Established Risk Models Research Articles

Reverse association of omega-3/omega-6 polyunsaturated fatty acids ratios with carotid atherosclerosis in patients on hemodialysis

Background and aimsOmega-3 (n-3) polyunsaturated fatty acids (PUFAs) are widely recognized to have beneficial effects against cardiovascular disease. We investigated the association of n-3 PUFAs levels with carotid atherosclerosis in patients on hemodialysis (HD), who are at high risk for cardiovascular events. MethodsCarotid ultra-sound was performed in a total of 461 patients on HD (male 67%, age 67 ± 12years, diabetes rate 46%). Intima-media thickness (IMT) and the plaque score (PS) in carotid arteries were measured. Carotid atherosclerosis was defined as IMT >1.2 mm and/or PS > 5.0. The levels of n-6 PUFAs [dihomo-gamma-linolenic acid (DHLA) and arachidonic acid (AA)] and n-3 PUFAs [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] were also measured prior to carotid ultra-sound. ResultsCarotid atherosclerosis was observed in 94 patients (20.4%). Individual PUFAs levels were comparable between patients with and without carotid atherosclerosis. However, the ratio of EPA/AA and that of n-3/n-6 PUFAs were significantly lower in patients with carotid atherosclerosis compared to those without (median 0.36 vs. 0.41, p = 0.031 and 0.85 vs. 0.93, p = 0.041, respectively]. After adjustment for other confounders, the ratio of EPA/AA (OR 0.30, 95% CI 0.12–0.70, p = 0.0055) and the ratio of n-3/n-6 PUFAs (OR 0.45, 95% CI 0.25–0.80, p = 0.0066) showed an independent reverse association with carotid atherosclerosis. In addition, the area under receiver-operating characteristic curves for carotid atherosclerosis was significantly greater in an established risk model with EPA/AA and n-3/n-6 ratios than in the established risk model alone. ConclusionsThese data suggest that low ratios of both EPA/AA ratio and n-3/n-6 PUFAs were closely associated with carotid atherosclerosis in patients on HD.

Plasma Neutrophil Gelatinase-Associated Lipocalin as a Predictor of Cardiovascular Events in Patients with Chronic Kidney Disease.

Background. Our aim was to assess plasma neutrophil gelatinase-associated lipocalin (NGAL) as a predictor of cardiovascular (CV) events in patients with chronic kidney disease (CKD) and no history of CV events. Methods. This was a prospective observational cohort study of 252 patients with predialysis CKD. CV events were defined as CV death, acute coronary syndrome, and hospitalization for worsening heart failure, stroke, and aortic dissection. Results. During a median follow-up period of 63 months, 36 CV events occurred. On Cox stepwise multivariate analysis, plasma NGAL and B-type natriuretic peptide (BNP) were significant predictors of CV events. Kaplan-Meier incidence rates of CV event-free survival at 5 years were 96.6%, 92.9%, 85.9%, and 61.3%, respectively, among quartiles of plasma NGAL (P < 0.0001). The C-index for the receiver-operating characteristic curves for CV events was greater when plasma NGAL was added to an established risk model (0.801, 95% CI 0.717–0.885), compared to the model without plasma NGAL (0.746, 95% CI 0.653–0.840, P = 0.021). Conclusion. Elevated plasma NGAL could predict future CV events in CKD patients with no history of CV events and add incremental value to the established risk model.

Abstract 14598: The Novel Cardiac Biomarker Secretoneurin Provides Independent Prognostic Information in Severe Sepsis and Septic Shock: Data From the ALBIOS Study

Background: Plasma secretoneurin (SN) is directly correlated to cardiomyocyte Ca 2+ handling and provides independent prognostic information in cardiovascular disease. Whether SN may predict mortality in patients with severe sepsis or septic shock is not established. Methods: We measured SN levels in serial plasma samples collected on days 1, 2, and 7 in 958 patients enrolled in the multicenter, open-label, randomized, controlled ALBIOS trial, that tested either 20% albumin and crystalloid solutions or crystalloid solutions alone in patients with severe sepsis or septic shock. Endpoints were ICU or 90 day mortality. Results: SN levels on day 1 were higher in non-survivors compared to survivors, both for ICU mortality (235 [Q1-Q3 188-290] vs. 192 [155-246] pmol/L, p&lt;0.0001) and for 90 day mortality (227 [183-283] vs. 188 [154-234] pmol/L, p&lt;0.0001). Admission SN levels were influenced by age and lactate, creatinine and NT-proBNP levels. Stratifying patients according to SN quartiles on day 1 separated survivors and non-survivors during follow-up (Figure). After adjusting for clinical risk factors, SAPS II and SOFA scores, and cardiac biomarkers (hs-cTnT and NT-proBNP), SN levels (logarithmical transformed) on day 1 remained significantly associated with ICU mortality (OR 1.29 [95% CI 1.07-1.55], p=0.007) and 90 day mortality (OR 1.22 [1.02-1.47], p=0.03). SN levels on day 2, but not day 7, were also independently associated with ICU and 90 day mortality. SN levels on day 1 and 2 improved prognostic accuracy for ICU and 90 day mortality as assessed by the category-free net reclassification index. We found no interactions between SN levels and randomization to albumin replacement for prediction of mortality during follow-up. Changes in SN levels over time were not predictive of subsequent mortality. Conclusion: SN provides incremental information to established risk models and cardiovascular biomarkers in patients with severe sepsis and septic shock.

Exercise Capacity and Heart Rate Responses to Exercise as Predictors of Short-Term Outcome Among Patients With Stable Coronary Artery Disease

Although exercise capacity (EC) and autonomic responses to exercise predict clinical outcomes in various populations, they are not routinely applied in patients with coronary artery disease (CAD). We hypothesized that the composite index of EC and exercise heart rate responses would be a powerful determinant of short-term risk in CAD. Patients with angiographically documented stable CAD and treated with β blockers (n = 1,531) underwent exercise testing to allow the calculation of age- and gender-adjusted EC, maximal chronotropic response index (CRI), and 2-minute postexercise heart rate recovery (HRR, percentage of maximal heart rate). Cardiovascular deaths and hospitalization due to heart failure, registered during a 2-year follow-up (n = 39, 2.5%), were defined as the composite primary end point. An exercise test risk score was calculated as the sum of hazard ratios related to abnormal (lowest tertile) EC, CRI, and HRR. Abnormal EC, CRI, and HRR predicted the primary end point, involving 4.5-, 2.2-, and 6.2-fold risk, respectively, independently of each other. The patients with intermediate and high exercise test risk score had 11.1-fold (95% confidence interval 2.4 to 51.1, p = 0.002) and 25.4-fold (95% confidence interval 5.5 to 116.8, p <0.001) adjusted risk for the primary end point in comparison with the low-risk group, respectively. The addition of this risk score to the established risk model enhanced discrimination by integrated discrimination index and reclassification by categorical and continuous net reclassification index (p <0.001 for all). In conclusion, the composite index of EC and heart rate responses to exercise and recovery is a powerful predictor of short-term outcome in patients with stable CAD.

Utility of Established Risk Models to Predict Surgical Mortality in Acute Type-A Aortic Dissection.

The objective of this study was to determine the predictive value of 2 established risk models for surgical mortality in a contemporary cohort of patients undergoing repair of acute type-A aortic dissection. Retrospective analysis. Single tertiary care hospital. Seventy-nine consecutive patients undergoing emergent repair of acute type-A aortic dissection between 2008 and 2013. All patients underwent emergent repair of acute type-A aortic dissection. The receiver operating characteristic curve was compared for each scoring system. Of the 79 patients undergoing emergent repair of acute type-A aortic dissection, 23 (29.1%) were above the age of 70. Seventeen (21.5%) patients presented with hypotension, 25 (31.6%) presented with limb ischemia, and 10 (12.7%) presented with evidence of visceral ischemia. Overall operative mortality was 16.5%. Increasing age was the only preoperative variable associated with increased operative mortality. The areas under the receiver operating characteristic curve for operative mortality was 0.62 and 0.66 for the scoring systems developed by Rampoldi et al and Centofanti et al, respectively. The area under the receiver operating characteristic curve for operative mortality for age was 0.67. The areas under the receiver operating characteristic curve for operative mortality between the 2 scoring systems and for age were not statistically different. Existing predictive risk models for acute type-A aortic dissection provide moderate discriminatory power for operative mortality. Age as a single variable may provide equivalent discriminatory power for operative mortality as the established risk models.

Validation of the Intensive Care National Audit and Research Centre Scoring System in a UK Adult Cardiac Surgery Population.

The Intensive Care National Audit and Research Centre (ICNARC) scoring system was conceived in 2007, utilizing 12 physiologic variables taken from the first 24 hours of adult admissions to the general intensive care unit (ICU) to predict in-hospital mortality. The authors aimed to evaluate the ICNARC score in predicting mortality in cardiac surgical patients compared to established cardiac risk models such as logistic EuroSCORE as well as to the Acute Physiology and Chronic Health Evaluation (APACHE) II. Retrospective analysis of data collected prospectively. Single-center study in a cardiac intensive care in a regional cardiothoracic center. Patients undergoing cardiac surgery between January 2010 and June 2012. A total of 1,646 patients were scored preoperatively using the logistic EuroSCORE and postoperatively using ICNARC and APACHE II. Data for comparison of scoring systems are presented as area under the receiver operating characteristic curve. The mean age at surgery was 67 years±10.1. The mortality from all cardiac surgery was 3.2%. The mean logistic EuroSCORE was 7.31±10.13, the mean ICNARC score was 13.42±5.055, while the mean APACHE II score was 6.32±7.731. The c-indices for logistic EuroSCORE, ICNARC, and APACHE II were 0.801, 0.847 and 0.648, respectively. The authors have, for the first time, validated the ICNARC score as a useful predictor of postoperative mortality in adult cardiac surgical patients. This could have implications for postoperative management, focusing the utilization of resources as well as a method to measure and compare performance in the cardiothoracic ICU.

Incremental Utility of Iodine-123 Meta-Iodobenzylguanidine Imaging Beyond Established Heart Failure Risk Models

BackgroundNuclear myocardial imaging with iodine-123 meta-iodobenzylguanidine (123I-mIBG) is approved for risk stratification of patients with systolic heart failure (HF). Whether 123I-mIBG imaging provides incremental prognostic utility beyond established risk models remains unclear. Methods and ResultsIn a multicenter study, 961 patients with moderate systolic HF underwent 123I-mIBG imaging and were followed for cardiac death, progressive HF, or life-threatening arrhythmias over 2 years. We constructed 4 multivariable models, using variables from each of 4 published HF risk models, and patient-level scores were calculated both before and after adding the heart-to-mediastinum ratio (H/M) from 123I-mIBG imaging. Incremental utility was evaluated by calculating integrated discrimination improvement (IDI), which quantifies the increase in probability of experiencing the primary end point after adding H/M to each model. The composite end point occurred in 25% of patients. After adding H/M, absolute IDI ranged from 2.1% to 3.0%, representing 33%–59% relative improvements in risk stratification. Of note, hazard ratios for H/M were remarkably similar between risk models (0.40–0.44 for predicting the composite end point, 0.10–0.18 for mortality; all P < .001). ConclusionsDespite notable differences in predictor variables, patient populations, and analytic techniques from which each model was initially derived, adding 123I-mIBG data to HF risk models consistently identified patients at lower risk of experiencing adverse events.

Geriatric nutritional risk index accurately predicts cardiovascular mortality in incident hemodialysis patients

BackgroundCardiovascular disease (CVD) is a leading cause of death in end-stage renal disease (ESRD) patients. Protein-energy wasting (PEW) or malnutrition is common in this population, and is associated with increasing risk of mortality. The geriatric nutritional risk index (GNRI) has been developed as a tool to assess the nutritional risk, and is associated with mortality not only in elderly patients but also in ESRD patients. However, whether the GNRI could predict the mortality due to CVD remains unclear in this population. We investigated the prognostic value of GNRI at initiation of hemodialysis (HD) therapy for CVD mortality in a large cohort of ESRD patients. MethodsSerum albumin, body weight, and height for calculating GNRI were measured in 1568 ESRD patients. Thereafter, the patients were divided into quartiles according to GNRI levels [quartile 1 (Q1): <84.9; Q2: 85.0–91.1; Q3: 91.2–97.2; and Q4: >97.3], and were followed up for up to 10 years. ResultsGNRI levels independently correlated with serum C-reactive-protein levels (β=−0.126, p<0.0001). Rates of freedom from CVD mortality for 10 years were 57.9%, 73.3%, 80.8%, and 89.2% in Q1, Q2, Q3, and Q4, respectively (p<0.0001). The GNRI was an independent predictor of CVD mortality (hazard ratio 3.42, 95% confidence interval 2.05–5.70, p<0.0001 for Q1 vs. Q4). C-index was also greater in an established CVD risk model with GNRI (0.749) compared to that with albumin (0.730), body mass index (0.732), and alone (0.710). Similar results were observed for all-cause mortality. ConclusionGNRI at initiation of HD therapy could predict CVD mortality with incremental value of the predictability compared to serum albumin and body mass index in ESRD patients.

The combination of 9p21.3 genotype and biomarker profile improves a peripheral artery disease risk prediction model

Peripheral artery disease (PAD) is a highly morbid condition affecting more than 8 million Americans. Frequently, PAD patients are unrecognized and therefore do not receive appropriate therapies. Therefore, new methods to identify PAD have been pursued, but have thus far had only modest success. Here we describe a new approach combining genomic and metabolic information to enhance the diagnosis of PAD. We measured the genotype of the chromosome 9p21 cardiovascular-risk polymorphism rs10757269 as well as the biomarkers C-reactive protein, cystatin C, β2-microglobulin, and plasma glucose in a study population of 393 patients undergoing coronary angiography. The rs10757269 allele was associated with PAD status (ankle-brachial index < 0.9) independent of biomarkers and traditional cardiovascular risk factors (odds ratio = 1.92; 95% confidence interval, 1.29-2.85). Importantly, compared to a previously validated risk factor-based PAD prediction model, the addition of biomarkers and rs10757269 significantly and incrementally improved PAD risk prediction as assessed by the net reclassification index (NRI = 33.5%; p = 0.001) and integrated discrimination improvement (IDI = 0.016; p = 0.017). In conclusion, a model including a panel of biomarkers, which includes both genomic information (which is reflective of heritable risk) and metabolic information (which integrates environmental exposures), predicts the presence or absence of PAD better than established risk models, suggesting clinical utility for the diagnosis of PAD.

Walking Impairment Questionnaire Improves Mortality Risk Prediction Models in a High-Risk Cohort Independent of Peripheral Arterial Disease Status

The Walking Impairment Questionnaire (WIQ) is a subjective measure of patient-reported walking performance developed for peripheral arterial disease. The purpose of this study is to examine whether this simple tool can improve the predictive capacity of established risk models and whether the WIQ can be used in patients without peripheral arterial disease. At baseline we assessed the walking distance, stair-climbing, and walking speed WIQ category scores among individuals who were undergoing coronary angiography. During a median follow-up of 5.0 years, there were 172 mortalities among 1417 study participants. Adjusted Cox proportional hazards models showed that all 3 WIQ categories independently predicted future all-cause and cardiovascular mortality, including among individuals without peripheral arterial disease (P<0.001). Compared with the cardiovascular risk factors model, we observed significantly increased risk discrimination with a C-index of 0.741 (change in C-index, 0.040; 95% confidence interval, 0.011-0.068) and 0.832 (change in C-index, 0.080; 95% confidence interval, 0.034-0.126) for all-cause and cardiovascular mortality, respectively. Examination of risk reclassification using the net reclassification improvement index showed a 48.4% (P<0.001) improvement for all-cause mortality and a 77.4% (P<0.001) improvement for cardiovascular mortality compared with the cardiovascular risk factors model. All 3 WIQ categories independently predicted future all-cause and cardiovascular mortality. Importantly, we found that this subjective measure of walking ability could be extended to patients without peripheral arterial disease. The addition of the WIQ scores to established cardiovascular risk models significantly improved risk discrimination and reclassification, suggesting broad clinical use for this simple, inexpensive test.

Monitoring high-risk bladder cancer

Monitoring high-risk nonmuscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) is challenging since currently used clinical and pathological risk parameters are not accurate enough to address the individual risk of progression. In NMIBC, the use of urinary interleukin-2 and fluorescence in-situ hybridization predicts response to bacille-calmette-guerin treatment. In both NMIBC and MIBC, the detection of circulating tumor cells at initial diagnosis allows improved monitoring since its presence is associated with higher tumor stages, concomitant carcinoma in situ and shorter time to recurrence. Molecular urine markers, such as fluorescence-in-situ hybridization, help to identify high-risk cases early on. In MIBC, serum C-reactive protein and thrombocytosis have been recently incorporated into basic prognostic models and demonstrated an increase in the predictive accuracy of standard pathological risk factors. New serological and urine-based markers have been identified for monitoring high-risk bladder cancer, and demand incorporation into established clinicopathological risk models to tailor surveillance regimens and provide improved prognostication for the need of adjuvant treatment.

Invited Commentary

This study by Okada and colleagues [1Okada K. Omura A. Kano H. et al.Short and midterm outcomes of elective total aortic arch replacement combined with coronary artery bypass grafting.Ann Thorac Surg. 2012; 94: 530-536Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar] presents a large (n = 200) institutional experience with total aortic arch replacement (TAR) performed to treat nondissecting aneurysm. The 30-day mortality for the entire cohort was remarkably low at 0.5%, and hospital mortality was 3.5%. The authors examined the surgical outcomes of TAR with and without coronary artery bypass grafting (CABG). Unadjusted outcomes for the patients who underwent both TAR and CABG included higher operative mortality, lower survival, and a higher incidence of major cardiac and cerebrovascular events. Although CABG was associated with prolonged operative times—reflecting the greater complexity of a combined procedure—only operative time emerged as an important independent predictor of both perioperative and mid-term mortality. In established cardiac risk models, including the STS model and the Veterans Affairs Continuous Improvement in Cardiac Surgery Program, the addition of CABG to valve procedures increases risk independently of other patient-related comorbidities. In fact, in the Japanese thoracic aortic surgery model (cited by the authors as reference 9), the addition of unexpected CABG to a thoracic aortic procedure was independently associated with increased 30-day mortality, and the addition of any CABG was associated with an increased rate of the composite outcome of major morbidity and mortality. Beyond the immediate perioperative risk posed by CABG, coronary artery disease is a clearly an additional life-limiting disease that is palliated by CABG but perhaps not cured. Therefore, one would expect the TAR-plus-CABG cohort to have worse long-term survival than the TAR-only cohort. Although this study had an impressive sample size for a single-center TAR series, the number of patients and events is small; therefore, the study might not have had enough power to detect any increase in risk caused by the addition of CABG to TAR. The confidence intervals in some instances are wide and in others approach or encompass 1.0. Regardless of how concomitant CABG might affect TAR outcomes, this study serves as a good example of the excellent short- and mid-term outcomes achieved in modern-day TAR performed at an experienced center. These results set the bar high for emerging endovascular and hybrid approaches to treating aortic arch aneurysms. Short and Midterm Outcomes of Elective Total Aortic Arch Replacement Combined With Coronary Artery Bypass GraftingThe Annals of Thoracic SurgeryVol. 94Issue 2PreviewThis study was performed to investigate the early and late outcomes of total aortic arch replacement (TAR) with or without coronary artery bypass grafting (CABG). Full-Text PDF

Combined Values of Serum Albumin, C-Reactive Protein and Body Mass Index at Dialysis Initiation Accurately Predicts Long-Term Mortality

Background: Protein-energy wasting and chronic inflammation are prevalent in patients with end-stage renal disease (ESRD). We investigated the combination of serum albumin, C-reactive protein (CRP) and body mass index (BMI) at initiation of hemodialysis therapy as a predictor of all-cause and cardiovascular disease (CVD) mortality in Japanese ESRD patients. Methods: A total of 1,228 consecutive Japanese ESRD patients on hemodialysis therapy were enrolled and followed for up to 10 years. Patients were divided into quartiles according to levels of albumin, CRP and BMI. Furthermore, to clarify the joint role of these factors, albumin <3.5 g/dl, CRP >4.0 mg/l and BMI <19.6 were defined as risk factors using receiver operating characteristic analysis; thereafter, patients were divided into groups according to the positive number of these factors. Results: Adjusted hazard ratios (HRs) for lower serum albumin, elevated CRP and lower BMI for 10-year all-cause mortality were 1.97, 3.13 and 2.61, respectively. Regarding the combination of these variables, adjusted HRs for mortality were 2.31, 4.28 and 8.07, respectively, in patients having any one factor, any two factors and all three factors. The C-index for an established risk model with these three positive markers was the most accurate for predicting mortality (0.768), as compared to other models with one or two markers. Similar results were seen for CVD mortality. Conclusions: Serum albumin, CRP and BMI at the start of hemodialysis therapy were able to individually stratify the risk of long-term mortality in ESRD patients. Furthermore, a combination of these variables could more accurately predict mortality.

Abstract LB-326: Elucidating significant genetic associations between genes and lung cancer

Abstract Introduction: To further understand and elucidate the genetic risk factors for Lung Cancer (LC) will substantially improve cancer prevention, screening programs, and treatment options for this insidious disease. However, our previous attempts to increase the discriminatory power in an existing risk model with the inclusion of SNPs identified via GWAS have not been very successful. In this analysis, we reassess the increase in discriminatory power by including haplotypes based on existing GWAS-identified SNPs and additional single SNPs. Methods: Cases included 1154 histological-confirmed Caucasian lung cases from MD Anderson Cancer Center in Houston, Texas, and controls included 1137 individuals recruited through the Kelsey-Seybold Clinics in Houston, Texas. Genetic information from both populations was selected for 157 SNPs that exist in the Texas GWAS and were part of the top 200 SNPs as determined by a previously published meta-analysis of 10 different lung cancer GWAS datasets (Landi et al. 2009). Plink and Haploview were used to determine the top SNPs and top haplotype blocks respectively. Then, univariate logistic regression was used to determine the best genetic model for the top SNPs. Joint logistic risk model regression was used to determine haplotype risk for each individual haplotype block. Finally, multivariate logistic regression was used to develop the final extended model that included the original set of risk factors from the Spitz model plus additional haplotypes and SNPs. We evaluated increase in discriminatory power by evaluated change in the area under the receiver-operating characteristic curve and the net reclassification index. Results: The discriminatory power for the original Spitz model was 66.1% (95% CI = 0.638-0.683). With the inclusion of only single SNPs in to the model, the discriminatory power increased by 4.5% to 70.6% (95% CI = 0.684-0.727, p-value = &amp;lt;0.0001). Adding the top 6 haplotypes further increased the discriminatory power to 71.9% (95% CI = 0.697-0.739). The net reclassification index results show that this increase in discriminatory power is evident for both cases (23.47%) and controls (23.43%). Conclusions: Inclusion of genetic variants into an established epidemiologic risk model can substantially increase the discriminatory power; however, selection and modeling of these variants needs to be carefully done. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-326. doi:1538-7445.AM2012-LB-326

Pexelizumab, an Anti-C5 Complement Antibody for Primary Coronary Revascularization: A New Insight from Old Versions

Pexelizumab, an anti-C5 complement antibody, as adjunctive therapy to reduce reperfusion injury after coronary revascularization in acute myocardial infarction and severe coronary artery disease had been approved in animal studies and further demonstrated clinical benefits in phase II study: the COMMA trial and phase III study: the PRIMOCABG trial. However, the negative results of pexelizumab were observed in the COMPLY trial and the APEX-AMI trial. In the APEX-AMI trial, the effectiveness of pexelizumab has reasoned to be prominent in high-risk patients. Similarly, an exploratory analysis of the combined PRIMO-CABG I and II data set using an established predictive risk model demonstrated a mortality benefit for high-risk surgical patients. Accordingly, the result of these trials supported a moderational model to explain the usefulness of pexelizumab affected by the baseline risk profiles of patients. In this regard, we have commented that pexelizumab may be hazardous to patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention without using adequate anti-thrombotic agents (glycoprotein IIb-IIIa antiplatelet inhibitors, clopidogrel and haparin non-responders) according to the results of the experiment by professor Røger and coworkers and the mathematic estimations of the relative risks. Herein, we proposed a mediational model to account for the effectiveness of pexelizumab.

High-Sensitivity Cardiac Troponin I Measurement for Risk Stratification in a Stable High-Risk Population

Past investigations regarding the utility of high-sensitivity cardiac troponin I (cTnI) assays have been focused primarily on the acute coronary syndrome setting. We assessed whether such assays can predict future ischemic cardiovascular events in a stable high-risk population. We quantified serum cTnI using an investigational high-sensitivity assay (hs-cTnI IUO, Beckman Coulter) in 2572 participants from the Heart Outcomes Prevention Evaluation (HOPE) study. The derived ROC curve cutoff and the 99th percentile for the hs-cTnI assay were assessed by Kaplan-Meier and Cox analyses for the primary outcome [composite of myocardial infarction (MI), stroke, and cardiovascular death] at 4.5 years of follow-up. We also assessed individual outcomes (MI, stroke, cardiovascular death) and the combined outcome (MI/cardiovascular death) by regression analyses to determine hazard ratios (HRs) and c statistics in models that included established risk factors, C-reactive protein, and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Participants with hs-cTnI >6 ng/L (ROC cutoff) were at higher risk for the primary outcome (HR 1.38, 95% CI 1.09-1.76; P = 0.008, adjusted models). For the individual outcomes, participants with hs-cTnI above the 99th percentile (≥10 ng/L) had higher risk for cardiovascular death (HR 2.15, 95% CI 1.32-3.52; P = 0.002) and MI (HR 1.49, 95% CI 1.05-2.10; P = 0.025) but not stroke (HR 1.38, 95% CI 0.76-2.47; P = 0.288, adjusted models). Addition of hs-cTnI to an established risk model with NT-proBNP also yielded a higher c statistic for the combined outcome of MI/cardiovascular death. The investigational Beckman Coulter hs-cTnI assay provides prognostic information for future MI and cardiovascular death in a stable high-risk population.

TH‐B‐BRA‐01: Educational Course Therapy

Long‐term survivors of radiation therapy have an increased risk of developing second cancers, cardiovascular disease, and many other late effects. Population‐based epidemiological studies have established risk models to quantify the relationship between excess risk and radiation dose. The quantification of radiation‐related late effects and the use of modern delivery techniques to reduce such effects is an important and growing area of research in medical physics.Currently, in the United States there are more than ten million cancer survivors and this number is rapidly increasing due to improved treatments, more frequent screening, and greater life expectancy. As the population of survivors increases so too does the need to minimize the likelihood of cancer therapy related late effects and specifically those related to radiation therapy. This continuing education session will focus on the two most commonly reported late effects from radiation therapy, second cancers and cardiac toxicity.This session will provide an overview of the dosimetric techniques currently used in late effects studies, dose response models, and how data in the literature can be translated into clinical practice (now and in the future). The specific learning objectives for this session include:1. To provide a general overview of the methods used in epidemiological studies of radiation‐related late effects.2. To present an overview of the current knowledge on radiation‐related cardiac toxicity.3. To present an overview of the current knowledge on radiation‐related second cancers.4. To improve understanding of the results of late effects studies and their effect on the future practice of medical physics.

Effects of C5 complement inhibitor pexelizumab on outcome in high-risk coronary artery bypass grafting: Combined results from the PRIMO-CABG I and II trials

The previous Pexelizumab for Reduction of Infarction and Mortality in Coronary Artery Bypass Graft Surgery I (PRIMO-CABG I) trial (n = 3099) indicated that C5 complement inhibition with pexelizumab might reduce myocardial infarction (MI) and postoperative mortality. PRIMO-CABG II was designed to investigate the safety and efficacy of terminal complement inhibition in reducing perioperative MI and mortality in patients undergoing CABG surgery who have 2 or more predefined preoperative risk factors. PRIMO-CABG II, a randomized, double-blind, placebo-controlled trial, enrolled 4254 patients undergoing CABG with or without valve surgery at 249 hospitals in North America and Western Europe from June 2004 to July 2005. The patients were randomly assigned to receive intravenous pexelizumab or placebo. The primary composite endpoint was the incidence of death or MI within 30 days of randomization. The PRIMO-CABG II trial did not meet its prespecified primary endpoint of death or MI at 30 days, the secondary endpoints of death at 30 days, or the development of new or worsening congestive heart failure (relative risk 0.91, 0.82, and 1.01, respectively; P > .05). However, in a combined analysis of both pivotal trials, PRIMO-CABG I and II (n = 7353), death at 30 days was significantly reduced for the greatest risk subset (n = 2156, pexelizumab 5.7% vs placebo 8.1%, P = .024). Furthermore, this mortality reduction persisted throughout the 180-day follow-up period (pexelizumab 11.1% vs placebo 14.4%, P = .036). Pexelizumab was associated with a nonsignificant 6.7% reduction in the primary composite endpoint of death or MI at postoperative day 30 in CABG patients enrolled in the PRIMO-CABG II trial, despite the suggestion of a more favorable treatment effect in the previous PRIMO-CABG I trial. However, an exploratory analysis of the combined PRIMO I and II data set using an established predictive risk model showed a mortality benefit for high-risk surgical patients.

Aortic Valve Replacement: Mortality Predictions of Surgeons Versus Risk Model

We compared the abilities of surgeons and of an established risk model to predict operative mortality after aortic valve replacement (AVR), and we investigated scenarios that give rise to discrepancies between these predictions. We reviewed all AVR procedures performed at a Veterans Affairs institution between 1993 and 2008 (n = 317). The abilities of the Continuous Improvement in Cardiac Surgery Program (CICSP) risk model and of the surgeons to predict operative mortality were assessed by computing the area under the receiver operating characteristic curve (AUC). We investigated cases in which there was a significant discrepancy (2-fold or greater) between the surgeons' and the CICSP model's predictions. The predictive abilities of both the surgeons and the CICSP risk model were good-AUC values were 0.73 and 0.75, respectively (P = 0.84)-but the surgeons' mean estimate of mortality risk (8.3% +/- 8.3%) exceeded both the CICSP model's estimate (6.6% +/- 8.3%) (P < 0.0001) and the actual mortality rate (5.4%). There was significant discrepancy between the two sources of prediction in 38% (122/317) of cases. In this subset of cases, the CICSP did not adjust for factors that influenced risk stratification by the surgeon in 33% (40/122) of cases; the most common of these factors were anticipation of a more extensive procedure, severe pulmonary disease other than chronic obstructive pulmonary disease, hepatic disease, and pulmonary hypertension. Both surgeons and the CICSP model performed well in risk-stratifying AVR patients, but the surgeons tended to overestimate the risk. The CICSP model did not capture some disease entities considered relevant in estimating mortality by surgeons.

Operative Mortality after Aortic Valve Replacement: Predictions Made by Surgeons versus Risk Model

Background: Risk models are useful tools for computing risk-adjusted outcomes. However, the models are only as good as the data on which they are based and therefore have limitations. Our aim was to compare the abilities of surgeons and an established risk model to predict operative mortality after aortic valve replacement (AVR). We also investigated scenarios that give rise to discrepancies between surgeons' and the risk model's predictions. Methods: The Veterans Affairs Continuous Improvement in Cardiac Surgery Program (CICSP) is a prospective database and a well-validated cardiac surgery risk model.