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Context: Little is known regarding the extent to which patient-reported health status, including symptom burden, physical limitation, and quality of life, is determined by psychosocial vs physiological factors among patients with chronic disease.Objective: To compare the contributions of depressive symptoms and measures of cardiac function to the health status of patients with coronary artery disease.Design, Setting, and Participants: Cross-sectional study of 1024 adults with stable coronary artery disease recruited from outpatient clinics in the San Francisco Bay Area between September 2000 and December 2002. Main Measures Measurement of depressive symptoms using the Patient Health Questionnaire (PHQ); assessment of cardiac function by measuring left ventricular ejection fraction on echocardiography, exercise capacity on treadmill testing, and ischemia on stress echocardiography; and measurement of a range of health status outcomes, including symptom burden, physical limitation, and quality of life, using the Seattle Angina Questionnaire. Participants were also asked to rate their overall health as excellent, very good, good, fair, or poor.Results: Of the 1024 participants, 201 (20%) had depressive symptoms (PHQ score > or =10). Participants with depressive symptoms were more likely than those without depressive symptoms to report at least mild symptom burden (60% vs 33%; P<.001), mild physical limitation (73% vs 40%; P<.001), mildly diminished quality of life (67% vs 31%; P<.001), and fair or poor overall health (66% vs 30%; P<.001). In multivariate analyses adjusting for measures of cardiac function and other patient characteristics, depressive symptoms were strongly associated with greater symptom burden (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.3-2.7; P =.002), greater physical limitation (OR, 3.1; 95% CI, 2.1-4.6; P<.001), worse quality of life (OR, 3.1; 95% CI, 2.2-4.6; P<.001), and worse overall health (OR, 2.0; 95% CI, 1.3-2.9; P<.001). Although decreased exercise capacity was associated with worse health status, left ventricular ejection fraction and ischemia were not.Conclusions: Among patients with coronary disease, depressive symptoms are strongly associated with patient-reported health status, including symptom burden, physical limitation, quality of life, and overall health. Conversely, 2 traditional measures of cardiac function-ejection fraction and ischemia-are not. Efforts to improve health status should include assessment and treatment of depressive symptoms. [ABSTRACT FROM AUTHOR]

Context: Transgenic animal experiments suggest that increased expression of transforming growth factor beta1 (TGF-beta1) is protective against early tumor development, particularly in breast cancer. A T-->C (thymine to cytosine) transition in the 29th nucleotide in the coding sequence results in a leucine to proline substitution at the 10th amino acid and is associated with increased serum levels of TGF-beta1.Objective: To determine whether an association exists between this TGF-beta1 polymorphism and breast cancer risk.Design, Setting, and Participants: The Study of Osteoporotic Fractures, a prospective cohort study of white, community-dwelling women aged 65 years or older who were recruited at 4 US centers between 1986 and 1988. Three thousand seventy-five women who provided sufficient clinical information, buffy coat samples, and adequate consent for genotyping are included in this analysis.Main Outcome Measure: Breast cancer cases during a mean (SD) follow-up of 9.3 (1.9) years, verified by medical chart review and compared by genotype.Results: Risk of breast cancer was similar in the 1124 women with the T/T genotype (56 cases; 5.4 per 1000 person-years) and the 1493 women with the T/C genotype (80 cases; 5.8 per 1000 person-years) but was significantly lower (P =.01) in the 458 women with the C/C genotype (10 cases; 2.3 per 1000 person-years). In analyses that adjusted for age, age at menarche, age at menopause, estrogen use, parity, body mass index, and bone mineral density, women with the C/C genotype had a significantly lower risk of developing breast cancer compared with women with the T/T or T/C genotype (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.17-0.75). There was no significant difference between the risk for women with the T/C genotype compared with women with the T/T genotype (adjusted HR, 1.04; 95% CI, 0.73-1.48).Conclusions: Our findings suggest that TGF-beta1 genotype is associated with risk of breast cancer in white women aged 65 years or older. Because the T allele is the common variant and confers an increased risk, it may be associated with a large proportion of breast cancer cases. [ABSTRACT FROM AUTHOR]

Context: Calcium deposits in coronary and extracoronary arterial beds may indicate the extent of atherosclerosis. However, the incremental predictive value of vascular calcification, beyond traditional coronary risk factors, is not clearly established.Objective: To evaluate risk factors for aortic arch calcification and its long-term association with cardiovascular diseases in a population-based sample.Design and Setting: Cohort study conducted at a health maintenance organization in northern California.Participants: A total of 60,393 women and 55,916 men, aged 30 to 89 years at baseline who attended multiphasic health checkups between 1964 and 1973 and for whom incidence of hospitalizations and/or mortality data were ascertained using discharge diagnosis codes and death records through December 31, 1997 (median follow-up, 28 years).Main Outcome Measure: Hospitalization for or death due to coronary heart disease, ischemic stroke, hemorrhagic stroke, or peripheral vascular disease, as associated with aortic arch calcification found on chest radiograph at checkup from 1964-1973.Results: Aortic arch calcification was present in 1.9% of men and 2.6% of women. It was independently associated with older age, no college education, current smoking, and hypertension in both sexes, but it was inversely related to body mass index and family history of myocardial infarction. In women, aortic arch calcification was also associated with black race and elevated serum cholesterol level. After adjustment for age, educational attainment, race/ethnicity, cigarette smoking, alcohol consumption, body mass index, serum cholesterol level, hypertension, diabetes, and family history of myocardial infarction, aortic arch calcification was associated with an increased risk of coronary heart disease (in men, relative risk [RR], 1.27; 95% confidence interval [CI], 1.11-1.45; in women, RR, 1. 22; 95% CI, 1.07-1.38). Among women, it was also independently associated with a 1.46-fold increased risk of ischemic stroke (95% CI, 1.28-1.67).Conclusion: In our population-based cohort, aortic arch calcification was independently related to coronary heart disease risk in both sexes as well as to ischemic stroke risk in women. JAMA. 2000;283:2810-2815 [ABSTRACT FROM AUTHOR]

Context: A patient's coronary heart disease (CHD) risk must be correctly classified to successfully apply risk-based guidelines for treatment of hypercholesterolemia.Objective: To determine the classification accuracy of the National Cholesterol Education Program (NCEP) CHD risk-stratification system and compare it with a simple revised system that gives greater weight to age as a CHD risk factor.Design: Modeling of 10-year CHD risk, using equations from the Framingham Heart Study applied to a cross-sectional survey of the US population.Subjects: The 3284 subjects aged 20 to 74 years surveyed in the Second National Health and Nutrition Examination Survey (1978-1982) who had fasting lipid levels measured.Main Outcome Measures: The area under the receiver operating characteristic curve (AUC) for 10-year CHD risk for the NCEP and revised scales.Results: Among all adults with a low-density lipoprotein cholesterol value of at least 4.1 mmol/L (160 mg/dL), the NCEP system showed fairly good discrimination (AUC=0.90), though there was a substantial decline among men 35 to 74 years old and women 55 to 74 years old (AUC=0.81). By contrast, the revised system showed superior performance in all hypercholesterolemic adults (AUC=0.94-0.97) as well as in the subgroup of men 35 to 74 years old and women 55 to 74 years old (AUC=0.94-0.96).Conclusions: Simple modifications of the NCEP treatment criteria result in a substantially improved ability to discriminate between higher and lower CHD risk groups. Unlike the NCEP system, this revised system retains its classification ability in all age groups studied. [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis that bone mineral density (BMD) is associated with the risk of developing breast cancer in older women.Design: Prospective cohort study with mean (SD) follow-up of 3.2 (1.6) years.Setting: Four clinical centers, one each located in the following areas: Baltimore, Md; Minneapolis, Minn; Portland, Ore; and the Monongahela Valley in Pennsylvania.Participants: A total of 6854 nonblack women who were 65 years of age or older and enrolled in the Study of Osteoporotic Fractures.Measurements: Radius and calcaneus BMD by single photon absorptiometry at baseline; hip and spine BMD by dual-energy x-ray absorptiometry 2 years later.Main Outcome Measure: Breast cancer confirmed by medical record review.Results: A total of 97 women developed breast cancer. In the multivariate model, adjusting for age, the degree of obesity, and other important covariates, the risk of breast cancer was about 30% to 50% higher per 1 SD increase in BMD (relative risk, distal radius BMD=1.50; 95% confidence interval, 1.16-1.95). The age-adjusted incidence rate of breast cancer per 1000 person-years among women in the lowest quartile of distal radius BMD was 2.46, compared with 5.99 among women with the highest BMD. Women with BMD above the 25th percentile were at 2.0 to 2.5 times increased risk of breast cancer compared with women below the 25th percentile. Results were consistent across all BMD sites.Conclusions: Bone mineral density predicts the risk of breast cancer in older women. The magnitude of the association is similar to that observed between BMD and all fractures. Our findings suggest a link between 2 of the most common conditions affecting a woman's health. Identifying a common denominator for these conditions should substantially improve our understanding of their etiology and prevention. [ABSTRACT FROM AUTHOR]

Objective: To determine the incidence, predictors, and cost of atrial fibrillation and flutter (AFIB) following coronary artery bypass graft (CABG) surgery.Design: Prospective observational study (MultiCenter Study of Perioperative Ischemia).Setting: Twenty-four university-affiliated hospitals in the United States from 1991 to 1993.Subjects: A total of 2417 patients undergoing CABG with or without concurrent valvular surgery selected using a systematic sampling interval.Measurements: Detailed preoperative, intraoperative, and postoperative data collected on standardized reporting forms.Results: The overall incidence of postoperative AFIB was 27 percent. Independent predictors of postoperative AFIB included advanced age (odds ratio [OR], 1.24 per 5-year increase; 95 percent confidence interval [CI], 1.18-1.31); male sex (OR, 1.41; 95 percent CI, 1.09-1.81); a history of AFIB (OR, 2.28; 95 percent CI, 1.74-3.00); a history of congestive heart failure (OR, 1.31; 95 percent CI, 1.04-1.64); and a precardiopulmonary bypass heart rate of more than 100 beats per minute (OR, 1.59; 95 percent CI, 1.00-2.55). Surgical practices such as pulmonary vein venting (OR, 1.44; 95 percent CI, 1.13-1.83); bicaval venous cannulation (OR, 1.40; 95 percent CI, 1.04-1.89); postoperative atrial pacing (OR, 1.27; 95 percent CI, 1.00-1.62); and longer cross-clamp times (OR, 1.06 per 15 minutes; 95 percent CI, 1.00-1.11) also were identified as independent predictors of postoperative AFIB. Patients with postoperative AFIB remained an average of 13 hours longer in the intensive care unit and 2.0 days longer in the ward when compared with patients without AFIB.Conclusion: Postoperative AFIB is common after CABG surgery and has a significant effect on both intensive care unit and overall hospital length of stay. In addition to expected demographic factors, certain surgical practices increase the risk of postoperative AFIB. Randomized controlled trials are necessary to determine if modification of these surgical practices, especially in patients at high risk, would decrease the incidence of postoperative AFIB. [ABSTRACT FROM AUTHOR]

Context: Depressive symptoms predict adverse cardiovascular outcomes in patients with coronary heart disease, but the mechanisms responsible for this association are unknown., Objective: To determine why depressive symptoms are associated with an increased risk of cardiovascular events., Design and Participants: The Heart and Soul Study is a prospective cohort study of 1017 outpatients with stable coronary heart disease followed up for a mean (SD) of 4.8 (1.4) years., Setting: Participants were recruited between September 11, 2000, and December 20, 2002, from 12 outpatient clinics in the San Francisco Bay Area and were followed up to January 12, 2008., Main Outcome Measures: Baseline depressive symptoms were assessed using the Patient Health Questionnaire (PHQ). We used proportional hazards models to evaluate the extent to which the association of depressive symptoms with subsequent cardiovascular events (heart failure, myocardial infarction, stroke, transient ischemic attack, or death) was explained by baseline disease severity and potential biological or behavioral mediators., Results: A total of 341 cardiovascular events occurred during 4876 person-years of follow-up. The age-adjusted annual rate of cardiovascular events was 10.0% among the 199 participants with depressive symptoms (PHQ score > or = 10) and 6.7% among the 818 participants without depressive symptoms (hazard ratio [HR], 1.50; 95% confidence interval, [CI], 1.16-1.95; P = .002). After adjustment for comorbid conditions and disease severity, depressive symptoms were associated with a 31% higher rate of cardiovascular events (HR, 1.31; 95% CI, 1.00-1.71; P = .04). Additional adjustment for potential biological mediators attenuated this association (HR, 1.24; 95% CI, 0.94-1.63; P = .12). After further adjustment for potential behavioral mediators, including physical inactivity, there was no significant association (HR, 1.05; 95% CI, 0.79-1.40; P = .75)., Conclusion: In this sample of outpatients with coronary heart disease, the association between depressive symptoms and adverse cardiovascular events was largely explained by behavioral factors, particularly physical inactivity.

Context: Racial disparities in health care delivery and outcomes may be due to differences in health care access and, therefore, may be mitigated in an equal-access health care system. Few studies have examined racial differences in health outcomes in such a system., Objective: To study racial differences in mortality among patients admitted to hospitals in the Veterans Affairs (VA) system, a health care system that potentially offers equal access to care., Design, Setting, and Participants: Cohort study of 28 934 white and 7575 black men admitted to 147 VA hospitals for 1 of 6 common medical diagnoses (pneumonia, angina, congestive heart failure, chronic obstructive pulmonary disease, diabetes, and chronic renal failure) between October 1, 1995, and September 30, 1996., Main Outcome Measures: The primary outcome measure was 30-day mortality among black compared with white patients. Secondary outcome measures were in-hospital mortality and 6-month mortality., Results: Overall mortality at 30 days was 4.5% in black patients and 5.8% in white patients (relative risk [RR], 0.77; 95% confidence interval [CI], 0.69-0.87; P =.001). Mortality was lower among blacks for each of the 6 medical diagnoses. Multivariate adjustment for patient and hospital characteristics had a small effect (RR, 0.75; 95% CI, 0.66-0.85; P<.001). Black patients also had lower adjusted in-hospital and 6-month mortality. These findings were consistent among all subgroups evaluated., Conclusions: Black patients admitted to VA hospitals with common medical diagnoses have lower mortality rates than white patients. The survival advantage of black patients is not readily explained; however, the absence of a survival disadvantage for blacks may reflect the benefits of equal access to health care and the quality of inpatient treatment at VA medical centers.

Context: Management of patients with acute transient ischemic attack (TIA) varies widely, with some institutions admitting all patients and others proceeding with outpatient evaluations. Defining the short-term prognosis and risk factors for stroke after TIA may provide guidance in determining which patients need rapid evaluation., Objective: To determine the short-term risk of stroke and other adverse events after emergency department (ED) diagnosis of TIA., Design and Setting: Cohort study conducted from March 1997 through February 1998 in 16 hospitals in a health maintenance organization in northern California. Patients A total of 1707 patients (mean age, 72 years) identified by ED physicians as having presented with TIA., Main Outcome Measures: Risk of stroke during the 90 days after index TIA; other events, including death, recurrent TIA, and hospitalization for cardiovascular events., Results: During the 90 days after index TIA, 180 patients (10.5%) returned to the ED with a stroke, 91 of which occurred in the first 2 days. Five factors were independently associated with stroke: age greater than 60 years (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.1-2.7; P=.01), diabetes mellitus (OR, 2.0; 95% CI, 1.4-2.9; P<.001), symptom duration longer than 10 minutes (OR, 2.3; 95% CI, 1.3-4.2; P=.005), weakness (OR, 1.9; 95% CI, 1.4-2.6; P<.001), and speech impairment (OR, 1.5; 95% CI, 1.1-2.1; P=.01). Stroke or other adverse events occurred in 428 patients (25.1%) in the 90 days after the TIA and included 44 hospitalizations for cardiovascular events (2.6%), 45 deaths (2.6%), and 216 recurrent TIAs (12.7%)., Conclusions: Our results indicate that the short-term risk of stroke and other adverse events among patients who present to an ED with a TIA is substantial. Characteristics of the patient and the TIA may be useful for identifying patients who may benefit from expeditious evaluation and treatment.

Context: Recently, an algorithm based on the electrocardiogram (ECG) was reported to predict myocardial infarction (MI) in patients with left bundle-branch block (LBBB), but the clinical impact of this testing strategy is unknown., Objective: To determine the diagnostic test characteristics and clinical utility of this ECG algorithm for patients with suspected MI., Design: Retrospective cohort study to which an algorithm was applied, followed by decision analysis regarding thrombolysis made with or without the algorithm., Setting: University emergency department, 1994 through 1997., Patients: Eighty-three patients with LBBB who presented 103 times with symptoms suggestive of MI., Main Outcome Measures: Myocardial infarction determined by serial cardiac enzyme analyses and stroke-free survival., Results: Of 9 ECG findings assessed, none effectively distinguished the 30% of patients with MI from those with other diagnoses. The ECG algorithm indicated positive findings in only 3% of presentations and had a sensitivity of 10% (95% confidence interval, 2%-26%). The decision analysis showed that among 1000 patients with LBBB and chest pain, 929 would survive without major stroke if all received thrombolysis compared with 918 if the ECG algorithm was used as a screening test., Conclusions: The ECG is a poor predictor of MI in a community-based cohort of patients with LBBB and acute cardiopulmonary symptoms. Acute thrombolytic therapy should be considered for all patients with LBBB who have symptoms consistent with MI.

Should we measure blood cholesterol levels in all adults, or only in those at high risk of coronary heart disease (CHD)? Most men under the age of 35 years and women under the age of 45 years--roughly half the adult population--are at very low short-term risk of CHD. One consequence is that drug treatment to lower high blood cholesterol levels in the average young adult is an extremely expensive means of prolonging life; the estimated $1 million to $10 million per year of life is 100 to 1000 times the cost of other approaches. Individualized dietary treatment is somewhat cheaper but relatively ineffective. Another consequence of the low CHD risk in young adults is the greater likelihood that intervention may have harmful effects that outweight the benefits. Meta-analysis of primary prevention trials in middle-aged men reveal an increase in non-CHD deaths among those randomized to cholesterol interventions, an unexpected finding that is more substantial than the decrease in CHD deaths. This raises the possibility that one or more of the cholesterol interventions could have very serious adverse effects among young adults, whose risk of non-CHD death is normally 100 times their risk of CHD death. We conclude that the policy of screening and treating high blood cholesterol levels in young adults is neither cost-effective, nor does it satisfy ethical standards requiring strong evidence that preventive interventions do more good than harm. Fortunately, cholesterol screening in young adults is also not necessary: most CHD events associated with high blood cholesterol levels in this population will not occur for decades and can be prevented by treatment that is begun in middle age. Cholesterol screening and treatment in young adults should be limited to individuals with known coronary disease or other unusual factors that place them at high short-term risk of CHD death.

Objective: To identify predictors of postoperative myocardial ischemia in patients scheduled to undergo major noncardiac surgery., Design: Historical, clinical, laboratory, and physiological data were obtained prospectively before and during surgery to identify potential univariate predictors of postoperative myocardial ischemia, which then were entered into multivariate logistic models. Continuous two-lead electrocardiograms before, during, and after surgery were used to identify episodes of myocardial ischemia., Setting: Department of Veterans Affairs tertiary care hospital., Patients: A consecutive sample of 474 men at high risk for or with coronary artery disease who were scheduled to undergo major noncardiac surgery (95% compliance rate)., Main Outcome Measure: Significant variables identified by multivariate logistic models that are associated with postoperative myocardial ischemia., Results: Five major preoperative predictors of postoperative myocardial ischemia were identified: (1) left ventricular hypertrophy by electrocardiogram; (2) history of hypertension; (3) diabetes mellitus; (4) definite coronary artery disease; and (5) use of digoxin. The risk of postoperative myocardial ischemia increased progressively with the number of predictors present: in 22% of patients with no predictors, in 31% with one predictor, in 46% with two predictors, in 70% with three predictors, and in 77% with four predictors., Conclusion: Patients subgroups who are at high risk for developing postoperative myocardial ischemia and who might benefit the most from intensive Holter monitoring in the postoperative period now can be identified preoperatively.

Objectives: To determine the causes of and risk factors for mortality following noncardiac surgery., Design: Prospective cohort study., Setting: A university-affiliated Veterans Affairs medical center., Patients: Consecutive series of 474 men between the ages of 38 and 89 years (mean age, 68 years) who were undergoing major noncardiac surgery involving general anesthesia. All subjects had known coronary artery disease or were at high risk for coronary artery disease., Measurements and Results: During the initial hospitalization, 26 patients (5%) died, most commonly from sepsis (n = 6) or cardiac diseases (n = 6). Deaths occurred from postoperative days 2 to 69; half occurred more than 3 weeks after surgery. Multivariable analysis disclosed that a history of hypertension (odds ratio [OR] = 3.8; 95% confidence interval [CI], 1.1 to 13), a severely limited activity level (OR = 9.7; 95% CI, 2.5 to 37), and a creatinine clearance of less than 0.83 mL/s (OR = 6.8; 95% CI, 2.8 to 16) were all independently associated with an increased risk of postoperative mortality. The mortality rate in patients with two or more of these risk factors was 20%, nearly eight times higher (95% CI, 3.6 to 16) than those with one or no risk factors. An additional 82 patients died within the next 2 years; cancer, renal dysfunction, congestive heart failure, and obstructive pulmonary disease were independently associated with long-term mortality., Conclusions: Even in patients at high risk of cardiac complications following surgery, noncardiac causes of death are more common. Patients with a history of hypertension, severely limited activity, and reduced renal function appear to be at especially high risk of in-hospital mortality after noncardiac surgery.

Objective: To determine the long-term (2-year) cardiac prognosis of high-risk patients undergoing noncardiac surgery and to determine the predictors of long-term adverse cardiac outcome., Design: Prospective cohort study. Historical, clinical, and laboratory data were collected during the in-hospital period, and at 6 months, 1 year, and 2 years following surgery. Data were analyzed using proportional hazards models., Setting: University-affiliated Veterans Affairs medical center., Population: A consecutive sample of 444 patients with or at high risk for coronary artery disease who had undergone elective noncardiac surgery and were discharged from the hospital in stable condition., Main Outcome Measures: Cardiac death, myocardial infarction, unstable angina, progressive angina requiring coronary artery bypass graft surgery or coronary angioplasty, and new unstable angina requiring hospitalization., Results: Forty-seven patients (11%) had major cardiovascular complications during a 728-day (median) follow-up period: 24 had cardiac death; 11, nonfatal myocardial infarction; six, progressive angina requiring coronary artery bypass graft surgery or coronary angioplasty; and six, new unstable angina requiring hospitalization. Thirty percent of outcomes occurred within 6 months of surgery and 64% within 1 year. Five independent predictors of long-term outcome were identified. Three predictors reflected the preexisting chronic disease state: (1) the presence of known vascular disease (hazard ratio, 6.1; 95% confidence interval [CI], 2.5 to 15.0; P less than .0001); (2) a history of congestive heart failure (hazard ratio, 5.0; 95% CI, 2.0 to 12.0; P less than .0005); and (3) known coronary artery disease (hazard ratio, 3.7; 95% CI, 1.7 to 8.0; P less than .0007). Two predictors reflected acute postoperative ischemic events: (1) myocardial infarction/unstable angina (hazard ratio, 20; 95% CI, 7.5 to 53.0; P less than .0001) and (2) myocardial ischemia (hazard ratio, 2.2; 95% CI, 1.1 to 4.3; P less than .03). Patients surviving a postoperative in-hospital myocardial infarction had a 28-fold increase in the rate of subsequent cardiac complications within 6 months following surgery, a 15-fold increase within 1 year, and a 14-fold increase within 2 years (95% CI, 5.8 to 32; P less than .00001). Seventy percent of all long-term adverse outcomes were preceded by in-hospital postoperative ischemia that occurred at least 30 days (median, 282 days) before the long-term event. The development of congestive heart failure or ventricular tachycardia (without ischemia) during hospitalization was not associated with adverse long-term outcome., Conclusions: The incidence of long-term adverse cardiac outcomes following noncardiac surgery is substantial. At increased risk are patients with chronic cardiovascular disease; at highest risk are patients with acute perioperative ischemic events. We conclude that survivors of in-hospital perioperative ischemic events, specifically myocardial infarction, unstable angina, and postoperative ischemia, warrant more aggressive long-term follow-up and treatment than is currently practiced.

Objective: Transesophageal echocardiography (TEE) and 12-lead electrocardiography (ECG) are sophisticated techniques that are increasingly being used to monitor for myocardial ischemia during noncardiac surgery. We examined whether the routine use of these techniques has incremental clinical value in identifying patients at high risk for perioperative ischemic outcomes when compared with preoperative clinical data and intraoperative monitoring using continuous two-lead bipolar ECG., Design: Cohort study., Setting: Veterans Affairs medical center., Patients: A total of 332 men undergoing noncardiac surgery who had or were at high risk for coronary artery disease., Interventions: TEE, 12-lead ECG, and two-lead ECG were performed continuously during noncardiac surgery (47% vascular, 53% nonvascular). Monitoring results were not available to anesthesiologists or surgeons, and data were blindly analyzed after surgery., Main Outcome Measure: Perioperative ischemic outcomes (cardiac death, nonfatal myocardial infarction, unstable angina)., Results: In a subset of 285 patients who were adequately studied by all three techniques, 111 patients (39%) were identified as having intraoperative myocardial ischemia (by one or more monitoring techniques). By univariate analysis, intraoperative ischemia was associated with all perioperative cardiac outcomes, including ischemic outcomes, congestive heart failure, and ventricular tachycardia (P less than or equal to .02 for each of the three monitoring techniques). However, when monitoring results for TEE and 12-lead ECG were added to a multivariate model that included preoperative clinical data and continuous two-lead ECG results, the incremental value of TEE was small (odds ratio, 2.6; 95% confidence interval [CI], 1.2 to 5.7; P = .02) and that of 12-lead ECG was not significant (odds ratio, 1.5; 95% CI, 0.6 to 3.8). Furthermore, when the multivariate analysis was repeated with only ischemic outcomes, neither TEE nor 12-lead ECG retained significant associations (odds ratio, 2.2; 95% CI, 0.5 to 9.4, and odds ratio, 1.1; 95% CI, 0.2 to 6.1, respectively)., Conclusion: When compared with preoperative clinical data and intraoperative monitoring using two-lead ECG, routine monitoring for myocardial ischemia with TEE or 12-lead ECG during noncardiac surgery has little incremental clinical value in identifying patients at high risk for perioperative ischemic outcomes.

Objective: To determine the incidence, clinical predictors and prognostic importance of perioperative ventricular arrhythmias., Design: Prospective cohort study (Study of Perioperative Ischemia)., Setting: University-affiliated Department of Veterans Affairs Medical Center, San Francisco, Calif., Subjects: A consecutive sample of 230 male patients, with known coronary artery disease (46%) or at high risk of coronary artery disease (54%), undergoing major noncardiac surgical procedures., Measurements: We recorded cardiac rhythm throughout the preoperative (mean = 21 hours), intraoperative (mean = 6 hours), and postoperative (mean = 38 hours) periods using continuous ambulatory electrocardiographic monitoring. Adverse cardiac outcomes were noted by physicians blinded to information about arrhythmias., Main Results: Frequent or major ventricular arrhythmias (greater than 30 ventricular ectopic beats per hour, ventricular tachycardia) occurred in 44% of our patients: 21% preoperatively, 16% intraoperatively, and 36% postoperatively. Compared with the preoperative baseline, the severity of arrhythmia increased in only 2% of patients intraoperatively but in 10% postoperatively. Preoperative ventricular arrhythmias were more common in smokers (odds ratio [OR], 4.1; 95% confidence interval [CI], 1.2 to 15.0), those with a history of congestive heart failure (OR, 4.1; 95% CI, 1.9 to 9.0), and those with electrocardiographic evidence of myocardial ischemia (OR, 2.2; 95% CI, 1.1 to 4.7). Preoperative arrhythmias were associated with the occurrence of intraoperative and postoperative arrhythmias (OR, 7.3; 95% CI, 3.3 to 16.0, and OR, 6.4; 95% CI, 2.7 to 15.0, respectively). Nonfatal myocardial infarction or cardiac death occurred in nine men; these outcomes were not significantly more frequent in those with prior perioperative arrhythmias, albeit with wide CIs (OR, 1.6; 95% CI, 0.4 to 6.2)., Conclusion: Almost half of all high-risk patients undergoing noncardiac surgery have frequent ventricular ectopic beats or nonsustained ventricular tachycardia. Our results suggest that these arrhythmias, when they occur without other signs or symptoms of myocardial infarction, may not require aggressive monitoring or treatment during the perioperative period.

Americans consume an average of 37% of their energy intake as fat. Many authorities recommend restricting fat intake to 30% of energy intake to reduce the rates of coronary heart disease and perhaps of cancers of the breast, colon, and prostate. Based on the assumptions that underlie those recommendations, we estimated the effect of this dietary change on mortality. If all Americans restricted their intake of dietary fat by reducing consumption of saturated fat and accompanying dietary cholesterol, the corresponding reductions in serum cholesterol levels could reduce coronary heart disease mortality rates by 5% to 20%, depending on age. If the relationship between dietary fat and cancer is as strong as has been observed in some studies, the proportional effects on mortality from fat-related cancers could be even greater, although the absolute effects--given the lower mortality rates--would be smaller. Overall, if the assumptions are correct, about 42,000 of the 2.3 million deaths that would have occurred in adults each year in the United States could be deferred. This 2% benefit, equivalent to an increase in average life expectancy of 3 to 4 months, would accrue chiefly to people over the age of 65 years. If recent concerns about the possibly harmful effects of cholesterol lowering on mortality from noncardiovascular causes--which mainly affect younger persons--are valid, these relatively modest benefits would be overestimates of the actual effect.

Because some authorities have proposed blood cholesterol screening for children to prevent coronary heart disease, we reviewed published studies to estimate the potential risks and benefits of such screening. Childhood cholesterol levels are a poor predictor of high cholesterol levels in young adulthood and will be an even poorer predictor of coronary heart disease later in life. There is no evidence that blood cholesterol levels can be lowered more easily in children than in adults, and it seems unlikely that cholesterol reduction in childhood will be much more effective at preventing coronary heart disease than cholesterol reduction begun in middle age. Screening and interventions to lower blood cholesterol levels for millions of children would be expensive, could lead to labeling and family conflicts, and may cause malnutrition and increased noncardiovascular mortality. Because the benefits of cholesterol screening are unlikely to exceed these risks, we conclude that children should not be screened for high blood cholesterol levels.

To determine whether measurement of bone density predicts hip fracture in women, we prospectively studied 9703 nonblack women aged 65 years and older who had measurements of bone mineral density using single-photon absorptiometry in the calcaneus, distal radius, and proximal radius. During an average of 1.6 years of follow-up, 53 hip fractures occurred. The risk of hip fracture was inversely related to bone density at all three measurement sites. After adjusting for age, the relative risk of hip fracture was 1.66 for a decrease of 1 SD in the bone density at the calcaneus (95% confidence interval, 1.22 to 2.26), 1.55 (95% confidence interval, 1.13 to 2.11) at the distal radius, and 1.41 (95% confidence interval, 1.06 to 1.88) at the proximal radius. None of the three measurements was a significantly better predictor of hip fracture than the others. After adjusting for bone mineral density, the risk of hip fracture doubled for each 10-year increase in age (relative risk, 2.09; 95% confidence interval, 1.31 to 3.33). We conclude that decreased bone density in the appendicular skeleton is associated with an increased risk of hip fracture, but this accounts for only part of the age-related increase in risk of hip fracture among older women.

Three treatment regimens are currently recommended for penicillin-susceptible Neisseria gonorrhoeae infection of the cervix: ampicillin, tetracycline, and a combination of ampicillin and tetracycline. To evaluate the cost-effectiveness of these options, we developed a decision analysis model and analyzed the efficacy of each treatment in curing gonorrhea, as well as coexisting Chlamydia trachomatis infection, and in preventing subsequent pelvic inflammatory disease, ectopic pregnancy, and infertility. We included direct costs of medication and expenditures for management of unresolved infections and associated complications. Combination treatment is more than twice as cost-effective as tetracycline and seven times as cost-effective as ampicillin when the medical cost of managing pelvic inflammatory disease is considered. When the costs of ectopic pregnancies and infertility are included, the cost-effectiveness of combination treatment increases further.

Just as diagnostic tests are most helpful in light of the clinical presentation, statistical tests are most useful in the context of scientific knowledge. Knowing the specificity and sensitivity of a diagnostic test is necessary, but insufficient: the clinician must also estimate the prior probability of the disease. In the same way, knowing the P value and power, or the confidence interval, for the results of a research study is necessary but insufficient: the reader must estimate the prior probability that the research hypothesis is true. Just as a positive diagnostic test does not mean that a patient has the disease, especially if the clinical picture suggests otherwise, a significant P value does not mean that a research hypothesis is correct, especially if it is inconsistent with current knowledge. Powerful studies are like sensitive tests in that they can be especially useful when the results are negative. Very low P values are like very specific tests; both result in few false-positive results due to chance. This Bayesian approach can clarify much of the confusion surrounding the use and interpretation of statistical tests.