J-shaped Association Research Articles

J-shaped Association between Serum Uric Acid Levels and the Prevalence of a Reduced Kidney Function: A Cross-sectional Study Using Japanese Health Examination Data.

Objective While an association between a reduced kidney function and hyperuricemia has been reported, its association with hypouricemia is not well understood. The present study therefore investigated this association. Methods Using a large Japanese health examination dataset, we performed a multivariable logistic regression analysis to assess the association between serum uric acid (SUA) levels and a reduced kidney function. The covariates included the age, body mass index, alcohol intake, and the presence of hypertension, dyslipidemia, or diabetes. Patients This study included 227,672 patients (104,854 men; 46.1%), and the analyses were performed separately for men and women. The patients were classified into 5 groups: hypouricemia (SUA ≤2.0 mg/dL) (1st) and four other (2nd-5th) groups with SUA levels of ≤2.0, 2.1-5.1, 5.2-5.9, 6.0-6.8, ≥6.9 mg/dL in men and ≤2.0, 2.1-3.7, 3.8-4.4, 4.5-5.1, ≥5.2 mg/dL in women, respectively. Results The characteristics of the study population were as follows: men, age 55.9±14.9 years old, SUA 5.9±1.3 mg/dL, estimated glomerular filtration rate (eGFR) 80.0±17.2 mL/min/1.73 m2, and a reduced kidney function (eGFR <60.0 mL/min/1.73 m2) 9.4%; women, age 57.3±15.0 years old, SUA 4.5±1.1 mg/dL, eGFR 81.2±18.0 mL/min/1.73 m2, and a reduced kidney function 9.4%. Compared with the 2nd group, the other 4 groups groups had a significantly higher prevalence of a reduced kidney function [odds ratio (OR), 2.58; 95% confidence interval (CI), 1.64-4.06 in men; OR, 1.66; 95% CI, 1.16-2.39 in women]. Conclusion The prevalence of a reduced kidney function was high in both men and women in the hypouricemia and high-SUA groups. SUA levels and the prevalence of a reduced kidney function showed a J-shaped association.

Two distinct age-prognosis patterns in patients with esophageal cancer undergoing surgical and radiotherapy treatments: a combined analysis of 3JECROG and SEER databases.

Age is a known prognostic factor for various cancers. However, few studies explored the association between age and prognosis of esophageal cancer (EC) comprehensively, especially from a nonlinear perspective. Retrospective cohort study. Our study aims to explore the possible nonlinear associations between age and prognosis in EC patients receiving curative surgery and radiotherapy, respectively. Cox regression models with restricted cubic splines were used to model the possible nonlinear relationship between age and prognosis in surgical and radiotherapy groups, respectively. Surveillance, Epidemiology, and End Results database was used to validate the age-prognosis patterns found in Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group database. Age-prognosis patterns were further validated by survival comparisons between different age subgroups and in subsequent sensitivity and subgroup analyses. Primary endpoint is overall survival. Secondary endpoints are cancer-specific survival and progression-free survival. A total of 56,457 patients from two large cancer databases were included. Patients receiving surgery and radiotherapy showed two distinct nonlinear age-prognosis patterns. Age showed a U-/J-shaped association with prognosis in the radiotherapy group, with a nadir at approximately 65- to 70-years-old. As for surgical cohort, relative risk for all-cause mortality and cancer-specific mortality increased with age with p for nonlinearity <0.05. The above age-prognosis relationships were validated by sensitivity, subgroup, and comparative survival analyses. Youngest and middle-aged patients showed better survival results compared to that of other age subgroups in surgical and radiotherapy cohorts, respectively [Radiotherapy, youngest/middle: hazard ratio (HR) = 1.06, 95% confidence interval (CI): 1.02-1.10, p = 0.001; Radiotherapy, oldest/middle: HR = 1.21, 95% CI: 1.18-1.24, p < 0.001; Surgical, middle/youngest: HR = 1.19, 95% CI: 1.14-1.25, p < 0.001; surgical, oldest/youngest: HR = 1.85, 95% CI: 1.75-1.97, p < 0.001]. Patients receiving surgery and radiotherapy showed two distinct age-prognosis patterns. Younger and middle-aged patients were associated with better survival in surgical and radiotherapy groups, respectively. Additional studies are warranted to explore the underlying mechanisms and clinical implications of this phenomenon.

Association between air pollution and cerebrospinal fluid alpha-synuclein in urban elders: the CABLE study.

Increasing evidence suggests that air pollution has a significant impact on the development of synucleinopathies, but the potential neurobiological mechanisms are unknown. We aimed to explore the associations of air pollution (including ozone [O3], nitrogen dioxide [NO2], and particulate matter [PM2.5]) with CSF α-syn levels in urban older adults. We included 933 urban participants from the Chinese Alzheimer's Biomarker and LifestylE study. The 5-year average levels of air pollution exposure were estimated in the areas of residence. Multivariate linear regression was conducted to detect the correlation of air pollution with CSF α-syn levels. Subgroup analyses by age, gender, season, and history of coronary heart disease (CHD) were performed. Moreover, restricted cubic spline (RCS) models were applied to explore the potential nonlinear relationships. We found a significant correlation of CSF α-syn level with PM2.5 in urban participants. Specifically, multiple linear regression showed a significant negative association between PM2.5 and CSF α-syn level (p = 0.029), which was more significant in female, midlife, non-CHD, and cold season subgroups. Besides, RCS models showed that O3 had an inverse J-shaped association with CSF α-syn levels in urban participants (p for nonlinearity = 0.040), and the harmful effect possibly appeared when O3 was above 37.9 ppb. Long-term exposure to air pollution was associated with lower CSF α-syn levels, which may offer a new direction for exploring and preventing synucleinopathies.

The association of manganese levels with red cell distribution width: A population-based study.

Experimental and acute exposure studies imply that manganese affects red blood cell production. Nevertheless, the association between environmental exposure and red blood cell distribution width (RDW) has yet to be explored. This research sought to assess the correlation between blood manganese levels and RDW within the general population of the United States. Employing weighted multiple linear regression models, data from the 2011-2018 National Health and Nutrition Examination Survey (NHANES) were utilized to assess the correlation between manganese levels in the blood and RDW. Restricted cubic spline plots and two-piecewise linear regression models were also employed. The analysis included a total of 15882 participants in which we determined an independent positive relationship between blood manganese levels and RDW among participants(β = 0.079, P<0.001). Moreover, we identified a J-shaped association between blood manganese levels and RDW in total participants (inflection point for blood manganese: 7.32 ug/L) and distinct subgroups following adjusted covariates. Women exhibited a more pronounced association, even after controlling for adjusted covariates. We determined a J-shaped relationship between blood manganese levels and RDW with an inflection point at 7.32 ug/L for blood manganese. Nevertheless, fundamental research and large sample prospective studies are needed to determine the extent to which blood manganese levels correlate with RDW.

J-shaped association of serum uric acid concentrations with all-cause mortality in individuals with osteoarthritis: A prospective cohort study

ObjectiveThe purpose of this study was to explore the relationship between serum uric acid (SUA) concentrations and all-cause mortality in individuals with osteoarthritis (OA). MethodsAll participant data were retrieved from the National Health and Nutrition Examination Survey database. A total of 4671 participants (age range: 20 to 85 years old), including 2988 females and 1683 males, were included in this study. The determination of death outcome was based on the National Death Index (up to December 31, 2019). We explored the nonlinear relationship between SUA concentrations and all-cause mortality in OA patients by establishing a Cox proportional risk model and a two-segment Cox proportional risk model and ran an interaction test to identify the high-risk population for all-cause mortality. ResultsDuring 30,645 person-years of follow-up, the number of all-cause deaths for females and males was 736 and 516, respectively. After multivariate adjustment, we found a nonlinear relationship between SUA concentrations and all-cause mortality in both females and males with OA. In addition, we found a J-shaped relationship between SUA concentrations and all-cause mortality. The SUA concentration thresholds for all-cause mortality of females and males were stable at 5.6mg/dl and 6.2mg/dl, respectively. Compared with SUA concentrations below the inflection point, the all-cause mortality risk at higher SUA concentrations in females and males with OA increased by 20% (hazard ratio [HR]: 1.2, 95% confidence interval [CI]: 1.1 to 1.2) and 25% (HR: 1.2, 95% CI: 1.12 to 1.39), respectively. ConclusionsThere is a nonlinear relationship between SUA concentrations and all-cause mortality in the American OA population (J-shaped association). The all-cause mortality thresholds for SUA concentrations in females and males are 5.6mg/dl and 6.2mg/dl, respectively.

Association of cardiometabolic factors and insulin resistance surrogates with mortality in participants from the Korean Genome and Epidemiology Study

BackgroundSimple biochemical and anthropometric measurements such as fasting blood glucose (FBG), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), waist circumference (WC), and body mass index (BMI) are used to formulate insulin resistance (IR) indices. Whether these indices provide new predictive information for mortality remains unknown. This study examined the relationships of biochemical, anthropometric, and IR indices with mortality risk, as well as their predictive performance.MethodsThe data source was the Korean Genome and Epidemiology Study (2004–2020) involving 114,957 participants whose data were linked to death records. The IR indices- triglyceride-glucose index (TyG), TyG-BMI, TyG-WC, visceral adiposity index (VAI), lipid accumulation product (LAP), and metabolic score for insulin resistance (METS-IR) were computed using standard formulae. The associations were examined using restricted cubic splines. The predictive performance was compared using the log-likelihood ratio chi-square test.ResultsBody mass index was U-shaped, HDL-C was reverse J-shaped, and FBG and TG levels were J-shaped associated with all-cause mortality. Results showed U-shaped (TyG), J-shaped (TyG-BMI, VAI, LAP, and METS-IR), and reverse J-shaped (TyG-WC) associations with all-cause mortality. The percentages of new predictive information for all-cause mortality explained by the FBG level, BMI, TyG-BMI, and METIR were 3.34%, 2.33%, 1.47%, and 1.37%, respectively. Other IR indices and biochemical and anthropometric measurements provided < 1.0% of new predictive information. For cardiovascular disease mortality, the FBG, BMI, METIR, TyG-BMI, and HDL-C levels explained 2.57%, 2.12%, 1.59%, 1.30%, and 1.27% of new predictive information respectively. Moreover, the risks of cancer mortality explained by FBG level, VAI, and HDL-C level were 2.05%, 1.49%, and 1.28%, respectively.ConclusionsFasting blood glucose level is a superior predictor of mortality risk and may be used as a simple predictive and preventative factor.

Dysmagnesemia as a predictor of developing diabetic levels of hemoglobin A1c

The aim of this study was to assess the possible association between P-Mg and subsequent high levels of HbA1c. The study involves data from primary health care patients and data from patients treated in hospitals located in the capital region of Denmark. P-Mg and HbA1c levels were analyzed from 121,575 patients in the period 2010–2022. Patients were categorized in a diabetic and non-diabetic group. Out of 121,575 patients, 8,532 were categorized as diabetic. A reverse J-shaped association between P-Mg and HbA1c levels ≥ 48 mmol/mol was observed with nadir at P-Mg of 0.90 mmol/L. The unadjusted hazard ratio (HR) for having a first HbA1c measurement ≥ 48 mmol/mol is 1.54 (95% Cl 1.50; 1.57) per 0.1 mmol/L decrease in P-Mg when P-Mg is lower than 0.90 mmol/L. After adjusting for age and gender, the HR remained significant at 1.45 (95% Cl 1.41; 1.48). For P-Mg levels above 0.90 mmol/L, the unadjusted HR per 0.1 mmol/L increase in P-Mg was 1.04 (95% Cl 1.02; 1.06). After adjusting for age and gender the HR remained significant at 1.06 (95% Cl 1.05; 1.08). In conclusion, this study found that patients with dysmagnesemia have a higher risk of developing diabetes even after adjusting for age and gender. Hyper- or hypomagnesemia in patients could be a biomarker for predicting the risk of developing diabetes.

Causal associations of sleep traits with cancer incidence and mortality

To explore the correlation and causality between multidimensional sleep traits and pan-cancer incidence and mortality among patients with cancer. The multivariable Cox regression, linear and nonlinear Mendelian randomization (MR), and survival curve analyses were conducted to assess the impacts of chronotype, sleep duration, and insomnia symptoms on pan-cancer risk (N = 326,417 from United Kingdom Biobank) and mortality (N = 23,956 from United Kingdom Biobank). In the Cox regression, we observed a linear and J-shaped association of sleep duration with pan-cancer incidence and mortality among cancer patients respectively. In addition, there was a positive association of insomnia with pan-cancer incidence (HR, 1.03, 95% CI: 1.00–1.06, p = 0.035), all-cause mortality (HR, 1.17, 95% CI: 1.06–1.30, p = 0.002) and cancer mortality among cancer patients (HR, 1.25, 95% CI: 1.11–1.41, p &amp;lt; 0.001). In the linear MR, there was supporting evidence of positive associations between long sleep duration and pan-cancer incidence (OR, 1.41, 95% CI: 1.08–1.84, p = 0.012), and there was a positive association between long sleep duration and all-cause mortality in cancer patients (OR, 5.56, 95% CI: 3.15–9.82, p = 3.42E-09). Meanwhile, a strong association between insomnia and all-cause mortality in cancer patients (OR, 1.41, 95% CI: 1.27–1.56, p = 4.96E-11) was observed in the linear MR. These results suggest that long sleep duration and insomnia play important roles in pan-cancer risk and mortality among cancer patients. In addition to short sleep duration and insomnia, our findings highlight the effect of long sleep duration in cancer prevention and prognosis.

Different sedentary behaviors, genetic susceptibility of hypertension, and new-onset hypertension: Mediating effects of body mass index and grip strength.

The association between different sedentary behaviors and hypertension risk remains unclear. We aimed to explore the relationship between different domains of sedentary behaviors and new-onset hypertension, investigate whether genetic susceptibility to hypertension modifies the relationship, and examine the extent to which the relationship is mediated by body mass index (BMI) and grip strength. 212 714 participants without baseline hypertension in the UK Biobank were enrolled. The three major sedentary behaviors (TV-watching, nonoccupational computer use, and driving) were measured using touch screen questionnaires. The primary outcome was new-onset hypertension. During a median follow-up of 11.9 years, 13 983 participants developed hypertension. There was a linear positive association between TV-watching time and new-onset hypertension (p for nonlinearity =0.868). A J-shaped association was found for nonoccupational computer use time and driving time with new-onset hypertension, with an inflection point of 0.5 h/day for both (both p for nonlinearity <0.001). Polygenetic risk scores for hypertension (based on 118 related single-nucleotide polymorphisms) did not significantly modify these associations (all p-interactions >0.05). Furthermore, the detrimental effects of long-term sedentary behaviors on hypertension were mediated by BMI by 21%-30%, and the beneficial effects of limited sitting time (within 0.5 h/day) for driving and nonoccupational computer use were mediated by grip strength by 6-25%. There was a positive association for hands-independence sedentary behavior (TV-watching), and a J-shaped association for hands-dependence sedentary behaviors (nonoccupational computer use and driving) with new-onset hypertension, regardless of genetic risks of hypertension. These relationships were partly mediated by BMI and grip strength.

Association between body mass index and outcomes after autologous breast reconstruction: a nationwide inpatient database study in Japan.

Although autologous reconstruction following breast cancer surgery is common, little is known about the association between preoperative body mass index (BMI) and short-term surgical outcomes. This study investigated the association between BMI and short-term surgical outcomes in autologous breast reconstruction using a nationwide Japanese inpatient database. We retrospectively identified female patients with breast cancer who underwent breast reconstruction using a pedicled flap or free flap from July 2010 to March 2020. Multivariable regression analyses and restricted cubic spline analyses were conducted to investigate the associations between BMI and short-term outcomes with adjustment for demographic and clinical backgrounds. Of the 13,734 eligible patients, 7.1% and 22.2% had a BMI of < 18.5kg/m2 and > 25kg/m2, respectively. Compared with BMI of 18.5-21.9kg/m2, overweight (25.0-29.9kg/m2) and obese (≥ 30.0kg/m2) were significantly associated with higher occurrences of takebacks (odds ratio, 1.74 [95% confidence interval, 1.28-2.38] and 2.89 [1.88-4.43], respectively) and overall complications (1.37 [1.20-1.57] and 1.77 [1.42-2.20], respectively). In the restricted cubic spline analyses, BMI showed J-shaped associations with takebacks, overall complications, local complications, and wound dehiscence. BMI also demonstrated linear associations with postoperative surgical site infection, duration of anesthesia, duration of drainage, length of stay, and hospitalization costs. In autologous breast reconstruction following breast cancer surgery, a higher BMI was associated with takebacks, morbidity, a longer hospital stay, and higher total costs, whereas a lower BMI was associated with fewer surgical site infections, a shorter hospital stay, and lower total costs.

J-shaped association between serum uric acid levels and chronic kidney disease: a cross-sectional study using large health examination data

Abstract Introduction Hyperuricemia has been recognized as a risk for cardiovascular disease based on the results of many observational studies. On the other hand, a J-shaped association has been reported in which people with very low serum uric acid levels also have increased cardiovascular risk. Although renal dysfunction is closely associated with cardiovascular disease, there are no reports on whether serum uric acid levels and renal function show a J-shaped association. Hypouricemia, defined as a serum uric acid level of 2.0 mg/dL or less, is relatively common among Japanese, but the absence of symptoms and low prevalence (0.2% in men and 0.4% in women) have made epidemiological studies difficult. Therefore, we used the large-sized data from Japanese population that underwent health examinations and evaluated the association between serum uric acid levels and chronic kidney disease. Methods Data from 227,672 individuals (104,854 men and 122,818 women) who underwent health examinations between 2001 and 2018 were included. All analyses were performed separately for men and women because of sex differences in serum uric acid levels. Participants were classified according to serum uric acid (SUA) quartiles, with hypouricemia SUA below 2.0 mg/dL being classified as a separate category, resulting in five groups (men: ≤2.0, 2.1-5.1, 5.2-5.9, 6.0-6.8, ≥6.9 mg/dL; women: ≤2.0, 2.1-3.7, 3.8-4.4, 4.5-5.1, ≥5.2 mg/dL) to describe the characteristics. We defined chronic kidney disease (CKD) as an estimated glomerular filtration rate of less than 60 mL/min/1.73 m2 and examined the association between SUA category and CKD by univariable and multivariable logistic regression analysis, which included age, BMI, alcohol intake, presence of hypertension, dyslipidemia, and diabetes as covariates. Results The characteristics of the population were as follows. Men: age 56 ± 15 years, SUA 5.9 ± 1.3 mg/dL, eGFR 80 ± 17 mL/min/1.73 m2, CKD 9.4%; women: age 57 ± 15 years, SUA 4.5 ± 1.1 mg/dL, eGFR 81 ± 18 mL/min/1.73m2, CKD 9.4%. The results of univariable and multivariable analyses of the association between SUA categories and CKD by gender are shown in Table. Compared to the reference group (men, SUA 2.1-5.1 mg/dL; women, SUA 2.1-3.7 mg/dL), CKD risk was increased not only in the higher uric acid groups but also in the hypouricemia group with SUA 2.0 mg/dL or less. Conclusion For both men and women, serum uric acid levels and CKD prevalence showed a J-shaped association. Uric acid is itself an important antioxidant in vivo, and its absence may have induced a worsening of renal function due to increased oxidative stress.

Association of Chinese visceral adiposity index with clinical outcome in patients after endovascular thrombectomy

Background and purposeThe Chinese Visceral Adiposity Index (CVAI) is a reliable indicator of visceral adiposity dysfunction in the Chinese population. We aimed to evaluate the association between CVAI and clinical outcome in Chinese ischemic stroke patients who received endovascular thrombectomy (EVT). MethodsThis study retrospectively included patients with large vessel occlusive stroke receiving EVT treatment in 2 China stroke centers. Baseline CVAI was calculated after admission. Patients with a modified Rankin scale score ≥ 3 at 3 months after ischemic stroke were defined as poor outcome. Binary multivariate logistic regression models were utilized to explore the association between CVAI and the risk of 90-day unfavorable outcome. ResultsA total of 453 patients (mean age, 70.4 ± 12.1 years; 280 male) were included. During the 90-day follow-up, 236 (52.1 %) patients experienced poor outcome. After multivariable adjustment for potential confounders, increasing CVAI was associated with an increased risk of 90-day poor outcome (odds ratios, per-standard deviation increase: 1.521; 95 % confidence interval, 1.127−2.052; P = 0.006). Similar significant results were observed when the CVAI was analyzed as a categorical variable. Furthermore, the multiple-adjusted spline regression model showed an inverted J-shape association between CVAI and risk of unfavorable outcome (P = 0.048 for non-linearity). ConclusionsThis study demonstrated that CVAI is positively correlated with 90-day poor outcome in Chinese ischemic stroke patients after EVT.

Resting heart rate, cognitive function, and inflammation in older adults: a population-based study

BackgroundEmerging evidence has linked elevated resting heart rate (RHR) with poor cognitive function in older adults, but the mechanisms underlying their association are poorly understood.MethodsThis population-based cross-sectional study included 4510 dementia-free participants (age ≥ 65 years; 56.9% females; 38.3% no formal education) in the baseline examination of the Multidomain Interventions to Delay Dementia and Disability in Rural China study. Of these, 1,386 had data on serum proinflammatory cytokines and adhesion molecules. RHR was measured using 12-lead electrocardiograph. We used the Mini-Mental State Examination (MMSE) and a neuropsychological test battery to assess cognitive function. Data were analyzed using the general linear and restricted cubic splines models.ResultsPeople with high RHR were more likely to have cardiometabolic diseases and worse cognitive function (p < 0.05). There was an inverted J-shaped association of RHR with MMSE and attention scores. Having RHR ≥ 80 bpm (vs. 60–69 bpm) was significantly associated with the multivariable-adjusted β coefficients of − 0.58 [95% confidence interval (CI), − 1.00, − 0.16] for MMSE score and − 0.08 (− 0.15, − 0.01) for attention score. In the serum biomarker subsample, RHR was linearly associated with serum interleukin-6 (IL-6) (β coefficient = 0.19; 95%CI 0.14, 0.24), IL-8 (0.08; 0.02, 0.13), IL-10 (0.09; 0.04, 0.15), tumor necrosis factor-α (0.06; 0.01, 0.11), monocyte chemotactic protein-1 (0.09; 0.04, 0.15), intercellular adhesion molecule-1 (0.16; 0.11, 0.22), and vascular cell adhesion molecule-1 (0.11; 0.06, 0.16).ConclusionsThere is an inverted J-shaped association of RHR with attention and global cognition. Poor cognitive function and high RHR may be linked through systemic low-grade inflammation and endothelial injury.

Predictive value of the stress hyperglycemia ratio in dialysis patients with acute coronary syndrome: insights from a multi-center observational study

BackgroundVarious studies have indicated that stress hyperglycemia ratio (SHR) can reflect true acute hyperglycemic status and is associated with poor outcomes in patients with acute coronary syndrome (ACS). However, data on dialysis patients with ACS are limited. The Global Registry of Acute Coronary Events (GRACE) risk score is a well-validated risk prediction tool for ACS patients, yet it underestimates the risk of major events in patients receiving dialysis. This study aimed to evaluate the association between SHR and adverse cardiovascular events in dialysis patients with ACS and explore the potential incremental prognostic value of incorporating SHR into the GRACE risk score.MethodsThis study enrolled 714 dialysis patients with ACS from January 2015 to June 2021 at 30 tertiary medical centers in China. Patients were stratified into three groups based on the tertiles of SHR. The primary outcome was major adverse cardiovascular events (MACE), and the secondary outcomes were all-cause mortality and cardiovascular mortality.ResultsAfter a median follow-up of 20.9 months, 345 (48.3%) MACE and 280 (39.2%) all-cause mortality occurred, comprising 205 cases of cardiovascular death. When the highest SHR tertile was compared to the second SHR tertile, a significantly increased risk of MACE (adjusted hazard ratio, 1.92; 95% CI, 1.48–2.49), all-cause mortality (adjusted hazard ratio, 2.19; 95% CI, 1.64–2.93), and cardiovascular mortality (adjusted hazard ratio, 2.70; 95% CI, 1.90–3.83) was identified in the multivariable Cox regression model. A similar association was observed in both diabetic and nondiabetic patients. Further restricted cubic spline analysis identified a J-shaped association between the SHR and primary and secondary outcomes, with hazard ratios for MACE and mortality significantly increasing when SHR was > 1.08. Furthermore, adding SHR to the GRACE score led to a significant improvement in its predictive accuracy for MACE and mortality, as measured by the C-statistic, net reclassification improvement, and integrated discrimination improvement, especially for those with diabetes.ConclusionsIn dialysis patients with ACS, SHR was independently associated with increased risks of MACE and mortality. Furthermore, SHR may aid in improving the predictive efficiency of the GRACE score, especially for those with diabetes. These results indicated that SHR might be a valuable tool for risk stratification and management of dialysis patients with ACS.

Association of Gestational Free and Total Triiodothyronine With Gestational Hypertension, Preeclampsia, Preterm Birth, and Birth Weight: An Individual Participant Data Meta-analysis.

Triiodothyronine (T3) is the bioactive form of thyroid hormone. In contrast to thyroid-stimulating hormone and free thyroxine, we lack knowledge on the association of gestational T3 with adverse obstetric outcomes. To investigate the associaiton of gestational free or total T3 (FT3 or TT3) with adverse obstetric outcomes. We collected individual participant data from prospective cohort studies on gestational FT3 or TT3, adverse obstetric outcomes (preeclampsia, gestational hypertension, preterm birth and very preterm birth, small for gestational age [SGA], and large for gestational age [LGA]), and potential confounders. We used mixed-effects regression models adjusting for potential confounders. The final study population comprised 33 118 mother-child pairs of which 27 331 had data on FT3 and 16 164 on TT3. There was a U-shaped association of FT3 with preeclampsia (P = .0069) and a J-shaped association with the risk of gestational hypertension (P = .029). Higher TT3 was associated with a higher risk of gestational hypertension (OR per SD of TT3 1.20, 95% CI 1.08 to 1.33; P = .0007). A lower TT3 but not FT3 was associated with a higher risk of very preterm birth (OR 0.72, 95% CI 0.55 to 0.94; P = .018). TT3 but not FT3 was positively associated with birth weight (mean difference per 1 SD increase in TT3 12.8, 95% CI 6.5 to 19.1 g, P < .0001) but there was no association with SGA or LGA. This study provides new insights on the association of gestational FT3 and TT3 with major adverse pregnancy outcomes that form the basis for future studies required to elucidate the effects of thyroid function on pregnancy outcomes. Based on the current study, routine FT3 or TT3 measurements for the assessment of thyroid function during pregnancy do not seem to be of added value in the risk assessment for adverse outcomes.

Detrimental Effects of Alcohol on the Heart: Hypertension and Cardiomyopathy.

Epidemiological evidence suggests a J-shaped association between alcohol consumption and cardiovascular mortality, with higher cardiovascular event rates occurring among abstainers and heavy drinkers compared to moderate consumers. However, this hypothesis has been challenged by more recent studies. Furthermore, ethnicity, gender, type of alcoholic beverage, and pattern of alcohol intake, influence the relationship between alcohol and heart health. We undertook a review of the relavent literature utilizing PubMed. Heavy alcohol consumption causes resistant hypertension, cardiomyopathy, arrhythmias, hemorrhagic strokes, as well as hepatic cirrhosis and pancreatitis. Excessive drinking is the third most preventable cause of death worldwide behind hypertension and smoking. In this review, we discuss the effects of alcohol abuse on hypertension (a major cause of myocardial infarction and stroke) and alcoholic cardiomyopathy. Another article in this Special Issue "Alcohol and Heart Health" discusses the problem with alcohol and arrhythmias sudden cardiac death.

Challenges in undertaking nonlinear Mendelian randomization.

Mendelian randomization (MR) is a widely used method that exploits the unique properties of germline genetic variation to strengthen causal inference in relationships between exposures and outcomes. Nonlinear MR allows estimation of the shape of these relationships. In a previous paper, the authors applied linear and nonlinear MR to estimate the effect of BMI on mortality in UK Biobank, providing evidence for a J-shaped association. However, it is now clear that there are problems with widely used nonlinear MR methods, which draws attention to the likely erroneous nature of the conclusions regarding the shapes of several explored relationships. Here, the authors explore the utility and likely biases of these nonlinear MR methods with the use of a negative control design. Although there remains good evidence for a causal effect of higher BMI increasing the risk of mortality, the pattern of this association across different levels of BMI requires further characterization.

Uncoupling of the center-to-periphery arterial stiffness gradient and pulse pressure amplification in viral pneumonia infection

ObjectivesArterial stiffness is a common manifestation of viral pneumonia infections, including COVID-19. Nevertheless, the relationship between the center-to-periphery arterial stiffness gradient and pulse pressure amplification (PPA) in infectious diseases remains unclear. This study aimed to investigate this relationship utilizing arterial pressure volume index (API) and arterial velocity pulse index (AVI) ratio.MethodsAPI/AVI and PPA were measured in 219 participants with COVID-19 and 374 normal participants. Multiple linear regression was used to assess the association of API/AVI and PPA, and restricted cubic spline was used to investigate the non-linear relationship between API/AVI and PPA. Receiver operating characteristic curve (ROC) analysis was used to evaluate the effects of API/AVI in identifying COVID-19 infection and severe stage.ResultsThere was a significant J-shaped relationship between API/AVI and PPA in COVID-19 group, while a M-shaped relationship was observed in normal group. API/AVI decreased rapidly as PPA decreased until API/AVI decreased slowly at PPA of 1.07, and then API/AVI decreased slowly again at PPA of 0.78. ROC results showed that API/AVI demonstrated excellent accuracy in identifying COVID-19 infection (AUC = 0.781) and a high specificity (84.88%) in identifying severe stage.ConclusionsThere was a J-shaped association between the API/AVI and PPA in viral infected patients, while a M-shaped relationship in the normal participants. API/AVI is better for identifying infected and uninfected patients, with a high specificity in identifying those in severe stages of the disease. The attenuation or reversal of API/AVI may be associated with the loss of PPA coupling.

Early heart rate fluctuation and outcomes in critically ill patients with sepsis: A retrospective cohort study of the MIMIC-IV database

BackgroundHeart rate (HR) abnormalities are common in critically ill patients, but the significance of HR fluctuation in sepsis remains unclear. We aimed to assess the association of HR fluctuation with intensive care unit (ICU) mortality, hospital mortality, and 28-day mortality in patients with sepsis and identify the cutoff value of HR fluctuation associated with the lowest risk of death. MethodsWe conducted a retrospective cohort study using the medical information mart for the intensive care IV database. HR fluctuation, defined as the difference between maximum and minimum HR within the first 24 h of ICU admission, was analyzed for its association with outcomes using restricted cubic spline and multivariable Cox regression models. ResultsAmong 24,419 eligible patients with sepsis, HR fluctuation showed a J-shaped association with ICU mortality, hospital mortality, and 28-day mortality. The high HR fluctuation group (≥ 35 bpm) had a significantly increased risk of ICU mortality ([hazard ratio, 95% confidence interval] 1.12,1.02–1.22, P = 0.013), hospital mortality (1.10,1.02–1.19, P = 0.013), and 28-day mortality (1.11,1.03–1.20, P = 0.007) compared to the control group (HR fluctuation 25–34 bpm). The low HR fluctuation group (< 25 bpm) showed no significant difference in the risk of mortality compared to the control group. ConclusionsOur large-sample study suggests that early high HR fluctuation is indicative of poor prognosis in critically ill patients with sepsis. Early HR fluctuation may serve as a readily available “high-risk alert system” influencing therapeutic decision-making.

High triglyceride-glucose (TyG) index is associated with poor prognosis of heart failure with preserved ejection fraction

BackgroundThe impact of insulin resistance on the prognosis of heart failure with preserved ejection fraction (HFpEF) remains unknown. This study aimed to investigate the association between the triglyceride-glucose (TyG) index, an easily calculated marker of insulin resistance, and the long-term prognosis of HFpEF.MethodsA total of 823 patients with HFpEF were enrolled in the study. The TyG index was determined using the formula ln(fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). The primary endpoint was all-cause death. The secondary endpoints were cardiovascular (CV) death and heart failure (HF) rehospitalization. Restricted cubic spline, multivariate Cox proportional hazard models, and competing risk models were used for analyses.ResultsDuring a median follow-up period of 3.16 years, 147 (17.8%) all-cause deaths, 139 (16.8%) CV deaths, and 222 (27.0%) HF rehospitalizations occurred. Restricted cubic spline analysis revealed a J-shaped association between the TyG index and the mortality and rehospitalization rates. In the multivariate Cox proportional hazard models, compared with those in the lowest TyG index tertile, patients in the highest tertile exhibited the greatest susceptibility to all-cause death (HR 1.53, 95% CI 1.19–1.98) and CV death (HR 1.52, 95% CI 1.19–1.96). In the competing risk model, a significant association between the TyG index and HF rehospitalization was observed (HR 1.31, 95% CI, 1.07–1.61).ConclusionA high TyG index is associated with an increased risk of mortality and rehospitalization in patients with HFpEF. The TyG index may serve as a promising prognostic marker for patients with HFpEF.