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1.
Hackam DG  Anand SS 《JAMA》2003,290(7):932-940
Context  Atherosclerotic vascular disease is an enormous public health problem. A number of emerging risk factors for atherosclerosis have recently been proposed to help identify high-risk individuals. Objective  To review the epidemiological, basic science, and clinical trial evidence concerning 4 emerging risk factors: C-reactive protein, lipoprotein(a), fibrinogen, and homocysteine. Data Sources  Using the terms atherosclerosis, cardiovascular disease, risk factors, prevention, screening, C-reactive protein, lipoprotein(a), fibrinogen, and homocysteine, we searched the MEDLINE database from January 1990 to January 2003. Conference proceedings, abstract booklets, bibliographies of pertinent articles and books, and personal files were hand searched to identify additional articles. Study Selection  Original investigations and reviews of the epidemiology of atherosclerosis and the association of conventional and novel risk factors with vascular risk were selected. On the basis of the search strategy, 373 relevant studies were identified. Data Extraction  A diverse array of studies were examined, including randomized controlled trials, prospective cohort studies, systematic overviews, case-control, cross-sectional, and mechanistic studies. Data extraction was performed by one of the authors. Data Synthesis  The available epidemiological and basic science evidence supports, to varying degrees, independent associations between these 4 candidate risk factors and atherosclerotic vascular disease. However, there is relatively little data regarding the additive yield of screening for these factors over that of validated global risk assessment strategies currently in use. Furthermore, controlled intervention studies targeting individuals with these factors for proven risk-reduction therapies, or specifically treating these factors with available therapies, are few. The explanatory power of the major, established cardiovascular risk factors has been systematically underestimated. Conclusions  Although C-reactive protein, lipoprotein(a), fibrinogen, and homocysteine are associated with vascular disease risk, their optimal use in routine screening and risk stratification remains to be determined.   相似文献   

2.
Context  While current practice guidelines provide an evidence-based approach to management of acute coronary syndromes (ACS), application of the evidence by individual physicians has been suboptimal. Objective  To assess and synthesize the evidence regarding optimal management of non–ST-segment elevation ACS (NSTE-ACS). Data Sources  Systematic searches of peer-reviewed publications were performed in MEDLINE and the Cochrane Database from January 1990 through November 2004, with consultation by content experts. Search terms included antiplatelet therapy, antithrombotic therapy, angiotensin-converting enzyme inhibition, angiotensin receptor blockade, -blockade, hypertension, hyperlipidemia, cigarette smoking, diet, diabetes mellitus, exercise, myocardial ischemia, and coronary artery disease. Study Selection and Data Extraction  Criteria for selection of studies included controlled study design, English language, and clinical pertinence. Data quality was based on the publishing journal and relevance to clinical management of NSTE-ACS. Data Synthesis  While outcomes of controlled studies support a comprehensive approach in the management of patients with NSTE-ACS, many physicians perceive existing guidelines as lengthy and complex. After risk stratification to identify those patients most likely to benefit from an early invasive vs early conservative strategy, a comprehensive management plan can be assembled through an "ABCDE" approach. The elements of this include "A" for antiplatelet therapy, anticoagulation, angiotensin-converting enzyme inhibition, and angiotensin receptor blockade; "B" for -blockade and blood pressure control; "C" for cholesterol treatment and cigarette smoking cessation; "D" for diabetes management and diet; and "E" for exercise. Conclusion  An "ABCDE" approach for the management of NSTE-ACS provides a practical and systematic means to implement evidence-based medicine into clinical practice.   相似文献   

3.
Context  Aspirin therapy reduces the risk of cardiovascular disease in adults who are at increased risk. However, it is unclear if women derive the same benefit as men. Objective  To determine if the benefits and risks of aspirin treatment in the primary prevention of cardiovascular disease vary by sex. Data Sources and Study Selection  MEDLINE and the Cochrane Central Register of Controlled Trials databases (1966 to March 2005), bibliographies of retrieved trials, and reports presented at major scientific meetings. Eligible studies were prospective, randomized controlled trials of aspirin therapy in participants without cardiovascular disease that reported data on myocardial infarction (MI), stroke, and cardiovascular mortality. Six trials with a total of 95 456 individuals were identified; 3 trials included only men, 1 included only women, and 2 included both sexes. Data Extraction  Studies were reviewed to determine the number of patients randomized, mean duration of follow-up, and end points (a composite of cardiovascular events [nonfatal MI, nonfatal stroke, and cardiovascular mortality], each of these individual components separately, and major bleeding). Data Synthesis  Among 51 342 women, there were 1285 major cardiovascular events: 625 strokes, 469 MIs, and 364 cardiovascular deaths. Aspirin therapy was associated with a significant 12% reduction in cardiovascular events (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.79-0.99; P = .03) and a 17% reduction in stroke (OR, 0.83; 95% CI, 0.70-0.97; P = .02), which was a reflection of reduced rates of ischemic stroke (OR, 0.76; 95% CI, 0.63-0.93; P = .008). There was no significant effect on MI or cardiovascular mortality. Among 44 114 men, there were 2047 major cardiovascular events: 597 strokes, 1023 MIs, and 776 cardiovascular deaths. Aspirin therapy was associated with a significant 14% reduction in cardiovascular events (OR, 0.86; 95% CI, 0.78-0.94; P = .01) and a 32% reduction in MI (OR, 0.68; 95% CI, 0.54-0.86; P = .001). There was no significant effect on stroke or cardiovascular mortality. Aspirin treatment increased the risk of bleeding in women (OR, 1.68; 95% CI, 1.13-2.52; P = .01) and in men (OR, 1.72; 95% CI, 1.35-2.20; P<.001). Conclusions  For women and men, aspirin therapy reduced the risk of a composite of cardiovascular events due to its effect on reducing the risk of ischemic stroke in women and MI in men. Aspirin significantly increased the risk of bleeding to a similar degree among women and men.   相似文献   

4.
Schneider LS  Dagerman KS  Insel P 《JAMA》2005,294(15):1934-1943
Context  Atypical antipsychotic medications are widely used to treat delusions, aggression, and agitation in people with Alzheimer disease and other dementia; however, concerns have arisen about the increased risk for cerebrovascular adverse events, rapid cognitive decline, and mortality with their use. Objective  To assess the evidence for increased mortality from atypical antipsychotic drug treatment for people with dementia. Data Sources  MEDLINE (1966 to April 2005), the Cochrane Controlled Trials Register (2005, Issue 1), meetings presentations (1997-2004), and information from the sponsors were searched using the terms for atypical antipsychotic drugs (aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone), dementia, Alzheimer disease, and clinical trial. Study Selection  Published and unpublished randomized placebo-controlled, parallel-group clinical trials of atypical antipsychotic drugs marketed in the United States to treat patients with Alzheimer disease or dementia were selected by consensus of the authors. Data Extraction  Trials, baseline characteristics, outcomes, all-cause dropouts, and deaths were extracted by one reviewer; treatment exposure was obtained or estimated. Data were checked by a second reviewer. Data Synthesis  Fifteen trials (9 unpublished), generally 10 to 12 weeks in duration, including 16 contrasts of atypical antipsychotic drugs with placebo met criteria (aripiprazole [n = 3], olanzapine [n = 5], quetiapine [n = 3], risperidone [n = 5]). A total of 3353 patients were randomized to study drug and 1757 were randomized to placebo. Outcomes were assessed using standard methods (with random- or fixed-effects models) to calculate odds ratios (ORs) and risk differences based on patients randomized and relative risks based on total exposure to treatment. There were no differences in dropouts. Death occurred more often among patients randomized to drugs (118 [3.5%] vs 40 [2.3%]. The OR by meta-analysis was 1.54; 95% confidence interval [CI], 1.06-2.23; P = .02; and risk difference was 0.01; 95% CI, 0.004-0.02; P = .01). Sensitivity analyses did not show evidence for differential risks for individual drugs, severity, sample selection, or diagnosis. Conclusions  Atypical antipsychotic drugs may be associated with a small increased risk for death compared with placebo. This risk should be considered within the context of medical need for the drugs, efficacy evidence, medical comorbidity, and the efficacy and safety of alternatives. Individual patient analyses modeling survival and causes of death are needed.   相似文献   

5.
Context  The value of exercise testing in women has been questioned. Objective  To determine the prognostic value of exercise testing in a population-based cohort of asymptomatic women followed up for 20 years. Design and Setting  Near-maximal Bruce-protocol treadmill test data from the Lipid Research Clinics Prevalence Study (1972-1976) with follow-up through 1995. Participants  A total of 2994 asymptomatic North American women, aged 30 to 80 years, without known cardiovascular disease. Main Outcome Measures  Cardiovascular and all-cause mortality. Results  There were 427 (14%) deaths during 20 years of follow-up, of which 147 were due to cardiovascular causes. Low exercise capacity, low heart rate recovery (HRR), and not achieving target heart rate were independently associated with increased all-cause and cardiovascular mortality. There was no increased cardiovascular death risk for exercise-induced ST-segment depression (age-adjusted hazard ratio, 1.02; 95% confidence interval [CI], 0.57-1.80; P = .96). The age-adjusted hazard ratio for cardiovascular death for every metabolic equivalent (MET) decrement in exercise capacity was 1.20 (95% CI, 1.18-1.30; P<.001); for every 10 beats per minute decrement in HRR, the hazard ratio was 1.36 (95% CI, 1.19-1.55; P<.001). After adjusting for multiple other risk factors, women who were below the median for both exercise capacity and HRR had a 3.5-fold increased risk of cardiovascular death (95% CI, 1.57-7.86; P = .002) compared with those above the median for both variables. Among women with low risk Framingham scores, those with below median levels of both exercise capacity and HRR had significantly increased risk compared with women who had above median levels of these 2 exercise variables, 44.5 and 3.5 cardiovascular deaths per 10 000 person-years, respectively (hazard ratio for cardiovascular death, 12.93; 95% CI, 5.62-29.73; P<.001). Conclusion  The prognostic value of exercise testing in asymptomatic women derives not from electrocardiographic ischemia but from fitness-related variables.   相似文献   

6.
Long-term risk of cardiovascular events with rosiglitazone: a meta-analysis   总被引:15,自引:0,他引:15  
Singh S  Loke YK  Furberg CD 《JAMA》2007,298(10):1189-1195
Context  Recent reports of serious adverse events with rosiglitazone use have raised questions about whether the evidence of harm justifies its use for treatment of type 2 diabetes. Objective  To systematically review the long-term cardiovascular risks of rosiglitazone, including myocardial infarction, heart failure, and cardiovascular mortality. Data Sources  We searched MEDLINE, the GlaxoSmithKline clinical trials register, the US Food and Drug Administration Web site, and product information sheets for randomized controlled trials, systematic reviews, and meta-analyses published in English through May 2007. Study Selection  Studies were selected for inclusion if they were randomized controlled trials of rosiglitazone for prevention or treatment of type 2 diabetes, had at least 12 months of follow-up, and monitored cardiovascular adverse events and provided numerical data on all adverse events. Four studies were included after detailed screening of 140 trials for cardiovascular events. Data Extraction  Relative risks (RRs) of myocardial infarction, heart failure, and cardiovascular mortality were estimated using a fixed-effects meta-analysis of 4 randomized controlled trials (n = 14 291, including 6421 receiving rosiglitazone and 7870 receiving control therapy, with a duration of follow-up of 1-4 years). Results  Rosiglitazone significantly increased the risk of myocardial infarction (n = 94/6421 vs 83/7870; RR, 1.42; 95% confidence interval [CI], 1.06-1.91; P = .02) and heart failure (n = 102/6421 vs 62/7870; RR, 2.09; 95% CI, 1.52-2.88; P < .001) without a significant increase in risk of cardiovascular mortality (n = 59/6421 vs 72/7870; RR, 0.90; 95% CI, 0.63-1.26; P = .53). There was no evidence of substantial heterogeneity among the trials for these end points (I2 = 0% for myocardial infarction, 18% for heart failure, and 0% for cardiovascular mortality). Conclusion  Among patients with impaired glucose tolerance or type 2 diabetes, rosiglitazone use for at least 12 months is associated with a significantly increased risk of myocardial infarction and heart failure, without a significantly increased risk of cardiovascular mortality.   相似文献   

7.
Context  The effect of antihypertensive drugs on cardiovascular events in patients with coronary artery disease (CAD) and normal blood pressure remains uncertain. Objective  To compare the effects of amlodipine or enalapril vs placebo on cardiovascular events in patients with CAD. Design, Setting, and Participants  Double-blind, randomized, multicenter, 24-month trial (enrollment April 1999-April 2002) comparing amlodipine or enalapril with placebo in 1991 patients with angiographically documented CAD (>20% stenosis by coronary angiography) and diastolic blood pressure <100 mm Hg. A substudy of 274 patients measured atherosclerosis progression by intravascular ultrasound (IVUS). Interventions  Patients were randomized to receive amlodipine, 10 mg; enalapril, 20 mg; or placebo. IVUS was performed at baseline and study completion. Main Outcome Measures  The primary efficacy parameter was incidence of cardiovascular events for amlodipine vs placebo. Other outcomes included comparisons of amlodipine vs enalapril and enalapril vs placebo. Events included cardiovascular death, nonfatal myocardial infarction, resuscitated cardiac arrest, coronary revascularization, hospitalization for angina pectoris, hospitalization for congestive heart failure, fatal or nonfatal stroke or transient ischemic attack, and new diagnosis of peripheral vascular disease. The IVUS end point was change in percent atheroma volume. Results  Baseline blood pressure averaged 129/78 mm Hg for all patients; it increased by 0.7/0.6 mm Hg in the placebo group and decreased by 4.8/2.5 mm Hg and 4.9/2.4 mm Hg in the amlodipine and enalapril groups, respectively (P<.001 for both vs placebo). Cardiovascular events occurred in 151 (23.1%) placebo-treated patients, in 110 (16.6%) amlodipine-treated patients (hazard ratio [HR], 0.69; 95% CI, 0.54-0.88 [P = .003]), and in 136 (20.2%) enalapril-treated patients (HR, 0.85; 95% CI, 0.67-1.07 [P = .16]. Primary end point comparison for enalapril vs amlodipine was not significant (HR, 0.81; 95% CI, 0.63-1.04 [P = .10]). The IVUS substudy showed a trend toward less progression of atherosclerosis in the amlodipine group vs placebo (P = .12), with significantly less progression in the subgroup with systolic blood pressures greater than the mean (P = .02). Compared with baseline, IVUS showed progression in the placebo group (P<.001), a trend toward progression in the enalapril group (P = .08), and no progression in the amlodipine group (P = .31). For the amlodipine group, correlation between blood pressure reduction and progression was r = 0.19, P = .07. Conclusions  Administration of amlodipine to patients with CAD and normal blood pressure resulted in reduced adverse cardiovascular events. Directionally similar, but smaller and nonsignificant, treatment effects were observed with enalapril. For amlodipine, IVUS showed evidence of slowing of atherosclerosis progression.   相似文献   

8.
Andraws R  Berger JS  Brown DL 《JAMA》2005,293(21):2641-2647
Context  Although Chlamydia pneumoniae infection has been associated with the initiation and progression of atherosclerosis, results of clinical trials investigating antichlamydial antibiotics as adjuncts to standard therapy in patients with coronary artery disease (CAD) have been inconsistent. Objective  To conduct a meta-analysis of clinical trials of antichlamydial antibiotic therapy in patients with CAD. Data Sources  The MEDLINE and Cochrane Central Register of Controlled Trials databases were searched from 1966 to April 2005 for English-language trials of antibiotic therapy in patients with CAD. Bibliographies of retrieved articles were searched for further studies. Presentations at major scientific meetings (2003-2004) were also reviewed. Search terms included antibacterial agents, myocardial infarction, unstable angina, and coronary arteriosclerosis. Study Selection  Eligible studies were prospective, randomized, placebo-controlled trials of antichlamydial antibiotic therapy in patients with CAD that reported all-cause mortality, myocardial infarction, or unstable angina. Of the 110 potentially relevant articles identified, 11 reports enrolling 19 217 patients were included. Data Extraction  Included studies were reviewed to determine the number of patients randomized, mean duration of follow-up, and end points. End points of interest included all-cause mortality, myocardial infarction (MI), and a combined end point of MI and unstable angina. Data Synthesis  Event rates were combined using a random-effects model. Antibiotic therapy had no impact on all-cause mortality among treated vs untreated patients (4.7% vs 4.6%; odds ratio [OR], 1.02; 95% confidence interval [CI], 0.89-1.16; P = .83), on the rates of MI (5.0% vs 5.4%; OR, 0.92; 95% CI, 0.81-1.04; P = .19), or on the combined end point of MI and unstable angina (9.2% vs 9.6%; OR, 0.91; 95% CI, 0.76-1.07; P = .25). Conclusion  Evidence available to date does not demonstrate an overall benefit of antibiotic therapy in reducing mortality or cardiovascular events in patients with CAD.   相似文献   

9.
High-density lipoprotein as a therapeutic target: a systematic review   总被引:9,自引:0,他引:9  
Singh IM  Shishehbor MH  Ansell BJ 《JAMA》2007,298(7):786-798
Context  High-density lipoprotein cholesterol (HDL-C) is a cardiovascular risk factor that is gaining substantial interest as a therapeutic target. Objectives  To review the current and emerging strategies that modify high-density lipoproteins (HDLs). Data Sources  Systematic search of English-language literature (1965-May 2007) in MEDLINE and the Cochrane database, using the key words HDL-C and apolipoprotein A-I and the subheadings reverse cholesterol transport, CVD [cardiovascular disease] prevention and control, drug therapy, and therapy; review of presentations made at major cardiovascular meetings from 2003-2007; and review of ongoing trials from ClinicalTrials.gov and current guidelines from major cardiovascular societies. Study Selection and Data Extraction  Study selection was prioritized to identify randomized controlled trials over meta-analyses over mechanistic studies; identified studies also included proof-of-concept studies and key phase 1 through 3 trials of novel agents. Study eligibility was assessed by 2 authors; disagreements were resolved by consensus with the third. Data Synthesis  Of 754 studies identified, 31 randomized controlled trials met the inclusion criteria. Currently available therapeutic and lifestyle strategies, when optimized, increase HDL-C levels by 20% to 30%. While basic and small pilot studies have shown promise, proof that increasing HDL-C levels confers a reduction in major cardiovascular outcomes independent of changes in levels of low-density lipoprotein cholesterol or triglycerides has been more elusive. Some novel therapeutic agents in human studies appear to effectively increase HDL-C levels, whereas other novel strategies that target HDL metabolism or function may have minimal effect on HDL-C levels. Conclusions  At present there is modest evidence to support aggressively increasing HDL-C levels in addition to what is achieved by lifestyle modification alone. Ongoing clinical trials that target specific pathways in HDL metabolism may help expand cardiovascular treatment options.   相似文献   

10.
Mixed dementia: emerging concepts and therapeutic implications   总被引:9,自引:0,他引:9  
Langa KM  Foster NL  Larson EB 《JAMA》2004,292(23):2901-2908
Context  The prevalence of mixed dementia, defined as the coexistence of Alzheimer disease (AD) and vascular dementia (VaD), is likely to increase as the population ages. Objectives  To provide an overview of the diagnosis, pathophysiology, and interaction of AD and VaD in mixed dementia, and to provide a systematic literature review of the current evidence for the pharmacologic therapy of mixed dementia. Data Sources, Study Selection, and Data Extraction  The Cochrane Database of Systematic Reviews was searched using the keyword dementia. MEDLINE was searched for English-language articles published within the last 10 years using the keywords mixed dementia, the combination of keywords Alzheimer disease, cerebrovascular disorders, and drug therapy, and the combination of keywords vascular dementia and drug therapy. Evidence Synthesis  Dementia is more likely to be present when vascular and AD lesions coexist, a situation that is especially common with increasing age. The measured benefits in clinical trials for the treatment of mixed dementia are best described as statistically significant differences in cognitive test scores and clinician and caregiver impressions of change. In these studies, the control groups’ scores typically decline while the treatment groups improve slightly or decline to a lesser degree over the study period. Nevertheless, even the patients who experience treatment benefits eventually decline. Cholinesterase inhibitor (ChI) therapy for mixed dementia shows modest clinical benefits that are similar to those found for ChI treatment of AD. The N-methyl-D-aspartate (NMDA) antagonist memantine also shows modest clinical benefits for the treatment of moderate to severe AD and mild to moderate VaD, but it has not been studied specifically in mixed dementia. The treatment of cardiovascular risk factors, especially hypertension, may be a more effective way to protect brain function as primary, secondary, and tertiary prevention for mixed dementia. Conclusions  Currently available medications provide only modest clinical benefits once a patient has developed mixed dementia. Cardiovascular risk factor control, especially for hypertension and hyperlipidemia, as well as other interventions to prevent recurrent stroke, likely represent important strategies for preventing or slowing the progression of mixed dementia. Additional research is needed to define better what individuals and families hope to achieve from dementia treatment and to determine the most appropriate use of medication to achieve these goals.   相似文献   

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