Tracy Q. Callister

Identification of Patients at Increased Risk of First Unheralded Acute Myocardial Infarction by Electron-Beam Computed Tomography

BACKGROUND There is a clear relationship between absolute calcium scores (CS) and severity of coronary artery disease. However, hard coronary events have been shown to occur across all ranges of CS. METHODS AND RESULTS We conducted 2 analyses: in group A, 172 patients underwent electron-beam CT (EBCT) imaging within 60 days of suffering an unheralded myocardial infarction. In group B, 632 patients screened by EBCT were followed up for a mean of 32+/-7 months for the development of acute myocardial infarction or cardiac death. The mean patient age and prevalence of coronary calcification were similar in the 2 groups (53+/-8 versus 52+/-9 years and 96% each). In group B, the annualized event rate was 0.11% for subjects with CS of 0, 2.1% for CS 1 to 99, 4.1% for CS 100 to 400, and 4.8% for CS >400, and only 7% of the patients had CS >400. However, mild, moderate, and extensive absolute CSs were distributed similarly between patients with events in both groups (34%, 35%, and 27%, respectively, in group A and 44%, 30%, and 22% in group B). In contrast, the majority of events in both groups occurred in patients with CS >75th percentile (70% in each group). CONCLUSIONS Coronary calcium is present in most patients who suffer acute coronary events. Although the event rate is greater for patients with high absolute CSs, few patients have this degree of calcification on a screening EBCT. Conversely, the majority of events occur in individuals with high CS percentiles. Hence, CS percentiles constitute a more effective screening method to stratify individuals at risk.

Effect of HMG-CoA Reductase Inhibitors on Coronary Artery Disease as Assessed by Electron-Beam Computed Tomography

BACKGROUND Angiographic studies of the regression of coronary artery disease are invasive and costly, and they permit only limited assessment of changes in the extent of atherosclerotic disease. Electron-beam computed tomography (CT) is noninvasive and inexpensive. The entire coronary-artery tree can be studied during a single imaging session, and the volume of coronary calcification as quantified with this technique correlates closely with the total burden of atherosclerotic plaque. METHODS We conducted a retrospective study of 149 patients (61 percent men and 39 percent women; age range, 32 to 75 years) with no history of coronary artery disease who were referred by their primary care physicians for screening electron-beam CT. All patients underwent base-line scanning and follow-up assessment after a minimum of 12 months (range, 12 to 15), and a volumetric calcium score was calculated as an estimate of the total burden of plaque. Treatment with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors was begun at the discretion of the referring physician. Serial measurements of low-density lipoprotein (LDL) cholesterol were obtained, and the change in the calcium-volume score was correlated with average LDL cholesterol levels. RESULTS One hundred five patients (70 percent) received treatment with HMG-CoA reductase inhibitors, and 44 patients (30 percent) did not. At follow-up, a net reduction in the calcium-volume score was observed only in the 65 treated patients whose final LDL cholesterol levels were less than 120 mg per deciliter (3.10 mmol per liter) (mean [+/-SD] change in the score, -7+/-23 percent; P=0.01). Untreated patients had an average LDL cholesterol level of at least 120 mg per deciliter and at the time of follow-up had a significant net increase in mean calcium-volume score (mean change, +52+/-36 percent; P<0.001). The 40 treated patients who had average LDL cholesterol levels of at least 120 mg per deciliter had a measurable increase in mean calcium-volume score (25+/-22 percent, P<0.001), although it was smaller than the increase in the untreated patients. CONCLUSIONS The extent to which the volume of atherosclerotic plaque decreased, stabilized, or increased was directly related to treatment with HMG-CoA reductase inhibitors and the resulting serum LDL cholesterol levels. These changes can be determined noninvasively by electron-beam CT and quantified with use of a calcium-volume score.

SCCT guidelines for performance of coronary computed tomographic angiography: A report of the Society of Cardiovascular Computed Tomography Guidelines Committee

The increasing use of coronary computed tomographicangiographic (CTA) requires the establishment of standardsmeant to ensure reliable practice methods and qualityoutcomes. The Society of Cardiovascular ComputedTomography Guidelines Committee was formed to developrecommendations for acquiring, interpreting, and reportingof these studies in a standardized fashion. Indications andcontraindications for specific services or procedures are notincludedinthescopeofthese documents.Theserecommen-dations were produced as an educational tool for practi-tioners to improve the diagnostic care of patients, in theinterest of developing systematic standards of practice forcoronary CTA based on the best available data. Because ofthe highly variable nature of individual medical cases, anapproach to scan performance that differs from these guide-lines may represent an appropriate variation based on alegitimate assessment of an individual patient’s needs.

Age- and Sex-Related Differences in All-Cause Mortality Risk Based on Coronary Computed Tomography Angiography Findings Results From the International Multicenter CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry) of 23,854 Patients Without Known Coronary Artery Disease

OBJECTIVES We examined mortality in relation to coronary artery disease (CAD) as assessed by ≥64-detector row coronary computed tomography angiography (CCTA). BACKGROUND Although CCTA has demonstrated high diagnostic performance for detection and exclusion of obstructive CAD, the prognostic findings of CAD by CCTA have not, to date, been examined for age- and sex-specific outcomes. METHODS We evaluated a consecutive cohort of 24,775 patients undergoing ≥64-detector row CCTA between 2005 and 2009 without known CAD who met inclusion criteria. In these patients, CAD by CCTA was defined as none (0% stenosis), mild (1% to 49% stenosis), moderate (50% to 69% stenosis), or severe (≥70% stenosis). CAD severity was judged on a per-patient, per-vessel, and per-segment basis. Time to mortality was estimated using multivariable Cox proportional hazards models. RESULTS At a 2.3 ± 1.1-year follow-up, 404 deaths had occurred. In risk-adjusted analysis, both per-patient obstructive (hazard ratio [HR]: 2.60; 95% confidence interval [CI]: 1.94 to 3.49; p < 0.0001) and nonobstructive (HR: 1.60; 95% CI: 1.18 to 2.16; p = 0.002) CAD conferred increased risk of mortality compared with patients without evident CAD. Incident mortality was associated with a dose-response relationship to the number of coronary vessels exhibiting obstructive CAD, with increasing risk observed for nonobstructive (HR: 1.62; 95% CI: 1.20 to 2.19; p = 0.002), obstructive 1-vessel (HR: 2.00; 95% CI: 1.43 to 2.82; p < 0.0001), 2-vessel (HR: 2.92; 95% CI: 2.00 to 4.25; p < 0.0001), or 3-vessel or left main (HR: 3.70; 95% CI: 2.58 to 5.29; p < 0.0001) CAD. Importantly, the absence of CAD by CCTA was associated with a low rate of incident death (annualized death rate: 0.28%). When stratified by age <65 years versus ≥65 years, younger patients experienced higher hazards for death for 2-vessel (HR: 4.00; 95% CI: 2.16 to 7.40; p < 0.0001 vs. HR: 2.46; 95% CI: 1.51 to 4.02; p = 0.0003) and 3-vessel (HR: 6.19; 95% CI: 3.43 to 11.2; p < 0.0001 vs. HR: 3.10; 95% CI: 1.95 to 4.92; p < 0.0001) CAD. The relative hazard for 3-vessel CAD (HR: 4.21; 95% CI: 2.47 to 7.18; p < 0.0001 vs. HR: 3.27; 95% CI: 1.96 to 5.45; p < 0.0001) was higher for women as compared with men. CONCLUSIONS Among individuals without known CAD, nonobstructive and obstructive CAD by CCTA are associated with higher rates of mortality, with risk profiles differing for age and sex. Importantly, absence of CAD is associated with a very favorable prognosis.

Progression of Coronary Artery Calcium and Risk of First Myocardial Infarction in Patients Receiving Cholesterol-Lowering Therapy

Objective—Statins reduce cardiovascular risk and slow progression of coronary artery calcium (CAC). We investigated whether CAC progression and low-density lipoprotein (LDL) reduction have a complementary prognostic impact. Methods and Results—We measured the change in CAC in 495 asymptomatic subjects submitted to sequential electron-beam tomography (EBT) scanning. Statins were started after the initial EBT scan. Myocardial infarction (MI) was recorded in 41 subjects during a follow-up of 3.2±0.7 years. Mean LDL level did not differ between groups (118±25 mg/dL versus 122±30 mg/dL, MI versus no MI). On average, MI subjects demonstrated a CAC change of 42%±23% yearly; event-free subjects showed a 17%±25% yearly change (P =0.0001). Relative risk of having an MI in the presence of CAC progression was 17.2-fold (95% CI: 4.1 to 71.2) higher than without CAC progression (P <0.0001). In a Cox proportional hazard model, the follow-up score (P =0.034) as well as a score change >15% per year (P <0.001) were independent predictors of time to MI. Conclusions—Progression of CAC was significantly greater in patients receiving statins who had an MI compared with event-free subjects despite similar LDL control. Continued expansion of CAC may indicate failure of some patients to benefit from statin therapy and an increased risk of having cardiovascular events.

Aggressive Versus Moderate Lipid-Lowering Therapy in Hypercholesterolemic Postmenopausal Women Beyond Endorsed Lipid Lowering With EBT Scanning (BELLES)

Background—Women have been underrepresented in statin trials, and few data exist on the effectiveness and safety of statins in this gender. We used sequential electron-beam tomography (EBT) scanning to quantify changes in coronary artery calcium (CAC) as a measure of atherosclerosis burden in patients treated with statins. Methods and Results—In a double-blind, multicenter trial, we randomized 615 hyperlipidemic, postmenopausal women to intensive (atorvastatin 80 mg/d) and moderate (pravastatin 40 mg/d) lipid-lowering therapy. Patients also submitted to 2 EBT scans at a 12-month interval (mean interval 344±55 days) to measure percent change in total and single-artery calcium volume score (CVS) from baseline. Of the 615 randomized women, 475 completed the study. Mean±SD percent LDL reductions were 46.6%±19.9% and 24.5%±18.5 in the intensive and moderate treatment arms, respectively (P<0.0001), and National Cholesterol Education Program Adult Treatment Panel III LDL goal was reached in 85.3% and 58.8% of women, respectively (P<0.0001). The total CVS% change was similar in the 2 treatment groups (median 15.1% and 14.3%, respectively; P=NS), and single-artery CVS% changes and absolute changes were also similar (P=NS). In both arms, there was a trend toward a greater CVS progression in patients with prior cardiovascular disease, diabetes mellitus, and hypertension, whereas hormone replacement therapy had no effect on progression. Conclusions—In postmenopausal women, intensive statin therapy for 1 year caused a greater LDL reduction than moderate therapy but did not result in less progression of coronary calcification. The limitations of this study (too short a follow-up period and the absence of a placebo group) precluded determination of whether progression of CVS was slowed in both arms or neither arm compared with the natural history of the disease.

Continuous Probabilistic Prediction of Angiographically Significant Coronary Artery Disease Using Electron Beam Tomography

Background—We sought to incorporate electron beam tomography–derived calcium scores in a model for prediction of angiographically significant coronary artery disease (CAD). Such a model could greatly facilitate clinical triage in symptomatic patients with no known CAD. Methods and Results—We examined 1851 patients with suspected CAD who underwent coronary angiography for clinical indications. An electron beam tomographic scan was performed in all patients. Total per-patient calcium scores and separate scores for the major coronary arteries were added to logistic regression models to calculate a posterior probability of the severity and extent of angiographic disease. These models were designed to be continuous, adjusted for age and sex, corrected for verification bias, and independently validated in terms of their incremental diagnostic accuracy. The overall sensitivity was 95%, and specificity was 66% for coronary calcium to predict obstructive disease on angiography. With calcium scores >20, >80, and >100, the sensitivity to predict stenosis decreased to 90%, 79%, and 76%, whereas the specificity increased to 58%, 72%, and 75%, respectively. The logistic regression model exhibited excellent discrimination (receiver operating characteristic curve area, 0.842±0.023) and calibration (&khgr;2 goodness of fit, 8.95;P =0.442). Conclusions—Electron beam tomographic calcium scanning provides incremental and independent power in predicting the severity and extent of angiographically significant CAD in symptomatic patients, in conjunction with pretest probability of disease. This algorithm is most useful when applied to an intermediate-risk population.

Coronary Artery Calcium to Predict All-Cause Mortality in Elderly Men and Women

OBJECTIVES We sought to study the prognostic utility of coronary artery calcium (CAC) in the elderly. BACKGROUND The prognostic significance of CAC in the elderly is not well known. METHODS All-cause mortality was assessed in 35,388 patients (3,570 were >or=70 years old at screening, and 50% were women) after a mean follow-up of 5.8 +/- 3 years. RESULTS In older patients, risk factors and CAC were more prevalent. Overall survival was 97.9% at the end of follow-up. Mortality increased with each age decile with a relative hazard of 1.09 (95% confidence interval: 1.08 to 1.10, p < 0.0001), and rates were greater for men than women (hazard ratio: 1.53; 95% confidence interval: 1.32 to 1.77, p < 0.0001). Increasing CAC scores were associated with decreasing survival across all age deciles (p < 0.0001). Survival for a <40-year and >or=80-year-old man with a CAC score >or=400 was 88% and 19% (95% and 44% for a woman, p < 0.0001), respectively. Among the 20,562 patients with no CAC, annual mortality rates ranged from 0.3% to 2.2% for patients age 40 to 49 years or >or=70 years (p < 0.0001). The use of CAC allowed us to reclassify more than 40% of the patients >or=70 years old more often by excluding risk (i.e., CAC <400) in those with >3 risk factors. CONCLUSIONS Despite their limited life expectancy, the use of CAC discriminates mortality risk in the elderly. Furthermore, the use of CAC allows physicians to reclassify risk in the elderly.

Prevalence and Severity of Coronary Artery Disease and Adverse Events Among Symptomatic Patients With Coronary Artery Calcification Scores of Zero Undergoing Coronary Computed Tomography Angiography Results From the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) Registry

OBJECTIVES The purpose of this study was to describe the prevalence and severity of coronary artery disease (CAD) in relation to prognosis in symptomatic patients without coronary artery calcification (CAC) undergoing coronary computed tomography angiography (CCTA). BACKGROUND The frequency and clinical relevance of CAD in patients without CAC are unclear. METHODS We identified 10,037 symptomatic patients without CAD who underwent concomitant CCTA and CAC scoring. CAD was assessed as <50%, ≥50%, and ≥70% stenosis. All-cause mortality and the composite endpoint of mortality, myocardial infarction, or late coronary revascularization (≥90 days after CCTA) were assessed. RESULTS Mean age was 57 years, 56% were men, and 51% had a CAC score of 0. Among patients with a CAC score of 0, 84% had no CAD, 13% had nonobstructive stenosis, and 3.5% had ≥50% stenosis (1.4% had ≥70% stenosis) on CCTA. A CAC score >0 had a sensitivity, specificity, and negative and positive predictive values for stenosis ≥50% of 89%, 59%, 96%, and 29%, respectively. During a median of 2.1 years, there was no difference in mortality among patients with a CAC score of 0 irrespective of obstructive CAD. Among 8,907 patients with follow-up for the composite endpoint, 3.9% with a CAC score of 0 and ≥50% stenosis experienced an event (hazard ratio: 5.7; 95% confidence interval: 2.5 to 13.1; p < 0.001) compared with 0.8% of patients with a CAC score of 0 and no obstructive CAD. Receiver-operator characteristic curve analysis demonstrated that the CAC score did not add incremental prognostic information compared with CAD extent on CCTA for the composite endpoint (CCTA area under the curve = 0.825; CAC + CCTA area under the curve = 0.826; p = 0.84). CONCLUSIONS In symptomatic patients with a CAC score of 0, obstructive CAD is possible and is associated with increased cardiovascular events. CAC scoring did not add incremental prognostic information to CCTA.

Progression of coronary calcium on serial electron beam tomographic scanning is greater in patients with future myocardial infarction

We conducted an observational study relating the occurrence of acute myocardial infarction (MI) to coronary artery calcium progression in 817 asymptomatic subjects referred for sequential electron beam tomographic imaging (average interval 2.2 +/- 1.3 years). A calcium volume score (CVS) was used for plaque quantification. The yearly mean absolute and percent CVS changes in the 45 patients who had a MI were 147 +/- 152 and 47 +/- 50%, respectively, compared with 63 +/- 128 and 26 +/- 32%, respectively (p <0.001, p = 0.01), in patients without events.