Associations of osteoprotegerin with coronary artery calcification among women with systemic lupus erythematosus and healthy controls.

Objective We tested the hypothesis that higher circulating levels of osteoprotegerin (OPG) are related to higher levels of coronary artery calcification (CAC) among women with systemic lupus erythematosus (SLE) compared with healthy controls (HCs). Methods Among 611 women in two age- and race-matched SLE case-control studies, OPG was assayed in stored blood samples (HEARTS: plasma, n cases/controls = 122/124, and SOLVABLE: serum, n cases/controls = 185/180) and CAC was measured by electron beam computed tomography. Results In both studies, SLE patients had higher OPG and CAC levels than HCs. Higher OPG was associated with high CAC (>100 vs.100) among SLE, and with any CAC (>0 vs. 0) among HCs. Multivariable-adjusted OR (95% CI) for OPG tertile 3 vs. 1 was 3.58 (1.19, 10.76), p trend = 0.01 for SLE, and 2.28 (1.06, 4.89), p trend = 0.04 for HCs. Associations were attenuated when age-adjusted, but remained significant for HC women aged ≥ 40 and SLE women aged ≥ 50. ROC analyses identified 4.60 pmol/l as the optimal OPG cutpoint for predicting high CAC (>100) among SLE patients with sensitivity = 0.74 and specificity = 0.61, overall, but 0.92 and 0.52, respectively, for SLE patients aged ≥ 50. Conclusion Our cross-sectional results suggest that higher OPG levels are related to higher CAC levels among women with SLE vs. healthy controls.

Age and gender distributions of coronary artery calcium detected by electron beam tomography in 35,246 adults.

Electron beam tomography (EBT) is a noninvasive method used to detect coronary artery calcium (CAC). Due to the age-associated increase in incidence and magnitude of CAC, interpretation of results can be difficult. The purpose of this study was to develop a set of age- and gender-stratified CAC distributions to serve as standards for the clinical interpretation of EBT scans. Between 1993 and 1999, 35,246 asymptomatic subjects, 30 to 90 years of age, were self-referred for CAC screening using an Imatron EBT scanner. CAC score was calculated based on the number, areas, and peak computed tomographic density for each detected calcific lesion. CAC score in each coronary artery was equal to the sum of all lesions for that artery and the total CAC score was equal to the sum of the score of each artery. Total CAC scores were assigned to a percentile according to age and gender. CAC scores were reported at the 10th, 25th, 50th, 75th, and 90th percentiles for 16 age and/or gender groups. The prevalence of CAC increased with age for men and women. The extent of CAC differed significantly between men and women in the same age group. In summary, this study reports the distribution of CAC score by age and gender. Knowledge of the distribution of CAC, the effect of age on the total CAC score as well as the differences in total CAC scores that exist between men and women of similar age will assist the clinician in interpreting EBT CAC results.

Electron beam computed tomographic coronary calcium scanning: a review and guidelines for use in asymptomatic persons.

Coronary artery disease is the No. 1 cause of death in the developed world. Effective means of treatment such as drug therapy to lower cholesterol levels are available, but clinical application to patients at highest risk remains imprecise. Electron beam computed tomography (EBCT) has been suggested as a means to diagnose subclinical coronary disease and facilitate risk stratification, but no current interpretive consensus exists in clinical practice. We critically reviewed current, pertinent literature regarding EBCT coronary calcium scanning from a clinical perspective and, in particular, studies that evaluated it as a measure of atherosclerotic coronary disease. Additionally, we reviewed studies that quantified the EBCT "calcium score" in relationship to coronary heart disease events. The available data suggest that the EBCT calcium score can help identify persons at higher than anticipated risk of future coronary events: the greater the EBCT coronary calcium score, the greater the extent of atherosclerotic plaque disease. Based on the literature review, we offer EBCT interpretation guidelines as they relate to drug therapy and risk reduction in asymptomatic persons with borderline cholesterol levels. Considerable evidence shows that coronary calcium is specific for atherosclerotic plaque and that it can be sensitively detected and accurately quantified by using EBCT. The coronary calcium score can help guide initiation of clinical prevention programs as part of a risk stratification and management scheme aimed at improving outcomes in patients determined to be at highest risk of coronary disease for their respective age and gender.

Implementation of a four-year multimedia computer curriculum in cardiology at six medical schools.

The pressures of a changing health care system are making inroads on the commitment and effort that both basic science and clinical faculty can give to medical education. A tool that has the potential to compensate for decreased faculty time and thereby to improve medical education is multimedia computer instruction that is applicable at all levels of medical education, developed according to instructional design principles, and supported by evidence of effectiveness. The authors describe the experiences of six medical schools in implementing a comprehensive computer-based four-year curriculum in bedside cardiology developed by a consortium of university cardiologists and educational professionals. The curriculum consisted of ten interactive, patient-centered, case-based modules focused on the history, physical examination, laboratory data, diagnosis, and treatment. While an optimal implementation plan was recommended, each institution determined its own strategy. Major goals of the project, which took place from July 1996 to June 1997, were to identify and solve problems of implementation and to assess learners' and instructors' acceptance of the system and their views of its value. A total of 1,586 students used individual modules of the curriculum 6,131 times. Over 80% of students rated all aspects of the system highly, especially its clarity and educational value compared with traditional lectures. The authors discuss the aspects of the curriculum that worked, problems that occurred (such as difficulties in scheduling use of the modules in the third year), barriers to change and ways to overcome them (such as the type of team needed to win acceptance for and oversee implementation of this type of curriculum), and the need in succeeding years to formally assess the educational effectiveness of this and similar kinds of computer-based curricula.

Ability of the no-reflow phenomenon during an acute myocardial infarction to predict left ventricular dysfunction at one-month follow-up.

Despite angiographically successful opening of an infarct-related vessel within a 6-hour time frame, some patients do not recover left ventricular regional wall function in the infarct zone after an acute myocardial infarction (AMI). Recent evidence suggests that this finding is due to the no-reflow phenomenon, or failure to recover tissue perfusion despite patient epicardial arteries. We performed myocardial contrast echocardiography to assess tissue perfusion before and after opening of an infarct-related artery. Coronary angiograms, regional wall motion scoring, and myocardial contrast enhancement were graded by 3 observers. Of 24 patients with AMI, 7 (29%) failed to recover tissue perfusion in > or = 1 region of myocardium. Of 106 regions subtended by the infarct-related artery, 16 (15%), 43 (41%), and 47 (44%) regions had no-reflow, partial, or normal flow, respectively, after arterial patency was established. There was a spectrum of reperfusion patterns ranging from no-reflow to normal perfusion. One-month follow-up angiographic and myocardial contrast echocardiographic studies were performed in 12 of the 24 patients. At 1 month, all segments of myocardium that had immediate normal perfusion had regained normal wall motion. In contrast, 17 segments that had partial or no-reflow were identified. Of these 17, 3 regained normal function, 10 segments were hypokinetic, and 4 segments were akinetic. We conclude that myocardial contrast echocardiography can be used to identify the no-reflow phenomenon in up to 29% of patients with AMI. Additionally, we found that the immediate-reflow pattern can predict degree of left ventricular dysfunction at 1-month follow-up.

Influence of age and gender on the presence of coronary calcium detected by ultrafast computed tomography.

OBJECTIVES: This study sought to determine the relation between coronary calcification detected with ultrafast computed tomography and lumen narrowing defined with angiography and evaluated whether this relation is influenced by age and gender. BACKGROUND: Ultrafast computed tomography has been shown to be a sensitive method for detection of coronary calcification associated with atherosclerotic disease, but the relation between the extent of coronary calcification and degree of lumen narrowing and the possible influence of gender or age, or both, on this relation have not been clarified. METHODS: Seventy men and 70 women were studied with ultrafast computed tomography for analysis of coronary calcification and coronary angiography. Coronary atherosclerosis was considered present if any lumen irregularity was noted on angiography, and obstructive coronary artery disease was defined as a lumen diameter narrowing > or = 70%. RESULTS: Coronary calcification had a sensitivity of 88% for identification of patients with atherosclerotic disease and 97% for those with obstructive disease, with corresponding specificities of 55% and 41%, respectively. The sensitivity of coronary calcium for detection of atherosclerotic disease in women < 60 years old was 50%, significantly less than the 97% sensitivity in women > 60 years old and the 87% sensitivity in men < 60 years old (p < 0.05 for each comparison). Logistic regression analysis revealed a 1.81-fold increase in the likelihood of detecting coronary calcification in the atherosclerotic lesions of men compared with those in women (95% confidence interval 1.12 to 2.93, p = 0.016) when controlled for age and severity of coronary disease by angiography. CONCLUSIONS: Atherosclerotic lesions in women are less likely to have coronary calcium than lesions with a similar degree of lumen narrowing in men. Differences in the pattern of coronary calcification between men and women may provide insight into the gender differences observed in the clinical development of symptomatic coronary artery disease.

Platelet aggregation in patients with atrial fibrillation taking aspirin or warfarin.

BACKGROUND AND PURPOSE: Although warfarin and perhaps aspirin may be effective in preventing thromboembolism in patients with nonvalvular atrial fibrillation, some patients develop cerebral infarction despite these therapies. The purpose of this study was to determine inhibition of platelet aggregation in patients on aspirin and platelet reactivity in those on warfarin in the Stroke Prevention in Atrial Fibrillation study. METHODS: Twenty-four patients in the Stroke Prevention in Atrial Fibrillation study at the University of Illinois at Chicago, 17 on enteric-coated aspirin 325 mg/d and 7 on warfarin to produce an International Normalized Ratio of 2.0 to 4.5, had platelet aggregation studies performed during a 10-month period and interpreted by an investigator blinded to therapy. Epinephrine, adenosine diphosphate, collagen, and arachidonic acid were used as aggregating agents. Compliance was determined by pill count for those patients on aspirin. RESULTS: Seven patients taking aspirin had partial and 10 had complete inhibition of platelet aggregation. Three of seven patients on warfarin had hyperaggregable platelets. Compliance was 80% or greater for those patients taking aspirin. One patient on warfarin had partial inhibition of platelet aggregation. CONCLUSIONS: Some patients in the Stroke Prevention in Atrial Fibrillation trial on aspirin 325 mg/d did not achieve complete inhibition of platelet aggregation. Others had hyperaggregable platelets. These findings suggest platelet-dependent mechanisms for aspirin and warfarin failure to prevent stroke in these patients.

Variability in plasma lipoprotein profiles when comparing diltiazem and propranolol.

OBJECTIVE: To examine the effects of diltiazem and propranolol on plasma lipoproteins in a double-blind, comparative trial. PATIENTS: Twenty-one mild-to-moderate hypertensive patients. METHODS: Following discontinuation of previous antihypertensive treatments, and a 4-week, single-blind, placebo run-in, subjects were randomized to receive sustained-release diltiazem or propranolol. Total cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL), and very-low-density lipoproteins (VLDL) were measured during placebo administration and after 12-16 weeks of treatment. RESULTS: No significant changes in plasma lipoprotein concentrations were noted in either the diltiazem or propranolol group compared with baseline values or each other. Marked variation in HDL, LDL, and VLDL were noted following drug treatment and in eight subjects whose lipoprotein concentrations were remeasured prior to drug treatment during the placebo period. The alterations were bidirectional, and similar in magnitude to those found following drug treatment. CONCLUSIONS: In many cases, changes in plasma lipoproteins reported to be a consequence of antihypertensive treatment may merely reflect normal intrapatient variability.

Outcome of CPR in a large metropolitan area--where are the survivors?

STUDY OBJECTIVES: Survival from out-of-hospital cardiac arrest in cities with populations of more than 1 million has not been studied adequately. This study was undertaken to determine the overall survival rate for Chicago and the effect of previously reported variables on survival, and to compare the observed survival rates with those previously reported. DESIGN: Consecutive prehospital arrest patients were studied prospectively during 1987. SETTING: The study area was the city of Chicago, which has more than 3 million inhabitants in 228 square miles. The emergency medical services system, with 55 around-the-clock ambulances and 550 paramedics, is single-tiered and responds to more than 200,000 emergencies per year. TYPE OF PARTICIPANTS: We studied 3,221 victims of out-of-hospital cardiac arrest on whom paramedics attempted resuscitation. MEASUREMENTS AND MAIN RESULTS: Ninety-one percent of patients were pronounced dead in emergency departments, 7% died in hospitals, and 2% survived to hospital discharge. Survival was significantly greater with bystander-witnessed arrest, bystander-initiated CPR, paramedic-witnessed arrest, initial rhythm of ventricular fibrillation, and shorter treatment intervals. CONCLUSIONS: The overall survival rates were significantly lower than those reported in most previous studies, all based on smaller communities; they were consistent with the rates reported in the one comparable study of a large city. The single factor that most likely contributed to the poor overall survival was the relatively long interval between collapse and defibrillation. Logistical, demographic, and other special characteristics of large cities may have affected the rates. To improve treatment of cardiac arrest in large cities and maximize the use of community resources, we recommend further study of comparable metropolitan areas using standardized terms and methodology. Detailed analysis of each component of the emergency medical services systems will aid in making improvements to maximize survival of out-of-hospital cardiac arrest.

Hepatocyte transplantation for the low-density lipoprotein receptor-deficient state. A study in the Watanabe rabbit.

The Watanabe heritable hyperlipidemic (WHHL) rabbit reproduces human familial hypercholesterolemia due to a congenital low-density lipoprotein receptor deficiency and is characterized by elevated serum LDL cholesterol levels and early atherosclerosis. We attempted to transplant normal allogeneic hepatocytes into WHHL rabbits without chronic immunosuppression to cure the LDL receptor-deficient state. Livers from normal New Zealand White (NZW) rabbits were digested by intraportal perfusion of collagenase solution. Pure hepatocytes (PH) were obtained by Percoll gradient separation and nonparenchymal (NP) liver cells by pronase digestion. PH and NP were incubated with fluorescein isothiocyanate-monoclonal anti-rabbit class I, anti-class II, and anti-T cell antibodies and subjected to flow cytometry analysis. PH and NP were also used as stimulators in one way mixed lymphocyte-hepatocyte cultures (MLHC), before and after ultraviolet B light (UVB) exposure. Intraportal and intrasplenic injection of allogeneic PH were also performed in homozygous WHHL rabbits. PH were attached to collagen-coated dextran microcarriers (mc-PH) for intraperitoneal injection. Recipient control and transplanted WHHL rabbits received a single dose of cyclosporine subcutaneously (10 mg/kg/s.c.) at the time of transplantation. PH were mainly class I-positive (77.6%) and class II-negative (5.9%), while 31.5% of NP cells were class II-positive. In MLHC, PH did not stimulate proliferation, (stimulation index: 0.97 +/- 0.21), unlike NP (SI: 23.7). This latter response was abrogated by prior exposure of NP to UVB light. Intraportal injection of PH (n = 4) reduced serum LDL cholesterol to 60% of baseline, an effect lasting 2-3 weeks, and dose-dependent. Intraperitoneal mc-PH, 4 x 10(8) (n = 4), reduced serum LDL cholesterol levels to 45% of baseline more than 4 weeks posttransplant (P = 0.04). We conclude that transplantation of normal allogeneic NZW rabbit mc-PH reduces serum LDL cholesterol levels in homozygous WHHL rabbits without chronic immunosuppression. Longitudinal studies will establish if less atherosclerosis develops in mc-PH WHHL recipients than sham controls.

Near-total reduction in verapamil bioavailability by rifampin. Electrocardiographic correlates.

We evaluated the significance of the interaction between rifampin and verapamil in six volunteers who received single doses of verapamil, 10 mg intravenously (IV), then 120 mg orally two days later. Subjects were then given rifampin, 600 mg orally every day for 15 days. After 13 and 15 days of rifampin therapy, the IV and oral doses of verapamil were repeated. Electrocardiograms (ECG) were done and serum verapamil and norverapamil concentrations measured before and for 12 h after each dose. For IV verapamil, there was a small decrease in area under the serum concentration-time curve and an increase in clearance after rifampin therapy (p less than 0.05). There were no changes in elimination half-life, volume of distribution, or AUC for percentage of change in P-R interval-time curve (AUCPR). For oral verapamil, there were marked decreases in peak concentration, AUC, oral bioavailability (all p less than 0.005), and AUCPR (p less than 0.001) after rifampin treatment. There were no changes in time to peak concentration or elimination half-life. For oral verapamil, significant P-R interval prolongation occurred only before treatment with rifampin. The decrease in oral bioavailability and the abolition of ECG response confirm that a highly significant drug interaction exists between rifampin and verapamil given orally but not intravenously.

Acute hemodynamic effects of pindolol and propranolol in patients with dilated cardiomyopathy: relevance of intrinsic sympathomimetic activity.

The administration of beta-blocking agents to patients with poor left ventricular (LV) function may result in clinical and hemodynamic deterioration. The beta antagonist pindolol has intrinsic sympathomimetic activity (ISA) and therefore may be better tolerated. To test this hypothesis 30 patients with a precatheterization diagnosis of dilated cardiomyopathy were randomly assigned to three groups to receive intravenous injections of placebo, propranolol, or pindolol. The baseline ejection fraction and hemodynamics were similar for all groups. For propranolol 1 mg, 2 mg, 3 mg, and 4 mg doses were given 5 minutes apart until a maximum dose of 10 mg was reached, until a 25% reduction in the heart rate or mean arterial pressure occurred, or until clinical deterioration developed. For pindolol, 0.1 mg, 0.2 mg, 0.3 mg, and 0.4 mg boluses were used with the same end points. Baseline hemodynamics were measured and repeated 15 minutes after the last dose of each drug was administered. The mean number of doses given was similar for both groups: 3.3 doses for the propranolol group and 3.4 for the pindolol group. Compared to propranolol, pindolol caused less of a reduction in heart rate, cardiac output, cardiac index, stroke volume index, and stroke work index and less of an increase in the mean right atrial pressure, mean pulmonary arterial pressure, mean pulmonary capillary wedge pressure, left ventricular end-diastolic pressure, and pulmonary vascular resistance; there was a decrease in systemic vascular resistance. These differences were statistically significant for changes in heart rate, right atrial pressure, cardiac index, and systemic vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative validation of cineangiographic axial oblique biplane left ventricular volume measurement.

Axial oblique left ventriculography allows unique visualization of acquired and congenital cardiac lesions. However, validation of the accuracy of left ventricular (LV) volume with axial oblique projections is limited and clouded by orthogonal violations between biplane projections. Biplane cineradiographic volume measurement of 17 LV casts employing the axial projection 35 degrees right anterior oblique/55 degrees left anterior oblique/30 degrees cranial (35 degrees RAO/55 degrees LAO/30 degrees Cr) was performed and compared to the conventional postero-anterior/lateral (PA/Lat) and 30 degrees right anterior oblique/60 degrees left anterior oblique (30 degrees RAO/60 degrees LAO) views. LV volume was calculated from biplane cineradiograms by area length and Simpson's rule method. True LV volume by water displacement was 33 +/- 28 (mean +/- S.D.), range 15 to 112 ml. LV cast volume calculated by the area length method from cineradiograms was overestimated (p less than 0.002) but no different by Simpson's rule method (pNS). The ideal correlation was best approximated by the 35 degrees RAO/55 degrees LAO/30 degrees Cr biplane view calculated by Simpson's rule, r = 0.99, y = 3.5 + 0.9x, and standard error of estimate (SEE) = 4.3 ml. Biplane LV angiography with the axial projection permitted accurate LV volume measurement, and Simpson's rule provided the best representation of true volume.

Comparison of electrocardiography and thallium-201 myocardial scintigraphy for the detection of ergonovine-induced coronary artery spasm: angiographic correlation.

This study was performed to determine the sensitivity of thallium imaging vs ECG monitoring for detecting coronary artery spasm noninvasively following intravenous ergonovine administration as compared to simultaneous coronary angiography. Thirty-two patients with insignificant coronary artery disease and chest pain underwent 12-lead ECG monitoring, thallium imaging, and coronary arteriography following the administration of 0.05, 0.1, 0.2, and 0.3 mg of ergonovine given 5 minutes apart or until chest pain occurred. One minute following the last dose of ergonovine, 2.5 mCi of thallium-201 was injected intravenously, and a final ECG was recorded and repeat coronary arteriography performed. Within 10 minutes following the injection of thallium, imaging was performed in the 40-degree and 70-degree left anterior oblique and anterior projections. The ECG, thallium study, and coronary arteriogram were read blindly and results were compared. The ECG, angiogram, and thallium study were read as positive if the following occurred, respectively: greater than or equal to 1 mm ST segment elevation, depression, or T wave reversal; greater than 50% vessel narrowing,; and reversible perfusion defect. Five patients were excluded from analysis because of either catheter-induced spasm, suboptimal thallium studies, or protocol violations. Of the 27 patients included for analysis, six had chest pain, five had a positive angiogram, five had a positive thallium study, and one had a positive ECG. The sensitivity of thallium vs ECG monitoring was 80% vs 25%, and the accuracy was 92% vs 80%. We conclude that thallium imaging greatly increases the noninvasive detection of ergonovine-induced coronary spasm as compared with the ECG with no loss of accuracy.

Quantitative validation of cineangiographic biplane axial oblique right ventricular volume measurement.

Axial cranial oblique biplane views of the right ventricle (RV) permit unique assessment of the RV outflow tract, relationship of the great vessels, and anatomy of the proximal pulmonary arteries. This view may also be useful in assessment of RV free wall and RV septal wall motion. However, the accuracy of volumes derived from biplane angiocardiography with the use of the axial cranial oblique projection has not been adequately validated or compared to conventional views. Nineteen RV animal casts whose volume was determined by water displacement were filmed in conventional posteroanterior/lateral (PA/Lat), 30-degree right anterior oblique/60-degree left anterior oblique (30 degrees RAO/60 degrees LAO) views and in angulated 35-degree right anterior oblique/55-degree left anterior oblique/30-degree cranial (35 degrees RAO/55 degrees LAO/30 degrees Cr) view. Tracings of biplane cast images were analyzed for RV volume by Simpson's rule. RV cast volume was significantly overestimated by 12.2 +/- 6.8, 6.0 +/- 5.3, and 9.3 +/- 9.5 ml in PA/Lat, 30 degrees RAO/60 degrees LAO, and 35 degrees RAO/55 degrees LAO/30 degrees Cr views, respectively. The correlation coefficient (r) and the standard error of the estimate (SEE) for true vs calculated volume was 0.96, 0.98, and 0.97, and 6.8, 5.2, and 7.3 ml, respectively, for PA/Lat, 30 degrees RAO/60 degrees LAO, and 35 degrees RAO/55 degrees LAO/30 degrees Cr views. Although there was a high correlation of angiographic volumes with true volume in all three views, the 30 degrees RAO/60 degrees LAO projection had the most ideal regression characteristics with highest r value and the lowest SEE.(ABSTRACT TRUNCATED AT 250 WORDS)

Determination of left ventricular ejection fraction using ultrafast computed tomography.

We evaluated ultrafast CT as a method to measure left ventricular ejection fraction in 16 adults with congenital or acquired heart disease who underwent cardiac catheterization. CT scanning of the left ventricle was performed at 4 to 12 adjacent 1 cm levels (depending on heart size) at 50 msec/scan for one cardiac cycle, with the table positioned with an axial tilt of 10 to 20 degrees and a lateral slew of 5 to 10 degrees to best approximate the long axis of the left ventricle. Image enhancement was achieved by an injection of 25 ml of Renografin-76 via a peripheral vein, with scanning timed to coincide with maximal enhancement of the left ventricular cavity. Ejection fraction was computed by measuring the percent change in area of the left ventricle from diastole (largest area) to systole (smallest area) in a single slice at the mid-left ventricular level. Mean ejection fraction for the group was 58.1 +/- 15.1% (range 24% to 84%). The ejection fraction from left ventriculography, computed from biplane images using the Dodge (area-length) formula, was 59.6 +/- 12.3% (range 28% to 77%). There was an excellent correlation between left ventricular ejection fraction by CT and ventriculography (r = 0.91, y = 1.1x - 8.5, p less than 0.001). This study demonstrates that ultrafast CT can provide an accurate measure of left ventricular ejection fraction by simple methodology.