关于西罗莫司和紫杉醇洗脱支架用于新发冠状动脉病变的随机对照试验:REALITY试验

Context: Compared with bare metal stents, sirolimus-elut-ing and paclitaxel-eluting stents have been shown to markedly improve angiographic and clinical outcomes after percutaneous coronary revascularization, but their performance in the treatment of de novo coronary lesions has not been compared in a prospective multicenter study. Objective: To compare the safety and efficacy of sirolimus-eluting vs paclitaxel-eluting coronary stents. Design: Prospective, randomized comparative trial(the REALITY trial) conducted between August 2003 and February 2004, with angiographic follow-up at 8 months and clinical follow-up at 12 months. Setting: Ninety hospitals in Europe, Latin America, and Asia. Patients: A total of 1386 patients(mean age, 62.6 years; 73.1% men; 28.0% with diabetes)with angina pectoris and 1 or 2 de novo lesions(2.25-3.00 mm in diameter) in native coronary arteries. Intervention: Patients were randomly assigned in a 1 ∶ 1 ratio to receive a sirolimus-eluting stent(n=701) or a paclitaxel-eluting stent(n=685). Main Outcome Measures: The primary end point was in-lesion binary restenosis(presence of a more than 50% luminal diameter stenosis) at 8 months. Secondary end points included 1-year rates of target lesion and vessel revascularization and a composite end point of cardiac death, Q-wave or non-Q-wave myocardial infarction, coronary artery bypass graft surgery, or repeat target lesion revascularization. Results: In-lesion binary restenosis at 8 months occurred in 86 patients(9.6% ) with a sirolimus-eluting stent vs 95(11.1% ) with a paclitaxel-eluting stent(relative risk [RR], 0.84; 95% confidence interval [CI], 0.61-1.17; P=.31). For sirolimus- vs paclitaxel-eluting stents, respectively, the mean(SD) in-stent late loss was 0.09(0.43) mm vs 0.31(0.44) mm(difference,-0.22 mm; 95% CI,-0.26 to-0.18 mm; P<.001), mean(SD) in-stent diameter stenosis was 23.1% (16.6% ) vs 26.7% (15.8% )(difference,-3.60% ; 95% CI,-5.12% to-2.08% ; P< .001), and the number of major adverse cardiac events at 1 year was 73(10.7% ) vs 76(11.4% )(RR, 0.94; 95% CI, 0.69-1.27; P=.73). Conclusion: In this trial comparing sirolimus- and paclitaxel-eluting coronary stents, there were no differences in the rates of binary restenosis or major adverse cardiac events. Clinical Trial Registration: ClinicalTrials.gov Identifier:

选择性5-羟色胺再吸收抑制剂与新生儿持续性肺动脉高压患病风险

Background: Persistent pulmonary hypertension of the newborn(PPHN) is associated with substantial infant mortality and morbidity. A previous cohort study suggested a possible association between maternal use of the selective serotonin- reuptake inhibitor(SSRI) fluoxetine late in the third trimester of pregnancy and the risk of PPHN in the infant. We performed a case- control study to assess whether PPHN is associated with exposure to SSRIs during late pregnancy. Methods: Between 1998 and 2003, we enrolled 377 women whose infants had PPHN and 836 matched control women and their infants. Maternal interviews were conducted by nurses, who were blinded to the study hypothesis, regarding medication use in pregnancy and potential confounders, including demographic variables and health history. Results: Fourteen infants with PPHN had been exposed to an SSRI after the completion of the 20th week of gestation, as compared with six control infants(adjusted odds ratio, 6.1; 95 percent confidence interval, 2.2 to 16.8). In contrast, neither the use of SSRIs before the 20th week of gestation nor the use of non- SSRI antidepressant drugs at any time during pregnancy was associated with an increased risk of PPHN. Conclusions: These data support an association between the maternal use of SSRIs in late pregnancy and PPHN in the offspring; further study of this association is warranted. These findings should be taken into account in decisions as to whether to continue the use of SSRIs during pregnancy.

紫杉醇洗脱支架与血管内近距离放射疗法治疗裸金属支架内再狭窄的比较:TAXUSVISR随机试验

Context: Restenosis within bare-metal stents is often treated with repeat percutaneous coronary intervention, although subsequent recurrence rates are high, with vascular brachytherapy(VBT) affording the best results. The effectiveness of drug-eluting stents in this setting has not been established. Objective: To investigate the safety and efficacy of the polymer-based, slow-release paclitaxel-eluting stent in patients with restenotic lesions after prior stent implantation in native coronary arteries. Design, Setting, and Patients: Prospective, multicenter, randomized trial conducted between June 6, 2003, and July 16, 2004, at 37 North American academic and community-based institutions in 396 patients with in-stent restenosis of a previously implanted bare-metal coronary stent(vessel diameter, 2.5-3.75 mm; lesion length, ≤ 46 mm). Interventions: Patients were randomly assigned to undergo angioplasty followed by VBT with a β source(n=201) or paclitaxel-eluting stent implantation(n=195). Clinical and angiographic follow-up at 9 months was scheduled in all patients. Main Outcome Measure: Ischemia-driven target vessel revascularization at 9 months. Results: Diabetes mellitus was present in 139 patients(35.1% ). Median reference vessel diameter was 2.65 mm and median lesion length was 15.3 mm. In the VBT group, new stents were implanted in 22 patients(10.9% )and in the paclitaxel-eluting stent group, multiple stents were required in 57 patients(29.2% ), with median stent length of 24 mm. Follow-up at 9 months was complete in 194 patients in the VBT group and 191 patients in the paclitaxel-eluting stent group(96.5% and 97.9% , respectively). For VBT and paclitaxel-eluting stents, respectively, the number of events and 9-month rates for ischemic target lesion revascularization were 27(13.9% ) vs 12(6.3% )(relative risk [RR], 0.45; 95% confidence interval [CI], 0.24-0.86; P=.01); for ischemic target vessel revascularization, 34(17.5% ) vs 20(10.5% )(RR, 0.60; 95% CI, 0.36-1.00; P=.046); and for overall major adverse cardiac events, 39(20.1% ) vs 22(11.5% )(RR, 0.57; 95% CI, 0.35-0.93; P=.02), with similar rates of cardiac death or myocardial infarction(10 [5.2% ] vs 7 [3.7% ]; RR, 0.71; 95% CI, 0.28-1.83; P=.48) and target vessel thrombosis(5 [2.6% ] vs 3 [1.6% ]; RR, 0.61; 95% CI, 0.15-2.50; P=.72). Angiographic restenosis at 9 months was 31.2% (53 of 170 patients) with VBT and 14.5% (25 of 172 patients) with paclitaxel-eluting stents(RR, 0.47; 95% CI, 0.30-0.71; P< .001). Conclusion: Treatment of bare-metal in-stent restenotic lesions with paclitaxel-eluting stents rather than angioplasty followed by VBT reduces clinical and angiographic restenosis at 9 months and improves event-free survival. Trial Registration: ClinicalTrials. gov Identifier: NCT00287573.

老年人的甲状腺状况、心血管疾病风险以及死亡率

Context: Previous studies have suggested that subclinical abnormalities in thyroid-stimulating hormone levels are associated with detrimental effects on the cardiovascular system. Objective: To determine the relationship between baseline thyroid status and incident atrial fibrillation, incident cardiovascular disease, and mortality in older men and women not taking thyroid medication. Design, Setting, and Participants: A total of 3233 US community-dwelling individuals aged 65 years or older with baseline serum thyroid-stimulating hormone levels were enrolled in 1989-1990 in the Cardiovascular Health Study, a large, prospective cohort study. Main Outcome Measures: Incident atrial fibrillation, coronary heart disease, cerebrovascular disease, cardiovascular death, and all-cause death assessed through June 2002. Analyses are reported for 4 groups defined according to thyroid function test results: subclinical hyperthyroidism, euthyroidism, subclinical hypothyroidism, and overt hypothyroidism. Results: Individuals with overt thyrotoxicosis(n=4) were excluded because of small numbers. Eighty-two percent of participants(n=2639) had normal thyroid function, 15% (n=496) had subclinical hypothyroidism, 1.6% (n=51)had overt hypothyroidism, and 1.5% (n=47) had subclinical hyperthyroidism. After exclusion of those with prevalent atrial fibrillation, individuals with subclinical hyperthyroidism had a greater incidence of atrial fibrillation compared with those with normal thyroid function(67 events vs 31 events per 1000 person-years; adjusted hazard ratio, 1.98; 95% confidence interval, 1.29-3.03). No differences were seen between the subclinical hyperthyroidism group and euthyroidism group for incident coronary heart disease, cerebrovascular disease, cardiovascular death, or all-cause death. Likewise, there were no differences between the subclinical hypothyroidism or overt hypothyroidism groups and the euthyroidism group for cardiovascular outcomes or mortality. Specifically, individuals with subclinical hypothyroidism had an adjusted hazard ratio of 1.07(95% confidence interval, 0.90-1.28) for incident coronary heart disease. Conclusion: Our data show an association between subclinical hyperthyroidism and development of atrial fibrillation but do not support the hypothesis that unrecognized subclinical hyperthyroidism or subclinical hypothyroidism is associated with other cardiovascular disorders or mortality.

大剂量他汀类药物治疗对冠状动脉粥样硬化消退的影响:ASTEROID试验

Context: Prior intravascular ultrasound(IVUS) trials have demonstrated slowing or halting of atherosclerosis progression with statin therapy but have not shown convincing evidence of regression using percent atheroma volume(PAV), the most rigorous IVUS measure of disease progression and regression. Objective: To assess whether very intensive statin therapy could regress coronary atherosclerosis as determined by IVUS imaging. Design and Setting: Prospective, open-label blinded endpoints trial(A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden[ASTEROID]) was performed at 53 community and tertiary care centers in the United States, Canada, Europe, and Australia. A motorized IVUS pullback was used to assess coronary atheroma burden at baseline and after 24 months of treatment. Each pair of baseline and follow-up IVUS assessments was analyzed in a blinded fashion. Patients: Between November 2002 and October 2003, 507 patients had a baseline IVUS examination and received at least 1 dose of study drug. After 24 months, 349 patients had evaluable serial IVUS examinations. Intervention: All patients received intensive statin therapy with rosuvastatin, 40 mg/d. Main Outcome Measures: Two primary efficacy parameters were prespecified: the change in PAV and the change in nominal atheroma volume in the 10-mm subsegment with the greatest disease severity at baseline. A secondary efficacy variable, change in normalized total atheroma volume for the entire artery, was also prespecified. Results: The mean(SD) baseline low-density lipoprotein cholesterol(LDL-C) level of 130.4(34.3) mg/dL declined to 60.8(20.0) mg/dL, a mean reduction of 53.2%(P< .001). Mean(SD) high-density lipoprotein cholesterol(HDL-C) level at baseline was 43.1(11.1) mg/dL, increasing to 49.0(12.6) mg/dL, an increase of 14.7%(P< .001). The mean(SD) change in PAV for the entire vessel was -0.98%(3.15%), with a median of-0.79%(97.5%CI,-1.21%to-0.53%)(P<.001 vs baseline). The mean(SD) change in atheroma volume in the most diseased 10-mm subsegment was-6.1(10.1) mm3, with a median of-5.6 mm3(97.5%CI,-6.8 to-4.0 mm3)(P< .001 vs baseline). Change in total atheroma volume showed a 6.8%median reduction; with a mean(SD) reduction of -14.7(25.7) mm3, with a median of-12.5 mm3(95%CI,-15.1 to-10.5 mm3)(P< .001 vs baseline). Adverse events were infrequent and similar to other statin trials. Conclusions: Very high-intensity statin therapy using rosuvastatin 40 mg/d achieved an average LDL-C of 60.8 mg/dL and increased HDL-C by 14.7%, resulting in significant regression of atherosclerosis for all 3 prespecified IVUS measures of disease burden. Treatment to LDL-C levels below currently accepted guidelines, when accompanied by significant HDL-C increases, can regress atherosclerosis in coronary disease patients. Further studies are needed to determine the effect of the observed changes on clinical outcome.

青少年和成人中低心肺适应性的患病率及其与心血管疾病的相关性

Context: Population surveys indicate that physical activity levels are low in the United States. One consequence of inactivity, low cardiorespiratory fitness, is an established risk factor for cardiovascular disease(CVD) morbidity and mortality, but the prevalence of cardiorespiratory fitness has not been quantified in representative US population samples. Objectives: To describe the prevalence of low fitness in the US population aged 12 through 49 years and to relate low fitness to CVD risk factors in this population. Design, Setting, and Participants: Inception cohort study using data from the crosssectional nationally representative National Health and Nutrition Examination Survey 1999- 2002. Participants were adolescents(aged 12- 19 years; n=3110) and adults(aged 20- 49 years; n=2205) free from previously diagnosed CVD who underwent submaximal graded exercise treadmill testing to achieve at least 75% to 90% of their age predicted maximum heart rate. Maximal oxygen consumption(VO2max) was estimated by measuring the heart rate response to reference levels of submaximal work. Main Outcome Measures: Low fitness defined using percentile cut points of estimated VO2max from existing external referent populations; anthropometric and other CVD risk factors measured according to standard methods. Results: Low fitness was identified in 33.6% of adolescents(approximately 7.5 million US adolescents) and 13.9% of adults(approximately 8.5 million US adults); the prevalence was similar in adolescent females(34.4% ) and males(32.9% )(P=.40) but was higher in adult females(16.2% ) than in males(11.8% )(P=.03). Non-Hispanic blacks and Mexican Americans were less fit than non-Hispanic whites. In all age-sex groups, body mass index and waist circumference were inversely associated with fitness; age- and race-adjusted odds ratios of overweight or obesity(body mass index ≥ 25) ranged from 2.1 to 3.7(P >.01 for all), comparing persons with low fitness with those with moderate or high fitness. Total cholesterol levels and systolic blood pressure were higher and levels of high-density lipoprotein cholesterol were lower among participants with low vs high fitness. Conclusion: Low fitness in adolescents and adults is common in the US population and is associated with an increased prevalence of CVD risk factors.

咖啡、CYP1A2基因型和心肌梗死风险

Context: The association between coffee intake and risk of myocardial infarction(MI) remains controversial. Coffee is a major source of caffeine, which is metabolized by the polymorphic cytochrome P450 1A2(CYP1A2) enzyme. Individuals who are homozygous for the CYP1A2* 1A allele are “ rapid” caffeine metabolizers, whereas carriers of the variant CYP1A2* 1F are “ slow” caffeine metabolizers. Objective: To determine whether CYP1A2 genotype modifies the association between coffee consumption and risk of acute nonfatal MI. Design, Setting, and Participants: Cases(n=2014) with a first acute nonfatal MI and population-based controls(n=2014) living in Costa Rica between 1994 and 2004, matched for age, sex, and area of residence, were genotyped by restriction fragment-length polymorphism polymerase chain reaction. A food frequency questionnaire was used to assess the intake of caffeinated coffee. Main Outcome Measure: Relative risk of nonfatal MI associated with coffee intake, calculated using unconditional logistic regression. Results: Fifty-five percent of cases(n=1114) and 54% of controls(n=1082) were carriers of the slow * 1F allele. For carriers of the slow * 1F allele, the multivariate-adjusted odds ratios(ORs) and 95% confidence intervals(CIs) of nonfatal MI associated with consuming less than 1, 1, 2 to 3, and 4 or more cups of coffee per day were 1.00(reference), 0.99(0.69-1.44), 1.36(1.01-1.83), and 1.64(1.14-2.34), respectively. Corresponding ORs(95% CIs) for individuals with the rapid * 1A/* 1A genotype were 1.00, 0.75(0.51-1.12), 0.78(0.56-1.09), and 0.99(0.66-1.48)(P=.04 for gene × coffee interaction). For individuals younger than the median age of 59 years, the ORs(95% CIs) associated with consuming less than 1, 1, 2 to 3, or 4 or more cups of coffee per day were 1.00, 1.24(0.71-2.18), 1.67(1.08-2.60), and 2.33(1.39-3.89), respectively, among carriers of the * 1F allele. The corresponding ORs(95% CIs) for those with the * 1A/* 1A genotype were 1.00, 0.48(0.26-0.87), 0.57(0.35-0.95), and 0.83(0.46-1.51). Conclusion: Intake of coffee was associated with an increased risk of nonfatal MI only among individuals with slow caffeine metabolism, suggesting that caffeine plays a role in this association.

比伐卢定治疗急性冠状动脉综合征

背景：当前指南推荐对中危或高危急性冠状动脉综合征患者早期进行介入治疗，并同时应用抗栓治疗，包括阿司匹林、氯吡格雷、普通或低分子肝素以及糖蛋白Ⅱb／Ⅲa抑制剂。作者评估了在此类患者中应用比伐卢定行凝血酶特异性抗凝治疗的作用。方法：对13819例急性冠状动脉综合征患者，给予3种不同的抗凝治疗方案：普通肝素或依诺肝素加糖蛋白Ⅱb／Ⅲa抑制剂，比伐卢定加糖蛋白Ⅱb／Ⅲa抑制剂，单用比伐卢定。