Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: a randomized controlled trial

Context  Observational studies have reported associations between circulating total homocysteine concentration and risk of cardiovascular disease. Oral administration of folic acid and vitamin B₁₂ can lower plasma total homocysteine levels. Objective  To assess the effect of treatment with folic acid and vitamin B₁₂ and the effect of treatment with vitamin B₆ as secondary prevention in patients with coronary artery disease or aortic valve stenosis. Design, Setting, and Participants  Randomized, double-blind controlled trial conducted in the 2 university hospitals in western Norway in 1999-2006. A total of 3096 adult participants undergoing coronary angiography (20.5% female; mean age, 61.7 years) were randomized. At baseline, 59.3% had double- or triple-vessel disease, 83.7% had stable angina pectoris, and 14.9% had acute coronary syndromes. Interventions  Using a 2 x 2 factorial design, participants were randomly assigned to 1 of 4 groups receiving daily oral treatment with folic acid, 0.8 mg, plus vitamin B₁₂, 0.4 mg, plus vitamin B₆, 40 mg (n = 772); folic acid plus vitamin B₁₂ (n = 772); vitamin B₆ alone (n = 772); or placebo (n = 780). Main Outcome Measures  The primary end point was a composite of all-cause death, nonfatal acute myocardial infarction, acute hospitalization for unstable angina pectoris, and nonfatal thromboembolic stroke. Results  Mean plasma total homocysteine concentration was reduced by 30% after 1 year of treatment in the groups receiving folic acid and vitamin B₁₂. The trial was terminated early because of concern among participants due to preliminary results from a contemporaneous Norwegian trial suggesting adverse effects from the intervention. During a median 38 months of follow-up, the primary end point was experienced by a total of 422 participants (13.7%): 219 participants (14.2%) receiving folic acid/vitamin B₁₂ vs 203 (13.1%) not receiving such treatment (hazard ratio, 1.09; 95% confidence interval, 0.90-1.32; P = .36) and 200 participants (13.0%) receiving vitamin B₆ vs 222 (14.3%) not receiving vitamin B₆ (hazard ratio, 0.90; 95% confidence interval, 0.74-1.09; P = .28). Conclusions  This trial did not find an effect of treatment with folic acid/vitamin B₁₂ or vitamin B₆ on total mortality or cardiovascular events. Our findings do not support the use of B vitamins as secondary prevention in patients with coronary artery disease. Trial Registration  clinicaltrials.gov Identifier: NCT00354081      

Thorombolytic therapy with rescue percutaneous coronary intervention versus primary percutaneous coronary intervention in patients with acute myocardial infarction: a multicenter randomized clinical trial

Background Although thrombolytic therapy with rescue percutaneous coronary intervention （PCI） is a common treatment strategy for ST-segment elevation acute myocardial infarction （STEMI）, scant data are available on its efficacy relative to primary PCI, and comparison was therefore the aim of this study. Methods This multicenter, open-label, randomized, parallel trial was conducted in 12 hospitals on patients （age 〈70 years） with STEMI who presented within 12 hours of symptom onset （mean interval 〉3 hours）. Patients were randomized to three groups： primary PCI group （n=101）; recombinant staphylokinase （r-Sak） group （n=-104）; and recombinant tissue-type plasminogen activator （rt-PA） group （n=-106）. For all patients allocated to the thrombolytic therapy arm, coronary angiography was performed at 90 minutes after drug therapy to confirm infarct-related artery （IRA） patency; rescue PCI was performed in cases with TIMI flow grade 〈2. Bare-metal stent implantation was planned for all patients. Results After randomization it required an average of 113.4 minutes to start thrombolytic therapy （door-to-needle time）and 141.2 minutes to perform first balloon inflation in the IRA （door to balloon time）. Rates of IRA patency （TIMI flow grade 2 or 3） and TIMI flow grade 3 were significantly lower in the thrombolysis group at 90 minutes after drug therapy than in the primary PCI group at the end of the procedure （70.5% vs. 98.0%, P 〈0.0001, and 53.0% vs. 85.9%, P 〈0.0001, respectively）. Rescue PCI with stenting was performed in 117 patients （55.7%） in the thrombolytic therapy arm. Rates of patency and TIMI flow grade 3 were still significantly lower in the rescue PCI than in the primary PCI group （88.9% vs. 97.9%, P=-0.0222, and 68.4% vs. 85.0%, P=0.0190, respectively）. At 30 days post-therapy, mortality rate was significantly higher in the thrombolysis combined with rescue PCI group than in primary PCI group （7.1% vs. 0, P=0.0034）. Rates of death/MI and bleeding complications were significantly higher in the thrombolysis with rescue PCI group than in the primary PCI group （10.0% vs. 1.0%, P=-0.0380, and 28.10% vs. 8.91%, P=-0.O001, respectively）. Conclusions Thrombolytic therapy with rescue PCI was associated with significantly lower rates of coronary patency and TIMI flow grade 3, but with significantly higher rates of mortality, death/MI and hemorrhagic complications at 30 days, as compared with primary PCI in this group of Chinese STEMI patients with late presentation and delayed treatments.     

Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial

Context  Following percutaneous coronary intervention (PCI), short-term clopidogrel therapy in addition to aspirin leads to greater protection from thrombotic complications than aspirin alone. However, the optimal duration of combination oral antiplatelet therapy is unknown. Also, although current clinical data suggest a benefit for beginning therapy with a clopidogrel loading dose prior to PCI, the practical application of this therapy has not been prospectively studied. Objectives  To evaluate the benefit of long-term (12-month) treatment with clopidogrel after PCI and to determine the benefit of initiating clopidogrel with a preprocedure loading dose, both in addition to aspirin therapy. Design, Setting, and Participants  The Clopidogrel for the Reduction of Events During Observation (CREDO) trial, a randomized, double-blind, placebo-controlled trial conducted among 2116 patients who were to undergo elective PCI or were deemed at high likelihood of undergoing PCI, enrolled at 99 centers in North America from June 1999 through April 2001. Interventions  Patients were randomly assigned to receive a 300-mg clopidogrel loading dose (n = 1053) or placebo (n = 1063) 3 to 24 hours before PCI. Thereafter, all patients received clopidogrel, 75 mg/d, through day 28. From day 29 through 12 months, patients in the loading-dose group received clopidogrel, 75 mg/d, and those in the control group received placebo. Both groups received aspirin throughout the study. Main Outcome Measures  One-year incidence of the composite of death, myocardial infarction (MI), or stroke in the intent-to-treat population; 28-day incidence of the composite of death, MI, or urgent target vessel revascularization in the per-protocol population. Results  At 1 year, long-term clopidogrel therapy was associated with a 26.9% relative reduction in the combined risk of death, MI, or stroke (95% confidence interval [CI], 3.9%-44.4%; P = .02; absolute reduction, 3%). Clopidogrel pretreatment did not significantly reduce the combined risk of death, MI, or urgent target vessel revascularization at 28 days (reduction, 18.5%; 95% CI, -14.2% to 41.8%; P = .23). However, in a prespecified subgroup analysis, patients who received clopidogrel at least 6 hours before PCI experienced a relative risk reduction of 38.6% (95% CI, -1.6% to 62.9%; P = .051) for this end point compared with no reduction with treatment less than 6 hours before PCI. Risk of major bleeding at 1 year increased, but not significantly (8.8% with clopidogrel vs 6.7% with placebo; P = .07). Conclusions  Following PCI, long-term (1-year) clopidogrel therapy significantly reduced the risk of adverse ischemic events. A loading dose of clopidogrel given at least 3 hours before the procedure did not reduce events at 28 days, but subgroup analyses suggest that longer intervals between the loading dose and PCI may reduce events.      

冠心病患者血浆同型半胱氨酸水平与血清叶酸、维生素B12浓度的相关性研究

目的观察高同型半胱氨酸血症（HHCY）是否是人群发生冠心病（CHD）的独立危险因素,同时探讨CHD患者血中同型半胱氨酸（HCY）、叶酸、VitB12浓度的变化及其相关性。方法选择CHD患者123例,正常对照101例。采用荧光偏振免疫分析法测定血浆HCY水平,化学发光免疫分析法测定血清叶酸、VitB12浓度。结果（1）CHD组患者血浆HCY平均浓度（15．04±7．58）μmol／L显著高于正常对照组（10．08±3．11）μmol／L,P〈0．01,CHD组患者血清叶酸平均浓度（4．02±2．27）ng/ml显著低于对照组（5．93±2．76）ng／ml,P〈0．01,CHD组患者血清VitBt2平均浓度（303．63±130．51）pg／ml与正常对照组（292．17±94．05）pg/ml比较差异无显著性（P〉0．05）。CHD组HHCY的发生率（36．59％）亦明显高于对照组（9．90％,P〈0．01）。CHD病因的多元Logistic回归分析显示HCY是CHD发病的独立危险因素。HCY对于CHD的相对危险度（RR）为1．238。相关分析显示：CHD组血浆HCY水平与血清叶酸、与VitB12浓度呈显著负相关（P=0．000）。结论HHCY是CHD的独立危险因素。CHD组血浆HCY水平与血清叶酸、与VitB12浓度呈线性负相关。血浆HCY、叶酸浓度检测有助CHD的诊断。     

Fluvastatin for prevention of cardiac events following successful first percutaneous coronary intervention: a randomized controlled trial

Context  Percutaneous coronary intervention (PCI) is associated with excellent short-term improvements in ischemic symptoms, yet only three fifths of PCI patients at 5 years and one third of patients at 10 years remain free of major adverse cardiac events (MACE). Objective  To determine whether treatment with fluvastatin reduces MACE in patients who have undergone PCI. Design and Setting  Randomized, double-blind, placebo-controlled trial conducted at 77 referral centers in Europe, Canada, and Brazil. Patients  A total of 1677 patients (aged 18-80 years) recruited between April 1996 and October 1998 with stable or unstable angina or silent ischemia following successful completion of their first PCI who had baseline total cholesterol levels between 135 and 270 mg/dL (3.5-7.0 mmol/L), with fasting triglyceride levels of less than 400 mg/dL (4.5 mmol/L). Interventions  Patients were randomly assigned to receive treatment with fluvastatin, 80 mg/d (n = 844), or matching placebo (n = 833) at hospital discharge for 3 to 4 years. Main Outcome Measure  Survival time free of MACE, defined as cardiac death, nonfatal myocardial infarction, or reintervention procedure, compared between the treatment and placebo groups. Results  Median time between PCI and first dose of study medication was 2.0 days, and median follow-up was 3.9 years. MACE-free survival time was significantly longer in the fluvastatin group (P = .01). One hundred eighty-one (21.4%) of 844 patients in the fluvastatin group and 222 (26.7%) of 833 patients in the placebo group had at least 1 MACE (relative risk [RR], 0.78; 95% confidence interval [CI], 0.64-0.95; P = .01). This result was independent of baseline total cholesterol levels (above [RR, 0.76; 95% CI, 0.56-1.04] vs below [RR, 0.77; 95% CI, 0.57-1.02] the median). In subgroup analysis, the risk of MACE was reduced in patients with diabetes (n = 202; RR, 0.53; 95% CI, 0.29-0.97; P = .04) and in those with multivessel disease (n = 614; RR, 0.66; 95% CI, 0.48-0.91; P = .01) who received fluvastatin compared with those who received placebo. There were no instances of creatine phosphokinase elevations 10 or more times the upper limit of normal or rhabdomyolysis in the fluvastatin group. Conclusion  Fluvastatin treatment in patients with average cholesterol levels undergoing their first successful PCI significantly reduces the risk of major adverse cardiac events.      

Pexelizumab for acute ST-elevation myocardial infarction in patients undergoing primary percutaneous coronary intervention: a randomized controlled trial

Context  Reperfusion with percutaneous transluminal coronary intervention (PCI) is effective at improving outcomes in patients with acute ST-elevation myocardial infarction (STEMI). However, in patients without prompt reestablishment of brisk coronary flow and tissue perfusion, mortality remains high, providing an opportunity for novel treatments, including anti-inflammatory agents. Objective  To evaluate the effectiveness of pexelizumab, a humanized monoclonal antibody that binds the C5 component of complement, as an adjunct to PCI in improving 30-day mortality from STEMI. Design, Setting, and Patients  This trial was a prospective, multicenter, double-blind, placebo-controlled, phase 3 study of the intravenous administration of pexelizumab in conjunction with primary PCI in STEMI with prespecified high-risk electrocardiographic findings. The trial was intended to enroll 8500 patients, but in conjunction with the US Food and Drug Administration enrollment was modified to 5745 patients presenting from 296 hospitals in 17 countries from July 13, 2004, to May 11, 2006. Interventions  Two thousand eight hundred eighty-five patients were randomly assigned to receive placebo and 2860 to receive pexelizumab given as a 2-mg/kg intravenous bolus prior to PCI followed by 0.05-mg/kg per hour infusion over the subsequent 24 hours. Patients were randomized within 6 hours of symptom onset. Main Outcome Measures  The primary end point was all-cause mortality through day 30. Secondary end points were death through day 90 and the composite of death, cardiogenic shock, or congestive heart failure through days 30 and 90. Results  No difference in mortality through day 30 was observed between the pexelizumab and placebo treatment groups, with 116 patients (4.06%) and 113 patients (3.92%) who died in the respective groups (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.80-1.35; log-rank P = .78). The composite end points of death, shock, or heart failure were also similar with 257 patients (8.99%) receiving pexelizumab and 265 patients (9.19%) receiving placebo at 30 days (HR, 0.98; 95% CI, 0.83-1.16; P = .81) and 293 patients (10.24%) receiving pexelizumab and 293 patients (10.16%) receiving placebo at 90 days (HR, 1.01; 95% CI, 0.86-1.19; P = .91). Conclusion  In this large clinical trial of patients treated with primary PCI for STEMI, mortality was low and unaffected by administration of pexelizumab. Trial Registration  clinicaltrials.gov Identifier: NCT00091637      

Distal microcirculatory protection during percutaneous coronary intervention in acute ST-segment elevation myocardial infarction: a randomized controlled trial

Context  Atheromatous and thrombotic embolization during percutaneous coronary intervention (PCI) in acute myocardial infarction is common and may result in microcirculatory dysfunction, the prevention of which may improve reperfusion success, reduce infarct size, and enhance event-free survival. Objective  To determine whether protection of the distal microcirculation from thromboembolic debris liberated during primary PCI results in improved reperfusion and decreased infarct size. Design, Setting, and Patients  Prospective randomized controlled trial at 38 academic and community-based institutions in 7 countries enrolling 501 patients aged 18 years or older with ST-segment elevation myocardial infarction (STEMI) presenting within 6 hours of symptom onset and undergoing primary PCI or rescue intervention after failed thrombolysis. Interventions  Patients were randomized between May 20, 2002, and November 21, 2003, to receive PCI with a balloon occlusion and aspiration distal microcirculatory protection system vs angioplasty without distal protection. Main Outcome Measures  Coprimary end points were ST-segment resolution (STR) measured 30 minutes after PCI by continuous Holter monitoring and infarct size measured by technetium Tc 99m sestamibi imaging between days 5 and 14. Secondary end points included major adverse cardiac events. Results  Among 252 patients assigned to distal protection, aspiration was performed in 97% (242/251), all angioplasty balloon inflations were fully protected in 79% (193/245), and visible debris was retrieved from 73% (182/250). Complete STR was achieved in a similar proportion reperfused with vs without distal protection (63.3% [152/240] vs 61.9% [148/239], respectively; absolute difference, 1.4% [95% confidence interval, –7.7% to 10.5%; P = .78]), and left ventricular infarct size was similar in both groups (median, 12.0% [n = 229] vs 9.5% [n = 208], respectively; P = .15). Major adverse cardiac events at 6 months occurred with similar frequency in the distal protection and control groups (10.0% vs 11.0%, respectively; P = .66). Conclusions  A distal balloon occlusion and aspiration system effectively retrieves embolic debris in most patients with acute STEMI undergoing emergent PCI. Nonetheless, distal embolic protection did not result in improved microvascular flow, greater reperfusion success, reduced infarct size, or enhanced event-free survival.      

Abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after clopidogrel pretreatment: the ISAR-REACT 2 randomized trial

Context  No specifically designed studies have addressed the role of the glycoprotein IIb/IIIa inhibitor abciximab in patients with non–ST-segment elevation acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) after pretreatment with 600 mg of clopidogrel. Objective  To assess whether abciximab is associated with clinical benefit in high-risk patients with ACS undergoing PCI after pretreatment with 600 mg of clopidogrel. Design, Setting, and Patients  International, multicenter, randomized, double-blind, placebo-controlled study conducted from March 2003 through December 2005, enrolling 2022 patients (mean age, 66 years) with non–ST-segment elevation ACS undergoing PCI. Interventions  Patients were assigned to receive either abciximab (0.25 mg/kg of body weight bolus, followed by a 0.125-µg/kg per minute [maximum, 10 µg/min] infusion for 12 hours, plus heparin, 70 U/kg of body weight) or placebo (placebo bolus and infusion of 12 hours, plus heparin bolus, 140 U/kg). All patients received clopidogrel, 600 mg, at least 2 hours prior to the procedure, as well as 500 mg of oral or intravenous aspirin. Main Outcome Measures  The primary end point was a composite of death, myocardial infarction, or urgent target vessel revascularization occurring within 30 days after randomization; secondary end points were rates of in-hospital major and minor bleeding. Results  Of 2022 patients enrolled, 1012 were assigned to abciximab and 1010 to placebo. The primary end point was reached in 90 patients (8.9%) assigned to abciximab vs 120 patients (11.9%) assigned to placebo, a 25% reduction in risk with abciximab (relative risk [RR], 0.75; 95% CI, 0.58-0.97; P = .03). Among patients without an elevated troponin level, there was no difference in the incidence of primary end point events between the abciximab group (23/499 patients [4.6%]) and the placebo group (22/474 patients [4.6%]) (RR, 0.99; 95% CI, 0.56-1.76; P = .98), whereas among patients with an elevated troponin level, the incidence of events was significantly lower in the abciximab group (67/513 patients [13.1%]) compared with the placebo group (98/536 patients [18.3%]), which corresponds to an RR of 0.71 (95% CI, 0.54-0.95; P = .02) (P = .07 for interaction). There were no significant differences between the 2 groups regarding the risk of major and minor bleeding as well as need for transfusion. Conclusions  Abciximab reduces the risk of adverse events in patients with non–ST-segment elevation ACS undergoing PCI after pretreatment with 600 mg of clopidogrel. The benefits provided by abciximab appear to be confined to patients presenting with an elevated troponin level. Trial Registration  ClinicalTrials.gov Identifier: NCT00133003      

Thrombolytic therapy vs primary percutaneous coronary intervention for myocardial infarction in patients presenting to hospitals without on-site cardiac surgery: a randomized controlled trial

Context  Trials comparing primary percutaneous coronary intervention (PCI) and thrombolytic therapy for treatment of acute myocardial infarction (MI) suggest primary PCI is the superior therapy, although they differ with respect to the durability of benefit. Because PCI is often limited to hospitals that have on-site cardiac surgery programs, most acute MI patients do not have access to this therapy. Objective  To determine whether treatment of acute MI with primary PCI is superior to thrombolytic therapy at hospitals without on-site cardiac surgery and, if so, whether superiority is durable. Design  The Atlantic Cardiovascular Patient Outcomes Research Team (C-PORT) trial, a prospective, randomized trial conducted from July 1996 through December 1999. Setting  Eleven community hospitals in Massachusetts and Maryland without on-site cardiac surgery or extant PCI programs. Patients  Four hundred fifty-one thrombolytic-eligible patients with acute MI of less than 12 hours' duration associated with ST-segment elevation on electrocardiogram. Interventions  After a formal primary PCI development program was completed at all sites, patients were randomly assigned to receive primary PCI (n = 225) or accelerated tissue plasminogen activator (bolus dose of 15 mg and an infusion of 0.75 mg/kg for 30 minutes followed by 0.5 mg/kg for 60 minutes; n = 226). After initiation of assigned treatment, all care was determined by treating physicians. Main Outcome Measures  Six-month composite incidence of death, recurrent MI, and stroke; median hospital length of stay. Results  The incidence of the composite end point was reduced in the primary PCI group at 6 weeks (10.7% vs 17.7%; P = .03) and 6 months (12.4% vs 19.9%; P = .03) after index MI. Six-month rates for individual outcomes were 6.2% vs 7.1% for death (P = .72), 5.3% vs 10.6% for recurrent MI (P = .04), and 2.2% vs 4.0% for stroke (P = .28) for primary PCI vs thrombolytic therapy, respectively. Median length of stay was also reduced in the primary PCI group (4.5 vs 6.0 days; P = .02). Conclusions  Compared with thrombolytic therapy, treatment of patients with primary PCI at hospitals without on-site cardiac surgery is associated with better clinical outcomes for 6 months after index MI and a shorter hospital stay.      

卡马西平对癫痫患者血同型半胱氨酸、叶酸、维生素B12水平的影响

目的探讨卡马西平(Carbamazepine,CBZ)对血同型半胱氨酸(Homocysteine,Hcy)、叶酸、维生素B12(vitaminB12,VitB12)水平的影响。方法分别检测CBZ单药治疗癫痫患者(CBZ组)的血Hcy、叶酸、VitB12水平,并与未服用抗癫痫药的患者(癫痫对照组)及健康对照组进行比较。结果 CBZ组患者血Hcy水平明显高于癫痫对照组和正常对照组(P<0.01),叶酸水平低于癫痫对照组和正常对照组(P<0.05),VitB12水平有下降趋势,但与两对照组比较,差异无统计学意义(P>0.05)。结论 CBZ可引起癫痫患者血Hcy水平升高和叶酸水平降低;长期服用CBZ的癫痫患者应监测血Hcy、叶酸、VitB12浓度,及时补充叶酸和B族维生素,以预防血栓事件的发生。     

Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial

Context  Statin drugs reduce both atherogenic lipoproteins and cardiovascular morbidity and mortality. However, the optimal strategy and target level for lipid reduction remain uncertain. Objective  To compare the effect of regimens designed to produce intensive lipid lowering or moderate lipid lowering on coronary artery atheroma burden and progression. Design, Setting, and Patients  Double-blind, randomized active control multicenter trial (Reversal of Atherosclerosis with Aggressive Lipid Lowering [REVERSAL]) performed at 34 community and tertiary care centers in the United States comparing the effects of 2 different statins administered for 18 months. Intravascular ultrasound was used to measure progression of atherosclerosis. Between June 1999 and September 2001, 654 patients were randomized and received study drug; 502 had evaluable intravascular ultrasound examinations at baseline and after 18 months of treatment. Interventions  Patients were randomly assigned to receive a moderate lipid-lowering regimen consisting of 40 mg of pravastatin or an intensive lipid-lowering regimen consisting of 80 mg of atorvastatin. Main Outcome Measures  The primary efficacy parameter was the percentage change in atheroma volume (follow-up minus baseline). Results  Baseline low-density lipoprotein cholesterol level (mean, 150.2 mg/dL [3.89 mmol/L] in both treatment groups) was reduced to 110 mg/dL (2.85 mmol/L) in the pravastatin group and to 79 mg/dL (2.05 mmol/L) in the atorvastatin group (P<.001). C-reactive protein decreased 5.2% with pravastatin and 36.4% with atorvastatin (P<.001). The primary end point (percentage change in atheroma volume) showed a significantly lower progression rate in the atorvastatin (intensive) group (P = .02). Similar differences between groups were observed for secondary efficacy parameters, including change in total atheroma volume (P = .02), change in percentage atheroma volume (P<.001), and change in atheroma volume in the most severely diseased 10-mm vessel subsegment (P<.01). For the primary end point, progression of coronary atherosclerosis occurred in the pravastatin group (2.7%; 95% confidence interval [CI], 0.2% to 4.7%; P = .001) compared with baseline. Progression did not occur in the atorvastatin group (–0.4%; CI –2.4% to 1.5%; P = .98) compared with baseline. Conclusions  For patients with coronary heart disease, intensive lipid-lowering treatment with atorvastatin reduced progression of coronary atherosclerosis compared with pravastatin. Compared with baseline values, patients treated with atorvastatin had no change in atheroma burden, whereas patients treated with pravastatin showed progression of coronary atherosclerosis. These differences may be related to the greater reduction in atherogenic lipoproteins and C- reactive protein in patients treated with atorvastatin.      

同型半胱氨酸、叶酸及维生素B12与脑卒中的相关性研究

目的研究血浆中同型半胱氨酸(Hcy)、叶酸及维生素B12与不同类型脑卒中的关系。方法选择脑卒中患者112例(其中脑梗死45例、脑出血35例和短暂性脑缺血发作32例)为研究对象,健康体检者102例为对照组。采用酶联免疫分析法测定被检者血浆Hcy浓度,并同时测定叶酸和维生素B12。结果研究组血浆Hcy水平显著高于对照组,且与损伤程度有关(P0.01)。经相关回归分析研究结果显示,脑卒中患者血中Hcy水平明显高于对照组,与叶酸、维生素B12存在负相关,而与类型无关。结论脑卒中的发生与血中Hcy有相关性,血中Hcy可作为预测及评价脑卒中的重要指标之一。     

叶酸和维生素B12辅助治疗对老年冠心病慢性心力衰竭患者血清炎性因子、Hcy和NT-proBNP的影响

目的:探讨叶酸联合维生素B12辅助常规药物治疗老年冠心病慢性心力衰竭,对患者血清炎性因子、Hcy及NT-proBNP等指标水平的影响。方法:89例老年冠心病慢性心力衰竭患者作为研究对象,依据随机数据表法分为对照组(n=47)和观察组(n=42),对照组患者给予利尿剂、ACEI和β受体阻制剂三大类药物联合治疗,在此基础上,观察组患者辅以叶酸片和维生素B12治疗,两组均治疗8周。比较两组患者治疗前后的血清炎性因子(TNF-α、hs-CRP和visfatin)、Hcy及NT-proBNP水平。结果:治疗前,对照组与观察组的TNF-α、hs-CRP、visfatin、Hcy及NT-proBNP水平比较,差异不显著无统计学意义(P>0.05)。治疗后,与组内治疗前相比,两组的TNF-α、hs-CRP、visfatin、Hcy及NTproBNP水平均显著下降,差异有统计学意义(P<0.05),且治疗后观察组的上述指标水平均显著低于对照组,差异有统计学意义(P<0.05)。结论:叶酸联合维生素B12治疗老年冠心病心力衰竭,可有效降低患者的血清炎性因子、Hcy及NT-proBNP水平,具有一定的临床价值。     

Methylmalonic acidemia: 6 years'' clinical experience with two variants unresponsive to vitamin B12 therapy

Two infants with lethargy, vomiting, convulsions, coma and marked metabolic acidosis were found to have very high concentrations of methylmalonic acid in their serum and urine. In vitro studies of fibroblasts demonstrated that the infants had different variants of methylmalonic acidemia.

Vitamin B₁₂ was given in two different forms at 1 month of age and at 12 months of age. Each trial continued for 4 months but neither infant showed a clinical or biochemical response.

In both infants hyperglycinemia, neutropenia and thrombocytopenia developed during acute metabolic crises only. Hypoglycemia was found in patient 2. Hyperammonemia was severe in patient 2 during acute crises but never appeared in patient 1. When clinically well, both infants continued to excrete abnormal amounts of methylmalonic acid in the urine and both had persistent compensated metabolic acidosis.

Marked hyperuricemia developed in patient 1 at 18 months of age and led to progressive renal failure. Allopurinol therapy was necessary to keep the uric acid concentration within the normal range. Renal function returned to normal, as indicated by a marked increase in the renal clearance of creatinine and uric acid.

Patient 1 is physically and mentally retarded, and has moderate hypotonia, hepatomegaly and persistent vomiting. Patient 2 has developed normally.

The urine concentrations of methylmalonic acid in the four parents were normal.

     

叶酸联合维生素B12 对非小细胞肺癌患者化疗疗效的影响

目的 探讨叶酸联合维生素B12 对非小细胞肺癌患者化疗效果的影响。方法 选取2012 年5 月-2016 年2 月在郑州大学附属医院南阳医院接受化疗的非小细胞肺癌患者114 例，依据随机数表法分为观察组（叶酸+ 维生素B12+ 化疗）和对照组（常规化疗），比较两组患者的临床疗效、ECOG 评分、超敏C 反应蛋白（hs-CRP）、癌胚抗原（CEA）、CD4+/CD8+ 及不良反应。结果 观察组57 例，完全缓解6 例，部分缓解20 例，稳定25 例，进展6 例，稳定率为89.47%，缓解率为45.61%；对照组完全缓解3 例，部分缓解11 例，稳定23 例，进展20 例，稳定率为64.91%，缓解率为24.56%，两组患者的稳定率和缓解率比较，差异有统计学意义（P <0.05）。两组ECOG 评分比较，差异有统计学意义（P <0.05）。治疗前，两组患者的hs-CRP、CEA 及CD4+/CD8+ 比较，差异无统计学意义（P >0.05）。治疗结束后，两组患者的hs-CRP、CEA 及CD4+/CD8+ 比较，差异有统计学意义（P <0.05），两组患者的不良反应发生率比较，差异有统计学意义（P <0.05）。结论 叶酸联合维生素B12 能有效提高非小细胞肺癌患者化疗效果，改善患者免疫功能及血液学指标，降低不良反应发生率。     

结肠腺瘤性息肉患者血浆同型半胱氨酸、叶酸、维生素B12水平观察

选择我院消化内科诊断明确的结肠腺瘤性息肉患者120例（病例组）和同期正常健康体检者40例（对照组）,测定其血浆同型半胱氨酸（Hcy）、叶酸、维生素B12水平。结果显示,病例组的血浆Hcy水平高于对照组[（14．24±0．52）μmol／L与（10．93±0．81）μmol／L,P=0．0014],血浆叶酸水平低于对照组[（6．26±0．27）μg/L与（10．74±0．85）μg/L,P〈0．0001],而两组维生素B12水平比较差异无统计学意义（P=0．7100）。结肠多发息肉者Hey水平高于单发组,叶酸水平低于单发组（P=0．0092,P=0．0047）。随着病理类型加重,患者Hcy浓度逐渐升高,而叶酸水平逐渐下降。不同个例最大息肉所在部位及息肉分布患者血浆FA、Hcy和VitB12水平差异无统计学意义。提示结肠腺瘤性息肉患者存在血浆Hcy水平和FA水平改变,其间可能存在密切联系。     

Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women: a randomized controlled trial

Context  Hormone replacement therapy (HRT) and antioxidant vitamins are widely used for secondary prevention in postmenopausal women with coronary disease, but no clinical trials have demonstrated benefit to support their use. Objective  To determine whether HRT or antioxidant vitamin supplements, alone or in combination, influence the progression of coronary artery disease in postmenopausal women, as measured by serial quantitative coronary angiography. Design, Setting, and Patients  The Women's Angiographic Vitamin and Estrogen (WAVE) Trial, a randomized, double-blind trial of 423 postmenopausal women with at least one 15% to 75% coronary stenosis at baseline coronary angiography. The trial was conducted from July 1997 to January 2002 in 7 clinical centers in the United States and Canada. Interventions  Patients were randomly assigned in a 2 x 2 factorial design to receive either 0.625 mg/d of conjugated equine estrogen (plus 2.5 mg/d of medroxyprogesterone acetate for women who had not had a hysterectomy), or matching placebo, and 400 IU of vitamin E twice daily plus 500 mg of vitamin C twice daily, or placebo. Main Outcome Measure  Annualized mean (SD) change in minimum lumen diameter (MLD) from baseline to concluding angiogram of all qualifying coronary lesions averaged for each patient. Patients with intercurrent death or myocardial infarction (MI) were imputed the worst rank of angiographic outcome. Results  The mean (SD) interval between angiograms was 2.8 (0.9) years. Coronary progression, measured in mean (SD) change, worsened with HRT by 0.047 (0.15) mm/y and by 0.024 (0.15) mm/y with HRT placebo (P = .17); and for antioxidant vitamins by 0.044 (0.15) mm/y and with vitamin placebo by 0.028 (0.15) mm/y (P = .32). When patients with intercurrent death or MI were included, the primary outcome showed an increased risk for women in the active HRT group (P = .045), and suggested an increased risk in the active vitamin group (P = .09). Fourteen patients died in the HRT group and 8 in the HRT placebo group (hazard ratio [HR], 1.8; 95% confidence interval [CI], 0.75-4.3), and 16 in the vitamin group and 6 in the vitamin placebo group (HR, 2.8; 95% CI, 1.1-7.2). Death, nonfatal MI, or stroke occurred in 26 HRT patients vs 15 HRT controls (HR, 1.9; 95% CI, 0.97-3.6) and in 26 vitamin patients and 18 vitamin controls (HR, 1.5; 95% CI, 0.80-2.9). There was no interaction between the 2 treatment interventions. Conclusion  In postmenopausal women with coronary disease, neither HRT nor antioxidant vitamin supplements provide cardiovascular benefit. Instead, a potential for harm was suggested with each treatment.      

Effect of maintenance therapy with varenicline on smoking cessation: a randomized controlled trial

Context  The majority of cigarette smokers who achieve abstinence relapse within the first year and require many attempts before achieving permanent abstinence. Evidence to support pharmacological treatment for relapse prevention is insufficient. Objective  To determine whether smokers who quit after 12 weeks of treatment with varenicline, a selective 42 nicotinic acetylcholine receptor partial agonist, maintain greater continuous abstinence rates (defined as not a single "puff" of a cigarette) than placebo controls during an additional 12 weeks of treatment and until 52 weeks after treatment initiation. Design, Setting, and Participants  Randomized controlled trial conducted at multiple medical clinics in 7 countries with follow-up to 52 weeks after study baseline. Of 1927 cigarette smokers recruited between April 2003 and February 2004 and treated for 12 weeks with open-label varenicline titrated to 1 mg twice per day, 1236 (64.1%) did not smoke, use tobacco, or use nicotine replacement therapy during the last week of treatment and 62.8% (n = 1210) were randomized to additional treatment or placebo. Intervention  Participants were randomly assigned to receive either double-blind varenicline, 1 mg twice per day (n = 603), or placebo (n = 607) for an additional 12 weeks. Main Outcome Measures  Carbon monoxide–confirmed continued abstinence during weeks 13 to 24 and weeks 13 to 52 of the study. Results  The carbon monoxide–confirmed continuous abstinence rate was significantly higher for the varenicline group than for the placebo group for weeks 13 to 24 (70.5% vs 49.6%; odds ratio [OR], 2.48; 95% confidence interval [CI], 1.95-3.16; P<.001) as well as for weeks 13 to 52 (43.6% vs 36.9%; OR, 1.34; 95% CI, 1.06-1.69; P = .02). Adverse events reported in the open-label period were mostly mild; no difference in adverse events between varenicline and placebo was observed during the double-blind period. Conclusions  Smokers who achieved abstinence for at least 7 days at the end of 12 weeks of open-label varenicline treatment and were randomized to receive an additional 12 weeks of varenicline treatment showed significantly greater continuous abstinence in weeks 13 to 24 compared with placebo. This advantage was maintained through the nontreatment follow-up to week 52. Varenicline may be an efficacious, safe, and well-tolerated agent for maintaining abstinence from smoking. Trial Registration  clinicaltrials.gov Identifier: NCT00143286      

冠脉介入治疗中对比剂肾病发生的临床研究

目的:探讨经皮冠状动脉介入(PCI)治疗患者对比剂肾病(CIN)的发病率及危险因素。方法:选择2011年5月至2014年5月在韶关市第三人民医院接受PCI的180例患者作为研究对象,以术后72 h内血清肌酐(SCr)较术前升高25%或升高44.2μmo L/L(0.5 mg/d L)作为CIN的诊断标准,分析CIN的发病率及危险因素。结果:180例患者中年龄≥65岁者69例(38.3%),合并高血压124例(69.44%)、糖尿病62例(58.33%),术前e GFR<60 m L/min者85例(56.67%),服用血管紧张素转换酶抑制剂或血管紧张素受体拮抗剂106例(58.89%)、利尿剂19例(10.56%)、二甲双胍9例(5.00%)、他汀类药物163例(90.56%),对比剂用量≥150 m L者65例(36.11%)。180患者中14例(7.8%)发生CIN,CIN组与非CIN组患者在年龄≥65岁、对比剂用量≥150 m L等方面有明显差异(P<0.05)。Logistic多因素回归分析显示,年龄≥65岁、术前e GFR<60 m L/min、对比剂用量≥150 m L是CIN的独立危险因素,他汀类药物未能减少对围手术期对比剂的发生。结论:PCI患者的CIN发病率较高,年龄≥65岁、术前e GFR<60m L/min和对比剂用量≥150 m L是其独立危险因素。