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The occurrence and development of coronary heart disease (CHD) are closely linked to fluctuations in blood glucose levels. While the efficacy of intensified treatment guided by HbA1c levels remains uncertain for individuals with diabetes and CHD, this review summarizes the findings and conclusions regarding HbA1c in the context of CHD. Our review showed a curvilinear correlation between regulated level of HbA1c and therapeutic effectiveness of intensified glycemic control among patients with type 2 diabetes and coronary heart disease. It is necessary to optimize the dynamic monitoring indicators of HbA1c, combine genetic profiles, haptoglobin phenotypes for example and select more suitable hypoglycemic drugs to establish more appropriate glucose-controlling guideline for patients with CHD at different stage of diabetes.

Cardiovascular diseases represent the principal cause of death and comorbidity among people with diabetes. Ferroptosis, an iron-dependent non-apoptotic regulated cellular death characterized by lipid peroxidation, is involved in the pathogenesis of diabetic cardiovascular diseases. The susceptibility to ferroptosis in diabetic hearts is possibly related to myocardial iron accumulation, abnormal lipid metabolism and excess oxidative stress under hyperglycemia conditions. Accumulating evidence suggests ferroptosis can be the therapeutic target for diabetic cardiovascular diseases. This review summarizes ferroptosis-related mechanisms in the pathogenesis of diabetic cardiovascular diseases and novel therapeutic choices targeting ferroptosis-related pathways. Further study on ferroptosis-mediated cardiac injury can enhance our understanding of the pathophysiology of diabetic cardiovascular diseases and provide more potential therapeutic choices.

Background Inflammation plays a crucial role in the pathogenesis and progression of coronary artery disease (CAD). The neutrophil to lymphocyte ratio (NLR) is a novel inflammatory biomarker and its association with clinical outcomes in CAD patients with different glycemic metabolism after percutaneous coronary intervention (PCI) remains undetermined. Therefore, this study aimed to investigate the effect of NLR on the prognosis of patients undergoing PCI with or without type 2 diabetes mellitus (T2DM). Methods We consecutively enrolled 8,835 patients with CAD hospitalized for PCI at Fuwai hospital. NLR was calculated using the following formula: neutrophil (*10 9 /L)/lymphocyte (*10 9 /L). According to optimal cut-off value, study patients were categorized as higher level of NLR (NLR-H) and lower level of NLR (NLR-L) and were further stratified as NLR-H with T2DM and non-T2DM, and NLR-L with T2DM and non-T2DM. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCEs), defined as all-cause mortality, myocardial infarction (MI), stroke and target vessel revascularization. Results A total of 674 (7.6%) MACCEs were recorded during a median follow-up of 2.4 years. The optimal cut-off value of NLR was 2.85 determined by the surv_cutpoint function. Compared to those in the NLR-H/T2DM groups, patients in the NLR-L/non-T2DM, NLR-H/non-T2DM and NLR-L/T2DM groups were at significantly lower risk of 2-year MACCEs [adjusted hazard ratio (HR): 0.67, 95% confidence interval (CI): 0.52 to 0.87, P = 0.003; adjusted HR: 0.62, 95%CI: 0.45 to 0.85, P = 0.003; adjusted HR: 0.77, 95%CI: 0.61 to 0.97, P = 0.025; respectively]. Remarkably, patients in the NLR-L/non-T2DM group also had significantly lower risk of a composite of all-cause mortality and MI than those in the NLR-H/T2DM group (adjusted HR: 0.57, 95%CI: 0.35 to 0.93, P = 0.024). Multivariable Cox proportional hazards model also indicated the highest risk of MACCEs in diabetic patients with higher level of NLR than others (P for trend = 0.009). Additionally, subgroup analysis indicated consistent impact of NLR on MACCEs across different subgroups. Conclusions Presence of T2DM with elevated NLR is associated with worse clinical outcomes in CAD patients undergoing PCI. Categorization of patients with elevated NLR and T2DM could provide valuable information for risk stratification of CAD patients.

Background The triglyceride-glucose (TyG) index and the stress hyperglycaemia ratio (SHR) are both positively associated with cardiovascular (CV) risk in patients with coronary heart disease. However, the prognostic value of these two biomarkers has not been well elucidated in patients with chronic total occlusion (CTO). Therefore, this study aims to evaluate the association of the TyG index and the SHR with long-term prognosis in patients with CTO. Methods This prospective cohort study consecutively included 2740 angina patients with CTO from January 2017 to December 2018 at Fuwai Hospital. The outcomes are a composite of CV death and target vessel myocardial infarction (TVMI) and major CV cerebrovascular adverse events (MACCEs, including all-cause death, nonfatal MI, ischaemia-driven target vessel revascularization, and stroke). The association between biomarkers and prognosis was analysed by multivariable Cox proportional hazard models, and the predictive value was determined by a receiver-operating characteristic (ROC) curve. Results During the follow-up with a median time of 3 years, 179 (6.5%) cases of MACCEs and 47 (1.7%) cases of CV death or TVMI were recorded. Patients with a high TyG index (> 9.10) and a high SHR (> 0.87) showed a significantly increased risk of CV death/TVMI (TyG index: HR 4.23, 95% CI 1.58–11.37; SHR: HR 5.14, 95% CI 1.89–13.98) and MACCEs (TyG index: HR 2.47, 95% CI 1.54–3.97; SHR: HR 2.91, 95% CI 1.84–4.60) compared with those with a low Tyg index and a low SHR (TyG < 8.56, SHR < 0.76). The area under the curve (AUC) values were 0.623 (TyG index) and 0.589 (SHR) for CV death/TVMI and 0.659 (TyG index) and 0.624 (SHR) for MACCEs. Furthermore, patients with both a high TyG index and a high SHR showed the highest risk of clinical outcomes among patients with different levels of these two biomarkers, and the AUC for the TyG-SHR combination was larger than the TyG index alone in predicting MACCE risk. Conclusions The study revealed that a high TyG index and a high SHR were significantly correlated with poor prognosis in patients with CTO and suggested that these two biomarkers are reliable in predicting long-term prognosis in CTO patients.

Background The role of triglyceride-glucose (TyG) index, an insulin resistance indicator, in glycemic management for diabetic patients with coronary artery disease (CAD) was still unknown. Therefore, we aimed to explore the association between glycemic control and cardiovascular (CV) outcomes in patients with diabetes and CAD according to different TyG index levels. Methods A total of 9996 diabetic patients with angiograph-proven CAD were consecutively recruited from 2017 to 2018 at Fuwai Hospital. Patients were assigned into 3 groups according to TyG index tertiles (T) (T1: <8.895; T2: 8.895-9.400; T3: ≥9.400). According to American Diabetes Association guidelines, controlled glycemia was defined as targeting glycosylated hemoglobin Alc (HbA1c) < 7%. The primary endpoint was CV events including CV death, nonfatal myocardial infarction, and nonfatal stroke. Results During a median 3-year follow-up, 381 (3.8%) CV events occurred. Overall, high TyG index (T3) was associated with increased risk of CV events (hazard ratio [HR]: 1.40; 95% confidence interval [CI]: 1.02–1.94) compared with the lowest TyG index (T1) after multivariable adjustment. Upon stratification by the TyG index, in fully adjusted models, controlled glycemia was associated with reduced risk of CV events in the high TyG index (T3) subgroup (HR: 0.64; 95%CI: 0.42–0.96) but not in the low (T1; HR: 0.79; 95%CI: 0.53–1.16) and moderate (T2; HR: 0.84; 95%CI: 0.56–1.25) TyG index subgroups. Conclusions Controlled glycemia was associated with improved CV outcomes in patients with diabetes and established CAD, especially in those with high TyG index levels. Our study, for the first time, provided valuable information that TyG index could help making risk stratification on the glycemic management in diabetic patients with CAD.

Background Insulin resistance (IR), a hallmark of proceeding diabetes and cardiovascular (CV) disease, has been shown to predict prognosis in patients undergoing percutaneous coronary intervention (PCI). The triglyceride-glucose (TyG) index, triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and metabolic score for insulin resistance (METS-IR) have been shown to be simple and reliable non-insulin-based surrogates for IR. However, limited studies have determined the associations between distinct non-insulin-based IR markers and CV outcomes in patients undergoing complex PCI who are at higher risk of CV events after PCI. Therefore, this study aimed to investigate and compare the prognostic value of these markers in patients undergoing complex PCI. Methods This was a descriptive cohort study. From January 2017 to December 2018, a total of 9514 patients undergoing complex PCI at Fuwai Hospital were consecutively enrolled in this study. The 3 IR indices were estimated from the included patients. The primary study endpoint was CV events, defined as a composite of CV death, nonfatal myocardial infarction and nonfatal stroke. Results During a median follow-up of 3.1 years, 324 (3.5%) CV events occurred. Multivariable Cox regression models showed per-unit increase in the TyG index (hazard ratio [HR], 1.42; 95% confidence interval [CI] 1.13–1.77), rather than per-unit elevation in either Ln(TG/HDL-C ratio) (HR, 1.18; 95%CI 0.96–1.45) or METS-IR (HR, 1.00; 95%CI 0.98–1.02), was associated with increased risk of CV events. Meanwhile, adding the TyG index to the original model led to a significant improvement in C-statistics (0.618 vs. 0.627, P < 0.001), NRI (0.12, P = 0.031) and IDI (0.14%, P = 0.003), whereas no significant improvements were observed when adding Ln (TG/HDL-C ratio) or METS-IR (both P > 0.05) to the original model. Conclusions The TyG index, not TG/HDL-C ratio and METS-IR, was positively associated with worse CV outcomes in patients undergoing complex PCI. Our study, for the first time, demonstrated that the TyG index can serve as the suitable non-insulin-based IR marker to help in risk stratification and prognosis in this population.

The difference in estimated glomerular filtration rate (eGFR) derived from creatinine and cystatin C (eGFR ) has been noticed recently and the relationship with poor cardiovascular prognosis has been proven. However, primary prevention of the risk of coronary artery disease (CAD) is equally important but there is a lack of studies specifically investigating this implication. This prospective cohort study utilized data from the UK Biobank, including 437,536 participants without CAD at baseline. The primary outcome was defined as CAD. The eGFR was calculated by subtracting creatinine-based eGFR from cystatin C-based eGFR. Participants were then categorized into a negative, intermediate range, and positive group based on thresholds of -15 mL/min/1.73 m and 15 mL/min/1.73 m . Cox proportional risk models were used to evaluate the associations of eGFR with CAD and the relationship among different genetic risks of CAD. During a median follow-up of 13.8 years, CAD occurred in 36,797 participants. In the fully adjusted model, compared to midrange eGFR participants with a positive eGFR had a lower risk of CAD (HR 0.717, 95%CI 0.675-0.762), while with a negative eGFR had a higher risk (HR 1.433, 95%CI 1.399-1.468). When eGFR was treated as a continuous variable, a statistically significant trend toward a lower risk of CAD as eGFR increased (HR 0.982, 95% CI 0.981-0.982). Moreover, this relationship is independent of genetic susceptibility. eGFR was associated with CAD risk, where a high eGFR corresponded to a decreased likelihood of CAD onset no matter genetic susceptibility.

Background Stress hyperglycemia was positively associated with poor prognosis in individuals with acute myocardial infarction (AMI). However, admission glucose and stress hyperglycemia ratio (SHR) may not be the best indicator of stress hyperglycemia. We performed this study to evaluate the comparative prognostic value of different measures of hyperglycemia (fasting SHR, fasting plasma glucose [FPG], and hemoglobin A1c [HbA1c]) for in-hospital mortality in AMI patients with or without diabetes. Methods In this prospective, nationwide, multicenter China Acute Myocardial Infarction (CAMI) registry, 5,308 AMI patients including 2081 with diabetes and 3227 without diabetes were evaluated. Fasting SHR was calculated using the formula [(first FPG (mmol/l))/(1.59×HbA1c (%)-2.59)]. According to the quartiles of fasting SHR, FPG and HbA1c, diabetic and non-diabetic patients were divided into four groups, respectively. The primary endpoint was in-hospital mortality. Results Overall, 225 (4.2%) patients died during hospitalization. Individuals in quartile 4 had a significantly higher rate of in-hospital mortality compared with those in quartile 1 in diabetic cohort (9.7% vs. 2.0%; adjusted odds ratio [OR] 4.070, 95% CI 2.014–8.228) and nondiabetic cohort (8.8% vs. 2.2%; adjusted OR 2.976, 95% CI 1.695–5.224). Fasting SHR was also correlated with higher in-hospital mortality when treated as a continuous variable in diabetic and nondiabetic patients. Similar results were observed for FPG either as a continuous variable or a categorical variable. In addition, fasting SHR and FPG, rather than HbA1c, had a moderate predictive value for in-hospital mortality in patients with diabetes (areas under the curve [AUC] for fasting SHR: 0.702; FPG: 0.689) and without diabetes (AUC for fasting SHR: 0.690; FPG: 0.693). The AUC for fasting SHR was not significantly different from that of FPG in diabetic and nondiabetic patients. Moreover, adding fasting SHR or FPG to the original model led to a significant improvement in C-statistic regardless of diabetic status. Conclusions This study indicated that, in individuals with AMI, fasting SHR as well as FPG was strongly associated with in-hospital mortality regardless of glucose metabolism status. Fasting SHR and FPG might be considered as a useful marker for risk stratification in this population. Trial registration : ClinicalTrials.gov NCT01874691.

Background Coronary three-vessel disease (CTVD) accounts for one-third of the overall incidence of coronary artery disease, with heightened mortality rates compared to single-vessel lesions, including common trunk lesions. Dysregulated glucose metabolism exacerbates atherosclerosis and increases cardiovascular risk. The stress hyperglycemia ratio (SHR) is proposed as an indicator of glucose metabolism status but its association with cardiovascular outcomes in CTVD patients undergoing percutaneous coronary intervention (PCI) remains unclear. Methods 10,532 CTVD patients undergoing PCI were consecutively enrolled. SHR was calculated using the formula: admission blood glucose (mmol/L)/[1.59×HbA1c (%)–2.59]. Patients were divided into two groups (SHR Low and SHR High) according to the optimal cutoff value of SHR. Multivariable Cox regression models were used to assess the relationship between SHR and long-term prognosis. The primary endpoint was cardiovascular (CV) events, composing of cardiac death and non-fatal myocardial infarction (MI). Results During the median follow-up time of 3 years, a total of 279 cases (2.6%) of CV events were recorded. Multivariable Cox analyses showed that high SHR was associated with a significantly higher risk of CV events [Hazard Ratio (HR) 1.99, 95% Confidence interval (CI) 1.58–2.52, P  < 0.001). This association remained consistent in patients with (HR 1.50, 95% CI 1.08–2.10, P  = 0.016) and without diabetes (HR 1.97, 95% CI 1.42–2.72, P  < 0.001). Additionally, adding SHR to the base model of traditional risk factors led to a significant improvement in the C-index, net reclassification and integrated discrimination. Conclusions SHR was a significant predictor for adverse CV outcomes in CTVD patients with or without diabetes, which suggested that it could aid in the risk stratification in this particular population regardless of glucose metabolism status.