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Cardiovascular disease (CVD) is the leading cause of mortality in adults with hepatic steatosis (HS). However, risk factors for CVD in HS are unknown. We aimed to identify factors associated with coronary artery disease (CAD) and incident major adverse cardiovascular events (MACE) in individuals with HS. We performed a nested cohort study of adults with HS detected on coronary computed tomography in the PROspective Multicenter Imaging Study for Evaluation of chest pain (PROMISE) trial. Obstructive CAD was defined as ≥50% coronary stenosis. MACE included hospitalization for unstable angina, nonfatal myocardial infarction, or all-cause death. Multivariate modeling, adjusted for age, sex, atherosclerotic CVD (ASCVD) risk score and body mass index, identified factors associated with obstructive CAD. Cox regression, adjusted for ASCVD risk score, determined the predictors of MACE. A total of 959 of 3,756 (mean age 59.4 years, 55.0% men) had HS. Obstructive CAD was present in 15.2% (145 of 959). Male sex (adjusted odds ratio [aOR] = 1.83, 95% confidence interval [CI] 1.18-1.2.84; p = 0.007), ASCVD risk score (aOR = 1.05, 95% CI 1.03-1.07; p 0.001), and n-terminal pro-b-type natriuretic peptide (NT-proBNP; aOR = 1.90, 95% CI 1.38-2.62; p 0.001) were independently associated with obstructive CAD. In the 25-months median follow-up, MACE occurred in 4.4% (42 of 959). Sedentary lifestyle (adjusted hazard ratio [aHR] = 2.53, 95% CI 1.27-5.03; p = 0.008) and NT-proBNP (aOR = 1.50, 95% CI 1.01-2.25; p = 0.046) independently predicted MACE. Furthermore, the risk of MACE increased by 3% for every 1% increase in ASCVD risk score (aHR = 1.03, 95% CI 1.01-1.05; p = 0.02). Conclusion: In individuals with HS, male sex, NT-pro-BNP, and ASCVD risk score are associated with obstructive CAD. Furthermore, ASCVD, NT-proBNP, and sedentary lifestyle are independent predictors of MACE. These factors, with further validation, may help risk-stratify adults with HS for incident CAD and MACE.

Introduction: Immune checkpoint inhibitors (ICIs) treat an expanding range of cancers and the use of ICIs has been associated with an increase in atherosclerotic cardiovascular disease (ASCVD) events. The mechanisms involved in the increase in ASCVD with ICIs are incompletely understood. These same immune checkpoints targeted for cancer also regulate vascular function, yet there are no data testing the effect of ICIs on blood pressure. Hypothesis: Based on basic data on the role of these immune checkpoints in vascular function, we hypothesize that the use of ICIs would increase systolic and diastolic blood pressure. Methods: This was a single academic medical center study of 8,724 patients treated with an ICI. The primary analysis evaluated whether exposure to ICIs was associated with changes in blood pressure using repeated measures multivariate mixed linear regression models. The secondary analysis evaluated the effect of changes in blood pressure on all cause mortality using Cox proportional hazard models. Results: Of the 8,724 patients, 4,812 (55.2%) had a diagnosis of hypertension at ICI start. The average blood pressure at ICI start was 128.3±18.1/72.5±10.1mmHg. Among the entire cohort, there was a decrease of 2.9 mmHg in systolic blood pressure (95% CI: 2.70-3.02) after starting an ICI, and a drop of 1.6 mmHg (95% CI: 1.52-1.70) in diastolic blood pressure (adjusted, p Conclusions: Among a large cohort of patients, ICI therapy is associated with a drop in systolic and diastolic blood pressure. However, patients who had an increase of at least ≥20 mmHg in systolic blood pressure had lower risk of all-cause death.

Introduction: A disparity in health outcomes between black and white patients with coronary artery disease (CAD) has also been reported with pathophysiological differences in CAD and racial disparities in providing health care as potential explanations. Hypothesis: To determine racial disparity in emergency care of patients with suspected acute coronary syndrome (ACS) undergoing cardiac CT angiography (cCTA), which provides knowledge of underlying CAD status. Methods: We combined patient level data of the ACRIN-PA 4005 (American College of Radiology Imaging Network, Pennsylvania) and ROMICAT II (Rule Out Myocardial Infarction using Computer Assisted Tomography) trials, which enrolled patients presenting with suspicion of ACS who were randomized to cCTA as a first diagnostic test at 14 US sites. Sample was restricted to subjects with known CAD status based on cCTA. Self-reported race while the race ‘Black’ were defined as “a person having origins in any of the black racial groups of Africa” and the race ‘white’ as “a person having origins in any of the original peoples of Europe, the Middle East, or North Africa”. Results: We included 1,191 patients (53% white, 47% black). Pretest probability for ACS was similar (TIMI score, p=0.77) between black and white patients, while black patients had lower presence and extent of CAD (calcium score: 39.3±189.3 vs. 88.2±292.1, p Conclusions: After adjustment for underlying CAD, among patients in the ED with suspicion of ACS, those who are black received more downstream testing and were more frequently admitted to hospital than white patients.

Background High-risk plaque (HRP) features as detected by coronary computed tomography angiography (CTA) predict acute coronary syndrome (ACS). We sought to determine whether coronary CTA-specific definitions of HRP improve discrimination of patients with ACS as compared with definitions from intravascular ultrasound (IVUS). Methods and Results In patients with suspected ACS, randomized to coronary CTA in the ROMICAT II (Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography II) trial, we retrospectively performed semiautomated quantitative analysis of HRP (including remodeling index, plaque burden as derived by plaque area, low computed tomography attenuation plaque volume) and degree of luminal stenosis and analyzed the performance of traditional IVUS thresholds to detect ACS. Furthermore, we derived CTA-specific thresholds in patients with ACS to detect culprit lesions and applied those to all patients to calculate the discriminatory ability to detect ACS in comparison to IVUS thresholds. Of 472 patients, 255 patients (56±7.8 years; 63% men) had coronary plaque. In 32 patients (6.8%) with ACS, culprit plaques (n=35) differed from nonculprit plaques (n=172) with significantly greater values for all HRP features except minimal luminal area (significantly lower; all P P =0.014) and plaque burden (odds ratio: 5.71; P =0.008) were independently associated with ACS but not remodeling index (odds ratio: 0.78; P =0.673). Optimized CTA-specific thresholds for plaque burden (area under the curve: 0.832 versus 0.676) and degree of stenosis (area under the curve: 0.826 versus 0.721) showed significantly higher diagnostic performance for ACS as compared with IVUS-based thresholds (all P P =0.066). Conclusions CTA-specific definitions of HRP features may improve the discrimination of patients with ACS as compared with IVUS-based definitions. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov . Unique identifier: NCT01084239

Background— Data from broad populations have established associations between incidental carotid plaque and vascular events. Among people living with HIV (PLWHIV), the risk of vascular events is increased; however, whether incidental carotid plaque is increased and there is an association between incidental carotid plaque, plaque characteristics, and vascular events among PLWHIV is unclear. Methods and Results— Data from the multi-institutional Research Patient Data Registry were used. Presence and characteristics (high-risk plaque, including spotty calcification and low attenuation) of carotid plaque by computerized tomography among PLWHIV without known vascular disease were described. Data were compared with uninfected controls similar in age, sex, and cardiovascular risk factors, including diabetes mellitus, hyperlipidemia, and cigarette smoking to cases. Primary outcome was an atherosclerotic cardiovascular disease event, and secondary outcome was ischemic stroke. Cohort consisted of 209 PLWHIV (45±10 years, 72% male) and 168 controls. Using computerized tomography, PLWHIV without vascular disease had higher rates of any carotid plaque (34% versus 25%; P =0.04), noncalcified (18% versus 5%; P P =0.03). Over a follow-up of 3 years, 19 atherosclerotic cardiovascular disease events (9 strokes) occurred. Carotid plaque was independently associated with a 3-fold increase in atherosclerotic cardiovascular disease events among PLWHIV (hazard ratio, 2.91; confidence interval, 1.10–7.7, P =0.03) and a 4-fold increased risk of stroke (hazard ratio, 4.43; confidence interval, 1.17–16.70; P =0.02); high-risk plaque was associated with a 3-fold increased risk of atherosclerotic cardiovascular disease events and a 4-fold increased risk of stroke. Conclusions— There is an increase in incidental carotid plaque, noncalcified plaque, and high-risk plaque among PLWHIV, and the presence and characteristics of carotid plaque are associated with subsequent vascular events.

Background— Coronary artery calcification (CAC) may impair diagnostic assessment of coronary computed tomography angiography (CTA). We determined whether CAC affects efficiency of coronary CTA in patients with suspected acute coronary syndrome (ACS). Methods and Results— This is a pooled analysis of ACRIN-PA (American College of Radiology Imaging Network–Pennsylvania) 4005 and the ROMICAT-II trial (Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography) comparing an initial coronary CTA strategy to standard of care in acute chest pain patients. In the CTA arms, we investigated appropriateness of downstream testing, cost, and diagnostic yield to identify patients with obstructive coronary artery disease on subsequent invasive coronary angiography across CAC score strata (Agatston score: 0, >0–10, >10–100, >100–400, >400). Out of 1234 patients (mean age 51±8.8 years), 80 (6.5%) had obstructive coronary artery disease (≥70% stenosis) and 68 (5.5%) had ACS. Prevalence of obstructive coronary artery disease (1%–64%), ACS (1%–44%), downstream testing (4%–72%), and total (2337–8484 US$) and diagnostic cost (2310–6678 US$) increased across CAC strata ( P 400, cost to diagnose one ACS was lowest in this group (19 283 US$ versus 464 399 US$) as compared with patients without CAC. The diagnostic yield of invasive coronary angiography was highest in patients with CAC>400 (87% versus 38%). Conclusions— Downstream testing, total, and diagnostic cost increased with increasing CAC, but were found to be appropriate because obstructive coronary artery disease and ACS were more prevalent in patients with high CAC. In patients with acute chest pain undergoing coronary CTA, cost-efficient testing and excellent diagnostic yield can be achieved even with high CAC burden. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifiers: NCT01084239 and NCT00933400.

Background: AHA/ACC guidelines advise using 7.5% threshold of 10-year risk for atherosclerotic cardiovascular disease (ASCVD) events to determine eligibility for statin therapy. Coronary Computed Tomography Angiography (CTA) provides prognostic information for ASCVD events as well. We tested the hypothesis whether presence of non-obstructive CAD ( Methods: We performed a systematic literature review to identify studies that assessed the prognostic value of coronary CTA findings for ASCVD events. The characteristics of study subjects at baseline, follow-up information, and outcomes were collected. We selected studies that provided hazard ratio (HR) for ASCVD events in patients with non-obstructive CAD and performed a meta-analysis. We incorporated the pooled HR into the standard 10-year ASCVD pooled cohort equation and derived equivalents for the 7.5% 10 year event risk for those with and without non-obstructive CAD and performed a sensitivity analysis using the lower and upper bounds of the confidence intervals of the pooled HR from the meta-analysis. Results: We identified 20 studies (22,036 subjects, 53% male, median follow-up 31 months) that assessed the prognostic value of CAD as detected by CTA. The studies that provided HR for ASCVD events were used for the meta-analysis. The pooled HR for incident ASCVD was 3.2 (95% CI 1.5-6.7). Equivalents for the 7.5% 10 year event risk for those with non-obstructive CAD were as low as 2.0% (African American women) and for those with no CAD as high as 33.8% (African American men). (Table 1) Conclusions: Non-obstructive CAD is an independent predictor of ASCVD events. Incorporating information on the presence of non-obstructive CAD into the AHA/ACC ASCVD risk calculator provides gender and ethnicity specific equivalents for the 7.5% threshold, which may improve efficiency and accuracy of statin therapy.

Background— Acute rest single-photon emission computed tomography-myocardial perfusion imaging (SPECT-MPI) has high predictive value for acute coronary syndrome (ACS) in emergency department patients. Prior studies have shown excellent agreement between rest/stress computed tomography perfusion (CTP) and SPECT-MPI, but the value of resting CTP (rCTP) in acute chest pain triage remains unclear. We sought to determine the diagnostic accuracy of early rCTP, incremental value beyond obstructive coronary artery disease (CAD; ≥50% stenosis), and compared early rCTP to late stress SPECT-MPI in patients with CAD presenting with suspicion of ACS to the emergency department. Methods and Results— In this prespecified subanalysis of 183 patients (58.1±10.2 years; 33% women), we included patients with any CAD by coronary computed tomography angiography (CCTA) from Rule Out Myocardial Infarction Using Computer-Assisted Tomography I. rCTP was assessed semiquantitatively, blinded to CAD interpretation. Overall, 31 had ACS and 48 had abnormal rCTP. Sensitivity and specificity of rCTP for ACS were 48% (95% confidence interval [CI], 30%–67%) and 78% (95% CI, 71%–85%), respectively. rCTP predicted ACS (adjusted odds ratio, 3.40 [95% CI, 1.37–8.42]; P =0.008) independently of obstructive CAD, and sensitivity for ACS increased from 77% (95% CI, 59%–90%) for obstructive CAD to 90% (95% CI, 74%–98%) with addition of rCTP ( P =0.05). In a subgroup undergoing late rest/stress SPECT-MPI (n=81), CCTA/rCTP had noninferior discriminatory value to CCTA/SPECT-MPI (area under the curve, 0.88 versus 0.90; P =0.64) using a noninferiority margin of 10%. Conclusions— Early rCTP provides incremental value beyond obstructive CAD to detect ACS. CCTA/rCTP is noninferior to CCTA/SPECT-MPI to discriminate ACS and presents an attractive alternative to triage patients presenting with acute chest pain. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00990262.

Introduction: Highly sensitive troponin (hsTn) and coronary computed tomography angiography (CCTA) are promising diagnostic tools for triage of acute chest pain patients in the emergency department (ED). We determined whether a diagnostic strategy of initial hsTn I followed by early CCTA improves classification of ACS risk. Methods: We included ED patients with acute chest pain, negative electrocardiogram and conventional troponin who were enrolled in the ROMICAT II trial, randomized to CCTA and had hsTn I (hsVista, Siemens Diagnostics) measured at the time of presentation. The patients were categorized as having hsTn I < the limit of detection ( 99th percentile (>49 pg/mL), or intermediate. Core lab readers assessed CCTA for the presence of ≥50% stenosis and high-risk plaque features (positive remodeling, low CT attenuation Results: Overall, 160 patients met inclusion criteria (mean age 53±8 years, 40% women, ACS during index hospitalization 10.6%, n=19). The ACS rate was 0% (n=0/9) for patients with HsTn I < the limit of detection 8.6% (n=12/139) for patients with intermediate HsTn I and 53.8% (n=7/12) for patients with hsTnI > 99th percentile. No coronary plaque was present in 68 (42.5%), non-obstructive CAD in 70 (43.8%), ≥50% stenosis in 22 (13.8%), and high-risk plaque in 61 (38.1%) patients. The figure shows ACS risk stratification based on hsTn I followed by CCTA. The addition of CCTA increased the number of patients categorized as low risk from 9 to 96 and high risk from 12 to 25 and re-classified 63% of patients (n=100). The net gain in reclassification proportion was 0.47 (95%CI 0.16-0.78; p=0.003) for patients with ACS and 0.59 (95%CI 0.46-0.72; p Conclusions: A strategy of initial hsTn I at the time of ED presentation followed by early CCTA improved classification of ACS risk in patients with acute chest pain.