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Background Metformin is a first-line drug in type 2 diabetes mellitus (T2DM) treatment, yet whether metformin may increase all-cause or cardiovascular mortality of T2DM patients remains inconclusive. Methods We searched PubMed and Embase for data extracted from inception to July 14, 2020, with a registration in PROSPERO (CRD42020177283). This study included randomized controlled trials (RCT) assessing the cardiovascular effects of metformin for T2DM. This study is followed by PRISMA and Cochrane guideline. Risk ratio (RR) with 95% CI was pooled across trials by a random-effects model. Primary outcomes include all-cause mortality and cardiovascular mortality. Results We identified 29 studies that randomly assigned patients with 371 all-cause and 227 cardiovascular death events. Compared with untreated T2DM patients, metformin-treated patients was not associated with lower risk of all-cause mortality (RR: 0.98; 95%CI: 0.69–1.38; P  = 0.90), cardiovascular mortality (RR: 1.13; 95% CI: 0.60, 2.15; P  = 0.70), macrovascular events (RR: 0.87; 95%CI: 0.70–1.07; P  = 0.19), heart failure (RR: 1.02; 95% CI:0.61–1.71; P  = 0.95), and microvascular events (RR: 0.78; 95% CI:0.54–1.13; P  = 0.19). Combination of metformin with another hypoglycemic drug was associated with higher risk of all-cause mortality (RR: 1.49; 95% CI: 1.02, 2.16) and cardiovascular mortality (RR: 2.21; 95% CI: 1.22, 4.00) compared with hypoglycemic drug regimens with no metformin. Conclusion The combination of metformin treatment may impose higher risk in all-cause and cardiovascular mortality. This finding, at least in part, shows no evidence for benefits of metformin in combination in terms of all-cause/cardiovascular mortality and cardiovascular events for T2DM. However, the conclusion shall be explained cautiously considering the limitations from UK Prospective Diabetes Study (UKPDS).

Background To explore whether healthy lifestyle factors (HLFs) predict a lower risk of major macrovascular and microvascular events and death in people with type 2 diabetes (T2D) with a high risk of vascular complications. Methods Post hoc analyses of 11,133 participants with T2D in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial who were assigned a score ranging from 0 to 4 based on the number of baseline HLFs: never smoked, moderate-to-vigorous physical activity, ideal waist/hip ratio, and low-to-moderate alcohol consumption. Multivariable Cox models were used to determine associations of 0, 1, 2, and ≥ 3 HLFs with vascular events and all-cause mortality. Results Compared to participants with no HLFs, hazard ratios for participants with 3 or 4 HLFs were 0.68 (95% confidence interval [CI] 0.57–0.81) for the composite of major macrovascular or microvascular events, 0.58 (0.46–0.75) for major macrovascular events, 0.78 (0.61–0.99) for microvascular events, and 0.48 (0.37–0.63) for all-cause mortality during a median follow-up of 5 years. Each increment in HLF score was significantly associated with lower rates of these outcomes. There was no heterogeneity in the effect on any outcome by HLF across randomized intensive blood glucose control and blood pressure lowering treatments. Conclusions HLFs are associated with lower risks of major macrovascular and microvascular events and lower rates of death in high-risk adults with T2D.

This brief report take a further look on the first harmonic of radial pulse wave (C1) after the 1.8 ± 0.5 years follow-up and demonstrated that the quartile level of C1 independently predicts the risk of cardiovascular death, major adverse cardiovascular events, and microvascular outcomes in 2324 patients with type 2 diabetes.

This investigation explored the hypothesis that whether the coefficient of variation of the fourth harmonic amplitude of the radial pulse wave (C4CV) predicts the risk of macrovascular and microvascular events in patients with type 2 diabetes mellitus (T2DM). Radial pulse wave and brachial blood pressure were measured at baseline in 2324 patients with T2DM and C4CV was calculated using the Fourier series method. Macrovascular and microvascular events during follow‐up were determined by medical records. We plotted the Kaplan–Meier curve and performed a Cox proportional hazard model and a log‐rank test to estimate the effectiveness of C4CV as a risk predictor. We divided patients into quartile groups based on C4CV (<4.3%, 4.3% to 6.8%, 6.8% to 11.4%, and >11.4%). Compared with patients with C4CV < 4.3%, patients with C4CV> 11.4% had a double incidence of macrovascular events (hazard ratio, 2.13; 95% CI, 1.70–2.67) and microvascular events (hazard ratio, 2.08; 95% CI, 1.67–2.58), and the incidence of cardiovascular death was three times (hazard ratio, 3.03; 95% CI, 1.10–8.83). The Cox regression analysis demonstrated that the risk of both macrovascular and microvascular outcomes increases with the increase in quartile level of C4CV value (P < 0.0001). These associations remained after adjustment for age, gender, smoking, systolic blood pressure, diastolic blood pressure, dyslipidemia, diabetes duration, Hba1c, and cardiovascular disease (P < 0.0001). C4CV is a novel independent predictor of cardiovascular mortality, macrovascular events, and microvascular events in patients with T2DM. This study demonstrated that the coefficient of variation of the fourth harmonic amplitude of the radial pulse wave (C4CV) can independently predict the risk of cardiovascular mortality, macrovascular events, and microvascular events after a mean follow‐up of 1.8 years.

Background Angio-based microvascular resistance (AMR) was proposed as a tool to quantitatively assess coronary microvascular based on single angiographic projection. The aims of this study are to assess the diagnostic accuracy and prognostic significance of AMR in ST-segment elevation myocardial infarction (STEMI) patients. Methods AMR was measured (Of these, 22 patients measured index of microvascular resistance (IMR)) in 70 STEMI patients after primary percutaneous coronary intervention (pPCI). ST-segment resolution (STR) was assessed 2 h after pPCI simultaneously. Transthoracic echocardiography was performed within 1 day and approximately 1 year after pPCI. STEMI patients underwent pPCI were followed up for 7.3 years and the primary endpoint was the major adverse cardiac and cerebral events (MACCEs). Results AMR showed significant correlations with IMR ( R  = 0.334, P  = 0.005). AMR has good predictive power for STR after pPCI (area under the curve: 0.889, sensitivity: 94.59%, specificity: 75.76%) in receiver operating characteristic (ROC) curve. Low-AMR patients showed markedly improved left ventricular ejection fraction (LVEF) 1 year after pPCI (42(40–49) vs. 41(39–44), P  = 0.041). High-AMR patients showed higher risk for MACCEs than those with Low-AMR (HR = 3.90, P  = 0.02). In multivariate cox regression analysis, AMR was considered an independent predictor of MACCEs (HR: 1.153, P  = 0.020). Conclusions AMR is a reliable tool for the estimation of microvascular resistance and prognosis in the absence of intracoronary pressure-temperature sensor wire and adenosine based on single angiographic projection.

Coronary microvascular disease (CMVD) is not an uncommon complication after acute myocardial infarction (AMI), independent of prompt revascularization. It is a serious yet underdiagnosed disease that has a major impact on patient outcomes. Even when the infarct-related artery is successfully revascularized, a significant percentage of patients still have compromised microvascular circulation, which is linked to higher cardiovascular mortality and hospitalization for heart failure. The well-known invasive methods, such as the index of microvascular resistance (IMR) and the coronary flow reserve (CFR), have been considered as gold standards. However, they are constrained by their hazards and complexity. Non-invasive techniques, such as echocardiography Doppler for CFR assessment, positron emission tomography (PET), cardiac magnetic resonance imaging (CMR), and some other techniques provide alternatives, but their accessibility, cost and implementation during the peri-AMI period raise obstacles to their wider use. This review highlights both invasive and non-invasive modalities as it examines the diagnostic methods and prognostic significance of CMVD development early after AMI. Enhancing long-term results in this high-risk population requires a thorough understanding of pathophysiology and a commitment to larger diagnostic and prognostic studies for CMVD.

Glycemic variability (GV), independently of glycemic control, has emerged as a prognostic marker in patients with type 2 diabetes mellitus (DM). In this study, we assessed the prognostic value of long-term GV for predicting major adverse cardiovascular events (MACE) in our local population. We also assessed its prognostic value for diabetic microvascular complications (DMC) and its relationships with antidiabetic medications. This was a retrospective cohort study that recruited 680 patients with type 2 DM across 2015–2017. MACE were defined as: the composite of; total death, myocardial infarction (MI), stroke, hospitalization due to heart failure, and revascularization. GV was calculated for two glycemic control markers: glycated hemoglobin (G-Hb) and fasting blood sugar (FBS); via three metrics- standard deviation (SD), coefficient of variation (CV), and variability independent from the mean (VIM). Cox proportional hazard models and Kruskal-Wallis tests were used in the statistical analysis. 105 events classified as MACE were identified in 86 patients and 104 DMC in 98 patients in an average follow-up period of 78.43 months. Long-term GV was found to be an independent predictor of MACE, particularly for FBS-CV but not a predictor of DMC. FBS-CV ≥ 17.51% as compared with < 17.51% was a significant and independent predictor of MACE, with HR 1.589 (95% CI; 1.022, 2.472) ( P  = 0.040). DMC were predicted mainly by the duration of type 2 DM, and by the glycemic control; similarly represented by G-Hb and FBS. Patients on metformin, and dipeptidyl peptidase (DPP) 4 inhibitors, had the lowest GV, as compared with patients whose treatments included insulin/sulphonylureas ( P  < 0.001). In our population, long-term GV predicted MACE: with FBS-CV superior to the “gold standard” glycemic control marker G-Hb. Further, GV may be explained, partially at least, by the choice of antidiabetic medications: this finding might contribute to the cardiovascular protection attributed to one class rather than another.

Diabetic retinopathy (DR) is a severe microvascular diabetes complication and a leading cause of preventable blindness. Fibrates, being lipid-lowering agents, have been found to have promise in modifying DR progression. To determine fibrates' effectiveness and safety profile in reducing the incidence, progression, and severity of diabetic retinopathy. Randomized controlled trials and observational cohort studies that compared fibrate therapy with no fibrate therapy in patients with diabetes were eligible for this systematic review and meta-analysis. The outcomes of interest included the incidence of DR, long-term progression, progression to Proliferative Diabetic Retinopathy (PDR), and adverse effects. Risk of bias was assessed using the RoB 2 and ROBINS-I tools, and results were synthesized narratively due to heterogeneity in the study populations, follow-up durations, and diagnostic methods. Only 17 articles were eligible for inclusion in this study. Fibrates significantly reduced the incidence of diabetic retinopathy (OR 0.72 (95 % CI: 0.66–0.77), p < 0.001; I2 = 26.53 %) and slowed long-term progression (OR 0.67 (95 % CI: 0.57–0.79), p < 0.001).; I2 = 26.39 %) compared to placebo. Combining fibrates with statin reduces DR progression by 17 % compared to fibrate alone HR 0.84 (95 % CI: 0.80–0.89), p < 0.001; I2 = 31.7 %. While progression to proliferative diabetic retinopathy showed a favorable trend (RR 0.71 (95 % CI: 0.15–3.32), p = 0.67, the result was not statistically significant. Analysis of adverse events, including all-cause mortality (OR 0.86 (95 % CI: 0.62–1.19), p = 0.36; I2 = 0 %), revealed no significant safety benefits in comparison between fibrates and placebo. Fibrates significantly reduce both the incidence and long-term progression of diabetic retinopathy. Safety analyses revealed no significant difference between placebo and fibrates in reducing serious adverse events or all-cause mortality. What is known about this research topic?•Diabetic retinopathy (DR) is a leading cause of preventable blindness, with limited systemic therapies beyond glycemic and blood pressure control.•Fibrates, primarily lipid-lowering agents, have shown potential benefits for microvascular complications, including DR, in trials like FIELD and ACCORD Eye. What this study adds and its future implications•This meta-analysis confirms fibrates significantly reduce the incidence and long-term progression of DR, with fenofibrate showing the greatest benefit.•Although progression to proliferative DR showed only a favorable trend, no major safety concerns were identified.•These findings support fibrates as an affordable adjunctive therapy in DR management, particularly valuable for early disease stages and resource-limited settings. •Fibrates significantly reduce the incidence of diabetic retinopathy in diabetes.•Long-term progression of diabetic retinopathy is slowed by fibrate therapy.•Fenofibrate shows the strongest protective effect, especially in early-stage disease.•Progression to proliferative diabetic retinopathy trends lower with fibrates.•Fibrates demonstrate a neutral safety profile with no increased adverse events.

ObjectivesTo investigate the prognostic role of early post-infarction cardiac magnetic resonance (CMR) on long-term risk stratification of ST segment elevation myocardial infarction (STEMI) patients with preserved left ventricular ejection fraction (LVEF).MethodsSeventy-seven STEMI patients treated by primary percutaneous coronary intervention (PCI) and LVEF > 50% at CMR were included. The median time between STEMI and CMR was 5 days (IQR 2–8). LV volumes and function, area at risk (on T2 weighted images), infarcted myocardium (on late enhanced images), intramyocardial hemorrhage, and early and late microvascular obstruction (MVO) were detected and measured. CMR tissue determinants were correlated with the incidence of major adverse cardiovascular events (MACEs) over a 5-year follow-up.ResultsDuring median follow-up of 4 years (range 3 to 5 years), eight (10%) patients experienced MACE, yielding an annualized event rate of 2.1%. All CMR tissue markers were not significantly different between MACE and no-MACE patients, except for the presence of late MVO (50% vs. 16%, respectively; p = 0.044) and its extent (2.30 ± 1.64 g vs. 0.18 ± 0.12 g, respectively; p = 0.000). From receiver-operating characteristic (ROC) curve (area under the curve 0.89; 95% confidence interval, 0.75–1.0; p = 0.000), late MVO extent > 0.385 g was a strong independent predictor of MACE at long-term follow-up (sensitivity = 87%, specificity = 90%; hazard ratio = 2.24; 95% confidence interval, 1.51–3.33; p = 0.000).ConclusionsLate MVO extent after primary PCI on CMR seems to be a strong predictor of MACE at 5-year follow-up in patients with LVEF > 50%. Noticeably, late MVO extent > 0.385 g provided relevant prognostic insights leading to improved long-term risk stratification.Key Points• Tissue markers provided by cardiac magnetic resonance aid in prognostic stratification after myocardial infarction• The occurrence of late microvascular obstruction after acute myocardial infarction increases risk of major adverse events at 5-year follow-up.• The greater microvascular obstruction extent on late gadolinium enhanced images is related to an increased risk of adverse events in patients with myocardial infarction and preserved left ventricular function.

Background A guidewire‐free angiography‐derived microcirculatory resistance (AMR) derived from Quantitative flow ratio (QFR) exhibits good diagnostic accuracy for assessing coronary microvascular dysfunction (CMD), but there are no relevant studies supporting the specific application of AMR in patients with ST‐elevation myocardial infarction (STEMI). The study aims to evaluate CMD in patients with STEMI using the AMR index. Methods This study included patients with STEMI who underwent percutaneous coronary intervention (PCI) from June 1, 2020 to September 28, 2021. All patients were divided into two groups: the CMD (n = 215) and non‐CMD (n = 291) groups. After matching, there were 382 patients in both groups.1‐year follow‐up major adverse cardiac events (MACEs) were evaluated. Results After matching, the primary endpoint was achieved in 41 patients (10.7%), with 27 and 14 patients in the CMD and non‐CMD groups, respectively (HR 1.954 [95% CI 1.025–3.726]; 14.1% versus 7.3%, p = .042). Subgroup analysis revealed that 18 patients (4.7%) were readmitted for heart failure, with 15 and 3 in the CMD and non‐CMD groups, respectively (HR 5.082 [95% CI 1.471–17.554]; 7.9% versus 1.6%, p = .010). Post‐PCI AMR ≥ 250 was significantly associated with a higher risk of the primary endpoint and was its independent predictor (HR 2.265 [95% CI 1.136–4.515], p = .020). Conclusion The retrospective use of AMR with a cutoff value of ≥250 after PCI in patients with STEMI can predict a significant difference in the 1‐year MACE rates when compared with a propensity score‐matched group with normal AMR. A guidewire‐free and adenosine‐free angiography‐derived microcirculatory resistance (AMR) derived from quantitative flow ratio with flow velocity calculation exhibits good diagnostic accuracy for assessing coronary microvascular dysfunction. In our study, post‐PCI AMR ≥ 250 mmHg × s/m was significantly associated with a higher risk of the primary endpoint and was its independent predictor.