<正>冠状动脉粥样硬化性心脏病(冠心病)是美国成年人的首要死亡原因。2型糖尿病患者具有不成比例的冠心病高发病率和病死率。血脂异常、高血压、促血栓形成因子和促炎症因子均能促进肥胖糖尿病患者的动脉粥样硬化的发生发展。然而,造成糖尿病患者的冠心病发生风险大幅度增加的病理生理机制目前还不明确。

BACKGROUND:The benefit of coronary-artery revascularization before elective major vascular surgery is unclear.METHODS:We randomly assigned patients at increased risk for perioperative cardiac complications and clinically significant coronary artery disease to undergo either revascularization or no revascularization before elective major vascular surgery. The primary end point was long-term mortality.RESULTS:Of 5859 patients scheduled for vascular operations at 18 Veterans Affairs medical centers, 510 (9 percent) were eligible for the study and were randomly assigned to either coronary-artery revascularization before surgery or no revascularization before surgery. The indications for a vascular operation were an expanding abdominal aortic aneurysm (33 percent) or arterial occlusive disease of the legs (67 percent). Among the patients assigned to preoperative coronary-artery revascularization, percutaneous coronary intervention was performed in 59 percent, and bypass surgery was performed in 41 percent. The median time from randomization to vascular surgery was 54 days in the revascularization group and 18 days in the group not undergoing revascularization (P<0.001). At 2.7 years after randomization, mortality in the revascularization group was 22 percent and in the no-revascularization group 23 percent (relative risk, 0.98; 95 percent confidence interval, 0.70 to 1.37; P=0.92). Within 30 days after the vascular operation, a postoperative myocardial infarction, defined by elevated troponin levels, occurred in 12 percent of the revascularization group and 14 percent of the no-revascularization group (P=0.37).CONCLUSIONS:Coronary-artery revascularization before elective vascular surgery does not significantly alter the long-term outcome. On the basis of these data, a strategy of coronary-artery revascularization before elective vascular surgery among patients with stable cardiac symptoms cannot be recommended.

BackgroundInformation is limited regarding the effects of processes of care on cardiac surgical outcomes. Correspondingly, many recommended cardiac surgical processes of care are derived from animal experiments or clinical judgment. This report from the VA Cooperative Study in Health Services, “Processes, Structures, and Outcomes of Cardiac Surgery,” focuses on the relationships between 3 process groups (preoperative evaluation, intraoperative care, and supervision by senior physicians) and a composite outcome, perioperative mortality and morbidity. MethodsData on 734 risk, process, and structure variables were collected prospectively on 3988 patients who underwent coronary artery bypass grafting at 14 VA medical centers between 1992 and 1996. Data reduction was accomplished by examining data completeness and variation across sites and surgeon, using previously published data and clinical judgment. We then applied multivariable logistic regression to the 39 remaining processes of care to determine which were related to the composite outcome after adjusting for 17 patient-related risk factors and controlling for intraoperative complications. ResultsOur first analysis showed several measures of operative duration, the use of inotropic agents, transesophageal echo, lowest systemic temperature, and hemoconcentration/ultrafiltration, to be powerful predictors of the composite outcome. Because the use of inotropic agents and operative duration may be related to an intermediate outcome (eg, intraoperative complications), we performed a second analysis omitting these processes. The use of intraoperative transesophageal echo and hemoconcentration/ultrafiltration remained significantly associated with an increased risk of an event (odds ratios 1.60 and 1.36, respectively). ConclusionsOur results viewed in the context of past studies suggest the possibility that inotropic use, TEE, and hemoconcentration/ultrafiltration may have adverse effects on operative outcome. Further evaluation of these processes of care using observational data, as well as randomized trials when feasible, would be of interest.

Despite consensus guidelines, the optimal strategy for preoperative cardiac risk management among patients scheduled for major noncardiac surgery remains controversial. This study assesses current opinion about the role of preoperative coronary revascularization for patients with coronary artery disease scheduled for elective vascular surgery. Thirty-one practicing cardiologists recruited from 4 different regions reviewed case records, imaging tests, and coronary angiograms of 12 patients with coronary artery disease participating in the Coronary Artery Revascularization Prophylaxis (CARP) trial. The need for preoperative coronary revascularization was determined and results summarized using 3 categories: favoring conservative management, neutral, or recommending revascularization (either by percutaneous intervention or bypass surgery). We found recommendations were frequently disparate and often deviated from published guidelines (40% of the time). The likelihood of discordance between 2 cardiologists was 54%, with a 26% chance that recommendations for revascularization would be directly contradictory. Opinions were more often conservative (43%) or aggressive (40%) than neutral (17%). Similar inconsistency was found as to the preferred method of revascularization, with only 1 patient having complete agreement. Thus, this study reveals substantial differences of opinion among cardiologists across the country about the role of preoperative coronary artery revascularization for patients scheduled for elective vascular operations. Deviations from published guidelines are common, suggesting that current consensus statements need additional data to support their recommendations.

Background Controversy exists regarding the utility of continuous monitoring of mixed venous oxygen saturation (STvo2) during cardiac surgery. During a multicenter, prospective, observational study in the Department of Veterans Affairs (Cooperative Study #5), frequency of use of standard pulmonary artery catheterization (PAC) and STvo2-PAC was recorded. Here the authors relate these data to clinical outcomes. Methods Logistic and Cox regression models evaluating the association of PAC type with mortality, one or more postoperative complications, cardiac complications, time to extubation, and intensive care unit length of stay were constructed. The number of thermodilution cardiac outputs and arterial blood gas analyses performed in the first 24 h postoperatively were compared. Results Data from 3,265 patients undergoing myocardial revascularization (81.7%) or valve replacement-repair (18.3%) were considered. STvo2-PAC was used in 49% and PAC in 51% of patients. In the 14 hospitals, STvo2-PAC was used in all patients in four, in some patients in four, and never in six. No association of STvo2-PAC use with outcome were observed aside from unexplained hospital level effects. A small but statistically significant reduction in the number of arterial blood gas analyses (8 +/- 3 vs. 10 +/- 4, P < 0.0001, STvo2-PAC vs. PAC, respectively) and thermodilution cardiac outputs (14 +/- 8 vs. 15 +/- 9, P < 0.0001, STvo2-PAC vs. PAC, respectively) was observed with use of STvo2-PAC. Conclusions Despite higher cost, STvo2-PAC was commonly used in this cohort. Our analysis failed to detect associations with improved outcomes aside from a small reduction in resource utilization. The precise role of STvo2-PAC remains uncertain.

The present study was performed to ascertain whether the presence of mild renal failure (defined as a serum creatinine concentration of 1. 5 to 3.0 mg/dL) is an independent risk factor for adverse outcome after cardiac valve surgery. An extensive set of preoperative and postoperative data was collected in 834 prospectively evaluated patients undergoing cardiac valve surgery at 14 Veterans Affairs Medical Centers. Univariate and multivariable analyses were performed to determine whether an independent association of mild renal dysfunction with adverse outcomes was present. Patients with mild renal failure had significantly greater 30-day mortality rates (P = 0.001; 16% versus 6%) and frequency of postoperative bleeding (P = 0.023; 16% versus 8%), respiratory complications (P = 0.02, 29% versus 16%), and cardiac complications (P = 0.002; 18% versus 7%) than patients with normal renal function (serum creatinine <1.5 mg/dL) when controlling for multiple other variables. The presence of a serum creatinine concentration of 1.5 to 3.0 mg/dL is significantly and independently associated with adverse outcomes after cardiac valve surgery.

The chronic alcoholic patient is usually immunosuppressed, but the significance of this phenomenon in terms of bile duct injury is unclear. The immunoreactivity of the bile duct cells was examined in a series of 69 frozen liver biopsy specimens obtained from patients with alcoholic liver disease, comprising 29 cases of cirrhosis, 26 of alcoholic hepatitis, 10 cases of alcoholic fatty liver, and 4 specimens from normal livers. Liver diseases such as primary biliary cirrhosis and human hepatic allograft rejection, known to have an autoimmune basis, share the characteristic feature of damage to the bile duct epithelial cells. In both instances the damage seems to be immune mediated, but the nature of the antigens involved is not established. We used the avidin-biotin-peroxidase complex method to test in alcoholic liver disease far the expression of a battery of surface antigen markers that have been incriminated in tissue injury and are usually present in lymphoid cells but also expressed by epithelium. In this study we investigated the expression of the following molecules: HLA class I (ABC) and class II (HLA-DR, HLA-DP, HLA-DQ), CD29, CD45RA, CD45RO, CD56, interleukin 1(IL-l), IL-2, IL-4, interferon (IFN-gamma), tumor necrosis factor beta, and transforming growth factor beta 1 (TGF-beta 1). The bile duct epithelial cells strongly expressed HLA-ABC in all cases, CD56 in 47 of 55, IL-4 in 15 of 41, TGF-beta 1 in 14 of 25, and CD29 in 4 of 25 cases. The other markers including IFN-gamma, HLA-DR, HLA-DP, and HLA-DQ were not expressed by bile duct cells. The expression of HLA class I agrees with previous observations while the absence of class II expression does not. The expression by the bile duct epithelium of CD56 confirms our own previous report. A new observation is the finding of molecules such as IL-4, TGF-beta 1, and CD29 strongly expressed in the bile ducts cells. The presence of these molecules, taken together with the lack of IFN-gamma expression, contradicts previous speculations that attributed to IFN-gamma a role in the induction of major histocompatibility antigens and adhesion molecules in immune-mediated alcoholic liver disease.

BACKGROUND:Despite improving outcomes in cardiac surgical patients, stroke continues to remain a major complication. Few prospective studies are available on postoperative stroke. The present study was conducted to elucidate the incidence and predictors of stroke in a large group of cardiac surgical patients.METHODS AND RESULTS:Prospective data collected on 4,941 patients undergoing cardiac surgery were subjected to univariate and logistic regression analyses (98.4% men; 72% older than 60 years; 9.1% with history of prior stroke; 80.4% underwent isolated coronary artery bypass grafting). Stroke predictors include history of stroke and hypertension, older age, systolic hypertension, bronchodilator and diuretic use, high serum creatinine, surgical priority, great vessel repair, use of inotropic agents after cardiopulmonary bypass, and total cardiopulmonary bypass time (p < 0.05 for all comparisons). Median intensive care unit and hospital stays were longer, and hospital mortality and 6-month mortality were higher for patients with stroke (p < 0.001).CONCLUSIONS:Stroke after cardiac surgical procedures is a morbid event. Identification of predictors and development of strategies to modify these factors should lead to a lower incidence of stroke.

BACKGROUND:More than 600,000 coronary artery bypass graft (CABG) procedures are done annually in the United States. Some data indicate that 10 to 20% of patients who are undergoing a CABG procedure have a serum creatinine of more than 1.5 mg/dl. There are few data on the impact of a mild increase in serum creatinine concentration on CABG outcome.METHODS:We analyzed a Veterans Affairs database obtained prospectively from 1992 through 1996 at 14 of 43 centers performing heart surgery. We compared the outcome after CABG in patients with a baseline serum creatinine of less than 1.5 mg/dl (median 1.1 mg/dl, N = 3271) to patients with a baseline serum creatinine of 1.5 to 3.0 mg/dl (median 1.7, N = 631).RESULTS:Univariate analysis revealed that patients with a serum creatinine of 1.5 to 3.0 mg/dl had a higher 30-day mortality (7% vs. 3%, P < 0.001) requirement for prolonged mechanical ventilation (15% vs. 8%, P = 0.001), stroke (7% vs. 2%, P < 0.001), renal failure requiring dialysis at discharge (3% vs. 1%, P < 0.001), and bleeding complications (8% vs. 3%, P < 0.001) than patients with a baseline serum creatinine of less than 1.5 mg/dl. Multiple logistic regression analyses found that patients with a baseline serum creatinine of less than 1.5 mg/dl had significantly lower (P < 0.02) 30-day mortality and postoperative bleeding and ventilatory complications than patients with a serum creatinine of 1.5 to 3.0 mg/dl when controlling for all other variables.CONCLUSION:These results demonstrate that mild renal failure is an independent risk factor for adverse outcome after CABG.

Context Health-related quality of life has not been evaluated as a predictor of mortality following coronary artery bypass graft (CABG) surgery. Evaluation of health status as a mortality predictor may be useful for preoperative risk stratification.Objective To determine whether the Physical and Mental Component Summary scores from the preoperative Short-Form 36 (SF-36) health status survey predict mortality following CABG surgery after adjustment for known clinical risk variables.Design Prospective cohort study conducted between September 1992 and December. 1996.Setting Fourteen Veterans Affairs hospitals.Patients Of the 3956 patients undergoing CABG surgery only and who were enrolled in the Processes, Structures, and Outcomes of Care in Cardiac Surgery study, the 2480 who completed a preoperative SF-36.Main Outcome Measure All-cause mortality within 180 days after surgery.Results A total of 117 deaths (4.7%) occurred within 180 days of CABG surgery. The Physical Component Summary of the preoperative SF-36 was a statistically significant risk factor for 6-month mortality after adjustment for known clinical risk factors for mortality following CABG surgery. In multivariate analysis, a 10-point lower SF-36 Physical Component Summary score had an odds ratio (OR) of 1.39 (95% confidence interval [CI], 1.11-1.77; P = .006) for predicting mortality. The SF-36 Mental Component Summary score was not associated with 6-month mortality in multivariate analyses (OR, 1.09; 95% CI, 0.92-1.29; P = .31).Conclusions The Physical Component Summary score from the preoperative SF-36 is an independent risk factor for mortality following CABG surgery. The baseline Mental Component Summary score does not appear to be predictive of mortality. Preoperative patient: self-report of the physical component of health status may be helpful for risk stratification and clinical decision making for patients undergoing CABG surgery.

CONTEXT:Health-related quality of life has not been evaluated as a predictor of mortality following coronary artery bypass graft (CABG) surgery. Evaluation of health status as a mortality predictor may be useful for preoperative risk stratification.OBJECTIVE:To determine whether the Physical and Mental Component Summary scores from the preoperative Short-Form 36 (SF-36) health status survey predict mortality following CABG surgery after adjustment for known clinical risk variables.DESIGN:Prospective cohort study conducted between September 1992 and December 1996.SETTING:Fourteen Veterans Affairs hospitals.PATIENTS:Of the 3956 patients undergoing CABG surgery only and who were enrolled in the Processes, Structures, and Outcomes of Care in Cardiac Surgery study, the 2480 who completed a preoperative SF-36.MAIN OUTCOME MEASURE:All-cause mortality within 180 days after surgery.RESULTS:A total of 117 deaths (4.7%) occurred within 180 days of CABG surgery. The Physical Component Summary of the preoperative SF-36 was a statistically significant risk factor for 6-month mortality after adjustment for known clinical risk factors for mortality following CABG surgery. In multivariate analysis, a 10-point lower SF-36 Physical Component Summary score had an odds ratio (OR) of 1.39 (95% confidence interval [CI], 1.11-1.77; P=.006) for predicting mortality. The SF-36 Mental Component Summary score was not associated with 6-month mortality in multivariate analyses (OR, 1.09; 95% CI, 0.92-1.29; P=.31).CONCLUSIONS:The Physical Component Summary score from the preoperative SF-36 is an independent risk factor for mortality following CABG surgery. The baseline Mental Component Summary score does not appear to be predictive of mortality. Preoperative patient self-report of the physical component of health status may be helpful for risk stratification and clinical decision making for patients undergoing CABG surgery.

To evaluate the hepatic regenerative response in patients with alcoholic liver disease, sera from 263 patients with severe alcoholic hepatitis and/or cirrhosis were analyzed for hepatocyte growth factor (HGF) and α‐fetoprotein (AFP). HGF concentration was elevated above healthy controls in 95% of the patients (median level = 2.4 ng/ml), whereas AFP tended to be depressed below controls (median level = 4.1 ng/ml). Correlations with parameters of liver injury (i.e., ascites, encephalopathy, AST bilirubin, and protime) all showed a more significant correlation with HGF concentrations than those of AFP. Patients with HGF levels below the mean (4 ng/ml) exhibited significantly better survival (median survival = 35 months vs. 8.5 months for those with HGF ≥4 ng/ml; p= 0.007). Serum HGF levels were associated with various specific histologic features of alcoholic hepatitis that included, but were not exclusively related to, necrosis.

PURPOSE The anemia of chronic disease is mediated by the cytokines that modulate the immune response, such as tumor necrosis factor (TNF) and gamma-interferon (gamma-IFN), and is associated with a blunted serum erythropoietin (sEPO) response to anemia. Previous reports suggest that patients with liver disease (LD) also exhibit a blunted sEPO response to anemia, and that patients with alcoholic LD had altered cytokines, including elevated TNF levels. To investigate the pathogenesis of anemia in alcoholic LD, sEPO, TNF, and gamma-IFN levels were determined in patients who had participated in a Department of Veterans Affairs Cooperative study of alcoholic LD. METHODS sEPO, serum TNF-alpha, and serum gamma-IFN levels were evaluated in 40 patients with severe biopsy-proven alcoholic LD whose serum had been stored during the Department of Veterans Affairs Cooperative Study 275, and in 18 patients with iron deficiency (controls). RESULTS Mean hemoglobin (Hgb) was 11.2 +/- 0.3 g/dl for LD patients versus 11.4 +/- 0.4 g/dl for controls (p = 0.84). sEPO levels measured by ELISA were 29.6 +/- 4.1 units/liter in LD patients versus 25.4 +/- 5.4 units/liter in controls (p = 0.64). In both sets of patients, sEPO and Hgb were inversely related; the slopes of the two regression lines did not differ significantly (p = 0.92). TNF was detected in 3 of 40 LD patients and in 0 of 18 iron-deficient patients. Detection of TNF did not correlate with sEPO or Hgb, but did correlate strongly with severe caloric malnutrition (marasmus) and mortality at 6 months (p = 0.049 and 0.04, respectively). gamma-IFN was not detected. CONCLUSIONS These findings indicate that the sEPO response is preserved in patients with severe alcoholic LD, and suggest that anemia in LD arises from different mechanisms than does the anemia of chronic disease. TNF production in severe alcoholic LD is strongly correlated with caloric malnutrition and mortality.

Small cell carcinoma of the lung (SCCL) responds commonly to combination chemotherapy but resistance to therapy follows. Prior reports have suggested that a relationship may exist between plasma fibrinogen levels and response to therapy in SCCL. This study was designed to determine the possible predictive value of the fibrinogen level for tumor response (chemoresistance) in SCCL. Pretreatment fibrinogen levels were correlated with outcome and response to therapy in a cohort of 119 previously untreated patients with SCCL who were admitted to VA Cooperative Study 188. Higher pretreatment fibrinogen levels at diagnosis correlated significantly with more advanced stage of disease at entry ( P 0.001) and with reduced overall survival ( P 0.030). In addition, higher pretreatment fibrinogen levels were correlated significantly with a reduced likelihood of achieving subsequent disease regression with combination chemotherapy ( P = 0.005). Because several clinical trials have shown that anticoagulant therapy improves tumor response rates and survival of SCCL, we postulate that tumor cell thrombin generation not only promotes SCCL growth but may also be primarily responsible for both increased fibrinogen levels and for resistance to chemotherapy. These findings provide incentive for studies of thrombin effects on the development of multidrug esistance, and for new clinical trials of more potent and specific inhibitors of thrombin that may further improve tumor response and survival in SCCL. ©1995 Wiley‐Liss, Inc.

The authors made some preliminary judgments regarding the reliability and representativeness of the data in the early stages of the Veterans Affairs Cooperative Study entitled Processes, Structures, and Outcomes of Care in Cardiac Surgery (PSOCS).Preliminary PSOCS interobserver reliability and potential patient and site selection bias reported were based on comparisons with identical risk, procedure, and outcome data items collected independently in the Continuous Improvement in Cardiac Surgery Study. PSOCS interobserver reliability for this limited set of variables was good to excellent. At the six pilot centers, there were few important differences between patients entered into PSOCS and those not entered. The 14 Veterans Affairs medical centers that will participate in the full-scale PSOCS study and the 29 nonparticipating centers exhibited similar patient populations.A future study examining the process and structure variables of PSOCS will be valuable.

In both animal and human studies, ethanol seems to modulate host immune function. In a variety of animal studies, ethanol has been shown to decrease lymphocyte function and number. In human studies of patients with alcoholic hepatitis, these abnormalities were also seen with specific correlation with protein malnutrition. Hepatic pathological lesions were also correlated with lymphocyte subset infiltration. However, peripheral blood lymphocytes did not correlate consistently with hepatic histopathology.

This article describes the statistical methods and strategies to be used in establishing the linkages between processes and structures of care with risk-adjusted outcomes in a large multicenter Veterans Affairs cooperative study in health services of patients undergoing cardiac surgery. The statistical analyses consist of tests involving nine specific hypotheses related to the effect of processes and structures of care on risk-adjusted outcomes. From the statistical point of view, the major obstacles of this study are the need for data reduction and imputation of missing data. The former obstacle is addressed through the use of data-reduction techniques, such as principal components and cluster of variables. The latter is addressed through the use of classic and new techniques for imputation of missing data, such as MISSGEN, principal components for qualitative data, and the expectation and maximization algorithm. Data reduction and imputation of missing data are done with clinically derived variable groups called ''dimensions'' or ''subdimensions.'' The effect of processes and structures of care is assessed by a two-step process. First, outcomes are modeled using only patient risk factors. The selection of risk factors in the modeling process is discussed in detail. Second, these risk-adjusted outcomes are modeled using one of the nine process or structure subhypotheses. The relationship of the processes and structures of care dimensions and/or subdimensions that are linked to risk-adjusted outcomes are identified.

Accurate collection and successful management of data are problems common to all scientific studies. For studies in which large quantities of data are collected by means of questionnaires and/or forms, data base management becomes quite laborious and time consuming. Data base management comprises data collection, data entry, data editing, and data base maintenance. In this article, the authors describe the development of an interactive data base management (IDM) system for the collection of more than 1,400 variables from a targeted population of 6,000 patients undergoing heart surgery requiring cardiopulmonary bypass. The goals of the IDM system are to increase the accuracy and efficiency with which this large amount of data is collected and processed, to reduce research nurse work load through automation of certain administrative and clerical activities, and to improve the process for implementing a uniform study protocol, standardized forms, and definitions across sites.

BACKGROUND:Active nutrition therapy and the anabolic steroid oxandrolone (OX), in selected patients with severe alcoholic hepatitis, significantly improved liver status and survival. We report here on the changes in their nutritional parameters.METHODS:Protein energy malnutrition (PEM) was evaluated and expressed as percent of low normal in 271 patients initially, at 1 month and at 3 months. Active therapy consisted of OX plus a high caloric food supplement vs a matching placebo and a low calorie supplement.RESULTS:PEM was present in every patient; mean PEM score 60% of low normal. Most of the parameters improved significantly from baseline on standard care; the largest improvement seen in visceral proteins, the smallest in fat stores (skinfold thickness). Total PEM score significantly correlated with 6 month mortality (p = .0012). Using logistic regression analysis, creatinine height index, hand grip strength and total peripheral blood lymphocytes were the best risk factors for survival. When CD lymphocyte subsets replaced total lymphocyte counts in the equation, CD8 levels became a significant risk factor (p = .004). Active treatment produced significant risk factor (p = .004). Active treatment produced significant improvements in those parameters related to total body and muscle mass (ie, mid arm muscle area, p = .02; creatinine height index, p = .03; percent ideal body weight, p = .04).CONCLUSION:Deterioration in nutritional parameters is a significant risk factor for survival in severe patients with alcoholic hepatitis. This deterioration is reversible with standard hospital care. Active therapy further improves creatinine height index, mid arm muscle area and total lymphocyte counts. Hence, these later parameters appear to be the best indicators for follow-up assessments.