Established Risk Factor For Mortality Research Articles

Renal Hyperfiltration as a New Mechanism of Smoking-Related Mortality.

Renal hyperfiltration (RHF), an established risk factor for mortality, is prevalent among tobacco smokers. The aim of this study was to assess the mediating role of RHF in the association between smoking and mortality. Data of this study were retrieved from the cohort of the Kuopio Ischemic Heart Disease Risk Factor Study (KIHD), including 2064 males from Finland. Study participants were followed over a 35-year period. Using classic and counterfactual mediation analysis approaches, we estimated the mediative effect of RHF in the association between smoking and each of the following outcomes: All-cause mortality, cardiovascular disease (CVD) mortality, and non-CVD mortality. The risk of all-cause mortality in smokers was twice that in nonsmokers (hazard ratio [HR], 2.06; 95% confidence interval [CI]: 1.84 to 2.31). Under the counterfactual framework the direct effect of smoking on all-cause mortality, controlled for RHF, corresponded to an HR of 2.00 (95% CI: 1.78 to 2.30). Of the effect of smoking on mortality, 5% (p-value = .016) was mediated by RHF. This finding concerned particularly non-CVD mortality. RHF mediated the effect of smoking on non-CVD and all-cause mortality, but not on CVD mortality. The generalizability of our study results is however limited by its focus on a Finnish male cohort, underscoring the need for further investigation into RHF's broader implications across diverse populations. This study elucidates the complex interplay between smoking, renal hyperfiltration (RHF), and mortality, offering novel insights into the mediating role of RHF. Our findings demonstrate that RHF significantly mediates the relationship between smoking and non-cardiovascular disease (non-CVD), but not CVD mortality. This distinction underscores the multifaceted role of RHF beyond its established association with cardiovascular events. By highlighting the specific pathways through which RHF mediates some of the smoking-attributed mortality, this research contributes to our understanding of the mechanisms linking smoking to mortality.

Morbidity and mortality in tuberculosis associated immune reconstitution inflammatory syndrome in children living with HIV: A narrative review

Tuberculosis-associated immune reconstitution syndrome (TB-IRIS) is an increasingly recognized complication of children living with HIV who are receiving treatment for active tuberculosis (TB). The purpose of the study was to appraise available evidence of morbidity and mortality related to TB IRIS among the paediatric population. A non-systematic review of the literature was conducted by retrieving records from Scopus, PubMed and Google Scholar). Four specific research questions assessing the risk factors (age, undernutrition, extrapulmonary TB and degree of immunosuppression) for TB-IRIS were discussed. The search yielded 370 articles, subsequently screened for eligibility according to the inclusion criteria. The majority of the articles were adult studies. Six studies were identified: Three retrospective and three prospective studies. The majority of the studies were conducted in TB/HIV-endemic countries. Only one study addressed mortality due to TB-IRIS as an outcome. A total of 6 mortalities related to TB-IRIS were reported. Advanced immunosuppression is universally agreed as an established risk factor for mortality in TB-IRIS in children. The severe presentation was more common in children with extrapulmonary tuberculosis. There is a paucity of data available on mortality in HIV-infected children with TB-IRIS. Future research is needed to assess the predictive factors of morbidity and mortality in HIV-infected children with TB-IRIS especially in low resource and high endemic countries.

Sex differences in COVID-19 mortality risk in patients on kidney function replacement therapy

In the general population with COVID-19, the male sex is an established risk factor for mortality, in part due to a more robust immune response to COVID-19 in women. Because patients on kidney function replacement therapy (KFRT) have an impaired immune response, especially kidney transplant recipients due to their use of immunosuppressants, we examined whether the male sex is still a risk factor for mortality among patients on KFRT with COVID-19. From the European Renal Association COVID-19 Database (ERACODA), we examined patients on KFRT with COVID-19 who presented between February 1st, 2020, and April 30th, 2021. 1204 kidney transplant recipients (male 62.0%, mean age 56.4 years) and 3206 dialysis patients (male 61.8%, mean age 67.7 years) were examined. Three-month mortality in kidney transplant recipients was 16.9% in males and 18.6% in females (p = 0.31) and in dialysis patients 27.1% in males and 21.9% in females (p = 0.001). The adjusted HR for the risk of 3-month mortality in males (vs females) was 0.89 (95% CI 65, 1.23, p = 0.49) in kidney transplant recipients and 1.33 (95% CI 1.13, 1.56, p = 0.001) in dialysis patients (pinteraction = 0.02). In a fully adjusted model, the aHR for the risk of 3-month mortality in kidney transplant recipients (vs. dialysis patients) was 1.39 (95% CI 1.02, 1.89, p = 0.04) in males and 2.04 (95% CI 1.40, 2.97, p < 0.001) in females (pinteraction = 0.02). In patients on KFRT with COVID-19, the male sex is not a risk factor for mortality among kidney transplant recipients but remains a risk factor among dialysis patients. The use of immunosuppressants in kidney transplant recipients, among other factors, may have narrowed the difference in the immune response to COVID-19 between men and women, and therefore reduced the sex difference in COVID-19 mortality risk.

FC008: Sex Difference in COVID-19 Mortality Risk among Patients on Kidney Function Replacement Therapy

BACKGROUND AND AIMSIn the general population with COVID-19, male sex is an established risk factor for mortality. A more robust immune response to COVID-19 in women has been suggested to be one of the factors explaining this sex difference in mortality. Patients on kidney function replacement therapy (KFRT) have an impaired immune response, especially kidney transplant recipients due to their use of immunosuppressants. In this study, we therefore examined whether male sex is still a risk factor for mortality among patients on KFRT with COVID-19.METHODData were used from the European Renal Association COVID-19 Database (ERACODA) of kidney transplant recipients and dialysis patients who presented with COVID-19 between 1 February 2020 and 30 April 2021. The primary study outcome was 3-month mortality. As secondary outcomes, in-hospital mortality and 28-day mortality were examined. Associations were investigated using multivariable Cox proportional-hazards regression analysis. Assuming immunosuppressant use is among the main factors contributing to excess mortality in kidney transplant recipients compared with dialysis patients, we also investigated the association of type of KFRT with mortality by sex.RESULTSERACODA included 1204 kidney transplant recipients (male: 62.0%, mean age: 56.4 years) and 3206 dialysis patients (male: 61.8%, mean age: 67.7 years). Three-month mortality in kidney transplant recipients was 16.9% in males and 18.6% in females (P = 0.31) and in dialysis patients 27.1% in males and 21.9% in females (P = 0.001). In a model adjusted for age, frailty, smoking and comorbidities, the aHR for the risk of 3-month mortality in males (versus females) was 0.87 (95% CI: 63, 1.21, P = 0.41) in kidney transplant recipients and 1.32 (95% CI: 1.13, 1.55, P = 0.001) in dialysis patients (P for interaction = 0.03). In a fully adjusted model, the aHR for the risk of 3-month mortality in kidney transplant recipients (versus dialysis patients) was 1.26 (95% CI: 1.02, 1.56, P = 0.03) in males and 1.73 (95% CI: 1.31, 2.27, P < 0.001) in females (p for interaction = 0.03). Essentially similar results were obtained for in-hospital mortality and 28-day mortality.CONCLUSIONIn patients on kidney function replacement therapy with COVID-19, male sex is not a risk factor for mortality among kidney transplant receipts but remains a risk factor among dialysis patients. The use of immunosuppressants in kidney transplant recipients, among other factors, may have narrowed the difference in the immune response to COVID-19 between men and women, and therefore reduced the sex difference in COVID-19 mortality risk.

Timed up and go test predicts mortality in older adults in Peru: a population-based cohort study

BackgroundWhile there is evidence about stablished risk factors (e.g., raised blood pressure) and higher mortality risk in older population, less has been explored about other functional parameters like the Timed Up and Go test and the Gait Speed in older people at low- and middle-income countries. We aimed to study these mobility tests as predictors of mortality in a population of older people in Peru.MethodsPopulation-based prospective cohort study (2013–2020). Random sampling of people aged 60+ years in a community of Lima, Peru. Geriatricians conducted all clinical evaluations and laboratory tests were conducted in the local hospital. Participants were sought in the national vital registration system, and we collated cause (ICD-10) and date of death. We conducted a nested forward multivariate Cox proportional hazard model to identify all potential predictors of all-cause, communicable and non-communicable diseases mortality.ResultsAt baseline, there were 501 older people (mean age 70.6 and 62.8% were women), complete follow-up information was available from 427 people. Mean follow-up time was 46.5 months (SD = 25.3). In multivariate models, the Timed Up and Go test was associated with higher risk of all-cause mortality (HR = 1.05; 95% CI: 1.02–1.09). For cause-specific mortality, history of heart disease (HR = 2.25; 95% CI: 1.07–4.76) and age in years (HR = 1.05; 95% CI: 1.01–1.09) were predictors of non-communicable diseases mortality.ConclusionsIn addition to established risk factors for mortality in older population, the Timed Up and Go test, a functional parameter, raised as a relevant predictor of all-cause mortality.

The association between change of soluble tumor necrosis factor receptor R1 (sTNF-R1) measurements and cardiovascular and all-cause mortality-Results from the population-based (Cardiovascular Disease, Living and Ageing in Halle) CARLA study 2002-2016.

AimsSingle measurements of higher levels of soluble tumor necrosis factor receptor I (sTNF-R1) have been shown to be associated with increased risk of mortality. However, up to date, little is known about the underlying temporal dynamics of sTNF-R1 concentrations and their relation with mortality. We aimed to characterize the effect of changes in sTNFR-1 levels on all-cause and cardiovascular mortality, independent from other established risk factors for mortality, including other inflammatory markers.MethodsWe used data of the population based cohort study CARLA and included 1408 subjects with sTNF-R1 measured at baseline (2002–2006) and first follow-up (2007–2010). Cox proportional hazard models were used to assess the association of baseline and follow-up sTNF-R1 measurements with all-cause and cardiovascular mortality during ~10 years since the first follow-up after adjusting for relevant confounders.ResultsBased on 211 deaths among 1408 subjects, per each doubling of the baseline sTNF-R1, the risk of all-cause mortality was increased by about 30% (Hazard ratio 1.28, 95% Confidence Interval 0.6–2.7), while per each doubling of the follow-up level of sTNF-R1 mortality was 3-fold (3.11, 1.5–6.5) higher in a model including both measurements and adjusting for confounders. The results were mainly related to the cardiovascular mortality (5.9, 2.1–16.8 per each doubling of follow up sTNF-R1 value).ConclusionSolely the follow-up value, rather than its change from baseline, predicted future mortality. Thus, while sTNF-R1 levels are associated with mortality, particularly cardiovascular, over a long-time period in the general population, if they change, the earlier measurements play no or little role.

Early Results After Coronary Artery Bypass Grafting in Patients With Severe Ischemic Left Ventricular Dysfunction

Introduction. The number of patients with severe ischemic left ventricular dysfunction (ILVD), who undergo coronary artery bypass, increasing each year. ILVD is an established risk factor for mortality in patients after myocardial revascularization during the early and late postoperative periods.Aim of study. To evaluate the early results of surgical myocardial revascularization in patients with coronary artery disease (CAD) and severe ILVD.Material and methods. The study included 149 patients with coronary artery disease with severe left ventricular dysfunction (ejection fraction (EF) ≤39%), operated from January 2002 to December 2018. different variables were assessed (pre- and postoperative), including LV ejection fraction and end systolic volume index (ESVI).Results.The average age of the patients was 59.36±8.97 years (from 30 to 78 years), 93% of the patients were men. In 28 patients (19%), ILVD developed against the background of myocardial infarction (MI) and in 121 (81%) due to ischemic cardiomyopathy (ICMP) with a history of myocardial infarction. The mean EF before surgery was 36.64±3.17 (from 21 to 39%). In the postoperative period, there was an increase in EF, which averaged 44.92±4.92 (from 36 to 59%) (p value &lt;0.001). The mean LV ESVI before surgery was 60.23±11.52 ml/m2. In the immediate postoperative period ESVI decreased to 46.26±12.40 ml/m2(the value of p&lt;0.001). The average number of bypass coronary arteries in one patient was 3.9±0.87. There was also a decrease in the degree of mitral regurgitation in most patients after coronary artery bypass grafting (CABG) (p value &lt;0.001). Hospital mortality was 2% (3 patients).Conclusion. Coronary artery bypass grafting in patients with severe ischemic left ventricular dysfunction can be performed with low mortality. Surgical myocardial revascularization can be considered a safe and effective operation for patients with coronary artery disease with a satisfactory condition of the distal coronary arteries, low ejection fraction, and with a predominance of viable myocardium.

APOL1 Nephropathy Risk Alleles and Mortality in African American Adults: A Cohort Study

APOL1 nephropathy risk alleles are associated with the development of chronic kidney disease (CKD) in African Americans. Although CKD is an established risk factor for mortality, associations of APOL1 risk alleles with mortality are uncertain. Prospective cohort. 10,380 African American and 17,485 white American participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study. APOL1 nephropathy risk alleles. All-cause and cause-specific mortality. Cox proportional hazards models were used to examine the association of APOL1 high-risk genotypes (2 risk alleles) versus APOL1 low-risk genotypes (0/1 risk allele) with all-cause and cause-specific mortality in African Americans and examine the risk for all-cause mortality in African Americans with high-risk genotypes versus African Americans with low-risk genotypes and white Americans. APOL1 high-risk participants were younger and had a higher prevalence of albuminuria than low-risk participants. There was no statistically significant association ofAPOL1 high- versus low-risk genotypes withall-cause mortality in models adjusted forsociodemographic variables, comorbid conditions, and kidney function (HR, 0.88; 95% CI, 0.77-1.01). After further adjustment for genetic ancestry in a subset with available data, a statistically significant association emerged (HR, 0.81; 95% CI, 0.69-0.96). Associations differed by CKD status (Pinteraction=0.04), with African Americans with high-risk genotypes having lower risk for mortality than those with low-risk genotypes in fully adjusted models (HR, 0.78; 95% CI, 0.62-0.99) among those with CKD, but not those without CKD (HR, 0.84; 95% CI, 0.66-1.05). Compared with white Americans, African Americans with high-risk genotypes had a similar rate of mortality, whereas African Americans with low-risk genotypes had a higher rate of mortality (HR, 1.07; 95% CI, 1.00-1.14) in fully adjusted models. Lack of follow-up measures of kidney function. African Americans with high-risk APOL1 genotypes had lower mortality than those with low-risk genotypes in multivariable-adjusted models including genetic ancestry.

Growth differentiation factor-15 combined with N-terminal prohormone of brain natriuretic peptide increase 1-year prognosis prediction value for patients with acute heart failure: a prospective cohort study.

Background:Clinical assessment and treatment guidance for heart failure depends on a variety of biomarkers. The objective of this study was to investigate the prognostic predictive value of growth differentiation factor-15 (GDF-15) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in assessing hospitalized patients with acute heart failure (AHF).Methods:In total, 260 patients who were admitted for AHF in the First Affiliated Hospital of Nanjing Medical University were enrolled from April 2012 to May 2016. Medical history and blood samples were collected within 24 h after the admission. The primary endpoint was the all-cause mortality within 1 year. The patients were divided into survival group and death group based on the endpoint. With established mortality risk factors and serum GDF-15 level, receiver-operator characteristic (ROC) analyses were performed. Cox regression analyses were used to further analyze the combination values of NT-proBNP and GDF-15.Results:Baseline GDF-15 and NT-proBNP were significantly higher amongst deceased than those in survivors (P < 0.001). In ROC analyses, area under curve (AUC) for GDF-15 to predict 1-year mortality was 0.707 (95% confidence interval [CI]: 0.648–0.762, P < 0.001), and for NT-proBNP was 0.682 (95% CI: 0.622–0.738, P < 0.001). No statistically significant difference was found between the two markers (P = 0.650). Based on the optimal cut-offs (GDF-15: 4526.0 ng/L; NT-proBNP: 1978.0 ng/L), the combination of GDF-15 and NT-proBNP increased AUC for 1-year mortality prediction (AUC = 0.743, 95% CI: 0.685–0.795, P < 0.001).Conclusions:GDF-15, as a prognostic marker in patients with AHF, is not inferior to NT-proBNP. Combining the two markers could provide an early recognition of high-risk patients and improve the prediction values of AHF long-term prognosis.Clinical trial registration:ChiCTR-ONC-12001944, http://www.chictr.org.cn.

Abstract 936: Entropyx of Cardiac Rhythm Uniquely Predicts Mortality in a Multi-site Polysomnography (psg) Study of Ambulatory Asymptomatic Community Adults With Heart Failure

Introduction: Heart failure (HF) is associated with high rates of mortality and hospital readmission. Current strategies for risk stratification are limited. Recently, we introduced EntropyX, a novel measure of non-linear patterns underlying physiological variability using newer concepts of entropy estimation and machine learning. EntropyX of cardiac repolarization (EntropyX QT ) enhanced the predictive value of all established risk factors in a multicenter study of HF patients (PMID: 27044982). Herein, we test the hypothesis that EntropyX of ventricular activation (EntropyX RR ) during sleep enhances the performance of established mortality risk factors in asymptomatic community adults with HF. We interpret our results in context of fundamental mechanistic studies in animal models and modern theories of systems biology. Methods &amp; Results: We followed 96 NYHA class I HF adults in sinus rhythm for 6.5±3.0 years (1994-2011; SHHS NCT#00005275). Baseline exposures included demographics, history, medications, labs, PSG metrics [e.g., sleep disordered breathing (SDB)], ECG analyses [e.g., heart rate (HRV), QT variability (QTV)], and EntropyX RR . The cohort had mean age of 70±10 years, 49% women, 11% African Americans, and 46 deaths (48%; N=35 from cardiovascular events) over 4.6±2.6 years. After adjusting for exposures, the adjusted hazard ratios (4th to 1st quartile) for mortality for EntropyX RR was 2.3 (95% CI, 1.1-4.6) and age was 4.5 (1.9-10.3), consistent with machine learning-based classification and regression tree analysis. Addition of EntropyX RR to a multivariate model (comprised of age, diabetes, myocardial infarction, SDB) improved continuous net reclassification by 43% (37-48). Conclusions: EntropyX RR during sleep predicts mortality over follow-up of asymptomatic community adults with HF, independent of conventional risk factors and linear/deterministic measures (e.g., HRV, QTV, SDB). Unlike simpler concepts of RR variability, EntropyX RR is a fundamentally different measure, reflecting the complexity of multi-directional physiological network properties that regulate homeostatic function under changing conditions. This new paradigm complements conventional measures of risk and has potential for broad application.

IMPACT OF DIABETES MELLITUS ON IN-HOSPITAL OUTCOMES OF PATIENTS WITH SYSTOLIC AND DIASTOLIC HEART FAILURE (INSIGHTS FROM THE NATIONWIDE INPATIENT SAMPLE)

Diabetes mellitus (DM) is an established risk factor for mortality among patients with heart failure (HF). However, the impact of DM on in-hospital outcomes in this patient population remains less described. Using the 2010-2014 Nationwide Inpatient Sample, we identified the overall demographic

Psoas and Paraspinous Muscle Measurements on Computed Tomography Predict Mortality in European Americans with Type 2 Diabetes Mellitus.

Appendicular skeletal muscle mass index and muscle attenuation (density) are negatively associated with mortality in European-derived populations. The present analyses assessed association between axial skeletal muscle density and muscle index with mortality in European Americans with type 2 diabetes mellitus (T2D). Single-center observational study. Diabetes Heart Study. 839 European Americans with T2D. Computed tomography-measured psoas and paraspinous muscle mass index (cross sectional area/height2) and radiographic density (Hounsfield Units) were assessed in all participants. A Cox proportional hazards model was computed. The fully-adjusted model included covariates age, sex, body mass index, smoking, alcohol use, diabetes duration, insulin use, hormone replacement therapy (women), prevalent cardiovascular disease (CVD), hypertension, and coronary artery calcified atherosclerotic plaque mass score. Deaths were recorded in the National Death Index data through December 31, 2015. Participants included 428 women and 411 men with median (25th, 75th quartile) age 62.8 (56.1, 69.1) years and diabetes duration 8.0 (5.0, 14.0) years. After 11.9 (9.4, 13.3) years of follow-up, 314 (37.4%) of participants were deceased. In the fully-adjusted model, psoas muscle density (hazard ratio [HR] 0.81, p<0.001), psoas muscle index (HR 0.82, p=0.008), and paraspinous muscle density (HR 0.85, p=0.003) were inversely associated with mortality. Paraspinous muscle index was not significantly associated with mortality (HR 0.90, p=0.08). Results did not differ significantly between men and women. In addition to established risk factors for mortality and CVD, higher psoas muscle index, psoas muscle density, and paraspinous muscle density were significantly associated with lower all-cause mortality in European Americans with T2D.

Right atrial to left atrial volume index ratio is associated with increased mortality in patients with pulmonary hypertension.

Pulmonary hypertension (PH) is characterized by increased pulmonary vascular resistance leading to right heart failure. Elevated right atrial (RA) pressure reflects right ventricular (RV) pressure overload and is an established risk factor for mortality in PH. We hypothesized that PH patients with an increased ratio of RA to LA volume index (RAVI/LAVI), would have increased mortality. We evaluated the association of RAVI/LAVI with mortality in 124 patients seen at a single academic center's PH clinic after adjusting for the REVEAL risk score, an established risk score in PH. LA and RA volume indices were measured in the four-and two-chamber views by two independent researchers. Multivariable logistic regression was used to model the independent association of RAVI/LAVI with survival. Among 124 patients (mean age 62 ± 12.7 years, 68.6% female), each unit increase in RAVI/LAVI was associated with a nearly twofold increase in mortality (OR: 1.91, 95% CI: 1.20-3.04). In a multivariable logistic regression, each unit increase in RAVI/LAVI was associated with a nearly twofold increase in mortality (OR: 1.73, 95% CI: 1.003-2.998). Furthermore, RAVI/LAVI in the highest quartile (>1.42) was significantly associated with elevated right atrial pressure (RAP) to pulmonary artery wedge pressure ratio (RAP/PAWP) (0.76 ± 0.41, P = 0.02) compared with the lowest quartile (<0.77), suggesting an interaction between invasive hemodynamic data, atrial structural changes, and mortality in PH. Increased RAVI/LAVI in PH is associated with decreased survival and accounts for atrial structural remodeling related to invasive hemodynamics. These findings support further study of this index in predicting outcomes in PH.

Psoas and paraspinous muscle index as a predictor of mortality in African American men with type 2 diabetes mellitus

AimRecent studies revealed a correlation between skeletal muscle mass index and density with longevity; these studies largely evaluated appendicular skeletal muscles in older Caucasians. This retrospective cohort study assessed the association between axial skeletal muscles size and density with survival in African Americans with type 2 diabetes mellitus. MethodsPsoas and paraspinous muscle mass index (cross sectional area/height2) and radiographic density (in Hounsfield Units) were measured using computed tomography in African American-Diabetes Heart Study participants, 314 women and 256 men, with median (25th, 75th quartile) age 55.0(48.0, 62.0) and 57.0(50.0, 64.0) years, respectively. Covariates in fully-adjusted model included age, sex, BMI, smoking, hormone replacement therapy (women), cardiovascular disease, hypertension, coronary artery calcified plaque mass, carotid artery calcified plaque mass, and African ancestry proportion. ResultsAfter median of 7.1(5.9, 8.2) years follow-up, 30(9.6%) of women and 49(19.1%) of men were deceased. In fully-adjusted models, psoas muscle mass index and paraspinous muscle mass index were inversely associated with mortality in men (psoas muscle mass index, hazard ratio [HR] = 0.61, P = 0.004; paraspinous muscle mass index, HR = 0.64, P = 0.004), but not in women. Psoas and paraspinous muscle densities did not associate with all-cause mortality. A penalized Cox regression that involved all covariates and predictors associated with mortality showed that only paraspinous muscle mass index remained a significant predictor of mortality (HR = 0.65, P = 0.02). ConclusionIndependent from established risk factors for mortality, higher psoas and paraspinous muscle index associate with reduced all-cause mortality in middle-aged African American men with type 2 diabetes mellitus.

123 - Right Atrial to Left Atrial Volume Index Ratio is Associated with Mortality in Patients with Pulmonary Hypertension

Background: Pulmonary hypertension (PH) is a progressive condition characterized by increased pulmonary vascular resistance leading to right heart failure. Elevated right atrial (RA) pressure reflects right ventricular (RV) pressure overload in patients with PH and is an established risk factor for mortality. We hypothesized that in patients with PH, an increase in the ratio of RA to LA volume index, RA-LAVI, would be associated with increased mortality. Methods: We evaluated the association between RA-LAVI with long-term clinical outcomes after adjustment for REVEAL Risk Score, an established risk score in pulmonary hypertension. Patients in this study were from a tertiary academic center, with pulmonary hypertension, and had data available for both right heart catheterization (RHC) and transthoracic echocardiogram (TTE) within one year of each other. LA and RA volume indices were measured using the Biplane Disc summation Method in the four and two Chamber Views by two independent researchers. Multivariable logistic regression was used to model RA-LAVI ratio to mortality. Results: Among 124 patients (mean age 62 ± 12.7 years, 68.6% female), each unit increase in the RA-LAVI ratio was associated with a nearly two-fold increase in mortality (OR 1.912, 95% Cl 1.20–3.04). In the multivariable logistic regression model adjusted for the REVEAL Risk score, each unit increase in the RA-LAVI ratio was associated with a nearly two-fold increase in mortality (OR 1.734, 95% CI 1.003–2.998). Furthermore, RA-LAVI ratio in the highest quartile (>1.42) was significantly associated with elevated right atrial pressure (RAP) to pulmonary wedge capillary pressure (PWCP) ratio (RAP/PWCP) (0.76 ± 0.41, P = .02) compared to the lowest quartile (<0.77), suggesting an interaction between invasive hemodynamic data, atrial structural changes and mortality in PH patients. Conclusions: Increased RA-LAVI ratio in PH is associated with mortality, and accounts for atrial structural remodeling related to invasive hemodynamics. These findings support further study of this index for guiding risk stratification in PH patients.

Inflammation and premature aging in advanced chronic kidney disease.

Systemic inflammation in end-stage renal disease is an established risk factor for mortality and a catalyst for other complications, which are related to a premature aging phenotype, including muscle wasting, vascular calcification, and other forms of premature vascular disease, depression, osteoporosis, and frailty. Uremic inflammation is also mechanistically related to mechanisms involved in the aging process, such as telomere shortening, mitochondrial dysfunction, and altered nutrient sensing, which can have a direct effect on cellular and tissue function. In addition to uremia-specific causes, such as abnormalities in the phosphate-Klotho axis, there are remarkable similarities between the pathophysiology of uremic inflammation and so-called "inflammaging" in the general population. Potentially relevant, but still somewhat unexplored in this respect, are abnormal or misplaced protein structures, as well as abnormalities in tissue homeostasis, which evoke danger signals through damage-associated molecular patterns, as well as the senescence-associated secretory phenotype. Systemic inflammation, in combination with the loss of kidney function, can impair the resilience of the body to external and internal stressors by reduced functional and structural tissue reserves, and by impairing normal organ crosstalk, thus providing an explanation for the greatly increased risk of homeostatic breakdown in this population. In this review, the relationship between uremic inflammation and a premature aging phenotype, as well as potential causes and consequences, are discussed.

Short-term heart rate variability in dogs with sick sinus syndrome or chronic mitral valve disease as compared to healthy controls.

Heart rate variability is an established risk factor for mortality in both healthy dogs and animals with heart failure. The aim of this study was to compare short-term heart rate variability (ST-HRV) parameters from 60-min electrocardiograms in dogs with sick sinus syndrome (SSS, n=20) or chronic mitral valve disease (CMVD, n=20) and healthy controls (n=50), and to verify the clinical application of ST-HRV analysis. The study groups differed significantly in terms of both time - and frequency- domain ST-HRV parameters. In the case of dogs with SSS and healthy controls, particularly evident differences pertained to HRV parameters linked directly to the variability of R-R intervals. Lower values of standard deviation of all R-R intervals (SDNN), standard deviation of the averaged R-R intervals for all 5-min segments (SDANN), mean of the standard deviations of all R-R intervals for all 5-min segments (SDNNI) and percentage of successive R-R intervals >50 ms (pNN50) corresponded to a decrease in parasympathetic regulation of heart rate in dogs with CMVD. These findings imply that ST-HRV may be useful for the identification of dogs with SSS and for detection of dysautonomia in animals with CMVD.

Inferior vena cava diameter in acute decompensated heart failure as predictor of all-cause mortality.

Inferior vena cava (IVC) diameter can be used to approximate right atrial pressure in patients admitted for acute decompensated heart failure (ADHF). Recent studies linked IVC dilation to an increased risk of early re-admission and short-term mortality. Moreover, renal insufficiency (RI) is an established risk factor for mortality in ADHF and is associated with congestion. We hypothesized that the IVC diameter is a marker of all-cause mortality but its prognostic impact may be influenced by kidney function. We analyzed data of 1101 patients admitted for ADHF with available echocardiography of the IVC by chart review and death registry linkage. Patients were dichotomized according to a cut-off value of 21mm. Cox proportional hazards model was used to identify mortality predictors. A dilated IVC was detected in 474 (43.1%) patients. Overall, 400 (36.3%) patients died within 3 years. All-cause mortality was significantly higher in patients with dilated IVC [hazard ratio 1.45 (confidence interval 1.21-1.74); p < 0.001]. However, a dilated IVC was only associated with all-cause mortality in patients with RI function [hazard ratio 1.60 (confidence interval 1.26-2.03); p < 0.001] but not in patients with a preserved kidney function [hazard ratio 1.04 (confidence interval 0.72-1.50); P = 0.84]. IVC diameter was identified as an independent predictor for all-cause mortality in a Cox proportional hazards model with a significant interaction between IVC diameter and baseline kidney function. In conclusion, IVC dilation is a marker of high mortality risk in patients admitted for ADHF. However, this observation was confined to patients with RI.

Motoric cognitive risk syndrome and risk of mortality in older adults

IntroductionCognitive impairment is associated with increased mortality. We examined the association between motoric cognitive risk (MCR) syndrome, a predementia syndrome characterized by slow gait and cognitive complaints, and survival. MethodsA total of 11,867 nondemented participants aged >65 years from three established cohort studies in the United States and Europe were screened for MCR. Mortality risk of MCR was assessed with Cox and logistic regression models. ResultsAt baseline, 836 (7.0%) participants had MCR. Over a median follow-up of 28 months, 1603 participants died (758 in first 2 years). MCR was associated with increased mortality overall (adjusted hazard ratio, 1.69; 95% confidence interval [CI], 1.46–1.96) and 2-year mortality (adjusted odds ratio, 1.89; 95% CI, 1.50–2.38). The association remained after accounting for established mortality risk factors as well as baseline gait speed and memory performance. DiscussionMCR is associated with increased mortality. Older adults should be screened for MCR to identify at-risk individuals for dementia and death.

High estimated pulmonary artery systolic pressure predicts adverse cardiovascular outcomes in stage 2–4 chronic kidney disease

High estimated pulmonary artery systolic pressure (ePASP) is an established risk factor for mortality and cardiovascular (CV) events in the general population. High ePASP predicts mortality in dialysis patients but such a relationship has not been tested in patients with early CKD. Here we estimated the prevalence and the risk factors of high ePASP in 468 patients with CKD stage 2-4 and determined its prognostic power for a combined end point including cardiovascular death, acute heart failure, coronary artery disease, and cerebrovascular and peripheral artery events. High ePASP (35 mm Hg and above) was present in 108 CKD patients. In a multivariate logistic regression model adjusted for age, diabetes, hemoglobin, left atrial volume (LAV/BSA), left ventricular mass (LVM/BSA), and history of CV disease, age (OR, 1.06; 95% CI, 12 1.04-1.09) and LAV/BSA (OR, 1.05; 95% CI, 1.03-1.07) were the sole significant independent predictors of high ePASP. Elevated ePASP predicted a significantly high risk for the combined cardiovascular end point both in unadjusted analyses (HR, 2.70; 95% CI, 1.68-4.32) and in analyses adjusting for age, eGFR, hemoglobin, LAV/BSA, LVM/BSA, and the presence of diabetes and CV disease (HR, 1.75; 95% CI, 1.05-2.91). High ePASP is relatively common in patients with stage 2-4 CKD and predicts adverse CV outcomes independent of established classical and CKD-specific risk factors. Whether high ePASP is a modifiable risk factor in patients with CKD remains to be determined in randomized clinical trials.