Hazard Of All-cause Mortality Research Articles

Patient years lost due to cytomegalovirus serostatus mismatching in the scientific registry of transplant recipients.

The cytomegalovirus (CMV) mismatch rate in deceased donor kidney transplant (DDKT) recipients in the US remains above 40%. Since CMV mismatching is common in DDKT recipients, the cumulative effects may be significant in the context of overall patient and graft survival. Our primary objective was to describe the short- and long-term risks associated with high-risk CMV donor positive/recipient negative (D+/R-) mismatching among DDKT recipients with the explicit goal of deriving a mathematical mismatching penalty. We conducted a retrospective, secondary analysis of the Scientific Registry of Transplant Recipients (SRTR) database using donor-matched DDKT recipient pairs (N=105,608) transplanted between 2011-2022. All-cause mortality and graft failure hazard ratios were calculated from one year to ten years post-DDKT. All-cause graft failure included death events. Survival curves were calculated using the Kaplan-Meier estimation at 10 years post-DDKT and extrapolated to 20 years to provide the average graft days lost (aGDL) and average patient days lost (aPDL) due to CMV D+/R- serostatus mismatching. We also performed an age-based stratification analysis to compare the relative risk of CMV D+ mismatching by age. Among 31,518 CMV D+/R- recipients, at 1 year post-DDKT, the relative risk of death increased by 29% (p<0.001), and graft failure increased by 17% (p<0.001) as compared to matched CMV D+/R+ group (N=31,518). Age stratification demonstrated a significant increase in the risk associated with CMV mismatching in patients 40 years of age and greater. The aGDL per patient due to mismatching was 125 days and the aPDL per patient was 100 days. The risks of CMV D+/R- mismatching are seen both at 1 year post-DDKT period and accumulated throughout the lifespan of the patient, with the average CMV D+/R- recipient losing more than three months of post-DDKT survival time. CMV D+/R- mismatching poses a more significant risk and a greater health burden than previously reported, thus obviating the need for better preventive strategies including CMV serodirected organ allocation to prolong lifespans and graft survival in high-risk patients.

All-cause mortality before and after DAA availability among people living with HIV and HCV: An international comparison between 2010 and 2019

BackgroundAmong people living with HIV and hepatitis C virus (HCV), people who inject drugs (PWID) have historically experienced higher mortality rates. Direct-acting antivirals (DAA), which have led to a 90 % HCV cure rate independently of HIV co-infection, have improved mortality rates. However, DAA era mortality trends among PWID with HIV/HCV remain unknown. Using data from the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC), we compared pre/post-DAA availability mortality changes in three groups: PWID, men who have sex with men (MSM), and all other participants. MethodsWe included InCHEHC participants with HIV/HCV followed between 2010 and 2019 in Canada, France, the Netherlands, Spain, and Switzerland. All-cause mortality hazard was compared in the three groups, using Cox proportional hazards regression models adjusted for sex, age, advanced fibrosis/cirrhosis, and pre/post DAA availability. ResultsOf the 11,029 participants, 76 % were men, 46 % were PWID, baseline median age was 46 years (interquartile range [IQR] = 40;51), and median CD4 T-cell count was 490 cells/mm3 (IQR = 327;689). Over the study period (median follow-up = 7.2 years (IQR = 3.7;10.0)), 6143 (56 %) participants received HCV treatment, 4880 (44 %) were cured, and 1322 participants died (mortality rate = 1.81/100 person-years (PY) [95 % confidence interval (CI)=1.72–1.91]).Overall, PWID had higher mortality rates than MSM (2.5/100 PY [95 % CI = 2.3–2.6] vs. 0.8/100 PY [95 % CI = 0.7–0.9], respectively). Unlike women with other transmission modes, those who injected drugs had a higher mortality hazard than men who did not inject drugs and men who were not MSM (adjusted Hazard-Ratio (aHR) [95 % CI] = 1.3[1.0–1.6]). Post-DAA availability, mortality decreased among MSM in the Netherlands, Spain, and Switzerland and increased among PWID in Canada (aHR [95 % CI] = 1.73 [1.15–2.61]). ConclusionPost-DAA availability, all-cause mortality did not decrease in PWID. Determinants of cause-specific deaths (drug-related, HIV-related, or HCV-related) need to be identified to explain persistently high mortality among PWID in the DAA era.

All-cause and cause-specific mortality by spirometric pattern and sex - a population-based cohort study.

Chronic airway obstruction (CAO) and restrictive spirometry pattern (RSP) are associated with mortality, but sex-specific patterns of all-cause and specific causes of death have hardly been evaluated. To study the possible sex-dependent differences of all-cause mortality and patterns of cause-specific mortality among men and women with CAO and RSP, respectively, to that of normal lung function (NLF). Population-based prospective cohort study. Individuals with CAO [FEV1/vital capacity (VC) < 0.70], RSP [FEV1/VC ⩾ 0.70 and forced vital capacity (FVC) < 80% predicted] and NLF (FEV1/VC ⩾ 0.70 and FVC ⩾ 80% predicted) were identified within the Obstructive Lung Disease in Northern Sweden (OLIN) studies in 2002-2004. Mortality data were collected through April 2016, totally covering 19,000 patient-years. Cox regression and Fine-Gray regression accounting for competing risks were utilized to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, body mass index, sex, smoking habits and pack-years. The adjusted hazard for all-cause mortality was higher in CAO and RSP than in NLF (HR, 95% CI; 1.69, 1.31-2.02 and 1.24, 1.06-1.71), and the higher hazards were driven by males. CAO had a higher hazard of respiratory and cardiovascular death than NLF (2.68, 1.05-6.82 and 1.40, 1.04-1.90). The hazard of respiratory death was significant in women (3.41, 1.05-11.07) while the hazard of cardiovascular death was significant in men (1.49, 1.01-2.22). In RSP, the higher hazard for respiratory death remained after adjustment (2.68, 1.05-6.82) but not for cardiovascular death (1.11, 0.74-1.66), with a similar pattern in both sexes. The higher hazard for all-cause mortality in CAO and RSP than in NLF was male driven. CAO was associated with respiratory death in women and cardiovascular death in men, while RSP is associated with respiratory death, similarly in both sexes.

Comparisons of Percutaneous Ablation, Open or Laparoscopic Liver Resection for Barcelona Clinic Liver Cancer Stage 0-A Hepatocellular Carcinoma: A Concurrent Generalized Propensity Score Analysis.

Liver resection and ablation remain the most common therapeutic options for Barcelona Clinic Liver Cancer (BCLC) stage 0-A hepatocellular carcinoma (HCC), but there is a lack of evidence to show which is the most suitable therapy. This study aimed to make concurrent multi-arm comparisons of the short-term and long-term outcomes of percutaneous ablation (PA), open (OLR) or laparoscopic liver resection (LLR) for these patients. This was a retrospective observational cohort study. A series of generalized propensity score methods for multiple treatment groups were performed to concurrently compare the clinical outcomes of these three treatment options to balance potential confounders. Regression standardization was used to account for hazard of all-cause mortality and recurrence of intergroup differences. Of the 1778 patients included, 1237, 307 and 234 underwent OLR, LLR and PA, respectively. After overlap weighting, which was the optimal adjustment strategy, patients in the minimally invasive group (LLR and PA groups) had few postoperative complications and short postoperative hospital stays (both P < 0.001). The 5-year recurrence-free survival (RFS) rate and 5-year overall survival (OS) rate were significantly higher in the LLR group when compared with the OLR and PA groups (RFS: 55.6% vs 48.0% vs 30.2%, P < 0.001; OS: 89.1% vs 79.7% vs 84.0%, P = 0.020). Multivariable Cox analysis and regression standardization showed that LLR was an independent factor for better RFS when compared with OLR and PA. In subgroup analysis, the long-term outcomes of patients with BCLC stage A HCC were consistent with the whole population. In the observational study using various covariate adjustment analysis with excellent balance, LLR is not only minimally invasive, but also provides better RFS and equivalent OS for patients with BCLC stage 0-A HCC when compared with OLR and PA.

Association of advanced lung cancer inflammation index with all-cause and cardiovascular mortality in US patients with rheumatoid arthritis.

As a systemic autoimmune disorder, the prognosis of rheumatoid arthritis (RA) is intricately linked to inflammation. This study aimed to investigate the association between the advanced lung cancer inflammation index (ALI), a comprehensive indicator of inflammation combined with nutritional status, and all-cause and cardiovascular mortality among patients diagnosed with RA. The 2,305 RA patients from NHANES (2001-2018) included in the analysis were categorized into three groups according to ALI tertiles. Weighted Kaplan-Meier and multivariate COX regression analyses evaluated the relationship between ALI and mortality. The time-dependent characteristic curve (ROC) was used to assess the prediction accuracy of ALI. During a median follow-up of 7.92 years, 591 participants died from all causes, including 197 from cardiovascular diseases. Increased ALI was associated with a decreased probability of death. The full COX model revealed lower all-cause mortality hazard risks in the T2 (HR: 0.67, 95%CI: 0.54-0.83) and T3 (HR: 0.47 95%CI: 0.33-0.67, p for tend <0.001) groups compared to T1, and the risk of cardiovascular mortality was also lower in the groups of T2 (HR: 0.47, 95%CI: 0.31-0.70) and T3 (HR: 0.34, 95%CI: 0.19-0.62, p for trend <0.001). Furthermore, the ROC analysis underscored the strong predictive capability of ALI (AUC for 1-year all-cause and cardiovascular mortality were 0.73 and 0.79, respectively). This cohort study demonstrated the higher accuracy of ALI in predicting mortality in RA patients, highlighting the important clinical value of ALI in risk assessment and prognosis evaluation.

THE RELATIONSHIP BETWEEN 10-YEAR CHANGES IN COGNITIVE ABILITY AND SUBSEQUENT MORTALITY: FINDINGS FROM THE ACTIVE

Abstract Cognitive ability and cognitive decline have been linked with mortality in older adults. However, little was understood about the role of cognitive interventions on mortality outcomes in this population. Using twenty-year follow-up data from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) trial, we examined the association between cognitive change and mortality risk, and the effect of ACTIVE cognitive training (memory, reasoning, and speed of processing) on mortality risk. Mortality was ascertained through linkage to the National Death Index database. To model time to death as a function of cognitive change and training effect, we used shared growth-survival models with simultaneously estimated latent intercepts and slopes as predictors. Among the 2802 participants, 2021 died on or before the year 2019 (72.1%). Both higher baseline level and slower decline in global cognition were associated with lower hazards of all-cause mortality after adjusting for covariates (HR = 0.68, 95% CI 0.58, 0.79; HR = 0.42, 95% CI 0.40, 0.44, respectively). We did not observe any significant effects of ACTIVE cognitive training in memory, reasoning, or speed of processing on all-cause mortality. Our findings demonstrated the association between the trajectory of cognitive change and mortality among older adults, independent of cognitive training interventions. More work is needed to identify relevant timing as well as modalities of non-pharmaceutical interventions that can promote healthy longevity.

Vitamin K1 intake is associated with lower risk for all-cause and cardiovascular disease mortality in community-dwelling older Australian women

Background and aimsAssessing the relationship between vitamin K1 intakes, using region-specific food databases, with both all-cause, and cardiovascular disease (CVD) mortality warrants further investigation to inform future preventative strategies. Consequently, we examined the aforementioned associations in the Perth Longitudinal Study of Ageing Women (PLSAW). Methods and results1436 community-dwelling older Australian women (mean ± SD age 75.2 ± 2.7 years) completed a validated food frequency questionnaire at baseline (1998). Vitamin K1 intake was calculated based on an Australian vitamin K food database, supplemented with published data. All-cause and CVD mortality data was obtained from linked health records. Associations were examined using restricted cubic splines within Cox-proportional hazard models, adjusted for a range of cardiovascular and lifestyle related risk factors. Over 15 years of follow-up, 601 (41.9%) women died, with 236 deaths (16.4%) due to CVD. Compared to women with the lowest vitamin K1 intakes (Quartile 1, median 49.1 μg/day), those with the highest intakes (Quartile 4, median 119.3 μg/day) had lower relative hazards for all-cause mortality (HR 0.66 95%CI 0.51–0.86) and CVD mortality (HR 0.61 95%CI 0.41–0.92). A plateau in the inverse association was observed from vitamin K1 intakes of approximately ≥80 μg/day. ConclusionHigher vitamin K1 intakes were associated with lower risk for both all-cause and CVD mortality in community-dwelling older women, independent of CVD related risk factors. A higher intake of vitamin K1 rich foods, such as leafy green vegetables, may support cardiovascular health.

Parental Income Level and Risk of Developing Type 2 Diabetes in Youth

In recent years, the global incidence of type 2 diabetes in young people has increased, especially among minoritized, Indigenous, or financially disadvantaged populations. However, few studies have examined whether poverty is associated with increased risk of youth-onset type 2 diabetes. To examine the association of family income level with the risk of youth-onset type 2 diabetes. This nationwide, population-based retrospective cohort study used data from the 2008 National Health Insurance Research Database of Taiwan, with follow-up through December 31, 2019. Participants included children and adolescents aged 0 to 19 years. Data analysis was performed from June 9, 2022, to January 16, 2023. Family income, classified as very low, low, middle, and high. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for the risks of youth-onset type 2 diabetes and all-cause mortality for all income groups vs the high-income group. The cohort included a total of 5 182 893 children and adolescents (mean [SD] age, 11.2 [5.2] years; 2 477 807 girls [48.3%]). The mean (SD) follow-up duration was 9.0 (0.3) years. The incidence rates of youth-onset type 2 diabetes were 0.52 cases per 1000 person-years for the very-low-income group, 0.40 cases per 1000 person-years for the low-income group, 0.35 cases per 1000 person-years for the middle-income group, and 0.28 cases per 1000 person-years for the high-income group. Children and adolescents from very-low-income (aHR, 1.55; 95% CI, 1.41-1.71), low-income (aHR, 1.34; 95% CI, 1.27-1.41), and middle-income (aHR, 1.27; 95% CI, 1.20-1.34) families had a significantly higher hazard of youth-onset type 2 diabetes than those from high-income families. Children and adolescents from very-low-income (aHR, 2.18; 95% CI, 1.97-2.41), low-income (aHR, 1.51; 95% CI, 1.42-1.60), and middle-income (aHR, 1.22; 95% CI, 1.14-1.31) families also had a significantly higher hazard of all-cause mortality than those from high-income families. Children and adolescents who were older, female, and obese and had dyslipidemia, gout, or psychiatric disorders had a significantly higher risk of youth-onset type 2 diabetes than children without those characteristics. This population-based cohort study showed that children and adolescents from very-low-income to middle-income families had a higher hazard of youth-onset type 2 diabetes and mortality than those from high-income families. Further research to reveal the factors underlying this association may improve the accuracy of identifying individuals at greatest risk for developing type 2 diabetes in youth.

Sleep regularity and mortality: a prospective analysis in the UK Biobank.

Irregular sleep-wake timing may cause circadian disruption leading to several chronic age-related diseases. We examined the relationship between sleep regularity and risk of all-cause, cardiovascular disease (CVD), and cancer mortality in 88,975 participants from the prospective UK Biobank cohort. The sleep regularity index (SRI) was calculated as the probability of an individual being in the same state (asleep or awake) at any two time points 24 hr apart, averaged over 7 days of accelerometry (range 0-100, with 100 being perfectly regular). The SRI was related to the risk of mortality in time-to-event models. The mean sample age was 62 years (standard deviation [SD], 8), 56% were women, and the median SRI was 60 (SD, 10). There were 3010 deaths during a mean follow-up of 7.1 years. Following adjustments for demographic and clinical variables, we identified a non-linear relationship between the SRI and all-cause mortality hazard (p [global test of spline term]<0.001). Hazard ratios, relative to the median SRI, were 1.53 (95% confidence interval [CI]: 1.41, 1.66) for participants with SRI at the 5th percentile (SRI = 41) and 0.90 (95% CI: 0.81, 1.00) for those with SRI at the 95th percentile (SRI = 75), respectively. Findings for CVD mortality and cancer mortality followed a similar pattern. Irregular sleep-wake patterns are associated with higher mortality risk. National Health and Medical Research Council of Australia (GTN2009264; GTN1158384), National Institute on Aging (AG062531), Alzheimer's Association (2018-AARG-591358), and the Banting Fellowship Program (#454104).

Artificial intelligence calculated global longitudinal strain and left ventricular ejection fraction predicts cardiac events and all-cause mortality in patients with chest pain.

Assessment of left ventricular ejection fraction (LVEF) and myocardial deformation with global longitudinal strain (GLS) has shown promise in predicting adverse cardiovascular events. The aim of this study was to evaluate whether artificial intelligence (AI) calculated LVEF and GLS is associated with major adverse cardiac events (MACE) and all-cause mortality in patients presenting with chest pain. We studied 296 patients presenting with chest pain, who underwent transthoracic echocardiography (TTE). Clinical data, downstream clinical investigations and patient outcomes were collected. Resting TTE images underwent AI contouring for automated calculation of LVEF and GLS with Ultromics EchoGo Core 2.0. Regression analysis was performed to identify clinical and AI calculated parameters associated with MACE and all-cause mortality. During a median follow-up period of 7.8 years (IQR 6.4, 8.8), MACE occurred in 34 (11.5%) patients and all-cause mortality in 60 (20%) patients. AI calculated LVEF (Odds Ratio [OR] .96; 95% CI .93-.99 and .96; 95% CI .93-.99) and GLS (1.11; 95% CI 1.01-1.21 and 1.08; 95% CI 1.00-1.16) were independently associated with MACE and all-cause mortality, respectively. According to Cox proportional hazards, a LVEF<50% was associated with a 3.7 times MACE and 2.8 times all-cause mortality hazard rate compared to those with a LVEF≥50%. Those with a GLS≥15% was associated with a 2.5 times MACE and 2.3 times all-cause mortality hazard rate compared to those with a GLS≤15. AI calculated resting LVEF and GLS is independently associated with MACE and all-cause mortality in high CVD risk patients. These results may have significant clinical implications through improved risk stratification of patients with chest pain, accelerated workflow of labour-intensive technical measures, and reduced healthcare costs.

Gamma-Glutamyl Transferase as a prognostic risk factor in complex coronary disease: a serendipitous (re)discovery of machine learning in the SYNTAXES?

Abstract Background/Introduction Over the last decade, epidemiology and pathology studies have suggested that gamma-glutamyl transferase (GGT) has an independent role in the pathogenesis and clinical evolution of cardiovascular diseases associated with atherosclerosis. Recently, machine learning (ML) algorithms have identified pre-procedural GGT as a significant predictor of long-term mortality after coronary revascularization in the SYNTAX trial. Purpose The aim of this study is to investigate the impact of pre-procedural GGT on 10-year all-cause mortality in patients with three-vessel disease (3VD) and/or left main coronary artery disease (LMCAD) following revascularization. Methods The SYNTAX trial was a randomized trial comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in 1,800 patients with complex CAD. The present report is a post-hoc sub-analysis of the SYNTAXES study, an investigator-driven extended 10-year follow-up of the SYNTAX trial. Before revascularization, blood samples were taken for GGT as well as other biological markers and analyzed by an independent central chemistry laboratory. The primary endpoint was all-cause mortality at 10-years. The changes in hazard for all-cause mortality in GGT over time were modelled using restricted cubic spline functions in a Cox regression model adjusted by age and sex. Subsequently, we compared survival in four groups defined by gender specific GGT thresholds of &amp;lt;32 IU and ≥32 IU for females and &amp;lt;64 IU and ≥64 IU for males, in accordance with prior studies. Results Out of 1,800 patients enrolled in the SYNTAX study, 167 (9.3%) did not have a GGT available at baseline and 1,633 (90.7%) patients were included in the present study. The mean values of GGT for males and females were 43.5±48.5 and 36.4±46.1 U/L, respectively. In the overall population a 10 U/L increase in GGT was significantly associated with 10-year all-cause death (adjusted hazard ratio [HR] 95% confidence interval [CI]: 1.03 [1.02–1.04], p &amp;lt;0.001, Figure A). For Kaplan–Meier analysis, patients were stratified into four groups according to previously reported sex related GGT thresholds. Ten-year mortality was numerically higher in males (adjusted HR 1.31, 95% CI: 0.90–1.91), and significantly higher in females (adjusted HR 1.88, 95% CI: 1.16–3.05) among patients with higher versus lower GGT (Figure B). Furthermore, GGT was significantly associated with CRP, a surrogate-marker of inflammation, as well as established cardiovascular risk biomarkers such as TG, total cholesterol, and glucose. Conclusions Preprocedural GGT is an independent predictor of 10-year mortality following coronary revascularization in patients with 3VD and/or LMCAD. This long-term association has been identified using ML algorithms and should be corroborated using data from large biobanks.Figure AFigure B

Disease trajectories following myocardial infarction: insights from process mining of 145 million hospitalisation episodes

Abstract The number of survivors of MI has increased dramatically in recent decades, yet knowledge of post-myocardial infarction (MI) disease risk to date is limited. We investigated temporally ordered sequences of all conditions following MI in nationwide electronic health record data through the novel application of process mining. Here, we present, for the first time, the observed sequences of diseases that individuals accrue post MI. We conducted a national retrospective cohort study of all hospitalisations (145,670,448 episodes, 34,083,204 individuals) admitted to NHS hospitals in England (1st January 2008-31st January 2017, final follow up 27th March 2017). Through process mining we identified trajectories of all major disease diagnoses following MI and compared their adjusted relative risk (RR) and all-cause mortality hazard ratios (HR) to a risk-set matched non-MI control cohort using flexible parametric survival models. Among a total of 375,669 (1·1%) MI patients (872,450 episodes) and 1,878,345 (5·5%) matched non-MI patients (4,712,654 episodes), we identified 28,740 unique disease trajectories. The accrual of multiple circulatory diagnoses was more common amongst MI (RR 4·37, 95% CI 4·00-4·77) and conferred an increased risk of death (HR 1·32, 1·14-1·54) compared with matched controls. Further, trajectories featuring neuro-psychiatric diagnoses (including anxiety and depression) in conjunction with circulatory disorders, were markedly more common and had increased mortality post MI (HR ranging from 1·12 to 1·74) compared with non-MI individuals. Pathways involving both circulatory and digestive diseases appeared more frequently in the MI cohort versus matched controls (RR 4·03 [3·87-4·20] to 4·77 [4·28-5·32]). A number of trajectories including disorders of the eye/adnexa were also associated with an increased risk of death compared with matched controls (HR: 1·32, 1·11-1·57), with those eye/adnexa disorders consisting mainly of cataracts (77·6%). This study quantifies the relative risk and mortality burden associated with disease trajectories following MI from a nationwide hospitalisation cohort for the first time. These data show the significant ongoing cardiovascular disease burden following MI, and crucially highlight the excess accrual of neuro-psychiatric diagnoses conferring increased mortality compared with non-MI individuals. These data provide a clear opportunity for early intervention targets, such as increased focus on the psychological and behavioural pathways for survivors of MI, to mitigate ongoing adverse disease trajectories, multimorbidity and premature mortality. Further understanding of the factors contributing to these trajectories is required to facilitate identification of patients in the early post-MI setting who would benefit most from closer follow-up and prompt intervention.Trajectories: primary diseasesTrajectories: primary+secondary diseases

Influence of social deprivation on morbidity and all-cause mortality of cardiometabolic multi-morbidity: a cohort analysis of the UK Biobank cohort

BackgroundThe relation of social deprivation with single cardiometabolic disease (CMD) was widely investigated, whereas the association with cardiometabolic multi-morbidity (CMM), defined as experiencing more than two CMDs during the lifetime, is poorly understood.MethodsWe analyzed 345,417 UK Biobank participants without any CMDs at recruitment to study the relation between social deprivation and four CMDs including type II diabetes (T2D), coronary artery disease (CAD), stroke and hypertension. Social deprivation was measured by Townsend deprivation index (TDI), and CMM was defined as occurrence of two or more of the above four diseases. Multivariable Cox models were performed to estimate hazard ratios (HRs) per one standard deviation (SD) change and in quartile (Q1-Q4, with Q1 as reference), as well as 95% confidence intervals (95% CIs).ResultsDuring the follow up, 68,338 participants developed at least one CMD (median follow up of 13.2 years), 16,225 further developed CMM (median follow up of 13.4 years), and 18,876 ultimately died from all causes (median follow up of 13.4 years). Compared to Q1 of TDI (lowest deprivation), the multivariable adjusted HR (95%CIs) of Q4 (highest deprivation) among participants free of any CMDs was 1.23 (1.20 ~ 1.26) for developing one CMD, 1.42 (1.35 ~ 1.48) for developing CMM, and 1.34 (1.27 ~ 1.41) for all-cause mortality. Among participants with one CMD, the adjusted HR (95%CIs) of Q4 was 1.30 (1.27 ~ 1.33) for developing CMM and 1.34 (1.27 ~ 1.41) for all-cause mortality, with HR (95%CIs) = 1.11 (1.06 ~ 1.16) for T2D patients, 1.07 (1.03 ~ 1.11) for CAD patients, 1.07 (1.00 ~ 1.15) for stroke patients, and 1.24 (1.21 ~ 1.28) for hypertension patients. Among participants with CMM, TDI was also related to the risk of all-cause mortality (HR of Q4 = 1.35, 95%CIs 1.28 ~ 1.43).ConclusionsWe revealed that people living with high deprived conditions would suffer from higher hazard of CMD, CMM and all-cause mortality.

Abstract 12362: High Rates of Mortality in Uganda Following Acute Rheumatic Fever: Findings From a Community-Based Prospective Cohort Study

Introduction: Rheumatic heart disease (RHD) is the largest contributor to cardiac mortality in children worldwide. Little contemporary data exist on its antecedent illness, acute rheumatic fever (ARF). There is an urgent need to understand outcomes following ARF in RHD-endemic settings. We aimed to describe medium-term mortality, disease recurrence, and change in carditis among Ugandan children following ARF diagnosis, and to identify correlates of mortality. Methods: We conducted a prospective cohort study of children diagnosed with definite ARF in 2017-2020 during a community-based incidence study. Patients were enrolled in a national registry and followed with annual review, most recently in August 2022. Kaplan-Meier (KM) survival analysis was used to describe all-cause mortality and individual Cox proportional hazards regression models were used to identify correlates of death. Descriptive statistics were used to characterize changes in carditis. Results: Among 135 children with definite ARF, 22/135 (16.3%) experienced death, 19/135 (14.1%) cardiac death, 5/135 (3.7%) ARF recurrence, and 5/135 (3.7%) surgery over a median (interquartile range) of 4.25 (3.4, 5.1) years. KM analysis saw 14/22 (63.6%) of deaths occur by one year, 16/22 (72.7%) by two years, and 20/22 (90.9%) by three years. The presence of moderate/severe carditis (HR 14.1, 95% CI 4.2, 47.7) and PR prolongation (HR 3.9, 95% CI 1.5, 9.9) at diagnosis was associated with increased cardiac mortality. Among 107 survivors included in echocardiographic sub-analysis, 27/107 (25.2%) had improvement in carditis, 70/107 (65.4%) no change, and 10/107 (9.4%) progression. Conclusions: These are the first contemporary data from sub-Saharan Africa reviewing medium-term outcomes following ARF. Adverse outcome rates exceeded those reported elsewhere. Most decedents already had advanced cardiac involvement upon first ARF diagnosis, as evidenced by PR prolongation and high-grade carditis, suggesting a history of prior undiagnosed ARF recurrences that had already compounded into RHD. These data indicate that a high burden of ARF exists in the community that is undetected by current methods, emphasizing the need for better point-of-care diagnostics to improve early ARF detection.

Abstract 14635: Prognostic Value of Heart Rate Variability in Black Americans: The Jackson Heart Study

Background: The prognostic value of heart rate variability (HRV) in Black Americans (BAs), who have distinct cardiac risk profiles, is not well studied. We aimed to investigate the association between HRV, all-cause mortality, and cardiovascular events in the Jackson Heart Study (JHS). Methods: We analyzed data from JHS participants who had HRV readings at baseline (2000-2004). HRV was measured as the standard deviation between subsequent R-waves on a 12-lead EKG. Data were analyzed up to December 31, 2014. Outcomes of interest were all-cause mortality and cardiovascular events (composite of incident stroke and coronary heart disease). Cox regression models were used to estimate hazard ratios (HRs) for the hazard of events in participants with an HRV below the median versus those with an HRV above the median. Restricted cubic splines (RCS) were used to explore non-linear interactions. All analyses were adjusted for age, sex, smoking, clinically relevant comorbidities, and risk factors. Results: Among the 3627 participants (mean age: 55.1 years; female: 62.4%), the median [IQR] HRV was 22.3ms [13.7, 36.1]. At baseline, participants with HRV below the median had a higher prevalence of several cardiometabolic diseases. Adjusted Cox regression showed that HRV below the median was associated with a 32% increased hazard of all-cause mortality (HR: 1.32 [1.09, 1.60]; P = 0.005) and a non-significant increase in incident cardiovascular events (HR: 1.28 [0.99, 1.66]; P = 0.059); Figure 1A . RCS suggested HRV has a non-linear relationship with all-cause mortality (P-nonlinearity: 0.0076) and cardiovascular events (P-nonlinearity: 0.0162), with the hazard of events beginning to increase sharply at HRV &amp;lt;25ms ( Figure 1B ). Conclusion: BAs had a higher mortality hazard associated with lower HRV readings, specifically &amp;lt;25ms. Consumer wearable sensors commonly record HRV, and our findings suggest that HRV could serve as a practical prognostic tool for this population.

Abstract 13721: Coronary Artery Calcium for Risk Stratification Among Persons With Very-High High-Density Lipoprotein Cholesterol

Introduction: Persons with very-high high-density lipoprotein-cholesterol (HDL-C) may experience an increased mortality risk. However, the predictors of mortality among those with very-high HDL-C remain unknown. Hypothesis: Compared to traditional risk factors, coronary artery calcium (CAC) will more strongly stratify risk among individuals with very-high HDL-C. Aims: Among individuals with very-high HDL-C, to 1) calculate crude all-cause mortality rates across the burden of traditional risk factors and CAC, and 2) identify independent risk factors associated with all-cause mortality. Methods: There were 335 primary prevention patients from the CAC Consortium who had very-high HDL-C ( &gt; 80 mg/dL in men, &gt; 100 mg/dL in women) and available information on traditional CVD risk factors. Crude all-cause mortality rates were calculated per 1,000 person-years. Multivariable Cox proportional hazards regression assessed the association of traditional risk factors and CAC with mortality. Results: The mean age was 58.6 years old, 51.0% were women, 51.3% had prevalent CAC, and the median HDL-C was 100 mg/dL. There were 20 deaths (6.0%) over a median follow-up of 10.5 years, 7 (2.1%) of which were attributable to CVD. There was a stepwise higher crude mortality rate per 1,000 person-years across increasing CAC burden ( Central Illustration ). Independent of traditional risk factors, each 100 Agatston Unit increase in CAC score was associated with a 7% higher hazard of all-cause mortality (HR: 1.07, 95% CI: 1.01-1.12) and individuals with CAC &gt; 1000 experienced a 5.75-fold higher hazard of mortality when compared to CAC=0 (HR: 5.75, 95% CI: 1.26-26.24). Beyond age, no traditional risk factor was associated with mortality in multivariable analyses. Conclusion: Measurement of CAC on non-contrast cardiac computed tomography may facilitate risk assessment among individuals with very-high HDL-C.

Risk factors and mortality of SARS-CoV-2 reinfection during the Omicron era in Taiwan: A nationwide population-based cohort study

BackgroundPrior to 2022, Taiwan had effectively contained the domestic COVID-19 epidemic. However, during 2022, the country encountered multiple large outbreaks of COVID-19, with patients experiencing their first or second infection (reinfection) were both predominantly caused by the Omicron variant. Data are lacking on the risk factors and mortality of COVID-19 reinfection in Omicron era. MethodsIn this retrospective population-based cohort study, we recruited COVID-19 patients with their first episode confirmed between April 1, 2022 and June 11, 2022. A reinfection patient was defined as an individual who infected again by SARS-CoV-2 with an interval of more than 90 days. Demographic characteristics, severity of underlying diseases, and vaccination status were adjusted to identify risk factors for reinfection and to further evaluate the hazard of all-cause mortality within 30 days between reinfection and non-reinfection patients. ResultsThere were 28,588 reinfection patients matched with 142,940 non-reinfection patients included in this study. We found that being female, younger in age, having more severe underlying diseases, and not being fully vaccinated against COVID-19 were risk factors for reinfection. After adjusting for confounding factors, reinfection patients were at a significantly higher risk of all-cause mortality within 30 days (aHR = 4.29, 95% CI: 3.00–6.12, p < 0.001) comparing with non-reinfection patients. ConclusionDuring the SARS-CoV-2 Omicron era, reinfection patients were observed to have an increased risk of all-cause mortality. To reduce the disease burden and minimize the risk of reinfection, it is crucial for vulnerable patients to receive full vaccination and adhere to recommended precautions.

Association of Foot Symptoms With Decreased Time to All-Cause Mortality: The Johnston County Osteoarthritis Project.

Adults with foot symptoms (ie, pain, aching, or stiffness) may be at increased risk of reduced time to all-cause mortality. The purpose of this study was to evaluate whether foot symptoms are independently associated with all-cause mortality in older adults. We analyzed longitudinal data from 2613 participants from the Johnston County Osteoarthritis Project, a longitudinal population-based cohort of adults 45 years of age and older. Participants completed questionnaires at baseline to determine presence of foot symptoms and covariable status. Baseline walking speed was measured via an 8-foot walk test. To examine the association of foot symptoms with time to mortality, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression models, adjusted for potential confounders. We observed 813 deaths over 4 to 14.5 years of follow-up. At baseline, 37% of participants had foot symptoms, mean age was 63 years, mean body mass index was approximately 31 kg/m2 , 65% were women, and 33% were Black. Moderate to severe foot symptoms were associated with reduced time to mortality after adjustment for demographics, comorbidities, physical activity, and knee and hip symptoms (HR=1.30, 95% CI 1.09-1.54). Importantly, this association was not modified by walking speed or diabetes. Individuals with foot symptoms had an increased hazard of all-cause mortality compared with those with no foot symptoms. These effects were independent of key confounders and were not moderated by walking speed. Effective interventions to identify and manage at least moderate foot symptoms may reduce the risk of decreased time to mortality.

The Association Between Homelessness and Key Liver-Related Outcomes in Veterans With Cirrhosis.

Homelessness adversely affects patient outcomes in broad cohort studies; however, its impact on key liver-related outcomes in patients with cirrhosis is understudied. We aimed to address this knowledge gap using data from the Veterans Health Administration, a cohort disproportionately affected by homelessness. This was a retrospective cohort study of the Veterans Health Administration patients with incident cirrhosis diagnosis between January 2008 and February 2022. Homeless status was classified at baseline and as time-updating variable during follow-up. Inverse probability treatment weighted Cox regression was performed to evaluate the association between homelessness and outcomes of all-cause mortality, cirrhosis decompensation, and hepatocellular carcinoma. A total of 117,698 patients were included in the cohort, of whom 14,243 (12.1%) were homeless at baseline. In inverse probability treatment weighted Cox regression, homelessness was associated with a 24% higher hazard of all-cause mortality (hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.22-1.26, P < 0.001). However, in competing risk regression models, homelessness was associated with a reduced subhazard of decompensation (subhazard ratio 0.86, 95% CI 0.84-0.88, P < 0.001) and hepatocellular carcinoma (subhazard ratio 0.86, 95% CI 0.83-0.89, P < 0.001). In cause-specific mortality analysis, homeless patients had significantly increased non-liver-related and liver-related mortality; however, the magnitude of effect size was greater for non-liver-related mortality (csHR 1.38, 95% CI 1.35-1.40, P < 0.001). Homelessness in veterans with cirrhosis is associated with increased all-cause mortality; however, this is likely mediated primarily through non-liver-related factors. Future studies are needed to explore drivers of mortality and improve mitigation strategies in these patients.

Body mass index trajectories and mortality risk in Japan using a population-based prospective cohort study: the Japan Public Health Center-based Prospective Study.

Recent studies have found that long-term changes in weight during adulthood are associated with a high risk of mortality. The objective of this study was to characterize body mass index (BMI) trajectories during adulthood and to examine the association between BMI trajectories and risk of death in the Japanese population. The data were extracted from Japan Public Health Center-based Prospective Study-a population-based prospective cohort study in Japan with participants aged 40-69 years followed over 20 years. The participants were categorized into multiple BMI trajectory groups using the latent class growth model. The Cox proportional-hazards model was conducted using all-cause mortality and cause-specific mortality as outcomes and the identified BMI trajectory groups as a predictor. In total, 65 520 participants were included in the analysis. Six BMI trajectory groups were identified: underweight stable (Group 1), low-to-high normal (Group 2), high-to-low normal (Group 3), normal to overweight (Group 4), overweight to normal (Group 5) and normal to obese (Group 6). Our Cox models showed a higher hazard (risk) of all-cause mortality among participants in the BMI-declining groups [Group 3, adjusted hazard ratio (aHR): 1.10, 95% CI: 1.05-1.16; Group 5, aHR: 1.16, 95% CI: 1.08-1.26], underweight stable group (Group 1, aHR: 1.27, 95% CI: 1.21-1.33) and normal to obese group (Group 6, aHR: 1.22, 95% CI: 1.13-1.33) than Group 2 (low-to-high normal BMI trajectory). Stable underweight and weight loss were associated with a high risk of mortality, both of which were uniquely observed in a Japanese population.