Important Predictor Of All-cause Mortality Research Articles

Impact of Pre-Diagnostic Risk Factors on Short- and Long-Term Ovarian Cancer Survival Trajectories: A Longitudinal Observational Study.

Tumor- and treatment-related factors are established predictors of ovarian cancer survival. New studies suggest a differential impact of exposures on ovarian cancer survival trajectories (i.e., rapidly fatal to long-term disease). This study examined the impact of pre-diagnostic risk factors on short- and long-term ovarian cancer survival trajectories in the Canadian context. This population-based longitudinal observational study included women diagnosed with invasive epithelial ovarian cancer from 1995 to 2004 in Ontario. Data were obtained from medical records, interviews, and the provincial cancer registry. Extended Cox proportional hazard models estimated the association between risk factors and all-cause and ovarian cancer-specific mortality by survival time intervals (<3 years (i.e., short-term survival), 3 to <6 years, 6 to <10 years, and ≥10 years (i.e., long-term survival)). Among 1421 women, histology, stage, and residual disease were the most important predictors of all-cause mortality in all survival trajectories, particularly for short-term survival. Reproductive and lifestyle factors did not strongly impact short-term overall survival but were associated with long-term overall survival. As such, among long-term survivors, history of breastfeeding significantly decreased the risk of all-cause mortality (HR 0.65; 95% CI 0.46, 0.93; p < 0.05), whereas smoking history (HR 1.75; 95% CI 1.27, 2.40; p < 0.05) and obesity (HR 1.81; 95% CI 1.24, 2.65; p < 0.05) significantly increased the risk of all-cause mortality. The findings were consistent with ovarian cancer-specific mortality. These findings suggest that pre-diagnostic exposures differentially influence survival time following a diagnosis of ovarian cancer.

Predictive Value of the Hb/RDW Ratio for the Risk of All-Cause Death in Patients with Heart Failure with Different Ejection Fractions

Introduction: The prognostic value of the ratio of haemoglobin to red cell distribution width (HRR) in different types of heart failure (HF) is not well known. Method and Results: We analysed the long-term prognostic value of HRR in patients with HF using the Cox proportional risk model and Kaplan-Meier method. We reviewed consecutive 972 HF patients. The overall mortality rate was 45.68%. Mortality was 52.22% in the HFrEF group and 40.99% in the HFpEF + HFmrEF group. Cox regression showed that when HRR increased by 1 unit, the risk of all-cause death in all HF patients decreased by 22.8% (HR: 0.772, 95% CI: 0.724, 0.823, p < 0.001), in the HFpEF + HFmrEF group it decreased by 15.5% (HR: 0.845, 95% CI: 0.774, 0.923, p < 0.001), and in the HFrEF group it decreased by 36.1% (HR: 0.639, 95% CI: 0.576, 0.709, p < 0.0001). Subgroup analysis showed that there were interactions between the EF and HRR groups. The group in which HRR best predicted all-cause death from HF was group 1 (EF <40%, HRR <9.45), followed by group 2 (EF <40%, HRR ≥9.45), and group 3 (EF ≥40%, HRR <9.45). HRR had no predictive value in group 4 (EF ≥40%, HRR ≥9.45). Conclusion: HRR is an important predictor of all-cause mortality in patients with HF, especially HFrEF. There is an interaction between HRR group and LVEF group.

The impact of predictability of coronary flow reserve for non-cardiovascular mortality, all-cause mortality, cardiovascular mortality in dialysis population

Abstract Background In the clinical setting, ischemic heart disease (IHD) is a major problem not only in general patients but also in regular hemodialysis (HD) patients. 13N-ammonia positron emission tomography (13NH3PET) is an established and excellent diagnostic test for IHD. We have reported about the predictability of coronary flow reserve (CFR) in poor prognosis in HD population. Some prior studies show that low CFR predicts poor prognosis for not only cardiovascular event but also all-cause mortality. Although it is well-known that CFR is an important predictor, there are limited data about predictability of CFR for non-cardiovascular (non-CV) mortality. We investigated the prognostic predictability of all-cause mortality, cardiovascular (CV) mortality and non-CV mortality. Methods In total 1020, patients who underwent NH3+PET suspected of ischemic heart disease from May 2013 to May 2022 were included. They are divided into two groups according to CFR cut off value (CFR=2.0). 465 patients were included into low CFR group and 555 patients were included into high CFR group. We collected all-cause mortality, cardiovascular (CV) mortality and non-CV mortality. CV mortality was defined death from myocardial infarction, sudden death, stroke, heart failure, arrhythmia and ischemic colitis. We have followed them in 1282 days (median, 1st-3rd quartile was 510-2116). Results We found any cause death were 285 cases (the high CFR group vs the low CFR group; 165 (35.5%) vs 118 (21.3%), p&amp;lt;0.001), CV death were 121 cases (52 (9.4%) vs 68 (14.6%), p=0.010) and non-CV death were 164 cases (66(11.9%) vs 97 (20.9%, p&amp;lt;0.001)). Kaplan-Meier curve analysis and Cox regression model shows the low CFR groups shows poor prognosis for all-cause mortality (log rank; p&amp;lt;0.001, hazard ratio (HR); 1.9964, 95% confidential interval (CI); 1.576-2.529), CV mortality (log rank; p=0.0009, HR; 1.834, 95%CI; 1.278-2.633) and non-CV mortality (log rank; p&amp;lt;0.0001, HR; 2.213, 95%CI; 1.555-2.907). Furthermore, multivariate cox regression model shows the continuous value of CFR is an independent predictor for both all-cause mortality (HR0.180, 95%CI 0.074-0.435, p=0.0001) and non-CV mortality (HR0.553, 95% CI0.397-0.769, p=0.0004). Conclusion In dialysis population, CFR is an important predictor for all-cause mortality, CV mortality and non-CV mortality. In addition, CFR would predict non-CV death in HD population even though CFR is an index for IHD.

Implication of Serious Infections in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis for the First Cycle of Rituximab: A Pilot Study in a Single Korean Center.

This study investigated the clinical implications of serious infections in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) who received the first cycle of rituximab (RTX) during the first 6 months of follow-up. The medical records of 36 AAV patients treated with RTX were reviewed. A weekly dose of 375 mg/m2 RTX was administered for 4 weeks to all patients along with glucocorticoids. Serious infections were defined as those requiring hospitalization. All-cause mortality during the first 6 months of follow-up was counted. The follow-up duration was defined as the period from the first RTX infusion to 6 months after the first RTX infusion. The median age was 60.5 years, and 16 patients were male. Seven of 36 patients (19.4%) died and three AAV patients had five cases of serious infection such as enterocolitis, pulmonary aspergillosis, atypical pneumonia, cytomegalovirus pneumonia, and cellulitis. AAV patients with serious infections during the first 6 months of follow-up exhibited a significantly lower cumulative survival rate than those without serious infections (p<0.001). However, we found no independent predictor of serious infections using the Cox hazard model analysis. Serious infection is an important predictor of all-cause mortality in Korean patients with AAV who received their first cycle of RTX but there were no significant variables to predict the occurrence of serious infections at the first RTX. Thus, in cases refractory to other induction therapies, RTX should be strongly considered, despite an increase in mortality rate.

Is there an association between total physical activity level and VO2max among fitness club members? A cross-sectional study

BackgroundSince cardiorespiratory fitness is an important predictor for all-cause mortality, it is of interest to know if meeting the physical activity (PA) recommendations is associated with higher levels of maximal oxygen uptake (VO2max). We aimed to investigate the association between total PA level given as counts per minute (cpm) and minutes in moderate-to-vigorous PA (MVPA), and VO2max in new fitness club members.MethodsA total of 62 men and 63 women (≥ 18 years), defined as healthy (no disease considered to hinder PA) participated in this study. VO2max (mL kg−1 min−1) was measured with a cardiopulmonary exercise (modified Balke protocol), and total PA level was measured with ActiGraph GT1M for seven consecutive days. All participants accumulating ≥ 10 h of activity recordings ≥ 4 days were included in the data analysis. To examine associations between PA level and VO2max, a Pearson correlation and a multiple linear regression analysis adjusted for covariates were used.ResultsVO2max (mL kg−1 min−1) was 40.5 ± 7.2 in men and 35.1 ± 6.0 in women. Total PA level (cpm) and MVPA (min) were 352.4 ± 123.4 and 260.0 ± 132.6 in men and 361.4 ± 103.8 and 273.2 ± 137.0 in women. Total PA level (men: r = 0.346, p < 0.01, women: r = 0.267 p < 0.01) and MVPA (men: r = 0.359, p = < 0.01, women: r = 0.236, p = 0.03) was associated with VO2max. When adjusting for age and body fat percentage, total PA level and MVPA were no longer associated with VO2max (men: p = 0.11 and p = 0.79, women: p = 0.40 and p = 0.61). In men, age (β = − 0.469 p < 0.01) and body fat percentage (β = − 0.483, p < 0.01) were the strongest predictor for VO2max. For women, body fat percentage was the strongest predictor for VO2max (β = − 0.483, p < 0.01).ConclusionsTotal PA level and MVPA were associated with VO2max, but the association was low and diminished when adjusted for age and body fat percentage. Body fat percentage (men and women) and age (men) were more strongly associated with VO2max than total PA level and MVPA.

Pulmonary artery capacitance and pulmonary vascular resistance as prognostic indicators in acute pulmonary embolism.

AimsThe non-invasive calculation of right ventricular (RV) haemodynamics as pulmonary artery (PA) capacitance (PAC) and pulmonary vascular resistance (PVR) have proved to be feasible, easy to perform, and of high prognostic value. We, therefore, evaluated whether baseline PAC and PVR could predict clinical outcomes for patients with acute pulmonary embolism (PE).Methods and resultsWe prospectively followed 373 patients [mean (standard deviation) age, 64.1 (14.9) years; 58.4% were men, and 27.9% had cancer] who had acute PE and transthoracic echocardiography within 1 day of diagnosis from 1 March 2013 through 30 June 2020. Pulmonary artery capacitance was calculated as left ventricular stroke volume/(PA systolic pressure − PA diastolic pressure). Pulmonary vascular resistance was calculated as (tricuspid regurgitant velocity/RV outflow tract velocity time integral) × 10 + 0.16. These two variables were calculated retrospectively from the values obtained with transthoracic echocardiography. Pulmonary artery capacitance was acquired in 99 (27%) patients and PVR in 65 (17%) patients. Univariable and bivariable logistic regression analyses, and receiver operating characteristic curves were used to evaluate the ability of these haemodynamic measurements to predict mortality up to 6 months. After using bivariable models to adjust individually for age, cancer, and pulmonary hypertension. Pulmonary vascular resistance was associated with all-cause mortality at 3 months [area under the curve (AUC) 0.75, 95% confidence interval (CI) 0.61–0.86; P = 0.01], and 6 months (AUC 0.81; 95% CI 0.69–0.91; P≤ 0.03). Pulmonary artery capacitance was associated with all-cause mortality at 30 days (AUC 0.95; 95% CI 0.82–0.99; P < 0.001) and 3 months (AUC 0.84; 95% CI 0.65–0.99; P = 0.003).ConclusionNon-invasive measurement of RV haemodynamics could provide prognostic information of patients with acute PE. Pulmonary artery capacitance and PVR are potentially important predictors of all-cause mortality in these patients and should be explored in future studies.

How Much Delay Matters? How Time to Treatment Impacts Overall Survival in Early Stage Lung Cancer.

The aim of this study was to identify drivers of time from diagnosis to treatment (TTT) of surgically resected early stage non-small cell lung cancer (NSCLC) and determine the effect of TTT on post-resection survival. Large database studies that lack relevant comorbidity data have identified longer TTT asa driver of worse overall survival. From January 1, 2014 to April 1, 2018, 599 patients underwent lung resection for clinical stage I and II NSCLC. Random forest classification, regression, and survival were used to estimate likelihood of TTT = 0 (tissue diagnosis obtained at surgery), >0 (diagnosis obtained pre-resection), and effect of TTT on all-cause mortality. Patients with TTT > 0 (n = 413) had median TTT of 42 days (25-75 th percentile: 27-59 days). Patients with TTT = 0 (n = 186) had smaller tumors and higher percent predicted forced expiratory volume in 1 second (FEV 1 %). Patients with history of stroke, oncology consultation, invasive mediastinal staging, low and high extremes of FEV 1 % had longer TTT. Higher clinical stage, lack of preoperative stress test, anemia, older age, lower FEV1% and diffusion lung capacity, larger tumor size, and longer TTT were the most important predictors of all-cause mortality. One- and 5-year overall survival decreased when TTT was >50 days. Preoperative physiologic workup and multidisciplinary evaluation were the predominant drivers of longer TTT. Patients with TTT = 0have more favorable presentation and should be considered in TTT analyses for early stage lung cancer populations. The time needed to clinically stage and optimize patients for resection is not deleterious to overall survival until resection is performed after 50 days from diagnosis.

Abstract 12501: Admission Serum Chloride Concentrations and Mortality Outcomes in Heart Failure Patients

Introduction: Acute decompensated CHF is associated with a number of electrolyte abnormalities. Hyponatremia has been well established as having a close association with mortality in CHF patients, however in the past decade several robust retrospective studies have raised the intriguing possibility that chloride levels may be as or more significant than sodium levels as a mechanistic player in the pathophysiology of CHF, and a potential target for future therapeutics. Hypothesis: Admission chloride is related to all-cause mortality in CHF patients, even when adjusted for LVEF. Methods: 96 patients admitted to the Hospital of the University of Pennsylvania between 1/1/2017 and 12/31/2019 with a diagnosis of acute decompensated CHF were selected. The relationship between admission chloride on first admission during which patient received IV diuretics and all-cause mortality was analyzed by univariate regression, with multivariate adjustment for LVEF. Results: Per our univariate Cox proportional hazards regression model, admission chloride was inversely related with all-cause mortality in our population of CHF patients (HR per unit change 0.925; 95% CI: 0.864-0.990; p&lt;0.05) indicating a ~7.5% relative improvement in survival per unit increase in chloride. After multivariable adjustment for LVEF, admission chloride remained independently inversely related with mortality (HR per unit change 0.923; 95% CI: 0.859-0.991, p&lt;0.05). After multivariable adjustment for admission sodium however, admission chloride lost its significance with mortality (HR per unit change 0.953; p=0.213). Conclusions: Our study confirms that chloride levels are an important predictor of all-cause mortality in CHF patients, independent of LVEF. Figure 1 visually illustrates the worsening of cumulative mortality in patients within the lowest chloride tertile, although our Kaplan Meier survival curves remained just outside the bounds of significance (p=0.052).

Prevalence and Risk Factors for Cognitive Frailty in Aging Hypertensive Patients in China.

Hypertension is one of the most common chronic diseases and a major risk factor for stroke, myocardial infarction and cardiovascular death. Cognitive frailty is an important predictor of all-cause mortality and dementia in aging individuals. Hypertension is closely related to cognitive frailty and these two conditions often coexist in aging individuals. Few studies have explored the relationship between hypertension and cognitive frailty in the Chinese population. This study investigates the epidemiological characteristics of and factors related to cognitive frailty in aging Chinese patients with hypertension. In total, cognitive function, weakness, social support, depression and sociodemographic were assessed in 305 participants aged 60 and over. Univariate and multivariate logistic regression models were constructed. The prevalence of cognitive frailty in aging Chinese hypertensive patients was 9.8% (95% CI = 6.4–13.2%). After adjusting for confounding variables, logistic regression showed that the course of hypertension (6–10 years, OR = 8.588, 95% CI = 1.608–45.859;course of more than 10 years, OR = 9.020, 95%CI = 1.854–43.892), multimorbidity (OR = 11.231, 95% CI = 2.912–43.322), depression (OR = 6.917, 95% CI = 2.424–19.738) and social support (OR = 0.187, 95% CI = 0.071–0.492) were independently associated with cognitive frailty. The prevalence of cognitive frailty in aging patients with hypertension in China should not be ignored. The course of hypertension, multimorbidity and depression are the risk factors of cognitive frailty in the aging population and a better level of social support is the protective factor for cognitive frailty.

Prognostic model to identify and quantify risk factors for mortality among hospitalised patients with COVID-19 in the USA

ObjectivesTo develop a prognostic model to identify and quantify risk factors for mortality among patients admitted to the hospital with COVID-19.DesignRetrospective cohort study. Patients were randomly assigned to either training...

Prognostic role of left ventricular diastolic function assessed by speckle tracking echocardiography in patients after surgical ventricular repair

Abstract Background Assessment of left ventricular (LV) diastolic function brings important prognostic information for patients with heart failure and could be evaluated by speckle tracking echocardiography (STE). Less known about its role in patients planned for surgical ventricular repair due to LV aneurysm. Purpose The aim of this study was to evaluate the prognostic role of STE parameters of LV diastolic function for prediction of all-cause mortality in patients after surgical ventricular repair. Methods We retrospectively evaluated data of 163 consecutive pts (mean age 62.3±11.5 years, 74.8% males) with anteroapical LV aneurysm who underwent surgical ventricular repair combined with coronary artery bypass surgery (71.8%) Prognostic role for prediction of all-cause mortality was assessed for various STE parameters, including left atrial strain (LAS) measured as peak reservoir strain and for the ratio of early to late global longitudinal strain rate (GLSRe/GLSRa). Results During a median follow-up of 4.7 years (IQR: 1.6–8.9 years) there were 65 deaths, 5 year survival rate was 73.8 (95% CI 67–79%). Baseline ejection fraction, end-diastolic and end-systolic volumes of LV did not differ between pts who died and survived at 5 year after the surgery, whereas LAS was significantly higher and GLSRe/GLSRa was significantly lower in survivors. Cox proportional hazard model adjusted to demographic and clinical variables demonstrated that LAS and GLSRe/GLSRa were independent predictors of all-cause death, with HR of 0.79 (95% CI 0.66–0.95, p=0.012) for each 5% increase of LAS and HR of 1.24 (95% CI 1.1–1.4, p=0.001) for each 0.5 increase of GLSRe/GLSRa. Moreover, GLSRe/GLSRa remained an independent predictor after additional adjustment for LV end-systolic volume, sphericity index and presence of mitral insufficiency of grade 2 and higher. A significant difference in median survival time was demonstrated according to the following cut-offs: LAS ≥16.7% (12.1 vs. 6.4 years, p=0.01), GLSRe/GLSRa ratio ≥2.3 (3.3 years vs. 10.2 years, p=0.0005) (Figure). The classification and regression tree analysis with the application of all two-dimensional, Doppler and various speckle-tracking echocardiographic parameters revealed that GLSRe/GLSRa and LAS were the most important echocardiographic variables for risk stratification for 5-year mortality. Conclusion This study demonstrates that STE parameters of LV diastolic function are important predictors of all-cause mortality after surgical ventricular repair due to anteroapical aneurysm of LV and could be used in the preoperative decision-making process. Funding Acknowledgement Type of funding source: None

Identification of important risk factors for all-cause mortality of acquired long QT syndrome patients using random survival forests and non-negative matrix factorization

Acquired long QT syndrome (aLQTS) is often associated with poor clinical outcomes. The purpose of this study was to examine the important predictors of all-cause mortality of aLQTS patients by applying both random survival forest (RSF) and non-negative matrix factorization (NMF) analyses. Clinical characteristics and manually measured electrocardiographic (ECG) parameters were initially entered into the RSF model. Subsequently, latent variables identified using NMF were entered into the RSF as additional variables. The primary outcome was all-cause mortality. A total of 327 aLQTS patients were included. The RSF model identified 16 predictive factors with positive variable importance values: cancer, potassium, RR interval, calcium, age, JT interval, diabetes mellitus, QRS duration, QTp interval, chronic kidney disease, QTc interval, hypertension, QT interval, female, JTc interval, and cerebral hemorrhage. Increasing the number of latent features between ECG indices, which incorporated from n = 0 to n = 4 by NMF, maximally improved the prediction ability of the RSF-NMF model (C-statistic 0.77 vs 0.89). Cancer and serum potassium and calcium levels can predict all-cause mortality of aLQTS patients, as can ECG indicators including JTc and QRS. The present RSF-NMF model significantly improved mortality prediction.

A comparison of high versus low dose of exercise training in exercise-based cardiac rehabilitation: a randomized controlled trial with 12-months follow-up

Objective: To assess if a higher dose of exercise training in exercise-based cardiac rehabilitation could affect improvements in aerobic capacity and muscle strength. Design: Assessor-blinded randomized controlled trial with 12-months follow-up. Setting: Aarhus University Hospital, Aarhus, Denmark. Subjects: A total of 164 cardiac patients referred to exercise-based cardiac rehabilitation were recruited. Interventions: Patients were randomized to 1-hour exercise sessions either three times weekly for 12 weeks (36 sessions, high-dose group) or twice weekly for 8 weeks (16 sessions, low-dose group). The same standardized exercise and intensity protocol including aerobic and muscle strength training was used in all participants. Main measures: Primary outcome was changes in VO2peak. Secondary outcomes were changes in maximal workload, muscle strength and power. Measures were obtained at baseline, after termination of the rehabilitation programme and at follow-up after 6 and 12 months. Results: After the end of intervention, statistically significant between-group differences were seen in favour of the high-dose group in all outcomes: VO2peak 2.6 (mL kg−1 min−1) (95% confidence interval (CI): 0.4–4.8), maximal workload 0.3 W kg−1 (95%CI: 0.02–0.5), isometric muscle strength 0.7 N m kg−1 (95%CI: 0.1–1.2) and muscle power 0.3 W kg−1 (95%CI: 0.04–0.6). After 12 months, a significant between-group difference only persisted in VO2peak and maximal workload. Conclusion: A higher dose of exercise training had a small effect on all outcomes at termination of intervention. A long-term effect persisted in VO2peak and maximal workload. Although the effect was small, it is an important finding because VO2peak is the most important predictor of all-cause mortality in cardiac patients.

Sociodemographic, lifestyle and metabolic predictors of all-cause mortality in a cohort of community-dwelling population: an 18-year follow-up of the North West Adelaide Health Study

IntroductionStudies examining potential factors of all-cause mortality comprehensively at community level are rare. Using long-term community-based follow-up study, we examined the association of sociodemographic and behavioural characteristics, metabolic and chronic...

Reduced Cardiorespiratory Capacity in Children with Autism Spectrum Disorders.

Background—Children with autistic spectrum disorders (ASDs) are frequently hampered by motor impairment. It limits them from regularly practicing physical activities and results in a lower physical fitness even though low cardiorespiratory fitness is one of the most important predictors of all-cause mortality. This study aimed to investigate the cardiorespiratory fitness of boys with ASD compared to typically developed children. Methods—forty male children participated. Twenty were control children (CONT—10.0 ± 1.6 years) and 20 were ASD children (ASD—10.7 ± 1.2 years; intellectual quotient > 70). All participants completed an incremental exercise test on a treadmill. An evaluation of motor characteristics by three tests was conducted (muscular strength; explosive power; flexibility). Assessments of daily physical activity were obtained by questionnaires (PAQ-C) and by actigraphy. Results—in the ASD group, aerobic capacity values (VO2peak), effort duration and maximal speed were significantly lower compared to CONT (p < 0.05). Flexibility, explosive power and muscular strength were significantly lower in ASD compared to CONT (p < 0.05). Similarities between all children were observed for physical activity evaluation by actigraphy and with the PAQ-C. Conclusions—children with ASD had lower cardiorespiratory fitness than CONT despite similar physical activity levels. Our results suggested that the difference may be due to motor discrepancies.

Mother-daughter genetic relationship in central obesity

Central obesity is an important predictor of all-cause mortality. Children of obese parents bear a greater risk to develop obesity themselves. ObjectiveTo find possible correlations in central obesity and other cardio-metabolic parameters between mother and daughter. Subjects and methodsThe current study measured anthropometric, laboratory, radiologic and genetic data for 120 centrally obese mothers and their 200 daughters aged from 12 to 18 years old. ResultsTwenty-two percent of the daughters was overweight, 15.5% obese and 30% had central obesity. Genotype E3/E4 of apolipoprotein E was the most frequent genotype in mothers group (38.3%) and daughters with visceral obesity (46.7%) while E3/E3 was the most frequent genotype in daughters group without visceral obesity (42.9%). In both mothers and daughters, disturbed lipid profile was found in those with E3 allele, while increased BMI and weight were found among those with alleles E2 and E4 respectively. Daughters genotype E3/E4 had the highest significant values of most of the studied anthropometric measurements and lipid profile, while mother's genotype E4/E4 had the highest significant values of most of the studied anthropometric measurements and insulin. ConclusionA key role could be played by the mother in the primary prevention of central obesity due to the consistent association of central obesity indices between mothers and daughters.

Cardiovascular Event Prediction by Machine Learning: The Multi-Ethnic Study of Atherosclerosis.

Machine learning may be useful to characterize cardiovascular risk, predict outcomes, and identify biomarkers in population studies. To test the ability of random survival forests, a machine learning technique, to predict 6 cardiovascular outcomes in comparison to standard cardiovascular risk scores. We included participants from the MESA (Multi-Ethnic Study of Atherosclerosis). Baseline measurements were used to predict cardiovascular outcomes over 12 years of follow-up. MESA was designed to study progression of subclinical disease to cardiovascular events where participants were initially free of cardiovascular disease. All 6814 participants from MESA, aged 45 to 84 years, from 4 ethnicities, and 6 centers across the United States were included. Seven-hundred thirty-five variables from imaging and noninvasive tests, questionnaires, and biomarker panels were obtained. We used the random survival forests technique to identify the top-20 predictors of each outcome. Imaging, electrocardiography, and serum biomarkers featured heavily on the top-20 lists as opposed to traditional cardiovascular risk factors. Age was the most important predictor for all-cause mortality. Fasting glucose levels and carotid ultrasonography measures were important predictors of stroke. Coronary Artery Calcium score was the most important predictor of coronary heart disease and all atherosclerotic cardiovascular disease combined outcomes. Left ventricular structure and function and cardiac troponin-T were among the top predictors for incident heart failure. Creatinine, age, and ankle-brachial index were among the top predictors of atrial fibrillation. TNF-α (tissue necrosis factor-α) and IL (interleukin)-2 soluble receptors and NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) levels were important across all outcomes. The random survival forests technique performed better than established risk scores with increased prediction accuracy (decreased Brier score by 10%-25%). Machine learning in conjunction with deep phenotyping improves prediction accuracy in cardiovascular event prediction in an initially asymptomatic population. These methods may lead to greater insights on subclinical disease markers without apriori assumptions of causality. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005487.

The Effect of Physical Activity and Cardiorespiratory Fitness on All-Cause Mortality in Hong Kong Chinese Older Adults.

It is unclear whether physical activity (PA) could predict all-cause mortality independently of cardiorespiratory fitness, and there are relatively few studies evaluating the combined effect of PA and cardiorespiratory fitness on mortality. We invited 1,242 Chinese older adults aged 69-94 years from the MrOs and MsOs cohort (Hong Kong) study for a 7-year follow-up. PA was measured by the Physical Activity Scale of the Elderly (PASE). Cardiorespiratory fitness, expressed as maximal oxygen uptake (VO2max), was assessed by performing symptom-limited maximal exercise testing on an electrically braked bicycle ergometer and 6-m walk test. We aimed to examine the independent and combined effect of PA and VO2max with all-cause mortality by cox proportional hazards models. Ninety-nine deaths occurred over a mean follow-up of 5.3 ± 0.8 years. PA was inversely associated with all-cause mortality in unadjusted and fully-adjusted models, and the association was still significant after further adjusted for VO2max. In stratified analysis, PA was significantly related to all-cause mortality within both unfit and fit strata. As compared with those being active and fit, physically inactive and cardiorespiratory unfit individuals had the highest all-cause mortality risk. Physically active but unfit individuals and inactive but fit individuals had similar all-cause mortality risk. Among older adults, PA was an important predictor of all-cause mortality independently of VO2max. High cardiorespiratory fitness does not necessarily confer low mortality risk in physically inactive older adults.

Cardiopulmonary Fitness and Clinical Outcomes in Adults Followed in the Cooperative Study for Sickle Cell Disease

Introduction: Cardiopulmonary fitness is significantly reduced among individuals with sickle cell disease (SCD). Cardiopulmonary fitness is also an important predictor of morbidity and all-cause mortality in the general population. However, the relationship between fitness and clinical outcomes in SCD has not been well studied. The objectives of this analysis were to: 1) determine the factors associated with fitness in a cohort of adults with SCD, and 2) evaluate the relationship of fitness to hospitalization for pain and acute chest syndrome (ACS) and overall mortality. We hypothesized that clinical factors such as age, sex, hemoglobin, SCD genotype and cardiopulmonary disease significantly affect fitness, and that poor fitness is a predictor of more frequent hospitalizations for pain and ACS and higher mortality in adults with SCD.Methods: A cohort of adults with SCD was constructed from participants enrolled in phase 2 of the Cooperative Study of Sickle Cell Disease (CSSCD) who underwent exercise testing (modified Balke treadmill protocol). Primary measure for fitness was total treadmill duration. Retrospective pain or ACS hospitalization rates were calculated using events in the 3 years prior to exercise testing. Mortality and prospective hospitalization rates for pain and ACS were calculated using events after exercise testing with a minimum 6 month follow-up. Results of pulmonary function testing (PFT), echocardiography, and laboratory testing within 3 years of exercise testing were included in our analysis. Standard descriptive analyses were performed (SPSS V24). Multivariable negative binomial and Cox proportional hazards models were constructed to evaluate the relationship of fitness to ACS and pain hospitalization rates and mortality, respectively. Multivariable linear models were constructed to determine factors associated with fitness.Results: A total of 223 participants had valid exercise testing data (64% female, 70% hemoglobin SS or S/b0 thalassemia, mean age 43.3 ± 7.5 years, mean hemoglobin 9.1 ± 2.2 g/dl, mean follow-up 2.7 ± 0.7 years after exercise testing). Participants completed a mean of 11.6 ± 5.2 min on the treadmill, with 87% completing ≥ 3 stages but only 17% completing all 10 stages. We categorized fitness into tertiles of treadmill duration (5.7 vs. 11.8 vs. 18.1 min, p < 0.001). Age (45.2 vs. 43.1 vs. 41.3 years, p = 0.007), baseline hemoglobin (8.5 vs. 9 vs. 9.8 g/dl, p = 0.003), as well as the proportion of females (77 vs. 71 vs. 40%, p < 0.001) and participants with abnormal PFT (58 vs. 35 vs. 39%, p = 0.008), differed significantly across fitness tertiles. Pain or ACS hospitalization rates during the 3 years prior to exercise testing were not significantly different across fitness tertiles. Using multivariable linear regression, male sex (β = 3.1, p < 0.001), lower age at exercise testing (β = -0.14, p = 0.003), and higher hemoglobin (β = 0.44, p = 0.049) were independently associated with higher fitness, with abnormal PFT trending toward significance (β = -1.28, p = 0.07). In this model, genotype, tricuspid regurgitant jet velocity (TRJV) ≥ 2.5 m/s, and pain and ACS hospitalization rates prior to exercise testing were not significantly associated with fitness. Using a negative binomial regression model, we found that fitness did not predict future pain or ACS episodes after adjustment for age, sex, genotype, hemoglobin and TRJV. Fitness also did not predict survival in our cohort (hazard ratio, 0.97; 95% CI [0.84, 1.13], p = 0.71), in which death was reported in only 9 participants. In our Cox regression model, male sex (HR 7.1; 95% CI [1.3, 38.9]; p = 0.02) and lower hemoglobin (HR 0.56; 95% CI [0.36, 0.88]; p = 0.01) were independent predictors of death, but age at exercise testing, abnormal PFT and TRJV ≥ 2.5 m/s were not.Conclusions: In adults with SCD, lower fitness is significantly associated with female sex, older age, lower hemoglobin and abnormal PFT. Fitness did not predict survival or future pain or ACS events in the CSSCD. Given that cardiopulmonary fitness remains an important predictor of all-cause mortality in the general population, larger scale prospective studies in SCD are needed to evaluate the impact of regular exercise on improving fitness, quality of life, clinical outcomes and mortality in this population. DisclosuresBadawy:Ann & Robert H. Lurie Children’s Hospital of Chicago: Employment; Ann & Robert H. Lurie Children’s Hospital of Chicago: Research Funding; Salveo Health Communications LLC: Consultancy. Payne:National Center on Birth Defects and Developmental Disabilities: Employment. Liem:Ann & Robert H. Lurie Children’s Hospital of Chicago: Employment; Ann & Robert H. Lurie Children’s Hospital of Chicago: Research Funding; National Institute of Health: Research Funding.

Depressive symptoms but not chronic pain have an impact on the survival of patients undergoing maintenance hemodialysis.

IntroductionMore than 1/3 of patients with end-stage renal disease who are in a chronic dialysis program suffer from chronic pain and depression/anxiety. The aim of the study was to determine the impacts of symptoms of depression/anxiety, chronic pain and quality of life (QoL) on 6-year patient survival.Material and methodsObservational study of end-stage renal disease patients on maintenance hemodialysis (n = 205) who met the inclusion criteria. Patients from three dialysis centers in Lower Silesia were asked to complete a battery of validated questionnaires: the Hospital Anxiety and Depression Scale (HADS), the 36-item Short Form Health Survey Questionnaire, the Verbal Rating Scale (VRS) and the Visual Analog Scale (VAS). Clinical and biochemical data (dialysis adequacy) were recorded.ResultsOne hundred thirty from 205 enrolled hemodialysis patients (63.4%) suffered from chronic pain. Patients with pain were on maintenance dialysis for longer times and had higher levels of parathyroid hormone, more depressive symptoms and a lower QoL than those without pain. In the 6-year period, 96 (46.8%) patients died. The most common cause of death was cardiovascular disease in 44 (45.8%) patients. Highly depressed patients (HADS depression score > 8) exhibited higher mortality (< 8 vs. > 8 points; p = 0.016) independent of age, diabetes, cardiovascular disease, C-reactive protein or albumin level.ConclusionsChronic pain, although common among hemodialysis patients, did not lower survival. Depressive symptoms are an important predictor for all-cause mortality in hemodialysis patients, with the relationship independent of nutritional or inflammatory status.