Association of dietary inflammatory index with helicobacter pylori infection and mortality among US population.

BACKGROUND: Limited research has been conducted on the potential relationship between the dietary inflammation index (DII) and mortality, particularly in individuals with Helicobacter pylori (H. pylori) infection. This study aimed to investigate the association between the DII and H. pylori infection, as well as their respective impacts on all-cause mortality in a cohort of individuals with or without H. pylori infection. METHODS: Data from the 1999-2018 National Health and Nutrition Examination Survey (NHANES) were utilized for this study, with a final of 4370 participants included. Both univariable and multivariable-adjusted logistic regression analyses were employed to explore the relationship between H. pylori infection and pertinent covariates. Cox regression analysis, as well as restricted regression cubic spline analysis, were utilized to assess the association between DII and all-cause mortality among individuals with or without H. pylori infection. RESULTS: The findings demonstrated a positive correlation between DII scores and H. pylori infection, even after adjusting for potential confounding factors. Moreover, higher DII scores were significantly associated with an elevated risk of mortality exclusively in individuals with H. pylori infection, while no such association was observed in the uninfected population. Additional analysis using restricted cubic spline modeling revealed a positive linear relationship between DII scores as a continuous variable and the adjusted risk of all-cause mortality specifically in H. pylori-infected patients. CONCLUSION: The results of this study indicated that DII was positively correlated with an increased risk of H. pylori infection and was associated with a heightened risk of all-cause mortality solely in individuals with H. pylori infection. Consequently, DII might serve as a useful tool for risk stratification in the H. pylori-infected population among U.S. adults. Further research is warranted to elucidate the underlying mechanisms and potential clinical implications of these findings.

The impact of the stress hyperglycemia ratio on mortality and rehospitalization rate in patients with acute decompensated heart failure and diabetes.

BACKGROUND: The relationship between stress hyperglycemia and long-term prognosis in acute decompensated heart failure (ADHF) patients is unknown. This study investigated the associations of stress hyperglycemia with mortality and rehospitalization rates among ADHF patients with diabetes. METHODS: We consecutively enrolled 1904 ADHF patients. Among them, 780 were with diabetes. Stress hyperglycemia was estimated using the stress hyperglycemia ratio (SHR), which was calculated by the following formula: SHR = admission blood glucose/[(28.7 × HbA1c%) - 46.7]. All diabetic ADHF subjects were divided into quintiles according to the SHR. The primary endpoint was all-cause death at the 3-year follow-up. The secondary endpoints were cardiovascular (CV) death and heart failure (HF) rehospitalization at the 3-year follow-up. A Cox proportional hazards model and restricted cubic spline analysis were used to elucidate the relationship between the SHR and the endpoints in diabetic ADHF patients. Further analyses were performed to examine the relationships between SHR and the outcomes in heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). RESULTS: A total of 169 all-cause deaths were recorded during a median follow-up of 3.24 years. Restricted cubic spline analysis suggested a U-shaped association between the SHR and the mortality and rehospitalization rates. Kaplan-Meier survival analysis showed the lowest mortality in the 2nd quintile (P = 0.0028). Patients categorized in the highest range (5th quintile) of SHR, compared to those in the 2nd quintile, exhibited the greatest susceptibility to all-cause death (with a hazard ratio [HR] of 2.76 and a 95% confidence interval [CI] of 1.63-4.68), CV death (HR 2.81 [95% CI 1.66-4.75]) and the highest rate of HF rehospitalization (HR 1.54 [95% CI 1.03-2.32]). Similarly, patients in the lowest range (1st quintile) of SHR also exhibited significantly increased risks of all-cause death (HR 2.33, 95% CI 1.35-4.02) and CV death (HR 2.32, 95% CI 1.35-4.00). Further analyses indicated that the U-shape association between the SHR and mortality remained significant in both HFpEF and HFrEF patients. CONCLUSION: Both elevated and reduced SHRs indicate an unfavorable long-term prognosis in patients with ADHF and diabetes.

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

BACKGROUND: The 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. METHODS: A 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. RESULTS: During 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). CONCLUSION: A 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.

Short sleep duration and the risk of nonalcoholic fatty liver disease/metabolic associated fatty liver disease: a systematic review and meta-analysis.

PURPOSE: It is unclear whether or not nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated fatty liver disease (MAFLD) is related to short sleep duration. A meta-analysis was conducted to determine if inadequate sleep time increased the risk of NAFLD/MAFLD. METHODS: A comprehensive systematic literature review was conducted in the Embase, PubMed, and Cochrane Library databases from inception to August 1, 2022. Studies examining the correlation between inadequate sleep time and the risk of NAFLD/MAFLD were included. We pooled the odds ratios (ORs) and 95% confidence intervals (CIs) using a random-effects model. RESULTS: This meta-analysis included fifteen studies involving a total of 261,554 participants. In the pooled analysis, short sleep duration was found to be strongly correlated with an increased risk of NAFLD/MAFLD (OR, 1.15; 95% CI, 1.04-1.28; P = 0.01), with a moderate degree of heterogeneity between studies (I2 = 71.92%, Q = 49.87, P < 0.01). The sensitivity analysis suggested that the primary outcome was robust, and there was no significant publication bias. CONCLUSION: This meta-analysis indicates that inadequate sleep duration is strongly correlated with an elevated risk of NAFLD/MAFLD. The findings suggest that obtaining an adequate amount of sleep may be useful for preventing NAFLD/MAFLD, which is especially important given the low rate of response to pharmacotherapy.

Atherogenic index of plasma for non-diabetic, coronary artery disease patients after percutaneous coronary intervention: a prospective study of the long-term outcomes in China.

BACKGROUND: Non-diabetic coronary artery disease (CAD) patients are thought to encounter metabolic dysfunction and while these changes may be imperceptible to the patient they probably influence outcomes. At present, there is no system to support patients sensing these subtle changes, nor is there an established model for prognoses. The Atherogenic Index of Plasma (AIP) index has already proven useful for atherosclerosis although further research is needed, especially for those without hyperglycemia. METHODS: This is a prospective study of 5538 non-diabetic CAD patients who had received percutaneous coronary intervention (PCI). Participants were assigned to one of three groups according to their AIP index. High AIP index cases were then compared to low index patients according to major adverse cardiac events (MACE). Restricted cubic spline (RCS) analysis was also conducted to investigate interrelations between AIP index levels and hazard ratios (HR) for MACEs. RESULTS: Patients with a high AIP index encountered metabolic dysfunction compared to those with a low AIP index i.e., higher Body Mass Index (BMI), Total Cholesterol (TC), Triglycerides (TG), and uric acid as well as lower HDL-C. Each of the aforementioned interrelations were significant with p values of less than 0.001. There was also a significant increase in the number of MACEs in the high AIP index group compared to the low AIP index group (HR: 1.37, 95% CI 1.04-1.81; p = 0.025). A J-shaped RCS curve highlighted a change in the HR after the 0.18 juncture (HR per SD: 1.20, 95% CI 0.96-1.50). Further subgroup analysis supported the main findings, all with HRs greater than one. CONCLUSION: The AIP index could be used in prognostics for non-diabetic CAD patients 2 years after PCI. The relationship between hazard ratio and the AIP index appears to be J-shaped. Although, further multi-center studies designed for non-diabetic patients with potential metabolic dysfunction should be conducted to determine the value of the AIP index.

Association between liver fibrosis and thrombotic or bleeding events in acute coronary syndrome patients.

BACKGROUND: The prognostic implication of liver fibrosis in acute coronary syndrome (ACS) patients are scarce. We sought to evaluate whether liver fibrosis scores (LFS) were associated with thrombotic or bleeding events in patients with acute coronary syndrome. METHODS: We included 6386 ACS patients who underwent percutaneous coronary intervention (PCI). This study determined liver fibrosis with aspartate aminotransferase to platelet ratio index (APRI), aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT ratio), Forns score, and nonalcoholic fatty liver disease fibrosis score (NFS). The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause mortality (ACM), myocardial infarction (MI), and ischemic stroke (IS). RESULTS: During the follow-up, 259 (4.06%) MACCE and 190 (2.98%) bleeding events were recorded. As a continuous variable or a categorical variable stratified by the literature-based cutoff, LFS was positively associated with MACCE (p > 0.05) but not with bleeding events. Compared with subjects with low APRI scores, AST/ALT ratio scores, Forns scores, and NFS scores, subjects with high scores had a 1.57- to 3.73-fold increase risk of MACCE after adjustment (all p < 0.05). The positive relationship between LFS and MACCE was consistent in different subgroups. CONCLUSIONS: In ACS patients, increased LFS predicted an elevated risk of thrombotic events but not bleeding. LFS may contribute to thrombotic risk stratification after ACS.

Association of heart rate and diabetes among 0.5 million adults in the China Kadoorie biobank: Results from observational and Mendelian randomization analyses.

BACKGROUND AND AIMS: Observational studies have associated resting heart rate with incident diabetes. Whether the associations are causal remains unclear. We aimed to examine the shape and strength of the associations and assessed the causal relevance of such associations in Chinese adults. METHODS AND RESULTS: The China Kadoorie Biobank enrolled 512,891 adults in China. Cox proportional hazard regression models was conducted to estimate hazard ratios (HRs) for the associations of resting heart rate with type 2 diabetes and total diabetes. Among 92,724 participants, 36 single-nucleotide polymorphisms (SNPs) related to resting heart rate were used to construct genetic risk score. We used Mendelian randomization analyses to make the causal inferences. During a median follow-up of 9 years, 7872 incident type 2 diabetes and 13,349 incident total diabetes were documented. After regression dilution bias adjustment, each 10 bpm higher heart rate was associated with about a 26% higher risk of type 2 diabetes (HR, 1.26 [95% CI, 1.23, 1.29]) and 23% higher risk of total diabetes (HR, 1.23 [95% CI, 1.20, 1.26]). Instrumental variable analyses showed participants at top quintile compared with those at bottom quintile had 30% higher risk for type 2 diabetes (HR, 1.30 [95% CI, 1.17, 1.43]), and 10% higher risk for total diabetes (HR, 1.10 [95% CI, 1.02, 1.20]). CONCLUSIONS: This study provides evidence that resting heart rate is an important risk factor for diabetes risk. The results suggest that novel treatment approaches targeting reduction of high heart rate for incidence of diabetes may be worth further investigation.

Evaluation of a risk index for predicting short-term and long-term outcomes in patients with ST-elevation myocardial infarction.

OBJECTIVE: This study aimed to evaluate the usefulness of the admission risk index (RI) to predict short-term and long-term outcomes in a broad population with ST-elevation myocardial infarction (STEMI) using data from the Chinese Acute Myocardial Infarction Registry. BACKGROUND: The RI was developed as a simple tool to predict risk of death in STEMI patients. The performance in predicting short-term and long-term risk of death in Chinese patients receiving percutaneous coronary intervention and conservative treatment for STEMI remains unclear. METHODS: Age, heart rate (HR), and systolic blood pressure (SBP) were used to calculate RI using (HR×[age/10]2 )/SBP. We used the prediction tool to predict mortality over 12 months. RESULTS: The C-index of the admission RI for predicting in-hospital, 1-, 6-, and 12-months mortality were 0.78, 0.78, 0.78, and 0.77, respectively, compared with 0.75 of the Global Registry in Acute Coronary Events score. Based on the receiver operating characteristic curve analysis, the RI was categorized into quintiles for convenient clinical use, and it revealed a nearly 15-fold gradient of increasing mortality from 2.29 to 32.5% (p < .0001) while RI >34 had the highest mortality. By categorizing into five different risk groups, the short-term and long-term mortality of patients receiving different treatments could be distinguished. CONCLUSIONS: RI based on three routine variables and easily calculated by any medical practitioner is useful for predicting in-hospital and long-term mortality in patients with STEMI at the initial consultation with clinicians.

Thoracic Paravertebral Blockade Reduces Chronic Postsurgical Pain in Breast Cancer Patients: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect of multilevel single-shot thoracic paravertebral blockade (PVB) on the occurrence of chronic postsurgical pain (CPSP) in patients undergoing breast cancer surgery. DESIGN: A randomized controlled trial with two parallel groups. SETTING: A tertiary hospital. METHODS: Patients scheduled for breast cancer surgery were randomized to receive either ultrasound-guided multilevel single-shot PVB from T2 to T5 (the PVB group) or nothing (the control group). Surgery was then performed under general anesthesia. Patients were followed up for 12 months after surgery. The primary end point was incidence of CPSP at six months after surgery. RESULTS: A total of 218 patients were enrolled and randomized; of these, 208 and 204 completed six- and 12-month follow-up, respectively. The incidence of CPSP at six months was significantly lower in the PVB group (12.5% [13/104]) than in the control group (24.0% [25/104], relative risk = 0.52, 95% CI = 0.28-0.96, P = 0.031). Pain scores within 48 hours both at rest and with movement were lower in the PVB group than the control group (P = 0.006 and P < 0.001, respectively). The percentages of patients with neuropathic pain were also lower in the PVB group than the control group at both six and 12 months after surgery (P = 0.016 and 0.028, respectively). Adverse events did not differ between groups. CONCLUSIONS: For patients undergoing breast cancer surgery, multilevel single-shot PVB reduces the incidence of CPSP at six months; it also improves early postoperative analgesia and reduces neuropathic pain at six and 12 months after surgery.

Coronary Artery Disease: From Mechanism to Clinical Practice.

In most developed countries, coronary artery disease (CAD), mostly caused by atherosclerosis of coronary arteries, is one of the primary causes of death. From 1990s to 2000s, mortality caused by acute MI declined up to 50%. The incidence of CAD is related with age, gender, economic, etc. Atherosclerosis contains some highly correlative processes such as lipid disturbances, thrombosis, inflammation, vascular smooth cell activation, remodeling, platelet activation, endothelial dysfunction, oxidative stress, altered matrix metabolism, and genetic factors. Risk factors of CAD exist among many individuals of the general population, which includes hypertension, lipids and lipoproteins metabolism disturbances, diabetes mellitus, chronic kidney disease, age, genders, lifestyle, cigarette smoking, diet, obesity, and family history. Angina pectoris is caused by myocardial ischemia in the main expression of pain in the chest or adjoining area, which is usually a result of exertion and related to myocardial function disorder. Typical angina pectoris would last for minutes with gradual exacerbation. Rest, sit, or stop walking are the usual preference for patients with angina, and reaching the maximum intensity in seconds is uncommon. Rest or nitroglycerin usage can relieve typical angina pectoris within minutes. So far, a widely accepted angina pectoris severity grading system included CCS (Canadian Cardiovascular Society) classification, Califf score, and Goldman scale. Patients with ST-segment elevated myocardial infarction (STEMI) may have different symptoms and signs of both severe angina pectoris and various complications. The combination of rising usage of sensitive MI biomarkers and precise imaging techniques, including electrocardiograph (ECG), computed tomography, and cardiac magnetic resonance imaging, made the new MI criteria necessary. Complications of acute myocardial infarction include left ventricular dysfunction, cardiogenic shock, structural complications, arrhythmia, recurrent chest discomfort, recurrent ischemia and infarction, pericardial effusion, pericarditis, post-myocardial infarction syndrome, venous thrombosis pulmonary embolism, left ventricular aneurysm, left ventricular thrombus, and arterial embolism.

ASCL1 is a lineage oncogene providing therapeutic targets for high-grade neuroendocrine lung cancers.

Aggressive neuroendocrine lung cancers, including small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), represent an understudied tumor subset that accounts for approximately 40,000 new lung cancer cases per year in the United States. No targeted therapy exists for these tumors. We determined that achaete-scute homolog 1 (ASCL1), a transcription factor required for proper development of pulmonary neuroendocrine cells, is essential for the survival of a majority of lung cancers (both SCLC and NSCLC) with neuroendocrine features. By combining whole-genome microarray expression analysis performed on lung cancer cell lines with ChIP-Seq data designed to identify conserved transcriptional targets of ASCL1, we discovered an ASCL1 target 72-gene expression signature that (i) identifies neuroendocrine differentiation in NSCLC cell lines, (ii) is predictive of poor prognosis in resected NSCLC specimens from three datasets, and (iii) represents novel "druggable" targets. Among these druggable targets is B-cell CLL/lymphoma 2, which when pharmacologically inhibited stops ASCL1-dependent tumor growth in vitro and in vivo and represents a proof-of-principle ASCL1 downstream target gene. Analysis of downstream targets of ASCL1 represents an important advance in the development of targeted therapy for the neuroendocrine class of lung cancers, providing a significant step forward in the understanding and therapeutic targeting of the molecular vulnerabilities of neuroendocrine lung cancer.

Effects of levothyroxine in subclinical hypothyroidism and heart failure with reduced ejection fraction: An open-label randomized trial.

We report a randomized, multicenter, open-label trial (ClinicalTrials.gov: NCT03096613) to investigate the clinical benefits of levothyroxine (L-T4) administration in subclinical hypothyroidism (SCH) patients with heart failure with reduced ejection fraction (HFrEF). Overall, 117 patients were enrolled and received L-T4 plus standard HFrEF treatment (experimental group, N = 57) or standard HFrEF therapy alone (control group, N = 60). The change of 6-min walk test distance in the experimental group was significantly higher than that in the control group at 24 weeks (70.08 ± 85.76 m vs. 27.73 ± 82.00 m, mean difference [95% confidence interval (CI)] 46.90 [12.90, 80.90], p < 0.001). Improvements in New York Heart Association (NYHA) classification (p = 0.033) and thyroid function were significant. Adverse event incidence was similar between groups (risk ratio [95% CI]: 0.942 1.053 (0.424, 2.616); p = 0.628). L-T4 addition to HFrEF treatment improved activity tolerance, NYHA class, and thyroid function within 6 months, suggesting its potential for combined therapy in HFrEF patients with SCH. Future double-blind, placebo-controlled trials should be performed to confirm these results.

The application of large language models in medicine: A scoping review.

This study systematically reviewed the application of large language models (LLMs) in medicine, analyzing 550 selected studies from a vast literature search. LLMs like ChatGPT transformed healthcare by enhancing diagnostics, medical writing, education, and project management. They assisted in drafting medical documents, creating training simulations, and streamlining research processes. Despite their growing utility in assisted diagnosis and improving doctor-patient communication, challenges persisted, including limitations in contextual understanding and the risk of over-reliance. The surge in LLM-related research indicated a focus on medical writing, diagnostics, and patient communication, but highlighted the need for careful integration, considering validation, ethical concerns, and the balance with traditional medical practice. Future research directions suggested a focus on multimodal LLMs, deeper algorithmic understanding, and ensuring responsible, effective use in healthcare.

[Exercise echocardiography in the evaluation of obstructive types of hypertrophic cardiomyopathy].

OBJECTIVE: To assess the condition of left ventricular outflow tract obstruction (LVOTO) under resting conditions and physiological exercise in hypertrophic cardiomyopathy (HCM) patients. METHODS: A total of 60 patients with HCM and left ventricular outflow tract gradient (LVOTG) <50 mm Hg (1 mm Hg = 0.133 kPa) at rest were enrolled consecutively, and LVOTG at rest and exercise were measured by echocardiography. Of 51 patients with gradients <30 mm Hg at rest, 26 were latent LVOTO with exercise peak value LVOTG ≥ 30 mm Hg, 25 were non LVOTO with exercise peak value LVOTG < 30 mm Hg, and 9 were resting obstruction with LVOTG 30-49 mm Hg. The morphological characteristics of different types of obstruction were analyzed. RESULTS: Patients with latent LVOTO were more likely to have SAM (73.1% vs 8.0%) , narrow of LVOT (46.2% vs 4.0%) , higher resting gradients [(16.9 ± 7.2) mm Hg vs (7.1 ± 4.3) mm Hg] and mitral regurgitation grade at rest than patients with non-obstructive (all P values <0.05). The distribution of septal hypertrophy were different in the two groups (P < 0.05). Multivariate logistic regression analysis showed independent predictors of latent LVOTO were SAM (OR 6.431, 95%CI 2.323-291.112, P = 0.002) at rest and distribution of septal hypertrophy(OR 0.011, 95% CI 0.001-0.179, P = 0.008). CONCLUSIONS: Approximately half of patients with non-obstructive HCM at rest have latent LVOTO. SAM and distribution of septal hypertrophy may be useful to identify patients with latent obstruction.

Fibrosis-4 stage of liver fibrosis predicts cardiovascular outcomes in acute coronary syndrome patients with and without type 2 diabetes mellitus.

AIMS: We aim to analyze the effect of liver fibrosis, assessed by the Fibrosis-4 (FIB-4) index, on cardiovascular events in acute coronary syndrome (ACS) patients with and without type 2 diabetes mellitus (T2DM). METHODS: 6563 ACS patients undergoing PCI were analyzed in this study. Patients were divided into three groups according to literature-based FIB-4 cut-offs: < 1.45, 1.45-3.25, and ≥ 3.25. RESULTS: During the median 2.4-year follow-up, 270 major adverse cardiac and cerebrovascular events (MACCE) and 194 major bleeding were recorded. Intermediate or high FIB-4 scores were significantly associated with an elevated risk of MACCE, mortality, and MI but not associated with ischemic stroke and major bleeding. Further restricted cubic spline analysis showed that FIB-4 as a continuous variable was positively associated with an increased adjusted risk of MACCE. The results were consistent in subgroups with and without T2DM. CONCLUSIONS: Liver fibrosis staged by FIB-4 was correlated with an increased risk of MACCE, mortality, and MI in ACS patients who underwent PCI with and without T2DM. FIB-4 index may help risk stratification of ACS patients independent of T2DM status.

Association of triglyceride-glucose index with atherosclerotic cardiovascular disease and mortality among familial hypercholesterolemia patients.

BACKGROUND: Familial hypercholesterolemia (FH) is an inherited metabolic disorder with a high level of low-density lipoprotein cholesterol and the worse prognosis. The triglyceride-glucose (TyG) index, an emerging tool to reflect insulin resistance (IR), is positively associated with a higher risk of atherosclerotic cardiovascular disease (ASCVD) in healthy individuals, but the value of TyG index has never been evaluated in FH patients. This study aimed to determine the association between the TyG index and glucose metabolic indicators, insulin resistance (IR) status, the risk of ASCVD and mortality among FH patients. METHODS: Data from National Health and Nutrition Examination Survey (NHANES) 1999-2018 were utilized. 941 FH individuals with TyG index information were included and categorized into three groups: < 8.5, 8.5-9.0, and > 9.0. Spearman correlation analysis was used to test the association of TyG index and various established glucose metabolism-related indicators. Logistic and Cox regression analysis were used to assess the association of TyG index with ASCVD and mortality. The possible nonlinear relationships between TyG index and the all-cause or cardiovascular death were further evaluated on a continuous scale with restricted cubic spline (RCS) curves. RESULTS: TyG index was positively associated with fasting glucose, HbA1c, fasting insulin and the homeostatic model assessment of insulin resistance (HOMA-IR) index (all p < 0.001). The risk of ASCVD increased by 74% with every 1 unit increase of TyG index (95%CI: 1.15-2.63, p = 0.01). During the median 114-month follow-up, 151 all-cause death and 57 cardiovascular death were recorded. Strong U/J-shaped relations were observed according to the RCS results (p = 0.0083 and 0.0046 for all-cause and cardiovascular death). A higher TyG index was independently associated with both all-cause death and cardiovascular death. Results remained similar among FH patients with IR (HOMA-IR ≥ 2.69). Moreover, addition of TyG index showed helpful discrimination of both survival from all-cause death and cardiovascular death (p < 0.05). CONCLUSION: TyG index was applicable to reflect glucose metabolism status in FH adults, and a high TyG index was an independent risk factor of both ASCVD and mortality.

The changing landscape of drug clinical trials on cardiometabolic diseases in China, 2009-2021.

BACKGROUND: Cardiometabolic disease is a clinical syndrome characterized by multiple metabolic disorders, with atherosclerosis as the core and cardiovascular and cerebrovascular events as the outcome. Drug research and development (R&D) in cardiometabolic diseases has grown rapidly worldwide. However, the development of cardiometabolic drug clinical trials in China remains unclear. This study aims to depict the changing landscape of drug clinical trials for cardiometabolic diseases in China during 2009-2021. METHODS: The detailed information of drug trials on cardiometabolic diseases registered in the National Medical Products Administration (NMPA) Registration and Information Disclosure Platform was collected between January 1, 2009, and July 1, 2021. The landscape of cardiometabolic drug clinical trials was analyzed by the characteristics, time trends, indications, pharmacological mechanisms, and geographical distribution. RESULTS: A total of 2466 drug clinical trials on cardiometabolic diseases were extracted and analyzed. The annual number of drug trials increased rapidly in the past twelve years. Among all the trials, the bioequivalence trials (1428; 58.3%) accounted for the largest proportion, followed by phase I (555; 22.5%), phase III (278; 11.3%), phase II (169; 6.9%), and phase IV (26; 1.1%). Of 2466 trials, 2133 (86.5%) trials were monomer drugs, only 236 (9.6%) trials were polypills and 97 (3.9%) were traditional Chinese medicine (TCM) compounds. In terms of pharmacological mechanisms, the number of trials in dihydropyridine (DHP) calcium antagonists 321 (11.9%) ranked first, while trials in angiotensin receptor blocker (ARB) 289 (10.7%) and dipeptidyl peptidase-4 (DPP-4) inhibitor 205 (7.6%) ranked second and third place respectively. Of 236 chemical polypills trials, 23 (9.7%) polypills were the combination of DHP calcium antagonists and statins, while others were the combination of two same pharmacological effect agents. As for the geographical distribution of leading units, 36 trials were led by principal investigators (PI) units from Beijing, followed by Jiangsu (n = 29), Shanghai (n = 19), Guangdong (n = 19), and Hunan (n = 19), showing an uneven regional distribution. CONCLUSIONS: Great progress has been made in drug clinical trials on cardiometabolic diseases, especially in antihypertensive agents, hypoglycemic agents, and hypolipidemic agents. However, the insufficient innovation of first-in-class drugs and polypills should be carefully considered by all stakeholders in drug trials.

The triglyceride-glucose index as a potential protective factor for hypertrophic obstructive cardiomyopathy without diabetes: evidence from a two-center study.

OBJECTIVE: This study aimed to investigate the relationship between the TyG (Triglyceride-glucose index) and the prognosis of patients with HOCM (hypertrophic obstructive cardiomyopathy) without diabetes. RESEARCH DESIGN AND METHODS: A total of 713 eligible patients with HOCM were enrolled in this study and divided into two groups based on treatment: an invasive treatment group (n = 461) and a non-invasive treatment group (n = 252). The patients in both two groups were then divided into three groups based on their TyG index levels. The primary endpoints of this study were Cardiogenic death during long-term follow-up. Kaplan-Meier analysis was used to study the cumulative survival of different groups. Restricted cubic spline was used to model nonlinear relationships between the TyG index and primary endpoints. Myocardial perfusion imaging/Myocardial metabolic imaging examinations were performed to assess glucose metabolism in the ventricular septum of the HOCM patients. RESULTS: The follow-up time of this study was 41.47 ± 17.63 months. The results showed that patients with higher TyG index levels had better clinical outcomes (HR, 0.215; 95% CI 0.051,0.902; P = 0.036, invasive treatment group; HR, 0.179; 95% CI 0.063,0.508; P = 0.001, non-invasive treatment group). Further analysis showed that glucose metabolism in the ventricular septum was enhanced in HOCM patients. CONCLUSIONS: The findings of this study suggest that the TyG index may serve as a potential protective factor for patients with HOCM without diabetes. The enhanced glucose metabolism in the ventricular septum of HOCM patients may provide a potential explanation for the relationship between the TyG index and HOCM prognosis.

Multiple chromatin-bound protein kinases assemble factors that regulate insulin gene transcription.

During the onset of diabetes, pancreatic beta cells become unable to produce sufficient insulin to maintain blood glucose within the normal range. Proinflammatory cytokines have been implicated in impaired beta cell function. To understand more about the molecular events that reduce insulin gene transcription, we examined the effects of hyperglycemia alone and together with the proinflammatory cytokine interleukin-1beta (IL-1beta) on signal transduction pathways that regulate insulin gene transcription. Exposure to IL-1beta in fasting glucose activated multiple protein kinases that associate with the insulin gene promoter and transiently increased insulin gene transcription in beta cells. In contrast, cells exposed to hyperglycemic conditions were sensitized to the inhibitory actions of IL-1beta. Under these conditions, IL-1beta caused the association of the same protein kinases, but a different combination of transcription factors with the insulin gene promoter and began to reduce transcription within 2 h; stimulatory factors were lost, RNA polymerase II was lost, and inhibitory factors were bound to the promoter in a kinase-dependent manner.

[Comparison of dobutamine stress echocardiography and exercise echocardiography in evaluating left ventricular outflow tract obstruction in patients with hypertrophic cardiomyopathy].

OBJECTIVE: To compare left ventricular outflow tract (LVOT) gradient induced by dobutamine stress echocardiography (DSE) and exercise echocardiography (EE) in patients with hypertrophic cardiomyopathy (HCM). METHODS: DSE and EE were performed in 40 consecutive patients with HCM and LVOT gradient < 50 mm Hg (1 mm Hg = 0.133 kPa) at rest. Dobutamine was administered intravenously at incremental doses of 200, 400, 600, 800 and 1200 µg/min at 5 min intervals. LVOT gradients were measured at rest, at peak exercise and during each dose of DSE. RESULTS: LVOT gradient at rest was lower than 30 mm Hg in 36 patients and between 30 and 49 mm Hg in 4 patients. Of the 36 patients with LVOT gradient < 30 mm Hg at rest, mechanical LVOT obstruction (latent LVOTO) was evidenced in 17 patients during EE and in 18 patients during DSE and good consistency (91.7%, kappa value 0.833) was found between the two maneuvers. The provoked gradient was similar between DSE at 800 µg/min and EE at peak exercise (P = 0.181). In the 4 patients with LVOT gradient between 30 and 49 mm Hg [(38.8 ± 2.6) mm Hg], LVOT gradient increased to (85.3 ± 26.4) mm Hg during EE and (105.0 ± 28.0) mm Hg during DES. CONCLUSIONS: DES and EE are comparable and suitable provoke methods for identifying LVOT obstruction in patients with HCM.