Cox Proportional Hazards Regression Models Research Articles

Bereavement and type 1 diabetes in childhood: a register-based cohort study in Sweden.

The potential impact of childhood bereavement-a severe psychological stressor-on childhood type 1 diabetes development remains unclear. Here, we aimed to bridge this knowledge gap and assess whether bereavement characteristics influenced any impact. We conducted a register-based cohort study encompassing 3,598,159 children born in Sweden between 1987 and 2020. Childhood bereavement was defined as the death of a biological mother, father or sibling. Diagnosis of type1 diabetes in childhood (<18 years) was ascertained through the National Patient Register. We applied a Cox proportional hazards regression model to investigate the impact of childhood bereavement on type1 diabetes, while adjusting for potential confounders (including parental type1 diabetes status, country of birth and demographic characteristics). During follow-up, 86,226 children (2.4%) lost a family member, and 18,817 children (0.52%) were diagnosed with type 1 diabetes (median age at onset 9.1 years). We did not detect any overall association between childhood bereavement and type 1 diabetes (adjusted HR 1.04; 95% CI 0.93, 1.17). We found no influence of age at loss, cause of death, familial relationship to the deceased, and time since loss. In this large population-based Swedish study, we observed no evidence supporting a link between childhood bereavement and type 1 diabetes.

Efficacy, safety, and biomarker analysis of first-line immune checkpoint inhibitors with chemotherapy versus chemotherapy for advanced gastric cancer: a multicenter, retrospective cohort study

BackgroundRecent phase III randomized controlled trials have demonstrated that first-line immune checkpoint inhibitors (ICIs) improve prognosis in advanced HER-2-negative gastric cancer patients with programmed death ligand 1 (PD-L1) combined positive score (CPS) higher than 5. However, these findings are not confirmed in real-world settings, and the benefits in PD-L1 CPS < 5 patients remain controversial.MethodsIn this multicenter, retrospective cohort study, data from across thirteen medical centers were analyzed by inverse probability of treatment weighting for matching, alongside univariate and multivariate COX proportional hazard regression models. Genomic and transcriptomic analyses were conducted to identify efficacy prognostic models and resistance mechanisms.ResultsThis study included 573 patients with advanced gastric cancer, 265 treated with chemotherapy and 308 with ICIs plus chemotherapy. In the overall cohort and HER-2-negative patients, the combination therapy significantly improved progression-free survival and overall survival, without marked increases in severe adverse events. Notably, patients with PD-L1 CPS 1–4 showed significant overall survival prolongation and a trend towards improved progression-free survival with combination therapy. Patients with unknown PD-L1 status also benefitted from ICIs. SMARCA4 and BRCA2 mutations were more frequent in patients with responses, while CCNE1 and ZFHX3 alternation, alongside high “ABC transporters” signatures, were more common in non-responsive patients. A novel risk model, PGFIC, outperformed traditional biomarkers in predicting treatment outcomes.ConclusionsAdding ICIs to first-line treatment significantly prolongs survival in overall patients and in those with PD-L1 CPS 1–4 or unknown. This study also provides valuable insights into prognostic markers and resistance mechanisms, potentially guiding immunotherapy strategies.

Association of altitude with all-cause and cardiovascular mortality among patients with hypertension: a cohort study in Southwest China

BackgroundAvailable evidence falls short in assessing the risk of long-term outcomes among individuals with hypertension residing at various altitudes. We aimed to investigate the association between residential altitude and the risk of all-cause and cardiovascular disease (CVD) mortality among hypertensive patients.MethodsThis cohort study encompassed 67,275 hypertensive patients aged ≥35 years who participated in China’s Basic Public Health Service Program in 2018. Participants were categorized into four groups based on their residence altitude: <500 m, 500-1,499 m, 1,500-2,500 m, and > 2,500 m. The associations between residential altitude and the risks of all-cause and CVD mortality were analyzed using Cox proportional hazards regression models. The dose-response relationship was performed by the restricted cubic spline with multivariable adjusted models.ResultsAmong the 67,275 hypertensive patients included in the study (mean age of 63.9 years, with 45.3% male), 8,768 deaths were recorded, of which 5,666 were attributed to CVD. Following multivariate adjustment, when compared to the group residing at altitudes < 500 m, the groups living at altitudes of 500-1,499 m, 1500-2,500 m, and > 2,500 m exhibited significantly risks of all-cause mortality [HR = 1.45 (95% CI: 1.36–1.54), 1.35 (95% CI: 1.28–1.43), and 1.41 (95% CI: 1.28–1.54), respectively] and CVD mortality [HR = 1.47 (95% CI: 1.35–1.58), 1.42 (95% CI: 1.33–1.52), and 1.46 (95% CI: 1.31–1.62), respectively]. The restricted cubic spline curves revealed a nonlinear relationship between residential altitude and all-cause and CVD mortality. The risk of mortality was higher among participants with poorly controlled blood pressure, aged 65 years and above, and living in rural areas.ConclusionsThis study demonstrated a significant association between long-term residential high-altitude exposure and increased risks of all-cause and CVD mortality among hypertension patients. The implications of the findings call for a prioritization of public health resource allocation and early intervention efforts, especially for those living at high altitudes and in low-income areas where hypertension is prevalent.

New prognostic index for neoadjuvant chemotherapy outcome in patients with advanced high-grade serous ovarian cancer

BackgroundA validated prognostic index for the outcome of patients with advanced high-grade serous ovarian cancer (HGSOC) undergoing neoadjuvant chemotherapy (NACT) remains elusive. To address this need, we developed an ovarian neoadjuvant chemotherapy prognostic index (ONCPI) to improve predictive accuracy.MethodsWe encompassed an analysis of the clinicopathological characteristics of patients with advanced HGSOC who were administered platinum-based NACT. Blood inflammatory composite markers were calculated and converted into binary values using optimal cutoffs. Omental hematoxylin and eosin (H&E) stained slides were selected for the assessment of chemotherapy response score (CRS), which served as a measure of NACT efficacy. Logistic regression analysis and Cox proportional hazards regression model were utilized to construct a prognostic index.ResultsMultivariate logistic analysis showed that both CRS and neutrophil-to-lymphocyte ratio (NLR) independently influenced the response to platinum-based chemotherapy. Meanwhile, Kaplan–Meier and Cox regression analysis revealed that CRS score was significantly correlated with progression-free survival (PFS) and overall survival (OS), and patients with high NLR showed poor OS. We further developed an ovarian neoadjuvant chemotherapy prognostic index (ONCPI) based on the CRS and NLR. The area under the curve (AUC) value of ONCPI was 0.771 (P < 0.001, 95% CI: 0.656–0.887) for the prediction of platinum resistance. This AUC value surpasses that of the individual NLR and CRS, which were 0.670 (P = 0.018, 95% CI: 0.547–0.793) and 0.714 (P = 0.003, 95% CI: 0.590–0.839), respectively. Moreover, survival analysis suggested that patients with ONCPI of 0 and 1 were significantly associated with improved PFS and OS.ConclusionsThe ONCPI emerges as a significant prognostic marker for predicting NACT outcome in advanced HGSOC patients and holds promise for integration into clinical practice and risk-stratified trial design.

Mortality after high-risk myocardial infarction over the last 20 years: Insights from the VALIANT and PARADISE-MI trials.

The temporal changes in clinical profiles and outcomes of high-risk myocardial infarction survivors enrolled in clinical trials are poorly described. This study compares mortality rates, baseline characteristics, and the prognostic impact of therapies among participants of the VALIANT and PARADISE-MI trials. Exclusively VALIANT participants who matched the inclusion criteria of the PARADISE-MI trial were included in the analysis. Risk of death was compared between trials using Cox regression models. The impact of baseline characteristics and therapies on mortality was estimated by the magnitude reduction of β coefficients using Cox proportional hazards regression models. A total of 9617 VALIANT participants matched the inclusion criteria of the PARADISE-MI trial (n = 5661). All-cause mortality in PARADISE-MI was less than half that in VALIANT (4.2 vs 9.9 per 100 patient-years; hazard ratio [HR] 0.41, 95% confidence interval [CI] 0.37-0.46). This difference was reduced after adjustment for clinical variables but remained substantial (adjusted HR 0.68, 95% CI 0.58-0.80). The most important mediator of this reduction related to covariate adjustment was the use of percutaneous coronary intervention (PCI), accounting for almost half of the attenuation observed. Similar results were found for cardiovascular (CV) death, while no between-trial significant differences were found in the non-CV mortality risk. Cardiovascular mortality following high-risk myocardial infarction has significantly declined over time, while the risk for non-CV death has remained unchanged. This improvement is partially attributable to advancements in CV care, particularly the use of PCI. Continued efforts to implement guidelines and standardize the quality of care are needed to sustain this positive trend.

Fracture incidence in women: the impact of reproductive characteristics

BackgroundAlthough endogenous estrogen exposure, influenced by reproductive factors (RFs), is negatively associated with fracture risk, there is limited and conflicting information on the association between these factors and the incidence of fractures. This study aimed to evaluate the association between RFs and fracture incidence (FXI) separately.MethodsThis longitudinal study commenced in 1999 and concluded in 2021. It is performed on women without previous fractures and adjusted for confounders. RFs, including age at menarche, parity, abortion, duration of breastfeeding (BF), hormonal contraceptive use, and age at menopause, were exposure variables. The incidence of fractures was the primary outcome. A Cox proportional hazards regression model was used to estimate the associations between RFs and FXI outcomes.ResultsThe median (interquartile range) of follow-up time was 15.0 (12.1–17.0) years. A total of 19.9% (1324/6653)of the women were menopausal at baseline, and 13% (865/6653) of the remaining participants reached menopause at the end of follow-up. At the end of the follow-up, 222 (3.3%) participants had fractures. The mean age of participants at the initiation of the study and last follow-up were 35.8 (15.5) and 50.0 (15.3) years, respectively. After adjusting for potential confounders, the HR of FXI increased by 10% per one extra delivery (HR: 1.10,95% CI: (1.03, 1.18); p = 0.01), and by 12% per one-year increase in age at menarche (HR: 1.12, 95% CI: (1.02, 1.23); p = 0.02). The HR of FXI decreased by 3% per month extra exclusive BF (HR: 0.97,95% CI: (0.94, 0.99); p = 0.04).ConclusionsThe results elucidate that a longer duration of exclusive BF has a protective effect on FXI. In contrast, increasing age at menarche and the number of parities increase the risk of FXI.

Ramelteon exposure and survival of critically Ill sepsis patients: a retrospective study from MIMIC-IV

BackgroundThe effect of ramelteon, a melatonin receptor agonist, on survival in septic patients remains unknown. The purpose of this retrospective cohort study was to explore the relationship between ramelteon exposure and survival outcomes in septic patients.MethodsData from septic patients admitted to the intensive care unit (ICU) were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, with patients categorized into ramelteon exposure and non-exposure groups based on the use of ramelteon. The primary outcome was 30-day mortality, and secondary outcomes included 90-day mortality, in-hospital mortality, length of ICU stay, and hospital stay. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were employed to address confounding variables. Kaplan–Meier (K-M) analysis and Cox proportional hazards regression models for stepwise regression were utilized to assess the impact of ramelteon exposure on survival.ResultsThis study included 22,152 unexposed patients and 2,708 exposed patients, resulting in 2,607 matched pairs after PSM. Following PSM, ramelteon exposure was associated with significantly lower in-hospital mortality (11.6% vs.19.7%, p < 0.001), 30-day mortality (13.4% vs. 23.2%, p < 0.001), and 90-day mortality (22.1% vs. 30%, p < 0.001).K-M curves demonstrated a significant difference in 30-day and 90-day mortality between the two groups (P < 0.001), irrespective of PSM application. Both PSM (hazard ratio [HR] = 0.53, 95% confidence intervals [CIs] 0.47–0.61, p < 0.001) and IPTW models (HR = 0.59, 95% CI 0.50–0.70, p < 0.001) indicated a significant positive effect of ramelteon usage on 30-day mortality among septic patients compared to the non-exposure group.ConclusionsThis exploratory, retrospective study suggests an association between ramelteon exposure and reduced 30-day and 90-day mortality in septic patients compared with the non-exposure group. Considering the limitations of the retrospective design and the potential for unmeasured confounding, well-designed prospective studies and randomized controlled trials will be needed to confirm these findings.

Association between Home-Base Primary Care and Post-Discharge Outcomes among Older Adults in Korea

This study aimed to evaluate the association between home-based primary care (HBPC) and postdischarge outcomes in Korean older adults. HBPC was a service that provided medical care by visiting the homes of older adults with limited mobility. In this study, data from the National Health Insurance Service (NHIS) were used, and groups with and without HBPC services were matched 1:1 through propensity score matching. Cox proportional hazards model and linear regression analysis were performed to compare the HBPC group with the control group. Overall, 1580 older adults in Korea who used HBPC services after discharge from hospital and 1580 propensity score-matched older adults who did not use HBPC services were included. For 30-day readmission, hospitalizations, and admission to long-term care hospitals or facilities after discharge, this study used a Cox proportional hazards regression model. And linear regression analysis was performed considering that the dependent variable was a continuous variable to examine the average total medical costs after discharge from acute hospital. Older adults who used HBPC services exhibited a lower risk of readmission for the same disease (risk reduction of 0.66, 95% CI 0.50, 0.87) and hospitalization (risk reduction of 0.58, 95% CI 0.46, 0.73) compared with those who did not use HBPC services. The annual average total medical cost was $4764 lower for older adults who used HBPC services than for those who did not (95% CI -6469.49,-3057.52). There was no significant difference in the risk of admission to long-term care hospitals or facilities. HBPC services had a positive effect on reducing 30-day readmission due to the same disease, hospitalization, and annual average total medical costs among older adults after discharge.

Effect of Adjuvant Chemotherapy Cycles on Patients with Node-Negative Gastric Cancer Following Neoadjuvant Chemotherapy: Multicenter Cohort Study.

Research investigating the potential impact of postoperative adjuvant chemotherapy cycles on patients with lymph node-negative gastric cancer following neoadjuvant chemotherapy is currently sparse. This study aims to explore the effect of adjuvant chemotherapy cycles on the prognosis of this specific patient group. We analyzed clinicopathological data from patients at four institutions between 2010 and 2020. Independent risk factors associated with 3-year overall survival (OS) were identified using a Cox proportional hazards regression model. We enrolled a total of 219 patients in this study. Patients with lymph node-negative gastric cancer who received neoadjuvant chemotherapy and underwent at least five cycles of adjuvant chemotherapy (AC ≥ 5) after surgery had a significantly higher 3-year overall survival rate of 86.8% compared with those who received fewer than five cycles (AC < 5) with a survival rate of 68.1% (P = 0.016). Multivariate analysis identified several factors, including AC ≥ 5 (HR 0.367, 95% CI 0.166-0.815, P = 0.014), ypT stage ≥ 2 (HR 2.779, 95% CI 1.199-6.438, P = 0.017), and poorly differentiated tumors (HR 2.501, 95% CI 1.385-4.517, P = 0.002), as independently associated with 3-year OS in this patient group. Stratified analysis further revealed that AC ≥ 5 significantly enhanced long-term outcomes in patients with ypT stage ≥2 (3-year OS, 82.5% vs. 62.6%, P = 0.025) and in those with poorly differentiated tumors (3-year OS, 82.6% vs. 53.3%, P = 0.021). Patients who have lymph node-negative gastric cancer following neoadjuvant chemotherapy, with either ypT stage ≥ 2 or poorly differentiated gastric cancers, may experience benefits from undergoing at least five cycles of adjuvant chemotherapy.

Cigarette smoking, alcohol consumption and the risk of thyroid cancer in Japan: The JPHC Study.

Although cigarette smoking and alcohol consumption are established causes of cancer, most cohort studies and meta-analyses have reported inverse associations with thyroid cancer (TC) risk. However, epidemiological evidence for this possibility is limited in Asia, where TC histologic type differs from the West. Here, we examined the association between cigarette smoking or alcohol consumption and risk of TC in Japanese. We analyzed data from 101,849 Japanese of the Japan Public Health Center-based Prospective Study (JPHC Study). Cigarette smoking and alcohol consumption were assessed at baseline using a self-administered questionnaire. Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs). During a mean 18.7 years of follow-up, we identified 232 incident cases of TC. The multivariable adjusted HRs (95% CIs) in current cigarette smoking with ≥20 pack-years compared with never smoking were 0.65 (0.39-1.06) and 0.45 (0.23-0.88) combined for both sexes. After detailed adjustment for cigarette smoking, compared with no current alcohol consumption, HRs (95% CIs) were 0.90 (0.61-1.33) for any current consumption and 0.81 (0.33-1.97) for ≥300 g ethanol/week consumption combined for both sexes. We observed an inverse association between cigarette smoking and TC in Japan. While an inverse association between alcohol consumption and TC is suggested, the CI was wide and included 1. Cigarette smoking was shown to be potentially inversely associated with TC in Japanese, providing insight into risk factors in Asians. Further studies with larger sample sizes are needed to verify these findings.

Associations of plasma acylcarnitine and bile acid levels with incidence of coronary heart disease in Chinese adults

Objective: To explore the associations of plasma acylcarnitine and bile acid levels with the risk of incident coronary heart disease (CHD) in Chinese adults. Methods: The baseline survey of China Kadoorie Biobank (CKB) took place in 10 areas across China during 2004-2008, and the first resurvey took place from July to October 2008, with collection of data via questionnaire, physical examination and blood samples. The current study was based on 2 159 individuals with targeted mass spectrometry metabolomic measurements from the first resurvey of CKB. The associations of acylcarnitines and bile acids with incident CHD were assessed using Cox proportional hazards regression models. Unweighted metabolites scores were constructed to assess the overall effect of acylcarnitines and bile acids on incident CHD. The impact of metabolites on the performance of CHD prediction model was evaluated with the receiver operating characteristic (ROC) area under the curve (AUC). Follow-up for CHD incidence was censored on December 31, 2018. Results: The mean age of the participants was (53.1±9.8) years and 754 were males (34.9%). During (10.5±0.1) years of follow-up, 140 cases of CHD were recorded. Four metabolites including acylcarnitines C3-OH, C5:1, C5:1-DC, and deoxycholic acid (DCA) showed associations with CHD incidence and the HR (95%CI) were 1.474 (1.230-1.767), 0.761 (0.637-0.909), 0.773 (0.650-0.918), and 1.309 (1.113-1.539), respectively [false discovery rate (FDR)0.05]. All metabolite scores, including short-chain, medium-chain, long-chain acylcarnitines, primary and secondary bile acids scores were associated with the risk of CHD (FDR0.05). Compared to the traditional models, the addition of DCA or 4 key metabolites increased the AUC of the predictive model from 0.803 (0.761-0.845) to 0.812 (0.772-0.852) and 0.817 (0.778-0.857), respectively (all P0.05). Conclusions: Acylcarnitine and bile acid levels are associated with the risk of CHD, and DCA or 4 key metabolites can improve the predictive ability for CHD incidence.

Associations between self-reported sleep duration and incident cardiovascular diseases in a nationwide prospective cohort study of Chinese middle-aged and older adults

PurposeThis study explores the correlation between sleep duration and cardiovascular disease (CVD) among middle-aged and older adults in China. Furthermore, we aim to investigate the association between sleep duration and incident CVD in this population, while assessing potential variations across different age and gender subgroups.MethodsUtilizing data from the nationwide prospective survey of the China Health and Retirement Longitudinal Study (CHARLS) conducted in 2011, 2013, 2015, and 2018, involving 17,596 participants aged 45 years and above, we employed Cox proportional hazards regression models. These models were used to examine the impact of baseline sleep duration on CVD, considering age (middle-aged/elderly) and gender (male/female) groups.ResultsOver the 8-year follow-up, 2,359 CVD events were recorded. Compared to individuals sleeping 6–8 h per day, a short sleep duration (≤6 h/day) was significantly associated with an increased risk of CVD (HR: 1.17, 95% CI: 1.03–1.33). Subgroup analysis revealed a more pronounced relationship in participants aged ≥60 years, where both short sleep duration (≤6 h/day) (HR: 1.17, 95% CI: 1.02–1.35) and long sleep duration (&amp;gt;8 h/day) (HR: 1.20, 95% CI: 1.02–1.41) were significantly associated with an elevated risk of CVD. Specifically, among female participants, short sleep durations (≤6 h/day) was significantly associated with CVD (HR: 1.24, 95% CI: 1.05–1.47).ConclusionShort sleep durations can serve as predictive factors for CVD in China's population aged 45 and above, particularly among elderly female participants. Our study underscores the importance of considering sleep health as a critical aspect when formulating strategies for enhancing CVD prevention.

Insomnia symptoms and the risk of all-cause mortality among stroke survivors

BackgroundInsomnia is more frequently reported in stroke survivors but its independent role in mortality in stroke survivors is unknown. The purpose of this study was to investigate the association of insomnia symptoms with all-cause mortality among stroke survivors.MethodsThe Health and Retirement Study, a survey of Americans older than 50 years and their spouses of any age from 2002 to 2018 was used. Only participants with a history of stroke were included. The exposure variable of interest was insomnia symptoms including difficulty initiating sleep, difficulty maintaining sleep, waking up too early, and nonrestorative sleep. The outcome was all-cause mortality. Cox proportional hazards regression models were employed to investigate the association between insomnia symptoms and all-cause mortality.ResultsA total of 3,501 stroke survivors were included of which 55% were females. Over a mean follow-up of 6 years, 1,782 deaths occurred. Difficulty initiating sleep (HR = 1.87, 95% CI: 1.07, 3.25) and difficulty maintaining sleep (1.89, 95% CI: 1.09, 3.29) were associated with all-cause mortality only among male stroke survivors younger than 65 years old while nonrestorative sleep (HR = 1.31, 95% CI: 1.05, 1.62) was associated with all-cause mortality only among male stroke survivors aged 65 years and older. Furthermore, male stroke survivors younger than 65 years of age and older than 65 with insomnia symptom scores ranging from 5 to 8 (mean = 6.2) had a higher but statistically nonsignificant risk of all-cause mortality (HR = 1.56, 95% CI: 0.81, 3.01 and HR = 1.08 95% CI: 0.85, 1.38, respectively) compared to their counterparts without insomnia symptoms. There was no association between insomnia symptoms and all-cause mortality among female stroke survivors.ConclusionInsomnia symptoms were associated with an increased risk of death especially in male stroke survivors younger than 65 years of age. Future studies should explore the benefit of insomnia symptom management in stroke survivors.

Association of potassium disorders with the mode of death and etiology in patients with chronic heart failure: the INCOR-HF study

Observational studies suggest a U-shaped association between serum potassium (K⁺) levels and mortality in patients with chronic heart failure (CHF). However, the mode of death in patients with HF and K⁺ disorders remains speculative. To investigate the association between potassium disorders and the mode of death in patients with CHF. A retrospective cohort of 10,378 CHF outpatients was analyzed over an average of 3.28 ± 2.5 years. Kaplan-Meier method, Cox proportional hazards regression models, Poisson regression models adjusting for confounders, and e-value determination (e' > 1.6) were used to observe associations between potassium disorders and outcomes. Chagas etiology (p < 0.01) and triple HF therapy (p < 0.01) were associated with hyperkalemia. Atrial fibrillation was associated with hypokalemia (p < 0.01). Chronic kidney disease (CKD) (p < 0.01) and diabetes (p = 0.03) were associated with both. Hypertension was inversely related to hyperkalemia (p < 0.01); age was inversely related to hypokalemia. Associations with mortality were significant for Chagas (p < 0.01, e-value 2.16), stroke (p < 0.01, e-value 1.85), hypokalemia (p = 0.02, e-value 1.94), severe hyperkalemia (p = 0.08, e-value 1.93), and CKD (p < 0.01, e-value > 1.63). Decompensated HF or cardiogenic shock was the cause of death in 54% of patients with normokalemia, 67.8% with hypokalemia, 44.9% with mild hyperkalemia, 57.8% with moderate hyperkalemia, and 69% with severe hyperkalemia. Most patients with hypokalemia and severe hyperkalemia died from decompensated HF (p = 0.007). Data suggest hypokalemia and severe hyperkalemia, along with Chagas and CKD, are associated with death. Unexpectedly, progressive HF was the most frequent mode of death rather than arrhythmias. Further studies are needed to confirm these findings and explore the underlying mechanisms.

Triiodothyronine Is Associated with Incidence/Resolution of Steatotic Liver Disease: Longitudinal Study in Euthyroid Korean.

The positive relationship between triiodothyronine (T3) and steatotic liver disease (SLD) demonstrated only in crosssectional study. We aimed to evaluated whether total T3 (TT3) is associated with the development/resolution of SLD in longitudinal design. This retrospective, longitudinal, population-based cohort study included 1,665 South Korean euthyroid adults with ≥4 thyroid function test. We explored the impact of mean TT3 during follow-up on development/resolution of either SLD (diagnosed by ultrasound) or modified metabolic dysfunction-associated steatotic liver disease (MASLD) using Cox proportional hazards regression models. During about median 5 years follow-up, 807/1,216 (66.3%) participants among participants without SLD at baseline developed SLD, and 253/318 (79.5%) participants among participants with SLD at baseline SLD resolved fatty liver. Mean TT3 rather than thyroid stimulating hormone or mean free thyroxine was significantly related with development (adjusted hazard ratio [HR], 1.01; 95% confidence interval [CI], 1.00 to 1.02; P=0.002) and resolution (adjusted HR, 0.97; 95% CI, 0.96 to 0.99; P=0.005) of SLD. Compared with low mean TT3 group, high mean TT3 group was positively associated with development of SLD (adjusted HR,1.20; 95% CI, 1.05 to 1.38; P=0.008) and inversely associated with resolution of SLD (adjusted HR, 0.66; 95% CI, 0.51 to 0.85; P=0.001). The statistical significance remained for development (adjusted HR, 1.29; 95% CI, 1.10 to 1.51; P=0.001) and resolution (adjusted HR, 0.71; 95% CI, 0.54 to 0.94; P=0.018) of modified MASLD. In Korean euthyroid adults, TT3 level was associated with development and resolution of either SLD or modified MASLD.

Non-linear dose-response relationship between the visceral adiposity index and diabetes in adults with normoglycemia: a cohort study.

Previous studies have identified a positive link between the visceral adiposity index (VAI) and diabetes in specific populations. Our investigation focused on examining this association in normoglycemic adults in Japan. A cohort study of NAGALA (NAfld in the Gifu Area Longitudinal Analysis) was undertaken from 2004 to 2015 in Japan. The link between VAI and diabetes was evaluated using multivariate Cox proportional hazards regression and restricted cubic spline (RCS) regression models. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive value of the VAI for incident diabetes. Our study included 15,452 participants, with 8,418 men (54.48%) and 7,034 women (45.52%). The average age was 43.71 ± 8.90, and 373 participants (2.41%) developed diabetes. VAI was positively related to diabetes (HR=1.13, 95% CI 1.08-1.18). The inflection point of the non-linear relationship was observed at a VAI value of 4.67. For the VAI values up to 4.67, one unit increase in the VAI related to a 24% increase in new-onset diabetes (HR=1.24, 95% CI 1.12-1.37, p<0.0001). Subgroup analysis detected a more robust relationship in women (HR=1.40, 95% CI 1.14-1.70, p=0.0010). ROC analysis indicated that VAI, with an AUC of 0.7479 (95% CI: 0.7237-0.7720), had good predictive power. Our cohort study validated the positive and non-linear relationship between the VAI and diabetes in normoglycemic adults in Japan. The relevance was more marked in women than in men. For those with a VAI below 4.67, a further reduction in the VAI could potentially lead to a significant decrease in diabetes risk.

The Influence of Residential Segregation, Urbanicity, and Population Density on Hepatocellular Carcinoma Incidence among a Low Socioeconomic Population.

Hepatocellular carcinoma (HCC) is becoming a leading cause of cancer-related mortality in the United States, with notable disparities observed among racial and ethnic minorities. The objective of this study is to examine the association between social determinants of health (SDoH) and HCC incidence by race (White and Black individuals) using data from the Southern Community Cohort Study (SCCS). The SCCS is a prospective cohort study with participants recruited from 2002 to 2009. Incident HCC cases were identified during follow-up. Exposure measures, including residential segregation, social vulnerability, population density, rurality, and poverty, were assessed at baseline. Cox proportional hazards regression models were used to estimate hazard ratios associated with SDoH by race with the adjustment of known HCC risk factors. Among the 79,367 eligible participants, there were 491 incident HCC diagnosed, 378 of which were in Black individuals. In Black individuals, increased population density and urban residency were associated with an increased risk of HCC, even after adjusting for potential confounders (HR=1.49, 95%CI 1.04-2.13, HR= 1.70, 95%CI 1.20-2.41, respectively). In White individuals living in the least segregated areas (HR=2.83, 95%CI 1.39-5.78) and in urban settings (HR=2.34, 95%CI 1.17-4.65) had an increased HCC risk, while population density was not associated with risk. We found that individuals residing in urban populations had an increased risk of HCC. These findings underscore the complex interplay of SDoH factors and geographic influences on HCC disparities. Our findings highlight the need for targeted interventions and further research to address HCC health inequities.

Impact of Chinese visceral adiposity index on all-cause mortality risk in community-dwelling older adults: a prospective cohort study

BackgroundsWhether excess visceral fat tissue increases the risk of death in older individuals remains controversial.AimsTo investigate the association between the Chinese Visceral Adiposity Index (CVAI) and all-cause mortality risk in older Chinese individuals.MethodsThis cohort study utilized data of individuals aged ≥ 65 years in 2014 to 2018 wave from the Chinese Longitudinal Healthy Longevity Survey database. Older individuals in the 2014 wave were included and followed up in 2018. CVAI was calculated based on age, body size, and blood lipid parameters, with higher values indicating increased visceral fat. Survival status was determined from official death certificates, local primary healthcare providers, or the family members of participants. Kaplan-Meier survival curve and log-rank test were employed to analyze cumulative mortality risk through CVAI tertiles (tertile 1: CVAI index < 97.34; tertile 2: 97.43 ≤ CVAI index < 132.21; and tertile 3: CVAI index ≥ 132.21). A Cox proportional hazards regression model was used to assess the relationship between the CVAI groups and all-cause mortality risk. Additionally, a sensitivity analysis was performed by excluding participants who died within the first year of follow-up. A subgroup analysis was performed based on age and sex, and a restricted cubic spline plot was created to analyze the dose-response relationship between CVAI and mortality risk.ResultsA total of 1414 individuals were included, and the mean age of the participants was 84.6 (standard deviation: 10.9) years, of which 46.4% were women and 32.8% were died during a median follow-up time of 36.4 months. In the multivariable adjusted Cox regression model, we observed a significantly lower risk of mortality in the CVAI tertile 2 and 3 groups than in the tertile 1 group. The hazard ratios (HR) of the tertile 2 and 3 groups were 0.68 (95% CI, approximately 0.52–0.89) and 0.63 (95% CI, approximately 0.48–0.82), respectively. Subgroup analysis revealed that the protective effect of higher CVAI levels on mortality was more pronounced in participants aged 65–79 years and in women.ConclusionOur study established a linear relationship between CVAI and mortality risk among community-dwelling older adults, with higher CVAI levels associated with a lower risk of all-cause mortality. These findings highlight the potential importance of visceral adiposity in predicting mortality risk in community-dwelling older adults.

2-Fold More Cardiovascular Disease Events Decades Before Type 2 Diabetes Diagnosis: A Nationwide Registry Study

BackgroundThe risk of cardiovascular disease (CVD) is increased in individuals with type 2 diabetes mellitus (T2DM), but it remains uncertain how long an elevated CVD occurrence precedes diabetes diagnosis. ObjectivesThe aim of this study was to investigate CVD occurrence 30 years before, and 5 years after, T2DM diagnosis compared with matched comparisons. MethodsThis combined case-control and cohort study included all individuals diagnosed with T2DM in Denmark between 2010 and 2015, as well as general population comparisons matched by age and sex. CVD was defined as myocardial infarction or ischemic stroke. Conditional logistic regression was used to compute ORs for CVD prevalence in the 30-year period before T2DM diagnosis. Cox proportional hazards regression models were used to compute HRs for 5-year CVD incidence after T2DM diagnosis. ResultsThe study included 127,092 individuals with T2DM and 381,023 matched comparisons. In the 30-year period before T2DM diagnosis, 14,179 (11.2%) T2DM individuals and 17,871 (4.7%) comparisons experienced CVD. CVD prevalence was higher in those with T2DM than the comparisons in the entire period before T2DM diagnosis, with ORs ranging from 2.18 (95% CI: 1.91-2.48) in the earliest period (25-30 years before diagnosis) to 2.96 (95% CI: 2.85-3.08) in the latest period (<5 years before diagnosis). After T2DM diagnosis, 5-year CVD incidence was similarly increased in T2DM individuals vs comparisons (HR: 2.20; 95% CI: 2.12-2.27). ConclusionsIndividuals with T2DM had 2-fold more CVD events than matched comparisons starting 3 decades before T2DM diagnosis. This indicates that comprehensive preventive strategies may be initiated much earlier in individuals at risk of T2DM.

Construction and Validation of Cardiovascular Disease Prediction Model for Dietary Macronutrients-Data from the China Health and Nutrition Survey.

There are currently many studies on predictive models for cardiovascular disease (CVD) that do not use dietary macronutrients for prediction. This study aims to provide a non-invasive model incorporating dietary information to predict the risk of CVD in adults. The data for this study were obtained from the China Health and Nutrition Survey (CHNS) spanning the years 2004 to 2015. The dataset was divided into training and validation sets at ratio of 7:3. Variables were screened by LASSO, and the Cox proportional hazards regression model was used to construct the 10-year risk prediction model of CVD. The model's performance was assessed using the concordance index (C-index), receiver operating characteristic (ROC) curve, calibration plots, and decision curve analysis (DCA) for discrimination, calibration, and clinical utility. This study included 5,186 individuals, with males accounting for 48.1% and a mean age of 46.39 ± 13.74 years, and females accounting for 51.9% and a mean age of 47.36 ± 13.29 years. The incidence density was 10.84/1000 person years. The model ultimately incorporates 11 non-invasive predictive factors, including dietary-related, demographic indicators, lifestyle behaviors, and disease history. Performance measures for this model were significant (AUC = 0.808 [(95%CI: 0.778-0.837], C-index = 0.797 [0.765-0.829]). After applying the model to internal validation cohorts, the AUC and C-index were 0.799 (0.749-0.838), and 0.788 (0.737-0.838), respectively. The calibration and DCA curves showed that the non-invasive model has relatively high stability, with a good net return. We developed a simple and rapid non-invasive model predictive of CVD for the next 10 years among Chinese adults.