Profiles of histidine-rich glycoprotein associate with age and risk of all-cause mortality

Despite recognizing aging as a common risk factor of many human diseases, little is known about its molecular traits. To identify age-associated proteins circulating in human blood, we screened 156 individuals aged 50–92 using exploratory and multiplexed affinity proteomics assays. Profiling eight additional study sets (N = 3,987), performing antibody validation, and conducting a meta-analysis revealed a consistent age association (P = 6.61 × 10−6) for circulating histidine-rich glycoprotein (HRG). Sequence variants of HRG influenced how the protein was recognized in the immunoassays. Indeed, only the HRG profiles affected by rs9898 were associated with age and predicted the risk of mortality (HR = 1.25 per SD; 95% CI = 1.12–1.39; P = 6.45 × 10−5) during a follow-up period of 8.5 yr after blood sampling (IQR = 7.7–9.3 yr). Our affinity proteomics analysis found associations between the particular molecular traits of circulating HRG with age and all-cause mortality. The distinct profiles of this multipurpose protein could serve as an accessible and informative indicator of the physiological processes related to biological aging.

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Profiles of circulating histidine-rich glycoprotein associate with chronological age and risk of all-cause mortality

10.1101/464909 ◽

2018 ◽

Cited By ~ 2

Author(s):

Mun-Gwan Hong ◽

Tea Dodig-Crnković ◽

Xu Chen ◽

Kimi Drobin ◽

Woojoo Lee ◽

...

Keyword(s):

Meta Analysis ◽

Protein Profile ◽

Physiological Processes ◽

Risk Of Mortality ◽

Proteomics Approach ◽

All Cause Mortality ◽

Associated Proteins ◽

Antibody Validation ◽

Affinity Proteomics

1.SUMMARYDespite recognizing aging as risk factor of human diseases, little is still known about the molecular traits of biological age and mortality risk. To identify age-associated proteins circulating human blood, we screened 156 subjects aged 50-92 years using an exploratory and multiplexed affinity proteomics approach. We corroborated the top age-associated protein profile (adjusted P < 0.001) in eight additional study sets (N = 4,044 individuals), and confirmed a consistent age-associated increase (P = 6.61 × 10-6) by meta-analysis. Applying antibody validation determined circulating histidine-rich glycoprotein (HRG) as the target, and we observed that sequence variants influenced the antibodies ability to bind to the protein. Profiles of circulating HRG were associated to several clinical traits and predicted the risk of mortality during a follow-up period of 8.5 years (IQR = 7.7-9.3 years) after blood sampling (HR = 1.25 per SD; 95% CI = 1.12-1.39; P = 7.41 × 10-5). In conclusion, our affinity proteomics analysis found associations between the molecular traits of circulating HRG with age and all-cause mortality. This suggests that the profiles of multi-purpose protein HRG could serve as an accessible indicator of physiological processes related to aging.

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Effect of Digoxin Therapy on Mortality in Patients With Atrial Fibrillation: An Updated Meta-Analysis

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.731135 ◽

2021 ◽

Vol 8 ◽

Author(s):

Xiaoxu Wang ◽

Yi Luo ◽

Dan Xu ◽

Kun Zhao

Keyword(s):

Atrial Fibrillation ◽

Meta Analysis ◽

Cochrane Library ◽

Clinical Effects ◽

Hazard Ratios ◽

Risk Of Mortality ◽

Increased Risk ◽

All Cause Mortality ◽

The Cochrane Library

Background: Whether digoxin is associated with increased mortality in atrial fibrillation (AF) remains controversial. We aimed to assess the risk of mortality and clinical effects of digoxin use in patients with AF.Methods: PubMed, Embase, and the Cochrane library were systematically searched to identify eligible studies comparing all-cause mortality of patients with AF taking digoxin with those not taking digoxin, and the length of follow-up was at least 6 months. Hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted and pooled.Results: A total of 29 studies with 621,478 patients were included. Digoxin use was associated with an increased risk of all-cause mortality in all patients with AF (HR 1.17, 95% CI 1.13–1.22, P < 0.001), especially in patients without HF (HR 1.28, 95% CI 1.11–1.47, P < 0.001). There was no significant association between digoxin and mortality in patients with AF and HF (HR 1.06, 95% CI 0.99–1.14, P = 0.110). In all patients with AF, regardless of concomitant HF, digoxin use was associated with an increased risk of sudden cardiac death (SCD) (HR 1.40, 95% CI 1.23–1.60, P < 0.001) and cardiovascular (CV) mortality (HR 1.27, 95% CI 1.08–1.50, P < 0.001), and digoxin use had no significant association with all-cause hospitalization (HR 1.13, 95% CI 0.92–1.39, P = 0.230).Conclusion: We conclude that digoxin use is associated with an increased risk of all-cause mortality, CV mortality, and SCD, and it does not reduce readmission for AF, regardless of concomitant HF. Digoxin may have a neutral effect on all-cause mortality in patients with AF with concomitant HF.Systematic Review Registration:https://www.crd.york.ac.ukPROSPERO.

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Long-term systolic blood pressure and all-cause mortality in heart failure with preserved ejection fraction: an analysis of the TOPCAT trial

European Heart Journal ◽

10.1093/ehjci/ehaa946.0983 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

P Huang ◽

C Liu

Keyword(s):

Heart Failure ◽

Blood Pressure ◽

Ejection Fraction ◽

Funding Source ◽

Preserved Ejection Fraction ◽

Risk Of Mortality ◽

All Cause Mortality ◽

History Of

Abstract Background Lower systolic blood pressure (SBP) at admission or discharge was associated with poor outcomes in patients with heart failure and preserved ejection fraction (HFpEF). However, the optimal long-term SBP for HFpEF was less clear. Purpose To examine the association of long-term SBP and all-cause mortality among patients with HFpEF. Methods We analyzed participants from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) study. Participants had at least two SBP measurements of different times during the follow-up were included. Long-term SBP was defined as the average of all SBP measurements during the follow-up. We stratified participants into four groups according to long-term SBP: <120mmHg, ≥120mmHg and <130mmHg, ≥130mmHg and <140mmHg, ≥140mmHg. Multivariable adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for all-cause mortality associated with SBP level. To assess for nonlinearity, we fitted restricted cubic spline models of long-term SBP. Sensitivity analyses were conducted by confining participants with history of hypertension or those with left ventricular ejection fraction≥50%. Results The 3338 participants had a mean (SD) age of 68.5 (9.6) years; 51.4% were women, and 89.3% were White. The median long-term SBP was 127.3 mmHg (IQR 121–134.2, range 77–180.7). Patients in the SBP of <120mmHg group were older age, less often female, less often current smoker, had higher estimated glomerular filtration rate, less often had history of hypertension, and more often had chronic obstructive pulmonary disease and atrial fibrillation. After multivariable adjustment, long-term SBP of 120–130mmHg and 130–140mmHg was associated with a lower risk of mortality during a mean follow-up of 3.3 years (HR 0.65, 95% CI: 0.49–0.85, P=0.001; HR 0.66, 95% CI 0.50–0.88, P=0.004, respectively); long-term SBP of <120mmHg had similar risk of mortality (HR 1.03, 95% CI: 0.78–1.36, P=0.836), compared with long-term SBP of ≥140mmHg. Findings from restricted cubic spline analysis demonstrate that there was J-shaped association between long-term SBP and all-cause mortality (P=0.02). These association was essentially unchanged in sensitivity analysis. Conclusions Among patients with HFpEF, long-term SBP showed a J-shaped pattern with all-cause mortality and a range of 120–140 mmHg was significantly associated with better outcomes. Future randomized controlled trials need to evaluate optimal long-term SBP goal in patients with HFpEF. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): China Postdoctoral Science Foundation Grant (2019M660229 and 2019TQ0380)

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Prediction of all-cause mortality with malnutrition assessed by controlling nutritional status score in patients with heart failure: a systematic review and meta-analysis

Public Health Nutrition ◽

10.1017/s1368980021002470 ◽

2021 ◽

pp. 1-8

Author(s):

Huiyang Li ◽

Peng Zhou ◽

Yikai Zhao ◽

Huaichun Ni ◽

Xinping Luo ◽

...

Keyword(s):

Heart Failure ◽

Systematic Review ◽

Nutritional Status ◽

Meta Analysis ◽

Predictive Values ◽

Increased Risk ◽

Patients With Heart Failure ◽

All Cause Mortality ◽

Conut Score

Abstract Objective: The aim of this meta-analysis was to investigate the association between malnutrition assessed by the controlling nutritional status (CONUT) score and all-cause mortality in patients with heart failure. Design: Systematic review and meta-analysis. Settings: A comprehensively literature search of PubMed and Embase databases was performed until 30 November 2020. Studies reporting the utility of CONUT score in prediction of all-cause mortality among patients with heart failure were eligible. Patients with a CONUT score ≥2 are grouped as malnourished. Predictive values of the CONUT score were summarized by pooling the multivariable-adjusted risk ratios (RR) with 95 % CI for the malnourished v. normal nutritional status or per point CONUT score increase. Participants: Ten studies involving 5196 patients with heart failure. Results: Malnourished patients with heart failure conferred a higher risk of all-cause mortality (RR 1·92; 95 % CI 1·58, 2·34) compared with the normal nutritional status. Subgroup analysis showed the malnourished patients with heart failure had an increased risk of in-hospital mortality (RR 1·78; 95 % CI 1·29, 2·46) and follow-up mortality (RR 2·01; 95 % CI 1·58, 2·57). Moreover, per point increase in CONUT score significantly increased 16% risk of all-cause mortality during the follow-up. Conclusions: Malnutrition defined by the CONUT score is an independent predictor of all-cause mortality in patients with heart failure. Assessment of nutritional status using CONUT score would be helpful for improving risk stratification of heart failure.

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Sarcopenia Is Associated with Mortality in Adults: A Systematic Review and Meta-Analysis

Gerontology ◽

10.1159/000517099 ◽

2021 ◽

pp. 1-16

Author(s):

Jane Xu ◽

Ching S. Wan ◽

Kiriakos Ktoris ◽

Esmee M. Reijnierse ◽

Andrea B. Maier

Keyword(s):

Systematic Review ◽

Working Group ◽

Meta Analysis ◽

Nursing Home Residents ◽

Community Dwelling ◽

Risk Of Mortality ◽

European Working ◽

Subgroup Analyses ◽

Meta Analyses

Background: Sarcopenia can predispose individuals to falls, fractures, hospitalization, and mortality. The prevalence of sarcopenia depends on the population studied and the definition used for the diagnosis. Objective: This systematic review and meta-analysis aimed to investigate the association between sarcopenia and mortality and if it is dependent on the population and sarcopenia definition. Methods: A systematic search was conducted in MEDLINE, EMBASE, and Cochrane from 1 January 2010 to 6 April 2020 for articles relating to sarcopenia and mortality. Articles were included if they met the following criteria – cohorts with a mean or median age ≥18 years and either of the following sarcopenia definitions: Asian Working Group for Sarcopenia (AWGS and AWGS2019), European Working Group on Sarcopenia in Older People (EWGSOP and EWGSOP2), Foundation for the National Institutes of Health (FNIH), International Working Group for Sarcopenia (IWGS), or Sarcopenia Definition and Outcomes Consortium (SDOC). Hazard ratios (HR) and odds ratios (OR) were pooled separately in meta-analyses using a random-effects model, stratified by population (community-dwelling adults, outpatients, inpatients, and nursing home residents). Subgroup analyses were performed for sarcopenia definition and follow-up period. Results: Out of 3,025 articles, 57 articles were included in the systematic review and 56 in the meta-analysis (42,108 participants, mean age of 49.4 ± 11.7 to 86.6 ± 1.0 years, 40.3% females). Overall, sarcopenia was associated with a significantly higher risk of mortality (HR: 2.00 [95% CI: 1.71, 2.34]; OR: 2.35 [95% CI: 1.64, 3.37]), which was independent of population, sarcopenia definition, and follow-up period in subgroup analyses. Conclusions: Sarcopenia is associated with a significantly higher risk of mortality, independent of population and sarcopenia definition, which highlights the need for screening and early diagnosis in all populations.

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Renin-angiotensin system blocker and outcomes of COVID-19: a systematic review and meta-analysis

Thorax ◽

10.1136/thoraxjnl-2020-215322 ◽

2021 ◽

pp. thoraxjnl-2020-215322

Author(s):

Hyun Woo Lee ◽

Chang-Hwan Yoon ◽

Eun Jin Jang ◽

Chang-Hoon Lee

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Severe Disease ◽

Renin Angiotensin System ◽

Angiotensin Ii Receptor ◽

Angiotensin System ◽

Risk Of Mortality ◽

Increased Risk ◽

All Cause Mortality ◽

Receptor Blockers

BackgroundThe association of ACE inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) with disease severity of patients with COVID-19 is still unclear. We conducted a systematic review and meta-analysis to investigate if ACEI/ARB use is associated with the risk of mortality and severe disease in patients with COVID-19.MethodsWe searched all available clinical studies that included patients with confirmed COVID-19 who could be classified into an ACEI/ARB group and a non-ACEI/ARB group up until 4 May 2020. A meta-analysis was performed, and primary outcomes were all-cause mortality and severe disease.ResultsACEI/ARB use did not increase the risk of all-cause mortality both in meta-analysis for 11 studies with 12 601 patients reporting ORs (OR=0.52 (95% CI=0.37 to 0.72), moderate certainty of evidence) and in 2 studies with 8577 patients presenting HRs. For 12 848 patients in 13 studies, ACEI/ARB use was not related to an increased risk of severe disease in COVID-19 (OR=0.68 (95% CI=0.44 to 1.07); I2=95%, low certainty of evidence).ConclusionsACEI/ARB therapy was not associated with increased risk of all-cause mortality or severe manifestations in patients with COVID-19. ACEI/ARB therapy can be continued without concern of drug-related worsening in patients with COVID-19.

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Evaluation of a multimarker panel in chronic heart failure: a 10-year follow-up

Biomarkers in Medicine ◽

10.2217/bmm-2020-0722 ◽

2021 ◽

Author(s):

Susanne Bauer ◽

Christina Strack ◽

Ekrem Ücer ◽

Stefan Wallner ◽

Ute Hubauer ◽

...

Keyword(s):

Heart Failure ◽

Prognostic Role ◽

Blood Samples ◽

Kaplan Meier ◽

Risk Of Mortality ◽

Patients With Heart Failure ◽

All Cause Mortality ◽

Long Time

Aim: We assessed the 10-year prognostic role of 11 biomarkers with different pathophysiological backgrounds. Materials & methods/results: Blood samples from 144 patients with heart failure were analyzed. After 10 years of follow-up (median follow-up was 104 months), data regarding all-cause mortality were acquired. Regarding Kaplan–Meier analysis, all markers, except TIMP-1 and GDF-15, were significant predictors for all-cause mortality. We created a multimarker model with nt-proBNP, hsTnT and IGF-BP7 and found that patients in whom all three markers were elevated had a significantly worse long-time-prognosis than patients without elevated markers. Conclusion: In a 10-year follow-up, a combination of three biomarkers (NT-proBNP, hs-TnT, IGF-BP7) identified patients with a high risk of mortality.

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Sudden death in patients with sleep apnea: a systematic review and meta-analysis

10.1101/2020.05.06.20093641 ◽

2020 ◽

Author(s):

Emily S. Heilbrunn ◽

Paddy Ssentongo ◽

Vernon M. Chinchilli ◽

Anna E. Ssentongo

Keyword(s):

Sleep Apnea ◽

Sudden Death ◽

Cardiovascular Mortality ◽

Meta Analysis ◽

Cardiac Mortality ◽

Risk Of Death ◽

Risk Of Mortality ◽

Obstructive Sleep ◽

Increased Risk ◽

All Cause Mortality

AbstractBackgroundOver 1 billion individuals across the globe experience some form of sleep apnea, and this number is steadily rising. Obstructive sleep apnea (OSA) can negatively influence one’s quality of life and potentially increase the risk of mortality. However, this association between OSA and mortality has not been comprehensively and thoroughly explored. This meta-analysis was conducted to conclusively estimate the risk of death for all-cause mortality and cardiovascular mortality in OSA patients.Study Design4,613 articles from databases including PUBMED, OVID & Joana Briggs, and SCOPUS were comprehensively assessed by two reviewers (AES & ESH) for inclusion criteria. 28 total articles were included, with 22 of them being used for quantitative analysis. Pooled effects of all-cause mortality, cardiac mortality, and sudden death were calculated by utilizing the metaprop function in R Statistical Software and the random-effects model with appropriate 95% confidence intervals.ResultsAnalysis on 42,032 individuals revealed that those with OSA were twice as likely to die from cardiac mortality compared to those without sleep apnea (HR= 1.94, 95%CI 1.39-2.70). Likewise, individuals with OSA were 1.7 times as likely to die from all-cause sudden death compared to individuals without sleep apnea (HR= 1.74, 95%CI 1.40-2.10). There was a significant dose response relationship between severity of sleep apnea and incidence risk of death, where those with severe sleep apnea wereConclusionsIndividuals with obstructive sleep apnea are at an increased risk for all-cause mortality and cardiac mortality. Further research related to appropriate interventions and treatments are necessary in order to reduce this risk and optimize survival in this population.Key MessagesWhat is the key question?Are individuals with sleep apnea at an increased risk for cardiovascular mortality and sudden death?What is the bottom Line?Sleep apnea is associated with an increased risk of cardiovascular mortality and sudden death, with a dose response relationship, where those with severe sleep apnea are at the highest risk of mortality.Why read on?This is the first systematic review and meta-analyses to synthesize and quantify the risk of mortality in those with sleep apnea, highlighting important directions for future research.Prospero Registration IDCRD42020164941

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Sarcopenia and Frailty in PD: Impact on Mortality, Malnutrition, and Inflammation

Peritoneal Dialysis International ◽

10.3747/pdi.2017.00271 ◽

2018 ◽

Vol 38 (6) ◽

pp. 447-454 ◽

Cited By ~ 16

Author(s):

Yuka Kamijo ◽

Eiichiro Kanda ◽

Yoshitaka Ishibashi ◽

Masayuki Yoshida

Keyword(s):

Muscle Mass ◽

Secondary Outcome ◽

Related Factors ◽

Clinical Frailty Scale ◽

Risk Of Mortality ◽

All Cause Mortality ◽

Comorbidity Index ◽

The Relationship ◽

Worse Prognosis

Background It is known that sarcopenia is related to malnutrition-inflammation-atherosclerosis (MIA) syndrome and is an important problem in dialysis patients. The notion of frailty includes various physical, psychological, and social aspects. Although it has been reported that sarcopenia is associated with poor prognosis in patients with hemodialysis, reports on peritoneal dialysis (PD) patients are rare. In this study, we examined the morbidity and mortality of sarcopenia and frailty in PD patients. We also investigated the MIA-related factors. Methods We evaluated 119 patients cross-sectionally and longitudinally. The Asian Working Group for Sarcopenia criteria and the Clinical Frailty Scale (CFS) were used to diagnose sarcopenia and frailty. The primary outcome is all-cause mortality with sarcopenia and frailty. The secondary outcome is the relationship between various MIA-related factors. Results Morbidity of sarcopenia and frailty in PD patients was 8.4% and 10.9%, respectively. Old age, high values of Barthel Index, Charlson Comorbidity Index, CFS, and low values of body mass index (BMI), muscle strength, muscle mass, and slow walking were associated with sarcopenia. Interleukin-6, albumin, and prealbumin were significantly correlated with muscle mass. During follow-up, the presence of sarcopenia or frailty was associated with the risk of mortality. In multivariate analysis, CFS was related to the mortality rate of PD patients. Conclusions The presence of sarcopenia or frailty was associated with a worse prognosis.

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Abstract 309: Is Right Bundle Branch Block Associated with Poor Outcomes in the Setting of an Acute Coronary Syndrome? A Systematic Review and Meta-analysis

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.7.suppl_1.309 ◽

2014 ◽

Vol 7 (suppl_1) ◽

Author(s):

Ahmad Hazem ◽

Sunita Sharma ◽

Amit Sharma ◽

Cameron Leitch ◽

Roopalakshmi Sharadanant ◽

...

Keyword(s):

Systematic Review ◽

Acute Coronary Syndrome ◽

Right Bundle Branch Block ◽

Risk Ratio ◽

Meta Analysis ◽

Forest Plot ◽

Bundle Branch Block ◽

Coronary Syndrome ◽

All Cause Mortality

Importance: Up to 10% of patients with acute myocardial infarction (AMI) have right bundle branch block (RBBB), and RBBB has been associated with a higher risk of mortality. We performed a systematic review and meta-analysis to determine the prognostic significance of RBBB for patients with AMI. Acute coronary syndrome (ACS) Data Sources: We have systematically searched Ovid, Scopus and Web of Science through January 2014. Study Selection: Reviewers working independently and in duplicate screened all eligible abstracts, selecting studies that described all-cause mortality or cardiovascular death in patients with RBBB and suspected ACS. We excluded studies that reported unadjusted outcomes. Knowledge synthesis: We pooled risk ratio with hazard ratio in studies reporting those outcomes. When reported, odds ratio was converted into risk ratio using reported event rate in each study’s unexposed -read: non RBBB- group. Main Outcomes: All-cause mortality and cardiovascular mortality (death). Results: Eighteen studies were found that reported eligible data. All were observational studies, involving over 89,000 patients. In short-term follow up (up to 30 days), RBBB on presentation was associated with higher all-cause mortality rate, compared to patients without RBBB (RR 2.23, 95% CI 1.76-2.82). There was a trend for higher mortality at long-term follow up (range: 6 months-16 years) that did not reach statistical significance (RR 1.45, 95% CI 0.93-2.25). Figure-1 demonstrates the forest plot. Risk of bias was assessed with the Newcastle-Ottawa scale and majority of included studied were deemed moderate to high quality. Conclusion and Relevance: RBBB is associated with a more than 2-fold higher risk of all-cause mortality in patients with AMI at 30 days follow up. Patients with AMI and RBBB represent a high risk group for adverse outcomes. A sentence on the differential findings for new vs. old RBBB and association with outcomes could follow here.

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