Greater Risk Of All-cause Mortality Research Articles

Combined low vitamin D and K status amplifies mortality risk: a prospective study

ObjectiveTo explore the association of both plasma vitamin D and K concentrations with all-cause mortality, cardiovascular mortality, and cardiovascular events in the general population.MethodsWe studied 4742 participants of the Prevention of REnal and Vascular ENd-Stage Disease (PREVEND) Study. At baseline, vitamin D and K status was determined by measurement of 25-hydroxyvitamin D [25(OH)D] and dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP), respectively. Patients were categorized into: 25(OH)D < 50 or ≥ 50 nmol/L and dp-ucMGP < 361 or ≥ 361 pmol/L with 25(OH)D > 75 nmol/L and dp-ucMGP < 361 pmol/L as reference. Cause of death was coded according to International Classification of Diseases 9&10 codes from the 2001-2003 examination until date of death/event or censoring date (January 1st, 2017).ResultsMean age was 52.6 ± 11.9 years and 2513 (53%) were female. During a median of 14.2 year follow-up, 620 participants died of which 142 were due to cardiovascular causes. Combined low vitamin D and K status was present in 970 participants (20%) and was associated with a greater risk of all-cause mortality compared to high vitamin D and high vitamin K status group (n = 1424) after adjusting for potential confounders: hazard ratio 1.46 (95% confidence intervals 1.12–1.90). We observed similar trends, albeit non-significant for cardiovascular mortality, and cardiovascular events: 1.42 (0.79–2.55), 1.28 (0.93–1.77), respectively.ConclusionsCombined low vitamin D and K status are associated with increased all-cause mortality risk and possibly with cardiovascular mortality and cardiovascular events compared with adequate vitamin D and K status. Future studies should investigate the effect of combined vitamin D and K supplementation on clinical outcomes.

Examining veteran housing instability and mortality by homicide, suicide, and unintentional injury

ABSTRACT To examine the relationship between Veterans’ housing instability and mortality by homicide, suicide, and unintentional injury, this retrospective study examined administrative data from Veterans Health Administration (VHA) patients who responded to the Homelessness Screening Clinical Reminder (HSCR) between October 1, 2012 and September 30, 2016 and were searched through the National Death Index (NDI) for date and cause of death (N = 5,850,044). Analyses calculated survival time and compared mortality for three groups—(1) stably housed Veterans, (2) unstably housed Veterans, and (3) Veterans at imminent risk for housing instability—using adjusted Cox proportional hazards models. Stably housed Veterans had a significantly longer median survival time (3.3 years) than unstably housed Veterans and those at imminent risk for housing instability (2.5 and 2.6 years, respectively). Unstably housed Veterans and those at imminent risk for housing instability had greater risk of all-cause mortality (Adjusted Hazard Ratio [aHR] = 1.69 and 1.48, respectively) and of dying by homicide (aHR = 3.01 and 2.65, respectively), suicide (aHR = 1.75 and aHR = 1.80, respectively), and unintentional injury (aHR = 3.13 and aHR = 1.92, respectively) compared with stably housed Veterans. More proactive measures are needed to prevent external causes of mortality among Veterans who are unstably housed or at imminent risk for housing instability.

Association of Lower Plasma Homoarginine Concentrations with Greater Risk of All-Cause Mortality in the Community: The Framingham Offspring Study.

Lower circulating homoarginine concentrations have been associated with morbidity and mortality in patients with established cardiovascular disease (CVD). We assayed plasma homoarginine concentrations in 3331 Framingham Offspring Study participants attending examination cycle six (mean age 58.6 years, 53% women). We evaluated correlates of plasma homoarginine and related homoarginine to incident CVD and death. We also classified participants as having higher (upper quartile) versus lower (lower three quartiles) homoarginine and previously assayed asymmetric dimethylarginine (ADMA) concentrations, and created cross-classification groups. We observed 630 incident CVD events and 940 deaths during a median follow-up of 18 years. In multivariable regression analysis, homoarginine was associated positively with male sex, body mass index, anti-hypertensive medication use and systolic blood pressure, but inversely with age and smoking. Higher homoarginine levels were associated with a lower mortality risk (hazard ratio (HR) per SD increment, 0.83, 95% CI: 0.74–0.93) adjusting for standard CVD risk factors, and ADMA. Among the cross-classification groups, participants with higher homoarginine and lower ADMA had a lower mortality risk (HR, 0.81, 95% CI: 0.67–0.98) compared to those with low levels of both. Further studies are needed to dissect the mechanisms of the association of homoarginine and mortality over decades in the community.

Effects of waist to height ratio, waist circumference, body mass index on the risk of chronic diseases, all-cause, cardiovascular and cancer mortality

BackgroundGiven the fat redistribution in later stages of life, how the associations between abdominal obesity and the risk of morbidity and mortality have changed with age have not been elucidated,...

A comparison of stage-specific all-cause mortality between testicular sex cord stromal tumors and germ cell tumors: results from the National Cancer Database

BackgroundTesticular sex cord stromal tumors (SCSTs) are managed similarly to germ cell tumors (GCTs); however, few studies have directly compared outcomes between these tumor types. Using the National Cancer Database (NCDB), we sought to compare overall and stage-specific all-cause mortality (ACM) between SCSTs versus GCTs.MethodsNCDB was queried for patients diagnosed with SCSTs and GCTs between 2004 and 2013. Descriptive statistics were used to compare sociodemographic and clinical characteristics between groups. Univariable and multivariable Cox proportional hazards regression analyses were used to assess associations with ACM.ResultsWe identified 42,192 patients diagnosed with testicular cancer between 2004 and 2013, with 280 having SCSTs and 41,912 patients having GCTs. Median age for SCSTs and GCTs was 45 (interquartile range [IQR] 34–59) and 34 (IQR 27–43), respectively (p < 0.001). Median follow-up was 39 and 52 months, respectively. Overall, patients with SCSTs had greater risk of ACM compared to those with GCTs (HR 1.69, 95% CI 1.14–2.50). Private insurance, greater education, and fewer comorbidities were associated with reduced risk of ACM (p < 0.05 for all). Among those with stage I disease, tumor type was not associated with ACM on multivariable analysis. Among those with stage II/III disease, patients with SCSTs had increased risk of ACM compared to patients with GCTs (HR 3.29, 95% CI 1.89–5.72).ConclusionsPatients with advanced SCSTs had worse survival outcomes compared to those with advanced GCTs. These data suggest a need for further investigation to ascertain effective management recommendations for SCSTs.

Which serum uric acid levels are associated with increased cardiovascular risk in the general adult population?

Our aim was to determine the serum uric acid (SUA) levels associated with an increased risk of cardiovascular (CV) and all-cause death in the general adult population. We analyzed data obtained in two independent cross-sectional surveys performed in the Czech Republic in 2006-09 and 2015-18, involving 1% population random samples in nine districts, aged 25-64years, stratified by age and gender. Ten-year mortality data were obtained in a cohort with examination in 2006-09. Final analyses included 3542 individuals (48.2% men) examined in 2006-09, and 2304 (47.4% men) examined in 2015-18. From a cohort examined in 2006-09, 122 men and 60 women were reported dead (33% and 27% from CV disease). In men, there was no association of baseline SUA levels with baseline SCORE category or 10-yearmortality rates. In women, each 10µmol/L increase in baseline SUA levels was associated with an increase in baseline SCORE category (P<.001). Receiver operating characteristic curve analyses in women identified the baseline SUA cutoff values discriminating: 1. between low/intermediate and high/very high SCORE categories (309µmol/L), 2. CV mortality (325µmol/L), and 3. all-cause mortality (298µmol/L). After adjusting for confounders including SCORE, Cox regression analysis confirmed that the baseline SUA cutoffs of 309µmol/L and 325µmol/L were associated with 4-times (P=.010) and 6-times (P=.036) greater risk of CV mortality, whereas the cutoff of 298µmol/L was associated with 87% greater risk of all-cause mortality (P=.025). In conclusion, the SUA cutoff value of 309µmol/L identified women at high/very high SCORE category and was associated with 4-times greater risk of observed CV mortality over 10years.

P5496Sex differences in the association between diabetes and risk of cardiovascular disease, cancer, and all-cause and cause-specific mortality: a systematic review and meta-analysis of 5,016,608 participa

Abstract Background Previous meta-analyses, through internal, within-study comparisons of women and men participants, have observed that women with diabetes are at substantially higher risk of coronary heart disease (CHD), stroke and gastric cancer compared with affected men. However, the magnitude of the excess risk of these and other cause-specific outcomes that is conferred by diabetes for men and women is unknown. Purpose To estimate the relative effect of diabetes on risk of all-cause, cancer, cardiovascular disease (CVD), infectious disease and respiratory disease mortality in women compared with men. Methods Studies published from their inception to April 1, 2018, identified through a systematic search of PubMed and EMBASE and review of references. We used the sex-specific RRs to derive the women-to-men ratio of RRs (RRR) and 95% CIs from each study. Subsequently, the RRR for each outcome was pooled with random effects meta-analysis weighted by the inverse of the variances of the log RRRs. Results Forty-eight studies with 85 prospective cohorts met the inclusion criteria and were eligible for analysis. The pooled women to men RRR showed a 13% greater risk of all-cause mortality associated with diabetes in women than in men (RRR: 1.13, 95% CI: 1.07 to 1.19; P&lt;0.001, Figure 1). The pooled multiple-adjusted RRR indicated a 30% significantly greater excess risk of CVD mortality in women with diabetes compared with men (RRR: 1.30 95% CI: 1.13 to 1.49; P&lt;0.001). Compared with men with diabetes, women with diabetes had a 58% greater risk of coronary heart disease (CHD) mortality, but only an 8% greater risk of stroke mortality (RRRCHD: 1.58, 95% CI: 1.32 to 1.90; P&lt;0.001; RRRstroke: 1.08, 95% CI: 1.01 to 1.15; P&lt;0.001). However, no sex differences were observed among the population with or without diabetes, for all-cancer (RRR: 1.02, 95% CI: 0.98 to 1.06; P=0.21), infectious (RRR: 1.13, 95% CI: 0.90 to 1.38; P=0.33) and respiratory mortality RRR: 1.08, 95% CI: 0.95 to 1.23; P=0.26). Conclusions Compared with men with the same condition, women with diabetes have a 58% and 13% greater risk of CHD and all-cause mortality, respectively. This points to an urgent need to develop sex and gender specific risk assessment strategies and therapeutic interventions that target diabetes management for CHD prevention.

Nutritional Aspects in Diabetic CKD Patients on Tertiary Care.

Background and objectives: Diabetes is largely prevalent in the chronic kidney disease (CKD) population. Both conditions have metabolic and nutritional abnormalities that affect body composition and the presence of diabetes makes the dietary management of CKD patients more difficult. The aim of this study was to assess peculiar nutritional and functional aspects of diabetic patients in an adult/elderly CKD population, and their predictive significance. Materials and methods: This prospective cohort study included 144 out-patients aged >55 years, affected by stage 3b-4 CKD, on tertiary care clinic; 48 (40 males) were type 2 diabetics and 96 (80 males) were nondiabetics. The two groups have similar age, gender, and residual renal function (30 ± 9 vs. 31 ± 11 mL/min×1.73). All patients underwent a comprehensive nutritional and functional assessment and were followed for 31 ± 14 months. Results: Diabetic CKD patients showed higher waist circumference and fat body mass, lower muscle mass, and lower number of steps per day and average daily METs. Meanwhile, resting energy expenditure (REE), as assessed by indirect calorimetry, and dietary energy intake were similar as well as hand-grip and 6 min walking test. Diabetic patients did not show a greater risk for all-cause mortality and renal death with respect to nondiabetics. Middle arm muscle circumference, phase angle, serum cholesterol, and serum albumin were negatively related to the risk of mortality and renal death after adjustment for eGFR. Conclusions: CKD diabetic patients differed from nondiabetics for a greater fat mass, lower muscle mass, and lower physical activity levels. This occurred at the same REE and dietary energy intake. The outcome of diabetic or nondiabetic CKD patients on tertiary care management was similar in terms of risk for mortality or renal death. Given the same residual renal function, low levels of muscle mass, phase angle, serum albumin, and cholesterol were predictive of poor outcome. Overall, a malnutrition phenotype represents a major predictor of poor outcome in diabetic and nondiabetic CKD patients.

Sex differences in the association between diabetes and risk of cardiovascular disease, cancer, and all-cause and cause-specific mortality: a systematic review and meta-analysis of 5,162,654 participants

BackgroundStudies have suggested sex differences in the mortality rate associated with diabetes. We conducted a meta-analysis to estimate the relative effect of diabetes on the risk of all-cause, cancer, cardiovascular disease (CVD), infectious disease, and respiratory disease mortality in women compared with men.MethodsStudies published from their inception to April 1, 2018, identified through a systematic search of PubMed and EMBASE and review of references. We used the sex-specific RRs to derive the women-to-men ratio of RRs (RRR) and 95% CIs from each study. Subsequently, the RRR for each outcome was pooled with random-effects meta-analysis weighted by the inverse of the variances of the log RRRs.ResultsForty-nine studies with 86 prospective cohorts met the inclusion criteria and were eligible for analysis. The pooled women-to-men RRR showed a 13% greater risk of all-cause mortality associated with diabetes in women than in men (RRR 1.13, 95% CI 1.07 to 1.19; P < 0.001). The pooled multiple-adjusted RRR indicated a 30% significantly greater excess risk of CVD mortality in women with diabetes compared with men (RRR 1.30, 95% CI 1.13 to 1.49; P < 0.001). Compared with men with diabetes, women with diabetes had a 58% greater risk of coronary heart disease (CHD) mortality, but only an 8% greater risk of stroke mortality (RRRCHD 1.58, 95% CI 1.32 to 1.90; P < 0.001; RRRstroke 1.08, 95% CI 1.01 to 1.15; P < 0.001). However, no sex differences were observed in pooled results of populations with or without diabetes for all-cancer (RRR 1.02, 95% CI 0.98 to 1.06; P = 0.21), infectious (RRR 1.13, 95% CI 0.90 to 1.38; P = 0.33), and respiratory mortality (RRR 1.08, 95% CI 0.95 to 1.23; P = 0.26).ConclusionsCompared with men with the same condition, women with diabetes have a 58% and 13% greater risk of CHD and all-cause mortality, respectively, although there was a significant heterogeneity between studies. This points to an urgent need to develop sex- and gender-specific risk assessment strategies and therapeutic interventions that target diabetes management in the context of CHD prevention.

SUN-072 PROGNOSTIC VALUE OF SOLUBLE ST2 AND SOLUBLE LR11 ON MORTALITY AND CARDIOVASCULAR EVENT IN PERITONEAL DIALYSIS PATIENTS

Because end-stage renal disease (ESRD) patients are at high risk of cardiovascular (CV) disease, developing a biomarker for CV risk stratification has clinical importance. Soluble form of suppression of tumorigenicity 2 (sST2) and soluble low-density lipoprotein receptor relative with 11 ligand-binding repeats (sLR11) are emerging CV biomarkers, however, to date, the prognostic value of those has not been investigated in patients undergoing peritoneal dialysis (PD). We determined serum sST2 and sLR11 concentrations using enzyme-linked immunosorbent assay, and evaluated the association of those biomarkers with all-cause mortality and major adverse cardiac and cerebrovascular event (MACCE) in 74 prevalent PD patients. The median (interquartile range) concentrations of sST2 and sLR11 were 70.9 (57.8-89.8) ng/mL and 15.2 (12.3-19.6) ng/mL, respectively. During a median follow-up of 38.5 months, 13 (17.6%) patients died and MACCE was observed in 23 (31.3%) patients. When patients were dichotomized by the median value of sST2 and sLR11, Kaplan-Meier analyses showed that higher sST2 group was significantly associated with lower event-free survival rates (log-rank test; P=0.002 for all-cause death; P=0.01 for MACCE). In multivariable Cox analyses, higher sST2 was independent risk factor for all-cause mortality (per 1 standard deviation [SD] increase; hazard ratio [HR]=1.947; 95% confidence interval [CI]=1.124-3.371) and MACCE (per 1 SD increase; HR=1.647; 95% CI=1.079-2.516). In contrast, sLR11 did not have a significant association with all-cause mortality or MACCE. Furthermore, only sST2 provided a significant predictive value for all-cause mortality (AUC=0.699; P=0.03). sST2, not sLR11, was independently associated with greater risk of all-cause mortality and CV outcome in prevalent PD patients. Additional studies are needed to confirm these findings and examine underlying mechanism between new biomarkers and CV disease in ESRD populations

Effect of insurance type on perioperative outcomes after robotic-assisted pulmonary lobectomy for lung cancer

BackgroundInsurance type has been reported to be an independent predictor of overall survival in lung cancer patients. We studied the effect of insurance type on patient outcomes after minimally invasive pulmonary lobectomy for lung cancer. MethodsWe retrospectively analyzed 433 consecutive patients who underwent robotic-assisted pulmonary lobectomy by one surgeon during an 80-month period. Perioperative outcomes and intraoperative and postoperative complications were noted. Disposition at discharge after surgery (favorable, eg, transfer to home with self-care or with home health nursing and/or physical therapy, versus unfavorable, eg, long-term acute care or rehabilitation facility, hospice, or death) and 5-year overall survival (5-years OS) were also recorded. We used Pearson χ2, analysis of variance (ANOVA), and Kruskal-Wallis test to compare variables and Cox regression for survival analysis. ResultsThere were 107 patients (mean age 57.5 years) with private insurance, 118 (mean age 70.3 years) with public insurance (Medicare or Medicaid), 196 (mean age 71.8 year; P < .001) with combination insurance plans (Medicare plus a privately supplied supplemental), and 12 patients with no insurance (excluded owing to low sample size). There were more current smokers in the public insurance group, more former smokers in the combination insurance group, and more nonsmokers in the private insurance group (P = .03). There were more comorbidities in the public and combination insurance groups versus the private insurance group, including gastroesophageal reflux disease (P = .003), hypertension (P = .01), and hyperlipidemia (P < .001). The groups had no differences in tumor size or pathologic stage. There were higher numbers of intraoperative conversions to open lobectomy in the private and public insurance groups versus the combination insurance group (P = .001). Also, the private and combination insurance groups had more cases of favorable disposition at discharge after surgery compared with the public insurance group (P < .001). Multivariable regression analyses identified private insurance type as an independent predictor of favorable disposition at discharge (public versus private plan; odds ratio, 0.43; 95% confidence interval [CI], 0.22–0.85, P = .02) and 5-year OS (combination versus private plan; hazard ratio, 2.68; 95% CI, 1.26–5.67, P = .01; public versus private plan; HR, 2.84; 95% CI, 1.37–5.89; P = .01). ConclusionAlthough public or combination insurance type was associated with greater risk of all-cause mortality, and public insurance type was associated with less favorable disposition at discharge after surgery and overall conversion to open lobectomy, insurance type was not associated with increased intraoperative complications, hospital duration of stay, or in-hospital mortality after minimally invasive robotic-assisted pulmonary lobectomy.

Computer-aided Quantification of Pulmonary Fibrosis in Patients with Lung Cancer: Relationship to Disease-free Survival.

Background Interstitial lung abnormalities (ILAs) are present at CT in about 10% of individuals undergoing lung cancer screening. The relationship between histologic findings of ILAs and their influence on patient prognosis remains unknown. Purpose To evaluate the percentage of ILAs at preoperative CT, as measured by radiologists and a computer-aided detection (CAD) software, as a predictor of disease-free survival in patients with lung cancer. Materials and Methods This retrospective study evaluated 217 consecutive patients who underwent complete resection of lung cancer from April 2010 to December 2015. Two radiologists, blinded to the patients' clinical information, scored percentage fibrosis extent and determined whether ILAs and the usual interstitial pneumonia (UIP) pattern were present. They assessed ILA progression at follow-up CT. Two pathologists determined the presence of an UIP pattern. Percentage fibrosis extent was also measured by using CAD. Binary logistic regression analysis was performed to determine whether the CAD percentage fibrosis extent was associated with ILA at CT. Multivariable Cox regression analysis was used to evaluate the significance of CAD percentage fibrosis extent as a predictor of prognosis. Results The radiologists classified 47 patients with ILAs and 24 patients with a UIP pattern at chest CT. The pathologists detected a UIP pattern in 25 patients. CT abnormalities showed progression over a 2-year period in all patients with histologic evidence of UIP. After adjustment for age, sex, and smoking index, the CAD percentage fibrosis extent was independently associated with ILA (odds ratio: 3.1; 95% confidence interval [CI]: 2.1, 4.7; P < .001). After adjustment for age, forced expiratory volume in 1 second (percentage predicted) radiologist-assessed percentage fibrosis extent, and pathologic stage, CAD percentage fibrosis extent was independently associated with worse disease-free survival (hazard ratio: 1.3; 95% CI: 1.1, 1.6; P < .001). Conclusion Greater computer-aided detection percentage fibrosis extent at preoperative CT independently predicted worse disease-free survival in patients with lung cancer. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Goo in this issue.

251-OR: Relationship of Short-Term HbA1c Change with Vascular Events, Severe Hypoglycaemia, and Mortality

Objective: To examine the effects of change in glycaemic control on clinical outcomes in patients with type 2 diabetes. Research Design and Methods: Data were obtained from 9981 participants of the ADVANCE trial and ADVANCE-ON follow-up. Participants were categorized into 3 groups by glycated haemoglobin (HbA1c) change from baseline to 6 months, &amp;gt;0.25% decrease, &amp;gt;0.25% increase and minimal change (±0.25%). Adjusted Cox and logistic regression analyses examined relationships between HbA1c change and all-cause mortality, macrovascular events, microvascular events and severe hypoglycaemia. Results: Mean (±SD) age was 65.8±6.4 years, diabetes duration 7.9±6.4 years and HbA1c 7.5±1.6% at baseline. In the first 6 months, 48%, 22% and 30% of participants had an HbA1c decrease, minimal change or increase respectively. Median (IQR) follow-up was 9.4 (5.1-10.4) years. Compared to those with minimal HbA1c change at 6 months, participants with an HbA1c increase at 6 months had greater risk of risk of all-cause mortality [1.26 (1.11-1.43)], macrovascular events [1.26 (1.10-1.44)] and microvascular disease [1.36 (1.09-1.70) whereas participants with an HbA1c decrease did not have greater risk of all-cause mortality [0.99 (0.87-1.12)], macrovascular events [1.06 (0.93-1.21)] or microvascular disease [0.97 (0.77-1.21)]. Neither HbA1c increase [1.05 (0.83-1.33)] or decrease [1.16 (0.91-1.47)] was associated with greater risk of severe hypoglycaemia. These effects were similar when HbA1c change at 3 months was considered and in subgroup analyses by age, gender, diabetes duration, or baseline HbA1c. Conclusions: Increased rather than decreased HbA1c at 6 months was associated with increased risks of death and vascular events in type 2 diabetes. Disclosure N. Nanayakkara: None. T. Ohkuma: None. M. Woodward: Consultant; Self; Amgen Inc., Kirin. J. Chalmers: Research Support; Self; Idorsia. S. Zoungas: None.

Chronic Pain, Physical Activity, and All-Cause Mortality in the US Adults: The NHANES 1999-2004 Follow-Up Study.

The purposes of this study were (1) to examine the relationship between chronic pain and the risk of all-cause mortality and (2) to explore the role of physical activity (PA) in this relationship. Prospective cohort study. The National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2004. A total of 7384 adults aged ≥40 years old. Chronic pain and PA were assessed based on the responses to miscellaneous pain and leisure-time PA questionnaires collected during the household interview. The 2011 mortality data from the National Center for Health Statistics were linked to the NHANES participants. Cox proportional hazard analyses after accounting for the complex sampling design of the NHANES. After adjusting for several key covariates including sociodemographic variables, chronic health conditions, and unhealthy lifestyle behaviors, individuals with localized or widespread chronic pains showed greater risk of all-cause mortality when compared to individuals with no chronic pain (hazard ratios [HRs] = 1.26 and 1.41, respectively). However, the association was attenuated by further adjustment of PA levels, where engagement of PA ≥150 min/wk was associated with reduced risk of mortality regardless of chronic pain conditions (P for trends between <.001 and .028). The joint analysis further demonstrated that individuals with localized or widespread chronic pains who had PA ≥150 min/wk had lower risk of mortality (HRs = 0.53 and 0.58, respectively) when compared to those without chronic pain who reported no leisure time PA. This study highlighted the important role of PA in reducing the risk of mortality for individuals with chronic pain. Further public health efforts to promote PA in this vulnerable population group are required.

Association between atrial fibrillation and heart failure with different ejection fraction categories and its influence on outcomes

Background: The important role of atrial fibrillation (AF) in different types of heart failure (HF) according to ejection fraction (EF) is much less explored. In this study, we compared AF in HF with preserved (HFpEF), mid-range (HFmrEF) and reduced (HFrEF) EF with regard to prevalence, association, and prognostic role.Methods and results: A total of 405 inpatients with HF between February 2014 and June 2016 were prospectively analysed in this study. Patients were divided into three groups: HFrEF group (n = 109, 26.9%), HFmrEF group (n = 94, 23.2%), and HFpEF group (n = 202, 49.8%). There was a higher prevalence of AF in patients in the HFpEF and HFmrEF groups than in patients in the HFrEF. Several baseline variables were found to be independently associated with AF, including age, coronary heart disease, heart rate, left atrial diameter, and left ventricular (LV) end-diastolic diameter, regardless of EF category after multivariable adjustment. In addition, AF was found to be a more powerful predictor of all-cause mortality, HF rehospitalisation, and the composite event of all-cause mortality or rehospitalisation in HFpEF and HFmrEF patients, but not in HFrEF patients.Conclusions: HFmrEF resembled HFpEF rather than HFrEF with regard to both a higher prevalence of AF and a greater risk of all-cause mortality, HF rehospitalisation, and the composite event of all-cause mortality or rehospitalisation.

Association of Angiotensin Modulators With the Course of Idiopathic Pulmonary Fibrosis

Angiotensin peptides have been implicated in idiopathic pulmonary fibrosis (IPF) pathogenesis. Angiotensin modulators are used to treat arterial hypertension, a frequent comorbidity of IPF. This post hoc analysis evaluated associations of antihypertensive treatments with disease-related outcomes in IPF. All patients randomized to placebo (n= 624) in the CAPACITY and ASCEND studies were categorized by antihypertensive treatment at baseline. Outcomes of disease progression (first occurrence of≥ 10%absolute decline in %predicted FVC,≥ 50-m decline in 6-min walk distance, or death) and all-cause mortality were assessed over 52weeks. At baseline, 111 and 121 patients were receiving an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin II receptor blocker (ARB), respectively; 392 were receiving neither. In multivariable analyses adjusted for differences in baseline characteristics compared with the non-ACEi/ARB group, ACEi treatment (hazard ratio [HR], 0.6 [95%CI, 0.4-0.9]; P= .026), but not ARB (HR, 0.9 [95%CI, 0.6-1.2]; P= .413), was associated with slower disease progression. Furthermore, the increase in all-cause mortality associated with cardiovascular disease was not observed in the ACEi group (HR, 1.1 [95%CI, 0.5-2.9]; P= .782), which presented a similar percentage of IPF-related mortality as the non-ACEi/ARB group (3.6%vs3.6%). In contrast, patients in the ARB group had greater risk of all-cause mortality (HR, 2.5 [95%CI, 1.2-5.2]). These observations were validated in a pooled analysis that included patients from the INSPIRE trial. Prospective clinical trials are needed to evaluate whether angiotensin modulators may be beneficial to clinical outcomes in IPF. ClinicalTrials.gov; Nos.: NCT01366209, NCT00287716, NCT00287729, NCT00075998; URL: www.clinicaltrials.gov).

Previous Antithrombotic Therapy, Particularly Anticoagulant, Is Associated with Unfavorable Outcomes in Patients with Primary Spontaneous Intracerebral Hemorrhage Receiving Craniotomy: A Nationwide Population-Based Cohort Study

The impact of antithrombotic agents on patients with primary intracerebral hemorrhage (ICH) remains controversial, especially patients who require emergent craniotomy. This study was undertaken to evaluate clinical outcomes in operated patients with ICH with and without previous antithrombotic agents. This is a retrospective cohort study. Between January 2001 and December 2013, all patients with ICH who received emergent craniotomy and who were present in Taiwan's National Health Insurance Research Database were screened and divided into those with previous antiplatelet therapy, anticoagulant therapy, and nonantithrombotic therapy according to their health care claims data within 3 months of index admission. The primary end points included in-hospital mortality and complications and short-term outcome. Of 18,872 eligible patients, 16,251 (87.1%) did not receive any antithrombotic therapy, 2267 patients had antiplatelet therapy, and 354 patients had anticoagulation therapy. After propensity score matching, significantly more blood transfusions and craniectomies were identified in the patients with previous antithrombotic treatment compared with those undergoing nonantithrombotic therapy. Compared with the nonantithrombotic treatment cohort, patients under previous anticoagulant treatment had significantly higher in-hospital mortality (odds ratio, 2.12; 95% confidence interval, 1.45-3.10). Furthermore, during the 6-month follow-up period, previous anticoagulant therapy was independently associated with a greater risk of all-cause mortality (P= 0.001). The in-hospital and 6-month all-cause mortality of patients with previous antiplatelet treatment was not significantly different from patients with nonantithrombotic treatment. These findings suggested an increased risk of in-hospital mortality and poor short-term outcome among operated patients with ICH with previous antithrombotic therapy, particularly anticoagulant therapy, but not with antiplatelet therapy.

Morbidity, mortality and missed appointments in healthcare: a national retrospective data linkage study

BackgroundRecently, studies have examined the underlying patient and practice factors for missed appointments, but less is known about the impact on patient health. People with one or more long-term conditions who fail to attend appointments may be at risk of premature death. This is the first study to examine the effect of missed primary healthcare appointments on all-cause mortality in those with long-term mental and physical health conditions.MethodsWe used a large, nationwide retrospective cohort (n = 824,374) extracted from routinely collected general practice data across Scotland over a 3-year period from September 2013 until September 2016. This data encompasses appointment history for approximately 15% of the Scottish population, and was linked to Scottish deaths records for patients who had died within a 16-month follow-up period. We generated appointment attendance history, number of long-term conditions and prescriptions data for patients. These factors were used in negative binomial and Cox’s proportional hazards modelling to examine the risk of missing appointments and all-cause mortality.ResultsPatients with a greater number of long-term conditions had an increased risk of missing general practice appointments despite controlling for number of appointments made, particularly among patients with mental health conditions. These patients were at significantly greater risk of all-cause mortality, and showed a dose-based response with increasing number of missed appointments. Patients with long-term mental health conditions who missed more than two appointments per year had a greater than 8-fold increase in risk of all-cause mortality compared with those who missed no appointments. These patients died prematurely, commonly from non-natural external factors such as suicide.ConclusionsMissed appointments represent a significant risk marker for all-cause mortality, particularly in patients with mental health conditions. For these patients, existing primary healthcare appointment systems are ineffective. Future interventions should be developed with a particular focus on increasing attendance by these patients.

Clinical importance of thrombocytopenia in patients with acute coronary syndromes: a systematic review and meta-analysis

Thrombocytopenia (TP) is common in hospitalized patients. In the context of acute coronary syndromes (ACS), TP has been linked to adverse clinical outcomes. We present a systematic review and meta-analysis of the evidence on the clinical importance of preexisting and in-hospital acquired TP in the context of ACS. Specifically, we address (a) the prevalence and associated factors with TP in the context of ACS; and (b) the association between TP and all-cause mortality, major adverse cardiovascular events (MACEs), and major bleeding. We conducted systematic literature searches in MEDLINE and Web of Science. For the meta-analysis, we fit linear mixed models with a random study-specific intercept for the aggregate outcomes. A total of 16 studies and 190 915 patients were included in this study. Of these patients, 8.8% ± 1.2% presented with preexisting TP while 5.8% ± 1.0% developed TP after hospital admission. Preexisting TP was not statistically significantly associated with adverse outcomes. Acquired TP was associated with greater risk of all-cause mortality (risk difference [RD]: 4.3%; 95% confidence interval [CI]: 2–6%; p = 0.04), MACE (RD: 8.5%; 95% CI: 1–16.0%; p = 0.037), and major bleeding (RD: 11.9%; 95% CI: 5–19%; p = 0.005). In conclusion, TP is a prevalent condition in patients admitted for an ACS and identifies a high-risk patient population more likely to experience ischemic and bleeding complications, as well as higher mortality.

Effect of Asymptomatic Severe Aortic Stenosis on Outcomes of Individuals Aged 80 and Older.

To examine the effect of asymptomatic severe aortic stenosis (AS) on mortality late in life. Retrospective cohort study. Large medical center. Asymptomatic adults aged 80 and older (mean age 86 ± 4; N=1,060, n=569 women) with preserved left ventricular ejection fraction (LVEF; > 50%); 927 (87.5%) with no AS, 70 (6.6%) with nonsevere AS, and 63 (5.9%) with severe AS. Information was collected on demographic characteristics, comorbidities, and laboratory and echocardiographic data. Survival was assessed according to longest follow-up available. During a mean follow-up of 2.2 ± 2.3 years, there were 203 (19%) deaths, 51 of which were from cardiovascular causes. Four-year estimates of survival were 72% for no AS, 58% for nonsevere AS, and 23% for severe AS (p<.001). Univariable analysis showed that asymptomatic severe AS was significantly associated with greater risk of all-cause mortality (hazard ratio (HR)=3.06, 95% confidence interval (CI)=1.96-4.58, p<.001). After adjustment for age, sex, LVEF, hypertension, dyslipidemia, diabetes, atrial fibrillation, chronic kidney disease, and coronary artery disease, asymptomatic severe AS was an independent predictor of all-cause mortality (HR=3.16, 95% CI=1.97-4.88, p<.001). Asymptomatic severe AS has a major effect on prognosis even in very old adults.