Spline Model Research Articles

Electronic Nudges and Influenza Vaccination Among Patients With a History of Myocardial Infarction: Insights From 3 Nationwide Randomized Clinical Trials.

Influenza vaccination in patients with acute myocardial infarction (AMI) reduces major adverse cardiac events and is strongly recommended in clinical practice guidelines. Effective strategies to improve vaccination are needed in these high-risk patients. To evaluate whether electronically delivered behavioral nudges improve influenza vaccine uptake in patients with AMI across 3 nationwide implementation randomized clinical trials (RCTs). Nationwide Utilization of Danish Government Electronic Letter System for Increasing Influenza Vaccine Uptake (NUDGE-FLU), Nationwide Utilization of Danish Government Electronic Letter System for Confirming the Effectiveness of Behavioral Nudges in Increasing Influenza Vaccine Uptake Among Older Adults (NUDGE-FLU-2), and Nationwide Utilization of Danish Government Electronic Letter System for Increasing Influenza Vaccine Uptake Among Adults With Chronic Disease (NUDGE-FLU-CHRONIC) were RCTs conducted during the 2022 to 2023 and 2023 to 2024 influenza seasons in Denmark. Participants were randomized to either usual care or various behaviorally informed, electronically delivered, letter-based nudges. In a prespecified participant-level pooled meta-analysis, interaction of AMI status on the effects of letter-based nudges vs usual care was examined. Pooled treatment effects were estimated using binomial regression models with identity link, adjustment for trial, and 2-way clustered SEs at the household and participant levels. Effect modification by recency of AMI as a continuous variable was assessed using restricted cubic spline modeling in NUDGE-FLU-CHRONIC. Behaviorally informed, electronically delivered, letter-based nudges or usual care. The primary end point was influenza vaccination receipt. Of 2 146 124 individual randomizations (mean [SD] age, 71.1 [11.6] years; 1 114 725 female [51.9%]) across all 3 trials, 59 458 (2.8%) had a history of AMI. Improvement in vaccine uptake was similar in patients with vs without a history of AMI who received any nudge letter compared with usual care (+1.81 vs +1.32 percentage points; P for interaction by AMI status = .09). A letter highlighting the cardiovascular benefits of vaccination (ie, cardiovascular-gain frame) resulted in larger improvements in vaccine uptake among patients with (vs without) a history of AMI (+3.91 vs +2.03 percentage points; P for interaction by AMI status = .002). Among patients with AMI, the benefits of the cardiovascular-gain frame letter were more pronounced in those not vaccinated in the prior season (+13.7 vs +1.48 percentage points; P for interaction <.001). Among younger participants with chronic disease, the cardiovascular-gain frame letter was particularly effective in patients with more recent AMI (P for interaction by continuous recency of AMI <.001). Across 3 nationwide RCTs of Danish citizens, messaging emphasizing the cardiovascular benefits of vaccination improved influenza vaccination uptake, with greater benefits observed in patients with a history of AMI. This low-cost, scalable implementation strategy should be considered to encourage influenza vaccination in high-risk patients. ClinicalTrials.gov Identifiers: NCT05542004, NCT06030726, NCT06030739.

The impact of Life's Essentials 8 on sarcopenia prevalence among adults in the United States.

Sarcopenia is closely associated with cardiovascular disease. We aimed to examine the association of Life's Essential 8 (LE8), the recently updated measurement of cardiovascular health (CVH), with the presence of sarcopenia among US adults. This population-based cross-sectional study used data from the National Health and Nutrition Examination Survey in 2005-2006 and 2011-2018, and included adults aged 20 years or older. LE8 score was measured according to American Heart Association definitions. Sarcopenia was measured according to the National Institutes of Health definition, the ratio of appendicular skeletal muscle mass (ASM) to body mass index (BMI). Multivariable logistic and restricted cubic spline models were used to assess the associations between LE8 and sarcopenia. Among the 11,078 participants, 1021 (9.22 %) were diagnosed with sarcopenia. After adjusting for potential confounders, higher LE8, health behavior and health factors scores were associated with reduced odds ratios (OR) of sarcopenia (OR for per 10 scores increase in LE8, 0.65; 95 % CI 0.61-0.70; OR for per 10 scores increase in health behaviors score, 0.90; 95 % CI 0.84-0.97; OR for per 10 scores increase in health factors score, 0.67; 95 % CI 0.63-0.71). A non-linear dose-response relationship was observed between LE8 scores, health factors scores, and sarcopenia. The inversed association between LE8 score and sarcopenia was significantly stronger among males and participants with a high school education or above. LE8 was negatively associated with the prevalence of sarcopenia in a nonlinear fashion. Promoting adherence to optimal CVH levels may benefit to reduce the risk of sarcopenia.

Donor Time to Death and Kidney Transplant Outcomes in the Setting of a 3-Hour Minimum Wait Policy.

Lengthening waiting lists for organ transplant mandates the development of strategies to expand the deceased donor pool. Due to concerns regarding organ viability, most organ donation organizations internationally wait no longer than 1 to 2 hours for potential donation after circulatory death (DCD), possibly underutilizing an important organ source; UK policy mandates a minimum 3-hour wait time. To assess whether time to death (TTD) from withdrawal of life-sustaining treatment (WLST) is associated with kidney transplant outcomes. This population-based cohort study used data from the prospectively maintained UK Transplant Registry from all 23 UK kidney transplant centers from January 1, 2013, to December 31, 2021; follow-up was until the date of data extraction (October 2023). Participants comprised 7183 adult recipients of DCD kidney-alone transplants. Duration of TTD, defined as time from WLST to donor mechanical asystole. Primary outcome was 12-month estimated glomerular filtration rate (eGFR; for the main eGFR model, variables with significant right skew [histogram visual assessment] were analyzed on the log2 scale), with secondary outcomes of delayed graft function and graft survival (censored at death or 5 years). This study included 7183 kidney transplant recipients (median age, 56 years [IQR, 47-64 years]; 4666 men [65.0%]). Median donor age was 55 years (IQR, 44-63 years). Median TTD was 15 minutes (range, 0-407 minutes), with 885 kidneys transplanted from donors with TTD over 1 hour and 303 kidneys transplanted from donors with TTD over 2 hours. Donor TTD was not associated with recipient 12-month eGFR on adjusted linear regression (change per doubling of TTD, -0.25; 95% CI, -0.68 to 0.19; P = .27), nor with delayed graft function (adjusted odds ratio, 1.01; 95% CI, 0.97-1.06; P = .65) or graft survival (adjusted hazard ratio, 1.00; 95% CI, 0.95-1.07; P = .92). These findings were confirmed with restricted cubic spline models (assessing nonlinear associations) and tests of interaction (including normothermic regional perfusion). In contrast, donor asystolic time, cold ischemic time, and reperfusion time were independently associated with outcomes. Compared with a theoretical 1-hour maximum wait time, the UK policy (minimum 3-hour wait time) has been associated with 885 extra DCD transplants compared with 6298 transplants (14.1% increase). In this cohort study of DCD kidney recipients, donor TTD was not associated with posttransplant outcomes, in contrast to subsequent ischemic times. Altering international transplant practice to mandate minimum 3-hour donor wait times could substantially increase numbers of kidney transplants performed without prejudicing outcomes.

Exploring the Relationship Between Refractive Errors and Common Chronic Diseases Via Blood Biochemistry Tests: A Large Prospective Cohort Study.

The purpose of this study was to examine the association between refractive errors and common chronic diseases using blood biochemistry tests, and to investigate the associated modifiable risk factors, with the goal of informing and developing effective preventive strategies. A total of 116,245 participants with refractometry at baseline enrolled in the UK Biobank were included in this prospective cohort study. Restricted cubic spline and Cox proportional hazards models were used to detect associations between refractive error, blood biochemistry tests, and common chronic diseases. Interaction effects on the additive scale and effect modification analysis were used to explore excess modifiable risk factors for disease prevention. Spherical equivalent significantly associated with vitamin D, sex hormone binding globulin, apolipoprotein A, blood glucose, and aspartate aminotransferase levels. Subjects with myopia demonstrated a 13% higher risk of type 2 diabetes mellitus (T2DM) incidence compared to those without myopia (hazard ratio [HR] = 1.13, 95% confidence interval [CI] = 1.08-1.19) throughout a median follow-up of 9.12years. Interaction analysis revealed 15% (95% CI = 9%-21%) of this risk was due to myopia-obesity interaction. However, active engagement in physical activity could potentially mitigate this risk (HR = 1.06, 95% CI = 0.93-1.20). Refractive errors were associated with specific blood indicators, particularly noting the association between myopia and higher T2DM incidence in middle-aged and elderly populations. This effect interacts with obesity, and promoting physical activity among myopia individuals provides greater benefits in the prevention of T2DM compared to non-myopic individuals.

Association between life's essential 8 and cognitive impairment in older patients: results from NHANES 2011-2014.

This study aimed to examine the association between the American Heart Association's (AHA) newly revised Life's Essential 8 (LE8) algorithm, designed for assessing cardiovascular health (CVH), and cognitive impairment among older adults in the United States. This study employed a cross-sectional design, utilizing data from the 2011-2014 National Health and Nutrition Examination Survey to explore the relationship between CVH and cognitive impairment in older adults. CVH scores are assessed based on the AHA definition of the LE8, categorized into three tiers: low (0-49), medium (50-79), and high (80-100). Cognitive impairment is evaluated using three distinct scoring systems: the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST). The lowest quartile as the cut-off point; below or equal to the lower quartile was considered as low cognitive population, and above the lower quartile was normal population. To analyze the association, multivariable logistic regression and restricted cubic spline (RCS) models were employed. A significant negative correlation exists between the LE8 and cognitive impairment. After adjusting for multiple variables, the odds ratios (OR) for cognitive impairment, as measured by the CERAD, AFT, and DSST, were compared between patients with high and low CVH. The results indicated OR values of 0.60 (95% CI: 0.36-0.98), 0.72 (95% CI: 0.52-0.97), and 0.29 (95% CI: 0.16-0.53) for the CERAD, AFT, and DSST, respectively. Additionally, the RCS curve demonstrated a significant linear relationship between lifestyle factors encapsulated by the LE8 and cognitive impairment. The findings indicate higher adherence to LE8 was associated with lower odds of cognitive impairment. Furthermore, maintaining optimal CVH is crucial in preventing cognitive impairment.

Association between triglyceride glucose index and endometriosis in adults in the United States: A comprehensive study from the National Health and Nutrition Examination Survey (NHANES).

The triglyceride glucose (TyG) index has been well recognized as a reliable marker of insulin resistance and substantially correlated with the pathogenesis and progression of hypertension and cardiovascular diseases. However, no study has investigated the association between the TyG index and endometriosis. Therefore, this study aimed to uncover an association between the TyG index and endometriosis. This cross-sectional investigation employed the extensive dataset derived from the National Health and Nutrition Examination Survey (NHANES) (1999-2006). To explore the potential connection between the TyG and endometriosis, a multivariate weighted logistic regression model was established. The nonlinear relationship between the TyG index and the risk of endometriosis was explored using restricted cubic spline models (RCS). Furthermore, subgroup analyses were conducted. Ultimately, 2,508 individuals were included in this investigation. The findings unveiled a robust positive correlation between the TyG index and the susceptibility to endometriosis (OR [95% CI]: 1.52 [1.024,2.258]; P < 0.05). This positive association remained consistent across diverse subgroups. Age, birthplace, and whether one ovary was removed were identified as significant risk factors. In RCS analysis, the TyG index showed a nearly linear relationship with the risk of endometriosis (P-nonlinear > 0.05). The findings indicate a positive association between the TyG index and the risk of endometriosis, exhibiting an approximate non-linear relationship.

Association of oral health with nutritional status of the older adults: a cross-sectional study.

The potential association between oral health and nutritional status of the very old, has been poorly investigated. Thus, we carried out the cross-sectional study to evaluate the association of oral health with the nutritional status of the older adults. 210 participants aged over 75 years were included in the study. Nutritional status was assessed by the Short-form Mini-Nutritional Assessment (MNA-SF) and body composition measurement. Data were available for self-reported oral health (10-item Eating Assessment Tool (EAT-10) and Chewing Function Questionnaire (CFQ)) and specific experimental tests including salivary flow, tongue and lip pressure, occlusal force, water swallow test and taste test for the detection of oral functions. Spearman rank correlation was used to analyze the correlation between body composition and oral health. Logistic regression and restricted cubic spline models were applied to examine the association of oral health with malnutrition. The study reveals that poor oral health is related to the malnutrition. The tongue pressure and molar occlusal force were significantly associated with malnutrition in an L-shaped dose-response relationship after adjustment for potential confounding factors. The higher the tongue pressure and molar occlusal force, the lower the risk of malnutrition. Besides, the CFQ score, salty, sour, and bitter taste, are risk factors for malnutrition. The presence of malnutrition is significantly associated with poor oral health in older adults. Our study supposes that the design of food suitable for oral conditions of the older adults may be another feasible solution to the nutritional problems among them.

Dietary patterns and bone density among school-aged children: a cross-sectional study in China.

Diet is an essential modifiable determinant of bone health, yet the associations between dietary patterns (DPs) and bone mineral density (BMD) in Chinese children remain limited. This study aimed to investigate the relationship between overall diet and low BMD risk among school-aged children in China. A total of 1,099 children aged 9-12 in China were recruited for this cross-sectional study. A semi-quantified food frequency questionnaire (FFQ) was used to assess dietary intake. A priori numerical index, the Chinese Dietary Guidelines Index for Children and Adolescents [CDGI (2021)-C] was utilized to assess dietary quality. Specific DPs were identified by using principal components analysis (PCA). The BMD of the left forearm was assessed using dual-energy X-ray absorptiometry (DXA). Spearman correlation test was conducted to investigate the associations between DPs. Multivariate logistic regression analysis and restricted cubic spline models (RCS) were applied to explore the associations between DPs and BMD. Three distinct DPs were identified: the plant-animal balanced pattern, the grain-tuber-meat pattern, and the bean-dairy pattern. We found a weak but significant positive correlation of the CDGI (2021)-C with the plant-animal balanced pattern (R = 0.318, P < 0.001), and with the bean-dairy pattern (R = 0.266, P < 0.001), respectively. After adjusting for covariates, adherence to the CDGI (2021)-C (Q4 vs. Q1, OR = 0.45, 95% CI: 0.27-0.75), the plant-animal balanced pattern (Q4 vs. Q1, OR = 0.50, 95% CI: 0.31-0.81), and the bean-dairy pattern (Q3 vs. Q1, OR = 0.57, 95% CI: 0.33-0.96) were associated with a lower risk of low BMD. No significant association was observed between the grain-tuber-meat pattern and low BMD (Q4 vs. Q1, OR = 1.09; 95% CI: 0.90-1.31). Adherence to the CDGI (2021)-C and the plant-animal balanced pattern is advantageous for bone health and inversely correlated with the risk of low BMD among school-aged children in China. Additionally, moderate adherence to the bean-dairy pattern may also confer benefits to bone health. A balanced and overall healthy diet should be recommended in our daily life.

Impact of baseline dietary quality on the efficacy of a dietitian-guided weight reduction program.

This pre-post intervention study aimed to assess the relationship between baseline dietary quality and the efficacy of a dietitian-guided weight reduction program, which has not been thoroughly documented to date. Ninety-two consecutive obese or overweight patients visiting a tertiary center clinic for weight reduction were enrolled in this study. Participants received a dietitian-guided weight reduction education program aimed at reducing daily caloric intake by 500kcal and improving adherence to the Mediterranean diet for 3 months. Baseline dietary quality was assessed using the 14-item Taiwanese Mediterranean Diet Adherence Screener (T-MEDAS), where a higher T-MEDAS score reflects greater adherence to the Mediterranean diet. Additional covariates, including dietary behaviors, lifestyle factors, and comorbidities were also recorded. The primary outcome was the percentage of weight reduction at 3 months, analyzed using restricted cubic spline models and generalized estimating equations (GEE) to account for the correlation between weight change and the baseline T-MEDAS scores. Thirty-nine participants were excluded due to major illnesses, use of anti-obesity medications, or loss to follow-up. Among the remaining 53 participants (mean age 41.2 ± 12.8 years, 56.6% female), the average weight reduction was 3.9 ± 3.3% from a baseline weight of 98.5 ± 12.8kg. Participants who did not achieve a weight reduction of more than 5% had higher baseline T-MEDAS scores compared to those who did (5.4 ± 1.7 vs. 4.1 ± 1.8, p = 0.026). A restricted cubic spline model, adjusted for covariates including age, gender, diabetes mellitus (DM), dyslipidemia, and smoking, revealed a significant inverse relationship between higher baseline T-MEDAS scores and weight loss. After controlling for various confounders, GEE analysis demonstrated that higher baseline T-MEDAS scores were significantly associated with less weight loss (beta: -4.1, 95% CI: -5.6 to -2.6, p < 0.001). Higher baseline dietary quality was associated with reduced effectiveness of a dietitian-guided weight reduction program. This suggests that additional strategies may be required to improve the success of weight loss interventions in individuals with higher baseline dietary quality.

Abstract 4125581: Association Between Life’s Essential 8 and Premature Atherosclerotic Cardiovascular Disease: A Cross-sectional Study Among Young Adults in the United States

Background: Among patients presenting with atherosclerotic cardiovascular disease (ASCVD), the proportion of young individuals has increased in recent years. Life’s Essential 8 (LE8), containing two domains of health behaviors and health factors, is an updated monitoring measurement of cardiovascular health by assessing 8 modifiable risk factors. Objective: The objective of this study is to investigate the potential relationship between the LE8 score and a history of premature ASCVD among young adults residing in the United States. Methods: This population-based cross-sectional study utilized data from the National Health and Nutrition Examination Survey spanning 2005 to 2018, focusing specifically on adults aged 20 to 45. LE8 score was measured and categorized into low (0-49), moderate (50-79), and high (80-100) levels (Figure 1). Premature ASCVD status was determined by interviews conducted at enrollment, encompassing a self-reported composite disease history of coronary heart disease, angina pectoris, heart attack, and stroke. Following descriptive statistics, weighted multivariable logistic regression and restricted cubic spline models were employed to evaluate the associations between the LE8 score and premature ASCVD. Additionally, subscale and subgroup analysis were developed. Results: Among 17,499 participants, 9846 were eligible for analysis (weighted mean age, 32.7 years; male, 50.3%), and 167 had premature ASCVD history (weighted percentage, 1.46%). The weighted mean LE8 score of the study population was 71.99 (0.3). Following the adjustment for potential confounders, individuals with higher LE8 scores exhibited a reduced risk of developing premature ASCVD (Table 1). A nonlinear relationship was observed and similar patterns were also identified in the association of health behaviors and health factors scores with premature ASCVD (Figure 2). This inverse association was consistently observed across various subgroups, including sex, age strata, ethnicity, education, and income levels, with no significant interactions identified. Conclusions: The LE8 score and its subscale scores exhibited a negative, nonlinear association with premature ASCVD. Maintaining a healthy lifestyle and controlling modifiable risk factors are crucial in preventing premature ASCVD in the younger demographic. Further studies, encompassing prospective cohorts, are needed to confirm this finding.

Abstract 4144501: Effect of the Cardiac Myosin Activator Omecamtiv Mecarbil on Risk of Ventricular Arrhythmias in Heart Failure with Reduced Ejection Fraction: the GALACTIC-HF Trial

Introduction: The selective cardiac myosin activator, omecamtiv mecarbil (OM), has been shown to benefit individuals with HFrEF but the clinical experience of cardiac myosin activators and incidence of ventricular arrhythmias (VA) is limited. We investigated the prognostic role of VA and the associations between OM, VA occurrence, and outcomes in the GALACTIC-HF trial. Methods: GALACTIC-HF was a placebo-controlled trial testing the efficacy and safety of OM in participants with symptomatic chronic HF and LVEF≤35%. VA were captured based on safety adverse event reporting. Severe HF was defined according to the ESC-HFA criteria. Poisson regression models using restricted cubic splines model were used to assess the association between baseline LVEF and incidence rates of VA. Associations between incident VA and subsequent clinical outcomes were evaluated using time-updated Cox proportional hazard models. Results: Over a median follow-up of 21.8 months, 594 out of the 8,232 individuals randomized in the GALACTIC-HF trial experienced VA, with no statistically significant differences between study arms. Individuals with lower LVEF values were at greater risk of incident VA (per 10% decline: HR 1.37; 95% CI 1.21-1.55; p&lt;0.001) with no significant differences between study arms ( Figure, panel A ). Following VA occurrence, participants were at higher risk of the primary endpoint of CV death or HF events (adj HR 1.67; 95% CI 1.42-1.97; p&lt;0.001) and all-cause mortality (adj HR 2.07; 95% CI 1.77-2.42; p&lt;0.001). The treatment effects of OM on clinical outcomes were consistent in patients not experiencing VA and after VA events. Among the 2,258 participants with severe HF, OM did not affect the risk of VA (adj HR 0.95; 95% CI 0.70-1.29) and this was consistent across the range of LVEF; Figure, panel B . Conclusions: The occurrence of VA among patients with HFrEF is associated with a substantially higher risk of subsequent fatal and non-fatal events. OM did not increase the risk of VA and the beneficial treatment effects were maintained irrespective of VA occurrence. These findings reinforce the safety of OM use among individuals with HFrEF who are at risk of arrhythmic events.

Association between depression and diabetes among American adults using NHANES data from 2005 to 2020.

Depression impairs self-management in diabetic patients, exacerbates insulin resistance, and elevates glycated hemoglobin (HbA1c) levels, thereby increasing diabetes risk. This study analyzed data from 30,386 participants in the National Health and Nutrition Examination Survey (NHANES), assessing depression severity using the 9-item Patient Health Questionnaire (PHQ-9) and evaluating diabetes status through clinical markers such as HbA1c, random blood glucose, and fasting blood glucose. Participants were stratified by depression severity and diabetes status to examine the relationship between depression and diabetes risk. We applied descriptive statistics, logistic regression models, subgroup analyses, and restricted cubic spline (RCS) modeling to explore this association. The results revealed that greater depression severity was significantly associated with increased diabetes incidence, elevated HbA1c, fasting glucose, and insulin levels. Multivariate regression analysis confirmed a consistent positive correlation between depression severity and diabetes risk. Subgroup analyses further identified significant relationships between depression and various demographic and behavioral factors, including gender, race, BMI, smoking status, and prediabetic conditions. Additionally, the RCS model demonstrated a clear increase in diabetes risk with rising PHQ-9 scores. In conclusion, our study demonstrates that the severity of depression is positively correlated with the risk of diabetes, and this association may be closely linked to various glycemic and lipid metabolic parameters.

Influence of endoxifen on mammographic density-results from the KARISMA trial.

Monitoring metabolites of tamoxifen, such as endoxifen, has been suggested as a strategy to ascertain therapeutic effect of tamoxifen therapy but clinical guidelines are missing. Herein we aim to investigate the outcome of endoxifen concentrations of low dose tamoxifen, using change in mammographic breast density (MBD) as a proxy for therapy response. In the randomized KARISMA trial, including five doses of tamoxifen, measurements of plasma endoxifen concentrations, determination of CYP2D6 metabolizer status and MBD change over the trial period, were carried out. Association between endoxifen concentrations and relative MBD change after 6 months treatment was analysed using linear regression in a spline model. A total of 824 women (335 premenopausal, 489 postmenopausal) were included. In analyses of premenopausal women, a spline model described a MBD decrease, equivalent to the mean (-18.5%) seen in women exposed to 20 mg tamoxifen, at endoxifen concentrations of 2-3 ng/mL. The MBD decrease reached a nadir at endoxifen levels of 3 ng/mL and did not decrease further at higher endoxifen concentrations. Most intermediate and normal tamoxifen-metabolizers (≈ 90% of all participants) reached an endoxifen concentration of > 2 ng/mL at tamoxifen doses of 5 and 10 mg. No MBD decrease was seen in the postmenopausal group. We have identified a possible window of effect on MBD at endoxifen concentrations of 2-3 ng/mL in premenopausal women, which corresponds to the doses of 5 and 10 mg tamoxifen. Since MBD change was used as a surrogate marker for therapy response, results should be confirmed using clinically established outcomes measures. ClinicalTrials.gov ID: NCT03346200.

Associations of physiologic subtypes based on HOMA2 indices of β-cell function and insulin sensitivity with the risk of kidney function decline, cardiovascular disease, and all-cause mortality from the 4C study

BackgroundPrevious studies have been limited by their inability to differentiate between the effects of insulin sensitivity and β-cell function on the risk of kidney function decline, cardiovascular disease (CVD), and all-cause mortality. To address this knowledge gap, we aimed to investigate whether the physiological subtypes based on homeostasis model assessment-2 (HOMA2) indices of β-cell function (HOMA2-B) and insulin sensitivity (HOMA2-S) could be used to identify individuals with subsequently high or low of clinical outcome risk.MethodsThis retrospective cohort study included 7,317 participants with a follow-up of up to 5 years. Based on HOMA2 indices, participants were categorized into four physiologic subtypes: the normal phenotype (high insulin sensitivity and high β-cell function), the insulinopenic phenotype (high insulin sensitivity and low β-cell function), the hyperinsulinaemic phenotype (low insulin sensitivity and high β-cell function), and the classical phenotype (low insulin sensitivity and low β-cell function). The outcomes included kidney function decline, CVD events (fatal and nonfatal), and all-cause mortality. Cox regression models were used to calculate hazard ratios (HRs) for outcomes, and spline models were used to examine the dose-dependent associations of HOMA2-B and HOMA2-S with outcomes.ResultsA total of 1,488 (20.3%) were classified as normal, 2,179 (29.8%) as insulinopenic, 2,173 (29.7%) as hyperinsulinemic, and 1,477 (20.2%) as classical subtypes. Compared with other physiological subtypes, the classical subtype presented the highest risk of kidney function decline (classical vs. normal HR 11.50, 95% CI 4.31–30.67). The hyperinsulinemic subtype had the highest risk of CVD and all-cause mortality (hyperinsulinemic vs. normal: fatal CVD, HR 6.56, 95% CI 3.09–13.92; all-cause mortality, HR 4.56, 95% CI 2.97–7.00). Spline analyses indicated the dose-dependent associations of HOMA2-B and HOMA2-S with outcomes.ConclusionsThe classical subtype had the strongest correlation with the risk of kidney function decline, and the hyperinsulinemic subtype had the highest risk of CVD and all-cause mortality, which should be considered for interventions with precision medicine.Graphical abstract

Association between Lactate dehydrogenase and 28-day all-cause mortality in patients with non-traumatic Intracerebral hemorrhage: A retrospective analysis of the MIMIC-IV database.

Lactate dehydrogenase (LDH), a nonspecific inflammatory biomarker, has been used in the assessment of acute myocardial infarction, acute hepatitis, acute lung injury, and other severe diseases. However, no studies have evaluated the prognostic value of LDH in patients with non-traumatic intracerebral hemorrhage (ICH). This cohort study aims to assess the association between LDH levels and 28-day all-cause mortality in patients with non-traumatic ICH. Data for this retrospective cohort analysis were obtained from the MIMIC-IV (v2.2) database, and the study included patients with non-traumatic ICH as defined by the International Classification of Diseases, 9th and 10th editions. Patients were categorized into four distinct groups based on their LDH levels. The primary outcome of interest was the 28-day mortality rate. To analyze these associations and assess the consistency of interactions, subgroup analyses, Cox regression analysis, Kaplan-Meier (KM) curves, and nonlinear analysis were conducted. A total of 406 patients with non-traumatic ICH were enrolled in the study and were divided into quartiles based on LDH levels. The KM curve indicated that the 28-day all-cause mortality rate of patients in the Q4 group (LDH > 287.25) was significantly higher than in the Q1 (LDH < 194.7) (P < 0.001) and Q2 (194.7 < LDH < 233.0) (P < 0.001) groups, though not significantly different from Q3 (P = 0.140). Multivariate Cox proportional hazards analysis revealed that patients in the highest LDH quartile had a significantly increased risk of mortality compared to those in the lowest quartile across three models: unadjusted [HR, 3.401; 95% CI, 1.719-6.731; P < 0.001], partially adjusted [HR, 2.422; 95% CI, 1.211-4.846; P = 0.012], and fully adjusted [HR, 3.054; 95% CI, 1.522-6.126; P = 0.002]. Restricted cubic spline (RCS) models revealed an L-shaped association between LDH levels and the 28-day all-cause mortality rate, indicating a non-linear relationship (P < 0.001). No significant interactions were observed between LDH levels and other factors in the subgroup analyses (all P for interaction > 0.05). Our findings indicate a significant association between 28-day all-cause mortality and LDH levels in patients with non-traumatic intracerebral hemorrhage. Specifically, patients with elevated LDH levels within the first 24 hours of ICU admission are at a higher risk of mortality.

Association between prognostic nutritional index and mortality risk in patients with community-acquired pneumonia: a retrospective study

BackgroundThe prognostic nutritional index (PNI), reflecting the body’s immune-nutritional status, has been established as a correlate of prognosis across various diseases. However, its significance in community-acquired pneumonia (CAP) remains unclear. This study investigated the relationship between PNI and clinical outcomes in CAP patients.MethodsIn this retrospective cohort study, we aimed to evaluate the prognostic value of the PNI in adults with CAP admitted to the ICU. Participants were selected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database and categorized into quartiles (Q1–Q4) according to their PNI values. We employed Kaplan-Meier survival analysis, multivariate Cox regression, and restricted cubic spline (RCS) models to explore the association between PNI and the clinical outcomes of these CAP patients.ResultsIn this study, we included 1,608 patients with CAP. The observed 30-day and 90-day mortality rates stood at 30.85% and 39.99%, respectively. Patients with higher PNI levels exhibited a reduced risk of both 30-day and 90-day mortality. Following adjustment for confounders, PNI showed a significant negative association with 30-day mortality [HR, 0.93 (0.91–0.94), P < 0.001] and 90-day mortality [HR, 0.94 (0.92–0.95), P < 0.001]. RCS analysis revealed a consistent trend of declining all-cause mortality risk corresponding to increasing PNI values. PNI demonstrated predictive value for 30-day and 90-day mortality in CAP patients, with AUCs of 0.71 and 0.68, respectively. Combining PNI with CURB-65 enhanced the predictive value of CURB-65.ConclusionOur investigation identified a significant negative association between the PNI and the risk of mortality in patients with CAP. Additionally, the PNI demonstrated superior predictive value for mortality risk in CAP patients when compared to the CURB-65 scoring system.

Association of dietary anthocyanidins intake with all-cause mortality and cardiovascular diseases mortality in USA adults: a prospective cohort study

Anthocyanins, as a type of polyphenolic compound, have been discovered to offer multiple health benefits to humans, including anti-aging and anti-inflammatory properties. This prospective cohort study aims to examine the relationship of dietary intake of anthocyanin with all-cause mortality and cardiovascular diseases mortality in the US. The aim of this research was to explore the possible correlation between anthocyanin consumption and the mortality rate from all causes as well as from cardiovascular disease. Based on the Public Access NHANES-linked National Death Index files up to December 31, 2019, we identified mortality status and heart disease-specific causes of death. A multivariate Cox regression analysis was employed to evaluate the effects of anthocyanin intake on mortality outcomes, generating hazard ratios and 95% confidence intervals, adjusting for various demographic characteristics, lifestyle factors, and comorbid conditions. Additionally, we utilized Kaplan-Meier survival curves, subgroup analyses. In different scenarios, dietary anthocyanin intake was assessed using restricted cubic spline models. A total of 11,959 participants completed the final cohort, averaging 47.12 years of age (SD ± 0.35). Following adjustments for multiple variables, an inverse relationship was identified between anthocyanin intake in the highest quartile and all causes mortality, yielding a hazard ratio (HR) of 0.68 (95% CI: 0.52–0.89). Similarly, elevated anthocyanin consumption was linked to a reduction in heart disease mortality, with HR of 0.61 (95% CI: 0.38–0.97). Additionally, dose–response curve revealed a consistent decrease in both all-cause and cardiovascular mortality with increasing anthocyanin intake. Further subgroup analyses revealed that elevated intake of anthocyanins was linked to decreased all-cause mortality in White individuals and males. Moreover, high anthocyanin intake was significantly correlated with reduced all-cause mortality irrespective of hypertension or hyperlipidemia status. Our research indicates that an appropriate dietary intake of anthocyanins is associated with a reduction in overall mortality rates. Furthermore, the findings reveal a substantial association between anthocyanin intake and decreased mortality from cardiovascular diseases, suggesting that anthocyanins may effectively lower the risk of cardiovascular-related deaths.

Association of serum uric acid with all-cause and cardiovascular mortality in cardiovascular disease patients

The relationship between serum uric acid (SUA) and mortality in patients with cardiovascular disease (CVD) remains controversial. We aimed to explore the relationship between SUA and all-cause mortality (ACM) and cardiovascular mortality (CVM) in adult patients with CVD. This cohort study included 3977 patients with CVD from the National Health and Nutrition Examination Survey (2005–2018). Death outcomes were determined by linking National Death Index (NDI) records through December 31, 2019. We explored the association of SUA with mortality using weighted Cox proportional hazards regression models, subgroup analysis, Kaplan-Meier survival curves, weighted restricted cubic spline (RCS) models, and weighted threshold effect analysis among patients with CVD. During a median follow-up of 68 months (interquartile range, 34–110 months), 1,360 (34.2%) of the 3,977 patients with cardiovascular disease died, of which 536 (13.5%) died of cardiovascular deaths and 824 (20.7%) died of non-cardiovascular deaths. In a multivariable-adjusted model (Model 3), the risk of ACM (HR 1.38, 95% CI 1.16–1.64) and the risk of CVM (HR 1.39, 95% CI 1.04–1.86) for participants in the SUA Q4 group were significantly higher. In patients with CVD, RCS regression analysis revealed a nonlinear association (p < 0.001 for all nonlinearities) between SUA, ACM, and CVM in the overall population and in men. Subgroup analysis showed a nonlinear association between ACM and CVM with SUA in patients with CVD combined with chronic kidney disease (CKD), with thresholds of 5.49 and 5.64, respectively. Time-dependent ROC curves indicated areas under the curve of 0.61, 0.60, 0.58, and 0.55 for 1-, 3-, 5-, and 10-year survival for ACM and 0.69, 0.61, 0.59, and 0.56 for CVM, respectively. We demonstrate that SUA is an independent prognostic factor for the risk of ACM and CVM in patients with CVD, supporting a U-shaped association between SUA and mortality, with thresholds of 5.49 and 5.64, respectively. In patients with CVD combined with CKD, the association of the ACM and the CVM with SUA remains nonlinear.

Association between neutrophil-percentage-to-albumin ratio (NPAR) and metabolic syndrome risk: insights from a large US population-based study

Metabolic syndrome (MetS) is a cluster of conditions that increase the risk of cardiovascular disease and diabetes. This study aimed to investigate the association between Neutrophil-Percentage-to-Albumin Ratio (NPAR) and MetS in a large, nationally representative US population. We analyzed data from 28,178 participants in the National Health and Nutrition Examination Survey (NHANES) 2005–2018. Logistic regression models were used to evaluate the association between NPAR and MetS. Restricted cubic spline (RCS) models were employed to assess the dose-response relationship. Mediation analyses were conducted to explore potential mediating effects of serum uric acid and triglyceride-glucose (TyG) index. After adjusting for confounders, participants in the highest NPAR quartile had a 14% higher risk of MetS compared to those in the lowest quartile (OR 1.14, 95%CI 1.03–1.27, P = 0.010). RCS models revealed a monotonic increasing trend between NPAR and MetS risk (P for overall association = 0.002). Mediation analyses showed that serum uric acid and TyG index mediated 14.93% and 29.45% of the total effect of NPAR on MetS, respectively. Subgroup analyses indicated that the positive association between NPAR and MetS was more pronounced in Mexican Americans, individuals aged 20–65 years, those with lower income, males, current smokers, and moderate drinkers. Higher NPAR is associated with increased risk of MetS in the US adult population. This association is partially mediated by serum uric acid and TyG index. These findings suggest that NPAR may serve as a novel biomarker for MetS risk assessment and provide insights into potential mechanisms linking inflammation and metabolic disorders.

Association between dietary omega-3 fatty acid intake and all-cause mortality in patients with osteoarthritis: a population-based prospective cohort study

A correlation between omega-3 polyunsaturated fatty acids (omega-3 PUFAs) and osteoarthritis (OA) incidence has been established, but research on the long-term outlook of OA patients remains limited. This study investigates the association between omega-3 PUFA intake and the risk of all-cause and cardiovascular (CV) mortality in the U.S. OA population. A cohort of 3,467 OA patients from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018 was studied. Cox proportional hazards regression models, Kaplan-Meier curves, and subgroup analyses were used to evaluate the relationship between omega-3 PUFA intake and mortality. The dose-response relationship was examined using a restricted cubic spline (RCS) model. Among the 3,467 OA patients, there were 459 all-cause deaths and 175 CV deaths. Omega-3 PUFAs were significantly negatively correlated with all-cause mortality (95% CI: 0.59–0.93, p = 0.011) but not with CV mortality (95% CI: 0.29–1.04, p = 0.056). Higher omega-3 PUFA intake was associated with a 49% decrease in all-cause mortality. Kaplan-Meier curves showed lower all-cause mortality rates in those with higher omega-3 PUFA intake. The inverse correlation was more pronounced among individuals living with a partner. The dose-response analysis indicated a linear negative relationship between omega-3 PUFA intake and all-cause mortality. Increased intake of omega-3 PUFAs is associated with a decreased risk of all-cause mortality in OA patients.