Background: Premature coronary artery disease (PCAD) has become more common in recent years and is often associated with poor outcomes. Triglyceride-glucose (TyG) index is a simple and reliable surrogate for insulin resistance (IR) and is an independent predictor of cardiovascular prognosis. However, the prognostic value of the TyG index in patients with PCAD remains uncertain. Thus, this study aimed to investigate the prognostic value and predictive performance of the TyG index in patients with PCAD. Methods: A total of 526 young subjects (male < 45 years, female < 55 years) with angiographically proven CAD from January 2013 to December 2018 were included consecutively in this study. Their clinical and laboratory parameters were collected, and the TyG index was calculated as $$\mathrm{Ln}[\mathrm{fasting triglyceride }(\mathrm{TG}) (\mathrm{mg}/\mathrm{dL})\times \mathrm{fasting plasma glucose }(\mathrm{FPG}) (\mathrm{mg}/\mathrm{dL})/2]$$Ln [ fasting triglyceride ( TG ) ( mg / dL ) × fasting plasma glucose ( FPG ) ( mg / dL ) / 2 ] . The follow-up time after discharge was 40–112 months (median, 68 months; interquartile range, 49‒83 months). The primary endpoint was the occurrence of the major adverse cardiovascular events (MACE), defined as the composite of all-cause death, non-fatal myocardial infarction (MI), coronary artery revascularization, and non-fatal stroke. Results: The TyG index was significantly associated with traditional cardiovascular risk factors and the Gensini score (GS). Kaplan–Meier survival (MACE-free) curves by tertiles of the TyG index showed statistically significant differences (log-rank test, p = 0.001). In the fully adjusted Cox regression model, the Hazard ratio (95% CI) of MACE was 2.17 (1.15–4.06) in tertile 3 and 1.45 (1.11–1.91) for per SD increase in the TyG index. Time-dependent ROC analyses of the TyG for prediction of MACE showed the area under the curves (AUC) reached 0.631 at 3 years, 0.643 at 6 years, and 0.710 at 9 years. Furthermore, adding TyG index to existing risk prediction model could improve outcome prediction [C-statistic increased from 0.715 to 0.719, p = 0.007; continuous net reclassification improvement (NRI) = 0.101, p = 0.362; integrated discrimination improvement (IDI) = 0.011, p = 0.017]. Conclusion: The TyG index is an independent predictor of MACE in patients with PCAD, suggesting that the TyG index has important clinical implications for risk stratification and early intervention of PCAD.

Despite established associations between insulin resistance (IR)-related indices and cardiometabolic diseases (CMDs), most studies are limited to single CMD outcomes. The study aimed to examine the influence of IR-related indices on the incidence, predictive value, and progression trajectory of cardiometabolic multimorbidity (CMM), as well as potential biological mechanisms. This prospective study included 374,274 individuals from the UK Biobank who were free of CMDs at baseline. CMM was defined as the presence of two or more CMDs, including type 2 diabetes (T2D), coronary heart disease (CHD), and stroke. Five indices were developed to assess IR levels: triglyceride-glucose (TyG) index, TyG-body mass index (TyG-BMI), TyG-waist circumference (TyG-WC), TyG-waist-height ratio (TyG-WHtR), and triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio. Cox proportional hazards and multi-state models were utilized to examine the associations between IR-related indices and CMM incidence and transition, respectively, with results expressed as hazard ratios (HRs) and 95% confidence intervals (CIs). The predictive utility of these indices was assessed using the net reclassification index (NRI) and integrated discrimination improvement index (IDI). Mediation analyses were conducted to quantify the potential mediating roles of biomarkers. During a mean follow-up period of 13.7 years, 5048 (1.3%) individuals developed CMM. Elevated baseline IR-related indices were associated with higher risks of incident CMM. The HRs (95% CIs) for each 1-standard deviation increase were as follows: 1.30 (1.26–1.34) for the TyG index, 1.42 (1.39–1.46) for the TyG-BMI, 1.54 (1.49–1.59) for the TyG-WC, 1.52 (1.48–1.57) for the TyG-WHtR, and 1.19 (1.17–1.21) for the TG/HDL-C ratio. Besides, TyG-WHtR and TyG-WC exhibited significantly higher NRI and IDI, indicating superior predictive performance for CMM risk. These indices played critical yet distinct roles in the progression of CMM. For transitions from being free of CMDs to single CMDs, these indices had the strongest impact on T2D (all P < 0.001). Participants initially diagnosed with CHD were more likely to progress to CMM when exposed to higher IR-related indices (all P < 0.001). The effect sizes for TyG-WC and TyG-WHtR were greater than those of other indices across all transitions. Mediation analyses revealed that biomarkers associated with liver function, renal function, and inflammation collectively mediated approximately one-third of the associations of the TyG-WHtR and TyG-WC indices with incident CMM. Our findings highlight the critical role of IR-related indices, particularly TyG-WHtR and TyG-WC, in the incidence, progression, and prevention of CMM. The mediation effects of biomarkers indicate the potential for targeted interventions to reduce CMM risk in high-IR individuals.

The aim of this study was to investigate the relationship between lymphocyte to monocyte ratio (LMR) and the severity of coronary artery disease (CAD) by using Gensini score. A total of 199 patients, who had undergone coronary angiography, were included in the study and retrospectively analyzed. Among them, 49 patients who had normal coronary arteries were selected as the control group. Patients with CAD were divided into 2 groups, those with low Gensini score (≤40) and those with high Gensini score (≥40). Our results showed that LMR in the severe atherosclerosis group was significantly lower than those of the mild atherosclerosis group and the control group. There was a closely significant correlation between the Gensini score and LMR (r = −0.362, P < .001). Furthermore, multivariate logistic regression analysis demonstrated that LMR (odds ratio, 0.715; 95% confidence interval [CI], 0.551–0.927; P = .012) was independent predictors of severe atherosclerosis. Using an optimal LMR cut-off value of 5.06, LMR predicted severe atherosclerosis with a sensitivity of 57.1% and specificity of 69.7% (area under curve = 0.634; 95% CI, 0.545–0.724; P = .005). Then patients with CAD group was divided into 2 groups according to the LMR value of 5.06. Patients with LMR ≤ 5.06 had worse prognosis, with a higher rate of cardiovascular events during up to 1 year follow-up. Our study demonstrated that LMR was independently and positively associated with the severity of coronary atherosclerosis, providing a new insight in the application of inflammation index evaluating the severity of CAD. And LMR may be a useful predictor of future cardiovascular events in patients with CAD.

Background: The triglyceride–glucose (TyG) index is known as a reliable alternative marker of insulin resistance (IR), which has been regarded as a predictor of cardiovascular disease (CVD). However, whether TyG index can predict the risk and occurrence of CVD in non-diabetic population remains uncertain. The aim of this study was to explore the association between the TyG index and cardiovascular risk factors and to clarify the prognostic value of the TyG index for CVD, coronary heart disease (CHD) and stroke in non-diabetic general population in Eastern China. Methods: A total of 6095 cases without diagnosed diabetes and CVD were included. The TyG index was calculated as ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2) and the participants were divided into 4 groups according to the TyG index quartiles (Q1, Q2, Q3, Q4). The primary outcome was CVD, including CHD and stroke. Cox proportional hazards regression analysis was used to investigate the association between the TyG index and the risk of CVD. Results: During the 10-year follow-up, 357 (5.9%) participants of CVD, 224 (3.7%) participants of CHD and 151 (2.5%) participants of stroke were observed. The incidence of CVD increased with the TyG index quartiles. Multivariate Cox regression analysis showed that the hazard ratios [95% confidence interval (CI)] in Q4 group were respectively 1.484 (1.074–2.051) for CVD, 1.687 (1.105–2.575) for CHD and 1.402 (0.853–2.305) for stroke compared to Q1 group. Moreover, adding the TyG index to models with traditional risk factors yielded a significant improvement in discrimination and reclassification of incident CVD and CHD. Conclusions: The TyG index is associated with cardiovascular risk factors and can be used as a useful, low-cost predictive marker for CVD and CHD risk in non-diabetic population.

Previous studies suggested a beneficial effect of natriuretic peptides in animal models of cardiovascular disease, but the role of natriuretic peptide receptor C (NPRC) in the pathogenesis of atherosclerosis (AS) remains unknown. This study was designed to test the hypothesis that NPRC may promote AS lesion formation and instability by enhancing oxidative stress, inflammation, and apoptosis via protein kinase A (PKA) signaling. ApoE^−/− mice were fed chow or Western diet for 12 weeks and NPRC expression was significantly increased in the aortic tissues of Western diet-fed mice. Systemic NPRC knockout mice were crossed with ApoE^−/− mice to generate ApoE^−/−NPRC^−/− mice, and NPRC deletion resulted in a significant decrease in the size and instability of aortic atherosclerotic lesions in ApoE^−/−NPRC^−/− versus ApoE^−/− mice. In addition, endothelial cell-specific NPRC knockout attenuated atherosclerotic lesions in mice. In contrast, endothelial cell overexpression of NPRC aggravated the size and instability of atherosclerotic aortic lesions in mice. Experiments in vitro showed that NPRC knockdown in human aortic endothelial cells (HAECs) inhibited ROS production, pro-inflammatory cytokine expression and endothelial cell apoptosis, and increased eNOS expression. Furthermore, NPRC knockdown in HAECs suppressed macrophage migration, cytokine expression, and phagocytosis via its effects on endothelial cells. On the contrary, NPRC overexpression in endothelial cells resulted in opposite effects. Mechanistically, the anti-inflammation and anti-atherosclerosis effects of NPRC deletion involved activation of cAMP/PKA pathway, leading to downstream upregulated AKT1 pathway and downregulated NF-κB pathway. In conclusion, NPRC deletion reduced the size and instability of atherosclerotic lesions in ApoE^−/− mice via attenuating inflammation and endothelial cell apoptosis and increasing eNOS expression by modulating cAMP/PKA-AKT1 and NF-κB pathways. Thus, targeting NPRC may provide a promising approach to the prevention and treatment of atherosclerosis.

Currently, floating wind turbines (FWTs) may be the more economical and suitable systems with which to exploit offshore wind energy in deep waters. Among the various types of floating foundations for offshore wind farms, a tension leg platform (TLP) foundation can provide a relatively stable platform for currently available offshore wind turbines without requiring major modifications. In this study, a new multi-column TLP foundation (WindStar TLP) was developed for the NREL 5-MW offshore wind turbine according to site-specific environmental conditions, which are the same as the OC3-Hywind (NREL) conditions. The general arrangement, main structure and mooring system were also designed and investigated through hydrodynamic and natural frequency analyses. The complete system avoids resonance through the rotor excitations. An aero-hydro-servo-elastic coupled analysis was carried out in the time domain with the numerical tool FAST. Statistics of the key parameters were obtained and analysed and comparisons to MIT/NREL TLP are made. As a result, the design requirements were shown to be satisfied, and the proposed WindStar TLP was shown to have favourable motion characteristics under extreme wind and wave conditions with a lighter and smaller structure. The new concept holds great potential for further development.