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The Behavioral Risk Factor Surveillance System (BRFSS) collects telephone interview data on behaviors for the leading causes of premature death and disability. Its validity has never been adequately studied. The authors replicated BRFSS methodology to validate self-reported cardiovascular disease (CVD) risk factors. Nine-hundred and eleven subjects from three upstate New York counties were interviewed between 1/89 and 5/90. Interviewees were offered physical examinations and laboratory testing for CVD risk factors; 282 men and 344 women participated. The authors studied validity by comparing objectively measured to self-reported CVD risk factors. Sensitivities for self-reported hypertension, hypercholesterolemia, obesity, smoking, and diabetes were: 43, 44, 74, 82 and 75%, respectively. Only smoking sensitivity differed by gender: men, 77%; women, 86%. Specificity was > 85% for all risk factors, except hypercholesterolemia in men (75%). Prevalence was underreported for hypertension, hypercholesterolemia, obesity, and smoking by 43, 50, 25 and 17%, respectively. Results suggest telephone survey research includes physiologic measurements for blood pressure, cholesterol, height, weight, and smoking to validate self-reported CVD risk factors. When this is impossible, results such as these can be used, in similar samples, to correct risk factor prevalence rates from telephone surveys for misclassifications.

The present study compared the effects of diets rich in stearic acid (C18:0) versus one high in lauric and myristic acid (C12:0, C14:0) on platelet phospholipid fatty acid levels and concentrations of urinary thromboxane B2 (TXB2) and 6-keto-PGF1 alpha, which are stable metabolites of thromboxane A2 (TXA2) and PGI2 and indicators of cardiovascular hemostasis. A diet high in dairy butter (B) was the source of C12:0 and C14:0; C18:0 was provided by diets high in cocoa butter (CB), milk chocolate (CHOC) or CB+B in a 4:1 ratio (MIX). A randomized, crossover double-blind experimental design was used. Experimental subjects (n = 15) consumed each diet for 26 days, with a 1-month washout period between each experimental period. Urine and blood were collected from each subject at the beginning and end of each dietary period. Urinary TXB2 and 6-keto-PGF1 alpha were analyzed by radioimmunoassay (RIA). There were no effects of diet on the 24-hour excretion of either metabolite or on the ratio of 6-keto-PGF1 alpha/TXB2, even though there were significant changes in the eicosanoid precursor, arachidonic acid (C20:4n-6), in platelet phospholipids. C20:4n-6 levels increased (44.8% +/- 1.0% to 47.1% +/- 1.3%; P < .05) in the phosphatidylethanolamine phospholipid subclass in subjects on the B diet and decreased in the phosphatidylcholine subclass on the CB diet (16.5% +/- 1.0% to 14.2% +/- 1.1%; P < .05) compared with baseline values.(ABSTRACT TRUNCATED AT 250 WORDS)

Regression analyses were performed on individual data from our two previous clinical investigations to establish the cholesterolemic effects of individual fatty acids. Our principal objective was to determine the effects of stearic acid on plasma total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol levels. Our second objective was to determine the variation in the cholesterolemic response of individuals to changes (delta) in the major dietary fatty acids. The best-fitting linear regression equations relating delta TC and delta LDL (mg/dL) were as follows: delta TC = 2.3 delta C14:0 + 3.0 delta C16:0 - 0.8 delta C18:0 - 1.0 delta polyunsaturated fatty acids (PUFA) and delta LDL = 2.6 delta C14:0 + 2.9 delta C16:0 - 0.5 delta C18:0 - 0.7 delta PUFA, where delta fatty acid = change in intake expressed as percent of calories. Based on these equations, in which stearic acid has a significant, negative regression coefficient, and the other regression models analyzed, it appears that stearic acid has an independent cholesterol-lowering effect. Using the equation we developed, 75% of the actual cholesterolemic responses were within +/- 10 mg/dL of the predicted response. In summary, we have developed a predictive equation (similar to those developed by both Keys and Hegsted) to estimate changes in plasma TC and LDL cholesterol levels of young men in response to changes in dietary fatty acids. However, our predictive equation separates stearic acid from the other long-chain saturated fatty acids (SFA) and indicates that it has an independent cholesterol-lowering effect. Thus, stearic acid is a unique long-chain SFA because of its effect on plasma cholesterol level.

The present studies were conducted to evaluate the cholesterolemic effects of whole-food diets high in stearic acid. In study no. 1, normocholesterolemic young men were fed diets high in stearic acid provided by cocoa butter (CB); oleic acid provided by olive oil (OO); linoleic acid provided by soybean oil (SO); and myristic acid (and lauric acid) provided by dairy butter (B). In study no. 2, different subjects with similar baseline characteristics were fed diets high in stearic acid provided by milk chocolate (C), CB, CB+B (4:1, MIX), and myristic (and lauric) acid provided by B. Both studies used a randomized, crossover, double-blind experimental design, and experimental subjects (n = 18 for study no. 1 and n = 15 for study no. 2) in each study consumed every diet for 26 days with a 1-month wash-out period between each experimental period. The diets provided 37% of calories from fat, of which 81% was provided by the test fat. Ten ounces (280 g) C was provided daily by the C diet. In study no. 1, the B diet was hypercholesterolemic, whereas the SO diet was hypocholesterolemic, compared with the other diets. The OO and SO diets were hypocholesterolemic compared with the CB diet. Low-density lipoprotein (LDL) cholesterol levels, in general, paralleled the changes in plasma total cholesterol levels. SO significantly decreased apolipoprotein (apo) B levels compared with the other diets. Plasma very-low density lipoprotein (VLDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and apo A-I levels were unaffected by the experimental diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Current recommendations from various international expert committees generally concur in their definitions of borderline and high triglyceride levels, with small but important differences between recommendations in the definition of normal levels. However, population-based data on triglyceride levels are poorly developed in most countries, making difficult any international comparisons of prevalences of hypertriglyceridemia using the new definitions. However, it is probable that there should be considerable differences in the prevalence of hypertriglyceridemia, probably due to a mixture of genetic and environmental influences. The management of hypertriglyceridemia must continue to emphasize the detection and correction of secondary causes, even though the specific secondary causes may vary between countries. Dietary and exercise interventions must deal with local customs and resources, including striking international differences in alcohol consumption. Pharmacologic therapies will likely increase in use if they follow the trends in countries with available data. Although various drugs are available, nicotinic acid and fibric acid derivatives remain the drugs of choice. Considerably more research is needed to describe these international differences in etiology, prevalence and management practices of hypertriglyceridemia.

Background: Patients with coronary artery disease (CAD) are at considerable risk for subsequent cardiovascular events. Although hyperlipidemia accentuates the risk, predictors of subsequent events with CAD and desirable total cholesterol (TC) (less than 5.2 mmol/l) have not been assessed., Methods and Results: A survival analysis was performed in a subset of 740 consecutive patients who underwent diagnostic coronary arteriography between 1977 and 1978. Eight-three men and 24 women with angiographically documented CAD and desirable TC were followed for subsequent cardiovascular events, including myocardial infarction and cardiovascular death. Over a 13-year period, 75% of CAD subjects with reduced high density lipoprotein cholesterol (HDL-C) (less than 0.9 mmol/l) developed a subsequent cardiovascular event compared with 45% of those with HDL-C greater than or equal to 0.9 mmol/l (p = 0.002). A Kaplan-Meier analysis revealed significantly greater survival from cardiovascular end points in patients with baseline levels of HDL-C greater than or equal to 0.9 mmol/l (p = 0.005). After 11 variables were tested, an age-adjusted Cox proportional-hazards model identified two pairs of independent predictors of subsequent cardiovascular events: they were a left ventricular ejection fraction (LVEF) less than 35% (relative risk [RR], 6.5; 95% confidence interval [CI], 2.8, 15.3; p less than 0.001) and reduced HDL-C (RR, 2.0; 95% CI, 1.2, 3.3; p = 0.01) in the first model and LVEF less than 35% (RR, 6.5; 95% CI, 2.7, 15.6; p less than 0.001) and TC:HDL ratio greater than or equal to 5.5 (RR, 1.9; 95% CI, 1.1, 3.1; p = 0.02) in the second model., Conclusions: Low HDL-C (or high TC:HDL-C) is strongly predictive of subsequent cardiovascular events in subjects with CAD, despite desirable TC. As such, identification of this potentially modifiable risk factor should be actively pursued in this high-risk subgroup.

Idiopathic dilated cardiomyopathy (IDC) is the primary indication for cardiac transplantation, with associated costs of approximately $177 million per year. Recognizing the economic implications of IDC, the increasing incidence, and the limited information on pathogenesis and prognosis, the National Heart, Lung, and Blood Institute convened a workshop on the Prevalence and Etiology of Idiopathic Dilated Cardiomyopathy on June 13 to 14, 1991. The difficulties of studying the disease were reviewed, including its relatively low prevalence, its potentially pluricausal nature, and the fact that it is often a diagnosis of exclusion. Still, it presents significant challenges to the cardiovascular scientific community, since the mechanism of myocardial damage and related etiologic and prognostic factors are virtually unknown. The development of more reliable measures of immune-mediated damage and noninvasive measures of impaired cardiac function present new research opportunities in this disorder. Standardized diagnostic criteria for use in observational and interventional trials were developed, and priorities for future research were proposed. Population-based registries and nested case-control studies, where feasible, are appropriate study designs for tracking incidence and prevalence, and for identifying risk factors, respectively. Interventional studies should focus on secondary prevention, through modifying immune-mediated damage in clinically evident dilated cardiomyopathy, and through prevention of sudden death in patients with the disorder. Primary prevention trials must await the identification of modifiable risk factors and of appropriate and effective interventions.

The predictors of premature coronary atherosclerosis were examined in 203 patients (99 men aged less than or equal to 50 years, and 104 women aged less than or equal to 60 years) undergoing elective diagnostic coronary arteriography. Age, cigarette smoking, hypertension, obesity, diabetes, positive family history of premature coronary artery disease (CAD), and plasma levels of total cholesterol, triglyceride, lipoproteins (i.e., very low, intermediate-, low-, and high-density [HDL] lipoproteins and their subfractions [HDL2 and HDL3], and lipoprotein [a]) and apolipoproteins (apoA-1, apoA-2 and apoB, respectively) were examined using univariate analyses and multivariate logistic regression. In men, age (p less than 0.05), smoking (p less than 0.05), and plasma triglyceride (p less than 0.02) and apoA-1 (p less than 0.05) levels were independently associated with CAD. In women, smoking (p less than 0.001) and plasma apoB levels (p less than 0.04) were the strongest variables independently associated with CAD. It is concluded that the "nontraditional" risk factors (plasma apoA-1 and apoB levels) are better predictors of premature CAD than are plasma lipoproteins and that smoking is the strongest of the traditional nonlipid risk factors.

Objective: --To determine the effect of filtered-coffee consumption on plasma lipoprotein cholesterol levels in healthy men., Design: --Randomized controlled trial with an 8-week washout period followed by an 8-week intervention period during which men were randomly assigned to drink 720 mL/d of caffeinated coffee, 360 mL/d of caffeinated coffee, 720 mL/d of decaffeinated coffee, or no coffee., Setting: --Outpatient clinical research center in a university medical center., Participants: --One hundred healthy male volunteers., Outcome Measure: --Changes in plasma lipoprotein cholesterol levels during the intervention period., Results: --Men who consumed 720 mL of caffeinated coffee daily had mean increases in plasma levels of total cholesterol (0.24 mmol/L, P = .001), low-density lipoprotein cholesterol (0.17 mmol/L, P = .04), and high-density lipoprotein cholesterol (0.08 mmol/L, P = .03). No significant changes in these plasma lipoprotein levels occurred in the other groups. Compared with the group who drank no coffee the group who drank 720 mL/d of caffeinated coffee had increases in plasma levels of total cholesterol (0.25 mmol/L, P = .02), low-density lipoprotein cholesterol (0.15 mmol/L, P = .17), and high-density lipoprotein cholesterol (0.09 mmol/L, P = .12) after adjustment for changes in diet., Conclusion: --Consumption of 720 mL/d of filtered, caffeinated coffee leads to a statistically significant increase in the plasma level of total cholesterol, which appears to be due to increases of both low-density lipoprotein and high-density lipoprotein cholesterol levels.

Control groups selected by random digit dialing are frequently used in case-control studies. Concern about the potential for bias in these control groups has been expressed, primarily because of low response rates. This study compares the characteristics of a hypothetical control group consisting of 341 men and women aged 40-74 years, selected by random digit dialing and participating in an interview in 1990, with the characteristics of 15,563 men and women aged 40-74 years who participated in a privately conducted census in the same upstate New York county in 1989. For most measures, no differences were seen between the random digit dialing sample and the census population. However, the hypothetical control group was more likely to have had their cholesterol checked in the past 2 years and was somewhat more likely to have had other screening tests as well. In addition, the hypothetical control group was somewhat better educated. The results suggest that, at least in this setting, control groups selected by random digit dialing are representative of the general population in most respects; however, caution should be used when studying the relation between screening tests and disease occurrence by means of case-control studies using controls selected by random digit dialing.

The value of serum total cholesterol measurement in predicting coronary heart disease (CHD) is well established in middle-aged men, but has been questioned in middle-aged women and older people of both sexes. To address this, the most recent follow-up data from 25 populations in 22 US and international cohort studies were presented and analyzed at a recent National Heart, Lung, and Blood Institute (NHLBI) workshop. Crude relative and absolute excess risks of fatal CHD were determined for individual studies and pooled across studies to determine pooled risk estimates. Serum total cholesterol and low-density-lipoprotein (LDL) cholesterol levels predicted fatal CHD in middle-aged (< 65 years) and older (> or = 65 years) men and women, though the strength and consistency of these relationships in older women were diminished. High-density-lipoprotein (HDL) cholesterol levels inversely predicted CHD in middle-aged men and women and in older women, but not in older men. Data for minority groups and for overseas populations were similar to those for white people in the United States. Relative risk estimates were generally lower for older than for middle-aged subjects, but absolute excess risk was greater. Older people and middle-aged women with elevated cholesterol levels are clearly at increased risk of coronary disease; whether this risk can be modified by dietary or drug therapy, and at what level intervention is appropriate, must not be determined.

Arteriographic case-control studies still have a role in defining associations and dose-response relations between newly purported risk factors and atherosclerotic coronary artery disease. They remain one of the better ways to sort out whether a risk factor acts to cause clinical coronary disease via effects on coronary atherosclerosis, infarction independent of atherosclerosis, or both. It remains unclear if the selection processes for coronary arteriography infuse bias into the selection of cases, though the report by Reed and Yano suggests it does not. Control group selection remains problematic, as it does for all case-control studies, and considerable effort should be exercised to avoid the many potential biases in selection of both cases and controls. In this latter statement there is agreement with authors Reed and Yano. However, the avoidance of arteriographic studies threatens to curb the initiation of that sequence of studies that can, in a relatively short duration of time, provide useful information on the potential for a risk factor intervention to inhibit coronary atherosclerosis and, possibly, clinical coronary events. This, then, raises the final point for emphasis. Arteriographic studies, be they case-control, prospective, or experimental, may be most powerful when paired with those using clinical endpoints. In addition to the chance for replication of findings with another set of endpoints, the issue of mechanism of action via the atherosclerotic process can be addressed. Interestingly, the Honolulu Heart Program, with its laudable efforts to collect both autopsy and arteriographic quantitations of atherosclerosis, provides perhaps the best illustration in the current literature of the power of using multiple endpoints for coronary artery disease to more completely elucidate the role of risk factors in the natural history of that disease.

Considerable progress has been made in recent years in our understanding of atherogenesis and, in particular, of how it relates to lipoprotein metabolism. In this conference, we attempt to re-evaluate the data on the relation between alcohol intake and coronary heart disease, emphasizing the effects of alcohol on lipoprotein metabolism. Epidemiologic data generally show an inverse correlation between coronary heart disease risk and moderate alcohol intake (variously defined but generally corresponding to 2 to 4 drinks per day). The potentially drastic effects of excessive alcohol intake on health, however, preclude any recommendation that patients increase their alcohol consumption. Equally, there may be no basis for prescribing moderate alcohol intake but, even here, the data are far from complete. The mechanism by which moderate alcohol intake "protects" remains unclear. Perhaps the best available hypothesis relates to the increased concentration of high-density lipoprotein (HDL) cholesterol associated with moderate alcohol intake. However, it should be stressed that we are still uncertain about the mechanisms linking a high HDL level to protection against coronary heart disease. If a high HDL level is only a marker (and not directly protective), raising HDL levels need not confer protection. Alcoholism, on the other hand, is associated with marked elevation of triglyceride-rich lipoproteins and is among the most common causes of hypertriglyceridemia. Moreover, once hepatic damage occurs, plasma HDL levels may actually be lower than normal. The determining point is that high alcohol intakes are associated with increased overall mortality. Until we know more about the metabolic and behavioral effects of alcohol and about its linkage to atherosclerosis, we have no basis for recommending either that patients increase their alcohol intake or that they start to drink if they do not already.

Development of strategies to prevent CHD in blacks is impeded by the virtual absence of clinical trials demonstrating the feasibility and effectiveness of interventions in blacks. The wholesale generalization that interventions effective (or ineffective) in whites are similarly effective in blacks may risk the employment of worthless or even dangerous interventions in blacks. Using available epidemiologic data, a number of risk factors may be more important in blacks than whites by virtue of higher prevalence, increased relative risk, or both. These may include hypertension, lipoprotein (a), smoking, diabetes, and obesity. Thus, health agencies might emphasize these risk factors when developing preventive programs targeted at black populations. Prevention programs may best seek to prevent the onset of risk factors found highly prevalent in black communities, rather than the costly and side-effect-prone interventions to treat risk factors once established. Thus, there is a role for community-based as well as a high-risk approaches. The community-based approaches should seek to work with organizations such as churches, which traditionally play strong roles in the black community. Physicians treating black patients should be aware of the potentially different roles played by risk factors, and treat aggressively those individuals identified to be at high risk. Risk factor management should be emphasized, rather than reduced, in patients with already established CHD. CHD has been clearly shown to be preventable; both blacks and whites should benefit from specific interventions aimed toward this worthy goal.

Serum levels of DHEA sulfate are inversely associated with cardiovascular death in men, and urinary dehydroepiandrosterone (DHEA) levels are inversely associated with clinical manifestations of coronary artery disease. These observations may be related to the antiproliferative effects of DHEA, resulting in inhibition of atherosclerotic intimal hyperplasia. To examine the relation between these steroids and a direct measure of coronary atherosclerosis, plasma DHEA and DHEA sulfate levels were determined in 206 middle-aged patients (103 men, 103 women) undergoing elective coronary angiography. Plasma DHEA sulfate levels were lower in men with at least one stenosis greater than or equal to 50% compared with those without any stenosis greater than or equal to 50% (4.9 +/- 2.7 versus 6.1 +/- 3.5 nmol/ml, p = 0.05). Levels of DHEA sulfate were also inversely related to the number of diseased coronary vessels (r = -0.20, p = 0.05) and a continuous measure of the extent of coronary atherosclerosis (r = -0.25, p = 0.01) in men. The association between DHEA sulfate levels and extent of coronary artery disease was independent of age and other conventional risk factors for coronary disease. In women, there was no association between plasma DHEA or DHEA sulfate levels and coronary disease. These data demonstrate a consistent, independent, inverse, dose-response relation between plasma DHEA sulfate levels and angiographically defined coronary atherosclerosis in men. Plasma DHEA sulfate may be another important and potentially modifiable risk factor for the development and progression of coronary atherosclerosis.

Although the postpericardiotomy syndrome is a common complication of cardiac operations, the most effective drug regimen for the treatment of this condition has not been established. The present study was designed to evaluate the effectiveness of nonsteroidal antiinflammatory drugs (NSAIDs) in the treatment of postpericardiotomy syndrome, in a double-blind, placebo-controlled randomized trial with a 10-day course of ibuprofen or indomethacin. Of 1019 adult patients undergoing cardiac operations during a 14-month period, a diagnosis of postpericardiotomy syndrome was made in 187, and 149 were enrolled in the study. Diagnosis was based on the presence of at least two of the following: fever, anterior chest pain, and friction rub. Drug efficacy was defined as the resolution of at least two of these criteria within 48 hours of drug initiation. Ibuprofen and indomethacin were 90.2% and 88.7% effective, respectively, and both were significantly more effective than placebo (62.5%, p = 0.003). The occurrence of side effects, including nausea, vomiting, renal failure, and fluid retention, was low in all groups (13.1% for ibuprofen, 16.1% for indomethacin, and 16.7% for placebo [p = not significant). Length of hospital stay, incidence of ischemic events, and accumulation of significant pericardial effusions were similar in all groups. The results of this study demonstrate that both ibuprofen and indomethacin provide safe and effective symptomatic treatment for postpericardiotomy syndrome.

Purpose: This study was designed to determine youthful precursors of alcohol abuse in physicians., Subjects and Methods: We analyzed data from an ongoing prospective study of 1,014 male medical students enrolled in the graduating classes of 1948-1964 at the Johns Hopkins School of Medicine. The cohort, now physicians aged 52 to 68 years, has been contacted regularly since medical school to identify major disease. In 1986, the CAGE alcoholism screening questionnaire was administered. Alcohol abuse was defined as self-admitted alcoholism, excessive consumption of four or more beverages per day on average, or a score of 2 or higher on the CAGE questionnaire., Results: By these criteria, 131 of 1,014 (12.9%) patients abused alcohol. Medical school precursors associated (p less than 0.05) with subsequent alcohol abuse were as follows: non-Jewish ancestry (relative odds [RO] = 3.1), lack of religious affiliation (RO = 4.1), cigarette use of one pack or more per day (RO = 2.6), regular use of alcohol (RO = 3.6), anxiety (RO = 1.8) or anger (RO = 1.8) as a reaction to stress, frequent use of alcohol in nonsocial settings (RO = 1.6), past history of alcohol-related difficulty (RO = 3.1), and maternal alcoholism or mental illness (RO = 1.9). Precursors found not to be associated with alcohol abuse included sleep habits, use of sedatives or amphetamines, interest in athletics or hobbies, and parental relationship., Conclusion: Our results suggest that there are several identifiable medical school precursors of alcohol abuse in physicians.

The detection of individuals with hypercholesterolemia has received world-wide support as a means of determining who would benefit from dietary and pharmacologic interventions. However, the clinician or public health practitioner should be aware of several issues that must be resolved before cholesterol screening can attain maximal impact. This review examines whether hypercholesterolemia is a condition worthy of screening programs and discusses the promises and pitfalls of individual and mass screening approaches.

Risk factors for cardiovascular disease are commonly obtained in freshman medical students for the purpose of increasing interest and awareness in preventive cardiology. What would be a normal range of values for this select group? This paper describes the major cardiovascular risk factors for 3,811 male and female freshman medical students from eight U.S. medical schools that were obtained in a standardized fashion as part of the Preventive Cardiology Academic Award (PCAA) programs at these institutions. The distributions of height, weight, Quetelet index, systolic and diastolic blood pressures, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and calculated low-density lipoprotein cholesterol are presented for male and female medical students stratified by race into white, black, Asian, and Hispanic groups. The sex and race distributions of cardiovascular risk factors such as previously diagnosed hypertension, diabetes mellitus, smoking, lack of regular exercise (three times a week or more), oral contraceptive use in women, and family history of coronary heart disease are presented. The cardiovascular risk of freshman medical students is compared to other epidemiologic studies of young adults. The use and limitations of these race- and sex-specific data on cardiovascular risk, including physiologic measurements, are discussed in the context of educational programs for medical students and house staff in preventive cardiology.

The National Cholesterol Education Program treatment guidelines define a plasma total cholesterol of less than 200 mg/dl as "desirable" and recommend no further evaluation of plasma lipid or lipoprotein levels in patients with coronary artery disease (CAD). To determine the prevalence of dyslipidemias in the presence of coexistent CAD and total cholesterol less than or equal to 200 mg/dl, a retrospective case-control study of 1,000 patients who underwent diagnostic coronary angiography was performed. Of 351 patients with total cholesterol less than or equal to 200 mg/dl, 76% of the men (244) and 44% of the women (107) had angiographically demonstrated CAD. In men with CAD and total cholesterol less than or equal to 200 mg/dl, there was a significantly greater prevalence of low levels of high density lipoprotein (HDL) cholesterol (less than or equal to 35 mg/dl), age greater than 50 years, systemic hypertension and diabetes mellitus compared to non-CAD control subjects. In women with CAD and total cholesterol less than or equal to 200 mg/dl, HDL cholesterol less than or equal to 45 mg/dl and diabetes mellitus were also significantly prevalent. Multiple logistic regression analyses revealed that HDL cholesterol, hypertension and age in men and very low density lipoprotein cholesterol in women were significantly associated with CAD after adjustment for other risk factors. These results suggest that a complete lipid and lipoprotein analysis be obtained in all patients with CAD, irrespective of the plasma (or serum) total cholesterol level.

An epidemiologic study of idiopathic dilated cardiomyopathy was carried out in order to identify possible risk factors for this often fatal cause of heart failure in young adults. Possible associations with black race and other genetic and environmental factors were examined by comparing newly diagnosed cases ascertained from four Baltimore hospitals (n = 95) with neighborhood controls (n = 95), matched on sex and 5-year age intervals. Matched and unmatched relative odds and conditional logistic regression coefficients were obtained to describe the associations. Statistically significant, independent associations were observed between idiopathic dilated cardiomyopathy and black race, low annual income, and history of asthma (p less than 0.05). The black predominance (relative odds = 2.7, 95% confidence interval 2.0-3.4) was not explained by income, alcohol consumption, cigarette usage, body mass index, hypertension, or asthma. A possible interactive effect was observed between black race and history of asthma and other atopic diseases. Thus, blacks, especially those with a history of hypersensitivity, may represent a high-risk subgroup in need of preventive care or early intervention.

This study tested the effectiveness of two conceptually different chart audit-based approaches to modifying physicians' clinical practices to conform with quality-assurance standards. The objective was to increase intern utilization of cholesterol management opportunities in the inpatient setting. Using a clinical trial study design, 29 internal medicine interns were randomly assigned to four intervention groups identified by the intervention they received: control, reminder checklists (checklists), patient-specific feedback (feedback), or both interventions (combined). Over a nine-month period, intern management of high blood cholesterol levels in internal medicine inpatients (n = 459) was monitored by postdischarge chart audit. During both a baseline and subsequent intervention period, interns documented significantly more cholesterol management for inpatients with coronary artery disease (CAD) than without CAD. During baseline, 27.3%, 24.3%, 21.7%, 12.4%, 5.4%, and 2.7% of all inpatient charts had intern documentation concerning a low-fat hospital diet, cholesterol history, screening blood cholesterol level assessment, follow-up lipid profile, nutritionist consult, and preventive cardiology consult, respectively. The feedback intervention significantly increased overall intern-documented cholesterol management among inpatients with CAD. The checklists significantly decreased overall intern-documented cholesterol management. Feedback appears to be an effective approach to increasing intern cholesterol management in inpatients.

Hypercholesterolemia is an important determinant of progressive atherosclerosis in both vein grafts and native vessels after coronary artery bypass surgery. We demonstrated that nearly half of all patients admitted for coronary bypass have elevated cholesterol levels before surgery. Of these, half are unaware of the elevations in cholesterol level, and few are undergoing any treatment. The results suggest that lipids should be measured before coronary bypass surgery to optimize postoperative risk reduction education.

Data were collected on 433 black medical students at Meharry Medical College (MMC) and 573 white medical students at The Johns Hopkins University School of Medicine (JHMS) during the period of 1958 through 1965 consisting of baseline measurement of some possible precursors of hypertension. Similar methods were employed in both cohorts. Comparison as to prevalence and significance of hypertension precursors revealed the following: Black males had significantly higher casual and resting blood pressures than whites (p less than 0.01); and higher mean changes in blood pressure following the cold pressor test. White males had a significantly higher mean change in heart rate following cold pressor test (p less than 0.01). Upon exercise black males had significantly higher mean change in blood pressure and heart rate (p less than 0.01). There appears to be more blood pressure lability in blacks as indicated by higher mean SBP + DBP changes following the cold pressor test, and by mean pulse pressure level at peak exercise. The difference in blood pressure lability observed between blacks and whites in young adulthood may be one of the earliest identifiers of later differences in the incidence of hypertension. However, of even more importance is the difference in blood pressure levels between the two groups, though both are normotensive.

Isoenzymes of glucose-6-phosphate dehydrogenase, used as cellular markers, showed that a minority of fatty streaks have clonal characteristics intermediate between those of normal arterial wall and those of fibrous plaques, suggesting that such streaks are evolving into fibrous plaques. "Intermediate" fatty streaks are found to cluster in patients in the middle-age years, suggesting that few fatty streaks evolve into plaques in the advanced years. It is suggested that two populations of fatty streaks exist: one destined, perhaps by its location or risk factors, to develop into fibrous plaques; and a second which remains as fatty streaks and never goes on to become fibrous plaques. This hypothesis helps to explain some of the evidence disclaiming the fatty streak as a forerunner of the atherosclerotic plaque.

Prior studies of the contribution of coronary disease risk factors to familial aggregation of premature coronary disease may have underestimated risk factors by relying on self-reported risk factor prevalence levels or, when risk factors have been measured, by using cut points in excess of the 90th percentile. To determine the actual prevalence of hyperlipidemia, hypertension and diabetes, and the awareness of these coronary risk factors in unaffected family members, 150 apparently coronary disease-free siblings of 86 people who had documented coronary disease before 60 years of age were studied. All subjects participated in a 1 day screening preceded by a self-administered risk factor questionnaire and a personal interview. Participation of both the index patients and siblings exceeded 86%. With the use of nationally established recommendations for blood pressure and lipids, which are based on coronary disease risk curves, screening revealed that 48% of brothers and 41% of sisters were hypertensive, 45% of brothers and 22% of sisters had a lipid abnormality, 38% of siblings were current cigarette smokers and 4.7% were diabetic. Two or more risk factors were present in 42% of brothers and 26% of sisters. More than 75% of siblings had one or more risk factors that would require intervention. When compared with a race-, gender- and age-matched reference population from the Lipid Research Clinics Prevalence Study, distributions for blood pressure and for total and low density lipoprotein cholesterol were higher for the siblings in every gender and age group.(ABSTRACT TRUNCATED AT 250 WORDS)

A modified Minitek system (BBL Microbiology Systems, Cockeysville, Md.) for species identification of coagulase-negative staphylococci was compared with the Staph-Ident system (Analytab Products, Plainview, N.Y.). The conventional method of Kloos and Schleifer (J. Clin. Microbiol. 1:82-88, 1975) was used as the reference method for identification. When tested with 78 coagulase-negative staphylococcal isolates from 63 children with cancer. Minitek concurred with the conventional identification in 67 (86%) isolates and Staph-Ident concurred in 61 (78%) isolates. Identification of species other than Staphylococcus epidermidis was better with Staph-Ident (19 of 23 isolates) than with Minitek (14 of 23 isolates). Concordance of results was likewise high, 88% (7 of 8) for Minitek and 100% (8 of 8) for Staph-Ident in studies with eight coagulase-negative staphylococcal strains obtained from the American Type Culture Collection (Rockville, Md.). We conclude that the modified Minitek system is a practical and reliable test for identifying coagulase-negative staphylococci in clinical microbiology laboratories. Its versatility and larger repertoire of biochemical tests may offer advantages over the Staph-Ident system.

Human tissue plasminogen activator holds promise for the dissolution of coronary thrombi by intravenous administration and without systemic anticoagulation. Prior animal experiments have been conducted only in vessels without disease. To test the thrombolytic efficacy of recombinant tissue plasminogen activator in the presence of diseased intima, an established model of atherosclerosis was utilized. The aorta of 16 New Zealand white rabbits (2 to 3 kg) was made atherosclerotic by balloon endothelial denudation and concurrent 1% cholesterol feeding for 8 weeks. An aged (24 hour) heterologous (human) clot, labeled with I-125 fibrinogen was injected into the distal aorta and produced thrombotic occlusion. After 1 hour of thrombosis (control period), recombinant tissue plasminogen activator (100,000 IU approximately equal to 1 mg protein, n = 6) or streptokinase (100,000 IU, n = 5) or saline solution (n = 5) was systemically infused over 30 minutes. Serial blood samples, obtained to determine fractional change in blood radioactivity over time, showed a fourfold increase of blood radioactivity after tissue plasminogen activator and streptokinase infusion compared with the control period (47,400 +/- 3,300 [mean +/- standard error] versus 11,800 +/- 300 counts/min, p less than 0.001). Time to 50% of maximal thrombolysis was 41 +/- 14 minutes (+/- standard deviation) for tissue plasminogen activator versus 63 +/- 16 minutes for streptokinase (p less than 0.01). In six of six rabbits receiving tissue plasminogen activator and four of five rabbits receiving streptokinase, reestablishment of distal aortic flow was detected via the indwelling catheter within 25 minutes of drug infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

The surfaces of 8 aortas from women heterozygous for G-6-PD isoenzymes were mapped for an examination of the relationships of monoclonality, lesion type, lesion thickness, and age of the patient. The percent B isoenzyme value of samples of normal intima (n = 315), fatty steak (n = 68), or fibrous plaque (n = 64) was used to define monoclonality, expressed as the [Z] score, the number of standard deviations from the mean percent B isoenzyme of samples of underlying media. Intimal thickness increased significantly with type of lesion, such that intima less than fatty streak less than fibrous plaque, and with the age of the patient. The percentage of monoclonal portions also increased with lesion type, such that 1% of samples of normal intima were monoclonal, compared with 4.4% of fatty streaks and 12.5% of fibrous plaques (P less than 0.005). Monoclonality increased with intimal thickness when normal intima, fatty streaks, and fibrous plaques were combined (P = 0.0001). When examined separately, normal intima showed a direct correlation between monoclonality and intimal thickness. In contrast, the monoclonality of fatty streaks was inversely associated with thickness (P = 0.016) and the monoclonality of fibrous plaques not related to thickness. When entered into a multiple regression model, lesion type and age, but not lesion thickness, significantly predicted monoclonality. The lack of association of intimal thickness with monoclonality suggests that it is the type of lesion that determines monoclonality and not merely its thickness. This implies that mechanisms other than clonal selection are responsible for the monoclonal characteristics of human atherosclerotic lesions.

Cardiovascular reactivity to stress is hypothesized to be a marker for subsequent neurogenic cardiovascular disease, but few prospective studies of this hypothesis are available. We studied 910 white male medical students who had their blood pressure and pulse rate measured before and during a cold pressor test in the years 1948-1964. Hypertensive status (requiring drug treatment) was ascertained by annual questionnaires in the 20- to 36-year follow-up period. An association was observed between maximum change in systolic blood pressure and later hypertension, with a cumulative incidence of hypertension by age 44 of 6.7%, 3.0%, and 2.4% for a change in systolic blood pressure in the upper, middle two, and lowest quartiles, respectively (Kaplan-Meier, p less than 0.02). After adjustment for study entry age, Quetelet Index, cigarette smoking, pretest systolic blood pressure, and paternal or maternal history of hypertension in a Cox model, the association persisted. The excess risk associated with systolic blood pressure reactivity was not apparent until the population aged some 20 years and was most apparent among those in whom hypertension developed before age 45 (relative risk = 2.5, 95% confidence intervals = 1.47, 4.71 for a 20 mm Hg change). Diastolic blood pressure and heart rate changes were not associated with later hypertension. These data suggest that persons prone to later hypertension manifest an altered physiology at a young age.

Using isoenzymes of glucose-6-phosphate dehydrogenase (G-6-PD) as cellular markers, a study was made of atherosclerotic fibrous plaques and fatty streaks in aortas of black women heterozygous for G-6-PD. Of 29 fibrous plaques, 26 (89.7%) contained only one isoenzyme (17, A; 9, B), the other three containing both A and B. Of 28 fatty streaks, five (17.8%) contained only one isoenzyme (2, A; 3, B), the remaining 23 containing both A and B. Normal uninvolved aorta contained both A and B isoenzymes in 99 of 101 samples. These results confirm the monoclonal character of atherosclerotic fibrous plaques; this strands in contrast to the fatty streaks which most commonly contain the two isoenzymes. The studies on the fatty streaks are inconclusive at this stage in determining whether the streak is the forerunner of the fibrous plaque.

Two hypotheses have been proposed to explain the origin of monoclonal cell populations within human atherosclerotic plaques. The first of these proposes a mutational origin: the second suggests that the single clone of cells with the greatest proliferative advantage is selected following repetitive intimal injury. If the selection hypothesis is true, monoclonality should be observed more frequently in the layer of plaque most recently formed. Glucose-6-phosphate dehydrogenase (G-6-PD) isoenzymes were used as cellular markers in aortas of females heterozygous for the A and B isoenzymes. Ten plaques were divided into 45 portions, each of which was subdivided into upper layer, lower layer, and underlying media. No predominance of monoclonality was observed in the upper or lower layers of plaque, with 53% of samples from each layer being monoclonal. In all, 73% of portions of plaque contained at least one monoclonal layer. The layers tended to resemble each other in their clonal characteristics, with 60% of portions having layers with the same clonal characteristics. A significant correlation between isoenzyme distributions in upper and lower layers of the same portion was observed. No consistent trends in isoenzyme distribution in the three layers of each portion were observed. The results are interpreted as providing no evidence for clonal selection as the mechanism by which human atherosclerotic plaques become monoclonal.

Although the use of arteriography to define coronary artery disease is considered the optimal method for determining associations of risk factors with atherosclerosis, the strengths of associations found have varied greatly between arteriographic studies. To assess whether such associations are affected by changes in the arteriographic definition of absence of disease, the authors evaluated one sample of patients undergoing coronary arteriography. The prevalence of specific risk factors by the extent of atherosclerosis (0-24, 25-49, and greater than or equal to 50% maximal stenosis) was determined, as were their associations with coronary artery disease (greater than or equal to 50% stenosis), using persons with 0-24 or 0-49% maximal stenosis, separately, as control groups. Among both males and females, analysis showed increased prevalence of risk factors with increasing atherosclerosis, with greater similarity of those who had moderate atherosclerosis to the cases than to those who had minimal atherosclerosis. The strength of association of arteriographically defined coronary disease with age, hypertension, diabetes, low and high density lipoprotein cholesterol, smoking, and family history generally varied inversely with the extent of atherosclerosis permitted within the control group. These findings indicate that epidemiologic understanding of associations of risk factors with atherosclerosis may be weakened by including persons with moderate, subclinical atherosclerosis within the control group.

Using 14 personality measures obtained while the subjects were in medical school, the resulting profiles of 972 physicians were clustered into five groups using a two-stage cluster analysis procedure. Subjects were followed over a 30-year period to determine the cumulative survival rate (proportion of subjects remaining free of cancer) in each group. Statistically significant group differences in survival rate were found, with the group characterized by acting out and emotional expression having the most favorable curve (less than 1% developing cancer). The group characterized as "loners," who may well have suppressed their emotions, had the most unfavorable survival curve and was 16 times more likely to develop cancer than was the group characterized by acting out and emotional expression.

Atherosclerotic plaques in man have monoclonal characteristics. One possible explanation for this observation is that clonal selection occurs as cells proliferate at sites of intimal injury. To test whether such clonal selection could occur during the formation of an intimal "scar", the clonal characteristics of human cutaneous scars were studied with the use of glucose-6-phosphate dehydrogenase (G-6-PD) as a cellular marker. Scars from 7 black women heterozygous for the A and B isoenzymes of G-6-PD were divided into 870 portions consisting of contiguous normal skin, scar margin, outer scar, and inner scar. Portions were further divided into surface and deeper portions of scar. In 4 of the 7 cases, significant differences were observed between the mean percentage of total activity in the B isoenzyme band in portions of scar and portions of skin. Significant differences between surface and deeper portions of both skin and scar were also observed in 5 cases. The variance of isoenzyme values from portions of scars was not significantly greater than that within portions of skin. It is concluded that the results are consistent with clonal selection occurring during the healing of skin wounds. However, the magnitude of the difference (no greater than a 5.7% B isoenzyme difference) is far too small to even partially explain the marked differences in isoenzyme patterns observed between atherosclerotic plaques and uninvolved aortic wall. The results do not support the idea that the monoclonality of human atherosclerotic plaques is due to clonal selection following the healing of an intimal injury.

Severe paroxysmal pulmonary hypertension with increased pulmonary vascular resistance precipitated by exposure to cold is postulated as the mechanism causing dyspnea and cardiopulmonary arrest in a patient with systemic sclerosis. Multiple exposures to cold air and a 0 degree C saline infusion resulted in the acute onset of dyspnea and peripheral vasoconstriction. Pressure readings from a Swann-Ganz catheter in place during the saline-induced dyspneic attack showed significant elevation of pulmonary arterial pressure and vascular resistance, suggesting that pulmonary vasospasm caused the attack.

Figure drawings obtained while subjects were in medical school were scored using two different scales: (a) Sophistication-of-Body-Concept, a scoring system that measures the overall quality of the drawings; and (b) Conventionality/deviancy of the drawings, as determined by the relative frequency with which 42 different characteristics occurred in the total sample of drawings. Figure drawings were obtained from 1951 to 1964. As of 1984, subjects were classified into 1 of 11 health outcome (disease) categories plus a "healthy" category. Statistical analysis included one-way analyses of variance and multiple logistic regression in which age and cigarette consumption were controlled. Several statistically significant differences among groups were noted with respect to Conventionality/deviancy, but not with respect to Sophistication-of-Body-Concept.

Because of recent evidence from in vitro studies suggesting that immediate hypersensitivity or other autoimmune mechanisms may play a role in the initiation or progression of idiopathic dilated cardiomyopathy (DCM), an epidemiologic study was carried out to examine possible associations with atopic diseases and other immunologic disorders. Newly diagnosed cases were ascertained from four Baltimore hospitals and were interviewed along with neighborhood controls identified using a random digit dialing technique. The cases and controls (N = 190) were matched on sex and 5-year age intervals and were compared in the analysis using matched and unmatched estimates of the relative odds and conditional logistic regression methods. A statistically significant, independent association was observed between idiopathic DCM and a history of asthma (p less than 0.05). The association was most pronounced among individuals who were less than 55 years of age (relative odds = 20.3, p less than 0.05), with 31.1% (14 of 45) of the patients who were under the age of 55 having a reported history of asthma. These findings support the theory that hypersensitivity mechanisms may be important in the development of idiopathic DCM. A treatment effect associated with asthma is an alternative possibility.

The female hybrid hare (Lepus timidus x Lepus europaeus) is heterozygous for electrophoretically separable, X-linked isoenzymes of glucose-6-phosphate dehydrogenase. The isoenzymes of this animal have been used as cellular markers in the study of the clonal origins of experimentally induced atherosclerotic lesions. Aortic lesions produced in the hybrid hare by feeding cholesterol and injuring the aortic wall with a catheter have been shown to have polyclonal characteristics and in this way are fundamentally different from atherosclerotic fibrous plaques in man.

Regional anesthesia is often preferred over general anesthesia for patients with cardiovascular disease because of presumed decreased risk of perioperative myocardial ischemia. However, few studies have addressed this issue directly. To determine whether the type of anesthesia is independently associated with myocardial ischemia, records of 134 patients undergoing peripheral vascular grafting under general or regional anesthesia were examined. There were no significant differences preoperatively between groups in ASA class, age, sex, or prevalence of angina, diabetes, or hypertension. Twelve patients developed myocardial ischemia or infarction within 7 days of operation; 11 of these 12 patients had received regional anesthesia (p less than 0.015). The association between anesthetic approach and perioperative myocardial ischemia or infarction remained after adjustment for preoperative factors associated with ischemia or with type of anesthesia. General anesthesia does not appear to be associated with increased risk of myocardial ischemia, and stringent recommendations to avoid it in this population may be unfounded. A clinical trial is needed to define more clearly the risks and benefits of different types of anesthesia in high-risk patients.

PPS is a major cause of morbidity after cardiac surgery and may cause bypass graft closure and fatal cardiac tamponade. Little is known about its incidence and cause. To better define this syndrome characterized by postoperative fever, pericardial friction rub, and pericardial pain, we used two out of three of the preceding criteria to diagnose PPS. In a prospective epidemiologic study we followed 944 consecutive patients undergoing open-heart surgery between November 1984 and November 1985. The overall incidence was 17.8%. The incidence was increased in younger patients, in those with a history of prednisone use in the past, in patients with a past history of pericarditis, those with aortic valve replacement, and in patients who received enflurane or halothane anesthesia. PPS is a common syndrome. Knowledge of risk factors associated with PPS may allow its prevention and identification of patients who warrant early and aggressive treatment.

Purpose: Accelerated coronary atherosclerosis is a major cause of heart graft failure two years and more after heart transplantation, yet its etiology remains undetermined. We conducted this study to determine the prevalence of coronary risk-associated lipid abnormalities, and the relationship between lipid levels and exposure to corticosteroids and cyclosporine, in heart transplant recipients., Patients and Methods: The records of 92 consecutive heart transplant recipients from three different transplantation centers were reviewed. Patients from the three centers varied in age, in corticosteroid regimens, and in the proportion undergoing transplantation for ischemic cardiomyopathy. Although 11 patients were not receiving corticosteroids at the time of the study, all patients had received them immediately after transplantation. In addition to information pertaining to demographics, pretransplant medical history, rejection episodes, drug doses, renal function, and blood glucose levels, data on dietary intake and body weight were collected and plasma lipid levels were measured at the time of record review., Results: A significant number, 48 (52 percent), of heart transplant recipients were above the sex- and age-adjusted 75th percentile, and 35 (38 percent) were above the 90th percentile for total cholesterol in comparison with a general reference population. Similar elevations were found in low-density lipoprotein cholesterol, triglyceride, and high-density lipoprotein cholesterol levels. Bivariate analysis demonstrated cumulative prednisone exposure (r = 0.40, p = 0.0001) and cumulative cyclosporine exposure (r = 0.22, p = 0.04) but not diet or etiology of pretransplant heart disease to be significantly associated with age- or sex-adjusted total cholesterol percentiles. Low-density lipoprotein cholesterol percentiles were also correlated with cumulative prednisone (r = 0.37, p = 0.001) and cumulative cyclosporine exposure (r = 0.24, p = 0.02). Stepwise multiple linear regression analysis, however, demonstrated cumulative prednisone exposure to be the strongest predictor of both total and low-density lipoprotein cholesterol levels and percentiles (p = 0.0001), independent of cumulative cyclosporine exposure and other clinical variables., Conclusion: These data suggest that long-term corticosteroid exposure may result in an increased prevalence of unfavorable lipid profiles in heart transplant recipients.