The impact of triglyceride glucose-body mass index on all-cause and cardiovascular mortality in elderly patients with diabetes mellitus: evidence from NHANES 2007-2016.

BACKGROUND: The relationship between triglyceride glucose-body mass index (TyG-BMI) index and mortality in elderly patients with diabetes mellitus (DM) are still unclear. This study aimed to investigate the association between TyG-BMI with all-cause and cardiovascular mortality among elderly DM patients in the United States (US). METHODS: Patients aged over 60 years with DM from the National Health and Nutrition Examination Survey (2007-2016) were included in this study. The study endpoints were all-cause and cardiovascular mortality and the morality data were extracted from the National Death Index (NDI) which records up to December 31, 2019. Multivariate Cox proportional hazards regression model was used to explore the association between TyG-BMI index with mortality. Restricted cubic spline was used to model nonlinear relationships. RESULTS: A total of 1363 elderly diabetic patients were included, and were categorized into four quartiles. The mean age was 70.0 ± 6.8 years, and 48.6% of them were female. Overall, there were 429 all-cause deaths and 123 cardiovascular deaths were recorded during a median follow-up of 77.3 months. Multivariate Cox regression analyses indicated that compared to the 1st quartile (used as the reference), the 3rd quartile demonstrated a significant association with all-cause mortality (model 2: HR = 0.64, 95% CI 0.46-0.89, P = 0.009; model 3: HR = 0.65, 95% CI 0.43-0.96, P = 0.030). Additionally, the 4th quartile was significantly associated with cardiovascular mortality (model 2: HR = 1.83, 95% CI 1.01-3.30, P = 0.047; model 3: HR = 2.45, 95% CI 1.07-5.57, P = 0.033). The restricted cubic spline revealed a U-shaped association between TyG-BMI index with all-cause mortality and a linear association with cardiovascular mortality, after adjustment for possible confounding factors. CONCLUSIONS: A U-shaped association was observed between the TyG-BMI index with all-cause mortality and a linear association was observed between the TyG-BMI index with cardiovascular mortality in elderly patients with DM in the US population.

The prognostic value of the stress hyperglycemia ratio for all-cause and cardiovascular mortality in patients with diabetes or prediabetes: insights from NHANES 2005-2018.

BACKGROUND: The Stress hyperglycemia ratio (SHR) is a novel marker reflecting the true acute hyperglycemia status and is associated with clinical adverse events. The relationship between SHR and mortality in patients with diabetes or prediabetes is still unclear. This study aimed to investigate the predictive value of the SHR for all-cause and cardiovascular mortality in patients with diabetes or prediabetes. METHODS: This study included 11,160 patients diagnosed with diabetes or prediabetes from the National Health and Nutrition Examination Survey (2005-2018). The study endpoints were all-cause and cardiovascular mortality, and morality data were extracted from the National Death Index (NDI) up to December 31, 2019. Patients were divided into SHR quartiles. Cox proportion hazards regression was applied to determine the prognostic value of SHR. Model 1 was not adjusted for any covariates. Model 2 was adjusted for age, sex, and race. Model 3 was adjusted for age, sex, race, BMI, smoking status, alcohol use, hypertension, CHD, CKD, anemia, and TG. RESULTS: During a mean follow-up of 84.9 months, a total of 1538 all-cause deaths and 410 cardiovascular deaths were recorded. Kaplan-Meier survival analysis showed the lowest all-cause mortality incidence was in quartile 3 (P < 0.001). Multivariate Cox regression analyses indicated that, compared to the 1st quartile, the 4th quartile was associated with higher all-cause mortality (model 1: HR = 0.89, 95% CI 0.74-10.7, P = 0.226; model 2: HR = 1.24, 95% CI 1.03-1.49, P = 0.026; model 3: HR = 1.30, 95% CI 1.08-1.57, P = 0.006). The 3rd quartile was associated with lower cardiovascular mortality than quartile 1 (model 1: HR = 0.47, 95% CI 0.32-0.69, P < 0.001; model 2: HR = 0.66, 95% CI 0.45-0.96, P = 0.032; model 3: HR = 0.68, 95% CI 0.46-0.99, P = 0.049). There was a U-shaped association between SHR and all-cause mortality and an L-shaped association between SHR and cardiovascular mortality, with inflection points of SHR for poor prognosis of 0.87 and 0.93, respectively. CONCLUSION: SHR is related to all-cause and cardiovascular mortality in patients with diabetes or prediabetes. SHR may have predictive value in those patients.

Diabetes: a potential mediator of associations between polycyclic aromatic hydrocarbon exposure and stroke.

Epidemiological evidence suggests associations between exposure to polycyclic aromatic hydrocarbons (PAHs) and cardiovascular diseases (CVD), while diabetes is a common risk factor for CVD. The present study aims to clarify the effect of high PAH exposure on diabetes and stroke in general population. A total of 7849 individuals aged 20 years or older from the National Health and Nutrition Examination Survey 2007-2016 were included in the study. The logistic regression analysis modeled the association between PAH exposure and diabetes as well as stroke. The analysis yielded odds ratios (ORs) and 95% confidence intervals (CIs). The study also evaluated the potential mediating role of diabetes in the relation between PAH exposure and stroke via mediating effect analyses. Of the 7849 eligible participants, 1424 cases of diabetes and 243 cases of stroke were recorded. After adjusting for covariates including age, gender, smoking status, drinking status, education level, marital status, physical activity, hypertension, low-density lipoprotein cholesterol, and BMI, the ORs for stroke in the highest quartile (Q4) of total urinary PAHs were 1.97 (95% CI 1.11-3.52, P = 0.022) as compared to the lowest quartile (Q1) of total urinary PAHs. The ORs for diabetes in the Q4 of total urinary PAHs were 1.56 (95% CI 1.15-2.12, P = 0.005), while the ORs between Q4 and Q1 for stroke and diabetes concerning exposure to 2-hydroxynaphthalene were 2.23 (95% CI 1.17-4.25, P = 0.016) and 1.40 (95% CI 1.07-1.82, P = 0.015), respectively. The mediation analysis found that diabetes accounted for 5.00% of the associations between urinary PAHs and the prevalence of stroke. Urinary metabolites of PAH have been linked to stroke and diabetes. Increasing the risk of diabetes may play a significant role in mediating the association between exposure to PAHs and increased risk of stroke. Monitoring and improving glucose metabolism in individuals with high exposure to PAHs may aid in reducing the prevalence of stroke.

Non-linear associations of HOMA2-IR with all-cause mortality in general populations: insights from NHANES 1999-2006.

BACKGROUND: The association between homeostatic model assessment (HOMA2-IR) and mortality in obese and non-obese populations has not been clearly explained. METHODS: A total of 7,085 individuals aged ≥ 20 years from the 1999-2006 National Health and Nutrition Examination Survey were included in the study. Study endpoints were all-cause and cardiovascular mortality. Multivariate Cox proportional hazards regression models with restricted cubic spline analysis were used for analysis. RESULTS: In the study populations, a total of 1666 all-cause deaths and 555 cardiovascular (CV) deaths were recorded during a mean follow-up of 195.53 months. Notably, a significant difference in obesity was observed in the association between HOMA2-IR and mortality. After adjustment for multiple variables, HOMA2-IR was positively associated with all-cause mortality in all participants, in those with normal BMI, and in those with obesity. Conversely, tertile 2 of HOMA2-IR was associated with a lower risk of all-cause mortality in participants with obesity compared with tertile 1 (adjusted hazard ratio, 0.68; 95% confidence interval, 0.52-0.89; P = 0.005). Results from restricted cubic spline analysis showed a J-shaped association between HOMA2-IR and all-cause and CV mortality. In addition, a nonlinear U-shaped correlation with all-cause (P for nonlinear < 0.001) and CV (P for nonlinear = 0.002) mortality was observed in the population with obesity, with inflection points of HOMA2-IR identified at 1.85 and 1.75. Below the inflection point of 1.85, a negative relationship between HOMA2-IR and all-cause mortality was observed. CONCLUSIONS: Elevated HOMA2-IR showed a notable correlation with increased risk of all-cause mortality. It was noteworthy that excessively reduced levels of insulin resistance showed a distinct association with increased mortality in individuals with obesity.

Radiofrequency catheter ablation for pulmonary hypertension patients with atrial flutter.

AIMS: We aimed to evaluate the effects of radiofrequency catheter ablation (RFCA) and the factors influencing mortality after RFCA in patients with pulmonary hypertension (PH) and atrial flutter (AFL). METHODS AND RESULTS: Fifty-eight consecutive PH patients with AFL who underwent an electrophysiological study and RFCA between April 2013 and August 2021 were selected for this study. In the study population, pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) was the most common type of PH (n = 34, 59%), followed by idiopathic pulmonary arterial hypertension (IPAH) (n = 19, 33%). Typical atrial flutter was the most common type of atrial flutter (n = 50, 86.2%). Sinus rhythm was restored in 53 (91.4%) patients during RFCA. After a mean follow-up of 33.8 months, AFL recurred in a total of 22 patients. Nine of them underwent repeat RFCA, and the site of the repeat ablation was not exactly the same as the first. At a median follow-up of 34.6 months after the last ablation, none of the patients who underwent repeat RFCA experienced AFL recurrence, and all of these patients survived. There were no procedure-related complications during hospitalization or follow-up. Univariate Cox regression analysis suggested that AFL recurrence after the last ablation was not associated with all-cause mortality. NT-proBNP (HR: 1.00024, 95% CI: 1.00008-1.00041, P = 0.004), pulmonary artery systolic pressure (PASP) (HR: 1.048, 95% CI: 1.020-1.076, P = 0.001), and IPAH (vs. PAH-CHD, HR: 7.720, 95% CI: 1.437-41.483, P = 0.017) were independent predictors of all-cause mortality in PH patients with AFL after RFCA. Receiver operating characteristic (ROC) curve analysis revealed that the area under the curve (AUC) of PASP for predicting all-cause mortality was 0.708. There was no significant difference in the Kaplan-Meier curves for all-cause mortality between patients with AFL recurrence after the last ablation and those without recurrence (P = 0.851). Patients with higher PASP (≥110 mmHg) and IPAH showed the lower survival rate in Kaplan-Meier curves. CONCLUSION: Repeat ablation was safe and feasible in patients with recurrent AFL and can maintain sinus rhythm. AFL recurrence was not associated with all-cause mortality, and patients with high PASP or IPAH were at higher risk for adverse outcomes.

Prognostic significance of quantitative electrocardiographic parameters in patients with non-high-risk pulmonary embolism.

BACKGROUND: Electrocardiogram (ECG) abnormalities indicating right ventricular strain have been reported to have prognostic value in severe cases of acute pulmonary embolism (PE). We aimed to analyze the prognostic significance of other quantitative ECG parameters in non-high-risk acute PE. METHODS: Consecutive patients with non-high-risk acute PE were prospectively enrolled. The following baseline ECG parameters were collected: rhythm, heart rate, QRS axis, right bundle branch block (RBBB) pattern, S1Q3T3 pattern, T-wave inversion, ST-segment elevation, Qr in lead V1, PR Interval, QRS complex duration, QT interval, P-wave amplitude and duration, R- and S-wave amplitudes. The primary endpoint was early discharge within three days. Associations between ECG parameters and early discharge were analyzed. RESULTS: Overall, 383 patients were enrolled (median age: 67 years, 57% female): 277 (72.3%) with low-risk and 106 (27.7%) with intermediate-risk. The two groups of patients differed in several ECG signs of right ventricular strain and many other quantitative parameters like R- and S-wave amplitudes. In the multivariate logistic regression analysis, the S-wave depth in lead V5 (S-V5) was the only independent prognostic factor for early discharge (odds ratio = 0.137, 95% confidence interval = 0.031-0.613, p = 0.009). The optimum cutoff value of S-V5 for predicting early discharge derived from the receiver operative characteristic curve was 0.15 mv (c-statistic = 0.66, p =0.003). CONCLUSIONS: Several ECG signs of right ventricular strain and many other quantitative parameters were associated with disease severity in non-high-risk acute PE. An S-V5 lesser than 0.15 mv was predictive for early discharge in these patients.

SGLT2 inhibitors for the prevention of atrial fibrillation: a systemic review and meta-analysis.

AIMS: Sodium-glucose co-transporter-2 (SGLT2) inhibitors are reported to have cardiac benefits. The effects of SGLT2 inhibitors on the prevention of atrial fibrillation (AF) remain inconclusive. We aimed to investigate whether SGLT2 inhibitors can prevent AF occurrence in patients with cardiometabolic diseases. METHODS: We searched MEDLINE, EMBASE, and the Cochrane CENTRAL database up to July 1, 2023. Randomized, placebo-controlled trials of SGLT2 inhibitors in patients with diabetes, heart failure, chronic kidney diseases, or cardiometabolic risk factors were included. The primary outcome was AF occurrence. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated in the overall population and selected subgroups. RESULTS: Forty-six trials comprising 101 100 patients were included. Overall, no significant risk reduction of AF occurrence was observed with SGLT2 inhibitors, although there was a favorable trend (RR 0.90, 95% CI 0.80-1.01). In trials with follow-up durations of over one year, a similar result was achieved (RR 0.90, 95% CI 0.80-1.01). The results were consistent across different SGLT2 inhibitors, with RRs (95%CIs) of 0.82 (0.60-1.12) for canagliflozin, 0.87 (0.73-1.03) for dapagliflozin, 0.97 (0.78-1.22) for empagliflozin, 0.99 (0.66-1.50) for sotagliflozin, and 0.87 (0.58-1.29) for ertugliflozin. Analyses in different doses of SGLT2 inhibitors yielded similar results. The associations between SGLT2 inhibitors and AF occurrence were also absent in patients with diabetes, heart failure, and chronic kidney diseases. CONCLUSION: For patients with cardiometabolic diseases or risk factors, SGLT2 inhibitors did not decrease the risk of AF occurrence, regardless of follow-up duration, type or dose of the drug, or the patient population.

The effects of SGLT2 inhibitors on the prevention of atrial fibrillation (AF) remain inconclusive. For patients with cardiometabolic diseases or risk factors, SGLT2 inhibitors did not decrease the risk of AF occurrence, regardless of follow-up duration, type or dose of the drug, or the patient population. Further research is warranted to investigate the potential benefit of SGLT2 inhibitors in AF.

Venous anatomy of the left ventricular summit region: Insights from high-speed rotational retrograde angiography.

INTRODUCTION: Mapping and ablation through the coronary venous system (CVS) have shown potential for ventricular arrhythmias originating from the left ventricular summit (LVS). Multielectrode catheters and balloons are frequently used for mapping and venous ethanol ablation (VEA). However, there is limited data on the venous size and drainage condition in the LVS region. This study aimed to investigate the morphology, angiographic size, and drainage condition of LV summit veins via high-speed rotational angiography (RA). METHODS: We measured and analyzed the size of the great cardiac vein (GCV), the anterior interventricular vein (AIV), veins near to the LVS, and other main tributaries of CVS in 102 patients undergoing electrophysiology study. RESULTS: Rotational retrograde angiography of LVS was successfully performed in 81 patients. The diameter of GCV at the level of the Vieussens valve and the distal end of GCV (junction of GCV-AIV) was larger in males than females (6.8 ± 1.1 vs. 5.6 ± 1.2 mm, p < .001; 5.2 ± 0.9 vs. 4.6 ± 0.8, p = .002, respectively) while no significant gender differences were observed in other tributaries. The LV summit veins presented downward drainage direction in half of the patients, indicating potential anatomic adjacency with His bundle. Left anterior oblique (LAO) 45° projection might provide the practical and optimal view of the LV summit veins. CONCLUSIONS: The coronary veins of the LVS region present various anatomical morphologies and ostium sizes. We provide a systematic description and angiographic size spectrum of CVS. RA could facilitate assessing the feature of CVS comprehensively.

Upregulation of miR-335-5p Contributes to Right Ventricular Remodeling via Calumenin in Pulmonary Arterial Hypertension.

Right ventricular (RV) failure determines the prognosis in pulmonary arterial hypertension (PAH), but the underlying mechanism is still unclear. Growing evidence has shown that microRNAs participate in RV remodeling. This study is undertaken to explore the role of miR-335-5p in regulating RV remodeling induced by PAH. Two PAH models were used in the study, including the monocrotaline rat model and hypoxia/su5416 mouse model. miRNA sequencing and RT-qPCR validation identified that miR-335-5p was elevated in the RV of PAH rats. In vitro, miR-335-5p expression was increased after angiotensin II treatment, and miR-335-5p inhibition relieved angiotensin II-induced cardiomyocyte hypertrophy. The luciferase reporter assay showed that calumenin was a target gene for miR-335-5p. Pretreatment with miR-335-5p inhibitors could rescue calumenin downregulation induced by angiotensin II in H9C2 cells. Moreover, intracellular Ca2+ concentration and apoptosis were increased after angiotensin II treatment, and miR-335-5p inhibition decreased intracellular Ca2+ accumulation and apoptosis. Finally, in vivo miR-335-5p downregulation (antagomir miR-335-5p) attenuated RV remodeling and rescued calumenin downregulation under conditions of hypoxia/su5416 exposure. Our work highlights the role of miR-335-5p and calumenin in RV remodeling and may lead to the development of novel therapeutic strategies for right heart failure.

m6A Modification-mediated GRAP Regulates Vascular Remodeling in Hypoxic Pulmonary Hypertension.

Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling induced by human pulmonary arterial smooth muscle cell (HPASMC) proliferation, migration, and apoptosis resistance. m6A (N6-methyladenosine) is the most prevalent RNA posttranscriptional modification in eukaryotic cells. However, its role in PAH remains elusive. We designed this study to investigate whether m6A modification and its effector proteins play a role in pulmonary vascular resistance. Lung samples were used to profile m6A concentrations in control subjects and patients with PAH. Bioinformatics analysis, real-time PCR, immunohistochemistry, and Western blotting were used to determine the role of m6A effectors in PAH. The biological effects of GRAP modified by m6A were investigated using in vitro and in vivo models. Furthermore, RIP-PCR was used to assess the writers and readers of GRAP. In this study, we revealed that m6A-modified GRAP mRNA was upregulated in PAH lung samples, cHx/Su-induced mouse models, and hypoxia-stimulated HPASMCs; however, GRAP mRNA and protein were abnormally downregulated. Functionally, overexpression of GRAP drastically alleviated the proliferative and invasive ability of PAH HPASMCs through inhibition of the Ras/ERK signaling pathway in vitro and in vivo. In addition, METTL14 (methyltransferase-like 14) and the m6A binding protein YTHDF2 were significantly increased in PAH. Moreover, we found that m6A-modified GRAP mRNA was recognized by YTHDF2 to mediate the degradation. GRAP expression was consistently negatively correlated with METTL14 and YTHDF2 in vivo and in vitro. Taken together, for the first time, our findings highlight the function and therapeutic target value of GRAP and extend our understanding of the importance of RNA epigenetics in PAH.

Pyruvate kinase M2 activation protects against the proliferation and migration of pulmonary artery smooth muscle cells.

Pyruvate kinase M2 (PKM2), which is encoded by PKM, is a ubiquitously expressed intracellular protein and is associated with proliferation cell phenotype. In PAH patients and PAH models, we found higher levels of PKM2 tyrosine 105 phosphorylation (phospho-PKM2 (Y105)) than in controls, both in vivo and in vitro. Here, we demonstrate that PKM2 stimulates inflammatory and apoptosis signalling pathways in pulmonary artery smooth muscle cells (PASMCs) and promotes PASMC migration and proliferation. PKM2 phosphorylation promoted the dimerization activation and nuclear translocation of STAT3, a transcription factor regulating proliferation, growth, and apoptosis. TLR2, a transmembrane protein receptor involved in both innate and adaptive immune responses, promoted PKM2 phosphorylation in hypoxia-induced PASMCs. Therefore, we hypothesized that PKM2 also affects the proliferation and migration of PASMCs. The proliferation of hypoxia-induced normal human pulmonary artery smooth muscle cells (normal-HPASMCs) was found to be inhibited by TEPP-46 (PKM2 agonist) and PKM2 siRNA using wound healing, 5-ethynyl-2'-deoxyuridine (EdU), and immunofluorescence (Ki67) assays. PASMCs isolated from PAH patients (PAH-HPASMCs) and hypoxia-treated rats (PAH-RPASMCs) also confirmed the above results. TEPP-46 treatment was found to improve hypoxia-induced pulmonary artery remodelling and right heart function in mice, and the link between PKM2 and STAT3 was also confirmed in vivo. In conclusion, PKM2 plays crucial roles in the proliferation and migration of PASMCs.