Risk Of Mortality In Individuals Research Articles

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.

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...

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...

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.

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 >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.

Physical activity attenuates the excess mortality risk from prolonged sitting time among adults with osteoporosis or osteopenia.

Osteoporosis is a common generalized skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture. This study aims to crystallize associations of physical activity (PA) and sedentary behaviour with the survival of adults with osteoporosis or osteopenia. A total of 3103 participants aged 50 years or older from the National Health and Nutrition Examination Survey (NHANES) were included in the study. All participants were diagnosed with osteopenia or osteoporosis. Multivariable Cox proportional hazards regression models were used to assess the association of PA and sedentary behaviour with overall mortality, cancer-related mortality, and cardiovascular disease (CVD)-related mortality. During 21349 person-years of follow-up, 675 deaths were documented. Highly active participants had a lower risk of all-cause (hazard ratios [HR] = 0.61; 95% confidence interval [CI], 0.42-0.87; P for trend = 0.004), cancer-specific (HR = 0.64; 95%CI, 0.35-1.17; P for trend = 0.132), CVD-specific (HR = 0.75; 95%CI, 0.45-1.25; P for trend = 0.452), and other (HR, 0.51; 95%CI, 0.29-0.88; P for trend = 0.005) mortality than inactive participants. And sitting time was not associated with mortality among physically active participants; while among those who were insufficiently active or inactive, longer sitting time was associated with increased risks of all-cause (HR per 1-h increase = 1.05; 95% CI, 1.01-1.09), cancer-specific (HR per 1 h increase = 0.98; 95% CI, 0.90-1.07), CVD-specific (HR per 1-h increase = 1.11; 95% CI = 1.04-1.18), and other (HR per 1-h increase = 1.05; 95% CI, 0.98-1.13) mortality in a dose-response manner. PA can attenuate the excess mortality risk from prolonged sitting for individuals with osteoporosis and/or osteopenia. The combination of prolonged sedentary behaviour with inactive (participants without any PA during a week) PA was associated with an increased risk of mortality. The all-cause mortality risk of individuals who engage in less than 150 min/wk PA and sit more than 8 h/d is 2.02 (95% CI, 1.37-2.99) times higher than that of individuals who engage in more than 150 min/wk PA and sit less than 4 h/d.

INDIPENDENT PROGNOSTIC VALUE OF SOLUBLE–SUPRESSION OF TUMORIGENICITY (S–ST2) IN PATIENTS AFFECTED BY PULMONARY HYPERTENSION

Abstract Introduction According to ESC 2022 guidelines, pulmonary hypertension (PH) is a hemodynamic condition characterized by mean pulmonary arterial pressure>20 mmHg. Pulmonary arterial hypertension (PAH) represents 5% of the PH, with an unfavorable prognosis primarily because of late diagnosis and treatment. In PAH, it is important to evaluate the individual patient mortality risk through a multiparametric approach: a three–layer model at diagnosis and a four–layer model based on WHO–FC, 6MWD and NT–proBNP at follow up, which allows better discrimination within the intermediate risk group helping therapeutic decision making. The only biomarker included in risk stratification is NT–proBNP; however, in previous studies soluble–Supression of Tumorigenicity 2(s–ST2), a marker of myocardial stress, resulted a strong predictor of death in heart failure and acute coronary syndromes. Aim The aim of this study is to analyze the prognostic value of s–ST2 in patients with pulmonary hypertension. Methods This is a prospective study conducted on 45 PH patients (75% PAH), which were followed for survival. They underwent echocardiography, venous sampling to measure s–ST2 levels, right heart catheterization. All the patients were followed for survival. Results During an average 18–month follow–up, 17 patients died, 76% of whom had pulmonary arterial hypertension (PAH). They showed significantly higher values of s–ST2. sST2>78 ng/ml represents a numerical value with the highest association with mortality in our study population: at 6–12 months the patients with sST2>78 ng/ml showed statistically significant early higher mortality in comparison with sST2 <78 ng/ml patients (Fig. 1). At multivariate analysis s–ST2>78 ng/ml is confirmed to be a statistically significant predictor of mortality, regardless of WHO functional class III–IV, PAPs and NT–proBNP. Furthermore, s–ST2 appears a better early mortality predictor than NT–proBNP, at the limit of statistical significance (Fig. 2). Conclusions In a population of patients with pulmonary hypertension (predominantly PAH) we define a numerical value of sST2>78 ng/ml, which is a prognostic discriminator, independent and incremental to NT–proBNP at short–term follow–up. It allows the clinician the appropriate planning of therapeutic strategies in a condition in which the earliness of therapy affects prognosis.

Clinical Implications of Remote Dielectric Sensing-Guided Management.

Background: Remote dielectric sensing (ReDS) systems can quantify the degree of pulmonary congestion rapidly and non-invasively. However, the clinical implications of ReDS-guided medication adjustment remain uncertain. Methods: Patients hospitalized to treat cardiovascular diseases, including heart failure, valvular disease, and coronary artery disease, and underwent ReDS measurement before index discharge between 2021 and 2022 were included. According to our institutional protocol, ReDS values were blinded to the attending clinicians until February 2022 (blind period). After the period, ReDS values were timely opened to the attending clinicians, and medications such as diuretics were adjusted according to the ReDS values (target value between 20% and 35%) before index discharge (open period). A composite primary outcome of all-cause death and heart failure readmissions was compared between the two groups. Results: A total of 183 patients were included (median 79 years old, 101 men), consisting of 138 patients in the blind period and 45 patients in the open period. During a median of 646 (401, 818) days after the index discharge, 33 patients experienced the primary outcome of interest. Management during the open period, where medications were adjusted according to ReDS values, was independently associated with a lower incidence of the primary outcome with an adjusted hazard ratio of 0.22 (95% confidence interval 0.05-0.94, p = 0.041), as compared with those of the blind period. Conclusions: According to the findings of the present retrospective study, ReDS-guided management may have the potential to reduce the risk of mortality and heart failure admission in individuals hospitalized for cardiovascular diagnoses. Further prospective randomized control trials involving those with a variety of background etiologies and clinical scenarios are warranted to validate our findings and establish optimal ReDS-guided management.

MASLD/MetALD and mortality in individuals with any cardio-metabolic risk factor: A population-based study with 26.7 years of follow-up.

A new term, metabolic dysfunction-associated steatotic liver disease (MASLD), has been proposed by a multi-society expert panel. However, it remains unclear whether hepatic steatosis per se in MASLD contributes to an increased risk of mortality in individuals with any cardio-metabolic risk factor (CMRF), which is also a significant risk factor for increased mortality. This study aimed to compare all-cause and cause-specific mortality between the "MASLD/MetALD" and "no steatotic liver disease (SLD)" groups in individuals with any CMRF. A population-based cohort study was conducted using 10,750 participants of the Third National Health and Nutrition Examination Survey. All-cause and cause-specific (cardiovascular, cancer, diabetes, and liver) mortality risks were compared between the "MASLD," "MetALD," and "no SLD" groups using the Cox proportional hazards model with complex survey design weights, adjusted for confounders. Over 26 years, the "MASLD" group did not show significantly increased all-cause (adjusted HR 1.04[95% CI: 0.95-1.14], p = 0.413), cardiovascular (0.88 [0.75-1.04], p = 0.139), or cancer (1.06[0.84-1.33], p = 0.635) mortality risk compared to the "no SLD" group in individuals with any CMRF. The MetALD group was associated with increased all-cause (1.41 [1.05-1.89], p = 0.022), cancer (2.35 [1.33-4.16], p = 0.004), and liver (15.04 [2.96-76.35], p = 0.002) mortality risk compared with the no SLD group. This trend was more pronounced in the MetALD group with advanced fibrosis assessed by Fibrosis-4 (FIB-4). In individuals with CMRF, the presence of steatotic liver disease (MASLD) alone did not increase the risk of mortality, except in cases with more alcohol consumption (MetALD). Therefore controlling metabolic risk factors and reducing alcohol consumption in people with MASLD or MetALD will be crucial steps to improve long-term health outcomes.

The association of body mass index variability with cardiovascular disease and mortality: a mediation analysis of pooled cohorts.

We aimed to investigate the effect of BMI variability on CVD and mortality and to explore the mediation effects of the main cardiovascular risk factors contributing to this association. Participants aged 40-65 years were pooled from three cohort studies(ARIC [Atherosclerosis Risk in Communities], MESA [Multi-ethnic Study of Atherosclerosis], and TLGS [Tehran Lipid and Glucose Study]. We employed root mean squared error of the fractional mixed model to calculate BMI variability in the measurement period. In the event assessment period, the hazard ratios for CVD and mortality were estimated using Cox proportional hazard regression models. In the next step, the mediation and interaction effects of fasting plasma glucose, total cholesterol, and systolic blood pressure were determined. A total of 19073 participants were included in this pooled analysis. During a median of 20.7 years of follow-up, 3900 (20.44%) CVD and 6480 (33.97%) all-cause mortality events were recorded. After adjusting for potential confounders, BMI variability was linked to the 1.3 (1.2-1.4) and 1.7 (1.6-1.8) increased risk of CVD and mortality, respectively. Fasting plasma glucose mediated approximately 24% and 8% of the effect of BMI variability on CVD and mortality, respectively. However, systolic blood pressure and total cholesterol did not have mediation effects in this association. High BMI variability is independently associated with the development of CVD and mortality. This association is partly mediated through fasting plasma glucose. Modern cardiometabolic therapies that lower fasting glucose may reduce the risk of future CVD and mortality in individuals with high BMI variability.

Association between biological aging and the risk of mortality in individuals with non-alcoholic fatty liver disease: A prospective cohort study

BackgroundThe biological process of aging plays an important role in nonalcoholic fatty liver disease (NAFLD) development. However, epidemiological evidence about the association of biological aging with mortality risk among people with NAFLD is limited. MethodsA total of 2199 participants with NAFLD from the National Health and Nutrition Examination Surveys (NHANES) III were included. The outcomes were all-cause and cause-specific (cardiovascular disease [CVD], cancer, and diabetes) mortality. We computed three BA measures, the Klemera-Doubal method (KDM) age, Phenotypic age, and homeostatic dysregulation (HD), by using 18 age-associated clinical biomarkers, and assessed their associations with mortality risk using Cox proportional hazards (CPH) models. ResultsAfter a median follow-up of 16 years, a total of 1077 deaths occurred. People with NAFLD who died during follow-up period exhibited higher baseline biological age (BA) and biological age accelerations (BAAs). The multivariate-adjusted CPH suggested that a one-standard deviation (SD) increase in KDM age acceleration, Phenotypic age acceleration, or HD was associated with a 3 %, 7 %, or 39 % elevated risk of all-cause mortality, respectively. The results of age-varying HRs showed that the associations of KDM age accelerations (AAs) and Phenotypic AAs with all-cause mortality appeared to be stronger in people with NAFLD younger than 45 years. ConclusionsBiological aging was positively associated with both all-cause and cause-specific mortality among people with NAFLD, particularly among younger individuals.

Association of diabetic retinopathy on all-cause and cause-specific mortality in older adults with diabetes: National Health and Nutrition Examination Survey, 2005–2008

To evaluate the effect of diabetic retinopathy (DR) status or severity on all-cause and cause-specific mortality among diabetic older adults in the United States using the most recent National Health and Nutrition Examination Survey (NHANES) follow-up mortality data. The severity of DR was graded according to the Early Treatment Diabetic Retinopathy Study (ETDRS) grading scale. Multiple covariate-adjusted Cox proportional hazards regression models, Fine and Gray competing risk regression models, and propensity score matching (PSM) methods were used to assess the risk of all-cause and cause-specific mortality in individuals with diabetes. All analyses adopted the weighted data and complex stratified design approach proposed by the NHANES guidelines. Time to death was calculated based on the time between baseline and date of death or December 31, 2019, whichever came first. Ultimately 1077 participants, representing 3,025,316 US non-hospitalized individuals with diabetes, were included in the final analysis. After a median follow-up of 12.24 years (IQR, 11.16–13.49), 379 participants were considered deceased from all-causes, with 43.90% suffering from DR, including mild DR (41.50%), moderate to severe DR (46.77%), and proliferative DR (PDR) (67.21%). DR was associated with increased all-cause, cardiovascular disease (CVD) and diabetes mellitus (DM)-specific mortality, which remained consistent after propensity score matching (PSM). Results of DR grading assessment suggested that the presence of mild, moderate to severe NPDR was significantly associated with increased risk of all-cause and CVD-specific mortality, while the presence and severity of any DR was associated with increased DM-specific mortality, with a positive trend. The presence of DR in elderly individuals with diabetes is significantly associated with the elevated all-cause and CVD mortality. The grading or severity of DR may reflect the severity of cardiovascular disease status and overall mortality risk in patients with diabetes.

Association of lifestyles and multimorbidity with mortality among individuals aged 60 years or older: Two prospective cohort studies

Lifestyles are associated with all-cause mortality, yet limited research has explored the association in the elderly population with multimorbidity. We aim to investigate the impact of adopting a healthy lifestyle on reducing the risk of all-cause mortality in older individuals with or without multimorbidity in both China and UK. This prospective study included 29,451 and 173,503 older adults aged 60 and over from Chinese Longitudinal Healthy Longevity Survey (CLHLS) and UK Biobank. Lifestyles and multimorbidity were categorized into three groups, respectively. Cox proportional hazards regression was used to estimate the Hazard Ratios (HRs), 95% confidence intervals (95% CIs), and dose-response for all-cause mortality in relation to lifestyles and multimorbidity, as well as the combination of both factors. During a mean follow-up period of 4.7 years in CLHLS and 12.14 years in UK Biobank, we observed 21,540 and 20,720 deaths, respectively. For participants with two or more conditions, compared to those with an unhealthy lifestyle, adopting a healthy lifestyle was associated with a 27%–41% and 22%–42% reduction in mortality risk in the CLHLS and UK Biobank, respectively; Similarly, for individuals without multimorbidity, this reduction ranged from 18% to 41%. Among participants with multimorbidity, individuals with an unhealthy lifestyle had a higher mortality risk compared to those maintaining a healthy lifestyle, with HRs of 1.15 (95% CI: 1.00, 1.32) and 1.27 (95% CI: 1.16, 1.39) for two conditions, and 1.24 (95% CI: 1.06, 1.45) and 1.73 (95% CI: 1.56, 1.91) for three or more conditions in CLHLS and UK Biobank, respectively. Adherence to a healthy lifestyle can yield comparable mortality benefits for older individuals, regardless of their multimorbidity status. Furthermore, maintaining a healthy lifestyle can alleviate the mortality risks linked to a higher number of diseases.

PHYSICAL ACTIVITY IS ASSOCIATED WITH IMPROVED SECONDARY PREVENTION OF CARDIOVASCULAR DISEASE IN THE UK BIOBANK

INTRODUCTION & AIM Physical activity (PA) is known to be associated with a decreased risk of all-cause and cardiovascular mortality in apparently healthy adults. The association between PA and risk of death for individuals with prevalent cardiovascular disease (CVD) at baseline is less well understood. Therefore, the aim of this study was to determine the association between PA levels and survival in individuals with prevalent CVD at baseline. METHODS A survival analysis involving 38,291 UK Biobank participants with prevalent CVD at baseline was conducted. Physical activity was assessed using accelerometry-calibrated PA which measures total energy expended in PA. Prevalent CVD, all-cause mortality, and CVD mortality were determined through ICD-10 codes and data linkage through death and hospital records. Cox proportional hazard models were used to estimate the risk of all-cause, overall cardiovascular, and specific CVD category mortality for quartiles of PA after adjusting for known confounders. RESULTS There were 6,540 all-cause deaths and 3,559 cardiovascular deaths with median follow up time of 11.98 years. The risk of all-cause and overall cardiovascular mortality reduced with increasing dose of PA (highest vs lowest PA; HR = 0.70, 95% CI: 0.64 - 0.76 and 0.70, 95% CI: 0.62 - 0.79, respectively). Those in the highest quartile of PA had a 41% reduced risk of dying from cerebrovascular disease and a 38% reduced risk of dying from and hypertensive diseases (including hypertensive heart disease with heart failure). CONCLUSION Higher levels of PA are associated with lower risk of all-cause and overall cardiovascular mortality in individuals with prevalent CVD at baseline. These findings highlight the importance of PA in secondary prevention of cardiovascular disease.

Establishment and assessment of mortality risk prediction model in patients with sepsis based on early-stage peripheral lymphocyte subsets.

This study is aimed to explore the value of lymphocyte subsets in evaluating the severity and prognosis of sepsis. The counts of lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and NK cells significantly decreased between day 1 and day 3 in both the survivor and the non-survivor groups. The peripheral lymphocyte subsets (PLS) at day 1 were not significantly different between the survivor and the non-survivor groups. However, at day 3, the counts of lymphocytes, CD3+ T cells, CD4+ T cells, and NK cells were remarkably lower in the non-survivor group. No significant differences in CD8+ T cells, or CD19+ B cells were observed. The PLS index was independently and significantly associated with the 28-day mortality risk in septic patients (OR: 3.08, 95% CI: 1.18-9.67). Based on these clinical parameters and the PLS index, we developed a nomograph for evaluating the individual mortality risk in sepsis. The area under the curve of prediction with the PLS index was significantly higher than that from the model with only clinical parameters (0.912 vs. 0.817). Our study suggests that the decline of PLS occurred in the early stage of sepsis. The new novel PLS index can be an independent predictor of 28-day mortality in septic patients. The prediction model based on clinical parameters and the PLS index has relatively high predicting ability.

Associations between cardiovascular diseases and cancer mortality: insights from a retrospective cohort analysis of NHANES data

BackgroundThis study explored the association of cardiovascular disease (CVD) with cancer mortality risk in individuals with or without a history of cancer, to better understand the interplay between CVD and cancer outcomes.MethodsUtilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018, a retrospective cohort analysis was conducted. This analysis accounted for the survey’s complex design to ensure national representativeness. The association of CVD with cancer mortality was assessed through multivariable Cox proportional hazards models.ResultsThe present study included 59,653 participants, of whom 54,095 did not have cancer and 5558 had a history of cancer. In individuals without cancer, heart failure (HF) was associated with an increased risk of mortality from cancer (HR, 1.36; 95% CI, 1.09–1.69; P = 0.005). In participants with cancer, HF correlated with a higher risk of mortality from cancer (HR, 1.76; 95% CI, 1.32–2.34; P < 0.001). Diabetes (DM), hypertension (HBP) and coronary heart disease (CHD) were not significantly associated with an increased risk of mortality from cancer. Significant differences were observed in the interaction between cancer and CHD (HR, 0.68; 95% CI, 0.53–0.87; P = 0.002). For cancer and HBP, a similar trend was noted (HR, 0.75; 95% CI, 0.62–0.91; P = 0.003). No significant differences were found in interactions between HF, DM and cancer.ConclusionsHF was associated with an increased risk of mortality from cancer, regardless of cancer history, while HBP, CHD and DM showed no significant association. These findings underscore the importance of understanding the mechanisms behind the increased risk of cancer mortality following HF.

Association of multiple metabolic and cardiovascular markers with the risk of cognitive decline and mortality in adults with Alzheimer's disease and AD-related dementia or cognitive decline: a prospective cohort study.

There is a scarcity of data stemming from large-scale epidemiological longitudinal studies focusing on potentially preventable and controllable risk factors for Alzheimer's disease (AD) and AD-related dementia (ADRD). This study aimed to examine the effect of multiple metabolic factors and cardiovascular disorders on the risk of cognitive decline and AD/ADRD. We analyzed a cohort of 6,440 participants aged 45-84 years at baseline. Multiple metabolic and cardiovascular disorder factors included the five components of the metabolic syndrome [waist circumference, high blood pressure (HBP), elevated glucose and triglyceride (TG) concentrations, and reduced high-density lipoprotein cholesterol (HDL-C) concentrations], C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), factor VIII, D-dimer, and homocysteine concentrations, carotid intimal-medial thickness (CIMT), and urine albumin-to-creatinine ratio (ACR). Cognitive decline was defined using the Cognitive Abilities Screening Instrument (CASI) score, and AD/ADRD cases were classified using clinical diagnoses. Over an average follow-up period of 13 years, HBP and elevated glucose, CRP, homocysteine, IL-6, and ACR concentrations were significantly associated with the risk of mortality in the individuals with incident AD/ADRD or cognitive decline. Elevated D-dimer and homocysteine concentrations, as well as elevated ACR were significantly associated with incident AD/ADRD. Elevated homocysteine and ACR were significantly associated with cognitive decline. A dose-response association was observed, indicating that an increased number of exposures to multiple risk factors corresponded to a higher risk of mortality in individuals with cognitive decline or with AD/ADRD. Findings from our study reaffirm the significance of preventable and controllable factors, including HBP, hyperglycemia, elevated CRP, D-dimer, and homocysteine concentrations, as well as, ACR, as potential risk factors for cognitive decline and AD/ADRD.

Difference in association of carbohydrate intake with all-cause mortality between middle-aged and older Korean adults with and without diabetes mellitus: A prospective study

The relationship between diet and health, particularly the role of carbohydrates, has been extensively studied. However, carbohydrate intake based on individual health conditions remains unclear. Here, we aimed to investigate whether the association between carbohydrate intake and all-cause mortality varied between individuals with and without diabetes mellitus (DM). This prospective cohort study used data from the Korean Genome and Epidemiology Study (KoGES). Overall, 143,050 participants were included, with 10.1% having DM. Dietary intake was assessed using a semiquantitative food frequency questionnaire. Cox proportional hazards regression models were used to assess the association between carbohydrate intake and mortality after adjusting for confounders. The study showed that 5436 deaths occurred during the median follow-up period of 10.1 years. A significant interaction between carbohydrate intake and DM was observed in the study population (interaction p=0.061). Higher carbohydrate intake proportion was associated with an increased risk of all-cause mortality among individuals with DM (adjusted hazard ratio [HR], p-value=1.10 [1.01-1.20], p=0.032). Conversely, no association was observed between the proportion of carbohydrate intake and all-cause mortality in participants without DM. Additionally, both total sugar and added sugar intakes were associated with an increased risk of all-cause mortality in participants with DM (adjusted HR, p-value=1.02 [1.01-1.04], p<0.001 and 1.18 [1.13-1.24], p<0.001). High carbohydrate (%) and added sugar intake were associated with an increased mortality risk in individuals with DM. Reducing carbohydrate intake and opting for healthy carbohydrates to mitigate mortality risk may be beneficial for individuals with DM, particularly when compared with the general population.

Triglyceride-glucose index and mortality risk in individuals with or without chronic kidney disease: Insights from a national survey of United States adults, 1999–2018

Background and aimsThe Triglyceride-Glucose Index (TyG) has been proposed as a predictor to mortality, yet its association remains incompletely understood for individuals with or without chronic kidney disease (CKD). Methods and resultsWe analyzed data from the National Health and Nutrition Examination Survey spanning the years 1999–2018. CKD was defined as eGFR level <60 ml/min/1.73 m2 or urinary albumin creatinine ratio ≥30 mg/g. We employed the Cox proportional-hazards model to evaluate the incident risk of mortality associated with TyG among both non-CKD and CKD individuals. In the current analysis, 19,426 individuals were without CKD, while 2975 individuals had CKD. The overall mean TyG was 8.65, with significant difference between non-CKD and CKD individuals (8.60 vs 8.95, P < 0.001). The TyG index exhibited linear associations with incident cardiovascular disease (CVD) mortality and all-cause mortality among non-CKD and CKD individuals, respectively. A per-unit increase in the TyG index was significantly associated with CVD mortality for both non-CKD (HR = 1.24, 95%CI = 1.09–1.41) and CKD participants (HR = 1.19, 95%CI = 1.04–1.36), with no significant difference in the associations between the two groups (P = 0.091). For both non-CKD and CKD participants, TyG index was significantly associated with CVD mortality and all-cause mortality among those with age <65, but not for those with age ≥65. ConclusionsOur findings underscore the TyG index's as a valuable predictive tool for assessing the risk of all-cause and CVD mortality in both individuals with and without CKD.