Association of multiple risk factors and insulin resistance with increased prevalence of asymptomatic coronary artery disease by an electron-beam computed tomographic study.

The insulin resistance syndrome, consisting of resistance to insulin and several metabolic abnormalities, is associated with an increased risk of symptomatic coronary artery disease. Asymptomatic persons with increased coronary calcification have increased coronary plaque and an increased likelihood of future cardiovascular events. Electron-beam computed tomography-derived coronary artery calcium scores, metabolic and anthropometric parameters, and fasting and stimulated concentrations of glucose and insulin were measured in 1160 asymptomatic men and women. Coronary artery calcium scores were positively correlated with glucose, insulin, and homeostasis model assessment (HOMA) insulin resistance. Calcium scores were positively correlated with intra-abdominal adiposity, age, total cholesterol/high density lipoprotein (HDL) ratio, low density lipoprotein, triglycerides, blood pressure, and HOMA beta cell function and inversely correlated with HDL and peripheral fat. These correlations, except for 2-hour glucose, remained significant for all subjects with fasting serum glucose <126 mg/dL or all subjects with fasting serum glucose 110 mg/dL. In a multivariate analysis, age, sex, family history of premature coronary artery disease, intra-abdominal adiposity, low density lipoprotein, and smoking independently predicted calcium scores. Blood pressure, HDL, triglycerides, glucose, insulin, and HOMA insulin resistance or beta cell function were not independently correlated with coronary artery calcium scores. Asymptomatic individuals with insulin resistance have elevated coronary calcium scores. The association between insulin resistance and coronary calcification persists with impaired glucose tolerance and normal fasting serum glucose. Central/visceral adiposity may be a determinant of insulin resistance and atherosclerosis even in asymptomatic nondiabetic persons.

Rationale and design of the St. Francis Heart Study: a randomized clinical trial of atorvastatin plus antioxidants in asymptomatic persons with elevated coronary calcification.

Early detection of asymptomatic subjects who are at risk for future cardiovascular events may allow for earlier medical treatment in order to prevent disease progression and future events. Electron-beam computed tomography accurately identifies people with increased coronary calcification, which is correlated with increased coronary plaque mass, increased likelihood of obstructive coronary disease, and increased likelihood of future cardiovascular events. The St. Francis Heart Study is a single-center combination study of men and women 50-70 years old that includes a natural history study of the relation between calcium scores and cardiovascular events (n = 5582), the association of calcium scores with traditional and nontraditional coronary disease risk factors (n = 1160), and a randomized clinical trial designed to assess the benefit of combination treatment with atorvastatin, vitamin C, and vitamin E, as compared to placebos, in subjects with elevated age- and gender-adjusted coronary calcification (n = 1007). Mean follow-up duration will be 4 years. The study is proceeding on schedule with anticipated completion by August 2002. It should provide important information regarding the benefits of treating asymptomatic men and women who have elevated coronary artery calcium, using cholesterol reduction and antioxidant therapy. The article describes the design of the St. Francis Heart Study.

Early reinfarction after fibrinolysis: experience from the global utilization of streptokinase and tissue plasminogen activator (alteplase) for occluded coronary arteries (GUSTO I) and global use of strategies to open occluded coronary arteries (GUSTO III) trials.

BACKGROUND: Trials report a 2% to 6% incidence of reinfarction after fibrinolysis for acute myocardial infarction (MI). We combined the Global Utilization of Streptokinase and Tissue plasminogen activator (alteplase) for Occluded coronary arteries (GUSTO I) and Global Use of Strategies To Open occluded coronary arteries (GUSTO III) populations to better define frequency, timing, and clinical predictors of in-hospital reinfarction. METHODS AND RESULTS: In 55 911 patients with ST-segment elevation myocardial infarction (MI) who were receiving fibrinolysis, we compared baseline characteristics and mortality rate by reinfarction incidence and developed multivariable logistic regression models to predict in-hospital reinfarction and composite of death or reinfarction. Reinfarction occurred in 2258 patients (4.3%) a median of 3.8 days after fibrinolysis; rates did not differ between GUSTO I (4.0%) and GUSTO III (4.2%) or by fibrinolytic assignment (streptokinase, 4.1%; alteplase, 4.3%; reteplase, 4.5%; combined streptokinase and alteplase, 4.4%; P=0.55). Advanced age, shorter time to fibrinolysis, non-US enrollment, nonsmoking status, prior MI or angina, female sex, anterior MI, and lower systolic blood pressure were associated significantly with reinfarction. Patients with reinfarction had higher mortality at 30 days (11.3% versus 3.5% without reinfarction; odds ratio, 3.5; P<0.001) and from 30 days to 1 year (4.7% versus 3.2%; hazard ratio, 1.5; P<0.001). Significant multivariate predictors of in-hospital death or reinfarction included age, Killip class, systolic and diastolic blood pressures, heart rate, anterior MI, smoking status, prior MI, sex, and country of enrollment (all P<0.001). CONCLUSIONS: Reinfarction occurs infrequently after fibrinolysis but confers increased risk of 30-day and 1-year mortality. Some predictors of reinfarction differ from known predictors of death after MI. Improved treatment and prevention strategies for reinfarction deserve study.

Potential use of Ca++ scanning to determine the need for and intensity of lipid-lowering therapy in asymptomatic adults.

Deficiencies in traditional cardiovascular risk-factor assessment in asymptomatic individuals have led to the use of electron beam computed tomography (CT) scanning as a screening test for coronary artery disease. This novel approach is based on a secure pathologic foundation: the risk of coronary disease events is proportional to the severity and extent of underlying coronary atherosclerosis, and in middle-aged and elderly adults, calcified plaque is closely related to total plaque. Electron beam CT measures coronary calcium quickly, easily, accurately, and with a high degree of reproducibility. Coronary calcium is three to nine times higher in persons with fatal or nonfatal myocardial infarction than in age-matched controls, and four observational outcomes studies have demonstrated that the electron beam CT-derived coronary calcium score predicts fatal and nonfatal myocardial infarction. In symptomatic persons undergoing cardiac catheterization, electron beam CT is more closely associated with the severity of coronary atherosclerosis than are standard coronary risk factors. Preliminary evidence in asymptomatic persons indicates that the coronary calcium score also predicts coronary disease events more accurately than standard risk factors.

Prediction of coronary events with electron beam computed tomography.

OBJECTIVES: We sought to determine the prognostic accuracy of electron beam computed tomographic (EBCT) scanning of the coronary arteries at three to four years. BACKGROUND: Coronary artery calcium scores determined by EBCT correlate with the severity of coronary artery disease. However, previous reports of the prognostic accuracy of EBCT scanning for coronary events in asymptomatic individuals are conflicting. METHODS: Asymptomatic men and women undergoing coronary EBCT completed initial and follow-up evaluations, which included past medical history, the Rose angina questionnaire and interim cardiovascular events. Reported coronary events (death, nonfatal myocardial infarction [MI] and revascularization procedures) were confirmed without knowledge of the scan results. RESULTS: Information was obtained in 1,172 (99.6%) of 1,177 eligible subjects (baseline age 53 +/- 11 years, 71% men). During an average follow-up of 3.6 years, 39 subjects sustained coronary events: three coronary deaths, 15 nonfatal MIs and 21 coronary artery revascularization procedures. The mean coronary artery calcium score was 764 +/- 935 among subjects with events as compared with 135 +/- 432 among those without events (p < 0.0001). For the prediction of all coronary events and of nonfatal MIs and deaths, the areas under the receiver-operator characteristics curve were 0.84 and 0.86, respectively, and a coronary calcium score > or =160 was associated with odds ratios of 15.8 and 22.2, respectively. The odds ratios for all events remained high (14.3 to 20.2) after adjustment for self-reported cardiovascular risk factors. CONCLUSIONS: In asymptomatic adults, EBCT of the coronary arteries predicts coronary death and nonfatal MI and the need for revascularization procedures.

Management of patients with acute coronary syndromes in the United States by platelet glycoprotein IIb/IIIa inhibition. Insights from the platelet glycoprotein IIb/IIIa in unstable angina: receptor suppression using integrilin therapy (PURSUIT) trial.

BACKGROUND: A multinational, randomized, placebo-controlled trial (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy, PURSUIT) demonstrated that the platelet glycoprotein IIb/IIIa receptor antagonist eptifibatide reduced the incidence of death or myocardial infarction among patients with acute ischemic syndromes without ST-segment elevation. Because of expected differences in practice patterns, a prospectively planned analysis of outcomes as a function of regions of the world was performed. The current study provides a detailed assessment of eptifibatide among the subgroup of patients enrolled within the United States. METHODS AND RESULTS: Patients presenting with chest pain within the previous 24 hours and ischemic ECG changes or creatine kinase-MB elevation were eligible for enrollment. Of the 10 948 patients randomized worldwide, 4035 were enrolled within the United States. Patients were allocated to placebo or eptifibatide infusion for up to 72 to 96 hours. Other medical therapies and revascularization strategies were at the discretion of the treating physician. Eptifibatide reduced the rate of the primary end point of death or myocardial infarction by 30 days from 15.4% to 11.9% (P=0.003) among patients in the United States. The treatment effect was achieved early and maintained over a period of 6 months (18.9% versus 15.2%; P=0.004). Bleeding events were more common in patients receiving eptifibatide but were predominantly associated with invasive procedures. The magnitude of clinical benefit from eptifibatide was greater among patients in the United States than elsewhere in the world. CONCLUSIONS: Platelet glycoprotein IIb/IIIa receptor blockade with eptifibatide reduces the incidence of death or myocardial infarction among patients treated for acute ischemic syndromes without ST-segment elevation within the United States.

Serum concentration of calcium, 1,25 vitamin D and parathyroid hormone are not correlated with coronary calcifications. An electron beam computed tomography study.

BACKGROUND: The amount of coronary artery calcification, measured using electron beam computed tomography, is correlated with the volume of coronary artery atherosclerotic plaque, the severity of stenosis by angiography, and with the likelihood of future cardiovascular events. The deposition of calcium in atherosclerotic plaques may also be influenced by determinants of calcium metabolism, thus contributing to the variance of the relation between coronary artery calcification and extent of atherosclerosis. Our objective was to determine whether this variance could be explained by differences in the parameters of calcium metabolism. DESIGN AND METHODS: We measured serum concentrations of calcium, 1,25(OH)2 vitamin D and parathyroid hormone (PTH) in 50 subjects undergoing angiography for clinical indications, and evaluated the correlations between these concentrations and calcium deposition in the coronary arteries, and the ratio of calcium deposition to extent of atherosclerosis using coronary angiography. RESULTS AND CONCLUSIONS: Serum concentrations of calcium 1,25(OH)2 vitamin D and PTH were not correlated with coronary calcification or the ratio of coronary calcification to the extent of coronary stenosis. We conclude that, in subjects undergoing coronary angiography, the variance of the relationship between coronary atherosclerosis and coronary calcium is not a result of differences in serum concentrations of calcium, 1,25(OH)2 vitamin D or PTH.

Comparison of electron beam computed tomography scanning and conventional risk factor assessment for the prediction of angiographic coronary artery disease.

OBJECTIVE: To determine whether electron beam computed tomography (CT) adds to conventional risk factor assessment in the prediction of angiographic coronary artery disease. BACKGROUND: Electron beam CT scanning can be used to predict the severity of coronary atherosclerosis, but whether it does so independently of conventional risk factors is unclear. METHODS: Electron beam CT scans were performed and conventional risk factors were measured in 290 men and women undergoing coronary arteriography for clinical indications. The association of the electron beam CT-derived coronary artery calcium score and conventional risk factors with the presence and severity of angiographically defined coronary atherosclerosis was analyzed by logistic regression and receiver-operator characteristics analysis. RESULTS: Age, the ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol and the coronary calcium score were significantly and independently associated with the presence of any coronary disease and obstructive coronary disease. In association with any coronary disease, odds ratios for age, the ratio of total cholesterol to HDL cholesterol and calcium score, highest quartile vs. lowest quartile, were 6.01 (95% confidence interval 2.87 to 12.56), 3.14 (1.56 to 6.31) and 94.08 (21.06 to 420.12), respectively. For obstructive coronary disease, highest quartile vs. lowest quartile, the respective odds ratios for age, the ratio of total cholesterol to HDL and calcium score were 3.86 (1.86 to 8.00), 4.11 (1.98 to 8.52) and 34.12 (12.67 to 91.86). Male gender was also significantly associated with any coronary disease (odds ratio 2.19, p=0.04) and obstructive coronary disease (odds ratio 2.07, p=0.04). Cigarette smoking was significantly associated with any coronary disease (odds ratio=2.74, p=0.004), and diabetes was significantly associated with obstructive disease (odds ratio 3.16, p=0.01). After adjustment for the coronary calcium score and other risk factors, it was determined that triglycerides, family history and hypertension were not significantly associated with any disease state. A coronary calcium score >80 (Agatston method) was associated with an increased likelihood of any coronary disease regardless of the number of risk factors, and a coronary calcium score > or = 170 was associated with an increased likelihood of obstructive coronary disease regardless of the number of risk factors (p < 0.001). CONCLUSIONS: Electron beam CT scanning offers improved discrimination over conventional risk factors in the identification of persons with any angiographic coronary disease or angiographic obstructive coronary disease.

Correlations between vascular calcification and atherosclerosis: a comparative electron beam CT study of the coronary and carotid arteries.

PURPOSE: Electron beam CT (EBCT)-derived coronary artery calcium scores correlate with the extent of atherosclerosis, but there is a substantial variance about the general relationship between coronary calcification and coronary atherosclerosis. The relationship between calcification and atherosclerosis may also differ in various arteries. This study was designed to evaluate whether the relation between carotid artery intima-media thickness (IMT) and carotid artery calcium could be used as a correction factor to improve the correlation between coronary calcification and coronary atherosclerosis. METHOD: We measured atherosclerosis in the coronary and carotid arteries by angiography and ultrasonography, respectively, and quantified coronary and carotid calcium deposition with EBCT in 50 subjects. The correlation between the findings in the carotid and coronary arteries was investigated. RESULTS: Coronary artery calcium score correlated with coronary angiography and with carotid calcium score. Coronary stenosis correlated with carotid IMT. There was no meaningful correlation of carotid IMT and carotid calcium. CONCLUSION: There is an intraindividual variation in the relationship of plaque mass to calcification among different vessels. The relation between carotid artery calcification and carotid IMT is not predictive of the relation between coronary artery calcification and coronary obstruction.

Coronary angioplasty volume-outcome relationships for hospitals and cardiologists.

OBJECTIVE: To assess the relationship between each of 2 provider volume measures (annual hospital volume and annual cardiologist volume) for percutaneous transluminal coronary angioplasty (PTCA) and 2 outcomes of PTCA (in-hospital mortality and same-stay coronary artery bypass graft [CABG] surgery). DESIGN: Cohort study, using data from January 1, 1991, through December 31, 1994, from the Coronary Angioplasty Reporting System of the New York State Department of Health. SETTING: Thirty-one hospitals in New York State in which PTCA was performed during 1991-1994. PATIENTS: All 62670 patients discharged after undergoing PTCA in these hospitals during 1991-1994. MAIN OUTCOME MEASURES: Rates of in-hospital mortality and CABG surgery during the same stay as the PTCA. RESULTS: The overall in-hospital mortality rate for patients undergoing PTCA in New York during 1991-1994 was 0.90%, and the same-stay CABG surgery rate was 3.43%. Patients undergoing PTCA in hospitals with annual PTCA volumes less than 600 experienced a significantly higher risk-adjusted in-hospital mortality rate of 0.96% (95% confidence interval [CI], 0.91%-1.01%) and risk-adjusted same-stay CABG surgery rate of 3.92% (95% CI, 3.76%-4.08%). Patients undergoing PTCA by cardiologists with annual PTCA volumes less than 75 had mortality rates of 1.03% (95% CI, 0.91%-1.17%) and same-stay CABG surgery rates of 3.93% (95% CI, 3.65%-4.24%); both of these rates were also significantly higher than the rates for all patients. Also, same-stay CABG surgery rates for patients undergoing PTCA in hospitals with annual volumes of 600 to 999 performed by cardiologists with annual volumes of 75 to 174 (2.99%; 95% CI, 2.69%-3.31 %) and 175 or more (2.84%; 95% CI, 2.57%-3.14%) were significantly lower than the overall statewide rate (3.43%). CONCLUSIONS: In New York State, both hospital PTCA volume and cardiologist PTCA volume are significantly inversely related to in-hospital mortality rate and same-stay CABG surgery rate for patients undergoing PTCA.

Relation of coronary calcium score by electron beam computed tomography to arteriographic findings in asymptomatic and symptomatic adults.

Coronary arteriography was performed on 18 asymptomatic, apparently healthy adults with elevated coronary calcium scores. To extend the range of observation to subjects with low calcium scores, arteriograms from 18 patients with exertional dyspnea and/or valvular heart disease and low calcium scores were also analyzed; these 18 patients were considered asymptomatic from the point of view of coronary artery disease (CAD). For the comparison of symptomatic and asymptomatic persons, 3 age and sex-matched symptomatic patients were also selected for each of the original 18 asymptomatic subjects. Arteriograms were analyzed by computer-assisted quantitative coronary arteriography at a remote site without knowledge of the calcium score or any other patient characteristics. In the 18 asymptomatic subjects with elevated calcium scores, the mean calcium score was 573 +/- 504 (Agatston method) and the mean worst stenosis was 45% +/- 16%. For all 36 patients without symptoms of CAD, worst stenosis was closely correlated with the square root of the calcium score (r = 0.85, p <0.0001). Patients with symptomatic coronary disease and calcium scores < 1,000 had stenoses more severe than asymptomatic persons with similar calcium scores. Most asymptomatic adults with elevated calcium scores have nontrivial, nonobstructive CAD or preclinical obstructive CAD, and the relation between coronary calcium score and severity of stenosis is highly significant. These data indicate that electron beam tomography can be used to estimate the severity of CAD in asymptomatic persons.

Effects of integrelin, a platelet glycoprotein IIb/IIIa receptor antagonist, in unstable angina. A randomized multicenter trial.

BACKGROUND: Although aspirin is beneficial in patients with unstable angina, it is a relatively weak inhibitor of platelet aggregation. The effect of Integrelin, which inhibits the platelet fibrinogen receptor glycoprotein (GP) IIb/IIIa, on the frequency and duration of Holter ischemia was evaluated in 227 patients with unstable angina. METHODS AND RESULTS: Patients received intravenous heparin and standard ischemic therapy and were randomized to receive oral aspirin and placebo Integrelin; placebo aspirin and low-dose Integrelin. 45 micrograms/kg bolus followed by a 0.5 microgram.kg-1. min-1 continuous infusion; or placebo aspirin and high-dose Integrelin, 90 micrograms/kg bolus followed by a 1.0-microgram.kg-1, min-1 constant infusion. Study drug was continued for 24 to 72 hours, and Holter monitoring was performed. Patients randomized to high-dose Integrelin experienced 0.24 +/- 0.11 ischemic episodes (mean +/- SEM) on Holter lasting 8.41 +/- 5.29 minutes over 24 hours of study drug infusion. Patients randomized to aspirin experienced a greater number (1.0 +/- 0.33, P < .05) and longer duration (26.2 +/- 9.8 minutes, P = .01) of ischemic episodes than the high-dose Integrelin group. There was no evidence of rebound ischemia after withdrawal of study drug. In 46 patients, platelet aggregation was rapidly inhibited by Integrelin in a dose-dependent fashion. The number of clinical events was small, and there were no bleeding differences in the three treatment arms. CONCLUSIONS: Intravenous Integrelin is well tolerated, is a potent reversible inhibitor of platelet aggregation, and added to full-dose heparin reduces the number and duration of Holter ischemic events in patients with unstable angina compared with aspirin.

Predictive value of electron beam computed tomography of the coronary arteries. 19-month follow-up of 1173 asymptomatic subjects.

BACKGROUND: Coronary electron beam computed tomography (EBCT) detects atherosclerotic coronary artery disease by measuring calcium deposition in the walls of coronary arteries. EBCT-derived coronary artery calcium (CAC) scores correlate with the severity of underlying coronary artery disease. METHODS AND RESULTS: We followed 1173 asymptomatic patients who underwent EBCT between September 1993 and March 1994. During average follow-up of 19 months, 18 subjects had 26 cardiovascular events: 1 death, 7 myocardial infarctions, 8 coronary artery bypass graft procedures, 9 coronary angioplasties, and 1 nonhemorrhagic stroke. For CAC score thresholds of 100, 160, and 680, EBCT had sensitivities of 89%, 89%, and 50% and specificities of 77%, 82%, and 95%, respectively. Odds ratios ranged from 20.0 to 35.4 (P < .0001 for all). CONCLUSIONS: Coronary EBCT predicts future atherosclerotic cardiovascular disease events in asymptomatic subjects.

Effect of early enalapril therapy on left ventricular function and structure in acute myocardial infarction.

Infarct expansion starts within hours to days after transmural myocardial injury. Previous echocardiographic and left ventriculographic studies demonstrated that angiotensin-converting enzyme (ACE) inhibitor therapy limits left ventricular dilatation, particularly in patients with anterior wall acute myocardial infarction (AMI) or impaired left ventricular function. Forty-three patients with an acute Q-wave AMI were randomized within 24 hours of symptom onset to intravenous enalaprilat (1 mg) or placebo. Patients were then given corresponding oral therapy and followed for 1 month. Predrug and 1-month gated blood pool scans were obtained in 32 patients to evaluate changes in cardiac volumes and ejection fraction. Twenty-three patients underwent magnetic resonance imaging at 1 month to evaluate left ventricular infarct expansion. Blood pressure decreased at 6 hours but returned to baseline in both groups after 1 month of therapy. The change in cardiac volumes from baseline to 1 month differed between the placebo (end-diastolic volume +16 +/- 5 ml, end-systolic volume +8 +/- 6 ml), and enalapril (end-diastolic volume -8 +/- 9 ml and end-systolic volume -14 +/- 7 ml) groups (p < 0.05 vs placebo). Global and infarct zone ejection fractions improved significantly at 1 month in the enalapril group (+6 +/- 3% and 19 +/- 5%, respectively) but did not change over 1 month in the placebo group. Infarct segment length and infarct expansion index by magnetic resonance imaging were significantly less in those treated with enalapril, suggesting less infarct expansion in this group. Thus, early administration of enalaprilat to patients presenting with a first Q-wave AMI prevents cardiac dilatation and infarct expansion.

Observations of ventilation during resuscitation in a canine model.

BACKGROUND: Fear of infection limits the willingness of laymen to do cardiopulmonary resuscitation (CPR). This study assessed the time course of change in arterial blood gases during resuscitation with only chest compression (no ventilation) in an effort to identify the time for which ventilation could be deferred. METHODS AND RESULTS: Aortic pressures and arterial blood gases were monitored in seven 20- to 30-kg dogs in ventricular fibrillation (VF) at 2-minute intervals during chest compression alone (no ventilation) at 80 to 100 compressions per minute. Before the induction of ventricular fibrillation, all animals were intubated and ventilated with room air, 10 mL/kg. The endotracheal tube was removed when VF was induced. Pre-VF arterial pH, PCO2, and O2 saturation were (mean +/- SEM) 7.39 +/- 0.02, 27.0 +/- 1.5 mm Hg, and 97.5 +/- 0.5%, respectively, with aortic pressures being 143.2 +/- 5.7/116.2 +/- 4.6 mm Hg. At 4 minutes of chest compression alone, the corresponding values were 7.39 +/- 0.03, 24.3 +/- 3.1 mm Hg, and 93.9 +/- 3.0%, with an arterial pressure of 48.1 +/- 7.7/22.6 +/- 3.9 mm Hg. Mean minute ventilation during the fourth minute of CPR, measured with a face mask-pneumotachometer, was 5.2 +/- 1.1 L/min. CONCLUSIONS: These data suggest that in the dog model of witnessed arrest, chest compression alone during CPR can maintain adequate gas exchange to sustain O2 saturation > 90% for > 4 minutes. The need for immediate ventilation during witnessed arrest should be reexamined.