The diagnosis of coronary-artery disease has become increasingly complex. Many different results, obtained from tests with substantial imperfections, must be integrated into a diagnostic conclusion about the probability of disease in a given patient. To approach this problem in a practical manner, we reviewed the literature to estimate the pretest likelihood of disease (defined by age, sex and symptoms) and the sensitivity and specificity of four diagnostic tests: stress electrocardiography, cardiokymography, thallium scintigraphy and cardiac fluoroscopy. With this information, test results can be analyzed by use of Bayes' theorem of conditional probability. This approach has several advantages. It pools the diagnostic experience of many physicians and integrates fundamental pretest clinical descriptors with many varying test results to summarize reproducibly and meaningfully the probability of angiographic coronary-artery disease. This approach also aids, but does not replace, the physician's ju...

https://www.nejm.org/doi/pdf/10.1056/NEJM197906143002402

Analysis of Probability as an Aid in the Clinical Diagnosis of Coronary-Artery Disease

The role of lipid peroxidation and antioxidants in oxidative modification of LDL.

ContextAntioxidant supplements are used for prevention of several diseases.ObjectiveTo assess the effect of antioxidant supplements on mortality in randomized primary and secondary prevention trials.Data Sources and Trial SelectionWe searched electronic databases and bibliographies published by October 2005. All randomized trials involving adults comparing beta carotene, vitamin A, vitamin C (ascorbic acid), vitamin E, and selenium either singly or combined vs placebo or vs no intervention were included in our analysis. Randomization, blinding, and follow-up were considered markers of bias in the included trials. The effect of antioxidant supplements on all-cause mortality was analyzed with random-effects meta-analyses and reported as relative risk (RR) with 95% confidence intervals (CIs). Meta-regression was used to assess the effect of covariates across the trials.Data ExtractionWe included 68 randomized trials with 232 606 participants (385 publications).Data SynthesisWhen all low- and high-bias risk trials of antioxidant supplements were pooled together there was no significant effect on mortality (RR, 1.02; 95% CI, 0.98-1.06). Multivariate meta-regression analyses showed that low-bias risk trials (RR, 1.16; 95% CI, 1.05-1.29) and selenium (RR, 0.998; 95% CI, 0.997-0.9995) were significantly associated with mortality. In 47 low-bias trials with 180 938 participants, the antioxidant supplements significantly increased mortality (RR, 1.05; 95% CI, 1.02-1.08). In low-bias risk trials, after exclusion of selenium trials, beta carotene (RR, 1.07; 95% CI, 1.02-1.11), vitamin A (RR, 1.16; 95% CI, 1.10-1.24), and vitamin E (RR, 1.04; 95% CI, 1.01-1.07), singly or combined, significantly increased mortality. Vitamin C and selenium had no significant effect on mortality.ConclusionsTreatment with beta carotene, vitamin A, and vitamin E may increase mortality. The potential roles of vitamin C and selenium on mortality need further study.

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Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: Systematic review and meta-analysis

Background Interest in the antioxidant vitamin E as a possible protective nutrient against coronary disease has intensified with the recognition that oxidized low-density lipoprotein may be involved in atherogenesis. Methods In 1980, 87,245 female nurses 34 to 59 years of age who were free of diagnosed cardiovascular disease and cancer completed dietary questionnaires that assessed their consumption of a wide range of nutrients, including vitamin E. During follow-up of up to eight years (679,485 person-years) that was 97 percent complete, we documented 552 cases of major coronary disease (437 nonfatal myocardial infarctions and 115 deaths due to coronary disease). Results As compared with women in the lowest fifth of the cohort with respect to vitamin E intake, those in the top fifth had a relative risk of major coronary disease of 0.66 (95 percent confidence interval, 0.50 to 0.87) after adjustment for age and smoking. Further adjustment for a variety of other coronary risk factors and nutrients, includi...

https://www.nejm.org/doi/pdf/10.1056/NEJM199305203282003

Vitamin E consumption and the risk of coronary disease in women.

Effects of weight reduction on blood lipids and lipoproteins: a meta-analysis.

Transthoracic electrical impedance; quantitative evaluation of a non-invasive measure of thoracic fluid volume.

Quantitative evaluation of vitamin E in the treatment of angina pectoris.

The comparative inotropic effects of six clinically used antiarrhythmic agents.

The reliability of graded maximal exercise treadmill testing and right atrial pacing in diagnosing significant obstructive coronary artery disease was evaluated in 74 consecutive patients referred to a cardiac unit with chest pain consistent with angina pectoris. The results of maximal exercise testing and right atrial pacing, with regard to the presence or absence of the patient's characteristic chest pain or discomfort and ischemic ST segment depression, were compared with the findings determined by selective coronary arteriography. Ischemic ST segment depression was defined as a downward displacement of one full mm or more of a horizontal or downward sagging ST segment. Forty-nine of the 74 patients studied were found to have significant coronary arteriographic obstruction, i.e., greater than 75% obstruction of one major coronary artery. The occurrence of the patient's characteristic chest pain or discomfort during maximal exercise testing or right atrial pacing is an excellent indicator of the presenc...

Diagnosis of Obstructive Coronary Disease by Maximal Exercise and Atrial Pacing

Changes in human circulatory physiology occurring in the minutes after intracardiac injection of angiographic contrast material have been well documented, but little information is available for the period of left ventricular opacification. The immediate and instantaneous effect on left ventricular function of the rapid intracardiac injection of 1 ml/kg body weight of 75 percent sodium-meglumine diatrizoate (Hypaque M®) into the pulmonary artery, left atrium or left ventricle in 43 adult patients was studied by measurement during angiography of (1) peak aortic root blood velocity in 28 patients, (2) instantaneous stroke volume (computed from the velocity tracing) in 28 patients, (3) heart rate in 41 patients, (4) left ventricular end-diastolic pressure in 17 patients, and (5) left ventricular end-diastolic and end-systolic volumes (calculated from the single-plane cineangiogram) in 14 patients. During left ventricular opacification, variables 1 through 4 differed only slightly from control values; the only statistically significant changes were in peak velocity after pulmonary arterial injection (114 percent of control, control = 100 percent), heart rate after left atrial injection (93 percent of control) and left ventricular end-diastolic pressure after left ventricular injection (110 percent of control). Sequential left ventricular end-diastolic and end-systolic volumes measured over 3 to 5 cardiac cycles demonstrated no significant change. We conclude that measurements based on angiographic left ventricular volumes should be valid and correspond closely to the control state. The major hemodynamic changes secondary to contrast injection occur later, beginning 15 to 30 seconds after injection.

J.Richard Warbasse

Papers

Transthoracic electrical impedance; quantitative evaluation of a non-invasive measure of thoracic fluid volume.

Quantitative evaluation of vitamin E in the treatment of angina pectoris.

The comparative inotropic effects of six clinically used antiarrhythmic agents.

Diagnosis of Obstructive Coronary Disease by Maximal Exercise and Atrial Pacing

Immediate hemodynamic effects of cardiac angiography in man.