Risk Of Mortality In Individuals Research Articles

Association of Insulin Resistance With Cardiovascular Disease and All-Cause Mortality in Type 1 Diabetes: Systematic Review and Meta-analysis.

The association of insulin resistance (IR) with cardiovascular disease (CVD) and all-cause mortality in type 1 diabetes (T1D) remains unclear. To investigate whether IR is associated with CVD and all-cause mortality among individuals with T1D. PubMed, Embase, and the Cochrane Library databases were searched from inception to 31 October 2023. Observational studies reporting the associations between IR, as calculated by the estimated glucose disposal rate (eGDR), and the risk of CVD and all-cause mortality in individuals with T1D were eligible for inclusion. Data from eight selected studies were extracted, pooled by random-effects models, and results are presented as hazard ratios (95% CIs). Eight studies involving 21,930 individuals were included, of which five studies involving 19,960 individuals with T1D reported the risk of CVD. During a median follow-up of 10 years, there were 2,149 cases of incident CVD. The pooled hazard ratio for composite CVD outcome per 1-unit increase in the eGDR index was 0.83 (95% CI 0.78-0.90, I2 = 58.9%). Five studies involving 19,403 individuals reported the risk of all-cause mortality. During a median follow-up of 10 years, 1,279 deaths were observed. The pooled hazard ratio for all-cause mortality per 1-unit increase in the eGDR index was 0.84 (95% CI 0.81-0.87, I2 = 0%). The small number of available studies restricted our ability to perform meta-regression analyses or more detailed subgroup analyses. IR, as calculated by the eGDR, may be an additional risk factor for CVD and all-cause mortality in T1D.

DNA Methylation-derived biological age and long-term mortality risk in subjects with type 2 diabetes

BackgroundIndividuals with type 2 diabetes (T2D) face an increased mortality risk, not fully captured by canonical risk factors. Biological age estimation through DNA methylation (DNAm), i.e. the epigenetic clocks, is emerging as a possible tool to improve risk stratification for multiple outcomes. However, whether these tools predict mortality independently of canonical risk factors in subjects with T2D is unknown.MethodsAmong a cohort of 568 T2D patients followed for 16.8 years, we selected a subgroup of 50 subjects, 27 survived and 23 deceased at present, passing the quality check and balanced for all risk factors after propensity score matching. We analyzed DNAm from peripheral blood leukocytes using the Infinium Human MethylationEPIC BeadChip (Illumina) to evaluate biological aging through previously validated epigenetic clocks and assess the DNAm-estimated levels of selected inflammatory proteins and blood cell counts. We tested the associations of these estimates with mortality using two-stage residual-outcome regression analysis, creating a reference model on data from the group of survived patients. ResultsDeceased subjects had higher median epigenetic age expressed with DNAmPhenoAge algorithm (57.49 [54.72; 60.58] years. vs. 53.40 [49.73; 56.75] years; p = 0.012), and accelerated DunedinPoAm pace of aging (1.05 [1.02; 1.11] vs. 1.02 [0.98; 1.06]; p = 0.012). DNAm PhenoAge (HR 1.16, 95% CI 1.05–1.28; p = 0.004) and DunedinPoAm (HR 3.65, 95% CI 1.43–9.35; p = 0.007) showed an association with mortality independently of canonical risk factors. The epigenetic predictors of 3 chronic inflammation-related proteins, i.e. CXCL10, CXCL11 and enRAGE, C-reactive protein methylation risk score and DNAm-based estimates of exhausted CD8 + T cell counts were higher in deceased subjects when compared to survived.ConclusionsThese findings suggest that biological aging, as estimated through existing epigenetic tools, is associated with mortality risk in individuals with T2D, independently of common risk factors and that increased DNAm-surrogates of inflammatory protein levels characterize deceased T2D patients. Replication in larger cohorts is needed to assess the potential of this approach to refine mortality risk in T2D.

Synergistic impact of psoriasis and hypertension on all-cause mortality risk: A prospective cohort study.

The linkage between psoriasis and hypertension has been established through observational studies. Despite this, a comprehensive assessment of the combined effects of psoriasis and hypertension on all-cause mortality is lacking. The principal aim of the present study is to elucidate the synergistic impact of psoriasis and hypertension on mortality within a representative cohort of adults residing in the United States. The analysis was conducted on comprehensive datasets derived from the National Health and Nutrition Examination Study spanning two distinct periods: 2003-2006 and 2009-2014. The determination of psoriasis status relied on self-reported questionnaire data, whereas hypertension was characterized by parameters including systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg, self-reported physician diagnosis, or the use of antihypertensive medication. The assessment of the interplay between psoriasis and hypertension employed multivariable logistic regression analyses. Continuous monitoring of participants' vital status was conducted until December 31, 2019. A four-level variable amalgamating information on psoriasis and hypertension was established, and the evaluation of survival probability utilized the Kaplan-Meier curve alongside Cox regression analysis. Hazard ratios (HRs) and their associated 95% confidence intervals (CIs) were computed to scrutinize the correlation between psoriasis/hypertension and all-cause mortality. In total, this study included 19,799 participants, among whom 554 had psoriasis and 7,692 had hypertension. The findings from the logistic regression analyses indicated a heightened risk of hypertension among individuals with psoriasis in comparison to those devoid of psoriasis. Throughout a median follow-up spanning 105 months, 1,845 participants experienced all-cause death. In comparison to individuals devoid of both hypertension and psoriasis, those with psoriasis alone exhibited an all-cause mortality HR of 0.73 (95% CI: 0.35-1.53), individuals with hypertension alone showed an HR of 1.78 (95% CI: 1.55-2.04), and those with both psoriasis and hypertension had an HR of 2.33 (95% CI: 1.60-3.40). In the course of a stratified analysis differentiating between the presence and absence of psoriasis, it was noted that hypertension correlated with an elevated risk of all-cause mortality in individuals lacking psoriasis (HR 1.77, 95% CI: 1.54-2.04). Notably, this association was further accentuated among individuals with psoriasis, revealing an increased HR of 3.23 (95% CI: 1.47-7.13). The outcomes of our investigation demonstrated a noteworthy and positive association between psoriasis, hypertension, and all-cause mortality. These findings indicate that individuals who have both psoriasis and hypertension face an increased likelihood of mortality.

The association between frailty biomarkers and 20-year all-cause and cardiovascular mortality among community-dwelling older adults

ABSTRACT Objectives While several biomarkers were previously associated with frailty and mortality, data are still contradicting. We aimed to evaluate the association between novel biomarkers and frailty among community-dwelling older adults to enhance understanding of the pathophysiology of frailty. Methods Nine hundred and sixty-three older adults were screened during the third phase (1999–2008) of the Israel study on Glucose Intolerance, Obesity, and Hypertension (GOH). Frailty was defined as sedentary individuals, past 10 years hospitalizations, or at least one of the following: body mass index (BMI) <21 kg/m2; albumin <3.2 g/dl; ≥2 major baseline diseases. Biomarkers were evaluated for their association with frailty, all-cause, and cardiovascular mortality. Results Mean baseline age was 72 ± 7 years, 471 (49%) were women, and 195 (20%) were classified as frail. Median follow-up for cardiovascular and all-cause mortality was 11 and 13 years, with 179 (18.6%) and 466 (48.4%) deaths recorded, respectively. Multivariable logistic regression showed greater odds for frailty with lower quartile of alanine aminotransferase (ALT) (OR = 1.8, 95%CI: 1.2–2.8, p = 0.01), and for each 5 µmol/L increment in homocysteine levels (OR = 1.3, 95%CI: 1.1–1.5, p = 0.001). Multivariate Cox regression showed greater all-cause and cardiovascular mortality risk for individuals with low ALT (HR = 1.6, 95%CI: 1.3–2.0, p < 0.001 and HR = 1.5, 95% CI: 1.0–2.2, p = 0.03, respectively), and high homocysteine (HR = 1.1, 95%CI: 1.1–1.3, p = 0.003 and HR = 1.2, 95%CI: 1.0–1.3, p = 0.04, respectively). Homocysteine association with mortality was more pronounced in those with baseline ischemic heart disease (IHD) compared with subjects free of IHD (P for interaction = 0.01). Conclusions Lower ALT and higher homocysteine were associated with frailty, all-cause and cardiovascular mortality. These available and low-cost biomarkers underscore the nutritional and metabolic aspects of frailty when screening high-risk older adults, especially those with IHD, and may be considered as preferable screening biomarkers to be tested among these individuals for frailty and mortality risk.

Development and Validation of a Risk Mortality Prediction Model for Patients with Pulmonary Tuberculosis Complicated by Severe Community-Acquired Pneumonia in the Intensive Care Unit.

The mortality rate from pulmonary tuberculosis (PTB) complicated by severe community-acquired pneumonia (SCAP) in the intensive care unit (ICU) remains high. We aimed to develop a rapid and simple model for the early assessment and stratification of prognosis in these patients. All adult patients with PTB complicated by SCAP admitted to the ICU of a tertiary hospital in Chengdu, Sichuan, China between 2019 and 2021 (development cohort) and 2022 (validation cohort) were retrospectively included. Data on demographics, comorbidities, laboratory values, and interventions were collected. The outcome was the 28-day mortality. Stepwise backward multivariate Cox analysis was used to develop a mortality risk prediction score model. Receiver operating characteristic (ROC) and calibration curves were used to evaluate the model's predictive efficiency. Decision curve analysis (DCA) was used to validate the model's clinical value and impact on decision making. Overall, 357 and 168 patients were included in the development and validation cohorts, respectively. The Pulmonary Tuberculosis Severity Index (PTSI) score included long-term use of glucocorticoid, body mass index (BMI) <18.5 kg/m2, diabetes, blood urea nitrogen (BUN) ≥7.14 mmol/L, PO2/FiO2 <150 mmHg, and vasopressor use. The area under the ROC curve (AUC) values were 0.817 (95% CI: 0.772-0.863) and 0.814 for the development and validation cohorts, respectively. The PTSI score had a higher AUC than the APACHE II, SOFA, and CURB-65 score. The calibration curves indicated good calibration in both cohorts. The DCA of the PTSI score indicated the high clinical application of the model compared with the APACHE II and SOFA scores. This prognostic tool was designed to rapidly evaluate the 28-day mortality risk in individuals with PTB complicated by SCAP. It can stratify this patient group into relevant risk categories, guide targeted interventions, and enhance clinical decision making, thereby optimizing patient care and improving outcomes.

Associations of hypertension, diabetes and heart disease risk with body mass index in older Chinese adults: a population-based cohort study

ObjectiveObesity is a well-established risk factor for disease. Controversy exists regarding the relative risk of morbidity and mortality in individuals who are overweight or underweight compared with individuals with a...

Developing a nomogram for forecasting the 28-day mortality rate of individuals with bleeding esophageal varices using model for end-stage liver disease scores

BackgroundThis study aimed to create a nomogram using the model for end-stage liver disease (MELD) that can better predict the risk of 28-day mortality in patients with bleeding esophageal varices. MethodsData on patients with bleeding esophageal varices were retrospectively collected from the Medical Information Mart for Intensive Care database. Variables were selected using the least absolute shrinkage and selection operator logistic regression model and were used to construct a prognostic nomogram. The nomogram was evaluated against the MELD model using various methods, including receiver operating characteristic (ROC) curve analysis, calibration plotting, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA). ResultsA total of 280 patients were included in the study. The patient’s use of vasopressin and norepinephrine, respiratory rate, temperature, mean corpuscular volume, and MELD score were included in the nomogram. The area under the ROC curve, NRI, IDI, and DCA of the nomogram indicated that it performs better than the MELD alone. ConclusionA nomogram was created that outperformed the MELD score in forecasting the risk of 28-day mortality in individuals with bleeding esophageal varices.

Associations of dietary magnesium intake with the risk of atherosclerotic cardiovascular disease and mortality in individuals with and without type 2 diabetes: A prospective study in the UK Biobank

BackgroundThe association between dietary magnesium (Mg) intake and the risk of atherosclerotic cardiovascular disease (ASCVD) remains uncertain. We aimed to examine the associations of dietary Mg intake with the risk of ASCVD events and mortality in individuals with and without type 2 diabetes. MethodsA total of 149,929 participants (4603 with type 2 diabetes) from the UK Biobank were included in the analyses. The hazard ratios (HRs) and 95 % confidence intervals (CIs) were estimated using Cox proportional hazard models. Furthermore, interactions of dietary Mg intake with type 2 diabetes status were examined on multiplicative and additive scales. ResultsDuring a median follow-up of 12.0 and 12.1 years, 7811 incident ASCVD events and 5000 deaths (including 599 ASCVD deaths) were documented, respectively. There were significantly negative associations between sufficient dietary Mg intake (equal to or greater than the recommended daily intake) and the risk of ASCVD incidence (HR 0.63 [95 % CI 0.49;0.82]), ASCVD mortality (0.45 [0.24;0.87]), and all-cause mortality (0.71 [0.52;0.97]) in participants with type 2 diabetes, whereas no significant association was observed in participants without type 2 diabetes (1.01 [0.94;1.09] for ASCVD incidence; 1.25 [0.93;1.66] for ASCVD mortality; 0.97 [0.88;1.07] for all-cause mortality). Multiplicative and additive interactions of dietary Mg intake with type 2 diabetes status were both observed. ConclusionSufficient dietary Mg intake was significantly associated with lower risks of ASCVD events and mortality in individuals with type 2 diabetes but not in those without type 2 diabetes. Our findings provide insight into the importance of dietary Mg intake for reducing modifiable cardiovascular burden in individuals with type 2 diabetes, which may inform future personalized dietary guidelines.

One-year mortality risk in older individuals with femoral intertrochanteric fracture: a tertiary center in China

BackgroundThe accelerated growth of older individuals worldwide has increased the number of patients presenting with fragility hip fractures. Having a hip fracture can cause excess mortality, and patients with hip fracture have a higher risk of death than those without hip fracture. Most studies have treated hip fracture as a single, homogeneous condition, but hip fracture includes two major anatomic types: intertrochanteric fracture and femoral neck fracture. Few studies have specifically evaluated 1-year mortality risk in older individuals with femoral intertrochanteric fracture. The aim of this study was to evaluate 1-year mortality and factors associated with mortality in older individuals with femoral intertrochanteric fracture.MethodsA retrospective review was conducted of 563 patients ≥ 65 years old who underwent surgery for femoral intertrochanteric fractures at our institution between January 2010 and August 2018. Patient demographics, comorbidities, and treatment were collected by retrospective chart review. Age, sex, Body Mass Index (BMI), American Society of Anesthesiologists (ASA) classification, Charlson comorbidity index (CCI), Arbeitsgemeinschaft Für Osteosynthesefragen (AO) fracture classification, haemoglobin value at admission, time to surgery, operation time, and intraoperative blood loss were risk factors to be tested. Multivariable logistic regression was used to evaluate associations between variables and death.ResultsAmong the 563 patients, 49 died within 1 year after surgery, and the 1-year mortality rate was 8.7%. Multivariate analysis identified age > 80 years (OR = 4.038, P = 0.011), haemoglobin < 100 g/l (OR = 2.732, P = 0.002), ASA score ≥ 3 (OR = 2.551, P = 0.005), CCI ≥ 3 (OR = 18.412, P = 0.018) and time to surgery > 14 d (OR = 3.907, P = 0.030) as independent risk factors for 1-year mortality. Comorbidities such as myocardial infarction and chronic pulmonary disease were associated with 1-year mortality after adjusting for age > 80 years and time to surgery > 14 days.ConclusionsPatients over 80 years old with haemoglobin < 100 g/l, ASA score ≥ 3, CCI ≥ 3, and multiple comorbidities, especially myocardial infarction and chronic pulmonary disease before surgery, are at a higher risk of 1-year mortality. Doctors should pay more attention to these vulnerable patients, and a surgical delay greater than 14 days should be avoided.

Diabetic foot disease carries an intrinsic high risk of mortality and other severe outcomes in type 2 diabetes: a propensity score-matched retrospective population-based study

BackgroundTo evaluate the association between diabetic foot disease (DFD) and the incidence of fatal and non-fatal events in individuals with type 2 diabetes (T2DM) from primary-care settings.MethodsWe built a cohort of people with a first DFD episode during 2010–2015, followed up until 2018. These subjects were 1 to 1 propensity score matched to subjects with T2DM without DFD. The incidence of all-cause mortality, the occurrence of new DFD, amputations, cardiovascular diseases, or composite outcome, including all-cause mortality and/or cardiovascular events during the follow-up period, were calculated. A Cox proportional hazard analysis was conducted to evaluate the hazard ratios (HR) for different events.ResultsOverall, 11,117 subjects with T2DM with a first episode of DFD were compared with subjects without DFD. We observed higher incidence rates (IRs) for composite outcome (33.9 vs. 14.5 IR per 100 person-years) and a new DFD episode event (22.2 vs. 1.1 IR per 100 person-years) in the DFD group. Compared to those without DFD, those with a first episode of DFD had a higher HR for all events, with excess rates particularly for amputation and new DFD occurrence (HR: 19.4, 95% CI: 16.7–22.6, HR: 15.1, 95% CI: 13.8–16.5, respectively) was found.ConclusionsAlthough DFD often coexists with other risk factors, it carries an intrinsic high risk of morbidity and mortality in individuals with T2DM. DFD should be regarded as a severe complication already at its onset, as it carries a poor clinical prognosis.Graphical

Systemic inflammatory biomarkers are novel predictors of all-cause and cardiovascular mortality in individuals with osteoarthritis: a prospective cohort study using data from the NHANES

BackgroundChronic inflammation may contribute to increased mortality risk in individuals with osteoarthritis (OA), but research on the prognostic value of inflammatory biomarkers is limited. We aimed to evaluate the associations of the systemic immune–inflammation index (SII) and systemic inflammation response index (SIRI) with all-cause and cardiovascular mortality among US adults with OA.MethodsThis cohort study included 3545 adults with OA aged ≥ 20 years from the National Health and Nutrition Examination Survey 1999–2020. The SII and SIRI were calculated using complete blood cell count data. Participants were categorized as having a higher or lower SII and SIRI using cutoff points derived by the maximally selected rank statistics method. Cox proportional hazards models, Fine–Gray competing risk regression models and time-dependent receiver operating characteristic (ROC) analysis were used to evaluate the associations between the SII/SIRI and mortality in OA patients.ResultsOver a median follow-up of 5.08 (3.42–9.92) years, 636 (17.94%) deaths occurred, including 149 (4.20%) cardiovascular deaths. According to multivariable-adjusted models involving demographic, socioeconomic, and health factors, OA patients with a higher SII had a twofold greater risk of all-cause mortality than patients with a lower SII (HR 2.01; 95% CI: 1.50–2.68). Similarly, a higher SIRI was associated with an 86% increased risk of all-cause mortality relative to a lower SIRI (HR 1.86; 95% CI: 1.46–2.38). Similar to the trend found with all-cause mortality, patients with an elevated SII and SIRI had a 88% and 67% increased risk of cardiovascular mortality, respectively, compared to patients with a lower SII (HR 1.88; 95% CI: 1.16–3.03) and SIRI (HR 1.67; 95% CI: 1.14–2.44). Time-dependent ROC curves showed that both the SII and SIRI have moderate and valid performance in predicting short- and long-term mortality in patients with OA.ConclusionsHigher SII and SIRI values were associated with greater all-cause and cardiovascular mortality among US adults with OA.

Association of leukocyte telomere length with risk of all-cause and cardiovascular mortality in middle-aged and older individuals without cardiovascular disease: a prospective cohort study of NHANES 1999–2002

BackgroundLeukocyte telomere length (LTL) shorting was significantly associated with mortality. This study aimed to investigate the potential association between LTL and all-cause mortality as well as cardiovascular disease (CVD) mortality in middle-aged or older individuals without a history of CVD.MethodsA total of 4174 participants from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2002 were included in this analysis. Cox proportional hazards regression models were utilized to estimate the association between LTL and mortality outcomes. Restricted cubic spline (RCS) curves were employed to evaluate the potential non-linear association.ResultsOver a median follow-up period of 217 months, the weighted rates of all-cause mortality and CVD mortality were 28.58% and 8.32% respectively. Participants in the highest LTL group exhibited a significantly decreased risk of both all-cause mortality (HR: 0.65, 95% CI: 0.54–0.78, P < 0.001) and CVD mortality (HR: 0.64, 95% CI: 0.45–0.93, P < 0.001) compared to those in the lowest group. Kaplan-Meier survival curves further supported a significant association between shorter telomere length and increased risks of both all-cause and CVD mortality (log-rank test P < 0.001). RCS curves demonstrated a linear dose-response relationship between LTL and all-cause mortality as well as CVD mortality. Subgroup and sensitivity analyses confirmed the robustness of the results.ConclusionShorter leukocyte telomere length could serve as a potential biomarker for risk stratification of all-cause and CVD mortality among middle-aged and older individuals without a history of CVD.

The independent and joint associations of vitamin B12 and methylmalonic acid on the risk of mortality in individuals with metabolic dysfunction-associated steatotic liver disease.

To investigate the independent and joint associations of vitamin B12 and methylmalonic acid (MMA) with all-cause, cardiovascular disease (CVD), and cancer mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). We included 6797 individuals with MASLD from the U.S. National Health and Nutrition Examination Survey. Serum MMA was measured using gas/liquid chromatography-mass spectrometry. Serum vitamin B12 was measured using commercial kits. The separate and joint associations of dietary intake and serum vitamin B12 (cutoff: 400 pg/mL) and MMA (cutoff: 250 nmol/L) levels with mortality were assessed by Cox proportional hazards regression. During a median follow-up of 9.3 years, 1604 deaths were documented, including 438 from CVD and 365 from cancer. In MASLD patients, dietary intake and serum vitamin B12 did not associate with mortality, while MMA was associated with a 1.35-fold increased risk of all-cause mortality (P-trend < 0.001). The adjusted hazard ratios for the joint association of vitamin B12 and MMA with all-cause and CVD mortality were 1 in the B12lowMMAlow group (reference), 1.02 (0.87-1.20) and 1.15 (0.90-1.47) in the B12highMMAlow group, 1.55 (1.29-1.86) and 1.84 (1.28-2.65) in the B12lowMMAhigh group, and 1.82 (1.49-2.21) and 2.28 (1.40-3.71) in the B12highMMAhigh group, respectively. The joint association was modified by serum folate (P-interaction = 0.001). In MASLD patients, MMA rather than dietary and serum vitamin B12 was positively associated with all-cause mortality. The joint effect of high levels of MMA and vitamin B12 showed the strongest associations with all-cause and CVD mortality, with a significant interaction with serum folate.

Association of C-reactive protein with all-cause and cause-specific mortality in people with gout

AimsTo test the association of C-reactive protein (CRP) with all-cause and cause-specific mortality in people with gout.MethodsThis cohort study included 502 participants with gout from the National Health and Nutrition Examination Survey. Multivariate Cox regression analysis, subgroup analysis, and restricted cubic spline (RCS) analyses were utilized to examine the association of CRP levels with all-cause, cardiovascular, and cancer mortality.ResultsAfter adjusting for multiple variables, Cox regression analysis showed that compared with individuals in the lowest tertile of CRP levels, those in the middle and highest tertiles experienced increases in all-cause mortality risk of 74.2% and 149.7%, respectively. Similarly, the cancer mortality risk for individuals in the highest tertile of CRP levels increased by 283.9%. In addition, for each standard deviation increase in CRP, the risks of all-cause and cancer mortality increased by 25.9% and 35.4%, respectively (P < 0.05). Subgroup analyses demonstrated that the association between CRP levels and all-cause mortality remained significant across subgroups of age (≤ 60 and > 60 years), gender (male), presence or absence of hypertension, non-diabetes, cardiovascular disease, non-cardiovascular disease and non-cancer. Furthermore, the association with cancer mortality was significant in subgroups including males, those without hypertension and cancer, and those with or without diabetes. However, the association with cardiovascular mortality was only significant in the non-hypertension subgroup (P < 0.05). Nonlinear association of CRP with all-cause mortality and linear association with cancer mortality were also confirmed (P for nonlinearity = 0.008 and 0.135, respectively).ConclusionsCRP levels were associated with increased all-cause and cancer mortality among individuals with gout.

Epigenetic predictors of species maximum life span and other life-history traits in mammals.

By analyzing 15,000 samples from 348 mammalian species, we derive DNA methylation (DNAm) predictors of maximum life span (R = 0.89), gestation time (R = 0.96), and age at sexual maturity (R = 0.85). Our maximum life-span predictor indicates a potential innate longevity advantage for females over males in 17 mammalian species including humans. The DNAm maximum life-span predictions are not affected by caloric restriction or partial reprogramming. Genetic disruptions in the somatotropic axis such as growth hormone receptors have an impact on DNAm maximum life span only in select tissues. Cancer mortality rates show no correlation with our epigenetic estimates of life-history traits. The DNAm maximum life-span predictor does not detect variation in life span between individuals of the same species, such as between the breeds of dogs. Maximum life span is determined in part by an epigenetic signature that is an intrinsic species property and is distinct from the signatures that relate to individual mortality risk.

Association between Long-Term Exposure to PM2.5 Inorganic Chemical Compositions and Cardiopulmonary Mortality: A 22-Year Cohort Study in Northern China.

Particulate matter with diameters ≤2.5 μm (PM2.5) has been identified as a significant air pollutant contributing to premature mortality. Nevertheless, the specific compositions within PM2.5 that play the most crucial role remain unclear, especially in areas with high pollution concentrations. This study aims to investigate the individual and joint mortality risks associated with PM2.5 inorganic chemical compositions and identify primary contributors. In 1998, we conducted a prospective cohort study in four northern Chinese cities (Tianjin, Shenyang, Taiyuan, and Rizhao). Satellite-based machine learning models calculated PM2.5 inorganic chemical compositions, including sulfate (SO4 2-), nitrate (NO3 -), ammonium (NH4 +), and chloride (Cl-). A time-varying Cox proportional hazards model was applied to analyze associations between these compositions and cardiorespiratory mortality, encompassing nonaccidental causes, cardiovascular diseases (CVDs), nonmalignant respiratory diseases (RDs), and lung cancer. The quantile-based g-computation model evaluated joint exposure effects and relative contributions of the compositions. Stratified analysis was used to identify vulnerable subpopulations. During 785,807 person-years of follow-up, 5812 (15.5%) deaths occurred from nonaccidental causes, including 2932 (7.8%) from all CVDs, 479 (1.3%) from nonmalignant RDs, and 552 (1.4%) from lung cancer. Every interquartile range (IQR) increase in SO4 2- was associated with mortality from nonaccidental causes (hazard ratio: 1.860; 95% confidence interval: 1.809, 1.911), CVDs (1.909; 1.836, 1.985), nonmalignant RDs (2.178; 1.975, 2.403), and lung cancer (1.773; 1.624, 1.937). In the joint exposure model, a simultaneous rise of one IQR in all four compositions increased the risk of cardiorespiratory mortality by at least 36.3%, with long-term exposure to SO4 2- contributing the most to nonaccidental and cardiopulmonary deaths. Individuals with higher incomes and lower education levels were found to be more vulnerable. Long-term exposure to higher levels of PM2.5 inorganic compositions was associated with significantly increased cardiopulmonary mortality, with SO4 2- potentially being the primary contributor. These findings offer insights into how PM2.5 sources impact health, aiding the development of more effective governance measures.

Identification of novel biomarkers for anti-Toxoplasma gondii IgM detection and the potential application in rapid diagnostic fluorescent tests.

Toxoplasmosis, while often asymptomatic and prevalent as a foodborne disease, poses a considerable mortality risk for immunocompromised individuals during pregnancy. Point-of-care serological tests that detect specific IgG and IgM in patient sera are critical for disease management under limited resources. Despite many efforts to replace the T. gondii total lysate antigens (TLAs) by recombinant antigens (rAgs) in commercial kits, while IgG detection provides significant specificity and sensitivity, IgM detection remains comparatively low in sensitivity. In this study, we attempted to identify novel antigens targeting IgM in early infection, thereby establishing an IgM on-site detection kit. Using two-dimensional gel electrophoresis (2DE) and mouse serum immunoblotting, three novel antigens, including EF1γ, PGKI, and GAP50, were indicated to target T. gondii IgM. However, rAg EF1γ was undetectable by IgM of mice sera in Western blotting verification experiments, and ELISA coated with PGKI did not eliminate cross-reactivity, in contrast to GAP50. Subsequently, the lateral flow reaction employing a strip coated with 0.3 mg/mL purified rAg GAP50 and exhibited remarkable sensitivity compared with the conventional ELISA based on tachyzoite TLA, which successfully identified IgM in mouse sera infected with tachyzoites, ranging from 103 to 104 at 5 dpi and 104 at 7 dpi, respectively. Furthermore, by using standard T. gondii-infected human sera from WHO, the limit of detection (LOD) for the rapid fluorescence immunochromatographic test (FICT) using GAP50 was observed at 0.65 IU (international unit). These findings underline the particular immunoreactivity of GAP50, suggesting its potential as a specific biomarker for increasing the sensitivity of the FICT in IgM detection.

Association between C-reactive protein/albumin ratio and all-cause mortality in patients with stroke: Evidence from NHANES cohort study

Background and aimsThe inflammatory nutritional status is widely associated with the long-term prognosis of non-fatal stroke. The objective of this study is to examine the correlation between the C-reactive protein to albumin ratio (CAR), a new marker indicating both inflammatory and nutritional status, and the overall mortality rate among stroke patients. Methods and resultsData were obtained from the National Health and Nutrition Examination Survey (NHANES) database and corresponding public-use mortality data from the linked National Death Index (NDI). The study utilized maximally selected rank statistics to determine the optimal cutoff points for the CAR. Subsequently, participants were stratified into higher- and lower-CAR groups based on these cutoff points. The Kaplan-Meier survival method was used to study overall survival probability. Multivariable Cox proportional regression models were employed to calculate the Hazard Ratio (HR) and corresponding confidence interval (CI). Restricted cubic spline (RCS) model was applied to detect potential non-linear relationship between CAR and mortality risk. Furthermore, stratified and sensitive analyses were performed to examine the robustness and reliability of the results. The study, encompassing 1043 participants with an average age of 64.61 years, identified a cutoff value of 0.32 for CAR, with notable variances observed across gender and age cohorts. Over an average follow-up period of 116 months, 679 instances of all-cause mortality were documented. Kaplan-Meier survival analysis unveiled noteworthy disparities in survival probabilities between groups categorized by high and low CAR levels (p = 0.00081). Continuous CAR analysis consistently demonstrated a positive correlation between elevated CAR values and heightened risk (HR = 1.78 (1.36, 2.33)) of all-cause mortality among stroke patients. Similarly, individuals in the high CAR group exhibited adjusted HR of 1.34 (0.96, 1.89) for all-cause mortality compared to their low CAR counterparts. Subgroup and sensitive analysis consistently reinforced these findings. Smoothing curve fitting further validated CAR's significance as a prognostic indicator of all-cause mortality, indicating a linear relationship. ConclusionElevated CAR is associated with increased long-term risk of mortality for individuals who have experienced a stroke, suggesting that CAR could serve as a survival indicator.

Relationship between serum apolipoprotein B and risk of all-cause and cardiovascular disease mortality in individuals with hypertension: a prospective cohort study

BackgroundDyslipidemia frequently coexists with hypertension in the population. Apolipoprotein B (ApoB) is increasingly considered a more potent predictor of cardiovascular disease (CVD). Abnormal levels of serum ApoB can potentially impact the mortality risk.MethodsThe prospective cohort study employed data from the National Health and Nutrition Examination Survey (NHANES), which was performed between 2005 and 2016, with follow-ups extended until December 2019. Serum ApoB concentrations were quantified using nephelometry. In line with the NHANES descriptions and recommendations, the reference ranges for ApoB concentrations are 55–140 and 55–125 mg/dL for men and women, respectively. Participants were categorized into low, normal, and high ApoB levels. The low and high groups were combined into the abnormal group. In this study, all-cause mortality (ACM) and CVD mortality (CVM) were the endpoints. Survey-weighted cox hazards models were used for evaluating the correlation between serum ApoB levels and ACM and CVM. A generalized additive model (GAM) was employed to examine the dose-dependent relationship between ApoB levels and mortality risk.ResultsAfter a median of 95 (interquartile range: 62–135) months of follow-up, 986 all-cause and 286 CVD deaths were recorded. The abnormal ApoB group exhibited a trend toward an elevated risk of ACM in relative to the normal group (HR 1.22, 95% CI: 0.96–1.53). The risk of CVM was elevated by 76% in the ApoB abnormal group (HR 1.76, 95% CI: 1.28–2.42). According to the GAM, there existed a nonlinear association between serum ApoB levels and ACM (P = 0.005) and CVM (P = 0.009).ConclusionsIn the US hypertensive population, serum Apo B levels were U-shaped and correlated with ACM and CVM risk, with the lowest risk at 100 mg/dL. Importantly, abnormal Apo B levels were related to an elevated risk of ACM and CVM. These risks were especially high at lower Apo B levels. The obtained findings emphasize the importance of maintaining appropriate Apo B levels to prevent adverse outcomes in hypertensive individuals.

#1265 Circulating neutrophils in diabetic kidney disease—the relationship with long-term cardiovascular outcomes

Abstract Background and Aims Neutrophils play important roles in the pathogenesis of cardiovascular inflammation and affects cardiovascular disease (CVD) outcomes. The relationship of circulating neutrophil counts with cardiovascular disease (CVD) and all-cause mortality in patients with type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD) remains unclear. Method We retrieved data from 44,494 participants in the National Health and Nutrition Examination Surveys (NHANES) from 2005 to 2020, and investigated the associations between circulating neutrophil counts, kidney functions and CVD mortality in T2DM and DKD patients. Clinical predictive models and risk scores for long-term mortality were constructed. Results Among the cohort of 44,332 patients (18% with T2DM and 82% without T2DM), a total of 2,220 patients were diagnosed with diabetic kidney disease (DKD) and 775 of them experienced mortality (31.5% related to CVD) during a follow-up of 6.18 (range: 5.94-6.42) years. The weighted mean of peripheral neutrophil count level (×109 /L) in DKD participants was 4.98. DKD patients in the highest quintile of neutrophil count exhibited a positive correlation with urine albumin-creatinine ratio (uACR) and a negative association with estimated glomerular filtration rate (eGFR), when compared to those in the lowest quintile. In the multivariate logistic regression analysis with RCS, circulating neutrophil counts showed a U-shaped association with CVD mortality. Neutrophil counts of 3.68 × 109 /L and 3.69 × 109 /L were associated with the lowest risk of CVD mortality and all-cause mortality respectively in DKD patients. Clinical predictive models showed good diagnostic performance for 5- and 10-year CVD mortality-free survival (all ROC AUC values &amp;gt;0.75). Conclusion In this study, higher peripheral neutrophil count was associated with an increased risk of cardiovascular mortality in DKD individuals. Our clinical predictive models may help identify at-risk patients for more aggressive CVD risk factors control.