Cumulative blood pressure predicts risk of stroke in individuals with type 2 diabetes.

AIMS: To determine whether cumulative blood pressure (BP) could predict stroke in individuals with type 2 diabetes (T2D). METHODS: BP levels at baseline and the initial three visits were obtained from individuals participating in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial who had not experienced a stroke. Cumulative elevations in BP were assessed by adding the weighted mean BP values at various time intervals. The association of cumulative BP with stroke was evaluated by a multivariate-adjusted Cox proportional hazard model analysis. RESULTS: Overall, 8282 participants were included (62.10% males and 37.90% females; mean age, 62.73 years). With a median follow-up period of 6.36 years, 324 (3.91%) and 305 (3.68%) patients had any and nonfatal stroke events, respectively. Only baseline systolic BP (SBP) independently predicted any stroke after adjustment for potential confounders, whereas cumulative SBP and pulse pressure independently predicted elevated stroke events. A strong dose-response relationship between cumulative BP and stroke was identified, and conventional risk factors combined with cumulative SBP improved prediction efficiency. CONCLUSION: Cumulative SBP independently predicts stroke in individuals with T2D and provides an incremental predictive value for stroke compared with baseline BP assessments. TRIAL REGISTRATION: URL: http://www. CLINICALTRIALS: gov. Unique identifier: NCT00000620).

Dapagliflozin impedes endothelial cell senescence by activating the SIRT1 signaling pathway in type 2 diabetes.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) clinically reduce atherosclerosis and lower blood pressure. However, their impact on endothelial dysfunction in type 2 diabetes (T2D) remains unclear. In this study, we investigated the protective effect and underlying mechanism of the SGLT2 inhibitor dapagliflozin in diabetes. Methods: Vascular reactivity was measured to assess the vasoprotective effect of dapagliflozin in a mouse model of high glucose (HG)-induced T2D. Pulse wave velocity was measured to quantify arterial stiffness. Protein expression was assessed by western blotting and immunofluorescence, oxidative stress was evaluated using dihydroethidium, nitric oxide was evaluated using the Griess reaction, and cellular senescence was assessed based on senescence-associated beta-galactosidase (SA-ß-gal) activity and the expression of senescence markers. Furthermore, the endothelial nitric oxide synthase (eNOS) acetylation status was determined and eNOS interactions with SIRT1 were evaluated by coimmunoprecipitation assays. Results: Dapagliflozin protected against impaired endothelium-dependent vasorelaxation and improved arterial stiffness in the mouse model of T2D; mouse aortas had significantly reduced levels of senescence activity and senescence-associated inflammatory factors. HG-induced increases in senescence activity, protein marker levels, and oxidative stress in vitro were all ameliorated by dapagliflozin. The decreases in eNOS phosphorylation and nitric oxide (NO) production in senescent endothelial cells were restored by dapagliflozin. SIRT1 expression was reduced in HG-induced senescent endothelial cells, and dapagliflozin restored SIRT1 expression. SIRT1 inhibition diminished the antisenescence effects of dapagliflozin. Coimmunoprecipitation showed that SIRT1 was physically associated with eNOS, suggesting that the effects of dapagliflozin are dependent on SIRT1 activation. Conclusion: These findings indicate that dapagliflozin protects against endothelial cell senescence by regulating SIRT1 signaling in diabetic mice.

Development and Validation of a Novel Prognostic Tool to Predict Recurrence of Paroxysmal Atrial Fibrillation after the First-Time Catheter Ablation: A Retrospective Cohort Study.

There is no gold standard to tell frustrating outcomes after the catheter ablation of paroxysmal atrial fibrillation (PAF). The study aims to construct a prognostic tool. We retrospectively analyzed 315 patients with PAF who underwent first-time ablation at the Second Xiangya Hospital of Central South University. The endpoint was identified as any documented relapse of atrial tachyarrhythmia lasting longer than 30 s after the three-month blanking period. Univariate Cox regression analyzed eleven preablation parameters, followed by two supervised machine learning algorithms and stepwise regression to construct a nomogram internally validated. Five factors related to ablation failure were as follows: female sex, left atrial appendage emptying flow velocity ≤31 cm/s, estimated glomerular filtration rate <65.8 mL/(min·1.73 m2), P wave duration in lead aVF ≥ 120 ms, and that in lead V1 ≥ 100 ms, which constructed a nomogram. It was correlated with the CHA2DS2-VASc score but outperformed the latter evidently in discrimination and clinical utility, not to mention its robust performances in goodness-of-fit and calibration. In addition, the nomogram-based risk stratification could effectively separate ablation outcomes. Patients at risk of relapse after PAF ablation can be recognized at baseline using the proposed five-factor nomogram.

Association of the cumulative triglyceride-glucose index with major adverse cardiovascular events in patients with type 2 diabetes.

BACKGROUND: The triglyceride-glucose (TyG) index is a reliable surrogate marker of insulin resistance and is associated with major adverse cardiovascular events (MACEs) in patients with type 2 diabetes mellitus (T2DM). However, the long-term effect of the TyG index on the incidence of MACEs remains unclear. We aimed to investigate the association between the cumulative TyG index and the risk of MACEs in patients with T2DM. METHODS: This post-hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial assessed patients' (T2DM > 3 months) cumulative TyG index and MACE data from the study database. Five fasting blood glucose and triglyceride measurements, at baseline and the first four visits, were taken from 5695 participants who had not experienced MACEs. Cumulative exposure to the TyG index was calculated as the weighted sum of the mean TyG index value for each time interval (value × time). Multivariable-adjusted Cox proportional hazard models and restricted cubic spline analysis were used to determine the association between the cumulative TyG index and MACEs. The incremental predictive value of the cumulative TyG index was further assessed. RESULTS: Over a median follow-up of 5.09 years, 673 (11.82%) MACEs occurred, including 256 (4.50%) cardiovascular disease (CVD) deaths, 288 (5.06%) non-fatal myocardial infarctions (MIs), and 197 (3.46%) strokes. The risk of developing MACEs increased with the cumulative TyG index quartile. After adjusting for multiple potential confounders, the hazard ratios for the very high cumulative TyG index group versus the low group were 1.59 (95% confidence interval [CI], 1.17-2.16), 1.97 (95% CI 1.19-3.26), and 1.66 (95% CI 1.02-2.70) for overall MACEs, CVD death, and non-fatal MI, respectively. Restricted cubic spline analysis also showed a cumulative increase in the risk of MACEs with an increase in the magnitude of the cumulative TyG index. The addition of the cumulative TyG index to a conventional risk model for MACEs improved the C-statistics, net reclassification improvement value, and integrated discrimination improvement value. CONCLUSIONS: In patients with T2DM, the cumulative TyG index independently predicts the incidence of MACEs, and monitoring the long-term TyG index may assist with optimized-for-risk stratification and outcome prediction for MACEs. Trial registration URL: http://www. CLINICALTRIALS: gov . Unique identifier: NCT00000620.