Prognostic value of quantitative high-speed myocardial perfusion imaging.

BACKGROUND: We studied the prognostic value of fully automated quantitative analysis software applied to new solid-state, high-speed (HS) SPECT-myocardial perfusion imaging (MPI). METHODS: 1,613 consecutive patients undergoing exercise or adenosine HS-MPI were followed for 2.6 ± 0.5 years for all-cause mortality (ACM). Automated quantitative software was used to compute stress total perfusion deficit (sTPD) and was compared to semi-quantitative visual analysis. MPI was characterized as 0% (normal), 1%-4% (minimal perfusion defect), 5%-10% (mildly abnormal), and >10% (moderately/severely abnormal). RESULTS: During follow-up, 79 patients died (4.9%). Annualized ACM increased with progressively increasing sTPD; 0% (0.87%), 1%-4% (1.94%), 5%-10% (3.10%), and >10% (5.33%) (log-rank P < .0001). While similar overall findings were observed with visual analysis, only sTPD demonstrated increased risk in patients with minimal perfusion defects. In multivariable analysis, sTPD > 10% was a mortality predictor (HR 3.03, 95% CI 1.30-7.09, P = .01). Adjusted mortality rate was substantial in adenosine MPI, but low in exercise MPI (9.0% vs 1.0%, P < .0001). CONCLUSIONS: By quantitative analysis, ACM increases with increasing perfusion abnormality among patients undergoing stress HS-MPI. These findings confirm previous results obtained with visual analysis using conventional Anger camera imaging systems.

Evaluation of California Non-Comprehensive Death File Against National Death Index.

The National Death Index (NDI) by the Centers for Disease Control and Prevention and Death Master File (DMF) by Social Security Administration are the two most broadly utilized data files for mortality outcomes in clinical research. NDI's high costs and the elimination of protected death records from California in DMF calls for alternative death files. The recently emerged California Non-Comprehensive Death File (CNDF) serves as an alternative source for vital statistics. This study aims to evaluate the sensitivity and specificity of CNDF compared to NDI. Of 40,724 consented subjects in the Cedars-Sinai Cardiac Imaging Research Registry, 25,836 eligible subjects were queried through the NDI and the CDNF. After exclusion of death records to establish the same temporal and geographic availability of data, NDI identified 5,707 exact matches, while CNDF identified 6,051 death records. CNDF had a sensitivity of 94.3% and specificity of 96.4% compared to NDI exact matches. NDI also produced 581 close matches: all were verified as deaths by CNDF through matching death date and patient identifiers. Combining all NDI death records, CNDF had a sensitivity of 94.8% and specificity of 99.5%. CNDF is a reliable source for obtaining mortality outcomes and providing additional mortality validation. The use of CNDF can aid and replace the use of NDI in the state of California.

Do psychological risk factors predict the presence of coronary atherosclerosis?

OBJECTIVE: To assess how clinical and psychological variables compare in their ability to predict coronary artery calcium (CAC) in a broad spectrum of subjects. Although prior studies reported contradictory findings on the association between psychological risk factors and CAC, psychological risk factors have not yet been compared with concurrent clinical coronary risk factors for their association to CAC measurements. METHODS: We performed research CAC scans in three cohorts: 1,111 healthy volunteers; 138 asymptomatic patients; and 600 symptomatic patients. All subjects completed questionnaires designed to assess clinical and psychological coronary artery disease (CAD) risk factors, including measurements of depression, hostility, social support, perceived stress, job strain, and optimism. A serum sample was obtained to assess lipid parameters and glucose. All variables were compared for their correlation to CAC scores. RESULTS: We observed a marked lack of association between psychosocial risk factors and CAC scores in each cohort. For symptomatic patients only, there was a modest negative correlation between depression and CAC scores (r = -.19, p < .001). Most CAD risk factors were also not associated with CAC. Once age and gender were considered as multivariable predictors of CAC, neither psychological nor CAD risk factors added to prediction of CAC. CONCLUSIONS: Both psychological and clinical risk factors are poorly correlated with concurrent measurements of CAC. Given our findings and previously established associations of these risk factors to cardiac events, further assessment of the relationship between chronicity of these risk factors and coronary atherosclerosis could be of interest. Our findings cast doubt on the use of CAC scanning as a surrogate means for assessing the clinical significance of both concurrently measured psychological and clinical risk factors.

Prognostic value of automated vs visual analysis for adenosine stress myocardial perfusion SPECT in patients without prior coronary artery disease: a case-control study.

PURPOSE: We aimed to evaluate the prognostic value of automated quantitative hypoperfusion parameters derived from adenosine stress myocardial perfusion SPECT (MPS) for predicting sudden or cardiac death (CD) in case-controlled patients with suspected coronary artery disease (CAD). METHODS: We considered patients with available adenosine stress Tc-99m sestamibi MPS scans and follow-up information. 81 CD patients from a registry of 428 patients documented by the National Death Index were directly matched in a retrospective case-control design to patients without CD by key clinical parameters (age by deciles, gender, no early revascularization, pre-test likelihood categories, diabetes, and chest pain symptoms). Multivariable analysis of stress MPS total perfusion deficit (STPD) and major clinical confounders were used as predictors of CD. Visual 17-segment summed stress segmental scores (VSSS) obtained by an expert reader, were compared to STPD. RESULTS: CD patients had higher stress hypoperfusion measures compared to controls [STPD: 7.0% vs 3.6% (P < .05), VSSS: 5.3 vs 2.1 (P < .05)]. By univariate analysis, STPD and VSSS have similar predictive power (the areas under receiver operator characteristics curves: STPD = 0.64, VSSS = 0.63; Kaplan-Meier models: χ(2) = 7.59, P = .0059 for STPD and χ(2) = 11.10, P = .0009 for VSSS). The multiple Cox proportional hazards regression models with continuous perfusion measures showed that STPD had similar power to normalized VSSS as a predictor for CD (χ(2) = 4.92; P = .027) vs (χ(2) = 8.90; P = .003). CONCLUSIONS: Quantitative analysis is comparable to expert visual scoring in predicting CD in a case-controlled study.

Comparison of the atherosclerotic burden among asymptomatic patients vs matched volunteers.

BACKGROUND: While asymptomatic patients should have a lower risk of cardiac events compared to symptomatic patients referred for cardiac stress testing, comparable event rates have been noted in some prior prognostic studies. To test if a high burden of undetected atherosclerosis among asymptomatic patients helps explain such findings, we compared atherosclerotic burden, as measured by coronary artery calcium (CAC) scanning, in propensity-matched groups of volunteers and asymptomatic patients. METHODS: CAC scans were performed on a research basis in 136 asymptomatic patients referred for exercise myocardial perfusion SPECT and in 1,398 volunteers. We performed matching by propensity scores to compare volunteers with the same CAD risk factor profile as our asymptomatic patients. RESULTS: Among our matched groups, asymptomatic patients had significantly greater mean CAC scores than volunteers (394 ± 805 vs 151 ± 349, P = .001), primarily due to a higher frequency of CAC scores >1,000 (15.4% vs 2.5%, P < .001). Inducible myocardial ischemia by SPECT was present in 7% of patients, but was selectively concentrated among those with CAC scores >1,000, occurring in 27.0% of such patients vs only 1.9% among patients with CAC scores <1,000 (P < .0001). CONCLUSIONS: In contrast to asymptomatic volunteers, asymptomatic patients referred for cardiac stress testing possess more extensive atherosclerosis as measured by CAC. Among asymptomatic patients with high CAC scores, the frequency of concomitant inducible myocardial ischemia is high. These results help explain prior prognostic studies concerning asymptomatic patients and indicate the importance of making a clinical distinction between healthy subjects and asymptomatic patients with respect to atherosclerotic risk.

Use of coronary calcium scanning for predicting inducible myocardial ischemia: Influence of patients' clinical presentation.

BACKGROUND: The selection of patients for cardiac stress tests is generally based on assessment of chest pain symptoms, age, gender, and risk factors, but recent data suggest that coronary artery calcium (CAC) measurements can also be used to predict inducible myocardial ischemia. However, the potential influence of clinical factors on the relationship between CAC measurements and inducible ischemia has not yet been investigated. METHODS AND RESULTS: We prospectively performed CAC scanning in 648 patients undergoing exercise myocardial perfusion single photon emission computed tomography. The frequency of ischemia on myocardial perfusion single photon emission computed tomography was assessed according to CAC magnitude after dividing patients according to chest pain symptom class and Bayesian likelihood of angiographically significant coronary artery disease (ASCAD). Estimates of ASCAD likelihood and CAC scores were poorly correlated. The frequency of inducible myocardial ischemia was very low among patients with a low ASCAD likelihood if CAC scores were less than 400. By contrast, the threshold for increasing ischemia occurred at low CAC scores among patients with a high ASCAD likelihood. When characterized by chest pain classification, asymptomatic and nonanginal chest pain patients had a low frequency of ischemia if CAC scores were less than 400, whereas lower CAC scores did not exclude ischemia among typical angina or atypical angina patients. CONCLUSIONS: CAC scores predict myocardial ischemia, with a threshold score of greater than 400 among patients with a low likelihood of ASCAD and those who are asymptomatic or have nonanginal chest pain. These data appear to extend the pool of patients for whom CAC scanning may be useful in ascertaining the need for cardiac stress testing.

Quantitative global plaque characteristics from coronary computed tomography angiography for the prediction of future cardiac mortality during long-term follow-up.

AIMS: Adverse plaque characteristics determined by coronary computed tomography angiography (CTA) have been associated with future cardiac events. Our aim was to investigate whether quantitative global per-patient plaque characteristics from coronary CTA can predict subsequent cardiac death during long-term follow-up. METHODS AND RESULTS: Out of 2748 patients without prior history of coronary artery disease undergoing CTA with dual-source CT, 32 patients suffered cardiac death (mean follow-up of 5 ± 2 years). These patients were matched to 32 controls by age, gender, risk factors, and symptoms (total 64 patients, 59% male, age 69 ± 10 years). Coronary CTA data sets were analysed by semi-automated software to quantify plaque characteristics over the entire coronary tree, including total plaque volume, volumes of non-calcified plaque (NCP), low-density non-calcified plaque (LD-NCP, attenuation <30 Hounsfield units), calcified plaque (CP), and corresponding burden (plaque volume × 100%/vessel volume), as well as stenosis and contrast density difference (CDD, maximum percent difference in luminal attenuation/cross-sectional area compared to proximal cross-section). In patients who died from cardiac cause, NCP, LD-NCP, CP and total plaque volumes, quantitative stenosis, and CDD were significantly increased compared to controls (P < 0.025 for all). NCP > 146 mm³ [hazards ratio (HR) 2.24; 1.09-4.58; P = 0.027], LD-NCP > 10.6 mm³ (HR 2.26; 1.11-4.63; P = 0.025), total plaque volume > 179 mm³ (HR 2.30; 1.12-4.71; P = 0.022), and CDD > 35% in any vessel (HR 2.85;1.4-5.9; P = 0.005) were associated with increased risk of future cardiac death, when adjusted for segment involvement score. CONCLUSION: Among quantitative global plaque characteristics, total, non-calcified, and low-density plaque volumes as well as CDD predict cardiac death in long-term follow-up.

Gated myocardial perfusion single photon emission computed tomography in the clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial, Veterans Administration Cooperative study no. 424.

BACKGROUND: Stress gated myocardial perfusion single photon emission computed tomography (gSPECT) is increasingly used before and after intercurrent therapeutic intervention and is the basis for ongoing evaluation in the Department of Veterans Affairs clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial. METHODS AND RESULTS: The COURAGE trial is a North American multicenter randomized clinical trial that enrolled 2287 patients to aggressive medical therapy vs percutaneous coronary intervention plus aggressive medical therapy. Three COURAGE nuclear substudies have been designed. The goals of substudy 0 are to examine the diagnostic accuracy of the extent and severity of inducible ischemia at baseline in COURAGE patients compared with patient symptoms and quantitative coronary angiography and to explore the relationship between inducible ischemia and the benefit from revascularization when added to medical therapy. Substudy 1 will correlate the extent and severity of provocative ischemia with the frequency, quality, and instability of recurrent symptoms in postcatheterization patients. Substudy 2 (n = 300) will examine the usefulness of sequential gSPECT monitoring 6 to 18 months after therapeutic intervention. Together, these nuclear substudies will evaluate the role of gSPECT to determine the effectiveness of aggressive risk-factor modifications, lifestyle interventions, and anti-ischemic medical therapies with or without revascularization in reducing patients' ischemic burdens. CONCLUSIONS: The unfolding of evidence on the application of gSPECT in trials such as COURAGE defines a new era for nuclear cardiology. We hope the evidence that emerges from the COURAGE trial will further establish the role of nuclear imaging in the evidence-based management of patients with stable coronary disease.

Computer-aided detection and evaluation of lipid-rich plaque on noncontrast cardiac CT.

OBJECTIVE: Noncontrast electron beam CT (EBCT) and MDCT are established for the assessment of calcified plaque, but not lipid-rich plaque. We developed software to identify lipid-rich plaque with noncontrast electron beam tomography (EBT) and MDCT. MATERIALS AND METHODS: A computer algorithm was developed to automatically find contiguous lipid-rich lesions with voxel intensities below a calculated patient-specific lipid threshold. Lipid density and lipid inhomogeneity in Hounsfield units were calculated in the proximal left coronaries of three populations: 34 low-risk patients (low-risk group < 6% Framingham risk score, no calcium), 31 high-risk patients (high-risk group > 20% Framingham risk score, no calcium), and 37 patients with calcified plaque (calcium group). RESULTS: The mean lipid density was -19.6 +/- 3.0 (SD) H in the low-risk group, -25.3 +/- 8.2 H in the high-risk group, and -34.3 +/- 13.0 H in the calcium group (p < 0.05). The mean lipid inhomogeneity was 17.7 +/- 3.6 H in the low-risk group, 21.5 +/- 5.5 H in the high-risk group, and 29.0 +/- 7.6 H in the calcium group (p < 0.05). The mean interscan variability in lipid density and lipid inhomogeneity were 2.0 +/- 3.3 H and 2.1 +/- 3.6 H, respectively. In five patients, the locations of lipid-rich plaque correlated well with available intravascular sonography findings. CONCLUSION: Our method may be able to identify lipid-rich plaque on noncontrast cardiac CT.

Metabolic syndrome and diabetes are associated with an increased likelihood of inducible myocardial ischemia among patients with subclinical atherosclerosis.

OBJECTIVE: Coronary artery calcification (CAC) is associated with cardiac events and the likelihood of inducible myocardial ischemia. Because metabolic syndrome contributes to atherosclerosis, we assessed whether it also influences the relationship between CAC levels and myocardial ischemia. RESEARCH DESIGN AND METHODS: We evaluated 1,043 patients without known coronary artery disease (CAD) who underwent stress myocardial perfusion scintigraphy (MPS) and computed tomography. Metabolic syndrome was defined by modified National Cholesterol Education Program criteria. Metabolic abnormalities were present in 313 patients (30%), including 140 with diabetes (with or without metabolic syndrome) and 173 who had metabolic syndrome without diabetes. RESULTS: Although CAC scores <100 identified a low likelihood ( approximately 2%) of ischemia, the presence (versus absence) of metabolic abnormalities (metabolic syndrome or diabetes) was a predictor of more frequent ischemia among patients with CAC scores of 100-399 (13.0 vs. 3.6%, P < 0.02) and CAC scores >/=400 (23.4 vs. 13.6%, P = 0.03). Similar trends were observed when patients with metabolic syndrome and diabetes were considered separately. Multiple logistic regression revealed the odds of MPS ischemia to be 4.3-fold greater per SD of log CAC (P < 0.001) and 2.0-fold greater in the presence of metabolic abnormalities (P < 0.01). CONCLUSIONS: Among patients with CAC scores >/=100, metabolic abnormalities, and even metabolic syndrome in the absence of diabetes predicted a higher likelihood of inducible ischemia. These findings suggest the need for assessment of metabolic status when interpreting the results of CAC imaging among patients undergoing such testing because of suspected CAD.

Dyspnea predicts mortality among patients undergoing coronary computed tomographic angiography.

The prognostic implications of dyspnea and typical angina in patients referred for coronary CT angiography have not been examined. We examined features associated with incident mortality risk among individuals undergoing coronary computed tomographic angiography (CCTA) presenting with dyspnea, typical angina, and neither of these symptoms. 1147 consecutive individuals without known CAD (mean 61 years, 61.6 %men) undergoing CCTA comprised the study population 132 with dyspnea, 218 with typical angina, and 797 without dyspnea or typical angina (reference group). Mortality risk in relation to dyspnea or typical angina was evaluated with multivariable Cox proportional hazards models compared to reference. In addition, the prognosis associated with dyspnea or typical angina was assessed among age matched subgroups. Patients with dyspnea had a greater prevalence of C70 % stenosis (p\0.001) and coronary segments with plaque (p = 0.02) compared to the other two groups. During a follow-up of 3.1 years, 52 individuals died. By multivariable Cox models, compared to patients in reference group, dyspnea patients experienced higher mortality (HR 2.0, 95 % CI 1.0­4.0, p = 0.049) while typical angina patients did not (HR 1.1, 95 % CI 0.6­2.3, p = 0.76). In the matched group, the patients with dyspnea (HR 2.2, 95 % CI 1.1­4.3, p = 0.03) still had significantly reduced survival compared to the other two groups, while those with typical angina did not (HR 1.2, 95 % CI 0.6­2.6,p = 0.62). Dyspnea is associated with increased mortality ate compared to patients with typical angina and those with neither of these symptoms among patients undergoing CCTA.

Relationship between stress-induced myocardial ischemia and atherosclerosis measured by coronary calcium tomography.

OBJECTIVES: We assessed the relationship between stress-induced myocardial ischemia on myocardial perfusion single-photon emission computed tomography (MPS) and magnitude of coronary artery calcification (CAC) by X-ray tomography in patients undergoing both tests. BACKGROUND: There has been little evaluation regarding the relationship between CAC and inducible ischemia or parameters that might modify this relationship. METHODS: A total of 1,195 patients without known coronary disease, 51% asymptomatic, underwent stress MPS and CAC tomography within 7.2 +/- 44.8 days. The frequency of ischemia by MPS was compared to the magnitude of CAC abnormality. RESULTS: Among 76 patients with ischemic MPS, the CAC scores were >0 in 95%, >or=100 in 88%, and >or=400 in 68%. Of 1,119 normal MPS patients, CAC scores were >0, >or=100, and >or=400 in 78%, 56%, and 31%, respectively. The frequency of ischemic MPS was <2% with CAC scores <100 and increased progressively with CAC >or=100 (p for trend <0.0001). Patients with symptoms with CAC scores >or=400 had increased likelihood of MPS ischemia versus those without symptoms (p = 0.025). Absolute rather than percentile CAC score was the most potent predictor of MPS ischemia by multivariable analysis. Importantly, 56% of patients with normal MPS had CAC scores >or=100. CONCLUSIONS: Ischemic MPS is associated with a high likelihood of subclinical atherosclerosis by CAC, but is rarely seen for CAC scores <100. In most patients, low CAC scores appear to obviate the need for subsequent noninvasive testing. Normal MPS patients, however, frequently have extensive atherosclerosis by CAC criteria. These findings imply a potential role for applying CAC screening after MPS among patients manifesting normal MPS.

Social network and coronary artery calcification in asymptomatic individuals.

BACKGROUND: Psychosocial factors are associated with the development of coronary artery disease. However, studies examining psychosocial factors as risk indicators for coronary artery calcification (CAC) have been inconclusive. METHODS: Seven hundred eighty-three participants (mean age 57.4 +/- 9.3 years, 47% female) underwent CAC imaging using electron beam tomography. Psychosocial measures included social network (number of people in the household, marital status), socioeconomic status (education, income, and work status), history of depression, and current depressive symptoms as assessed with the Center for Epidemiologic Studies Depression (CES-D) scale. Assessments were also made for lipid profile, blood glucose, blood pressure, and health behaviors (smoking status, exercise, and diet). RESULTS: Calcification was present in 351 (44.8%) participants (CAC score range 0-3022; mean 111.5 +/- 307.2). Indicators of social isolation (being single or widowed) were independently associated with elevated risk for the presence of CAC, even after adjustment for age, sex, systolic blood pressure, blood glucose, and low-density lipoprotein (adjusted odds ratios 1.80, 95% confidence interval [CI] = 1.05-3.10, and 2.48, 95% CI = 1.02-6.03, respectively). By contrast, health behaviors, socioeconomic status, and depressive symptoms were not related to CAC. CONCLUSIONS: Social network indices such as being single or widowed are associated with CAC, independent of age and coronary risk factors. Because coronary calcification has been identified as a potential marker of early atherosclerosis, these findings may partially explain the predictive value of limited social networks for future adverse cardiovascular health outcomes.

Relation of thoracic aortic and aortic valve calcium to coronary artery calcium and risk assessment.

Aortic calcium, aortic valve calcium (AVC), and coronary artery calcium (CAC) have been associated with cardiovascular event risk. We examined the prevalence of thoracic aortic calcium (TAC) and AVC in relation to the presence and extent of CAC, cardiovascular risk factors, and estimated risk of coronary heart disease (CHD). In 2,740 persons without known CHD aged 20 to 79 years, CAC was assessed by electron beam- or multidetector-computed tomography. We determined the prevalence of TAC and AVC in relation to CAC, CHD risk factors, and predicted 10-year risk of CHD. A close correspondence of TAC and AVC was observed with CAC. TAC and AVC increased with age; by the eighth decade of life, the prevalence of TAC was similar to that of CAC (>80%), and 36% of men and 24% of women had AVC. Age, male gender, and low-density lipoprotein cholesterol were directly related to the likelihood of CAC, TAC, and AVC; higher diastolic blood pressure and cigarette smoking additionally predicted CAC. Body mass index and higher systolic and lower diastolic blood pressures were also related to TAC, and higher body mass index and lower diastolic blood pressure were related to AVC. Calculated risk of CHD increased with the presence of AVC and TAC across levels of CAC. TAC and AVC provided incremental value over CAC in association with the 10-year calculated risk of CHD. If longitudinal studies show an incremental value of aortic and aortic valve calcium over that of CAC for prediction of cardiovascular events, future guidelines for risk assessment incorporating CAC assessment may additionally incorporate the measurement of aortic and/or aortic valve calcium.

Relationship of dyspnea vs. typical angina to coronary artery disease severity, burden, composition and location on coronary CT angiography.

OBJECTIVE: Symptom presentations suspicious for coronary artery disease (CAD) vary widely. While dyspnea is associated with worse prognosis than typical angina (TypAng) for patients referred for non-invasive CAD imaging, the relation of dyspnea vs. TypAng to adverse measures of CAD prognosis-including severity, burden, composition, and myocardium at risk-has not been examined. METHODS: We studied 1443 consecutive individuals without known CAD (mean 61 ± 13 years, 61.6% men) undergoing coronary computed tomographic angiography (CCTA) who presented with dyspnea (n = 170), TypAng (n = 249) or no dyspnea or TypAng (n = 1024). Multivariable logistic regression was performed to evaluate the association of dyspnea or TypAng to obstructive CAD (≥70% stenosis), plaque burden (total segments with plaque), composition (noncalcified, partially calcified) and location (proximal, mid, or distal location in a coronary artery). RESULTS: By multivariable logistic regression, both dyspnea (OR1.9, 95% CI 1.1-3.3, p = 0.02) and TypAng (OR1.9, 95% CI 1.2-3.1, p = 0.01) were associated with obstructive CAD as compared to individuals without dyspnea or TypAng, while dyspnea (OR1.8, 95% CI 1.1-3.1, p = 0.02), but not TypAng (OR1.1, 95% CI 0.7-1.6, p = 0.76) was associated with plaque in the proximal portions of coronary arteries. Neither symptom type was associated with differences in plaque burden nor composition. CONCLUSION: Both dyspnea and TypAng are associated with higher rates of obstructive CAD compared to those without dyspnea or TypAng, but only dyspnea is associated with coronary plaque in proximal vessel portions.

Mortality risk as a function of the ratio of pulmonary trunk to ascending aorta diameter in patients with suspected coronary artery disease.

Although an increased pulmonary trunk (PT) diameter to ascending aorta (AA) diameter ratio (PT/AA ratio) is associated with pulmonary hypertension, the prognostic utility of this metric remains unexamined. We investigated whether an increase in the PT/AA ratio, as measured using coronary computed tomographic angiography, is associated with the risk of all-cause death. We identified 1,326 consecutive patients (mean age 61 ± 13 years; 60% men) without known coronary artery disease who underwent coronary computed tomographic angiography. Patients with a history of congenital or valvular heart disease or aortic enlargement (≥4 cm) were excluded. The PT and AA diameters were measured at the PT bifurcation level. The patients were categorized by PT/AA deciles, with the ≥90th percentile (PT/AA ratio 0.9) considered elevated. All-cause death associated with a PT/AA ratio <0.9 versus ≥0.9 was evaluated using multivariate Cox proportional hazard models. During 2.9 ± 1.0 years of follow-up, 58 patients died. Patients with a PT/AA ratio ≥0.9 experienced 2.5-fold greater annualized mortality compared to those with <0.9 (3.1% vs 1.3%, p = 0.004). Adjusting for age, gender, heart rate, dyslipidemia, smoking, and coronary artery disease extent, the patients with a PT/AA ratio ≥0.9 experienced a greater mortality risk compared to patients with PT/AA ratio <0.9 (hazard ratio 3.2, 95% confidence interval 1.6 to 6.6, p = 0.001). In the 1,059 patients with left ventricular ejection fraction measurements, a lower left ventricular ejection fraction was observed in the PT/AA ratio ≥0.9 group (p <0.05). In conclusion, incrementally and independent of the traditional coronary artery disease risk factors, an elevated PT/AA ratio was associated with increased mortality risk in patients without known coronary artery disease undergoing coronary computed tomographic angiography.

Pericardial fat burden on ECG-gated noncontrast CT in asymptomatic patients who subsequently experience adverse cardiovascular events.

OBJECTIVES: We aimed to evaluate whether pericardial fat has value in predicting the risk of future adverse cardiovascular outcomes. BACKGROUND: Pericardial fat volume (PFV) and thoracic fat volume (TFV) can be routinely measured from noncontrast computed tomography (NCT) performed for calculating coronary calcium score (CCS) and may predict major adverse cardiac event (MACE) risk. METHODS: From a registry of 2,751 asymptomatic patients without known cardiac artery disease and 4-year follow-up for MACE (cardiac death, myocardial infarction, stroke, late revascularization) after NCT, we compared 58 patients with MACE with 174 same-sex, event-free control subjects matched by a propensity score to account for age, risk factors, and CCS. The TFV was automatically calculated, and PFV was calculated with manual assistance in defining the pericardial contour, within which fat voxels were automatically identified. Independent relationships of PFV and TFV to MACE were evaluated using conditional multivariable logistic regression. RESULTS: Patients experiencing MACE had higher mean PFV (101.8 +/- 49.2 cm(3) vs. 84.9 +/- 37.7 cm(3), p = 0.007) and TFV (204.7 +/- 90.3 cm(3) vs. 177 +/- 80.3 cm(3), p = 0.029) and higher frequencies of PFV >125 cm(3) (33% vs. 14%, p = 0.002) and TFV >250 cm(3) (31% vs. 17%, p = 0.025). After adjustment for Framingham risk score (FRS), CCS, and body mass index, PFV and TFV were significantly associated with MACE (odds ratio [OR]: 1.74, 95% confidence interval [CI]: 1.03 to 2.95 for each doubling of PFV; OR: 1.78, 95% CI: 1.01 to 3.14 for TFV). The area under the curve from receiver-operator characteristic analyses showed a trend of improved MACE prediction when PFV was added to FRS and CCS (0.73 vs. 0.68, p = 0.058). Addition of PFV, but not TFV, to FRS and CCS improved estimated specificity (0.72 vs. 0.66, p = 0.008) and overall accuracy (0.70 vs. 0.65, p = 0.009) in predicting MACE. CONCLUSIONS: Asymptomatic patients who experience MACE exhibit greater PFV on pre-MACE NCT when they are compared with event-free control subjects with similar cardiovascular risk profiles. Our preliminary findings suggest that PFV may help improve prediction of MACE.

Prognostic accuracy of B-natriuretic peptide measurements and coronary artery calcium in asymptomatic subjects (from the Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research [EISNER] study).

B-type natriuretic peptide (BNP) has prognostic implications in patients with acute and chronic cardiac symptoms. Its prognostic role in asymptomatic patients with evidence of subclinical disease remains unclear. The population of this study included 2,458 asymptomatic adults (47% women) with an average Framingham risk score of 8.8 +/- 7% who underwent computed tomographic evaluation of coronary artery calcium (CAC). BNP levels were measured using the Triage CardioProfilER panel method. Cox proportional-hazards models were used to estimate time to a cardiovascular (CV) event (n = 84; 16 deaths, 12 myocardial infarctions, 8 cerebrovascular accidents or transient ischemic attacks, and 48 diagnoses of incident symptomatic coronary disease). Relative risk was calculated. The median follow-up time was 3.9 years (25th and 75th percentiles 2.9 and 4.0). The relative hazard for a CV event ranged from 2.2 to 7.5 for BNP values of 40 to 99.9 and > or =100 pg/ml (p <0.0001) compared to BNP <40 pg/ml. Similarly, CAC score was also highly predictive of CV events, with elevated hazard ratios of 2.8- to 48.7-fold for scores of 11 to 100 to > or =1,000 (p <0.0001) compared to no CAC. In a stepwise model, BNP was the second greatest estimator of CV outcomes (p = 0.016) after CAC (p <0.0001), even in models that included blood pressure and age. Hypertension, age > or =65 years, and CAC contained 28.4%, 40.7%, and 56.8%, respectively, of BNP risk. The combination of BNP > or =100 pg/ml and CAC score > or =400 identified 52.4% and 35.7% of CV events in patients with hypertension and in elderly patients beyond the Framingham risk score. In conclusion, BNP and CAC are independently predictive of CV events.

Myeloperoxidase, subclinical atherosclerosis, and cardiovascular disease events.

OBJECTIVES: We evaluated whether myeloperoxidase (MPO) predicts future cardiovascular disease (CVD) events in asymptomatic adults and whether subclinical atherosclerosis may affect this relation. BACKGROUND: Myeloperoxidase is a leukocyte-derived enzyme-generating reactive oxidant species that has been shown to predict risk of CVD in selected populations. METHODS: We studied 1,302 asymptomatic adults (mean age 59 years, 47% women) without known CVD who were followed for 3.8 years. We measured MPO by the use of immunoassay. Coronary artery calcium (CAC), a measure of subclinical atherosclerosis, was measured by computed tomography with the Agatston score categorized as none/minimal (0 to 9), mild (10 to 99), and moderate/significant (> or = 100). Cox regression, adjusted for age, sex, and other risk factors, examined the relation of CAC and/or MPO with incident CVD events. RESULTS: Persons with MPO levels at or above compared with below the median (257 pM) were more likely (p < 0.05 to p < 0.001) to be women, have a higher body mass index, greater low-density lipoprotein cholesterol, greater systolic and diastolic blood pressure, and lower high-density lipoprotein cholesterol. Mean MPO levels increased according to CAC categories (p trend = 0.02). Incident CVD events were more likely in those at or above versus below the median MPO level (4.6% vs. 2.3%, p = 0.02), even after adjustment for age, sex, CAC, and risk factors (hazard ratio [HR]: 1.9, 95% confidence interval: 1.0 to 3.6, p = 0.04). Combining CAC and MPO categories, CVD incidence ranged from 0.6% in those with a CAC score of 0 to 9 to 7.1% (adjusted HR: 9.2, p < 0.001) in those with CAC scores of > or = 100 and MPO below the median and 14.0% (adjusted HR: 19.5, p < 0.0001) in those with CAC scores of > or = 100 and MPO at or above the median. CONCLUSIONS: Our study suggests persons with both increased levels of both MPO and CAC are at an increased risk of CVD events. Imaging of subclinical atherosclerosis combined with assessment of biomarkers of plaque vulnerability may help improve CVD risk stratification.

Thoracic aortic calcium versus coronary artery calcium for the prediction of coronary heart disease and cardiovascular disease events.

OBJECTIVES: This study compared the ability of coronary artery calcium (CAC) and thoracic aortic calcium (TAC) to predict coronary heart disease (CHD) and cardiovascular disease (CVD) events. BACKGROUND: Coronary artery calcium has been shown to strongly predict CHD and CVD events, but it is unknown whether TAC, also measured within a single cardiac computed tomography (CT) scan, is of further value in predicting events. METHODS: A total of 2,303 asymptomatic adults (mean age 55.7 years, 38% female) with CT scans were followed up for 4.4 years for CHD (myocardial infarction, cardiac death, or late revascularizations) and CVD (CHD plus stroke). Cox regression, adjusted for Framingham risk score (FRS), examined the relation of Agatston CAC and TAC categories, and log-transformed CAC and TAC with the incidence of CHD and CVD events and receiver-operator characteristic (ROC) curves tested whether TAC improved prediction of events over CAC and FRS. RESULTS: A total of 53% of subjects had Agatston CAC scores of 0; 8% 1 to 9; 19% 10 to 99; 12% 100 to 399; and 8% > or =400. For TAC, proportions were 69%, 5%, 12%, 8%, and 7%, respectively; 41 subjects (1.8%) experienced CHD and 47 (2.0%) CVD events. The FRS-adjusted hazard ratios (HR) across increasing CAC groups (relative to <10) ranged from 3.7 (p = 0.04) to 19.6 (p < 0.001) for CHD and from 2.8 (p = 0.07) to 13.1 (p < 0.001) for CVD events; only TAC scores of 100 to 399 predicted CHD and CVD (HR: 3.0, p = 0.008, and HR: 2.3, p = 0.04, respectively); these risks were attenuated after accounting for CAC. Findings were consistent when using log-transformed CAC and TAC Agatston and volume scores. The ROC curve analyses showed CAC predicted CHD and CVD events over FRS alone (p < 0.01); however, TAC did not further add to predicting events over FRS or CAC. CONCLUSIONS: This study found that CAC, but not TAC, is strongly related to CHD and CVD events. Moreover, TAC does not further improve event prediction over CAC.