To examine the relation between measures of adiposity and depressive symptoms in a large well characterized community-based sample, we examined the relations of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) to depressive symptoms in 1581 women (mean age 52.2 years) and 1718 men (mean age 49.8 years) in the Framingham Heart Study. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression (CES-D) scale. Regression models were created to examine the association between each fat depot (exposure) and depressive symptoms (outcome). Sex specific models were adjusted for age, body mass index, smoking, alcohol consumption, diabetes, hypertension, total and HDL cholesterol, lipid lowering treatment, CVD, menopause, C-reactive protein, and physical activity. Mean CES-D scores were 6.8 and 5.6 in women and men. High levels of depressive symptoms were present in 22.5% of women and 12.3% of men. In women, one standard deviation increase in VAT was associated with a 1.3 point higher CES-D score after adjusting for age and BMI (p<0.01) and remained significant in the fully adjusted model (p=0.03). The odds ratio of depressive symptoms per 1 standard deviation increase in VAT in women was 1.33 (p=0.015); results were attenuated in fully adjusted models (OR 1.29, p=0.055). In men, the association between VAT and CES-D score and depressive symptoms was not significant. SAT was not associated with CES-D score or depressive symptoms. This study supports an association between VAT and depressive symptoms in women. Further work is needed to uncover the complex biologic mechanisms mediating the association.
We sought to characterize associations between aminotransferase levels and cardiometabolic risk after accounting for visceral adipose tissue (VAT) and insulin resistance.
Methods and Results
Participants (n=2621) from the Framingham Heart Study (mean age 51, 49.8% women) were included. Sex-specific linear and logistic regressions were used to evaluate associations between aminotransferase levels and cardiometabolic risk factors. In multivariable models, increased ALT levels were associated with elevated blood pressure, fasting plasma glucose, and triglycerides and lower HDL levels (all p ≤ 0.007). Further, each 1 standard deviation (SD) increase in ALT corresponded to an increased odds of hypertension, diabetes, the metabolic syndrome, impaired fasting glucose, and insulin resistance estimated by HOMA-IR (OR 1.29–1.85, all p ≤ 0.002). Associations with ALT persisted after additional adjustment for VAT, insulin resistance, and BMI with the exception of HDL cholesterol in both sexes and blood pressure in women. Results were materially unchanged when moderate drinkers were excluded, when the sample was restricted to those with ALT<40 U/L, and when the sample was restricted to those without diabetes. Similar trends were observed for AST levels, but associations were more modest.
Aminotransferase levels are correlated with multiple cardiometabolic risk factors above and beyond VAT and insulin resistance.
liver function tests; obesity; visceral fat; insulin resistance; cardiometabolic risk factors
Perivascular fat may have a local adverse effect on the vasculature. We evaluated whether thoracic periaortic adipose tissue (TAT), a type of perivascular fat, and visceral adipose tissue (VAT) are associated with vascular function.
Design and Methods
TAT and VAT were quantified in Framingham Heart Study participants using multidetector computed tomography; vascular function was assessed using brachial artery vasodilator function, peripheral arterial tone and arterial tonometry (n= 2735, 48% women, mean age 50 years, mean BMI 27.7 kg/m2). Using multiple linear regression, we examined relations between TAT, VAT, and vascular measures while adjusting for cardiovascular risk factors.
Mean TAT and VAT volumes were 13.2 and 1763 cm3. TAT and VAT were associated with multiple vascular function measures after multivariable adjustment. After BMI adjustment, TAT and VAT remained negatively associated with peripheral arterial tone and inverse carotid femoral pulse wave velocity (p<0.02); TAT was negatively associated with hyperemic mean flow velocity (p=0.03). Associations of TAT with vascular function were attenuated after VAT adjustment (all p>0.06).
Thoracic periaortic and visceral fat are associated with microvascular function and large artery stiffness after BMI adjustment. These findings support the growing recognition of associations between ectopic fat and vascular function.
obesity; vascular function; arterial stiffness; perivascular adipose tissue; visceral adipose tissue
This study evaluated the association of timing of lipid levels and lipid genetic risk score (GRS) with subclinical atherosclerosis.
Atherosclerosis is a slowly progressive disorder influenced by suboptimal lipid levels. Long-term versus contemporary lipid levels may more strongly impact the development of coronary artery calcium (CAC).
Framingham Heart Study (FHS) Offspring Cohort participants (n=1156, 44%M, 63±9 years) underwent serial fasting lipids [low-density lipoprotein (LDL-C), high-density lipoprotein, and triglycerides], Exam 1 (1971–1975) – Exam 7 (1998–2001). FHS Third Generation Cohort participants (n=1954, 55%M, 45±6 years) had fasting lipid profiles assessed, 2002–2005. Computed tomography (2002–2005) measured CAC. Lipid GRSs were computed from significantly associated single nucleotide polymorphisms. The association between early, long-term average, and contemporary lipids, and lipid GRS, with elevated CAC was assessed using logistic regression.
In FHS Offspring, Exam 1 and long-term average versus Exam 7 lipid measurements, including untreated lipid levels, were strongly associated with elevated CAC. In the FHS Third Generation, contemporary lipids were associated with CAC. The LDL-C GRS was associated with CAC (age/sex-adjusted OR 1.14, 95%CI 1.00–1.29, p=0.04). However, addition of the GRS to the lipid models did not result in a significant increase in the OR or C-statistic for any lipid measure.
Early and long-term average lipid levels, as compared with contemporary measures, are more strongly associated with elevated CAC. Lipid GRS was associated with lipid levels but did not predict elevated CAC. Adult early and long-term average lipid levels provide important information when assessing subclinical atherosclerosis and cardiovascular risk.
Lipids; Genetic risk score; Coronary artery calcium
Perivascular adipose tissue may be associated with the amount of local atherosclerosis. We developed a novel and reproducible method to standardize volumetric quantification of periaortic adipose tissue by computed tomography (CT) and determined the association with anthropometric measures of obesity, and abdominal adipose tissue.
Measurements of adipose tissue were performed in a random subset of participants from the Framingham Heart Study (n=100) who underwent multidetector CT of the thorax (ECG triggering, 2.5 mm slice thickness) and the abdomen (helical CT acquisition, 2.5 mm slice thickness). Abdominal periaortic adipose tissue (AAT) was defined by a 5 mm cylindrical region of interest around the aortic wall; thoracic periaortic adipose tissue (TAT) was defined by anatomic landmarks. TAT and AAT were defined as any voxel between −195 HU to −45HU and volumes were measured using dedicated semiautomatic software. Measurement reproducibility and association with anthropometric measures of obesity, and abdominal adipose tissue were determined.
The intra- and inter-observer reproducibility for both AAT and TAT was excellent (ICC: 0.97, 0.97; 0.99, and 0.98, respectively). Similarly, the relative intra-and inter-observer difference was small for both AAT (−1.85±1.28% and 7.85±6.08%; respectively) and TAT (3.56±0.83% and −4.56±0.85%, respectively). Both AAT and TAT were highly correlated with visceral abdominal fat (r=0.65 and 0.77, p<0.0001 for both) and moderately correlated with subcutaneous abdominal fat (r=0.39 and 0.42, p<0.0001 and p=0.009), waist circumference (r=0.49 and 0.57, p<0.0001 for both), and body mass index (r=0.47 and 0.58, p<0.0001 for both).
Standardized semiautomatic CT-based volumetric quantification of periaortic adipose tissue is feasible and highly reproducible. Further investigation is warranted regarding associations of periaortic adipose tissue with other body fat deposits, cardiovascular risk factors, and clinical outcomes.
Adipose Tissue; Intra-Abdominal Fat; Tomography; Spiral Computed; Framingham Heart Study; Metabolic Risk Factors
Abdominal aortic calcium (AAC) is associated with incident cardiovascular disease but the age and sex-related distribution of AAC in a community-dwelling population free of standard cardiovascular disease risk factors has not been described. A total of 3285 participants (aged 50.2±9.9 years) in the Framingham Heart Study Offspring and Third Generation cohorts underwent abdominal multidetector computed tomography (MDCT) scanning during 1998-2005. The presence and amount of AAC was quantified (Agatston score) by an experienced reader using standardized criteria. A healthy referent subsample (N=1656, 803 men) free of hypertension, hyperlipidemia, diabetes, obesity and smoking was identified, and participants were stratified by sex and age group (<45, 45-54, 55-64, 65-74, ≥75 years). The prevalence and burden of AAC increased monotonically and supralinearly with age in both sexes but was greater in men than women in each age group. Below age 45 <16% of referent-subsample participants had any quantifiable AAC, while above age 65 nearly 90% of referent participants had >0 AAC. Across the entire study sample, AAC prevalence and burden similarly increased with greater age. Defining the 90th percentile of referent group AAC as “high,” the prevalence of high AAC was 19% for each sex in the overall study sample. AAC also increased across categories of 10-year coronary heart disease risk, as calculated using the Framingham Risk Score, in the entire study sample. We found AAC to be widely prevalent, with the burden of AAC associated with 10-year coronary risk, in a white, free-living adult cohort.
atherosclerosis; aorta; calcification; computed tomography; epidemiology
Our objective was to assess whether impaired fasting glucose (IFG) and obesity are independently related to coronary artery calcification (CAC) in a community-based population.
RESEARCH DESIGN AND METHODS
We assessed CAC using multidetector computed tomography in 3,054 Framingham Heart Study participants (mean [SD] age was 50  years, 49% were women, 29% had IFG, and 25% were obese) free from known vascular disease or diabetes. We tested the hypothesis that IFG (5.6–6.9 mmol/L) and obesity (BMI ≥30 kg/m2) were independently associated with high CAC (>90th percentile for age and sex) after adjusting for hypertension, lipids, smoking, and medication.
High CAC was significantly related to IFG in an age- and sex-adjusted model (odds ratio 1.4 [95% CI 1.1–1.7], P = 0.002; referent: normal fasting glucose) and after further adjustment for obesity (1.3 [1.0–1.6], P = 0.045). However, IFG was not associated with high CAC in multivariable-adjusted models before (1.2 [0.9–1.4], P = 0.20) or after adjustment for obesity. Obesity was associated with high CAC in age- and sex-adjusted models (1.6 [1.3–2.0], P < 0.001) and in multivariable models that included IFG (1.4 [1.1–1.7], P = 0.005). Multivariable-adjusted spline regression models suggested nonlinear relationships linking high CAC with BMI (J-shaped), waist circumference (J-shaped), and fasting glucose.
In this community-based cohort, CAC was associated with obesity, but not IFG, after adjusting for important confounders. With the increasing worldwide prevalence of obesity and nondiabetic hyperglycemia, these data underscore the importance of obesity in the pathogenesis of CAC.
Pericardial adipose tissue (PAT) is a pathogenic fat depot associated with coronary atherosclerosis and cardiovascular events. We hypothesized that higher PAT is associated with coronary high-risk lesions as determined by cardiac CT.
We included 358 patients (38% female; median age 51 years) who were admitted to the ED with acute chest pain and underwent 64-slice CT angiography. The cardiac CT data sets were assessed for presence and morphology of CAD and PAT. Coronary high-risk lesions were defined as >50% luminal narrowing and at least two of the following characteristics: positive remodeling, low-density plaque, and spotty calcification. PAT was defined as any pixel with CT attenuation of −190 to −30 HU within the pericardial sac.
Based on cardiac CT, 50% of the patients (n = 180) had no CAD, 46% (n = 165) had CAD without high-risk lesions, and 13 patients had CAD with high-risk lesions. The median PAT in patients with high-risk lesions was significantly higher compared to patients without high-risk lesions and without any CAD (151.9 [109.0–179.4] cm3 vs. 110.0 [81.5–137.4] cm3, vs. 74.8 [58.2–111.7] cm3, respectively p = 0.04 and p < 0.0001). These differences remained significant after adjusting for traditional risk factors including BMI (all p < 0.05). The area under the ROC curve for the identification of high-risk lesions was 0.756 in a logistic regression model with PAT as a continuous predictor.
PAT volume is nearly twice as high in patients with high-risk coronary lesions as compared to those without CAD. PAT volume is significantly associated with high risk coronary lesion morphology independent of clinical characteristics and general obesity.
Coronary artery disease; Cardiac CT angiography; Pericardial fat; Adipose tissue; Vulnerable plaque; High-risk lesions
Although early cardiac computed tomographic angiography (CCTA) might improve the management of emergency department (ED) patients with acute chest pain, it could also result in increased testing, costs, and radiation exposure. ROMICAT II was a randomized comparative effectiveness trial enrolling patients 40 to 74 years old without known coronary artery disease who presented to the ED with chest pain but without ischemic electrocardiographic (ECG) changes or elevated initial troponin and who required further risk stratification. Overall, 1000 patients at 9 sites within the United States were randomized to either CCTA as the first diagnostic test following serial biomarkers or to standard of care, which included no testing or functional testing such as exercise ECG, stress radionuclide imaging, or stress echocardiography. Test results were provided to ED physicians, yet patient management was not driven by a study protocol in either arm. Data were collected on diagnostic testing, cardiac events, and cost of medical care for the index hospitalization and during the following 28 days. The primary end point was length of hospital stay. Secondary end points were cumulative radiation exposure, resource utilization, and costs of competing strategies. Tertiary end points were institutional, physician, and patient characteristics associated with primary and secondary outcomes. Rate of missed acute coronary syndrome within 28 days was the safety end point. The ROMICAT II will provide rigorous data on whether CCTA is more efficient than standard of care in the management of patients with acute chest pain at intermediate risk for acute coronary syndrome.
The goal of this study was to determine the ability of a single, resting high-sensitivity troponin T (hsTnT) measurement to predict abnormal myocardial perfusion imaging (MPI) in patients presenting with acute chest pain to the emergency department (ED).
HsTnT assays precisely detect very low levels of troponin T, which may be a surrogate for the presence and extent of myocardial ischemia.
We included all patients from the ROMICAT I (Rule Out Myocardial Infarction Using Computer Assisted Tomography) trial, an observational cohort study, who underwent both single-photon emission computed tomography (SPECT)-MPI stress testing and 64-slice computed tomography angiography (CTA) and in whom hsTnT measurements were available. We assessed the discriminatory value of hsTnT for abnormal SPECT-MPI and the association of reversible myocardial ischemia by SPECT-MPI and the extent of coronary atherosclerosis by CTA to hsTnT levels.
Of the 138 patients (mean age 54 ± 11 years, 46% male), 19 (13.7%) had abnormal SPECT-MPI. Median hsTnT levels were significantly different between patients with normal and abnormal SPECT-MPI (9.41 pg/ml [interquartile range (IQR): 5.73 to 19.20 pg/ml] vs. 4.89 pg/ml [IQR: 2.34 to 7.68 pg/ml], p = 0.001). Sensitivity of 80% and 90% to detect abnormal SPECT-MPI was reached at hsTnT levels as low as 5.73 and 4.26 pg/ml, respectively. Corresponding specificity was 62% and 46%, and negative predictive value was 96% and 96%, respectively. HsTnT levels had good discriminatory ability for prediction of abnormal SPECT-MPI (area under the curve: 0.739, 95% confidence interval: 0.609 to 0.868). Both reversible myocardial ischemia and the extent of coronary atherosclerosis (combined model r2 = 0.19 with partial of r2 = 0.12 and r2 = 0.05, respectively) independently and incrementally predicted the measured hsTnT levels.
In patients with acute chest pain, myocardial perfusion abnormalities and coronary artery disease are predicted by resting hsTnT levels. Prospective evaluations are warranted to confirm whether resting hsTnT could serve as a powerful triage tool in chest pain patients in the ED before diagnostic testing and improve the effectiveness of patient management.
coronary computed tomographic angiography; high-sensitivity troponin T; myocardial perfusion imaging; single-photon emission computed tomography
Cardiac resynchronization therapy has become an integral part in the step-care approach to manage patients with heart failure. Cardiac imaging remains central to appropriate patient selection and optimal left ventricular lead placement, both of which are important determinants of response to cardiac resynchronization therapy. One of the biggest limitations with current imaging modalities is the inability of a single technique to address each, the anatomic (venous anatomy), mechanical (dyssynchrony), and structural (extent of scar location) issues accompanying cardiomyopathy. We present here the potential concept of using cardiac computed tomography as a single modality to acquire functional and anatomic information, and also to show the possibility of integrating this with real time fluoroscopy.
cardiac resynchronization therapy; computed tomography; dyssynchrony; left ventricular lead placement; heart failure; coronary veins
The objective was to determine the association of four clinical risk scores and coronary plaque burden as detected by computed tomography (CT) with the outcome of acute coronary syndrome (ACS) in patients with acute chest pain. The hypothesis was that the combination of risk scores and plaque burden improved the discriminatory capacity for the diagnosis of ACS.
The study was a subanalysis of the Rule Out Myocardial Infarction Using Computer-Assisted Tomography (ROMICAT) trial—a prospective observational cohort study. The authors enrolled patients presenting to the emergency department (ED) with a chief complaint of acute chest pain, inconclusive initial evaluation (negative biomarkers, nondiagnostic electrocardiogram [ECG]), and no history of coronary artery disease (CAD). Patients underwent contrast-enhanced 64-multidetector-row cardiac CT and received standard clinical care (serial ECG, cardiac biomarkers, and subsequent diagnostic testing, such as exercise treadmill testing, nuclear stress perfusion imaging, and/or invasive coronary angiography), as deemed clinically appropriate. The clinical providers were blinded to CT results. The chest pain score was calculated and the results were dichotomized to ≥10 (high-risk) and <10 (low-risk). Three risk scores were calculated, Goldman, Sanchis, and Thrombolysis in Myocardial Infarction (TIMI), and each patient was assigned to a low-, intermediate-, or high-risk category. Because of the low number of subjects in the high-risk group, the intermediate- and high-risk groups were combined into one. CT images were evaluated for the presence of plaque in 17 coronary segments. Plaque burden was stratified into none, intermediate, and high (zero, one to four, and more than four segments with plaque). An outcome panel of two physicians (blinded to CT findings) established the primary outcome of ACS (defined as either an acute myocardial infarction or unstable angina) during the index hospitalization (from the presentation to the ED to the discharge from the hospital). Logistic regression modeling was performed to examine the association of risk scores and coronary plaque burden to the outcome of ACS. Unadjusted models were individually fitted for the coronary plaque burden and for Goldman, Sanchis, TIMI, and chest pain scores. In adjusted analyses, the authors tested whether the association between risk scores and ACS persisted after controlling for the coronary plaque burden. The prognostic discriminatory capacity of the risk scores and plaque burden for ACS was assessed using c-statistics. The differences in area under the receiver-operating characteristic curve (AUC) and c-statistics were tested by performing the −2 log likelihood ratio test of nested models. A p value <0.05 was considered statistically significant.
Among 368 subjects, 31 (8%) subjects were diagnosed with ACS. Goldman (AUC = 0.61), Sanchis (AUC = 0.71), and TIMI (AUC = 0.63) had modest discriminatory capacity for the diagnosis of ACS. Plaque burden was the strongest predictor of ACS (AUC = 0.86; p < 0.05 for all comparisons with individual risk scores). The combination of plaque burden and risk scores improved prediction of ACS (plaque + Goldman AUC = 0.88, plaque + Sanchis AUC = 0.90, plaque + TIMI AUC = 0.88; p < 0.01 for all comparisons with coronary plaque burden alone).
Risk scores (Goldman, Sanchis, TIMI) have modest discriminatory capacity and coronary plaque burden has good discriminatory capacity for the diagnosis of ACS in patients with acute chest pain. The combined information of risk scores and plaque burden significantly improves the discriminatory capacity for the diagnosis of ACS.
Cardiovascular disease is increased in HIV patients, but the specific mechanisms are unknown.
To assess arterial wall inflammation in HIV, using 18fluorine-2-deoxy-D-glucose Positron Emission Tomography (18FDG-PET), in relationship to traditional and non-traditional risk markers, including sCD163, a marker of macrophage activation.
Design, Setting, and Participants
81 participants were investigated in a cross-sectional study from November 2009 to July 2011. 27 HIV-infected participants without known cardiac disease underwent cardiac 18FDG-PET and coronary CT imaging for coronary calcium (CAC). Two separate non-HIV control groups were compared. One control group (n=27) was matched to the HIV group for age, gender and Framingham Risk Score (FRS) and had no known atherosclerotic disease (FRS-Matched Controls). The second control group (n=27) was matched on gender and selected based on the presence of known atherosclerotic disease (Atherosclerotic Controls).
Main Outcome Measure
Arterial inflammation was prospectively determined as the ratio of FDG uptake in the arterial wall of the ascending aorta/blood background, as the target to background ratio (TBR).
HIV participants demonstrated well-controlled HIV disease (CD4 641±288 cells/mm3, HIV RNA <48 [<48, <48] copies/mL). All were receiving ART (duration 12±4 yrs). The mean Framingham Risk Score (FRS) was low in both HIV and FRS-Matched Controls (6.4 (4.8–8.0) vs. 6.6 (4.9–8.2), P=0.87). Arterial inflammation in the aorta (Aortic TBR) was higher in the HIV vs. FRS-Matched Control Participants (2.23 (2.07–2.40) vs. 1.89 (1.80–1.97), P<0.001), but was similar compared to Atherosclerotic Controls (2.23 (2.07–2.40) vs. 2.13 (2.03–2.23), P=0.29). Aortic TBR remained significantly higher in the HIV group vs. the FRS-Matched Controls after adjusting for traditional cardiovascular risk factors (P=0.002) and in stratified analyses among participants with undetectable viral load, zero calcium, FRS<10, and LDL< 100 mg/dL (2.59 mmol/L) (all P<0.01). Aortic TBR was associated with sCD163 (P=0.04) but not with CRP (P=0.65) or D-Dimer (P=0.08) among HIV-infected patients.
Persons infected with HIV, compared to non-infected controls with similar cardiac risk factors, had signs of increased arterial inflammation which was associated with circulating markers of macrophage activation.
We aimed to determine predictors of image quality in consecutive patients who underwent coronary computed tomography (CT) for the evaluation of acute chest pain.
Method and Materials
We prospectively enrolled patients who presented with chest pain to the emergency department. All subjects underwent contrast-enhanced 64-slice coronary multi-detector CT. Two experienced readers determined overall image quality on a per-patient basis and the prevalence and characteristics of non-evaluable coronary segments on a per-segment basis.
Among 378 subjects (143 women, age: 52.9±11.8 years), 345 (91%) had acceptable overall image quality, while 33 (9%) had poor image quality or were unreadable. In adjusted analysis, patients with diabetes, hypertension and a higher heart rate during the scan were more likely to have exams graded as poor or unreadable (odds ratio [OR]: 2.94, p=0.02; OR: 2.62, p=0.03; OR: 1.43, p=0.02; respectively). Of 6,253 coronary segments, 257 (4%) were non-evaluable, most due to severe calcification (48%). The presence of non-evaluable coronary segments was associated with age (OR: 1.08 annually, 95%-confidence interval [CI]: 1.05–1.12 p<0.001), baseline heart rate (OR: 1.35 per 10 beats/min, 95%-CI: 1.11–1.67, p=0.003), diabetes, hypertension, and history of coronary artery disease (OR: 4.43, 95%-CI: 1.93–10.17, p<0.001; OR: 2.27, 95-CI: 1.01–4.73, p=0.03; OR: 5.12, 95%-CI: 2.0–13.06, p<0.001; respectively).
Coronary CT permits acceptable image quality in more than 90% of patients with chest pain. Patients with multiple risk factors are more likely to have impaired image quality or non-evaluable coronary segments. These patients may require careful patient preparation and optimization of CT scanning protocols.
cardiac computed tomography; coronary CT angiography; coronary artery disease; acute chest pain; image quality
Cocaine users represent an Emergency Department (ED) population that has been shown to be at increased risk for ACS; however, there is controversy about whether this higher risk is mediated through advanced atherosclerosis. Thus, we aimed to determine whether history of cocaine use is associated with acute coronary syndrome (ACS) and coronary artery disease using coronary computed tomography (CT). In this matched cohort study, we selected patients with a history of cocaine use and age- and gender-matched controls from a large cohort of consecutive patients who presented with acute chest pain to the ED. Coronary atherosclerotic plaque as detected by 64-slice coronary CT was compared between the groups. Among 412 patients, 44 had a history of cocaine use (9%) and were matched to 132 controls (mean age: 46±6 years, 86% male). History of cocaine use was associated with a 6-fold higher risk for ACS (odds ratio: 5.79, 95%-confidence interval: 1.24–27.02, p=0.02), but was not associated with a higher prevalence of any plaque, calcified plaque, or non-calcified plaque (p=1.0, p=1.0; and p=0.58, respectively) or the presence of significant stenosis (p=0.09). History of cocaine use was also not associated with the extent of any, calcified, or non-calcified plaque (p=0.67, p=0.30, and p=0.12, respectively). These associations persisted after adjustment for other cardiovascular risk factors. In conclusion, among ED patients presenting with acute chest pain, history of cocaine use is associated with an increase in risk for ACS; however, this was not attributable to a higher presence or extent of coronary atherosclerotic plaque.
We tested the hypothesis that the assessment of lesion morphology helped to detect acute coronary syndrome (ACS) during index hospitalization among patients with acute chest pain who had a significant stenosis on coronary computed tomography angiography (CTA). Patients who presented to the emergency department with chest pain but no objective signs of myocardial ischemia (non-diagnostic ECG and negative initial biomarkers) underwent CTA. CTA was analyzed for the degree and length of stenosis, plaque area and volume, remodeling index, CT attenuation of plaque, and spotty calcium in all patients with a significant stenosis (>50% in diameter) in CTA. ACS during the index hospitalization was determined by the panel of 2 physicians blinded to results of CTA. For lesion characteristics associated with ACS, we determined cutpoints optimized for diagnostic accuracy and created lesion scores. For each score, we determined odds ratio and discriminatory capacity for the prediction of ACS. Of the overall population of 368 patients, 34 had significant stenosis and among those 21 had ACS. Score A (remodeling index+spotty calcium: OR 3.5, 95%CI 1.2–10.1, AUC 0.734), B (remodeling index+spotty calcium+stenosis length: OR 4.6, 95%CI 1.6–13.7, AUC 0.824) and C (remodeling index+spotty calcium+stenosis length+volume of <90HU plaque: OR 3.4, 95%CI 1.5–7.9, AUC 0.833) were significantly associated with ACS. In conclusion, among patients presenting with acute chest pain and with a stenosis on coronary CTA, a CT-based score incorporating morphologic characteristics of coronary lesions had a good discriminatory value for the detection ACS during index hospitalization.
cardiac computed tomography; coronary computed tomography angiography; acute coronary syndrome; coronary atherosclerotic plaque
9p21.3 is among the most strongly replicated regions for cardiovascular disease (CVD). There are few reports of sequencing the associated 9p21.3 interval. We set out to sequence the 9p21.3 region followed by a comprehensive study of genetic associations with clinical and subclinical CVD and its risk factors, and with copy number variation and gene expression, in the Framingham Heart Study (FHS).
Methods and Results
We sequenced 281 individuals (n=94 with myocardial infarction, n=94 with high coronary artery calcium levels, and n=93controls free of elevated coronary artery calcium or myocardial infarction) followed by genotyping and association in >7,000 additional FHS individuals. We assessed genetic associations with clinical and subclinical CVD, risk factor phenotypes, and gene expression levels of protein-coding genes CDKN2A and CDKN2B as well as the non-coding gene ANRIL in freshly harvested leukocytes and platelets. Within this large sample we found strong associations of 9p21.3 variants with increased risk for myocardial infarction, higher coronary artery calcium levels, and larger abdominal aorta diameters, and no evidence for association with traditional CVD risk factors. No common protein-coding variation, variants in splice donor or acceptor sites, or CNV events were observed. By contrast, strong associations were observed between genetic variants and gene expression, particularly for a short isoform of ANRIL and for CDKN2B.
Our thorough genomic characterization of 9p21.3 suggests common variants likely account for observed disease associations, and provide further support for the hypothesis that complex regulatory variation affecting ANRIL and CDKN2B gene expression may contribute to increased risk for clinically apparent and subclinical coronary artery disease and aortic disease.
genetics; myocardial infarction; risk factors; atherosclerosis; calcium
Compared to troponin alone, a dual-marker strategy with natriuretic peptides may improve acute coronary syndrome (ACS) diagnosis with a single blood draw and provide physiologic information regarding underlying heart disease. We evaluate the value of adding natriuretic peptides (myocyte stress markers) to troponins (myocardial injury markers) for diagnosing ACS in emergency department (ED) patients with chest pain.
In 328 patients (53 ± 12 years, 63% men) with an initially negative conventional troponin and nonischemic electrocardiogram who underwent 64-slice cardiac computed tomography (CT), we measured conventional troponin-T (cTnT), high-sensitivity troponin-T (hsTnT), N-terminal pro-B type natriuretic peptide (NT-proBNP), and mid-regional pro-atrial natriuretic peptide (MR-proANP). ACS was defined as myocardial infarction or unstable angina. CT was evaluated for coronary plaque, stenosis, and regional wall motion abnormality (RWMA).
Patients with ACS (n=29, 9%) had higher concentrations of each biomarker compared to those without (all p <0.01). Adding natriuretic peptides, especially NT-proBNP, to both cTnT orhsTnT improved the C-statistics and net reclassification index for ACS, largely driven by correctly reclassifying events. Dual-negative marker results improved sensitivity (cTnT 38% to 83–86%, hsTnT 59% to 86–90%; all p <0.01) and negative predictive value (cTnT94% to 97–98%, hsTnT 96% to 97–98%) for ACS. Patients with dual-negative markers had the lowest percentage of CT coronary plaque, stenosis, and RWMA (all p-trend <0.001).
Among ED patients with low-intermediate likelihood of ACS, combining natriuretic peptides with either conventional or highly-sensitive troponin improved discriminatory capacity and allowed for better reclassification of ACS, findings supported by structural and functional CT results.
natriuretic peptides; troponins; acute coronary syndrome; emergency department; computed tomography
Efforts to reduce radiation from cardiac computed tomography (CT) are essential. Using a prospectively triggered, high-pitch dual source CT (DSCT) protocol, we aim to determine the radiation dose and image quality (IQ) in patients undergoing pulmonary vein (PV) imaging.
Methods and Results
In 94 patients (61±9 years, 71% male) who underwent 128-slice DSCT (pitch 3.4), radiation dose and IQ were assessed and compared between 69 patients in sinus rhythm (SR) and 25 in atrial fibrillation (AF). Radiation dose was compared in a subset of 19 patients with prior retrospective or prospectively triggered CT PV scans without high-pitch. In a subset of 18 patients with prior magnetic resonance imaging (MRI) for PV assessment, PV anatomy and scan duration were compared to high-pitch CT. Using the high-pitch protocol, total effective radiation dose was 1.4 [1.3, 1.9] mSv, with no difference between SR and AF (1.4 vs 1.5 mSv, p=0.22). No high-pitch CT scans were non-diagnostic or had poor IQ. Radiation dose was reduced with high-pitch (1.6 mSv) compared to standard protocols (19.3 mSv, p<0.0001). This radiation dose reduction was seen with SR (1.5 vs 16.7 mSv, p<0.0001) but was more profound with AF (1.9 vs 27.7 mSv, p=0.039). There was excellent agreement of PV anatomy (kappa 0.84, p<0.0001), and a shorter CT scan duration (6 minutes) compared to MRI (41 minutes, p<0.0001).
Using a high-pitch DSCT protocol, PV imaging can be performed with minimal radiation dose, short scan acquisition, and excellent IQ in patients with SR or AF. This protocol highlights the success of new cardiac CT technology to minimize radiation exposure, giving clinicians a new low-dose imaging alternative to assess PV anatomy.
arrhythmia (Heart Rhythm Disorders); atrial fibrillation; imaging; pulmonary vein isolation; computed tomography
It is unclear whether an evaluation incorporating coronary computed tomographic angiography (CCTA) is more effective than standard evaluation in the emergency department in patients with symptoms suggestive of acute coronary syndromes.
In this multicenter trial, we randomly assigned patients 40 to 74 years of age with symptoms suggestive of acute coronary syndromes but without ischemic electrocardiographic changes or an initial positive troponin test to early CCTA or to standard evaluation in the emergency department on weekdays during daylight hours between April 2010 and January 2012. The primary end point was length of stay in the hospital. Secondary end points included rates of discharge from the emergency department, major adverse cardiovascular events at 28 days, and cumulative costs. Safety end points were undetected acute coronary syndromes.
The rate of acute coronary syndromes among 1000 patients with a mean (±SD) age of 54±8 years (47% women) was 8%. After early CCTA, as compared with standard evaluation, the mean length of stay in the hospital was reduced by 7.6 hours (P<0.001) and more patients were discharged directly from the emergency department (47% vs. 12%, P<0.001). There were no undetected acute coronary syndromes and no significant differences in major adverse cardiovascular events at 28 days. After CCTA, there was more downstream testing and higher radiation exposure. The cumulative mean cost of care was similar in the CCTA group and the standard-evaluation group ($4,289 and $4,060, respectively; P=0.65).
In patients in the emergency department with symptoms suggestive of acute coronary syndromes, incorporating CCTA into a triage strategy improved the efficiency of clinical decision making, as compared with a standard evaluation in the emergency department, but it resulted in an increase in downstream testing and radiation exposure with no decrease in the overall costs of care. (Funded by the National Heart, Lung, and Blood Institute; ROMICAT-II ClinicalTrials.gov number, NCT01084239.)
The incremental value of regional left ventricular function (LVF) over coronary assessment to detect acute coronary syndrome (ACS) is uncertain.
Methods and Results
We analyzed 356 patients (mean age 53±12 years, 62% male) with acute chest pain and inconclusive initial ED evaluation. Patients underwent 64-slice contrast-enhanced cardiac CT prior to hospital admission. Caregivers and patients remained blinded to the results. Regional LVF and presence of coronary atherosclerotic plaque and significant stenosis (>50%) were separately assessed by two independent readers. Incremental value of regional LVF to predict ACS was determined in the entire cohort and in subgroups of patients with nonobstructive CAD, inconclusive assessment for stenosis (defined as inability to exclude significant stenosis due to calcium or motion), and significant stenosis. During their index hospitalization, 31 patients were ultimately diagnosed with ACS (8 myocardial infarction, 22 unstable angina), of which 74% (23 patients) had regional LV dysfunction. Adding regional LVF resulted in a 10% increase in sensitivity to detect ACS by cardiac CT (87%, 95%-confidence interval [CI]: 70–96%) and significantly improved the overall accuracy (c-statistic: 0.88 vs. 0.94 and 0.79 vs. 0.88, for extent of plaque and presence of stenosis; respectively; both p<0.03). The diagnostic accuracy of regional LVF for detection of ACS has 89% sensitivity and 86% specificity in patients with significant stenosis (n=33) and 60% sensitivity and 86% specificity in patients with inconclusive coronary CTA (n=33).
Regional LVF assessment at rest improves diagnostic accuracy for ACS in patients with acute chest pain, especially in those with coronary artery disease and thus may be helpful to guide further management in patients at intermediate risk for ACS.
Clinical Trial Registration
URL: http://clinicaltrials.gov/ct2/show/NCT00990262. Unique Identifier: NCT00990262
computed tomography; left ventricular function; acute coronary syndrome; emergency department
Twelve-lead surface electrocardiography (ECG) and computed tomography (CT) are used to evaluate for myocardial ischemia and coronary artery disease (CAD), respectively. We aimed to determine features on resting ECG that predict coronary artery stenosis by cardiac CT. In 309 acute chest pain patients, we compared the initial triage resting ECG to contrast-enhanced 64-slice cardiac CT angiography. We assessed for 6 quantitative (QT interval, QTc interval, QTc > 440 ms, gender-specific QTc, QT dispersion and QRS duration) and 4 qualitative ECG parameters (ST depression >0.05 to ≤0.1 mV, T wave inversion ≥0.1 mV, T wave flattening, and any T wave abnormalities) and for the presence of coronary stenosis by CT (>50% luminal narrowing). Specificities of these ECG parameters were excellent (83.6–97.0%) while sensitivities were poor (12.2–29.3%). For coronary stenosis detection, the ECG features with the greatest performance were the presence of ST depression (positive likelihood ratio [LR+] 4.09) and T wave inversion (LR+ 4.58). In multivariable analyses, the risk for coronary stenosis increased by 33–41% for every 20 ms prolongation of the QTc interval after adjusting for age, gender, and cardiac risk factors or adjustment for Framingham risk score. Similarly, there was an increase of fourfold with the presence of ST depression >0.05 to ≤0.1 mV or T wave inversion ≥0.1 mV. In acute chest pain patients, resting ECG features of QTc interval prolongation, mild ST depression, and T wave inversion are independently associated with the presence of CT coronary stenosis and their presence suggests an increase risk of CAD.
Electrocardiography; Coronary artery stenosis; Computed tomography; Acute chest pain; Emergency department
Limited data exist regarding the use of a genetic risk score for predicting risk of incident cardiovascular disease (CVD) in US based samples.
Methods and Results
Using findings from recent GWAS, we constructed genetic risk scores (GRS) comprised of 13 genetic variants associated with myocardial infarction (MI) or other manifestations of CHD and 102 genetic variants associated with CHD or its major risk factors. We also updated the 13 SNP GRS with 16 SNPs recently discovered by GWAS. We estimated the association, discrimination and risk reclassification of each GRS for incident cardiovascular events and for prevalent coronary artery calcium (CAC).
In analyses adjusted for age, sex, CVD risk factors and parental history of CVD, the 13 SNP GRS was significantly associated with incident hard CHD (HR 1.07, 95% CI 1.00-1.15, p=0.04), CVD (hazard ratio [HR] per-allele 1.05, 95% confidence interval [CI] 1.01-1.09; p=0.03), and high CAC (defined as >75th age and sex-specific percentile; odds ratio [OR] per-allele 1.18, 95% CI 1.11-1.26, p=3.4 × 10-7). The GRS did not improve discrimination for incident CHD or CVD but led to modest improvements in risk reclassification. However, significant improvements in discrimination and risk reclassification were observed for the prediction of high CAC. The addition of 16 newly discovered SNPs to the 13 SNP GRS did not significantly modify these results.
A GRS comprised of 13 SNPs associated with coronary disease is an independent predictor of cardiovascular events and of high CAC, modestly improves risk reclassification for incident CHD and significant improves discrimination for high CAC. The addition of recently discovered SNPs did not significantly improve the performance of this GRS.
Genetics; single nucleotide polymorphisms; cardiovascular disease; coronary heart disease; risk prediction; reclassification