Greater Risk Of All-cause Mortality Research Articles

CRP, C-Peptide, and Risk of First-Time Cardiovascular Events and Mortality in Early Type 2 Diabetes: A Danish Cohort Study

We investigated the relationship between hs-CRP, a marker of low-grade inflammation, alone or in combination with C-peptide, a marker of hyperinsulinemia/insulin resistance, and risk for cardiovascular events (CVEs) and mortality in patients recently diagnosed with type 2 diabetes (T2D). In patients with recent-onset T2D, we measured serum hs-CRP (n = 7,301) and C-peptide (n = 5,765) in the prospective Danish Centre for Strategic Research in Type 2 Diabetes cohort study. Patients with no prior CVE (n = 6,407) were followed until first myocardial infarction, stroke, coronary revascularization, or cardiovascular death, and all patients (n = 7,301) were followed for all-cause mortality. We computed adjusted hazard ratios (aHRs) by Cox regression and tested for the interaction between hs-CRP and C-peptide. During follow-up (median 4.8 years), high (>3 mg/L) versus low (<1 mg/L) hs-CRP was associated with increased CVE risk (aHR 1.45 [95% CI 1.07-1.96]) and with even greater risk of all-cause mortality (2.47 [1.88-3.25]). Compared with patients with low hs-CRP (≤3 mg/L) and low C-peptide (<1,470 pmol/L), those with high levels of both biomarkers had the highest CVE (1.61 [1.10-2.34]) and all-cause mortality risk (2.36 [1.73-3.21]). Among patients with high C-peptide, risk of CVEs did not differ by low or high hs-CRP, whereas risk of all-cause mortality did. The finding of high hs-CRP as a stronger prognostic biomarker of all-cause mortality than of CVEs may facilitate improved early detection and prevention of deadly diseases besides CVEs. Conversely, elevated C-peptide as a strong CVE biomarker supports the need to target hyperinsulinemia/insulin resistance in T2D CVE prevention.

All-cause mortality risk with different metabolic abdominal obesity phenotypes: the Rural Chinese Cohort Study.

We aimed to investigate the association of metabolic obesity phenotypes with all-cause mortality risk in a rural Chinese population. This prospective cohort study enrolled 15704 Chinese adults (38·86 % men) with a median age of 51·00 (interquartile range: 41·00-60·00) at baseline (2007-2008) and followed up during 2013-2014. Obesity was defined by waist circumference (WC: ≥ 90 cm for men and ≥ 80 cm for women) or waist-to-height ratio (WHtR: ≥ 0·5). The hazard ratio (HR) and 95 % CI for the risk of all-cause mortality related to metabolic obesity phenotypes were calculated using the Cox hazards regression model. During a median follow-up of 6·01 years, 864 deaths were identified. When obesity was defined by WC, the prevalence of participants with metabolically healthy non-obesity (MHNO), metabolically healthy obesity (MHO), metabolically unhealthy non-obesity (MUNO) and metabolically unhealthy obesity (MUO) at baseline was 12·12 %, 2·80 %, 41·93 % and 43·15 %, respectively. After adjusting for age, sex, alcohol drinking, smoking, physical activity and education, the risk of all-cause mortality was higher with both MUNO (HR = 1·20, 95 % CI 1·14, 1·26) and MUO (HR = 1·20, 95 % CI 1·13, 1·27) v. MHNO, but the risk was not statistically significant with MHO (HR = 0·99, 95 % CI 0·89, 1·10). This result remained consistent when stratified by sex. Defining obesity by WHtR gave similar results. MHO does not suggest a greater risk of all-cause mortality compared to MHNO, but participants with metabolic abnormality, with or without obesity, have a higher risk of all-cause mortality. These results should be cautiously interpreted as the representation of MHO is small.

Depression with obstructive sleep apnea lead to high cardiovascular disease morbidity/all-cause mortality: Findings from the SHHS cohort.

The aim of this study is to explore the association between depression and obstructive sleep apnea, and cardiovascular disease morbidity/all-cause mortality using Sleep Heart Health Study data. This post hoc analysis of a prospective study used patient data from the Sleep Heart Health Study conducted between 1995 and 1998. The association between depression and obstructive sleep apnea, and cardiovascular disease morbidity/all-cause mortality was explored using multivariable Cox proportional hazard models. A total of 4918 participants, 656 (13.3%) with obstructive sleep apnea (obstructive sleep apnea group), 1614 (32.8%) with depression (depression group), 482 (9.8%) with depression and obstructive sleep apnea (depression and obstructive sleep apnea group), and 2166 (44%) with neither obstructive sleep apnea nor depression (health group), were included. The incidence of cardiovascular disease was 24.5%, 31.0%, 31.6% and 41.7% for healthy, depression, obstructive sleep apnea, and depression and obstructive sleep apnea groups, respectively. The risk of cardiovascular disease in depression and obstructive sleep apnea participants was increased compared with that in healthy participants, which was consistent across various definitions of obstructive sleep apnea (hazard ratio [95% confidence interval]: 1.24 [1.06-1.47]; 1.25 [1.05-1.49]; 1.28 [1.06-1.54]; 1.55 [1.22-1.96] for apnea-hypopnea index ≥ 10 per hr, 15 per hr, 20 per hr, 30 per hr, respectively). The risk of all-cause mortality was increased in the depression and obstructive sleep apnea participants (hazard ratio: 1.46; 95% confidence interval: 1.07-1.99) compared with that in healthy participants when the definition of obstructive sleep apnea was apnea-hypopnea index ≥ 30. Participants with depression and obstructive sleep apnea might be at a greater risk of cardiovascular disease, and those with higher apnea-hypopnea index might be at a greater risk of all-cause mortality.

Associations of daily diet-related greenhouse gas emissions with the incidence and mortality of chronic diseases: a systematic review and meta-analysis of epidemiological studies.

Although the entire process extending from food production to dietary consumption makes a large contribution to total greenhouse gas (GHG) emissions, little and inconsistent evidence exists on the epidemiological associations of daily diet-related GHG emissions with chronic disease risk or all-cause mortality. This systematic review and meta-analysis explored the observational epidemiological relationship between daily diet-related GHG emissions and health outcomes, including the risk of chronic diseases and all-cause mortality. Original articles published in English until May 2022 were identified by searching PubMed, Ovid-Embase, Web of Science, CINAHL, and Google Scholar. The extracted data were pooled using both fixed-effects and random-effects meta-analyses and presented as hazard and risk ratios (RRs) with 95% confidence intervals (CIs). In total, 7 cohort studies (21 study arms) were included for qualitative synthesis and meta-analysis. The GHG emissions of dietary consumption showed a significant positive association with the risk of chronic disease incidence and mortality in both fixed-effects and random-effects models (fixed: RR, 1.04; 95% CI, 1.03 to 1.05; random: RR, 1.04; 95% CI, 1.02 to 1.06). This positive association was robust regardless of how daily diet-related GHG emissions were grouped. More strongly animal- based diets showed higher GHG emissions. However, there were only a few studies on specific chronic diseases, and the subgroup analysis showed insignificant results. There was no evidence of publication bias among the studies (Egger test: p=0.79). A higher GHG-emission diet was found to be associated with a greater risk of all-cause mortality.

COPING VARIABILITY AND ITS ASSOCIATION WITH ALL-CAUSE MORTALITY

Abstract Coping strategies – cognitive, behavioral, and emotional tactics used to manage stressors – are associated with morbidity and mortality. Between-strategy coping variability, defined as (un)evenness in usage across coping strategies, may reflect context-specific coping and account for additional variance in health outcomes beyond mean strategy use. This study examined prospective associations of mean coping strategy use and between-strategy coping variability with time to death in 823 men from the Normative Aging Study. In Cox proportional hazard models, 1-SD higher in mean usage of positive action, negative action, prayer, withdrawal, and substance use strategies was associated with 17-32% greater risk of all-cause mortality over 27 years, after adjusting for baseline demographics, health status, and depression. Contrary to prior research, mortality risk did not differ by coping variability. We will consider findings within the stress and coping framework and discuss implications for biobehavioral pathways linking coping to all-cause mortality.

The association of disparities in neighborhood median household income and mortality in patients admitted to the hospital with atrial fibrillation

BackgroundLower neighborhood median household income (nMHI) is associated with increased adverse outcomes in patients with atrial fibrillation (AF). However, its effect on mortality is yet unknown. MethodsData from the regional United States (U.S.) electronic medical records database, Research Action for Health Network (REACHnet), was extracted for adult patients with AF at Tulane Medical Center over 10 years. Annual nMHI & neighborhood high school graduation (HSG) data was collected from the US Census bureau. Only African Americans (AA) and Caucasians (CC) who had socioeconomic data were included. Low nMHI and low HSG were defined as ≤$25,000 & <90% respectively. High nMHI and HSG were defined as >$50,000 & ≥90% respectively. Primary endpoints were all cause and cardiovascular (CV) mortality. Cox-proportional hazard ratios were used to evaluate the endpoints. ResultsWe included 4616 patients diagnosed with AF. During a median follow up of 4.6 years, 434 patients died of which 32.7% patients had CV mortality. There was a stepwise decrease in incidence of both all-cause and CV mortality as nMHI increased. Patients with low nMHI had the greatest risk of all-cause mortality (HR 1.9, C.I. 1.2–3.2, P 0.004). The association between low nMHI and all-cause mortality persisted after adjusting for age, sex, race, HSG and stroke risk factors using CHA2DS2VASC, delta CHA2DS2VASC scores and oral anticoagulant use. CV mortality followed a similar trend as all-cause mortality, however, this association was not significant after adjusting for the above variables. Apart from low nMHI, CHA2DS2VASC delta CHA2DS2VASC were statistically significant independent predictors of both all-cause and CV mortality. ConclusionLow nMHI is an independent risk factor for all cause and CV mortality in AF. Higher burden of co-morbidities is the driving force behind this disparity. Future studies should evaluate the role of educational and therapeutic intervention in these populations to reduce mortality.

Cognitive impairment assessed by Mini-Mental State Examination predicts all-cause and CVD mortality in Chinese older adults: A 10-year follow-up study.

Cognitive impairment (CI) has been demonstrated as a useful proxy measure of mortality in Western populations. However, the predictive value of CI in Chinese populations is unknown. We aimed to explore whether CI is independently associated with increased long-term all-cause and cardiovascular disease (CVD) mortality in Chinese older adults and the association of performance in specific MMSE sub-domains to subsequent mortality. A total of 4,499 older adults [mean (SD) age, 70.3(6.7) years] who received a sample investigation from 2011 to 2014 were followed up till 2021 for mortality. The Mini-Mental State Examination was used to assess cognitive function, and Cox's proportional hazard models were used to evaluate the effects of cognitive function on the risk of all-cause and CVD mortality. Demographic characteristics, lifestyle, and health status were included as covariates. During a 10-year follow-up, a total of 667 (14.8%) died. In the fully adjusted model, compared with cognitively normal participants with CI had a 1.33-fold [HR, 1.33; (95% CI, 1.10-1.61)] greater risk of all-cause mortality and a 1.45-fold [HR, 1.45; (95% CIs, 1.11-1.92)] greater risk of CVD mortality. After a similar multivariable adjustment, a per-SD increase in MMSE scores was associated with a reduced risk of all-cause mortality [HR, 0.85; (95% CI, 0.78-0.93)] and CVD mortality [HR, 0.74; (95% CI, 0.65-0.84)]. In the unadjusted model, MMSE sub-domains (apart from immediate recall) were associated with mortality. But only orientation and calculation and attention were still independently associated with all-cause and CVD mortality in a multivariable model. These findings confirmed that CI is a marker of all-cause and CVD mortality risk in Chinese older adults, independently of other commonly assessed risk factors, and some sub-domains of the MMSE may have stronger associations with mortality. Further research is needed to identify the mechanisms underlying the observed associations.

Associations of Minor Histocompatibility Antigens with Clinical Outcomes Following Allogeneic Hematopoietic Cell Transplantation

Introduction Donor T-cell recognition of tumor-presented minor histocompatibility antigens (mHAs) is thought to be a central mediator of the therapeutic graft versus leukemia (GvL) effect following allogeneic hematopoietic cell transplantation (alloHCT). In contrast, graft versus host disease (GvHD) develops when donor T-cells react to mHAs presented by normal recipient cells. While the role of mHAs in outcomes following alloHCT is recognized, it has not been well-characterized. It remains unclear whether GvL and GvHD are mediated by the cumulative effect of total mHAs in a donor-recipient pair (DRP) or individual immunodominant mHAs. We hypothesized that an increased mHA count and individual mHAs would be associated with lower relapse and disease-related mortality (DRM) and/or increased GvHD mortality. To this end, we predicted genome-wide mHA peptides in a large patient population and analyzed the associations between clinical outcomes and 1) the total number of predicted class I and class II mHAs, and (2) individual and groups of mHAs. Methods The study population consisted of 2249 European American DRPs in the DISCOVeRY-BMT dataset treated for Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) with alloHCT. To predict mHAs in a DRP, we translated nonsynonymous SNP alleles present in alloHCT recipients, but absent in their donor, into all possible peptides of varying lengths that would encompass the altered amino acid. To identify mHAs most likely to be immunogenic, peptides were filtered based on (1) source protein gene expression data in GvL and GvHD target tissues, including AML, liver, skin, and colon, from UCSC's Xena Dataset repository and (2) recipient HLA binding affinity from netMHCpan. To test the association of mHA count and individual mHAs with all-cause mortality (OS) and leukemia-free survival (LFS) we used cox proportional hazard models and competing risk models for DRM, treatment-related mortality (TRM), and GvHD mortality. Individual mHA analyses were stratified by HLA type to recognize that T-cell responses depend on HLA-mHA complexes. Models were adjusted for clinical covariates. Bonferroni correction for multiple testing was based on the number of independent SNPs. Results Patients with a class I mHA count greater than the population median had a 39% (HR=1.39, 95%CI 1.005,1.772, P=0.046) increase in hazard of GvHD mortality compared to those with a count less than the median. Patients with a class II mHA count greater than the population median had a decreased overall survival compared to those with a count less than the median (Fig. 1, P=0.029). In recipients with HLA-B*08:01, the class I mHA DLRCKYISL was associated with increased risk of GVHD mortality (HR=2.84, 95%CI 1.52,5.31, P=0.01). Within HLA-B*40:01, WEHGPTSLL was associated with decreased LFS (HR=1.94, 95%CI 1.27,2.95, P=0.044). Within HLA-C*03:04, STSPTTNVL was associated with increased risk of DRM (HR=2.32, 95%CI 1.5,3.6, P=0.008). In recipients with HLA-DRB1*15:01, the class II mHA YQEIAAIPSAGRERQ was associated with increased risk of TRM (HR=3.05, 95%CI 1.75,5.31, P=0.02). Two mHAs, WEHGPTSLL and STSPTTNVL, were found within the HLA haplotype B*40:01-C*03:04. Recipients with both mHAs (versus neither) had a greater hazard of 1-year all-cause mortality (HR=3.58, P=7.9×10-5) and DRM (HR=3.65, P=0.003) (Fig. 2). Patients with either mHA (versus neither) had greater 1-year all-cause mortality (HR=1.69, P=0.008) and increased DRM (HR=2.05, P=0.008) Conclusions The number of class I mHAs in a DRP was associated with increased GvHD mortality, which is consistent with our hypothesis. We also found two mHAs correlated with GvHD mortality and DRM which may represent increased GvH effects driven by these peptides. However, contrary to our hypothesis, an increased number of class II mHAs was correlated with greater risk of all-cause mortality that may be due to decreased LFS. Similarly, we found two mHAs correlated with increased DRM and decreased LFS. These two mHAs are found in an HLA haplotype where they exhibit a dose effect relationship with the risk of DRM and decreased OS. These findings may reflect an unexpectedly attenuated GvL effect that requires further investigation. Our study reports the first large scale investigation of the role of predicted mHA peptides in clinical outcomes following alloHCT. If validated, these results may be used to help guide clinical decision making. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Abstract 15411: Life After the Valve, Analyzing Post-Procedural Anemia and Mortality in Transcatheter Aortic Valve Replacement Patients

Introduction: Transcatheter Aortic Valve Replacement (TAVR) has become the primary therapeutic option for many patients with severe aortic stenosis (AS). As a result, anemia is a prevalent co-morbidity amongst the TAVR population. Recent studies have demonstrated pre-procedural anemia is associated with increased long-term mortality in TAVR patients. However, the comparison of TAVR patients’ post-procedural anemia and its effect on mortality has not been fully investigated. Methods: Retrospective analysis of electronic medical records from 2018-2021 at the University of Illinois at Chicago and Jesse Brown VA Medical Center identified TAVR patients. Primary outcomes included all-cause mortality and significant bleeding at 6-months and 12-months post-TAVR. Results: We included 160 patients in the analysis. They were 122 males, 56.88% non-white, and an average age of 73.88. At 6-months, patients who experienced all-cause mortality had an average hemoglobin of 9.85 (g/dL) compared to an average hemoglobin of 11.31 in those patients that survived (p = 0.020). There was no significant difference in major bleeding events between the two groups (p = 0.974) as well as no significant difference in past-medical history, including hypertension, hyperlipidemia (HLD), diabetes mellitus, history of stroke and history of myocardial infarction. At 12-months, patients who experienced all-cause mortality had an average hemoglobin of 10.18 compared to an average hemoglobin of 11.36 in those patients that survived (p = 0.014). There was no significant difference in major bleeding events (p = 0.753) and no significant difference in past-medical history, except for hyperlipidemia. The prevalence of HLD was 59.09% in those that experienced all-cause mortality compared to 78.72% in those that did not (p = 0.045). Conclusions: Our results suggest that patients with lower hemoglobin levels after TAVR are at a greater risk of all-cause mortality compared to those with higher hemoglobin levels. These patients may benefit from closer follow-up after the procedure.

Ascertainment of aortic valve disease using administrative claims

Abstract Background Administrative claims may be useful for characterizing patients with aortic stenosis (AS) and aortic regurgitation (AR) and estimating disease prevalence. However, the accuracy of diagnostic codes for aortic valve disease has not been well studied. Purpose To evaluate the validity of International Classification of Diseases, 10th Revision (ICD-10) codes for identification of AS and AR. Methods Using a large, transthoracic echocardiographic (TTE) report dataset linked to Medicare Fee-for-service (FFS) claims, 2017–2018, the performance of candidate claims to ascertain AS/AR status using standard TTE definitions was evaluated. Recursive partitioning with 10-fold cross validation was used to build the optimal prediction tree for AS/AR status using all ICD-10 codes as candidate predictors. The optimal performing claims algorithm was tested against patient outcomes in a separate 100% sample of Medicare FFS inpatient and outpatient claims, 2017–2019. Results Of those included in the derivation dataset (N=5497, mean age 74.4±11.0 years, 49.7% female), any AS or AR was present in 24% and 38.8%, respectively. The code I35.0 was optimal for identification of any AS with a sensitivity and specificity for any AS of 53.1% and 94.8%, respectively (Table 1). Amongst those with an I35.0 code, 40.3% had severe AS. Claims were unable to distinguish disease severity (i.e. severe vs. non-severe) or subtypes (e.g. bicuspid or rheumatic AS), and were insensitive and nonspecific for AR of any severity. Among all Medicare beneficiaries who received an TTE (N=3,783,249), those with an I35.0 code, compared to those without, had a higher risk of all-cause mortality (HR 1.65, 95% CI 1.63–1.67), heart failure hospitalization (HR 2.17, 95% CI 2.11–2.24), and aortic valve replacement (HR 32.35, 95% CI 31.46–33.27) (Table 2). Conclusions Amongst those receiving TTE, the ICD-10 code I35.0 in any position was optimal for identification of AS and identified a population at significant greater risk of all-cause mortality, heart failure hospitalization, and receipt of aortic valve replacement. Though 40.3% of those with I35.0 had severe AS, claims were unable to distinguish disease severity of subtype. Claims may be feasibly used to identify those with AS who may be at risk for adverse valve-related cardiovascular events and require future treatment. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): National, Heart, Lung, and Blood Institute

Sex- and age-specific all-cause mortality in insomnia with hypnotics: Findings from Japan multi-institutional Collaborative Cohort Study

ObjectiveFindings on the increased mortality risk in individuals with insomnia are inconsistent across studies. Rather than improving insomnia by sleep control, hypnotic use may be one factor in the increased risk of death; however, the effects of hypnotics on mortality remains unclear. This study aimed to examine the association between all-cause mortality and hypnotic use in a large sample, while adjusting for the effects of comorbidities. MethodsOverall, 92,527 individuals aged 35–69 years were followed up for mortality in the Japan Multi-Institutional Collaborative Cohort Study. Regular use of hypnotics was assessed using a self-administered questionnaire. Since cancer history carries a substantial risk of death and is associated with the treatment of insomnia with hypnotics, participants with a cancer history were excluded. The hazard ratio (HR) and 95% confidence interval (CI) for all-cause mortality related to hypnotic use were estimated using a Cox proportional hazard model with adjustments for covariates including sleeping hours and comorbidities (body mass index, ischemic heart disease, stroke, and diabetes). ResultsDuring the follow-up (mean, 8.4 ± 2.5 years), 1,492 mortalities were recorded, and the prevalence of taking hypnotics was 4.2%. Hypnotic use was associated with significantly greater risk of all-cause mortality, even after adjustment for the covariates (HR, 1.32; 95% CI, 1.07–1.63). The association between hypnotic use and all-cause mortality was robust in males (HR, 1.51; 95% CI, 1.15–1.96), and participants aged <60 years (HR, 1.75; 95% CI, 1.21–2.54). ConclusionsOur study revealed sex-age specific associations between hypnotic use and all-cause mortality.

Dynapenia in all-cause mortality and its relationship with sedentary behavior in community-dwelling older adults

The aim of the present study was to investigate the relationship of dynapenia combined with sedentary behavior (SB) on the risk of mortality in older adults living in a Brazilian community. A total of 322 participants aged ≥ 60 years from the ELSIA (Longitudinal Study of Elderly Health in Alcobaça) prospective cohort were included. Dynapenia was diagnosed when the handgrip strength was < 27 ​kg for men and < 16 ​kg for women. The exposure time to SB was assessed considering the total time spent sitting during one day in the week and one day on the weekend. When combined with dynapenia, we derived the construction of four groups: best behavior (absence of dynapenia and low SB), intermediate behavior (absence of dynapenia and high SB; presence of dynapenia and low SB) and worst behavior (presence of dynapenia and high SB). Mortality was assessed by the follow-up time until death and/or censorship. During the 5-year follow-up of the study, 55 participants progressed to death. In the adjusted models, the dynapenia and the time spent exposed to SB were analyzed in a combined way, the older adults with worse behavior (high SB and dynapenia) had higher risk ratios for mortality (hazard ratio 2.46; 95% confidence interval 1.01–5.97) than the best behavior group. Older adults with dynapenia are at greater risk for all-cause mortality, which is aggravated by the addition of longer exposure to SB.

Treatment Outcome with High versus low-to-moderate Dosing of Corticosteroids in Early vis-a-vis Late-onset Hypoxic Cases of COVID-19: A Multicentric Retrospective Cohort Study

Background: Corticosteroid dosing in COVID-19 cases associated with early-onset and late-onset hypoxia have not been separately explored.Methods: In this retrospective cohort study, we divided hypoxic COVID-19 cases into groups based on timing of initiation of corticosteroids relative to onset of symptoms; Group-A (≤6th day), Group-B (7th-9th day) and Group-C (≥10th day), each group being sub-grouped into high and low-to-moderate dose corticosteroid recipients. Cox regression with propensity-scoring was used to compare 28 days-mortality between high and low-to-moderate dose recipients separately in Group-A, Group-B, Group-C.Results: Among 505 patients included, propensity-score matched Cox regression showed greater risk of all-cause mortality among high dose recipients in Group-A [HR= 7.35, 95%CI 3.36-16.11, p-value<0·01, N=114] and Group-B [HR=3.17, 95%CI 1.65-6.07, p-value<0·01, N=251]. In Group-C, mortality was lowest [12.8% (18/140)] with no significant difference between sub-groups [HR=2.52, 95%CI 0.22-29.15, p-value=0.459, N=140]. Kruskal-Wallis Test between Group-A, Group-B and Group-C for six pre-defined exposure variables showed significant differences for Neutrophil:Lymphocyte Ratio (NLR).Conclusion: When steroids were initiated early (owing to an earlier onset of hypoxic symptoms), a high dose of corticosteroid was associated with greater overall 28 days-mortality compared to a low-to-moderate dose. NLR, a marker for individual immune response, varied between treatment groups.

Comparative Safety and Effectiveness of Roux-en-Y Gastric Bypass and Sleeve Gastrectomy for Weight Loss and Type 2 Diabetes Across Race and Ethnicity in the PCORnet Bariatric Study Cohort

Bariatric surgery is the most effective treatment for severe obesity; yet it is unclear whether the long-term safety and comparative effectiveness of these operations differ across racial and ethnic groups. To compare outcomes of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) across racial and ethnic groups in the National Patient-Centered Clinical Research Network (PCORnet) Bariatric Study. This was a retrospective, observational, comparative effectiveness cohort study that comprised 25 health care systems in the PCORnet Bariatric Study. Patients were adults and adolescents aged 12 to 79 years who underwent a primary (first nonrevisional) RYGB or SG operation between January 1, 2005, and September 30, 2015, at participating health systems. Patient race and ethnicity included Black, Hispanic, White, other, and unrecorded. Data were analyzed from July 1, 2021, to January 17, 2022. RYGB or SG. Percentage total weight loss (%TWL); type 2 diabetes remission, relapse, and change in hemoglobin A1c (HbA1c) level; and postsurgical safety and utilization outcomes (operations, interventions, revisions/conversions, endoscopy, hospitalizations, mortality, 30-day major adverse events) at 1, 3, and 5 years after surgery. A total of 36 871 patients (mean [SE] age, 45.0 [11.7] years; 29 746 female patients [81%]) were included in the weight analysis. Patients identified with the following race and ethnic categories: 6891 Black (19%), 8756 Hispanic (24%), 19 645 White (53%), 826 other (2%), and 783 unrecorded (2%). Weight loss and mean reductions in HbA1c level were larger for RYGB than SG in all years for Black, Hispanic, and White patients (difference in 5-year weight loss: Black, -7.6%; 95% CI, -8.0 to -7.1; P < .001; Hispanic, -6.2%; 95% CI, -6.6 to -5.9; P < .001; White, -5.9%; 95% CI, -6.3 to -5.7; P < .001; difference in change in year 5 HbA1c level: Black, -0.29; 95% CI, -0.51 to -0.08; P = .009; Hispanic, -0.45; 95% CI, -0.61 to -0.29; P < .001; and White, -0.25; 95% CI, -0.40 to -0.11; P = .001.) The magnitude of these differences was small among racial and ethnic groups (1%-3% of %TWL). Black and Hispanic patients had higher risk of hospitalization when they had RYGB compared with SG (hazard ratio [HR], 1.45; 95% CI, 1.17-1.79; P = .001 and 1.48; 95% CI, 1.22-1.79; P < .001, respectively). Hispanic patients had greater risk of all-cause mortality (HR, 2.41; 95% CI, 1.24-4.70; P = .01) and higher odds of a 30-day major adverse event (odds ratio, 1.92; 95% CI, 1.38-2.68; P < .001) for RYGB compared with SG. There was no interaction between race and ethnicity and operation type for diabetes remission and relapse. Variability of the comparative effectiveness of operations for %TWL and HbA1c level across race and ethnicity was clinically small; however, differences in safety and utilization outcomes were clinically and statistically significant for Black and Hispanic patients who had RYGB compared with SG. These findings can inform shared decision-making regarding bariatric operation choice for different racial and ethnic groups of patients.

The impact of chronic pre-dialysis hyponatremia on clinical outcomes in maintenance hemodialysis patients

ObjectiveChronic pre-dialysis hyponatremia is not rare in maintenance hemodialysis (MHD) patients. However, the association between chronic pre-dialysis hyponatremia and mortality is uncertain due to multiple potential confounders such as hyperglycemia, fluid overload, and malnutrition. This study aimed to more comprehensively evaluate the association between chronic pre-dialysis hyponatremia and clinical outcomes in MHD patients.MethodsWe analyzed the data of 194 MHD patients with regular real-time measurements of pre-dialysis serum sodium from July 2015 to March 2021. Hyponatremia was defined as SNa ≤ 135 mmol/L and normonatremia as SNa > 135 mmol/L and < 145 mmol/L. We evaluated the association of baseline pre-dialysis serum sodium (SNa) and time-averaged SNa (TASNa) levels with all-cause mortality or new major adverse cardiovascular events (MACE) in MHD patients. Furthermore, the SNa levels were glucose, serum albumin, and fluid overload adjusted. The associations between SNa levels and all-cause mortality or new MACE were analyzed using time-varying Cox regression models.ResultsAmong the total of 194 patients, 24 patients died and 45 new MACE occurred during a mean 35.2-month follow-up period. The baseline pre-dialysis SNa level was 137.1 ± 2.8 mmol/L (127–144 mmol/L). Kaplan–Meier survival analysis showed that there were no significant differences in all-cause mortality or new MACE between hyponatremia and normonatremia groups according to baseline pre-dialysis SNa or glucose-corrected SNa (gcSNa). The mean values of both TASNa and time-averaged glucose-corrected SNa (TAgcSNa) were 136.9 ± 2.4 mmol/L and 138.3 ± 2.0 mmol/L, respectively. Kaplan–Meier survival analysis showed that patients with pre-dialysis hyponatremia had higher all-cause mortality or new MACE compared with normonatremia patients whether grouped on TASNa or TAgcSNa. Cox models showed an increased risk of all‐cause mortality and new MACE in MHD patients with pre-dialysis hyponatremia based on TASNa or TAgcSNa. Even after full adjustment including time-dependent age and dialysis vintage, gender, diabetes, time-averaged weight gain (TAWG), and serum albumin, patients with pre-dialysis hyponatremia based on TASNa (HR 2.89; 95% CI 1.18–7.04; model 3) or TAgcSNa (HR 5.03; 95% CI 1.87–13.57; model 3) had approximately twofold or fourfold greater risk of all-cause mortality, respectively, compared with those with normonatremia. The risk of new MACE was also significantly elevated in patients with pre-dialysis hyponatremia based on TASNa (HR 3.86; 95% CI 2.13–7.01; model 1) or TAgcSNa (HR 2.43; 95% CI 1.14–5.15; model 1). After adjustment for time-dependent age and dialysis vintage, gender, diabetes, TAWG, and serum albumin, patients with pre-dialysis hyponatremia based on TASNa (HR 2.33; 95% CI 1.16–4.68; model 3) had a higher risk of new MACE compared with those with normonatremia.ConclusionsPre-dialysis time-averaged hyponatremia is independently associated with increased risks of all-cause mortality or new MACE in MHD patients. The baseline SNa level is not a predictor of clinical outcomes due to its variation over time. Hyperglycemia, fluid overload, and malnutrition do not have a significant impact on the risk association between chronic hyponatremia and all-cause mortality or new MACE in MHD patients.

Heart rate recovery and risk of cardiovascular disease and all-cause mortality: a systematic review of prospective cohort studies

Abstract Funding Acknowledgements Type of funding sources: None. Purpose An attenuated decrease of heart rate recovery (HRR) immediately after exercise is an indicator of autonomic dysfunction and has been linked with a higher risk of cardiovascular disease and all-cause mortality in both healthy and clinical population. However, the evidence regarding its potential prognostic value varies across studies making its implementation in clinical practice for risk assessment difficult. The purpose of the present systematic review is therefore, to investigate the predictive value of heart rate recovery in CVD disease and all-cause mortality, in an evidenced-based manner to encourage its incorporation in clinical practice Methods and Results A systematic review was performed through a comprehensive search on PubMed that focused only on prospective cohort studies. Of the studies retrieved, a total of 13 eligible articles were included in this systematic review with nine of them enrolling 37 457 participants and 709 CVD cases for cardiovascular events, and 12 comprising 45 905 participants and 4 301 deaths for all-cause mortality.The study quality of the included studies was rated moderate to high (4-8) with high heterogeneity (I² = 0.0001). Results revealed no statistically significant difference in HRR for patients with and without cardiovascular events M=-2672.16, at 95% CI [-7341.6,1997.32] ; P-value = .234 as well as for people who died and those who did not M= -3141.667, at 95% CI [-7627.448,1344.144], P-value = .151. Also, the association between CVD and mortality was presented statistically significant, Chi-Square = p&amp;lt;0.0001 while a further analyses of heart rate recovery revealed that when distinguished between low and high, it was found to have a strong positive association with all-cause mortality, Chi-Square = p&amp;lt;0.0001. Conclusion The current systematic review findings indicated that a low HRR is directly linked with greater all-cause mortality risk. Also, given the strong association found between CVD and mortality, the study further supported that even though indirectly, a low HRR is also associated with an increased risk of cardiovascular events, supporting the notion that HRR has a prognostic value and could be used in clinical practice.

Thoracic Aortic Diameter and Cardiovascular Events and Mortality among Women and Men.

Background Thoracic aortic diameter may have a role as a biomarker for major adverse cardiovascular events. Purpose To evaluate the sex-specific association of the diameters of the ascending (AA) and descending (DA) thoracic aorta with risk of stroke, coronary heart disease, heart failure, cardiovascular mortality, and all-cause mortality. Materials and Methods Study participants from the population-based Rotterdam Study who underwent multidetector-row CT between 2003 and 2006 were evaluated. Cox proportional hazard models were conducted to evaluate the associations of AA and DA diameters indexed and not indexed for body mass index (BMI) with cardiovascular events and mortality for men and women. Hazard ratios (HRs) were calculated per 1-unit greater SD of aortic diameters. Results A total of 2178 participants (mean age, 69 years; 55% women) were included. Mean follow-up was 9 years. Each 0.23-mm/(kg/m2) larger BMI-indexed AA diameter was associated with a 33% higher cardiovascular mortality risk in women (HR, 1.33; 95% CI: 1.03, 1.73). Each 0.16-mm/(kg/m2) larger BMI-indexed DA diameter was associated with a 38% higher risk of stroke (HR, 1.38; 95% CI: 1.07, 1.78) and with a 46% greater risk of cardiovascular mortality (HR, 1.46; 95% CI: 1.10, 1.94) in women. Larger BMI-indexed AA and DA diameters were associated with greater risk of all-cause mortality in both sexes. Conclusion Larger ascending and descending thoracic aortic diameters indexed by body mass index were associated with greater risk of adverse cardiovascular outcomes and mortality in women and men. Clinical trial registration no. NTR6831 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Williams in this issue.

Aspirin and Statin Therapy for Nonobstructive Coronary Artery Disease: Five-year Outcomes from the CONFIRM Registry.

In this cohort study, 5-year data from the Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry (ie, CONFIRM) were examined to identify associations of baseline aspirin and statin use with mortality, major adverse cardiovascular events (MACE), and myocardial infarction (MI) in individuals without substantial (≥50%) stenosis. In this prospective cohort study, all participants in the registry underwent coronary CT angiography and were classified as having no detectable coronary plaque or having nonobstructive coronary artery disease (CAD) (1%-49% stenosis). Participants with obstructive (≥50%) stenosis were excluded from analysis. The study commenced in June 2003 and was completed in March 2016. All unadjusted and risk-adjusted analyses utilized the Cox proportional hazard model with hospital sites modeled using shared frailty. A total of 6386 participants with no detectable plaque or with nonobstructive CAD were included (mean age, 56.0 years ± 13.3 [SD], 52% men). The mean follow-up period was 5.66 years ± 1.10. Nonobstructive CAD (n = 2815, 44% of all participants included in the study) was associated with a greater risk of all-cause mortality (10.6% [298 of 2815] vs 4.8% [170 of 3571], P < .001) compared to those without CAD (n = 3571, 56%). Baseline aspirin and statin use was documented for 1415 and 1429 participants, respectively, with nonobstructive CAD, and for 1560 and 1565 participants without detectable plaque, respectively. In individuals with nonobstructive CAD, baseline aspirin use was not associated with a reduction in MACE (10.9% [102 of 936] vs 14.7% [52 of 355], P = .06), all-cause mortality (9.6% [95 of 991] vs 10.9% [46 of 424], P = .468), or MI (4.4% [41 of 936] vs 6.2% [22 of 355], P = .18). On multivariate risk-adjusted analysis, baseline statin use was associated with a lower rate of MACE (hazard ratio, 0.59; 95% CI: 0.40, 0.87; P = .007). Neither therapy improved clinical outcomes for participants with no detectable plaque. In participants with nonobstructive CAD, baseline use of statins, but not of aspirin, was associated with improved clinical outcomes. Neither therapy was associated with benefit in participants without plaque.Keywords: Aspirin, Statin, Coronary Artery Disease, CT Angiography, Nonobstructive Coronary Artery DiseaseClinical trial registration no. NCT01443637 Supplemental material is available for this article. © RSNA, 2022See also the commentary by Canan and Navar in this issue.

Mortality-causing mechanisms and healthcare resource utilisation of treatment-resistant depression: A six-year population-based cohort study

SummaryBackgroundFew studies investigated the mechanisms of treatment-resistant depression (TRD) leading to the worsened survival outcome, and economic evidence was mostly restricted to short follow-ups. We aimed to examine the association and potential mediators between TRD and all-cause mortality, and estimate a longer-term associated health resource utilisation pattern.MethodsThis was a population-based cohort study using territory-wide electronic medical records in Hong Kong. Incident depression patients diagnosed in 2014 were followed up from the first diagnosis to death or December 2019 for TRD identification. We matched the TRD cohort 1:4 to the non-TRD cohort on propensity scores estimated by age, sex, history of physical disorders, and history of psychiatric conditions before depression diagnoses.Findings18% of incident patients developed TRD within six years of follow-up. Cox model showed that patients with TRD had 1⋅52-fold (95% CI: 1⋅14–2⋅02) greater risk of all-cause mortality, compared with non-TRD patients. Path analysis suggested that post-TRD psychiatric conditions significantly mediated 41⋅6% of mortality in patients with TRD (p=0.003). TRD was associated with 1⋅8-fold (95%CI: 1⋅63–2⋅00) higher healthcare costs compared to non-TRD patients over six years in negative binomial regression, with higher costs for both psychiatric and non-psychiatric services utilisation in all settings.InterpretationIdentifying patients with TRD and subsequent monitoring for post-TRD psychiatric diagnoses could be a way to reduce premature mortality. Multidisciplinary care involving both psychiatric and general medical professionals is also warranted to relieve the multifaceted impacts on healthcare resources and overall cost.FundingUnconditional educational grant from Janssen.

Effectiveness of the d-ROMs oxidative stress test to predict long-term cardiovascular mortality

BackgroundThe long-term prognostic value of the derivatives of reactive oxidative metabolites (d-ROMs) oxidative stress test, which measures hydroperoxide in blood, has not been fully investigated. Methods and resultsWe administered the d-ROMs test to 265 patients with cardiovascular disease (204 men, 61 women; age, 65 ± 13 years) and followed these patients for up to 10 years. During the observational period of 5.82 (2.47–8.34) years, 31 (12%) patients died, including 20 (8%) of cardiovascular death, and 33 (12%) had major adverse cardiovascular events (MACEs). Cox regression analysis revealed that patients with a d-ROMs value ≥395 U.CARR had a greater risk for all-cause mortality [unadjusted hazard ratio (95% confidence interval), 3.586 (1.772–7.257)], cardiovascular death [7.034 (2.805–17.640)], and MACEs [4.440 (2.237–8.814)] (p < 0.001 for all). In a model adjusted for age, sex, estimated glomerular filtration rate, C-reactive protein, diabetes, hypertension, hyperlipidemia, coronary artery diseases, current smoking, and log-transformed brain natriuretic peptide, all-cause death [2.311 (1.059–5.135), p = 0.036], cardiovascular death [4.398 (1.599–12.099), p = 0.004], MACEs [2.696 (1.266–5.739), p = 0.010] were still significant in patients with high d-ROMS values. ConclusionA high d-ROMs value is an independent predictor of the long-term risk of cardiovascular mortality. A d-ROMs value of 395 U.CARR was considered to be an appropriate threshold for distinguishing prognosis.