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Physical inactivity is highly associated with mortality, especially in patients with coronary heart disease. We evaluated the effect of perceived health competence, a patient's belief in his or her ability to achieve health-related goals, on cumulative physical activity levels in the Mid-South Coronary Heart Disease Cohort Study. The Mid-South Coronary Heart Disease Cohort Study consists of 2,587 outpatients (32% were female) with coronary heart disease at an academic medical center network in the United States. Cumulative physical activity was quantified in metabolic equivalent (MET)-minutes per week with the International Physical Activity Questionnaire. We investigated associations between the 2-item Perceived Health Competence Scale (PHCS-2) and MET-minutes/week after adjusting for co-morbidities and psychosocial factors with linear regression. Nearly half of participants (47%) exhibited low physical activity levels (<600 MET-minutes/week). Perceived health competence was highly associated with physical activity after multivariable adjustment. A nonlinear relation was observed, with the strongest effect on physical activity occurring at lower levels of perceived health competence. There was effect modification by gender (p = 0.03 for interaction). The relation between perceived health competence and physical activity was stronger in women compared with men; an increase in the PHCS-2 from 3 to 4 was associated with a 73% increase in MET-minutes/week in women (95% confidence interval 43% to 109%, p <0.0001) compared with a 53% increase in men (95% confidence interval 27% to 84%, p <0.0001). In conclusion, low perceived health competence was strongly associated with less physical activity in patients with coronary heart disease and may represent a potential target for behavioral interventions., (Published by Elsevier Inc.)

RG7652 (MPSK3169A), a fully human immunoglobulin G1 (IgG1) monoclonal antibody directed against proprotein convertase subtilisin/kexin type 9 (PCSK9), blocks the interaction between PCSK9 and low-density lipoprotein (LDL) receptor. EQUATOR (ClinicalTrials.govNCT01609140), a randomized, double-blind, and dose-ranging phase 2 study, evaluated RG7652 in patients (1) at high risk for or (2) with coronary heart disease (CHD). The primary end point was change in LDL cholesterol (LDL-C) from baseline to day 169. Patients (n = 248; median age, 64 years; 57% men; 52% with established CHD; 82% on statins) with baseline LDL-C levels of 90 to 250 mg/dl (mean, 126 mg/dl) continuing on standard-of-care therapy were randomized to receive 1 of 5 RG7652 doses or placebo, subcutaneously every 4, 8, or 12 weeks for 24 weeks. Significant dose-dependent reductions in LDL-C levels from baseline to nadir (56 to 74 mg/dl [48% to 60%]) were observed in all RG7652-dosed patients; effects persisted to day 169 with the highest doses (reduction vs placebo up to 62 mg/dl [51%]) with no unexpected safety signals. RG7652 reduced apolipoprotein B and lipoprotein(a) levels. LDL-C subfraction analysis by nuclear magnetic resonance spectroscopy revealed a prominent decrease in large LDL-C and some decrease in small LDL particles. There was significant reduction in mean particle size of LDL-C on day 169 but no significant reductions in systemic markers of inflammation (high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-alpha). RG7652 reduced LDL-C levels and was well tolerated in patients at high risk for or with CHD on standard-of-care therapy. In conclusion, RG7562 treatment affected large LDL-C and, to a lesser extent, small LDL-C particles; RG7562 did not affect systemic circulating pro-inflammatory cytokines or high-sensitivity C-reactive protein., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Although the prevalence of coronary heart disease (CHD) in the United States has increased during the past 25 years, cardiovascular mortality has decreased due to advances in CHD therapy and prevention. We sought to determine the proportion of patients with CHD who die from cardiovascular versus noncardiovascular causes and the causes and predictors of death, in a cohort of patients with CHD. The Heart and Soul Study enrolled 1,024 participants with stable CHD from 2000 to 2002 and followed them for 10 years. Causes of mortality were assigned based on detailed review of medical records, death certificates, and coroner reports by blinded adjudicators. During 7,680 person-years of follow-up, 401 participants died. Of these deaths, 42.4% were cardiovascular and 54.4% were noncardiovascular. Myocardial infarction, stroke, and sudden death accounted for 72% of cardiovascular deaths. Cancer, pneumonia, and sepsis accounted for 67% of noncardiovascular deaths. Independent predictors of cardiac mortality were older age, inducible ischemia on stress echocardiography, higher heart rate at rest, smoking, lower hemoglobin, and higher N-terminal pro-brain natriuretic peptide (all p values <0.05); independent predictors of noncardiac mortality included older age, inducible ischemia, higher heart rate, lower exercise capacity, and nonuse of statins (all p values <0.05). In conclusion, mortality in this cohort was more frequently due to noncardiovascular causes, and predictors of noncardiovascular mortality included factors traditionally associated with cardiovascular mortality., (Published by Elsevier Inc.)

Left ventricular hypertrophy (LVH) diagnosed by electrocardiography (ECG-LVH) and echocardiography (echo-LVH) are independently associated with an increased risk of cardiovascular disease (CVD) events. However, it is unknown if ECG-LVH retains its predictive properties independent of LV anatomy. We compared the risk of CVD associated with ECG-LVH and echo-LVH in 4,076 participants (41% men, 86% white) from the Cardiovascular Health Study, who were free of baseline CVD. ECG-LVH was defined with Minnesota ECG Classification criteria from baseline ECG data. Echo-LVH was defined by gender-specific LV mass values normalized to body surface area (male: >102 g/m(2); female: >88 g/m(2)). ECG-LVH was detected in 144 participants (3.5%) and echo-LVH in 430 participants (11%). Over a median follow-up of 10.6 years, 2,274 CVD events occurred. In a multivariate Cox regression analysis adjusted for common CVD risk factors, ECG-LVH (hazard ratio [HR] 1.84, 95% CI 1.51 to 2.24) and echo-LVH (HR 1.35, 95% CI 1.19 to 1.54) were associated with an increased risk for CVD events. The association between ECG-LVH and CVD events was not substantively altered with further adjustment for echo-LVH (HR 1.76, 95% CI 1.45 to 2.15). In conclusion, the association of ECG-LVH with CVD events is not dependent on echo-LVH. This finding provides support to the concept that ECG-LVH is an electrophysiological marker with predictive properties independent of LV anatomy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Outcomes of percutaneous coronary intervention (PCI) versus medical therapy (MT) in the management of stable ischemic heart disease (SIHD) remain controversial, with some but not all studies showing improved results in patients with ischemia. We sought to elucidate whether PCI improves mortality compared to MT in patients with objective evidence of ischemia (assessed using noninvasive imaging or its invasive equivalent). We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing PCI to MT in patients with SIHD. To maintain a high degree of specificity for ischemia, studies were only included if ischemia was defined on the basis of noninvasive stress imaging or abnormal fractional flow reserve. The primary outcome was all-cause mortality. We identified 3 RCTs (Effects of Percutaneous Coronary Interventions in Silent Ischemia After Myocardial Infarction II, Fractional Flow Reserve versus Angiography for Multivessel Evaluation 2, and a substudy of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation trial) enrolling a total of 1,557 patients followed for an average of 3.0 years. When compared with MT in this population of patients with objective ischemia, PCI was associated with lower mortality (hazard ratio 0.52, 95% confidence interval 0.30 to 0.92, p=0.02). There was no evidence of study heterogeneity or bias among included trials. In this meta-analysis of published RCTs, PCI was shown to have a mortality benefit over MT in patients with SIHD and objective assessment of ischemia using noninvasive imaging or its invasive equivalent. In conclusion, this study provides insight into the management of a higher-risk SIHD population that is the focus of the ongoing International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The extent to which angina pectoris (AP) predicts secondary cardiovascular events beyond independent of measures of disease severity is unknown. We evaluated the association between AP frequency and secondary events in patients with stable coronary heart disease (CHD). We administered the Seattle Angina Questionnaire to 1,023 participants with stable CHD enrolled from September 2000 to December 2002 and followed for a median of 8.9 years. We used Cox proportional hazards to evaluate the association of AP frequency with death and subsequent hospitalization for AP, revascularization, myocardial infarction (MI), or heart failure. At enrollment, 633 (62%) participants reported no AP, 279 (27%) reported monthly AP, and 111 (11%) reported daily or weekly AP. During follow-up, 396 participants died, 204 were hospitalized for AP, 194 for revascularization, 140 for MI, and 188 for heart failure. Compared with participants without AP, participants with daily or weekly AP were more likely to be hospitalized for AP (hazard ratio [HR] 3.3; 95% confidence interval [CI] 2.3 to 4.7; p<0.001), revascularization (HR 2.0; 95% CI 1.3 to 2.9; p=0.001), or heart failure (HR 1.6; 95% CI 1.0 to 2.5; p=0.03) and more likely to die (HR 1.5; 95% CI 1.1 to 2.0; p=0.01). AP was not independently associated with MI (HR 1.3; 95% CI 0.8 to 2.3; p=0.29). After adjusting for demographics, co-morbidities, treadmill exercise capacity, ejection fraction, and inducible ischemia, frequency of AP remained independently associated with hospitalization for AP (HR 2.4; 95% CI 1.6 to 3.6; p<0.001), revascularization (HR 1.7; 95% CI 1.1 to 2.7; p=0.02), and death (HR 1.4; 95% CI 1.0 to 2.0; p=0.045). In conclusion, in outpatients with stable CHD, AP frequency predicts higher rates of secondary cardiovascular events and death, independent of objective measures of disease severity., (Copyright © 2014 Elsevier Inc. All rights reserved.)

This study sought to determine whether left atrial (LA) dysfunction independently predicts ischemic stroke. Atrial fibrillation (AF) impairs LA function and is associated with ischemic stroke. However, ischemic stroke frequently occurs in patients without known AF. The direct relation between LA function and risk of ischemic stroke is unknown. We performed transthoracic echocardiography at rest in 983 subjects with stable coronary heart disease. To quantify LA dysfunction, we used the left atrial function index (LAFI), a validated formula incorporating LA volumes at end-atrial systole and diastole. Cox proportional hazards models were used to evaluate the association between LAFI and ischemic stroke or transient ischemic attack (TIA). Over a mean follow-up of 7.1 years, 58 study participants (5.9%) experienced an ischemic stroke or TIA. In patients without known baseline AF or warfarin therapy (n = 893), participants in the lowest quintile of LAFI had >3 times the risk of ischemic stroke or TIA (hazard ratio 3.3, 95% confidence interval 1.1 to 9.7, p = 0.03) compared with those in the highest quintile. For each standard deviation (18.8 U) decrease in LAFI, the hazard of ischemic stroke or TIA increased by 50% (hazard ratio 1.5, 95% confidence interval 1.0 to 2.1, p = 0.04). Among measured echocardiographic indexes of LA function, including LA volume, LAFI was the strongest predictor of ischemic stroke or TIA. In conclusion, LA dysfunction is an independent risk factor for stroke or TIA, even in patients without baseline AF., (Published by Elsevier Inc.)

The predictive ability of the CHADS2 index to stratify stroke risk may be mechanistically linked to severity of left atrial (LA) dysfunction. This study investigated the association between the CHADS2 score and LA function. We performed resting transthoracic echocardiography in 970 patients with stable coronary heart disease and normal ejection fraction and calculated baseline LA functional index (LAFI) using a validated formula: (LA emptying fraction×left ventricular outflow tract velocity time integral)/LA end-systolic volume indexed to body surface area. We performed regression analyses to evaluate the association between risk scores and LAFI. Among 970 subjects, mean CHADS2 was 1.7±1.2. Mean LAFI decreased across tertiles of CHADS2 (42.8±18.1, 37.8±19.1, 36.7±19.4, p<0.001). After adjustment for age, sex, race, systolic blood pressure, hyperlipidemia, myocardial infarction, revascularization, body mass index, smoking, and alcohol use, high CHADS2 remained associated with the lowest quartile of LAFI (odds ratio 2.34, p=0.001). In multivariable analysis of component co-morbidities, heart failure, age, and creatinine clearance<60 ml/min were strongly associated with LA dysfunction. For every point increase in CHADS2, the LAFI decreased by 4.0%. Secondary analyses using CHA2DS2-VASc and R2CHADS2 scores replicated these results. Findings were consistent when excluding patients with baseline atrial fibrillation. In conclusion, CHADS2, CHA2DS2-VASc, and R2CHADS2 scores are associated with LA dysfunction, even in patients without baseline atrial fibrillation. These findings merit further study to determine the role of LA dysfunction in cardioembolic stroke and the value of LAFI for risk stratification., (Published by Elsevier Inc.)

The association between incomplete revascularization (IR) and long-term mortality after stenting in the era of drug-eluting stents is not well understood. In the present study, we test the hypothesis that IR is associated with a greater risk of long-term (5-year) mortality after stenting for multivessel coronary disease. Using data from the Percutaneous Coronary Intervention Reporting System of New York State, 21,767 patients with multivessel disease who underwent stenting during October 2003 to December 2005 were identified. Complete revascularization (CR) was achieved in 6,844 patients (31.4%), and 14,923 patients (68.6%) were incompletely revascularized. The CR and IR patients were propensity matched on a 1:1 ratio on the number of diseased vessels, the presence of total occlusion, type of stents, and the probability of achieving CR estimated using a logistic model with established risk factors as independent variables. Patients were followed for vital status until December 31, 2008 using the National Death Index. Differences in survival between the matched CR and IR patients were compared. Among the 6,511 pairs of propensity-matched patients, the 5-year survival rate for IR was lower compared with CR (79.3% vs 81.4%, p = 0.004), and the risk of death during follow-up was 16% greater for IR compared with CR (hazard ratio 1.16, 95% confidence interval 1.06 to 1.27, p = 0.001). In addition, subgroup analyses demonstrated that the association between IR and long-term mortality was not dependent on major patient risk factors. In conclusion, IR is associated with an increased risk of long-term mortality after stenting for multivessel disease in the era of drug-eluting stents., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The national observational study of diagnostic and interventional cardiac catheterization (ONACI) is a prospective multicenter registry of the French Society of Cardiology including all interventional cardiology procedures performed from 2004. We aimed to evaluate "real-world" management of patients with coronary artery disease in France from this registry. The present study was focused on data collected from 2004 to 2008. Patient demographics and co-morbidities, invasive parameters, treatment options, and procedural techniques were prospectively collected. Patients were recruited from 99 hospitals (55% of patients were hospitalized in private clinics and 45% in public institutions). During a 5-year period, a total of 298,105 patients underwent coronary angiography and 176,166 patients underwent percutaneous coronary intervention. Diagnosis was acute coronary syndrome in 22%, stable angina or silent ischemia in 23%, and atypical chest pain in 9% of cases. Normal coronary arteries or nonsignificant coronary narrowing were found in 26% of patients. Radial access was increasingly used over the years regardless of the indication. The average number of percutaneous coronary interventions per procedure was 1.5 ± 0.7 (range, 1.3 ± 0.7 to 1.5 ± 0.7) and that of stents per procedure was 1.5 ± 0.8 (range, 1.5 ± 0.8 to 1.6 ± 0.8). Drug-eluting stents were used in 45% (range, 34% to 62%), increasing from 2004 to 2006, and then decreasing after the 2006 controversy. In conclusion, ONACI is one of the largest catheterization registries during this period, providing a detailed and comprehensive global description of the spectrum and management of patients with suspected coronary artery disease undergoing cardiac catheterization., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Women with angina pectoris and abnormal stress test findings commonly have no epicardial coronary artery disease (CAD) at catheterization. The aim of the present study was to develop a risk score to predict obstructive CAD in such patients. Data were analyzed from 337 consecutive women with angina pectoris and abnormal stress test findings who underwent cardiac catheterization at our center from 2003 to 2007. Forward selection multivariate logistic regression analysis was used to identify the independent predictors of CAD, defined by ≥50% diameter stenosis in ≥1 epicardial coronary artery. The independent predictors included age ≥55 years (odds ratio 2.3, 95% confidence interval 1.3 to 4.0), body mass index <30 kg/m(2) (odds ratio 1.9, 95% confidence interval 1.1 to 3.1), smoking (odds ratio 2.6, 95% confidence interval 1.4 to 4.8), low high-density lipoprotein cholesterol (odds ratio 2.9, 95% confidence interval 1.5 to 5.5), family history of premature CAD (odds ratio 2.4, 95% confidence interval 1.0 to 5.7), lateral abnormality on stress imaging (odds ratio 2.8, 95% confidence interval 1.5 to 5.5), and exercise capacity <5 metabolic equivalents (odds ratio 2.4, 95% confidence interval 1.1 to 5.6). Assigning each variable 1 point summed to constitute a risk score, a graded association between the score and prevalent CAD (ptrend <0.001). The risk score demonstrated good discrimination with a cross-validated c-statistic of 0.745 (95% confidence interval 0.70 to 0.79), and an optimized cutpoint of a score of ≤2 included 62% of the subjects and had a negative predictive value of 80%. In conclusion, a simple clinical risk score of 7 characteristics can help differentiate those more or less likely to have CAD among women with angina pectoris and abnormal stress test findings. This tool, if validated, could help to guide testing strategies in women with angina pectoris., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Several coronary disease scoring systems have been developed to predict procedural risk during revascularization. Many vary in complexity, do not specifically account for myocardium at risk, and are not applicable across all patient subsets. The British Cardiovascular Intervention Society myocardial jeopardy score (BCIS-JS) addresses these limitations and is applicable to all patients, including those with coronary artery bypass grafts or left main stem disease. We assessed the prognostic relevance of the BCIS-JS in patients undergoing percutaneous coronary intervention (PCI). A total of 663 patients who underwent PCI with previous left ventricular function assessment were retrospectively assessed for inclusion, incorporating 221 with previous coronary artery bypass grafting. Blinded observers calculated the BCIS-JS, before (BCIS-JS(PRE)) and after (BCIS-JS(POST)) PCI, using the revascularization index (RI) (RI = [BCIS-JS(PRE) - BCIS-JS(POST)]/BCIS-JS(PRE)), quantifying the extent of revascularization, 1 indicating full revascularization and 0 indicating no revascularization. The primary end point all-cause mortality, tracked via the Office of National Statistics. A total of 660 patients were included (66 ± 10.7 years), with 43 deaths (6.5%) occurring during 2.6 ± 1.1 years after PCI. All-cause mortality was directly related to BCIS-JS(PRE) (hazard ratio [HR] 2.96, 95% confidence interval [CI] 1.71 to 5.15, p = 0.001) and BCIS-JS(POST) (HR 4.02, 95% CI 2.41 to 6.68, p = 0.001). A RI of <0.67 was associated with increased mortality compared to a RI of ≥0.67 (HR 4.13, 95% CI 1.91 to 8.91, p = 0.0001). On multivariate analysis, a RI <0.67 (HR 1.99, 95% CI 1.03 to 3.87, p = 0.04), left ventricular dysfunction (HR 2.03, 95% CI 1.25 to 3.30, p = 0.004) and renal impairment (HR 3.75, 95% CI 1.48 to 8.64, p = 0.005) were independent predictors of mortality. In conclusion, the BCIS-JS predicts mortality after PCI and can assess the degree of revascularization, with more complete revascularization conferring a survival advantage in the medium term., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The prognostic relevance of quantitative an intracoronary occlusive electrocardiographic (ECG) ST-segment shift and its determinants have not been investigated in humans. In 765 patients with chronic stable coronary artery disease, the following simultaneous quantitative measurements were obtained during a 1-minute coronary balloon occlusion: intracoronary ECG ST-segment shift (recorded by angioplasty guidewire), mean aortic pressure, mean distal coronary pressure, and mean central venous pressure (CVP). Collateral flow index (CFI) was calculated as follows: (mean distal coronary pressure minus CVP)/(mean aortic pressure minus CVP). During an average follow-up duration of 50 ± 34 months, the cumulative mortality rate from all causes was significantly lower in the group with an ST-segment shift <0.1 mV (n = 89) than in the group with an ST-segment shift ≥0.1 mV (n = 676, p = 0.0211). Factors independently related to intracoronary occlusive ECG ST-segment shift <0.1 mV (r(2) = 0.189, p <0.0001) were high CFI (p <0.0001), intracoronary occlusive RR interval (p = 0.0467), right coronary artery as the ischemic region (p <0.0001), and absence of arterial hypertension (p = 0.0132). "High" CFI according to receiver operating characteristics analysis was ≥0.217 (area under receiver operating characteristics curve 0.647, p <0.0001). In conclusion, absence of ECG ST-segment shift during brief coronary occlusion in patients with chronic coronary artery disease conveys a decreased mortality and is directly influenced by a well-developed collateral supply to the right versus left coronary ischemic region and by the absence of systemic hypertension in a patient's history., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Cardiac allograft vasculopathy (CAV) is a major impediment to long-term graft survival after heart transplantation. Intravascular ultrasound (IVUS) is more sensitive than coronary angiography for diagnosis, but the identification of specific plaque components or plaque composition is limited. In addition, there is an evident need for other noninvasive tools for diagnosing CAV. The aim of this study was to assess the utility of 2 new techniques for evaluating CAV: optical coherence tomography (OCT), and new high-sensitivity troponin T (hsTnT) assays. In 21 heart transplantation patients, coronary arteriography with IVUS and OCT were performed. Maximal intimal thickness (MIT) and luminal area at the most severe site were measured using the 2 techniques. Immediately before cardiac catheterization, blood samples were obtained and hsTnT levels measured. The evaluation of CAV by OCT showed a good correlation with IVUS measurements, with a mean difference in MIT of 0.0033 (95% confidence interval -0.049 to 0.043), taking advantage of lower interobserver variability (r = 0.94 for OCT vs r = 0.78 for IVUS) and better plaque characterization. When independent predictors of MIT were assessed in a multiple linear regression model, time after transplantation (β = 0.488, p = 0.004) and hsTnT (β = 0.392, p = 0.011) were the only independent predictors of MIT (R(2) = 0.591). In conclusion, this study is the first to evaluate 2 new techniques, OCT and hsTnT, in the challenging setting of CAV. The findings suggest that OCT provides lower interobserver variability and better plaque characterization than IVUS. Also, hsTnT could become a useful tool for ruling out CAV., (Copyright © 2012 Elsevier Inc. All rights reserved.)

This study compared strain values from 2-dimensional (2D) and real-time 3-dimensional (3D) speckle tracking with hyperenhancement transmural extent by magnetic resonance imaging (MRI). The study included 18 control subjects (mean age 51 ± 10 years) and 25 patients (20 men, mean age 62 ± 16 years) with ischemic left ventricular (LV) dysfunction (mean LV ejection fraction 41 ± 9%) referred for viability assessment using MRI. Longitudinal, radial, and circumferential strain values were computed using 2D speckle tracking. From analysis of 3D speckle tracking, conventional strain markers (longitudinal, radial, and circumferential) and 2 new 3D strain indexes (area and 3D strains) were obtained from apical view 3D datasets. A hyperenhancement transmural extent segment (16-segment model) was defined as delayed contrast enhancement >50%. Overall, 661 of 688 segments (96%) were analyzable by MRI and 3D speckle tracking. All 3D strain components in hyperenhancement transmural extent segments (n = 154) were lower than in nontransmural necrosis (n = 219) and control (n = 288) segments. Longitudinal strain by 3D, but not by 2D, differentiated nontransmural segments with scar <25%. All 3D global strain indexes correlated with LV ejection fraction (r(2) = 0.67 to 0.26, p <0.05 for all comparisons), whereas only area, longitudinal, and circumferential 3D strains correlated with global scar extent. The best reproducibility was provided by 3D longitudinal (6%) and area (8%) strains. In conclusion, longitudinal and area strains by 3D speckle tracking provide an accurate and reproducible measurement of myocardial deformation that correlate with infarct size in patients with ischemic LV dysfunction., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Preβ-1 high-density lipoprotein (HDL) plays a key role in reverse cholesterol transport by promoting cholesterol efflux. Our aims were (1) to test previous associations between preβ-1 HDL and coronary heart disease (CHD) and (2) to investigate whether preβ-1 HDL levels also are associated with risk of myocardial infarction (MI). Plasma preβ-1 HDL was measured by an ultrafiltration-isotope dilution technique in 1,255 subjects recruited from the University of California-San Francisco Lipid and Cardiovascular Clinics and collaborating cardiologists. Preβ-1 HDL was significantly and positively associated with CHD and MI even after adjustment for established risk factors. Inclusion of preβ-1 HDL in a multivariable model for CHD led to a modest improvement in reclassification of subjects (net reclassification index 0.15, p = 0.01; integrated discrimination improvement 0.003, p = 0.2). In contrast, incorporation of preβ-1 HDL into a risk model of MI alone significantly improved reclassification of subjects (net reclassification index 0.21, p = 0.008; integrated discrimination improvement 0.01, p = 0.02), suggesting that preβ-1 HDL has more discriminatory power for MI than for CHD in our study population. In conclusion, these results confirm previous associations between preβ-1 HDL and CHD in a large well-characterized clinical cohort. Also, this is the first study in which preβ-1 HDL was identified as a novel and independent predictor of MI above and beyond traditional CHD risk factors., (Copyright © 2011. Published by Elsevier Inc.)

The objective of the present study was to evaluate the association between adiponectin levels and incidence of coronary heart disease (CHD). We performed a prospective case-control analysis nested in the EPIC-Norfolk cohort. Participants were apparently healthy men and women 45 to 79 years of age who developed fatal or nonfatal CHD during an average follow-up period of 7.7 ± 1.1 years. In total 1,035 participants with incident CHD were matched for age, gender, and enrollment time to 1,920 controls who remained free of CHD over the study follow-up. Baseline nonfasting plasma adiponectin concentrations were determined by enzyme-linked immunosorbent assay. Adiponectin levels were lower in participants with CHD than in matched controls (men 8.74 vs 9.13 μg/ml, p = 0.01; women 12.6 vs 13.4 μg/ml, p = 0.03). A 1-μg/ml increment in adiponectin was associated with decreased CHD risk (odds ratio 0.78, 95% confidence interval 0.63 to 0.96, p = 0.02, in men; odds ratio 0.73, 95% confidence interval 0.55 to 0.96, p = 0.03, in women). However, this association was no longer significant after adjustment for established cardiovascular risk factors. Stratification of participants according to metabolic syndrome status showed that men and women with metabolic syndrome had a higher CHD risk, irrespective of their adiponectin levels. In conclusion, although a low adiponectin concentration is associated with an increased CHD risk, findings of the present study do not suggest that its measurement is useful to refine CHD risk assessment once traditional risk factors and clinical features of the metabolic syndrome have been considered., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The prevalence and clinical correlates of left ventricular (LV) wall motion abnormalities (WMAs), associated with morbidity and mortality, have not been well-characterized in the population. Framingham Heart Study Offspring Cohort participants (n = 1,794, 844 men, age 65 ± 9 years) underwent cine cardiovascular magnetic resonance for evaluation of LV function. A subset (n = 1,009, 460 men) underwent cardiac multidetector computed tomography for analysis of coronary artery calcium. The presence of coronary heart disease and heart failure (CHD-HF) were assessed in relation to the presence of WMAs. WMAs were present in 117 participants (6.5%) and were associated with male gender, elevated hemoglobin A1c, LV mass, LV end-diastolic volume, and lower LV ejection fraction. Of the 1,637 participants without CHD-HF, 68 (4.2%) had WMAs. In this group, WMAs were associated with obesity, hypertension, and Framingham coronary heart disease risk score in the age- and gender-adjusted analyses and were associated with male gender and hypertension on multivariate analysis. Most subjects with WMAs were in the greatest coronary artery calcium groups. The presence of coronary artery calcium greater than the seventy-fifth percentile and Agatston score >100 were associated with a greater than twofold risk of WMAs in the age- and gender-adjusted analysis but were no longer significant when additionally adjusted for CHD-HF. Previous Q-wave myocardial infarction was present in 29% of the 117 participants with WMAs. In conclusion, in the present longitudinally followed free-living population, 4.2% of the participants without CHD-HF had WMAs. WMAs were associated with the clinical parameters associated with cardiovascular disease risk. Aggressive risk factor modification may be prudent for subjects with WMAs, particularly those free of clinical CHD-HF., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Improved accuracy in predicting coronary heart disease (CHD) risk in patients with diabetes and kidney disease is needed. The addition of albuminuria to established methods of CHD risk calculation was reported in the Strong Heart Study (SHS) cohort. In this study, the addition of estimated glomerular filtration rate (eGFR) was evaluated using data from 4,549 American Indian SHS participants aged 45 to 74 years. After adjustment for Framingham CHD risk factors, hazard ratios for eGFR as a predictor of CHD were 1.69 (95% confidence interval 1.34 to 2.13) in women and 1.41 (95% confidence interval 0.94 to 2.13) in men. Models including albuminuria, eGFR, or both scored higher in discriminatory power than models using conventional risk factors alone in women; in men, the improvement was seen only for albuminuria and the combination of albuminuria and eGFR. Hosmer-Lemeshow assessments showed good calibration for the models using eGFR alone in both genders, followed by models including albuminuria alone in both genders. Adding eGFR improved the net reclassification improvement (NRI) in women (0.085, p = 0.0004) but not in men (0.010, p = 0.1967). NRI and integrated discrimination improvement (IDI) were improved in both genders using albuminuria and eGFR (NRI 0.135, p <0.0001, and IDI 0.027, p <0.0001 in women; NRI 0.035, p <0.0196, and IDI 0.008, p <0.0156 in men). Therefore, a risk calculator including albuminuria enhances CHD prediction compared to a calculator using only standard risk factors in men and women. Including eGFR alone improves risk prediction in women, but for men, it is preferable to include eGFR and albuminuria. In conclusion, this enhanced calculator should be useful in estimating CHD risk in populations with high prevalence of diabetes and renal disease., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Little is known about electrocardiographic (ECG) characteristics of menopausal women with or at increased risk of coronary heart disease (CHD). Data from 10,101 participants in the Raloxifene Use for The Heart (RUTH) trial were used to correlate baseline ECG abnormalities with clinical characteristics. Baseline characteristics that were statistically significantly associated (p ≤ 0.05) with ECG findings in univariate analyses were used to derive multivariate model selection. Of 59% normal electrocardiograms, 50% were from women with CHD and 69% from women at increased risk of CHD. In the women with CHD, 59% reported a previous myocardial infarction (MI); 43% had a normal electrocardiogram, and 49% had a definite ECG Q-wave MI. Women in the increased-risk group had not reported a previous MI, yet 11% had a definite ECG Q-wave MI. Of women reporting hypertension, 35% had ECG evidence of left ventricular hypertrophy, but 58% did not have an abnormal electrocardiogram. Significantly more women with diabetes in the increased-risk and documented CHD cohorts had abnormal electrocardiograms (p < 0.01 for the 2 cohorts). Percent abnormal electrocardiograms increased with increasing age (55 to 64, 65 to 74, and ≥ 75 years, p < 0.01) in all cohorts. Angina and coronary artery bypass graft surgery, but not percutaneous coronary intervention, predicted an abnormal electrocardiogram. In conclusion, there were high percentages of normal electrocardiograms in the increased-risk and documented CHD groups of RUTH participants, with substantial discrepancy between MI history and ECG MI documentation, and increasing age was the predominant correlate with an abnormal electrocardiogram in all 3 cohorts., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Electrocardiographic (ECG) Q- and ST-T-wave abnormalities predict coronary heart disease (CHD) and total mortality. No comparison has been made of the classification of these abnormalities by the 2 most widely used ECG coding systems for epidemiologic studies-the Minnesota Code (MC) and Novacode (NC). We evaluated 12-lead electrocardiograms from 64,597 participants (49 to 79 years old, 82% non-Hispanic white) in the Women's Health Initiative clinical trial in 1993 to 1998, with a maximum of 11 years of follow-up. We used MC and NC criteria to identify Q-wave, ST-segment, and T-wave abnormalities for comparison. In total, 3,322 participants (5.1%) died during an average 8-year follow-up, and 1,314 had incident CHD in the baseline cardiovascular disease-free group. Independently, ECG myocardial infarction criteria by the MC or NC were generally equivalent and were strong predictors for CHD death and total mortality (hazard ratio 1.62, 95% confidence interval 1.05 to 2.51 for CHD death; hazard ratio 1.36, 95% confidence interval 1.09 to 1.71 for total mortality) in a multivariable analytic model. Electrocardiograms with major ST-T abnormalities by the MC or NC coding system were stronger in predicting CHD deaths and total mortality than was the presence of Q waves alone. In conclusion, the ECG classification systems for myocardial infarction/ischemia abnormalities from the MC and NC are valuable and useful in clinical trials and epidemiologic studies. ST-T abnormalities are stronger predictors for CHD events and total mortality than isolated Q-wave abnormalities., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Cross-sectional studies have reported inverse associations of B-type natriuretic peptide (BNP) with the body mass index (BMI). We evaluated whether changes in the BMI are associated with changes in BNP. A nested prospective cohort study of a lifestyle intervention (low-fat, whole-foods diet, exercise, stress management, and social support) was conducted. BNP, BMI, and other biomarkers were measured at baseline and 3 months. A total of 131 subjects, 56 with coronary heart disease (CHD) and 75 at high risk, with > or =3 CHD risk factors and/or diabetes mellitus, were enrolled. At 3 months, the mean BMI had decreased (34.4 to 31.7 kg/m(2), p <0.001), BNP had increased (median 18 to 28 pg/ml, p <0.001), and low-density lipoprotein, C-reactive protein, apolipoprotein B (all p <0.002), and angina frequency (p = 0.017) and severity (p = 0.052) had decreased. The subjects' physical limitations had decreased and their physical functioning had improved (all p <0.001). The percentage of change in BNP was inversely associated with the percentage of change in insulin (r = -0.339, p = 0.005, n = 63 nondiabetics). It was also inversely associated with the percentage of change in BMI (r = -0.28, p = 0.002, n = 116), and this association remained significant (p = 0.029) in multiple regression analyses controlling for age, gender, CHD, diabetes mellitus, percentage of change in lifestyle index, and beta-blocker use. The metabolic changes related to adipose tissue lipolysis could explain these findings. In conclusion, BNP increased in subjects experiencing weight loss while following a lifestyle intervention, and angina pectoris, physical limitations, and other CHD risk factors decreased. Therefore, in this context, increasing BNP might not indicate worsening disease or a worsening prognosis. Thus, the proposed use of BNP in monitoring disease progression should take into account changes in the BMI during the same period., (Copyright 2010 Elsevier Inc. All rights reserved.)

Previous studies have compared bivalirudin and unfractionated heparin (UFH) plus the routine use of glycoprotein IIb/IIIa inhibitors. They have demonstrated that bivalirudin can decrease bleeding complications without a significant increase in ischemic complications, resulting in a better net clinical outcome, as defined by the efficacy (ischemic complications) or safety (bleeding complications) end point. The aim of the present study was to compare bivalirudin and UFH plus protamine in patients undergoing elective percutaneous coronary intervention and pretreated with clopidogrel and aspirin. We randomly assigned 850 patients with stable or unstable coronary artery disease to bivalirudin or UFH followed by protamine at the end of the percutaneous coronary intervention. The primary end point was in-hospital major bleeding. The main secondary end points were the 1-month composite of death, myocardial infarction, unplanned target vessel revascularization; and the 1-month net clinical outcome. The rate of major bleeding (primary end point) was 0.5% in patients randomized to bivalirudin and 2.1% in patients randomized to UFH (p = 0.033). At 30 days, the rate of major bleeding was 0.9% in the bivalirudin arm and 2.8% in the UFH arm (p = 0.043). The composite of death, myocardial infarction, and target vessel revascularization rate and the net clinical outcome rate was 2.8% and 6.4% (p = 0.014) and 3.3% and 7.8% (p = 0.004), respectively, in the bivalirudin and UFH arms. In conclusion, in percutaneous coronary intervention patients pretreated with clopidogrel and aspirin, bivalirudin was associated with less major bleeding and fewer ischemic complications and a better net clinical outcome than UFH., (Copyright 2010 Elsevier Inc. All rights reserved.)

Heart failure (HF) is a common public health problem, and many new cases are now recognized to occur in patients with preserved left ventricular ejection fraction. beta Blockers improve the outcomes of patients with known left ventricular systolic dysfunction, but whether beta blockers provide similar protection among patients with left ventricular diastolic dysfunction is unclear. We studied the association between use of beta blockers and subsequent hospitalization for HF in patients with diastolic dysfunction and stable coronary heart disease. We evaluated medication use and performed echocardiography at baseline in a prospective cohort of 911 outpatients with known coronary heart disease from the Heart and Soul Study. Hospitalizations for HF were assessed by blinded review of the medical records during an average follow-up of 5.2 years. Of the 911 participants, 118 (13%) had diastolic dysfunction, of whom 2 were lost to follow-up. Of the 116 remaining patients, 19 (25%) of the 77 using beta blockers were hospitalized for HF compared to 16 (41%) of the 39 not using beta blockers (age-adjusted hazard ratio 0.51, 95% confidence interval 0.26 to 1.00; p = 0.05). This association remained after additional adjustment for gender, smoking, history of myocardial infarction, diabetes, and creatinine (hazard ratio 0.46, 95% confidence interval 0.23 to 0.93; p = 0.03). The results were similar after excluding 31 participants with a history of self-reported HF (hazard ratio 0.33, 95% confidence interval 0.13 to 0.86; p = 0.02) and 24 participants with concurrent systolic dysfunction (hazard ratio 0.36, 95% confidence interval 0.14 to 0.89; p = 0.03). In conclusion, the use of beta blockers is associated with a decreased risk of hospitalization for HF in patients with diastolic dysfunction and stable coronary heart disease., (Published by Elsevier Inc.)

Previous studies have suggested that patients with coronary artery disease (CAD) in rural areas may have worse outcomes due to limited availability of specialists, fewer resources, and less institutional funding. Data were collected from hospitals participating in the Get With the Guidelines-Coronary Artery Disease Program (GWTG-CAD) from January 2000 to December 2008. In-hospital outcomes and quality of care were stratified by care at rural versus urban hospitals. Multivariate logistic regression analysis was used to determine the association of rural locale with in-hospital mortality, length of stay, and compliance with the GWTG-CAD performance measurements including (1) early aspirin use, (2) smoking cessation counseling and discharge prescriptions of (3) aspirin, (4) angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers for left ventricular systolic dysfunction, (5) beta-blockers, and (6) lipid-lowering therapy and a composite of all 6 measurements. Data were collected from 22,096 patients at 71 rural centers and 329,938 patients at 477 urban centers. Unadjusted rates of compliance with performance measurements were lower in rural (range 82.4% to 90.5%) compared to urban (range 81.3% to 95.0%) hospitals including the composite (74.7% vs 80.6%, p <0.0001). In multivariate analysis, rural status was not independently associated with lower compliance with any of the performance measurements. Unadjusted mortality rates were higher in rural versus urban hospitals (5.7% vs 4.4%, p <0.0001), but this was not significant in multivariate analysis (odds ratio 1.05, 95% confidence interval 0.87 to 1.26). In conclusion, within the GWTG-CAD quality improvement initiative, patients with CAD treated at rural hospitals receive similar quality of care and have similar outcomes as those at urban centers., (Copyright 2010 Elsevier Inc. All rights reserved.)

The purpose of this study was to evaluate the prognostic significance of QRS duration in patients with suspected coronary artery disease (CAD) referred for noninvasive evaluation of myocardial ischemia by dobutamine stress echocardiography. QRS duration is a prognostic marker in patients with previous myocardial infarction and/or heart failure. The relation between QRS duration and outcome of patients without known heart disease has not been evaluated. A total of 1,227 patients (707 men, mean age 61 +/- 14 years) with suspected CAD underwent dobutamine stress echocardiography for evaluation of myocardial ischemia. Patients were followed to determine predictors of cardiac events and to assess the incremental significance of QRS duration compared to clinical and dobutamine stress echocardiographic data. During a mean follow-up of 4.2 +/- 2.4 years, 280 patients (23%) died (129 cardiac deaths), and 60 (5%) had a nonfatal infarction. Annualized cardiac death rates were 2.0% in patients with QRS duration <120 ms and 4.4% in patients with QRS duration >or=120 ms, respectively (p <0.0001). Annualized event rates for cardiac death/nonfatal infarction were 2.8% in patients with QRS duration <120 ms and 4.8% in patients with QRS duration >or=120 ms (p = 0.0001). Multivariate models identified age, male gender, smoking, QRS duration >or=120 ms, and an abnormal dobutamine stress echocardiogram as independent predictors of cardiac death and the combined end point cardiac death/nonfatal infarction. In conclusion, QRS duration is an independent predictor of cardiac death and cardiac death/nonfatal infarction in patients with suspected CAD. This risk is persistent after adjustment for clinical variables, left ventricular function, and myocardial ischemia.

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.

Alcohol has diverse effects on the cardiovascular system. Moderate drinking is associated with a decreased risk of cardiovascular disease, yet increasing amounts of alcohol consumption are known to increase blood pressure. These opposing effects have led to interest in the effect of moderate alcohol consumption on the risk of coronary heart disease (CHD) in patients with hypertension. To test the hypothesis that moderate alcohol consumption decreases the risk of myocardial infarction (MI) in patients with hypertension, we used data on 5,164 participants in the Physicians' Health Study who were apparently healthy and free of CHD at baseline. Incident MI was ascertained by annual follow-up questionnaires and validated through review of medical records. Cox proportional hazard model was used to compute multivariable-adjusted hazard ratios with corresponding 95% confidence intervals. From 1982 to 2008, 623 cases of MI occurred. Compared to subjects consuming <1 drink per week, hazard ratios for MI were 1.05 (95% confidence interval 0.85 to 1.28), 0.78 (95% confidence interval 0.64 to 0.97), and 0.57 (95% confidence interval 0.35 to 0.95) for alcohol consumption of 1 to 4, 5 to 7, and >8 drinks per week adjusted for age, body mass index, smoking, exercise, diabetes, multivitamin use, vegetable intake, breakfast cereal intake, and cholesterol (p for trend <0.0022). Similar inferences could be made for the secondary outcomes of angina pectoris and any CHD (which included MI, angina pectoris, and previous revascularization). In conclusion, our data demonstrated an inverse relation between moderate alcohol consumption and CHD in hypertensive men.

It is unclear whether visceral obesity is largely responsible for an increased risk of coronary artery disease. In the present study, 1,054 men underwent coronary artery calcium (CAC) scoring and abdominal computed tomography. Risk factor information, body mass index, waist circumference, and waist-to-hip ratio were collected for all participants. The total fat, visceral fat, and subcutaneous fat areas were also quantified at the level of the umbilicus using computed tomography. We then investigated the association of these obesity parameters with the CAC score. Participants with a CAC score >10 had a larger waist circumference (97 +/- 12 vs 95 +/- 12 cm, p <0.001), a larger total fat area (434 cm(2), interquartile range 339 to 565, vs 415 cm(2), interquartile range 315 to 521; p = 0.005), a larger visceral fat area (200 cm(2), interquartile range 143 to 256, vs 175 cm(2), interquartile range 124 to 225; p <0.001), and a greater waist-to-hip ratio (0.93 +/- 0.07 vs 0.91 +/- 0.07, p <0.001) than those with a CAC score of < or =10. Those with a CAC score >10 also tended to have a greater body mass index and larger subcutaneous fat area. After adjusting for traditional cardiovascular risk factors, however, only a large waist circumference (odds ratio 1.5, 95% confidence interval 1.04 to 2.0), a high total fat area (odds ratio 1.5, 95% confidence interval 1.1 to 2.1), and a high waist-to-hip ratio (odds ratio 1.6, 95% confidence interval 1.2 to 2.3) remained significantly associated with a CAC score >10. In conclusion, the measures of central obesity were more strongly associated with the CAC score than either the parameters assessing overall obesity or other more direct measures of visceral adiposity. These findings suggest that the total amount of central obesity is more important than the relative distribution of visceral versus subcutaneous fat.

Obesity is an independent risk factor for recurrent events among patients with established coronary heart disease (CHD). The goal of the present study was to identify potential mechanisms underlying this association. We measured the waist-to-hip ratio and body mass index in 979 outpatients with stable CHD and followed them for a mean of 4.9 years. We used proportional hazards models to evaluate the extent to which the association of obesity with subsequent heart failure (HF) hospitalization or cardiovascular (CV) events (myocardial infarction, stroke, or CHD death) was explained by baseline co-morbidities, cardiac disease severity, inflammation, insulin resistance, neurohormones and adipokines. Of the 979 participants, 128 (13%) were hospitalized for HF and 152 (16%) developed a CV event. Each standard deviation (SD) increase in the waist-to-hip ratio was associated with a 30% increased risk of HF hospitalization (unadjusted hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.1 to 1.6). This association was not attenuated after adjustment for potential mediators (HR 1.6, 95% CI 1.2 to 2.1). Likewise, each SD increase in the waist-to-hip ratio was associated with a 20% greater risk of CV events (unadjusted HR 1.2, 95% CI 1.0 to 1.4), and this remained unchanged after adjustment for potential mediators (adjusted HR 1.3, 95% CI 1.0 to 1.5). The body mass index was not associated with the risk of HF or CV events. In conclusion, abdominal obesity is an independent predictor of HF hospitalization and recurrent CV events in patients with stable CHD. This association does not appear to be mediated by co-morbid conditions, cardiac disease severity, insulin resistance, inflammation, neurohormones, or adipokines.

Although the presence of coronary heart disease (CHD) was the major determinant of perioperative mortality and long-term prognosis in patients with aortic aneurysm (AA) and peripheral artery disease (PAD), the prevalence and severity of CHD in patients with individual vascular diseases was unknown. Adenosine triphosphate-loading myocardial single-photon emission computed tomography therefore was performed in 788 patients with vascular diseases of the aorta and peripheral arteries, with AA in 500, PAD localized in the lower-limb arteries in 183, and combined AA and PAD in 105. Patients with known CHD, such as those with previous myocardial infarction or revascularization procedures, were excluded. Myocardial single-photon emission computed tomography was analyzed using a 20-segment model, and summed stress scores and summed difference scores were calculated. Stress-induced myocardial ischemia was defined as a summed difference score >or=2. The presence of myocardial ischemia was highest in patients with combined PAD and AA (73%), followed by PAD (55%; p = 0.005), and the lowest in patients with AA (37%; p <0.0001). Summed stress score was also the highest in patients with combined PAD and AA (11.6 +/- 9.9), followed by PAD (7.8 +/- 8.8; p <0.0001), and the lowest in patients with AA (4.0 +/- 6.2; p <0.0001 for both). Similarly, summed difference score was the highest in patients with combined PAD and AA (6.4 +/- 6.1), followed by PAD (4.4 +/- 5.7; p = 0.001) and AA (2.3 +/- 4.0; p <0.0001 for both). In conclusion, the prevalence of CHD in patients with PAD was >50%, and although myocardial ischemia was observed in only (1/3) of patients with AA, its prevalence not only doubled, but also indicated extensive myocardial ischemia when combined with PAD. Thus, cardiac evaluation was particularly important in patients with combined AA and PAD.

Abnormal heart rate recovery (HRR) after maximal exercise treadmill testing predicts adverse cardiac outcomes, although whether abnormal HRR on exercise treadmill testing should prompt further diagnostic cardiac testing is unknown. The aim of this study was to determine the prevalence of high-risk stress single-photon emission computed tomography myocardial perfusion imaging (MPI) findings in patients with abnormal HRR. A total of 509 men who had been referred for exercise stress MPI and were without other abnormal exercise treadmill testing findings (ischemic electrocardiographic changes or exercise treadmill testing-induced angina) were included in this study. Abnormal HRR was defined as a decrease in heart rate or=4, 49% vs 27%; p = 0.001), severe coronary heart disease (SSS >8, 36% vs 7%; p <0.001), left ventricular (LV) dysfunction (LV ejection fraction <50%; 25% vs 6%; p <0.001), and composite high-risk MPI findings (SSS >8 or LV ejection fraction <40%; 40% vs 9%; p <0.001) compared with those without abnormal HRR. On multivariate logistic regression analysis, abnormal HRR was found to be an independent predictor of mild or greater coronary heart disease (odds ratio [OR] 2.4, 95% confidence interval [CI] 1.4 to 4.3, p = 0.003), severe coronary heart disease (OR 5.5, 95% CI 2.7 to 11.0, p <0.001), and composite high-risk MPI findings (OR 4.3, 95% CI 2.1 to 8.6, p <0.001). In conclusion, abnormal HRR on exercise treadmill testing was associated with a high prevalence of abnormal and high-risk stress MPI findings, even in patients without other exercise treadmill testing findings that traditionally would prompt further testing. These findings suggest that further testing with stress MPI should be considered in patients with abnormal HRR on routine exercise treadmill testing.

The relative impact of body mass index (BMI) and exercise capacity on mortality in patients with an intermediate to high likelihood of coronary artery disease (CAD) is not clear. Thus, the effect of BMI and exercise capacity on all-cause mortality in patients referred for stress myocardial perfusion imaging was investigated. The outcome of 2,119 patients undergoing exercise stress myocardial perfusion imaging from 1995 to 1999 was assessed. Patients lacked known CAD, but were at intermediate to high risk. Mortality outcome data were obtained from the Social Security Administration Death Master File. There were 183 deaths during an average follow-up of 8.4 +/- 1.4 years. A Cox proportional hazards model identified age, Bruce protocol exercise time, BMI, male gender, and diabetes mellitus as significant predictors of all-cause mortality. In multivariate analysis, both exercise capacity and BMI correlated inversely with mortality, with higher chi-squared impact related to exercise capacity than BMI. In conclusion, both increased exercise capacity and BMI were associated with lower mortality in patients with an intermediate to high likelihood of CAD after controlling for confounding variables, supporting an inverse impact of BMI on mortality. The origin for this "obesity paradox" is unclear.

Chronic kidney disease (CKD) and anemia portend a higher risk of cardiac events and mortality. We sought to ascertain whether coronary artery disease (CAD) by myocardial perfusion single-photon emission computed tomography is more common in patients with CKD (glomerular filtration rate < or =60 ml/min/1.73 kg/m(2)) and/or anemia (hemoglobin level < or =13 g/L) and the impact of different degrees of CKD. One thousand five hundred eighty patients (mean age 65 +/- 10 years) underwent gated myocardial perfusion single-photon emission computed tomography and clinical evaluation. Patients were divided into 4 groups (group 1, no anemia/no CKD, n = 800; group 2, anemia/no CKD, n = 195; group 3, CKD/no anemia, n = 332; group 4, anemia/CKD, n = 253). Multivariate logistic regression analysis was undertaken to examine the association of these diagnoses with abnormal myocardial perfusion single-photon emission computed tomogram. Compared with patients with neither diagnosis, an abnormal scan was more common in those with anemia or CKD. Patients with anemia and CKD exhibited more severe CAD (mean summed stress score 6.8 vs 4.7, p <0.01). Established high-risk findings were more prevalent in patients with anemia and/or CKD, including a summed stress score > or =8, transient ischemic dilation, or a left ventricular ejection fraction < or =40% (group 1 28%, group 2 38%, group 3 38%, group 4 48%, all p values <0.01). Patients with moderate CKD demonstrated an increased risk of an abnormal scan (odds ratio 2.66, p <0.0001). After adjustment in multivariate analysis, anemia and CKD each remained predictors for an abnormal scan. The association was stronger in those with the 2 conditions (odds ratio for high-risk scan 1.89, p = 0.0002). In conclusion, in patients with suspected CAD, anemia and CKD are predictors of myocardial perfusion single-photon emission computed tomographic markers for worsened outcomes. The relation was independent of other risk factors, supporting the inclusion of anemia and CKD in global risk assessment for patients with suspected CAD.

Recent studies showed that such retinal vascular signs as quantitative retinal vascular caliber were associated with increased risk of incident coronary heart disease (CHD), but whether these retinal vascular signs add to the prediction of CHD over and above traditional CHD risk factors was not addressed. Whether these signs add to the prediction of CHD over and above the Framingham risk score in people (n = 9,155) without diabetes selected from the ARIC Study was investigated. Incident CHD was ascertained using standardized methods, and retinal vascular caliber and other retinal signs were measured from retinal photographs. After a mean of 8.8 years of follow-up, there were 700 incident CHD events. Women with wider retinal venular caliber (hazard ratio 1.27/1-SD increase, 95% confidence interval 1.08 to 1.50) and narrower retinal arteriolar caliber (hazard ratio 1.31/1-SD decrease, 95% confidence interval 1.10 to 1.56) had a higher risk of incident CHD after adjusting for Framingham risk score variables. Area under the receiver operator characteristic curve increased from 0.695 to 0.706 (1.7% increase) with the addition of retinal vascular caliber to the Framingham risk model. Risk prediction models with and without retinal vascular caliber both fitted the data and were well calibrated for women. In men, retinal vascular caliber was not associated with CHD risk after adjustment. Other retinal vascular signs were not associated with 10-year incident CHD in men or women. In conclusion, although retinal vascular caliber independently predicted CHD risk in women, the incremental predictive ability over that of the Framingham model was modest and unlikely to translate meaningfully into clinical practice.

To what extent the unavailability of coronary artery bypass graft (CABG) anatomy complicates the performance of diagnostic coronary angiography has not been studied. The medical and catheterization records and coronary angiograms of 367 consecutive CABG surgery patients who underwent 394 diagnostic coronary angiographic studies from October 1, 2004, to May 31, 2007, were retrospectively reviewed. The patients' mean age was 65+/-9 years, and 97% were men. The mean interval from CABG surgery to angiography was 8.3+/-6.1 years. Patent left internal mammary artery grafts were found in 75%, and the mean number of patent grafts was 2.1+/-1.0. Compared with angiograms with known CABG anatomy, angiograms with unknown CABG anatomy (26%) required significantly higher amounts of contrast (189+/-7 vs 158+/-4 ml), longer fluoroscopy times (14.0+/-0.7 vs 10.6+/-0.4 minutes), and more diagnostic catheters (3.0+/-0.1 vs 2.5+/-0.05) (p<0.001 for all comparisons). The unavailability of CABG anatomy remained associated with increased contrast, fluoroscopy, and catheter use after multivariate adjustment. Proximal anastomotic bypass markers were associated with lower contrast use but were seen in only 9% of patients. In conclusion, the unavailability of CABG anatomy significantly and independently increases the use of contrast, fluoroscopy, and catheters during diagnostic coronary angiography. Every effort should be made to obtain CABG anatomy before diagnostic angiography is performed.

Although exercise electrocardiography (ExECG) is commonly used to detect coronary artery disease, the diagnostic accuracy and reliability of positive (ischemic) results of ExECG in low- and intermediate-risk populations are limited. Accordingly, many patients with positive results of ExECG undergo secondary evaluation using noninvasive stress imaging such as exercise echocardiography. Functional capacity is a strong predictor of prognosis and, indirectly, of high-risk coronary artery disease. It was hypothesized that high functional capacity in patients with positive results of ExECG would predict (1) negative results on subsequent exercise echocardiography and (2) a low risk for late mortality. Results were analyzed in 104 consecutive patients (79 men, 25 women; mean age 49 years, range 27 to 76) referred for exercise echocardiography after positive results of ExECG with a treadmill workload of > or =10 METs. Late all-cause mortality was also determined in these patients. Exercise echocardiographic results were negative in 93% of patients (97 of 104; 92% of men [73 of 79] and 100% of women [25 of 25]) and positive in 7% (7 of 104). During a mean follow-up period of 7.2 +/- 1.9 years, there was 1 death. In conclusion, high functional capacity in patients with positive results of ExECG is associated with negative exercise echocardiographic results in most patients and very low late mortality. Patients with ischemic ST-segment response on ExECG who achieve workloads of > or =10 METs infrequently require additional noninvasive or invasive evaluation.

The difference between peak mitral annular velocity during early diastole (Ea) and the propagation velocity of left ventricular (LV) early diastolic filling flow (Vp) obtained using Doppler imaging as LV relaxation parameters was not fully elucidated. Thus, this issue was investigated in 117 patients with suspected coronary artery disease. During cardiac catheterization, LV volumes, the LV relaxation time constant Tp, and inertia force of late systolic aortic flow were obtained. Ea significantly and closely correlated with Tp (r = -0.70, p <0.0001) and significantly but weakly correlated with LV ejection fraction (r = 0.37, p <0.0001) and inertia force (r = 0.34, p = 0.0002). Conversely, Vp significantly and closely correlated with both LV ejection fraction (r = 0.66, p <0.0001) and inertia force (r = 0.72, p <0.0001) and significantly but weakly correlated with Tp (r = - 0.35, p = 0.0001). In conclusion, Ea and Vp reflect different aspects of LV behavior from end-systole to early diastole. Ea can be used to index LV relaxation, whereas Vp might not be a proper parameter of LV intrinsic relaxation because it is significantly dependent on LV systolic function and LV chamber size at end-systole. Both parameters are not interchangeable as those of LV early diastolic function. Vp may be a noninvasive parameter of LV elastic recoil.

Increase of cardiac troponins occurs in a variety of clinical situations in the absence of an acute coronary syndrome (ACS). Few data exist regarding the incidence, clinical characteristics, and predictive value of various cardiac diagnostic tests and outcome of patients with a non-ACS-related troponin increase. We studied 883 consecutive hospitalized patients with increased cardiac troponin I levels. The discharge diagnosis was reclassified and troponin increase attributed to ACS or another process. Clinical data and results of cardiac diagnostic tests were collected. Patients were followed for a median of 30 months. Three hundred eleven patients were classified as having a non-ACS-related troponin increase (35.2%). An alternative explanation for troponin increase was found in 99% of these patients. Troponin level had poor accuracy in discriminating patients with and without ACS (area under the receiver operating characteristics curve 0.63). Coronary angiography was frequently unhelpful in excluding a non-ACS-related troponin increase because 77% of patients in the non-ACS group had significant flow-limiting coronary artery disease. Patients with non-ACS-related troponin increase had significantly higher in-hospital (hazard ratio 2.8, 95% confidence interval 2.0 to 3.8) and long-term (hazard ratio 2.0, 95% confidence interval 1.6 to 2.5) mortalities compared with patients with ACS. In conclusion, cardiac troponin level is frequently increased in hospitalized patients in the absence of an ACS and portends poor short- and long-term outcomes. Most of these patients have an alternative explanation for cardiac troponin increase. Cardiac diagnostic procedures are frequently unhelpful in excluding a non-ACS-related troponin increase.

Heart rate (HR) profile during exercise predicts all-cause mortality. However, less is known about its relation to sudden (vs nonsudden) death in asymptomatic people. The relation of exercise HR parameters (HR at rest, target HR achievement, HR increase, and HR recovery) with sudden death, coronary heart disease (CHD) death, myocardial infarction, and all-cause mortality was assessed in 12,555 men who participated in MRFIT. Subjects were 35 to 57 years old without clinical CHD, but with higher than average Framingham risk. Trial follow-up was 7 years, and extended follow-up after the trial for all-cause mortality was 25 years. After adjusting for cardiac risk factors, having to stop exercise before achieving 85% of age-specific maximal HR was associated with increased risk of sudden death (hazard ratio 1.8, 95% confidence interval [CI] 1.3 to 2.5, p = 0.001), CHD death (hazard ratio 1.4, 95% CI 1.2 to 1.5, p <0.001), and all-cause mortality (hazard ratio 1.3, 95% CI 1.2 to 1.4, p <0.001). Increased HR at rest (p = 0.001), attenuated HR increase (p = 0.02), delayed HR recovery (p = 0.04), and exercise duration (p <0.0001) were independent predictors of all-cause death in the overall study population and also in the subgroup that achieved target HR. In conclusion, middle-aged men without clinical CHD who stopped exercise before reaching 85% of maximal HR had a higher risk of sudden death. Other exercise HR parameters and exercise duration predicted all-cause mortality.

The aim of this study was to test the safety and efficacy of a novel rapid desensitization procedure in patients with acetylsalicylic acid sensitivity and coronary artery disease who underwent cardiac catheterization and coronary stent implantation. Aspirin plays a key role in the secondary prevention of atherothrombotic events and thrombotic complications after stent implantation. Aspirin sensitivity not only limits patients to benefit from the long-term use of this antiplatelet agent but is also often an impediment to the implantation of bare-metal and drug-eluting coronary stents. Of 1,014 patients admitted for cardiac catheterization, 26 (2.6%) had histories of aspirin sensitivity characterized by respiratory or cutaneous manifestations (none had previous anaphylactic reactions); of these, 61.5% presented with acute coronary syndromes. All patients underwent a novel rapid desensitization challenge procedure before cardiac catheterization, except for those presenting with ST-elevation myocardial infarctions (n = 4), who underwent desensitization before hospital discharge. The desensitization procedure involved the oral administration of 6 sequential doses of aspirin (1, 5, 10, 20, 40, and 100 mg) over 5.5 hours without the use of corticosteroids or antihistamines. Patients were followed for 1 year to assess compliance with aspirin therapy and adverse events. The desensitization procedure was successful in 23 patients (88.5%). Percutaneous coronary intervention with stent implantation was performed in 22 patients (1.8 stents/patient). Drug-eluting stents were used in all patients except those who underwent primary percutaneous coronary intervention (n = 3), in whom bare-metal stents were used. Multivessel percutaneous coronary intervention was performed in 30.7% of patients. At follow-up, all patients who successfully responded to the desensitization procedure tolerated aspirin well, without developing allergic reactions. Aspirin was withdrawn in only 1 patient, because of a peptic ulcer. In conclusion, rapid desensitization is safe and highly effective in patients with aspirin sensitivity and coronary artery disease who undergo coronary stent implantation, including those who receive drug-eluting stents.

Physical and mental stressors result in increased inflammation markers in populations free of coronary artery disease (CAD). However, inflammatory responses to mental and exercise challenges have not been established in patients with CAD. This study investigated the responses of inflammatory markers, including C-reactive protein (CRP), interleukin-6 (IL-6), and soluble intercellular adhesion molecule-1, in patients with CAD after successful elective percutaneous coronary intervention (n = 36, 59 +/- 8 years of age, 33% women) and healthy controls without a history of CAD (n = 28, 54 +/- 10 years of age, 36% women). Increases in inflammatory markers were examined in response to mental challenge tasks (anger recall and mental arithmetic) and treadmill exercise. Stress echocardiography was used to rule out stress-induced ischemia as a possible confounding factor. Results showed that CRP increased significantly to mental challenge and exercise (p values <0.01), and CRP responses were higher in patients with CAD than in controls (change in mental arithmetic 0.19 +/- 0.11 vs 0.01 +/- 0.03 mg/L, p = 0.003; change in exercise 0.57 +/- 0.11 vs 0.08 +/- 0.0.03 mg/L, p = 0.001). Increased norepinephrine responses were related to larger CRP and IL-6 increases to mental challenge tasks (p values <0.05). Exercise elicited increased CRP, IL-6, and soluble intercellular adhesion molecule-1 levels (p values <0.01), and these responses were larger than with mental challenge tasks (p values <0.05). In conclusion, mental stress and exercise induce increased levels of inflammatory markers in patients with CAD. These stress-induced increases are larger than in healthy subjects, occur in the absence of myocardial ischemia, and are related to the neurohormonal stress response.

The aim of the study was to evaluate whether markers of myocardial injury and ischemia are helpful in detecting coronary artery disease (CAD) in patients with stable angina. Venous blood was obtained before and after a bicycle exercise test in 47 outpatients with suspected CAD for measurement of cardiac troponin I (cTnI), heart-type fatty acid binding protein, and glycogen phosphorylase BB. Patients with a coronary artery stenosis >/=70% in diameter (n = 33) were compared with patients with coronary narrowing <50% (controls, n = 14). None of the markers increased after bicycle exercise testing. cTnI measured before and after exercise was higher in the CAD group than in controls (p <0.001). The area under the curve for diagnosis was greater when the cTnI value was detectable than with stress testing alone. In conclusion, baseline cTnI was of value in detecting CAD and also during follow-up in predicting the need for further revascularization.

The ability of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) to predict mortality in various subsets of patients with coronary artery disease (CAD) is not known. The aim of present study was to investigate the ability of NT-pro-BNP to predict mortality in various subsets of patients with CAD. The study included 1,552 consecutive patients with angiographically proven CAD. Based on receiver-operating characteristic curve analysis, the best NT-pro-BNP level for mortality prediction was 721 ng/L (sensitivity 71.3%, specificity 71.3%). Patients were divided into 2 groups: the group with NT-pro-BNP level < or =721 ng/L (1,034 patients) and the group with NT-pro-BNP level >721 ng/L (518 patients). The primary end point of the study was mortality. The median follow-up was 3.6 years (interquartile range 3.3 to 4.6). In total there were 171 deaths: 49 deaths in the group with NT-pro-BNP < or =721 ng/L and 122 deaths in the group with NT-pro-BNP >721 ng/L (mortality estimates 6.6% vs 29.5%, odds ratio 5.2; 95% confidence intervals 3.9 to 7.0, p <0.001). In 28 subsets of patients, NT-pro-BNP level predicted mortality with odds ratio varying from 2.8 to 7.5. In conclusion, NT-pro-BNP is a reliable predictive marker of mortality in all subsets of patients with CAD.