Is typical angina still prognostically important? The influence of "treatment bias" upon prognostic assessments.

BACKGROUND: Since typical angina has become less frequent, it is unclear if this symptom still has prognostic significance. METHODS: We evaluated 38,383 patients undergoing stress/rest SPECT myocardial perfusion imaging followed for a median of 10.9 years. After dividing patients by clinical symptoms, we evaluated the magnitude of myocardial ischemia and subsequent mortality among medically treated versus revascularized subgroups following testing. RESULTS: Patients with typical angina had more frequent and greater ischemia than other symptom groups, but not higher mortality. Among typical angina patients, those who underwent early revascularization had substantially greater ischemia than the medically treated subgroup, including a far higher proportion with severe ischemia (44.9% vs 4.3%, P < 0.001) and transient ischemic dilation of the LV (31.3% vs 4.7%, P < 0.001). Nevertheless, the revascularized typical angina subgroup had a lower adjusted mortality risk than the medically treated subgroup (HR = 0.72, 95% CI: 0.57-0.92, P = 0.009) CONCLUSIONS: Typical angina is associated with substantially more ischemia than other clinical symptoms. However, the high referral of patients with typical angina patients with ischemia to early revascularization resulted in this group having a lower rather than higher mortality risk versus other symptom groups. These findings illustrate the need to account for "treatment bias" among prognostic studies.

Comparative predictors of mortality among patients referred for stress single-photon emission computed tomography versus positron emission tomography myocardial perfusion imaging.

BACKGROUND: There is currently little information regarding the usage and comparative predictors of mortality among patients referred for single-photon emission computed tomography (SPECT) versus positron emission tomography (PET) myocardial perfusion imaging (MPI) within multimodality imaging laboratories. METHODS: We compared the clinical characteristics and mortality outcomes among 15,718 patients referred for SPECT-MPI and 6202 patients referred for PET-MPI between 2008 and 2017. RESULTS: Approximately two-thirds of MPI studies were performed using SPECT-MPI. The PET-MPI group was substantially older and included more patients with known coronary artery disease (CAD), hypertension, diabetes, and myocardial ischemia. The annualized mortality rate was also higher in the PET-MPI group, and this difference persisted after propensity matching 3615 SPECT-MPI and 3615 PET-MPI patients to have similar clinical profiles. Among the SPECT-MPI patients, the most potent predictor of mortality was exercise ability and performance, including consideration of patients' mode of stress testing and exercise duration. Among the PET-MPI patients, myocardial flow reserve (MFR) was the most potent predictor of mortality. CONCLUSIONS: In our real-world setting, PET-MPI was more commonly employed among older patients with more cardiac risk factors than SPECT-MPI patients. The most potent predictors of mortality in our SPECT and PET-MPI groups were variables exclusive to each test: exercise ability/capacity for SPECT-MPI patients and MFR for PET-MPI patients.

Use of a Single-item Exercise Questionnaire Predicts Prognostic Risk among Patients undergoing Stress PET-MPI.

BACKGROUND: Exercise activity reduces mortality and favorably influences mediators of risk, including myocardial flow reserve (MFR) and chronotropic responsiveness. Comprehensive research regarding the relationship between exercise activity, MFR, and chronotropic response to pharmacological stress, as assessed by heart rate response (HRR) among patients undergoing PET myocardial perfusion imaging (MPI) has not been performed. Thus, we aimed to evaluate the relationship between exercise activity as assessed by a practical single-item questionnaire, MFR and HRR, and longitudinal clinical risk. METHODS: We studied outpatients who underwent pharmacological stress rubidium-82. PET-MPI and answered a self-reported one-item exercise activity questionnaire (0-10 scale) at the time of PET-MPI. HRR was calculated by the following equation: (stress HR-rest HR)/rest HR*100 (%). The primary outcome was death or myocardial infarction. RESULTS: Of 1,686 patients, 221 (13%) patients had hard events during our mean follow up of 3.8 years. Patients were divided into four groups: no/minimal exercise (n=551), low exercise (n=468), moderate exercise (n=485), and high exercise (n=182) based on the questionnaire. MFR and HRR increased with exercise activity in a stepwise manner. By Cox analysis adjusted for clinical and PET-MPI variables including MFR and HRR, exercise activity was independently associated with hard events (HR [95%CI] per activity scale, 0.95 [0.91-0.99]; p=0.028). CONCLUSIONS: Patients with higher exercise activity assessed by a practical single-item questionnaire had higher MFR and HRR. Exercise activity was an independent predictor of hard events in patients undergoing PET-MPI. Because of its ease of use, this single-item questionnaire should be applied among patients undergoing stress MPI.

Decline in typical angina among patients referred for cardiac stress testing.

OBJECTIVE: To evaluate temporal trends in the prevalence of typical angina and its clinical correlates among patients referred for stress/rest SPECT myocardial perfusion imaging (MPI). PATIENTS AND METHODS: We evaluated the prevalence of chest pain symptoms and their relationship to inducible myocardial ischemia among 61,717 patients undergoing stress/rest SPECT-MPI between January 2, 1991 and December 31, 2017. We also assessed the relationship between chest pain symptom and angiographic findings among 6,579 patients undergoing coronary CT angiography between 2011 and 2017. RESULTS: The prevalence of typical angina among SPECT-MPI patients declined from 16.2% between 1991 and 1997 to 3.1% between 2011 and 2017, while the prevalence of dyspnea without any chest pain increased from 5.9 to 14.5% over the same period. The frequency of inducible myocardial ischemia declined over time within all symptom groups, but its frequency among current patients (2011-2017) with typical angina was approximately three-fold higher versus other symptom groups (28.4% versus 8.6%, p < 0.001). Overall, patients with typical angina had a higher prevalence of obstructive CAD on CCTA than those with other clinical symptoms, but 33.3% of typical angina patients had no coronary stenoses, 31.1% had 1-49% stenoses, and 35.4% had ≥ 50% stenoses. CONCLUSIONS: The prevalence of typical angina has declined to a very low level among contemporary patients referred for noninvasive cardiac tests. The angiographic findings among current typical angina patients are now quite heterogeneous, with one-third of such patients having normal coronary angiograms. However, typical angina remains associated with a substantially higher frequency of inducible myocardial ischemia compared to patients with other cardiac symptoms.

Increasing frequency of dyspnea among patients referred for cardiac stress testing.

OBJECTIVE: To assess the frequency, change in prevalence, and prognostic significance of dyspnea among contemporary patients referred for cardiac stress testing. PATIENTS AND METHODS: We evaluated the prevalence of dyspnea and its relationship to all-cause mortality among 33,564 patients undergoing stress/rest SPECT-MPI between January 1, 2002 and December 31, 2017. Dyspnea was assessed as a single-item question. Patients were divided into three temporal groups. RESULTS: The overall prevalence of dyspnea in our cohort was 30.2%. However, there was a stepwise increase in the temporal prevalence of dyspnea, which was present in 25.6% of patients studied between 2002 and 2006, 30.5% of patients studied between 2007 and 2011, and 38.7% of patients studied between 2012 and 2017. There was a temporal increase in the prevalence of dyspnea in each age, symptom, and risk factor subgroup. The adjusted hazard ratio for mortality was higher among patients with dyspnea vs those without dyspnea both among all patients, and within each chest pain subgroup. CONCLUSIONS: Dyspnea has become increasingly prevalent among patients referred for cardiac stress testing and is now present among nearly two-fifths of contemporary cohorts referred for stress-rest SPECT-MPI. Prospective study is needed to standardize the assessment of dyspnea and evaluate the reasons for its increasing prevalence.

Development and validation of ischemia risk scores.

BACKGROUND: The likelihood of ischemia on myocardial perfusion imaging is central to physician decisions regarding test selection, but dedicated risk scores are lacking. We derived and validated two novel ischemia risk scores to support physician decision making. METHODS: Risk scores were derived using 15,186 patients and validated with 2,995 patients from a different center. Logistic regression was used to assess associations with ischemia to derive point-based and calculated ischemia scores. Predictive performance for ischemia was assessed using area under the receiver operating characteristic curve (AUC) and compared with the CAD consortium basic and clinical models. RESULTS: During derivation, the calculated ischemia risk score (0.801) had higher AUC compared to the point-based score (0.786, p < 0.001). During validation, the calculated ischemia score (0.716, 95% CI 0.684- 0.748) had higher AUC compared to the point-based ischemia score (0.699, 95% CI 0.666- 0.732, p = 0.016) and the clinical CAD model (AUC 0.667, 95% CI 0.633- 0.701, p = 0.002). Calibration for both ischemia scores was good in both populations (Brier score  < 0.100). CONCLUSIONS: We developed two novel risk scores for predicting probability of ischemia on MPI which demonstrated high accuracy during model derivation and in external testing. These scores could support physician decisions regarding diagnostic testing strategies.

Mortality risk among patients undergoing exercise versus pharmacologic myocardial perfusion imaging: A propensity-based comparison.

BACKGROUND: The increased risk associated with pharmacologic versus exercise testing is obscured by the higher prevalence of clinical risk factors among pharmacologic patients. Thus, we assessed comparative mortality in a large risk factor-matched group of exercise versus pharmacologic patients undergoing stress/rest SPECT myocardial perfusion imaging (MPI). METHODS: 39,179 patients undergoing stress/rest SPECT-MPI were followed for 13.3 ± 5.0 years for all-cause mortality (ACM). We applied propensity-matching to create pharmacologic and exercise groups with similar risk profiles. RESULTS: In comparison to exercise patients, pharmacologic patients had an increased risk-adjusted hazard ratio for ACM for each level of ischemia: increased by 3.8-fold (95%CI 3.5-4.1) among nonischemic patients, 2.5-fold (95%CI 2.0-3.2) among mildly ischemic patients, and 2.6-fold (95%CI 2.1-3.3) among moderate/severe ischemic patients. Similar findings were observed among a propensity-matched cohort of 10,113 exercise and 10,113 pharmacologic patients as well as in an additional cohort that also excluded patients with noncardiac co-morbidities. CONCLUSIONS: Patients requiring pharmacologic stress testing manifest substantially heightened clinical risk at each level of myocardial ischemia and even when myocardial ischemia is absent. These findings suggest the need to study the pathophysiological drivers of increased risk in association with pharmacologic testing and to convey this risk in clinical reports.

The prevalence and predictors of inducible myocardial ischemia among patients referred for radionuclide stress testing.

BACKGROUND: The frequency of inducible myocardial ischemia has declined in contemporary stress test cohorts, suggesting a need to re-evaluate its optimal use. To-date, however, a comprehensive analysis of the most potent predictors of myocardial ischemia among cardiac stress test patients has not been conducted. METHODS: We assessed 27,615 patients referred for stress-rest SPECT myocardial perfusion imaging between January 1, 2004 and December 31, 2017. Chi-square analysis was used to ascertain the most potent predictors of ischemia. RESULTS: Among our cohort, CAD status (presence/absence of known CAD), rest left ventricular ejection fraction (LVEF), and typical angina were the most potent predictors of ischemia. The frequency of ischemia was only 6.6% among patients with an LVEF > 55% but 38.1% for patients with LVEF < 45% (P < 0.001). The frequency of myocardial ischemia was fourfold higher among patients with known CAD vs no known CAD (28.0% vs 6.5%, P < 0.001) and approximately threefold higher among patients with typical angina vs patients with atypical symptoms (P < 0.001). CONCLUSIONS: The frequency of myocardial ischemia varies markedly according to the common clinical parameters and is particularly high among patients with known CAD, low LVEF, and typical angina. These observations may be used to develop more cost-effective strategies for referring patients for cardiac stress testing.

Prevalence and predictors of automatically quantified myocardial ischemia within a multicenter international registry.

BACKGROUND: The utility of cardiac stress testing depends on the prevalence of myocardial ischemia within candidate populations. However, a comprehensive assessment of the factors influencing frequency of myocardial ischemia within contemporary populations referred for stress testing has not been performed. METHODS: We assessed 19,690 patients undergoing nuclear stress testing from a multicenter registry. The chi-square test was used to assess the relative importance of features for predicting myocardial ischemia. RESULTS: In the overall cohort, LVEF, male gender, and rest total perfusion deficit (TPD) were the top three predictors of ischemia, followed by CAD status, age, typical angina, and CAD risk factors. Myocardial ischemia was observed in 13.6 % of patients with LVEF > 55 %, in 26.2 % of patients with LVEF 45 %-54 %, and in 48.3% among patients with LVEF < 45 % (P < 0.001). A similar pattern was noted for rest TPD (P < 0.001). Men had a threefold higher frequency of ischemia versus women (25.8 % vs. 8.4%, P < 0.001). Although the relative ranking of ischemia predictors varied among centers, LVEF and/or rest TPD were among the two most potent predictors of myocardial ischemia within each center. CONCLUSION: The prevalence of myocardial ischemia varied markedly according to clinical and imaging characteristics. LVEF and rest TPD are robust predictors of myocardial ischemia.

Comparison of diabetes to other prognostic predictors among patients referred for cardiac stress testing: A contemporary analysis from the REFINE SPECT Registry.

BACKGROUND: Diabetes mellitus (DM) is increasingly prevalent among contemporary populations referred for cardiac stress testing, but its potency as a predictor for major adverse cardiovascular events (MACE) vs other clinical variables is not well delineated. METHODS AND RESULTS: From 19,658 patients who underwent SPECT-MPI, we identified 3122 patients with DM without known coronary artery disease (CAD) (DM+/CAD-) and 3564 without DM with known CAD (DM-/CAD+). Propensity score matching was used to control for the differences in characteristics between DM+/CAD- and DM-/CAD+ groups. There was comparable MACE in the matched DM+/CAD- and DM-/CAD+ groups (HR 1.15, 95% CI 0.97-1.37). By Chi-square analysis, type of stress (exercise or pharmacologic), total perfusion deficit (TPD), and left ventricular function were the most potent predictors of MACE, followed by CAD and DM status. The combined consideration of mode of stress, TPD, and DM provided synergistic stratification, an 8.87-fold (HR 8.87, 95% CI 7.27-10.82) increase in MACE among pharmacologically stressed patients with DM and TPD > 10% (vs non-ischemic, exercised stressed patients without DM). CONCLUSIONS: Propensity-matched patients with DM and no known CAD have similar MACE risk compared to patients with known CAD and no DM. DM is synergistic with mode of stress testing and TPD in predicting the risk of cardiac stress test patients.

Metabolic syndrome, fatty liver, and artificial intelligence-based epicardial adipose tissue measures predict long-term risk of cardiac events: a prospective study.

BACKGROUND: We sought to evaluate the association of metabolic syndrome (MetS) and computed tomography (CT)-derived cardiometabolic biomarkers (non-alcoholic fatty liver disease [NAFLD] and epicardial adipose tissue [EAT] measures) with long-term risk of major adverse cardiovascular events (MACE) in asymptomatic individuals. METHODS: This was a post-hoc analysis of the prospective EISNER (Early-Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) study of participants who underwent baseline coronary artery calcium (CAC) scoring CT and 14-year follow-up for MACE (myocardial infarction, late revascularization, or cardiac death). EAT volume (cm3) and attenuation (Hounsfield units [HU]) were quantified from CT using fully automated deep learning software (< 30 s per case). NAFLD was defined as liver-to-spleen attenuation ratio < 1.0 and/or average liver attenuation < 40 HU. RESULTS: In the final population of 2068 participants (59% males, 56 ± 9 years), those with MetS (n = 280;13.5%) had a greater prevalence of NAFLD (26.0% vs. 9.9%), higher EAT volume (114.1 cm3 vs. 73.7 cm3), and lower EAT attenuation (-76.9 HU vs. -73.4 HU; all p < 0.001) compared to those without MetS. At 14 ± 3 years, MACE occurred in 223 (10.8%) participants. In multivariable Cox regression, MetS was associated with increased risk of MACE (HR 1.58 [95% CI 1.10-2.27], p = 0.01) independently of CAC score; however, not after adjustment for EAT measures (p = 0.27). In a separate Cox analysis, NAFLD predicted MACE (HR 1.78 [95% CI 1.21-2.61], p = 0.003) independently of MetS, CAC score, and EAT measures. Addition of EAT volume to current risk assessment tools resulted in significant net reclassification improvement for MACE (22% over ASCVD risk score; 17% over ASCVD risk score plus CAC score). CONCLUSIONS: MetS, NAFLD, and artificial intelligence-based EAT measures predict long-term MACE risk in asymptomatic individuals. Imaging biomarkers of cardiometabolic disease have the potential for integration into routine reporting of CAC scoring CT to enhance cardiovascular risk stratification. Trial registration NCT00927693.

CZT camera systems may provide better risk stratification for low-risk patients.

BACKGROUND: The photon sensitivity and spatial resolution of single-photon emission-computed tomography (SPECT) has been significantly improved by solid-state camera systems using cadmium zinc telluride (CZT) detectors. While the diagnostic accuracy of these systems is well established, there is little evidence directly comparing the prognostic utility to conventional NaI cameras. METHODS AND RESULTS: Retrospective analysis of patients undergoing SPECT between 2008 and 2012. Visual SPECT assessment was performed utilizing the 17-segment model to determine summed stress scores (SSS). We identified 12,830 consecutive patients, mean age 63.2 ± 13.7 and 56.1% male, 5072 of whom underwent CZT and 7758 NaI imaging. During a median follow-up duration of 7.0 years (IQR 5.5-8.2), a total of 2788 (21.7%) patients died. Compared to SSS 0, minimal perfusion abnormality (SSS 1-3) was associated with increased all-cause mortality with CZT camera (adjusted HR 1.32, P = .017) and NaI camera (adjusted HR 1.29, P = .001, interaction P = .803). Increasing stress abnormality was associated with a similar increase in risk with CZT or NaI imaging (interaction P > .500). In a propensity matched analysis, patients with normal perfusion stress perfusion assessed with a CZT was associated with decreased mortality compared to normal perfusion assessed by a NaI camera system (hazard ratio .88, 95% CI .78-.99, P = .040). CONCLUSIONS: Increasing stress perfusion abnormality was associated with similar increase in all-cause mortality with CZT or NaI cameras. CZT and NaI camera systems provide similar risk stratification, however, normal myocardial perfusion may be associated with a more benign prognosis when assessed with a CZT camera system.

Sex differences in calcified plaque and long-term cardiovascular mortality: observations from the CAC Consortium.

Aims: Pathologic evidence supports unique sex-specific mechanisms as precursors for acute cardiovascular (CV) events. Current evidence on long-term CV risk among women when compared with men based on measures of coronary artery calcium (CAC) remains incomplete. Methods and results: A total of 63 215 asymptomatic women and men were enrolled in the multicentre, CAC Consortium with median follow-up of 12.6 years. Pooled cohort equation (PCE) risk scores and risk factor data were collected with the Agatston score and other CAC measures (number of lesions and vessels, lesion size, volume, and plaque density). Cox proportional hazard models were employed to estimate CV mortality (n = 919). Sex interactions were calculated. Women and men had average PCE risk scores of 5.8% and 9.1% (P < 0.001). Within CAC subgroups, women had fewer calcified lesions (P < 0.0001) and vessels (P = 0.017), greater lesion size (P < 0.0001), and higher plaque density (P = 0.013) when compared with men. For women and men without CAC, long-term CV mortality was similar (P = 0.67), whereas detectable CAC was associated with 1.3-higher hazard for CV death among women when compared with men (P < 0001). Cardiovascular mortality was higher among women with more extensive, numerous, or larger CAC lesions. The relative hazard for cardiovascular disease (CVD) mortality for women and men was 8.2 vs. 5.1 for multivessel CAC, 8.6 vs. 5.9 for ≥5 CAC lesions, and 8.5 vs. 4.4 for a lesion size ≥15 mm3, respectively. Additional explorations revealed that women with larger sized and more numerous CAC lesions had 2.2-fold higher CVD mortality (P < 0.0001) as compared to men. Moreover, CAC density was not predictive of CV mortality in women (P = 0.51) but was for men (P < 0.001), when controlling for CAC volume and cardiac risk factors. Conclusion: Our overall findings support that measures beyond the Agatston score provide important clues to sex differences in atherosclerotic plaque and may further refine risk detection and focus preventive strategies of care.

The Synergistic Use of Coronary Artery Calcium Imaging and Noninvasive Myocardial Perfusion Imaging for Detecting Subclinical Atherosclerosis and Myocardial Ischemia.

PURPOSE OF REVIEW: This review aims to assess the synergistic use of coronary artery calcium (CAC) scanning and stress-rest SPECT myocardial perfusion imaging (MPI) for the workup of patients with suspected coronary artery disease (CAD). RECENT FINDINGS: The CAC score bears a proportional relationship to both the frequency of obstructive CAD and inducible ischemia. Consequently, the test can be used to improve the Bayesian assessment of pre-test CAD likelihood and assist in triaging patients for stress testing. The CAC score and MPI findings are synergistic for predicting cardiac risk, which increases for patients with abnormal MPI studies who also have CAC abnormality. CAC scanning also improves the diagnostic sensitivity of SPECT-MPI by identifying normal SPECT-MPI patients with subclinical atherosclerosis. Finally, CAC scanning helps improve the interpretation of borderline SPECT-MPI scan abnormalities. Combined, these findings indicate a clear benefit for incorporating CAC scanning into the diagnostic workup of patients who are candidates for the evaluation of chest pain symptoms by SPECT-MPI.

From Vitality to Vital Exhaustion and Other States of "Tense Tiredness": A New Biopsychosocial Risk Domain.

Fatigue is a common prodromal symptom for various medical conditions, including acute myocardial infarction. Fatigue is also the core component of vital exhaustion, which consists of a specific triad: excessive fatigue, increased irritability, and feelings of demoralization. In this issue of Psychosomatic Medicine, Frestad and Prescott present a meta-analysis of 16 studies, involving 53,337 participants, which found vital exhaustion to be associated with an increased risk of incident coronary heart disease (CHD) and recurrent cardiac events among individuals with established CHD. After discussing methodological limitations of the studies included in this meta-analysis, we describe these findings in terms of a larger genre of risk that is biopsychosocial in origin and tied to two types of tiredness: "calm tiredness" and "tense tiredness." The former is regenerative, while the latter enhances disease risk. We propose that besides vital exhaustion, other symptoms of negative affect may combine with tiredness to produce increased clinical risk, such as the presence of depressed mood, an inability to relax or recover after work, and symptoms of burnout. We further propose that vital exhaustion can be considered as part of a larger paradigm, ranging from a positive state of vitality to a negative state of exhaustion of vitality. We conclude this editorial by emphasizing the importance of improving vitality and the need to clarify biobehavioral mechanisms that play a role in the association between vital exhaustion and adverse CHD outcomes. New interventions are needed that target reducing exhaustion and improving vitality for individuals at high risk of CHD.

Comparison of the current reasons for undergoing pharmacologic stress during echocardiographic and radionuclide stress testing.

BACKGROUND: Symptom-limited exercise is the preferred method of cardiac stress testing, but pharmacologic testing has been increasing over time. The exact reasons for pharmacologic stress testing have not been rigorously categorized. Thus, we systematically explored the reasons for pharmacologic stress testing in patients referred for cardiac stress imaging. METHODS: We studied consecutive patients referred for stress imaging [stress echocardiography or radionuclide myocardial perfusion imaging (MPI)] at Mount Sinai St Luke's hospital between August 2013 and April 2014. Baseline information was obtained using a standardized questionnaire and a trained physician triaged the patient for symptom-limited exercise stress testing or pharmacologic stress testing. RESULTS: In total, 551(48%) of our entire stress cohort underwent cardiac imaging following initial exercise testing and 589 (52%) underwent imaging with initial pharmacologic stress testing. Deconditioning and inability to walk (primarily due to musculoskeletal conditions) constituted the top two reasons for performing pharmacologic stress, followed by frailty, left bundle branch block (for MPI), resting wall motion abnormality (for echocardiography), and failed exercise attempts. The reasons for performing pharmacologic stress testing were similar in the MPI and echocardiography patients, despite a much higher level of disease acuity in the MPI group. CONCLUSIONS: We have applied a systematic approach for categorizing the reasons for pharmacologic stress. These reasons are heterogeneous, but similar across MPI and echo stress laboratories.

Comparative effectiveness of coronary CT angiography vs stress cardiac imaging in patients following hospital admission for chest pain work-up: The Prospective First Evaluation in Chest Pain (PERFECT) Trial.

BACKGROUND: Because the frequency of cardiac event rates is low among chest pain patients following either performance of coronary CT angiography (CCTA) or stress testing, there is a need to better assess how these tests influence the central management decisions that follow from cardiac testing. The present study was performed to assess the relative impact of CCTA vs stress testing on medical therapies and downstream resource utilization among patients admitted for the work-up of chest pain. METHODS: The admitted patients were randomized in a 1:1 ratio to either cardiac imaging stress test or CCTA. Primary outcomes were time to discharge, change in medication usage, and frequency of downstream testing, cardiac interventions, and cardiovascular re-hospitalizations. We randomized 411 patients, 205 to stress testing, and 206 to CCTA. RESULTS: There were no differences in time to discharge or initiation of new cardiac medications at discharge. At 1 year follow-up, there was no difference in the number of patients who underwent cardiovascular downstream tests in the CCTA vs stress test patients (21% vs 15%, P = .1) or cardiovascular hospitalizations (14% vs 16%, P = .5). However, there was a higher frequency of invasive angiography in the CCTA group (11% vs 2%, P = .001) and percutaneous coronary interventions (6% vs 0%, P < .001). CONCLUSIONS: Randomization of hospitalized patients admitted for chest pain work-up to either CCTA or to stress testing resulted in similar discharge times, change in medical therapies at discharge, frequency of downstream noninvasive testing, and repeat hospitalizations. However, a higher frequency of invasive coronary angiography and revascularization procedures were performed in the CCTA arm. (ClinicalTrials.gov number, NCT01604655.).

Purpose in Life and Its Relationship to All-Cause Mortality and Cardiovascular Events: A Meta-Analysis.

OBJECTIVE: To assess the net impact of purpose in life on all-cause mortality and cardiovascular events. METHODS: The electronic databases PubMed, Embase, and PsycINFO were systematically searched through June 2015 to identify all studies investigating the relationship between purpose in life, mortality, and cardiovascular events. Articles were selected for inclusion if, a) they were prospective, b) evaluated the association between some measure of purpose in life and all-cause mortality and/or cardiovascular events, and c) unadjusted and/or adjusted risk estimates and confidence intervals (CIs) were reported. RESULTS: Ten prospective studies with a total of 136,265 participants were included in the analysis. A significant association was observed between having a higher purpose in life and reduced all-cause mortality (adjusted pooled relative risk = 0.83 [CI = 0.75-0.91], p < .001) and cardiovascular events (adjusted pooled relative risk = 0.83 [CI = 0.75-0.92], p = .001). Subgroup analyses by study country of origin, questionnaire used to measure purpose in life, age, and whether or not participants with baseline cardiovascular disease were included in the study all yielded similar results. CONCLUSIONS: Possessing a high sense of purpose in life is associated with a reduced risk for all-cause mortality and cardiovascular events. Future research should focus on mechanisms linking purpose in life to health outcomes, as well as interventions to assist individuals identified as having a low sense of purpose in life.