with subsequent electrocardiograms at 48 and 72 hours after baseline record and at discharge. Plasma CK-MB was assayed every 12 hours after baseline. A total of 76 patients (14%) progressed to Q-wave AMI. Compared to the 468 patients who retained non-Q-wave AMI, those patients who evolved Q-wave AMI were more likely to exhibit ST elevation greater than or equal to 1.0 mm in greater than or equal to 2 infarct-related leads (49 vs 32%, p less than 0.005), higher peak CK values with the index AMI (754 +/- 625 vs 611 +/- 604 IU; p = 0.0018) and a greater incidence of CK-MB-confirmed extensions (18.5 vs 5.5%, p less than 0.0001). For those patients progressing to Q-wave AMI within 48 hours of baseline electrocardiogram, CK-MB extension occurred in 9.5% (4 of 42) versus 29.4% (10 of 34) of those who progressed after 48 hours (p = 0.0262). A distinct minority (14%) of patients with non-Q-wave AMI will develop Q waves before discharge. The progression to Q-wave AMI after initial non-Q-wave AMI appears to involve 2 different mechanisms: temporal lag in the electrocardiogram, and actual extension by quantitative CK-MB criteria.     

Recurrent ischemia after acute myocardial infarction: clinical profile and significance of electrocardiographic ST changes during the attacks]

This study investigated the clinical characteristics of acute myocardial infarction (AMI) complicated by recurrent ischemia, especially relating to the electrocardiographic ST changes during the attacks. Fifty-six patients with AMI were complicated by recurrent ischemia (ischemia group), and 238 were not (non-ischemia group). The ischemia group was preceded by prior episodes of angina or myocardial infarction in 88%, as compared with 65% in the non-ischemia group (p less than 0.05). There were non Q wave infarction in 45% of the ischemia group, and 24% of the non-ischemia group (p less than 0.05). The overall in-hospital mortality rate was similar in the ischemia group (13%) and in the non-ischemia group (17%), although the causes were predominantly pump failure in the former and cardiac rupture in the latter. ST segment elevation occurred in 29 patients and ST depression occurred in 26 patients of the ischemia group during the attacks. Multivessel coronary arterial lesions were more frequently present in the latter subgroup than the former (38% vs 79%, p less than 0.05). The in-hospital cardiac deaths were also more frequently noted in the latter subgroup. Recurrent ischemia after AMI with concomitant electrocardiographic ST depression is a high risk subgroup, and, therefore, aggressive revascularization procedures may be indicated in such cases if suitable.     

Acute myocardial infarction in young adults. Analysis of risk factors and coronary angiography

Eighty patients aged under forty, survivors of an episode of acute myocardial infarction (AMI), were studied by means of angiography. Thirty five had anterior wall infarction, 26 diaphragmatic wall, 9 lateral side and 10 non Q AMI. Tobacco addiction (92% vs 71.9%) and hyperlipemia (34% vs 18.8% were higher (p less than 0.01) that in the total AMI population. They presented an average ejection fraction of 0.56 +/- 0.15 and only in three patients was under 0.30. One, 2 and 3 vessels disease respectively of 43%, 22% and 16%, similar to another series published. A 19% of patients with normal angiography coronaries was seen significantly higher (p less than 0.01) than the observed in AMI in older patients. In conclusion in spite of the good prognosis of this group of patients, is necessary to insist in primary preventive campaigns, mainly against tobacco addiction and hyperlipemia, in order to reduce the frequency of AMI in young people.     

Effect of hydrosoluble coenzyme Q10 on blood pressures and insulin resistance in hypertensive patients with coronary artery disease

In a randomised, double-blind trial among patients receiving antihypertensive medication, the effects of the oral treatment with coenzyme Q10 (60 mg twice daily) were compared for 8 weeks in 30 (coenzyme Q10: group A) and 29 (B vitamin complex: group B) patients known to have essential hypertension and presenting with coronary artery disease (CAD). After 8 weeks of follow-up, the following indices were reduced in the coenzyme Q10 group: systolic and diastolic blood pressure, fasting and 2-h plasma insulin, glucose, triglycerides, lipid peroxides, malondialdehyde and diene conjugates. The following indices were increased: HDL-cholesterol, vitamins A, C, E and beta-carotene (all changes P<0.05). The only changes in the group taking the B vitamin complex were increases in vitamin C and beta-carotene (P<0.05). These findings indicate that treatment with coenzyme Q10 decreases blood pressure possibly by decreasing oxidative stress and insulin response in patients with known hypertension receiving conventional antihypertensive drugs.     

丹参注射液降低血管内皮细胞氧化应激损伤，对心肌梗死患者心肌功能的保护效果

目的:探讨丹参注射液降低血管内皮细胞氧化应激损伤,对急性心肌梗死(AMI)患者心肌功能的保护效果。方法:120例行经皮冠脉介入治疗(PCI)的AMI患者被随机均分为常规治疗组和丹参组(在常规治疗组基础上加用丹参注射液),两组均治疗14d。治疗前后检测比较两组外周血超氧化物歧化酶(SOD)、丙二醛(MDA)、一氧化氮(NO)、诱导型一氧化氮合酶(iNOS)、高敏心肌肌钙蛋白T (hscTnT)、肌酸激酶同工酶(CK-MB)及LVEF、心肌梗死面积,并随访观察两组术后3个月内主要不良心血管事件(MACE)和用药不良反应发生情况。结果:与常规治疗组治疗后比较,丹参组外周血SOD水平[(20.76±1.58)U/ml比(25.81±1.45)U/ml]、LVEF [(52.44±6.74)%比(57.57±4.39)%]显著升高,外周血MDA [(8.84±0.47)pg/ml比(6.74±0.56)pg/ml]、NO [(19.11±1.58)μmol/L比(15.34±1.74)μmol/L]、iNOS [(80.37±1.65)U/ml比(73.28±2.76)U/ml]、hscTnT [(38.25±4.24)ng/ml比(26.85±3.23)ng/ml]、CK-MB [(63.26±5.64)U/L比(32.68±4.49)U/L]水平以及心肌梗死面积[(19.42±4.33)mm2比(13.58±3.25)mm2]均显著降低,P均=0.001。术后随访3个月,丹参组MACE发生率显著低于常规治疗组(20.00%比41.67%),P=0.010。两组治疗过程中,均无严重药物不良反应发生。结论:丹参注射液能够显著减轻AMI患者PCI术后血管内皮细胞氧化应激损伤,保护缺血再灌注心肌功能,改善预后,值得推广。     

乌司他丁对老年急性心肌梗死急诊溶栓患者心肌有保护作用

目的:探讨乌司他丁对老年急性心肌梗死（AMI）急诊溶栓患者心肌酶谱、氧化应激、炎性反应、心功能及近期预后的影响。方法：根据非随机临床同期对照研究及患者自愿原则将150例老年AMI患者分为对照组（急诊溶栓治疗）和观察组（在对照组基础上联合乌司他丁治疗）各75例，比较2组治疗前、后心肌酶谱、氧化应激、炎性反应、心功能指标及治疗后30d内主要不良心血管事件（MACE）发生率。结果：治疗前2组心肌肌钙蛋白I（cTnI）、肌酸激酶同工酶（CK-MB）、还原型谷胱甘肽（GSH）、超氧化物歧化酶（SOD）、丙二醛（MDA）、白介素（IL）-6、超敏C反应蛋白（hsCRP）、左心室舒张末期内径（LVEDD）、左室射血分数（LVEF）比较，差异无统计学意义（P均>0.05）；治疗后48、72h观察组hs-cTnT、CK-MB、MDA、IL-6、hsCRP水平和LVEDD较对照组低（P均＜0.05），GSH、SOD水平和LVEF较对照组高（P均＜0.05）。观察组治疗后30d内MACE发生率较对照组低（P＜0.05）。结论：乌司他丁对老年AMI患者再灌注心肌有保护作用，可明显降低治疗后30d内MACE发生率。     

Survival analysis within one year of first acute myocardial infarction: comparison between non-Q and Q wave myocardial infarction.

BACKGROUND: Non-Q wave Myocardial Infarction (non-Q AMI) is related pathophysiologically to Q wave AMI, as each represents different stages of plaque rupture and thrombosis. Post-hospital re-infarction and recurrent angina are more frequent in non-Q AMI than in Q wave AMI, offsetting the higher early risk with Q wave AMI, with one-year survival rates similar in the two types of MI. OBJECTIVES: 1--Evaluation of early (< or = 28 days) and one-year total mortality from first non-Q AMI in comparison to QMI. 2--Analysis of recurrent acute ischaemic events (non-fatal reinfarction and unstable angina) in both types of MI in the same periods of time. POPULATION AND METHODS: A retrospective study of 1146 patients, mean age 65 +/- 13 years, 65% male, admitted at CCU with a first MI, from January 1988 to December 1997 (minimum follow-up period of one year, mean follow-up 42 +/- 37 months). We compared the baseline demographics and clinical characteristics (coronary risk factors, previous angina, MI evolution, recurrent cardiac events, 28 day mortality and one year mortality) of patients with non-Q AMI (NQ group = 239) and Q wave AMI (Q group = 907). RESULTS: The NQ group patients were significantly older (mean age: 67 +/- 12.6 vs 65 +/- 12.5 years; p < 0.05), included fewer smokers (29% vs 43%; p < 0.001) and were more symptomatic before the index infarction (stable angina: 40% vs 30%; p < 0.05; unstable angina: 16% vs 6%; p < 0.001), when compared to the Q group patients. There were no significant differences in MI evolution, in Killip-Kimbal class > or = 2, recurrent angina and in-hospital mortality (Q-12% vs NQ-9%; ns), although there was a higher combined risk of arrhythmias and AV conduction disturbances in patients with QMI (Q-34% vs NQ-26%; p < 0.05). The combined risk of unstable angina and reinfarction at one year was significantly higher in group NQ (NQ-13% vs Q-8.1%; p < 0.05). The NQ group showed no significant difference in 28 day total mortality (NQ-14% vs Q-17%; ns) or at one year follow-up (NQ-24% vs Q-26%; ns) when compared to the Q group. CONCLUSION: 1--Despite a lower severity of non-Q AMI in the acute phase, 28 day and one year total mortality were similar in the two groups. 2--Patients with non-Q AMI showed a higher incidence of recurrent ischemic events at one year follow-up.     

Targeting oxidative stress in surgery: effects of ageing and therapy

In the current era cardiac surgeons are being called upon to operate upon older, sicker patients. The effect is to augment oxidative stress and increase the rate of post-operative complications and ultimately mortality. We have developed antioxidant-based pre-treatment regimes initially based on coenzyme Q(10). A randomised trial of coenzyme Q(10) in elective cardiac surgery patients demonstrated augmented plasma and cardiac mitochondrial membrane coenzyme Q(10) content, improved mitochondrial respiration and increased myocardial tolerance of oxidative stress. The addition of omega-3 polyunsaturated fatty acids, alpha-lipoic acid, selenium and magnesium orotate in a second clinical trial, improved post-operative recovery with demonstrable reductions in myocardial damage, rate of atrial fibrillation and length of hospital stay. Finally we performed a pilot study of this combined metabolic therapy regimen to which we added preoperative physical exercise and mental stress reduction with indications of further improvements in post-operative recovery. We conclude that simultaneously targeting a number of key deficiencies with a metabolic formulation prior to surgery results in peri- and post-operative clinical and economic benefits.     

Long-term efficacy of edaravone in patients with acute myocardial infarction.

BACKGROUND: The effect of edaravone, a free radical scavenger, on long-term prognosis and its efficacy with regards to scavenging injurious free radicals in patients with acute myocardial infarction (AMI) was examined. METHODS AND RESULTS: One hundred and one initial AMI patients were randomly assigned to receive 30 mg edaravone (n = 50) or a placebo (n = 51) intravenously just before reperfusion. The infarct size, using serum biomarkers and Q-wave formations, and the incidence of reperfusion arrhythmia between the groups were compared. Cardiovascular event-free curves were estimated by using the Kaplan - Meier method. In addition, the serum thioredoxin levels, an oxidative stress marker, to assess the antioxidant effect of edaravone was determined. In all cases, successful reperfusion was obtained within 6 h after the onset of symptoms. Infarct size and reperfusion arrhythmia were significantly attenuated in the edaravone group compared with the placebo group (p = 0.035 and p = 0.031). The cumulative event-free rate was significantly higher in the edaravone group than in the placebo group (p = 0.045). Serum thioredoxin levels were significantly lower in the edaravone group than in the placebo group throughout the acute phase. CONCLUSIONS: The present study suggests that the edaravone administration just prior to reperfusion might reduce oxidative stress and improve the long-term clinical outcomes of AMI patients.     

Increased risk of death and cardiac arrest from encainide and flecainide in patients after non-Q-wave acute myocardial infarction in the Cardiac Arrhythmia Suppression Trial

This report examines whether in the Cardiac Arrhythmia Suppression Trial death and cardiac arrest from encainide, flecainide and moricizine during the titration phase and from encainide and flecainide during the follow-up phase were related to presence (Q-wave acute myocardial infarction [Q-AMI]) or absence (non-Q-AMI) of pathologic Q waves. In all, 2,371 patients (70% with Q-AMI, 26% with non-Q-AMI, and 4% unknown) entered the titration phase, starting 117 ± 163 days after index AMI and lasting for an average of 21 days. For the titration phase, no significant differences existed between Q-AMI and non-Q-AMI patients for death and cardiac arrest rate, ventricular premature complex suppression rate, and nonrandomization rate. A total of 1,498 patients entered the follow-up phase of an average of 10 months (starting 129 ± 158 days after the index AMI), and were randomized to encainide or flecainide, or their matching placebos. In the placebo group, non-Q-AMI patients had a significantly lower rate of death and cardiac arrest than Q-AMI patients (1.0 and 4.6%, respectively; P = 0.04). Encainide and flecainide significantly elevated death and cardiac arrest rate in both non-Q-AMI patients (8.7%, p < 0.01) and Q-AMI patients (7.8%, P = 0.04). The relative risk for encainide or flecainide over placebo in the non-Q-AMI patients was 8.7, which was significantly higher than 1.7 observed for the Q-AMI patients (p = 0.03). None of the baseline characteristics had any significant interaction with encainide or flecainide.

In conclusion, during the relatively early post-AMI period, therapy with encainide, flecainide or moricizine resulted in similar rates of ventricular premature complex suppression and death/cardiac arrest between non-Q-AMI and Q-AMI groups. In contrast, during the late postmyocardial infarction period, therapy with encainide or flecainide was associated with a much steeper increase in death/cardiac arrest rate in the non-Q-AMI group than in the Q-AMI group.