Background Previous studies reported the prognostic value of the atherogenic index of plasma (AIP) in the course of atherosclerosis and other cardiovascular diseases (CVDs). Still, the predictive utility of the AIP is unknown among patients with type 2 diabetes mellitus (T2DM). Methods This was a secondary analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, which randomized 10,251 patients with long-lasting T2DM. ROC curve analysis was used to determine an optimal threshold for AIP, and the study population was divided into high and low AIP groups. Univariable and multivariable Cox proportional hazards regression analyses were used to determine the association between AIP and primary (major adverse cardiovascular events [MACEs], including nonfatal myocardial infarction, nonfatal stroke, and/or death from cardiovascular causes) and secondary outcomes (all-cause mortality). Stratified analyses were performed to control for the confounding factors. Results AIP was an independent risk factor for the prognosis of T2DM (HR = 1.309; 95% CI 1.084–1.581; P = 0.005). The threshold for AIP was determined to be 0.34 in the study population. After adjustments for confounding factors, multivariable analysis showed that AIP was associated with the risk of MACEs (Model 1: HR = 1.333, 95% CI 1.205–1.474, P < 0.001; Model 2: HR = 1.171, 95% CI 1.030–1.333, P = 0.016; Model 3: HR = 1.194, 95% CI 1.049–1.360, P = 0.007), all-cause mortality (Model 1: HR = 1.184, 95% CI 1.077–1.303, P < 0.001), cardiovascular death (Model 1: HR = 1.422, 95% CI 1.201–1.683, P < 0.001; Model 3: HR = 1.264, 95% CI 1.015–1.573, P = 0.036), and nonfatal myocardial infarction (Model 1: HR = 1.447, 95% CI 1.255–1.669, P < 0.001; Model 2: HR = 1.252, 95% CI 1.045–1.499, P = 0.015; Model 3: HR = 1.284, 95% CI 1.071–1.539, P = 0.007). Subgroup stratified analyses showed that AIP might interact with sex, a classical risk factor of cardiovascular events. Conclusions This study showed that AIP might be a strong biomarker that could be used to predict the risk of cardiovascular events in patients with T2DM. Trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000620.

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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.

Background. The impact of sex on the outcome of patients with acute coronary syndrome (ACS) has been suggested, but little is known about its impact on elderly patients with ACS. Methods. This study analyzed the impact of sex on in-hospital and 1-year outcomes of elderly (≥75 years of age) patients with ACS hospitalized in our department between January 2013 and December 2017. Results. A total of 711 patients were included: 273 (38.4%) women and 438 (61.6%) men. Their age ranged from 75 to 94 years, similar between women and men. Women had more comorbidities (hypertension (79.5% vs. 72.8%, p=0.050), diabetes mellitus (35.2% vs. 26.5%, p=0.014), and hyperuricemia (39.9% vs. 32.4%, p=0.042)) and had a higher prevalence of non-ST-segment elevation ACS (NSTE-ACS) (79.5% vs. 71.2%, p=0.014) than men. The prevalence of current smoking (56.5% vs. 5.4%, p<0.001), creatinine levels (124.4 ± 98.6 vs. 89.9 ± 54.1, p<0.001), and revascularization rate (39.7% vs. 30.0%, p=0.022) were higher, and troponin TnT and NT-proBNP tended to be higher in men than in women. The in-hospital mortality rate was similar (3.5% vs. 4.4%, p=0.693), but the 1-year mortality rate was lower in women than in men (14.7% vs. 21.7%, p=0.020). The multivariable analysis showed that female sex was a protective factor for 1-year mortality in all patients (OR = 0.565, 95% CI 0.351–0.908, p=0.018) and in patients with STEMI (OR = 0.416, 95% CI 0.184–0.940, p=0.035) after adjustment. Conclusions. Among the elderly patients with ACS, the 1-year mortality rate was lower in women than in men, which could be associated with comorbidities and ACS type.

As an important transcription factor, heat shock factor 1 (HSF1) plays an endogenous anti-inflammation role in the body and can alleviate multiple organ dysfunction caused by sepsis, which contributes to an uncontrolled inflammatory response. The NLRP3 inflammasome is a supramolecular complex that plays key roles in immune surveillance. Inflammation is accomplished by NLRP3 inflammasome activation, which leads to the proteolytic maturation of IL-1β and pyroptosis. However, whether HSF1 is involved in the activation of the NLRP3 inflammasome in septic acute lung injury (ALI) has not been reported. Here, we show that HSF1 suppresses NLRP3 inflammasome activation in transcriptional and post-translational modification levels. HSF1 can repress NLRP3 expression via inhibiting NF-κB phosphorylation. HSF1 can inhibit caspase-1 activation and IL-1β maturation via promoting NLRP3 ubiquitination. Our finding not only elucidates a novel mechanism for HSF1-mediated protection of septic ALI but also identifies new therapeutic targets for septic ALI and related diseases.

Background. Hyperuricemia is a risk factor for cardiovascular diseases, but the impact of hyperuricemia and sex-related disparities is not fully clear in elderly patients with acute coronary syndrome (ACS). Objective. To investigate the association between hyperuricemia and 1-year all-cause mortality in elderly patients with ACS. Methods. This retrospective cohort study included 711 consecutive ACS patients aged ≥75 years, hospitalized in our center between January 2013 and December 2017. Serum uric acid (sUA), in-hospital events, and 1-year follow-up were analyzed. Multivariable logistic regression models were used to explore the risk factors for in-hospital events and 1-year all-cause mortality. Results. sUA levels were higher in males than in females (381.4 ± 110.1 vs. 349.3 ± 119.1 μmol/l, P<0.001). Prevalence of hypertension (80.5% vs. 72.6%, P=0.020), atrial fibrillation (16.2% vs. 9.5%, P=0.008), and severe heart failure (61.0% vs. 44.2%, P<0.001) were higher in patients with hyperuricemia than in patients with normal sUA. During the 1-year follow-up, 135 patients died (19.0%); all-cause mortality was higher in patients with hyperuricemia than in patients with normal sUA (23.1% vs. 16.7%, P=0.039). Hyperuricemia is related to in-hospital ventricular tachycardia and 1-year all-cause mortality (OR = 1.799, 95% CI 1.050–3.081, P=0.033; OR = 1.512, 95% CI 1.028–2.225, P=0.036, respectively). Multivariable regression analysis models showed that hyperuricemia was an independent risk factor of 1-year all-cause mortality in women (OR = 2.539, 95% CI 1.001–6.453, P=0.050), but not in men (OR = 0.931, 95% CI 0.466–1.858, P=0.839) after adjustment for confounding variables. Conclusions. Hyperuricemia is an independent risk factor for 1-year all-cause mortality in elderly female patients with ACS.

Background and AimsThis study aimed to evaluate the association of the triglyceride-glucose (TyG) index with the cardiovascular incidence in patients with type 2 diabetes mellitus (T2DM).Methods and ResultsSecondary analysis in patients with long-lasting T2DM from the Action to Control Cardiovascular Risk in Diabetes study was performed. The primary outcome was the first occurrence of major adverse cardiovascular events (MACEs). The association between the baseline and trajectories of the TyG index and MACEs was evaluated by Cox proportional hazards regression analysis. During a median follow-up period of 8.8 years, 1,815 (17.8%) patients developed MACEs. After traditional cardiovascular risk factor adjustments, each 1-standard deviation increase in the TyG index was associated with a 19.00% higher MACE risk, similar to that in the TyG index quartile characterization. Four distinct trajectories of TyG indexes were identified: low (16.17%), moderate (40.01%), high (34.60%), and very high (9.30%). In multivariate analysis, high and very high TyG index trajectories showed a greater risk of future MACE incidence than the low TyG index trajectory. A similar association was observed between the TyG index and the occurrence of coronary heart disease.ConclusionsThe baseline and trajectories of the TyG index were significantly associated with the occurrence of MACEs in patients with T2DM.Clinical Trial Registrationhttp://www.clinicaltrials.gov. Unique identifier: NCT00000620.

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