Nonlinear U-shaped Association Research Articles

Risk related to gestational weight loss among individuals with obesity: a population-based cohort study.

There is no clear evidence on the risk of gestational weight loss (GWL) for individuals with obesity. Our study aimed to assess the association between GWL and adverse perinatal outcomes among individuals with obesity. This population-based retrospective cohort study examined individuals with prepregnancy BMI ≥ 30 kg/m2 who had a singleton pregnancy, using Ontario, Canada, birth registry data from 2012 to 2020. The primary outcome was a composite of adverse outcomes, including perinatal death and neonatal morbidity. The association between GWL and risk of adverse perinatal outcomes was estimated using generalized estimating equation models and restricted cubic spline regression analysis. Stratified analysis was conducted by obesity class. Of the 157,205 individuals with obesity, 6.1% experienced GWL. Compared with adequate gestational weight gain, GWL was associated with an increased risk of a composite of adverse perinatal outcomes (adjusted risk ratio: 1.31; 95% CI: 1.22-1.39). Similar results were observed in the stratified analysis. Restricted cubic spline regression analysis revealed that average weekly gestational weight changes displayed a nonlinear U-shaped association, with a higher risk of a composite of adverse perinatal outcomes noted in the extremities, particularly toward GWL and excessive weight gain. Our findings suggest that GWL may increase the risk of adverse perinatal outcomes across all obesity classes.

Systemic immune-inflammation index is associated with high risk for prostate cancer among the U.S. elderly: Evidence from NHANES 2001-2010.

The Systemic Immuno-Inflammation Index (SII) is a crucial clinical measure of inflammation, and there is currently no solid evidence linking SII to an increased risk of prostate cancer (PCa). Through the analysis of serum total prostate-specific antigen (tPSA), free prostate-specific antigen (fPSA), and the tPSA/fPSA (fPSA%) ratio, this study sought to investigate the relationship between SII and PCa risk among the U.S. elderly. Elderly male participants were gathered from the NHANES database between 2001 and 2010.SII was calculated by platelet count * neutrophil count/lymphocyte count. High risk individuals for prostate cancer were defined as those with tPSA > 4 ng/ml and fPSA% < 16%. Multivariate logistic regression models, restricted cubic spline curves, and subgroup analyses were used to assess the relationship between SII and PCa risk. This research comprised 2664 people in total, 137 (5.14%) of whom were deemed to be at high risk of developing PCa. Multivariate logistic regression analysis, after controlling for variables, revealed a significant positive correlation between high PCa risk and an increase in SII (p = 0.009). The RCS suggested a turning point at 9.01. Restricted cubic spline curves revealed a non-linear U-shaped association between SII and high PCa risk (p for nonlinear = 0.028). Education level, marital status, PIR, alcohol status, smoking status, rheumatoid arthritis status, and heart problem were not significantly correlated with this positive connection, according to subgroup analyses and interaction tests. The results of this study suggest that inflammation represented by SII is associated with high PCa risk.

Association of baseline sleep duration and sleep quality with seizure recurrence in newly treated patients with epilepsy.

Although sleep duration and sleep quality are considered to be significant factors associated with epilepsy and seizure risk, findings are inconsistent, and their joint association remains uncertain. This study aimed to determine independent and joint associations of these two modifiable sleep features with seizure recurrence risk in newly treated patients with epilepsy (PWE). This is a prospective cohort study of newly treated PWE at a comprehensive epilepsy center in northeast China between June 2020 and December 2023. Self-reported sleep duration and sleep quality were collected at baseline. All patients were followed for 12 months for recurrent seizures. Cox proportional hazard regression models were used to estimate the hazard ratios (HRs) of seizure recurrence. Models fitted with restricted cubic spline were conducted to test for linear and nonlinear shapes of each association. A total of 209 patients were included, and 103 experienced seizure recurrence during follow-up. Baseline short sleep was significantly associated with greater risk of seizure recurrence (adjusted HR = 2.282, 95% confidence interval [CI] = 1.436-3.628, p < .001). Sleep duration (h/day) and recurrent seizure risk showed a significant nonlinear U-shaped association, with a nadir at 8 h/day. Baseline poor sleep quality was significantly associated with greater risk of seizure recurrence (adjusted HR = 1.985, 95% CI = 1.321-2.984, p < .001). Pittsburgh Sleep Quality Index score and seizure recurrence risk exhibited a positive linear association. Participants with a combination of poor quality-short sleep showed the highest risk of seizure recurrence (adjusted HR = 3.13, 95% CI = 1.779-5.507, p < .001) compared to the referent good quality-intermediate sleep group. Baseline sleep duration and sleep quality were independently and jointly associated with risk of seizure recurrence in newly treated PWE. Our results point to an important potential role of baseline sleep duration and sleep quality in shaping seizure risk.

The association between alcohol consumption and pulmonary function: a scoping review.

The health effects of alcohol are well established but the influence on pulmonary function remains debated. Studies indicate that small amounts of alcohol are beneficial and heavy consumption is harmful, suggesting a U-shaped association. Our objective is to determine whether there is an association between alcohol intake and changes in pulmonary function parameters, exploring the potential protective effect of moderate alcohol consumption and the harm caused by heavy drinking. A comprehensive search from PubMed, Embase, Cochrane and CINAHL was carried out, and studies were evaluated using the JBI methodological framework for scoping reviews. Two independent reviewers conducted parallel screening and data extraction. A data extraction form was utilised to organise key themes, with qualitative analysis and visual representation of the results. Among 4427 screened abstracts, 179 underwent full-text review, resulting in 30 eligible studies. Of these, 10 showed a negative effect, nine reported no impact, nine exhibited a positive effect and two indicated a nonlinear U-shaped association between alcohol consumption and pulmonary function parameters. While the U-shaped curve hypothesis remains unconfirmed by the current literature, there are notable associations. Heavy alcohol consumption appears to negatively affect pulmonary function, while low to moderate intake shows a positive influence in included studies. However, the diversity in study quality, the nonstandardised alcohol intake quantification and the confounding role of smoking challenge definitive conclusions. The need for consistent, long-term international studies is evident to further explore this relationship while addressing the complex interplay between alcohol and smoking.

Non-linear associations of circulating total bilirubin concentration with the risk of nonalcoholic fatty liver disease and all-cause mortality

Introduction and ObjectivesAccumulating evidence has supported that mild elevated total bilirubin exerts antioxidant and anti-inflammatory properties in multiple metabolic diseases. We aimed to explore the association of circulating total bilirubin concentration with non-alcoholic fatty liver disease (NAFLD) risk and all-cause mortality and examine the potential nonlinear relationships between them. Material and MethodsWe used nationally representative data from the National Health and Nutrition Examination Survey (NHANES). NAFLD was assessed using the fatty liver index (FLI) and United States fatty liver index (USFLI), respectively. ResultsA total of 35 912 and 17 329 participants were included in FLI-NAFLD (case with NAFLD was diagnosed by FLI) and USFLI-NAFLD (case with NAFLD was diagnosed by USFLI) groups, respectively. The mean age of total population was 46.25 years, and 48.51% were male. Compared to participants with lowest quintile of total bilirubin concentration, those with highest quintile had lower risk of NAFLD in both FLI-NAFLD (OR: 0.48, 95% CI: 0.40, 0.59) and USFLI-NAFLD (OR: 0.55, 95% CI: 0.43, 0.70) groups. Compared to participants with lowest quintile of total bilirubin concentration, the association between total bilirubin concentration and all-cause mortality was not significant among those with highest quintile of total bilirubin concentration (HR: 0.89, 95% CI: 0.66, 1.20). The restricted spline curves showed the nonlinear U-shaped association of total bilirubin concentration with NAFLD risk and all-cause mortality. The segmented linear regression analysis showed negative associations between total bilirubin concentration and risk of NAFLD in both FLI-NAFLD (OR: 0.94, 95% CI: 0.93, 0.95) and USFLI-NAFLD (OR: 0.95, 95% CI: 0.93, 0.96) groups when total bilirubin concentration was below the turning point (FLI-NAFLD: 18.81 μmol/L; USFLI-NAFLD: 15.39 μmol/L) and these associations were not significant when total bilirubin concentration was higher than the turning point. Furthermore, all-cause mortality decreased (OR: 0.97, 95%CI: 0.95, 1.00) with increased total bilirubin concentration up to the turning point (11.97 μmol/L), and then all-cause mortality increased with increasing total bilirubin concentration (OR: 1.03, 95%CI: 1.02, 1.04). ConclusionsWe found that higher circulating total bilirubin concentration within the physiological range was associated with decreased risk of NAFLD and all-cause mortality among NAFLD patients.

The associations between dietary flavonoid intake and the prevalence of diabetes mellitus: Data from the National Health and Nutrition Examination Survey 2007-2010 and 2017-2018.

Diabetes mellitus (DM) is a prominent health concern worldwide, leading to the high incidence of disability and mortality and bringing in heavy healthcare and social burden. Plant-based diets are reported associated with a reduction of DM risk. Plant-based diets are rich in flavonoids, which possess properties such as scavenging free radicals and exerting both anti-inflammatory and antioxidant effects. However, whether dietary flavonoids are associated with the prevalence of DM remains controversial. The potential reasons for contradictory epidemiological outcomes on the association between dietary flavonoids and DM prevalence have not been determined. To address these limitations, we employed data from 22,481 participants in the National Health and Nutrition Examination Survey to explore the association between the intake of flavonoids and DM prevalence by weighted Logistic regression and weighted restricted cubic splines. We found that the prevalence of DM was inversely associated with the intake of total flavonoids in the second quartile [Odds Ratio (OR) 0.78 95% confidence interval (CI) (0.63, 0.97), p = 0.028], in the third quartile [0.76 (0.60, 0.97), p = 0.031], and in the fourth quartile [0.80 (0.65, 0.97), p = 0.027]. However, the p for trend was not significant [0.94 (0.88, 1.01), p = 0.096]. Moreover, the association between DM prevalence and the intake of total flavonoids was significantly influenced by race (p for interaction = 0.006). In Mexican Americans, there was a significant positive association between DM prevalence and total flavonoid intake within the third quartile [1.04 (1.02, 1.07), p = 0.003]. Total flavan-3-ol and subtotal catechin intake exhibited a non-linear U-shaped association with DM prevalence (p for non-linearity < 0.0001 and p for non-linearity < 0.0001, respectively). Compared to the first quartile of corresponding intakes, consumption within the third quartile of subtotal catechins [0.70 (0.55, 0.89), p = 0.005] and total flavan-3-ols [0.65 (0.50, 0.84), p = 0.002] was associated with a lower prevalence of DM. Taken together, our study may provide preliminary research evidence for personalized improvement of dietary habits to reduce the prevalence of diabetes.

Very high HDL-C (high-density lipoprotein cholesterol) is associated with increased cardiovascular risk in patients with NSTEMI (non-ST-segment elevation myocardial infarction) undergoing PCI (percutaneous coronary intervention)

BackgroundStudies in populations with or without cardiovascular disease have shown that very high HDL-C levels are associated with an increased risk of cardiovascular events. However, the exact relationship between HDL-C levels and long-term prognosis remains unknown in patients with myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI).MethodsThis was a post hoc secondary analysis of long-term follow-up results in patients undergoing PCI open-label, observational cohort study. Patients with MI who had undergone PCI were enrolled. Restricted cubic spline (RCS) analysis and logistic regression analysis were performed to assess the relationship between HDL-C levels and the risk of cardiovascular events.ResultsA total of 1934 patients with MI undergoing PCI were enrolled in our analysis and our population was divided in 3 groups according to the HDL-C plasma levels: HDL-C < 40 mg/dL (low HDL-C); HDL-C between 40 and 80 mg/ dL (medium HDL-C); and HDL-C > 80 mg/dL (high HDL-C). RCS analysis showed a nonlinear U-shaped association between HDL-C levels and major adverse cardiac and cerebrovascular events (MACCE) in patients with NSTEMI with adjusted variables. After adjusting for potential confounders, the follow-up analysis indicated that high risk group had elevated occurrence of MACCE than low risk group (HDL-C 35 and 55 mg/dL) (OR:1.645, P = 0.006).ConclusionsOur analysis demonstrated that there is a U-shaped association between HDL-C and MACCE in patients with NSTEMI undergoing PCI.

Decreased free fatty acid levels associated with adverse clinical outcomes in coronary artery disease patients with type 2 diabetes: findings from the PRACTICE study.

Increased free fatty acid (FFA) levels are known to be strongly associated with mortality in coronary artery disease (CAD) patients and the development of type 2 diabetes (T2DM). However, few studies have been large enough to accurately examine the relationship between FFA levels and mortality in CAD patients with T2DM. From December 2016 to October 2021, 10 395 CAD patients enrolled in PRACTICE, a prospective cohort study in China, were divided into four groups according to baseline FFA concentration. We investigated mortality, including all-cause mortality (ACM) and cardiac mortality (CM), as the primary endpoint. The secondary endpoints were major adverse cardiovascular and cerebrovascular events (MACCEs) and major adverse cardiovascular events (MACEs). The median follow-up time was 24 months. In the total cohort, there were 222 ACMs, 164 CMs, 718 MACEs, and 803 MACCEs recorded. After controlling for baseline variables, the association between FFA levels and the risk of mortality presented a non-linear U-shaped curve, with the lowest risk at 310 µmol/L. We also identified a non-linear U-shaped relationship for ischaemic events (MACE or MACCE) with the lowest risk at 500 µmol/L. Subgroup analysis showed that a U-shaped relationship between FFA and mortality or ischaemic events was observed only in individuals with T2DM but not in non-diabetic CAD patients. A non-linear U-shaped association was identified between baseline FFA levels and mortality or ischaemic events in CAD patients with T2DM.

U-shaped association of serum uric acid with cardiovascular disease risk scores and the modifying role of sex among Chinese adults

Background and aimsSerum uric acid (SUA) is involved in the development of cardiovascular disease (CVD). However, information on the dose-response relationship between SUA and CVD is limited in the Chinese population. This study aimed to investigate the potential nonlinear dose-response association of SUA with CVD risk in a Chinese population and to explore the effect of sex on these associations. Methods and resultsCross-sectional data, from 6252 Chinese adults aged 30–74 years who participated in the China Health and Nutrition Survey 2009, were stratified by SUA deciles. The 10-year risk of CVD was determined using the Framingham risk score. A restricted cubic spline (RCS) was incorporated into the logistic models to assess the nonlinear relationship between SUA and CVD. Among the participants, 65%, 20%, and 15% had low, moderate, and high 10-year CVD risks, respectively. Compared with the reference SUA strata of 225 to <249 μmol/L, CVD risk was significantly increased at SUA ≥294 μmol/L, with adjusted ORs ranging from 2.39 (1.33–4.33) to 4.25 (2.37–7.65). An increasingly higher nonsignificant CVD risk was found at SUA <225 μmol/L and showed a nonlinear U-shaped association. In the fitted RCS model, an approximate U-shaped association between SUA and CVD risk scores was found in women, but this significant nonlinear relationship was not found in men. ConclusionThis study showed that both lower and higher SUA levels were associated with a higher 10-year CVD risk among Chinese adults, forming a U-shaped relationship, and this pattern was particularly pronounced for women.

164 HIGH HDL CHOLESTEROL INCREASES CARDIOVASCULAR RISK IN HYPERTENSIVE PATIENTS

Abstract Background Emerging evidence suggests that elevated circulating levels of HDL-C (high-density lipoprotein cholesterol) could be linked to an increased mortality risk. However, to the best of our knowledge, the relationship between HDL-C and specific cardiovascular events has never been investigated in patients with hypertension. Methods To fill this knowledge gap, we analyzed the relationship between HDL-C levels and cardiovascular events in hypertensive patients within the Campania Salute Network in Southern Italy. Results We studied 11 987 patients with hypertension, who were followed for 25 534 person-years. Our population was divided in 3 groups according to the HDL-C plasma levels: HDL-C&amp;lt;40 mg/dL (low HDL-C); HDL-C between 40 and 80 mg/dL (medium HDL-C); and HDL-C&amp;gt;80 mg/dL (high HDL-C). At the follow-up analysis, adjusting for potential confounders, we observed a total of 245 cardiovascular events with a significantly increased risk of cardiovascular events in the low HDL-C group and in the high HDL-C arm compared with the medium HDL-C group. The spline analysis revealed a nonlinear U-shaped association between HDL-C levels and cardiovascular outcomes (Figure 1). Interestingly, the increased cardiovascular risk associated with high HDL-C was not confirmed in female patients. Conclusions Our data demonstrate that there is a U-shaped association between HDL-C and the risk of cardiovascular events in male patients with hypertension.

High HDL (High-Density Lipoprotein) Cholesterol Increases Cardiovascular Risk in Hypertensive Patients.

Emerging evidence suggests that elevated circulating levels of HDL-C (high-density lipoprotein cholesterol) could be linked to an increased mortality risk. However, to the best of our knowledge, the relationship between HDL-C and specific cardiovascular events has never been investigated in patients with hypertension. To fill this knowledge gap, we analyzed the relationship between HDL-C levels and cardiovascular events in hypertensive patients within the Campania Salute Network in Southern Italy. We studied 11 987 patients with hypertension, who were followed for 25 534 person-years. Our population was divided in 3 groups according to the HDL-C plasma levels: HDL-C<40 mg/dL (low HDL-C); HDL-C between 40 and 80 mg/dL (medium HDL-C); and HDL-C>80 mg/dL (high HDL-C). At the follow-up analysis, adjusting for potential confounders, we observed a total of 245 cardiovascular events with a significantly increased risk of cardiovascular events in the low HDL-C group and in the high HDL-C arm compared with the medium HDL-C group. The spline analysis revealed a nonlinear U-shaped association between HDL-C levels and cardiovascular outcomes. Interestingly, the increased cardiovascular risk associated with high HDL-C was not confirmed in female patients. Our data demonstrate that there is a U-shaped association between HDL-C and the risk of cardiovascular events in male patients with hypertension.

Can regional trade integration facilitate renewable energy transition to ensure energy sustainability in South Asia?

This paper primarily aimed to assess the impacts of regional trade integration on the prospects of undergoing renewable energy transition in selected South Asian economies between 1992 and 2015. The overall results from the econometric analyses, controlling for the cross-sectional dependency and slope heterogeneity issues, highlight the importance of promoting intra-regional trade among the South Asian economies to boost the renewable energy consumption shares and renewable electricity output shares in the total final energy consumption and aggregate electricity output figures, respectively. Besides, the non-linearity of the nexuses between intra-regional trade shares and renewable energy consumption shares and between intra-regional trade shares and renewable electricity output shares are also ascertained. The threshold intra-regional trade shares concerning the renewable energy consumption and renewable electricity output shares are predicted at 20.53% and 17.50%, respectively. However, the predicted threholds are significantly higher than the current average intra-regional trade share in South Asia. Moreover, the panel causality analysis reveals unidirectional causal relationships stemming from intra-regional trade shares to renewable energy consumption and renewable electricity output shares. Besides, greater FDI inflows are found to reduce the overall use of renewable energy while higher levels of economic growth and CO2 emissions are found to catalyze renewable energy use in South Asia. Furthermore, the results also implicate a non-linear U-shaped association between positive crude oil price shocks and renewable energy consumption and renewable electricity output shares. Therefore, these findings impose critically important policy implications for liberalizing the intra-regional trade barriers, reducing dirty foreign direct investment inflows, expediting economic growth, reducing fossil fuel dependency and abating carbon dioxide emissions to facilitate renewable energy transition in South Asia.

Nut Consumption and Renal Function Among Women at High Risk (FS10-05-19)

ObjectivesWomen with gestational diabetes (GDM) are at increased risk for renal complications later in life. Nut intake has been associated with reduced cardiometabolic risk, but few studies have examined its association with renal function. We examined associations of nut intake and renal function among women with prior GDM. MethodsWe studied 330 women from the Danish National Birth Cohort (1996–2002) with a GDM pregnancy who participated in a clinical exam 9 to 16 years after the index pregnancy as part of the Diabetes & Women’s Health Study (2012–2014) and were free of major chronic diseases at follow-up. Habitual past year intake of nine types of nuts was ascertained at follow-up using a food frequency questionnaire. Total nut intake was classified as none (<1 serving/mo), monthly (2–3 servings/mo), weekly (1–6 servings/wk), and daily (>1 serving/d). Estimated glomerular filtration rate (eGFR) via CKD-EPI equation and urine albumin-to-creatinine ratio (UACR) were calculated based on serum creatinine (mg/dL) and urine albumin (mg/L), and creatinine (mg/dL) measurements respectively. We estimated % differences with 95% confidence intervals (CI) in these outcomes by nut intake adjusted for current body mass index, age, physical activity, energy intake, and dietary variables. We explored possible non-linear relations using restricted cubic splines. ResultsA significant non-linear U-shaped association was detected between total nut consumption and UACR (P = 0.001) with lowest UACR levels among women with weekly consumption. Compared to women with weekly intake (n = 222), adjusted UACR levels were 86% [95% CI: 15%, 200%] and 23% [−1%, 54%] higher among women with no or monthly nut intake, respectively, while UACR levels were 118% [22%, 286%] higher among women with daily intake. Compared to weekly consumers, adjusted eGFR levels were 9% [0%, 19%] higher among daily consumers. ConclusionsModerate nut consumption may be beneficial to kidney health among women with prior GDM. Funding SourcesIntramural Research Program of the NICHD, March of Dimes Birth Defects Foundation, Innovation Fund Denmark, Health Foundation, Heart Foundation, EU, Danish Diabetes Academy supported by Novo Nordisk Foundation, and NIH Building Interdisciplinary Research Careers in Women’s Health Program.

Pre- and post-diagnosis body mass index and heart failure mortality: a dose-response meta-analysis of observational studies reveals greater risk of being underweight than being overweight.

To investigate the dose-response association between pre- and post-diagnosis body mass index (BMI) and heart failure (HF) mortality. Eligible observational studies were searched in databases, up to November 2017. We used random-effects generalized least squares spline models for trend estimation to derive pooled BMI unit-HF mortality relationship. Sixteen cohort studies (six pre-diagnosis and 10 post-diagnosis BMI) were included, comprising a total of 258,379 subjects with 13,201 deaths due to HF. A nonlinear U-shaped association was found between pre-diagnosis BMI and the risk of HF mortality, with a greater risk from being at the lowest extreme, rather than being at the top category. The combined hazard ratio of HF mortality among the highest compared to the lowest category of pre-diagnosis BMI was 1.24 (0.65-2.37, I2 =90.7%). No significant nonlinear association was found between post-diagnosis BMI and HF mortality as well as when comparing the highest to the lowest category of BMI. This meta-analysis showed those with both high and low pre-diagnosis BMI had higher risk for HF mortality, with a greater risk from being too underweight, rather than being obese. No significant association was found between post-diagnosis BMI and the risk of HF mortality. Further detailed investigations are needed to accurately examine the potential mechanistic links between BMI and health outcomes.

Vitamin D supplementation during pregnancy and the risk of wheezing in offspring: a systematic review and dose-response meta-analysis

Background: In the past few years, growing evidence supports a preventive role of vitamin D supplementation during pregnancy for wheezing or asthma in offspring. However, the optimal dose of vitamin D intake is unclear. We conducted a meta-analysis to examine the linear and nonlinear dose-response pattern of vitamin D intake during pregnancy and asthma or wheezing in offspring. Questions/purposes: The purpose of this study was to answer the following question: Which dose of vitamin D is more effective in preventing wheezing in offspring? Method: We identified relevant studies by searching PubMed, EMBASE and CENTRAL up to December 2017 and by hand-searching reference lists. Meta-analysis and subgroup analysis were performed. Fixed or random effects model linear trends analyses were conducted based on the heterogeneity test. Then, if the data did not show linear trends, we considered a nonlinear trend analysis instead. Results: A total of 6068 participants were included in the study. Our analysis showed an inverse relationship between the intake of vitamin D during pregnancy and the occurrence of wheezing in offspring (pooled OR = 0.68, 95% CI = 0.55–0.83, I2 = 24%, Z statistic = 3.64, p < 0.01). We found a nonlinear U-shaped association between vitamin D supplementation during pregnancy and asthma or wheezing in offspring, with the lowest risk at approximately 800 IU/d. Publication bias was shown in a funnel plot without Egger’s test. Conclusions: Vitamin D intake during pregnancy is inversely related to wheezing or asthma in offspring. Furthermore, the trend analysis indicates that offspring may benefit from approximately 800 IU/d vitamin D intake during pregnancy.

Multivariable analysis of the association between electrolyte disturbances and mortality in cats.

ObjectivesElectrolyte disorders have been individually associated with mortality in small populations of cats with specific conditions, but the associations and interactions between electrolyte disturbances and outcome have not been evaluated in a large, heterogeneous population. It was hypothesized that abnormalities of sodium, chloride, potassium and calcium concentrations would be independently and proportionately associated with death from natural causes and with all-cause mortality in cats.MethodsAn electronic database containing 7064 electrolyte profiles was constructed to assess the association between disorders of sodium, potassium, corrected-chloride and ionized calcium concentrations with non-survival by multivariable modelling. A second database containing 2388 records was used to validate the models constructed from the first database.ResultsAll four electrolytes assessed had non-linear U-shaped associations with case fatality rates, wherein concentrations clustered around the reference interval had the lowest case fatality rates, while progressively abnormal concentrations were associated with proportionately increased risk of non-survival (area under the receiver operator characteristic curve [AUROC] 0.689) or death (AUROC 0.750).Conclusions and relevanceMultivariable modelling suggested that these electrolyte disturbances were associated with non-survival and with death from natural causes independent of each other. The present study suggests that measurement of electrolyte concentrations is an important component of the assessment of cats in emergency rooms or intensive care units. Future studies should focus on confirming these associations in a prospective manner accounting for disease severity.

Electrolyte Disturbances Are Associated with Non-Survival in Dogs-A Multivariable Analysis.

Electrolyte disorders have been individually associated with mortality in small populations of dogs and cats with specific conditions, but the associations and interactions between electrolyte disturbances and outcome have not been evaluated in a large, heterogeneous population. It was hypothesized that abnormalities of sodium, chloride, potassium, and calcium concentrations would be independently and proportionately associated with death from natural causes and with all-cause mortality in dogs. An electronic database containing 33,117 electrolyte profiles was constructed to retrospectively assess the association between disorders of sodium, potassium, corrected chloride, and ionized calcium concentrations with non-survival and with death excluding euthanasia by multivariable modeling. A second database containing 11,249 records was used to validate the models constructed from the first database. All four electrolytes assessed had non-linear U-shaped associations with case fatality rates, wherein concentrations clustered around the reference interval had the lowest case fatality rates, while progressively abnormal concentrations were associated with proportionately increased risk of non-survival (AUROC 0.624) or death (AUROC 0.678). Multivariable modeling suggested that these electrolyte disturbances were associated with non-survival and with death from natural causes independent of each other. This study suggests that measurement of electrolyte concentrations is an important component of the assessment of dogs in emergency rooms or intensive care units. Future studies should focus on confirming these associations in a prospective manner accounting for disease severity.

White Blood Cell Subtypes Are Associated with a Greater Long-Term Risk of Death after Acute Myocardial Infarction.

We evaluated the association between white blood cell counts and long-term mortality rates in 2,129 patients (mean age, 65.3 ± 13.5 yr; 69% men) who had survived acute myocardial infarction. We obtained white blood cell counts and differential counts of white blood cell subtypes within the first 72 hours of hospital admission. The primary outcome was all-cause death at 1, 5, and 10 years after acute myocardial infarction. In regard to death in the long term, we found significant negative linear associations (lymphocytes), positive linear associations (neutrophils and the neutrophil-to-lymphocyte ratio), and nonlinear U-shaped associations (basophils, eosinophils, monocytes, and total white blood cell count). After multivariate adjustment for the Soroka Acute Myocardial Infarction risk score, lymphocytes (strongest association), neutrophil-to-lymphocyte ratio, and eosinophils were independently associated with death for up to 10 years after hospital discharge. The independent associations weakened over time. We conclude that lymphocyte count, neutrophil-to-lymphocyte ratio, and eosinophil count are independently and incrementally associated with death in the long term after acute myocardial infarction.

U-shaped association between telomere length and esophageal squamous cell carcinoma risk: a case-control study in Chinese population.

Telomeres play a critical role in biological ageing by maintaining chromosomal integrity and preventing chromosome ends fusion. Epidemiological studies have suggested that inter-individual differences of telomere length could affect predisposition to multiple cancers, but evidence regarding esophageal squamous cell carcinoma (ESCC) was still uncertain. Several telomere length-related single nucleotide polymorphisms (TLSNPs) in Caucasians have been reported in genome-wide association studies. However, the effects of telomere length and TL-SNPs on ESCC development are unclear. Therefore, we conducted a case-control study (1045 ESCC cases and 1433 controls) to evaluate the associations between telomere length, TL-SNPs, and ESCC risk in Chinese population. As a result, ESCC cases showed overall shorter relative telomere length (RTL) (median: 1.34) than controls (median: 1.50, P < 0.001). More interestingly, an evident nonlinear U-shaped association was observed between RTL and ESCC risk (P < 0.001), with odds ratios (95% confidence interval) equal to 2.40 (1.84-3.14), 1.36 (1.03-1.79), 1.01 (0.76-1.35), and 1.37 (1.03-1.82) for individuals in the 1st (the shortest), 2nd, 3rd, and 5th (the longest) quintile, respectively, compared with those in the 4th quintile as reference group. No significant associations were observed between the eight reported TL-SNPs and ESCC susceptibility. These findings suggest that either short or extremely long telomeres may be risk factors for ESCC in the Chinese population.

Low LDL-C and High HDL-C Levels Are Associated with Elevated Serum Transaminases amongst Adults in the United States: A Cross-sectional Study

BackgroundDyslipidemia, typically recognized as high serum triglyceride, high low-density lipoprotein cholesterol (LDL-C) or low high-density lipoprotein cholesterol (HDL-C) levels, are associated with nonalcoholic fatty liver disease (NAFLD). However, low LDL-C levels could result from defects in lipoprotein metabolism or impaired liver synthetic function, and may serve as ab initio markers for unrecognized liver diseases. Whether such relationships exist in the general population has not been investigated. We hypothesized that despite common conception that low LDL-C is desirable, it might be associated with elevated liver enzymes due to metabolic liver diseases.Methods and FindingsWe examined the associations between alanine aminotransferase (ALT), aspartate aminotransferase (AST) and major components of serum lipid profiles in a nationally representative sample of 23,073 individuals, who had no chronic viral hepatitis and were not taking lipid-lowering medications, from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010. ALT and AST exhibited non-linear U-shaped associations with LDL-C and HDL-C, but not with triglyceride. After adjusting for potential confounders, individuals with LDL-C less than 40 and 41–70 mg/dL were associated with 4.2 (95% CI 1.5–11.7, p = 0.007) and 1.6 (95% CI 1.1–2.5, p = 0.03) times higher odds of abnormal liver enzymes respectively, when compared with those with LDL-C values 71–100 mg/dL (reference group). Surprisingly, those with HDL-C levels above 100 mg/dL was associated with 3.2 (95% CI 2.1–5.0, p<0.001) times higher odds of abnormal liver enzymes, compared with HDL-C values of 61–80 mg/dL.ConclusionsBoth low LDL-C and high HDL-C, often viewed as desirable, were associated with significantly higher odds of elevated transaminases in the general U.S. adult population. Our findings underscore an underestimated biological link between lipoprotein metabolism and liver diseases, and raise a potential need for liver evaluation among over 10 million people with particularly low LDL-C or high HDL-C in the United States.