The role of residual inflammatory risk and LDL cholesterol in patients with in-stent restenosis undergoing percutaneous coronary intervention.

BACKGROUND: To evaluate the relationships between residual inflammatory risk [assessed by high-sensitivity C-reactive protein (hsCRP)], residual cholesterol risk [assessed by low-density lipoprotein cholesterol (LDL-C)] and clinical outcomes among patients who underwent percutaneous coronary intervention (PCI) for in-stent restenosis (ISR) lesions. METHODS: Between January 2017 and December 2018, a total of 2079 patients who underwent PCI for ISR were consecutively enrolled. The primary outcome was the rate of major adverse cardiac events (MACE), defined as a composite endpoint of all-cause death, spontaneous myocardial infarction (MI), or repeat revascularization. RESULTS: During a median follow-up of 36 months, 436 MACEs occurred. Baseline hsCRP was significantly associated with MACE (highest versus lowest quartile, adjusted hazard ratio [aHR] 1.90 [95 % CI, 1.39-2.59]; P < 0.001). By contrast, the baseline LDL-C quartile was not associated with MACE (highest versus lowest quartile, aHR 0.93 [95 % CI, 0.71- 1.22]; P = 0.59). Compared with patients without residual risk (hsCRP <2 mg/L and LDL-C < 70 mg/dL), participants with both residual inflammatory and LDL-C risk (hsCRP ≥2 mg/L and LDL-C ≥ 70 mg/dL) (aHR, 1.39 [95 % CI, 1.06-1.83]; P = 0.02) and those with residual inflammatory risk only (hsCRP ≥2 mg/L and LDL-C < 70 mg/dL) (aHR, 1.34 [95 % CI, 1.01-1.72]; P = 0.04) had significantly higher risks of MACE. CONCLUSIONS: In the current cohort of patients after ISR PCI, inflammation assessed by hsCRP predicted higher risk of adverse clinical outcomes, whereas the level of LDL-C was not associated with adverse prognosis.

J-shaped association between apolipoprotein B and CV outcomes in statin-treated patients with chronic coronary syndrome.

INTRODUCTION AND OBJECTIVES: The association between apolipoprotein B (apoB) and residual cardiovascular (CV) risk in patients with chronic coronary syndrome (CCS) remains unclear. We aimed to investigate the association between apoB levels and CV outcomes in statin-treated CCS patients. METHODS: We enrolled 8641 statin-treated CCS patients at Fuwai Hospital. The patients were divided into 5 groups based on to apoB quintiles (Q1 to Q5). The primary endpoint was 3-year CV events, including CV death, nonfatal myocardial infarction, and nonfatal stroke. RESULTS: During a median follow-up of 3.17 years, there were 232 (2.7%) CV events. After multivariable adjustment, a restricted cubic spline illustrated a J-shaped relationship between apoB levels and 3-year CV events, with the risk remaining flat until apoB levels exceeded 0.73 g/L, after which the risk increased (nonlinear P < .05). Kaplan-Meier curves showed the lowest CV event rate in the Q3 group (0.68-0.78 g/L). Compared with the Q3 group, multivariable Cox regression models revealed that both low (Q1, ≤ 0.57 g/L) and high (Q5, > 0.93 g/L) apoB levels were associated with an increased risk of major adverse cardiac events (all P < .05). Notably, patients with low apoB levels (Q1) had the highest risk of CV death (HR, 2.44; 95%CI, 1.17-5.08). CONCLUSIONS: Our analysis indicates that both low and high levels of apoB are associated with elevated CV risk, with the risk being particularly pronounced at higher levels (> 0.73 g/L).

Insulin-based or non-insulin-based insulin resistance indicators and risk of long-term cardiovascular and all-cause mortality in the general population: A 25-year cohort study.

OBJECTIVE: Although insulin resistance (IR) has been recognized to be a causal component in various diseases, current information on the relationship between IR and long-term mortality in the general population is limited and conclusions varied among different IR indicators and different populations. We aimed to assess associations between different measurements of IR with long-term all-cause mortality and cardiovascular mortality risk for the general population. RESEARCH DESIGN AND METHODS: We included 13,909 individuals from the Third National Health and Nutrition Examination Survey. Mortality was identified via National Death Index information until December 31, 2019. IR was measured using fasting insulin, homeostasis model assessment of IR (HOMA-IR), homeostasis model assessment of ß-cell function, quantitative insulin sensitivity check index (QUICKI), insulin-to-glucose ratio (IGR), triglyceride glucose (TyG) index, TyG-body mass index (TyG-BMI), and hypertriglyceridemic-waist phenotype. RESULTS: During median 25-year follow-up, 5,306 all-cause mortality events occurred. After multivariate adjustment, variables significantly associated with elevated all-cause mortality risk were (hazard ratio [95 % confidence interval]): higher insulin (1.07 [1.02;1.13]); HOMA-IR (1.08 [1.03;1.13]); IGR (1.05 [1.00;1.11]); TyG (1.07 [1.00;1.14]); TyG-BMI (1.24 [1.02;1.51]); lower QUICKI (0.91 [0.86-0.96]). After stratification by diabetes status, higher insulin, HOMA-IR, TyG-BMI and lower QUICKI were significantly associated with increased risk of all-cause mortality in both diabetes and non-diabetes populations (all P for interaction > 0.05). Higher TyG (adjusted HR 1.17 [1.09;1.26], P for interaction = 0.018) and hypertriglyceridemic-waist phenotype (adjusted HR 1.26 [1.08;1.46], P for interaction = 0.047) were significantly associated with increased risk of all-cause mortality in patients with diabetes, however, these associations could not be seen in people without diabetes. Similar results were observed between the above-mentioned IR indicators and cardiovascular death. CONCLUSIONS: Fasting insulin, HOMA-IR, TyG-BMI, and QUICKI may indicate mortality risk in diabetes and non-diabetes populations, with TyG and the hypertriglyceridemic-waist phenotype showing particular relevance for individuals with diabetes. Further studies are needed to validate these findings and determine their broader applicability.

Novel insights on dual antiplatelet therapy duration following stenting for angiography-detected moderate-to-severe calcified coronary lesions.

Dual antiplatelet therapy (DAPT), comprising both aspirin and the P2Y12 receptor inhibitor, is crucial in managing patients with coronary artery disease following percutaneous coronary intervention (PCI). The optimal duration for DAPT in patients with angiography-detected moderate-to-severe calcified coronary (MSCC) lesions who underwent PCI with drug-eluting stents (DES) implantation remains uncertain. We recruited patients with angiography-detected MSCC lesions who received DES implantation from the prospective Fuwai Percutaneous Coronary Intervention Registry. Patients were classified into two groups according to the duration of DAPT: those with a DAPT duration of one year or less, and those with a DAPT duration of more than one year. The primary endpoint was the major adverse cardiovascular and cerebrovascular event, which was defined as composed of all-cause death, nonfatal myocardial infarction, or nonfatal stroke. The key-safety endpoint was bleeding type 2, 3, or 5 according to the Bleeding Academic Research Consortium criteria. There were 1730 patients included in the study, and 470 (27.17 %) continued DAPT for more than one year after undergoing MSCC-PCI with DES implantation. The median follow-up time was 2.5 years. DAPT>1-year versus ≤1-year DAPT was significantly associated with a reduced risk of the primary outcome (1.59 % versus 3.19 %; adjusted hazard ratio=0.44; 95 % CI: 0.22-0.88). Similar trends were observed for all-cause death (0.16 % versus 1.91 %; P<0.001) and cardiovascular death (0.08 % versus 1.06 %; P=0.001). There was no significant difference in the key-safety endpoint between 2 regimens (1.75 % versus 0.85 %; adjusted hazard ratio=1.95; 95 % CI: 0.65-5.84). In conclusion, long-term DAPT after DES implantation in patients with MSCC lesions resulted in improved clinical outcomes at 2.5 years. This was achieved by reducing the risk of ischemia without increasing clinically significant bleeding.

Hemoglobin glycation index and cardiovascular outcomes in patients with diabetes and coronary artery disease: insights from a large cohort study.

BACKGROUND/OBJECTIVES: The hemoglobin glycation index (HGI) has been demonstrated to serve as a substitute for the individual bias in glycosylated hemoglobin A1c (HbA1c). Our objective was to assess the correlation between HGI and cardiovascular (CV) outcomes in patients with diabetes and coronary artery disease (CAD). SUBJECTS/METHODS: We sequentially recruited 11921 patients with diabetes and CAD at Fuwai Hospital. The patients were categorized into five groups based on their HGI quintiles, ranging from Q1 to Q5. The primary endpoint was the occurrence of major adverse cardiac events (MACEs), which included CV death and nonfatal myocardial infarction. RESULTS: During the median 3-year follow-up, 327 (2.7%) MACEs were observed. A U-shaped relationship between HGI and 3-year MACEs was demonstrated by restricted cubic spline (RCS) after multivariable adjustment (nonlinear P = 0.014). The Kaplan-Meier curves demonstrated that the Q2 group had the lowest risk of MACE (P = 0.006). When comparing the HGI Q2 group, multivariable Cox regression models showed that both low (Q1) and high (Q4 or Q5) HGI were linked to a higher risk of MACEs (all P < 0.05). Patients with a low HGI (Q1) had a significantly increased risk of all-cause and CV death, with a 1.70-fold increase in both cases (both P < 0.05). CONCLUSIONS: In individuals with diabetes and established CAD, HGI levels were found to have a U-shaped relationship with the occurrence of MACEs over a period of three years. Significantly, those with low HGI had an increased risk of CV death.

Technological Advances Are Associated With Better Clinical Outcomes of Percutaneous Coronary Intervention in Patients With Unprotected Left Main Disease.

BACKGROUND: Few large-scale studies have evaluated the effectiveness of percutaneous coronary intervention (PCI) technological advances in the treatment of patients with unprotected left main coronary artery disease (LM-CAD). We aim to identify independent factors that affect the prognosis of PCI in patients with unprotected LM-CAD and to assess the impact of PCI technological advances on long-term clinical outcomes. METHODS AND RESULTS: A total of 4512 consecutive patients who underwent unprotected LM-CAD PCI at Fuwai Hospital from 2004 to 2016 were enrolled. Multivariable Cox proportional hazards model was used to identify which techniques can independently affect the incidence of major adverse cardiac events (MACEs; a composite of cardiac death, myocardial infarction, or target vessel revascularization). The incidence of 3-year MACEs was 9.0% (406/4512). Four new PCI techniques were identified as the independent protective factors of MACEs, including second-generation drug-eluting stents (hazard ratio [HR], 0.61 [95% CI, 0.37-0.99]), postdilatation (HR, 0.75 [95% CI, 0.59-0.94]), final kissing balloon inflation (HR, 0.78 [95% CI, 0.62-0.99]), and using intravascular ultrasound (HR, 0.78 [95% CI, 0.63-0.97]). The relative hazard of 3-year MACEs was reduced by ≈50% with use of all 4 techniques compared with no technique use (HR, 0.53 [95% CI, 0.32-0.87]). CONCLUSIONS: PCI technological advances including postdilatation, second-generation drug-eluting stent, final kissing balloon inflation, and intravascular ultrasound guidance were associated with improved clinical outcomes in patients who underwent unprotected LM-CAD PCI.

Prognostic value of the stress-hyperglycaemia ratio in patients with moderate-to-severe coronary artery calcification: Insights from a large cohort study.

AIM: To evaluate the relationship between the stress-hyperglycaemia ratio (SHR) and the clinical prognosis of patients with moderate-to-severe coronary artery calcification (MSCAC). METHODS: We consecutively enrolled 3841 patients with angiography-detected MSCAC. The individuals were categorized into three groups based on SHR tertiles: T1 (SHR ≤ 0.77), T2 (0.77 < SHR ≤ 0.89) and T3 (SHR > 0.89). The SHR value was calculated using the formula SHR = [admission glucose (mmol/L)]/[1.59 × HbA1c (%) - 2.59]. The primary outcomes were major adverse cardiovascular and cerebrovascular events (MACCEs), including all-cause death, non-fatal myocardial infarction and non-fatal stroke. RESULTS: During a median follow-up of 3.11 years, 241 MACCEs were recorded. Kaplan-Meier survival analysis showed that the SHR T3 group had the highest incidence of MACCEs (P < .001). Moreover, findings from the restricted cubic spline analysis showed a significant and positive association between the SHR and MACCEs. This correlation remained consistent even after considering other variables that could potentially impact the results (Pnon-linear = .794). When comparing SHR T1 with SHR T3, it was found that SHR T3 was significantly associated with an increased risk of the primary outcome (adjusted hazard ratio = 1.50; 95% confidence interval: 1.10-2.03). CONCLUSIONS: Patients with MSCAC showed a positive correlation between the SHR and MACCE rate over a 3-year follow-up period. The study showed that an SHR value of 0.83 is the key threshold, indicating a poor prognosis. Future large-scale multicentre investigations should be conducted to determine the predictive value of the SHR in patients with MSCAC.

The impacts of percutaneous coronary intervention to treat chronic total occlusion of right coronary artery on the 5-year prognosis: A single-centered retrospective study.

BACKGROUND: Chronic total occlusions (CTO) occur in about 20% of patients referred for coronary angiography, and right coronary artery (RCA) CTO has been reported in 38-50% of the entire CTO population. Limited data on angiographic and procedural characteristics of RCA-CTO and the risk of adverse cardiac events asks for a detailed study. METHODS: From 2010 to 2013, patients with attempted revascularization of at least one CTO lesion were included and followed up to 5 years after PCI. Eligible patients are assigned to RCA-CTO and non-RCA-CTO groups based on their target vessels. The primary endpoint was major adverse cardiovascular events (MACEs; a composite of all-cause death, myocardial infarction (MI) or rehospitalization for heart failure), and secondary endpoints were cardiac death, target lesion revascularization (TLR) and target vessel revascularization (TVR). RESULTS: The present study included 2659 eligible patients, among which 1285 patients were assigned to the RCA-CTO group, whereas 1374 patients were assigned to the non-RCA-CTO group. Lesions in RCA had longer lesion length, higher J-CTO score, higher rates of severe vessel tortuosity, a higher percentage of Rentrop grade 2-3, and more likely to be re-try lesion than those in LAD or LCX (all P < 0.01). CTO lesions in RCA reached less successful recanalization and post-procedural TIMI 3 flow (all <0.01). Multivariate Cox analysis revealed that RCA-CTO was not associated with primary outcome MACEs. Besides MACEs, RCA-CTO was also not associated with cardiac death, but was significantly associated with TLR and TVR (adjusted HR: 1.37 [95% CI:1.07-1.76], P = 0.01; adjusted HR: 1.43 [95% CI:1.13-1.82], P = 0.003). CONCLUSION: RCA-CTO lesions, which had more complex angiographic features, independently contributed to TLR and TVR but not to MACEs or cardiac death in the 5 years of follow-up.

The effect of fasting plasma glucose on in-hospital mortality after acute myocardial infarction in patients with and without diabetes: findings from a prospective, nationwide, and multicenter registry.

OBJECTIVES: To evaluate the predictive value of fasting plasma glucose (FPG) for in-hospital mortality in patients with acute myocardial infarction (AMI) with different glucose metabolism status. METHODS: We selected 5,308 participants with AMI from the prospective, nationwide, multicenter CAMI registry, of which 2,081 were diabetic and 3,227 were nondiabetic. Patients were divided into high FPG and low FPG groups according to the optimal cutoff values of FPG to predict in-hospital mortality for diabetic and nondiabetic cohorts, respectively. The primary endpoint was in-hospital mortality. RESULTS: Overall, 94 diabetic patients (4.5%) and 131 nondiabetic patients (4.1%) died during hospitalization, and the optimal FPG thresholds for predicting in-hospital death of the two cohorts were 13.2 mmol/L and 6.4 mmol/L, respectively. Compared with individuals who had low FPG, those with high FPG were significantly associated with higher in-hospital mortality in diabetic cohort (10.1% vs. 2.8%; odds ratio [OR] = 3.862, 95% confidence interval [CI]: 2.542-5.869) and nondiabetic cohort (7.4% vs. 1.7%; HR = 4.542, 95%CI: 3.041-6.782). After adjusting the potential confounders, this significant association was not changed. Furthermore, FPG as a continuous variable was positively associated with in-hospital mortality in single-variable and multivariable models regardless of diabetic status. Adding FPG to the original model showed a significant improvement in C-statistic and net reclassification in diabetic and nondiabetic cohorts. CONCLUSIONS: This large-scale registry indicated that there is a strong positive association between FPG and in-hospital mortality in AMI patients with and without diabetes. FPG might be useful to stratify patients with AMI.

High stress hyperglycemia ratio predicts adverse clinical outcome in patients with coronary three-vessel disease: a large-scale cohort study.

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.

The effect of lipid-lowering therapy on lipid-related residual risk factors: a prospective study.

BACKGROUND: Remnant cholesterol (RC) and nonhigh-density lipoprotein cholesterol (nonHDL-C) are key risk factors for atherosclerotic cardiovascular disease (ASCVD), with apolipoprotein B (apoB) and lipoprotein(a) [Lp(a)] also contributing to its residual risk. However, real-world population-based evidence regarding the impact of current clinical LDL-C-centric lipid-lowering therapy (LLT) on achieving RC and nonHDL-C goals, as well as on modifying residual CVD risk factors is limited. METHODS: This prospective observational study enrolled 897 CVD patients from September, 2020 to July, 2021. All participants had previously received low-/moderate-intensity LLT and were discharged with either low-/moderate-intensity LLT or high-intensity LLT. After a median follow-up of 3 months, changes in RC, nonHDL-C, and other biomarkers were assessed. Multivariate logistic regression was performed to analyze the impact of the LLT on goal attainment. RESULTS: Among all patients, 83.50% transitioned to high-intensity LLT from low or moderate. After follow-up, the high-intensity group saw significantly greater reductions in RC (-20.51% vs. -3.90%, P = 0.025), nonHDL-C (-25.12% vs. 0.00%, P < 0.001), apoB (-19.35% vs. -3.17%, P < 0.001), triglycerides (-17.82% vs. -6.62%, P < 0.001), and LDL-C and total cholesterol. Spearman correlation analysis revealed that LDL-C reduction from current LLT was strongly correlated with nonHDL-C reduction (r = 0.87, P < 0.001). Patients who received high-intensity LLT had significant improvements in attainment of RC (from 44.2% to 60.7%, χ² = 39.23, P < 0.001) and nonHDL-C (from 19.4% to 56.9%, χ² = 226.06, P < 0.001) goals. Furthermore, multivariate logistic regression showed that high-intensity LLT was a protective factor for RC [odds ratio (OR) = 0.66; 95% confidence intervals (CI), 0.45-0.97; P = 0.033] and nonHDL-C goal attainment (OR = 0.51; 95% CI, 0.34-0.75; P < 0.001), without a significant increase of adverse reactions. CONCLUSION: Current levels of clinically prescribed LDL-C-centric treatment can reduce RC and other lipid-related residual risk factors, but high-intensity LLT is better at achieving nonHDL-C and RC goals than low-/moderate-intensity LLT, with a good safety profile. More targeted RC treatments are still needed to reduce residual lipid risk further.

The Neutrophil to Lymphocyte Ratio Modifies Lipoprotein (a)-Related Poor Prognosis in Patients After Percutaneous Coronary Intervention.

Lipoprotein (a) [Lp(a)] could contribute to coronary artery disease (CAD) through proinflammatory effects. The neutrophil to lymphocyte ratio (NLR) is an inflammatory biomarker. We consecutively enrolled 7,922 CAD patients to investigate the synergistic association of Lp(a) and NLR with prognosis in patients undergoing percutaneous coronary intervention (PCI). NLR was calculated as the neutrophil count divided by the lymphocyte count. Cutoff for NLR was a median of 2.07. The threshold value was set at 30 mg/dL for Lp(a). The primary endpoint was major adverse cardiac events (MACEs), including all-cause mortality and myocardial infarction. During 2 years follow-up, 111 (1.40%) MACEs occurred. Lp(a) > 30 mg/dL was associated with an increased MACE risk in participants with NLR ≥2.07 [adjusted hazard ratio (HR), 1.84; 95% CI, 1.12-3.03], but not in participants with NLR <2.07 (adjusted HR, 0.74; 95% CI, 0.38-1.45) (Pinteraction = 0.021). Subgroup analysis demonstrated that the synergistic association of Lp(a) and NLR with prognosis was more pronounced in female patients (Pinteraction = 0.028). This study suggested that combining Lp(a) and NLR may be useful for risk stratification in CAD population.

Association of Triglyceride Glucose-Derived Indices with Recurrent Events Following Atherosclerotic Cardiovascular Disease.

Background: Triglyceride glucose (TyG) and TyG-body mass index (TyG-BMI) are reliable surrogate indices of insulin resistance and used for risk stratification and outcome prediction in patients with atherosclerotic cardiovascular disease (ASCVD). Here, we inserted estimated average glucose (eAG) into the TyG (TyAG) and TyG-BMI (TyAG-BMI) as derived parameters and explored their clinical significance in cardiovascular risk prediction. Methods: This was a population-based cohort study of 9,944 Chinese patients with ASCVD. The baseline admission fasting glucose and A1C-derived eAG values were recorded. Cardiovascular events (CVEs) that occurred during an average of 38.5 months of follow-up were recorded. We stratified the patients into four groups by quartiles of the parameters. Baseline data and outcomes were analyzed. Results: Distribution of the TyAG and TyAG-BMI indices shifted slightly toward higher values (the right side) compared with TyG and TyG-BMI, respectively. The baseline levels of cardiovascular risk factors and coronary severity increased with quartile of TyG, TyAG, TyG-BMI, and TyAG-BMI (all P<0.001). The multivariate-adjusted hazard ratios for CVEs when the highest and lowest quartiles were compared from low to high were 1.02 (95% confidence interval [CI], 0.77 to 1.36; TyG), 1.29 (95% CI, 0.97 to 1.73; TyAG), 1.59 (95% CI, 1.01 to 2.58; TyG-BMI), and 1.91 (95% CI, 1.16 to 3.15; TyAG-BMI). The latter two showed statistical significance. Conclusion: This study suggests that TyAG and TyAG-BMI exhibit more information than TyG and TyG-BMI in disease progression among patients with ASCVD. The TyAG-BMI index provided better predictive performance for CVEs than other parameters.

Association of triglyceride-glucose index with adverse cardiovascular events in patients with established coronary artery disease according to different inflammatory status.

BACKGROUND AND AIMS: This study aimed to investigate the association of the triglyceride-glucose (TyG) index, a simple-but-reliable indicator of insulin resistance, with risk of cardiovascular (CV) events in coronary artery disease (CAD) patients with different inflammation status. METHODS AND RESULTS: We consecutively recruited 20,518 patients with angiograph-proven-CAD from 2017 to 2018 at Fuwai Hospital. Patients were categorized according to baseline TyG index tertiles (T) (tertile 1: ≤8.624; T2: 8.624-9.902 and T3: >9.902) and further assigned into 6 groups by high-sensitivity C-reactive protein (hsCRP) medians. The primary endpoint was CV events including CV death, nonfatal myocardial infarction and nonfatal stroke. During the 3.1-year-follow-up, 618 (3.0%) CV events were recorded. Overall, patients with high TyG index levels (T2 or T3) showed significantly increased risk of CV events (hazard ratio [HR]: 1.24; 95% confidence interval [CI]: 1.01-1.53; HR: 1.33; 95%CI: 1.05-1.68, respectively) compared with those with lowest Tyg index (T1) after adjusting for confounding factors. Upon stratification by hsCRP levels, elevated TyG index was associated with increased risk of CV events only in patients with hsCRP levels > median (per-1-unit-increase HR: 1.39; 95%CI: 1.11-1.74), rather than in those with hsCRP levels ≤ median. Furthermore, adding the TyG index to the predicting model led to a significant improvement in patients with hsCRP > median rather than in those with hsCRP ≤ median. CONCLUSIONS: We firstly found that elevated TyG index levels were associated with increased risk of CV events in CAD patients, especially in those with increased inflammatory status, suggesting that it could help in risk stratification and prognosis in this population.

Effectiveness and Safety of a Novel Intravascular Lithotripsy System for Severe Coronary Calcification: The CALCI-CRACK Trial.

BACKGROUND: Intravascular lithotripsy is effective and safe for managing coronary calcification; however, available devices are limited, and complex lesions have been excluded in previous studies. This study aimed to investigate the effectiveness and safety of a novel intravascular lithotripsy system for severe calcification in a population with complex lesions. METHODS: CALCI-CRACK (treatment of severe calcified coronary lesions with a novel intracoronary shock wave lithotripsy system) (ChiCTR2100052058) was a prospective, single-arm, multicentre study. The primary end point was the procedural success rate. Major safety end points included major adverse cardiovascular events (MACE) and target lesion failure (TLF) at 30 days and 6 months, and severe angiographic complications. Calcification morphology was assessed in the optical coherence tomography (OCT) subgroup. RESULTS: In total, 242 patients from 15 high-volume Chinese centres were enrolled, including 26.45% of patients with true bifurcation lesions, 3.31% with severely tortuous vessels, and 2.48% with chronic total occlusion, respectively. The procedural success rate was 95.04% (95% confidence interval 91.50%-97.41%), exceeding the prespecified performance goal of 83.4% (P < 0.001). The 30-day and 6-month MACE rates were 4.13% and 4.55%, respectively. TLF rates at those time points were 1.24% and 1.65%, respectively. Severe angiographic complications occurred in 0.42% of patients. In the OCT subgroup (n = 93), 93.55% of calcified lesions were fractured, and minimal lumen area increased from 1.55 ± 0.55 mm2 to 4.91 ± 1.22 mm2 after stent implantation, with acute gain rate of 245 ± 102%. CONCLUSIONS: The novel intravascular lithotripsy system is effective and safe for managing severely calcified coronary lesions in a cohort that included true bifurcation lesions, severely tortuous vessels, and chronic total occlusion. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), number ChiCTR2100052058.

Triiodothyronine induces a proinflammatory monocyte/macrophage profile and impedes cardiac regeneration.

Neonatal mouse hearts can regenerate post-injury, unlike adult hearts that form fibrotic scars. The mechanism of thyroid hormone signaling in cardiac regeneration warrants further study. We found that triiodothyronine impairs cardiomyocyte proliferation and heart regeneration in neonatal mice after apical resection. Single-cell RNA-Sequencing on cardiac CD45-positive leukocytes revealed a pro-inflammatory phenotype in monocytes/macrophages after triiodothyronine treatment. Furthermore, we observed that cardiomyocyte proliferation was inhibited by medium from triiodothyronine-treated macrophages, while triiodothyronine itself had no direct effect on the cardiomyocytes in vitro. Our study unveils a novel role of triiodothyronine in mediating the inflammatory response that hinders heart regeneration.

Molecular Imaging of Fibroblast Activation in Rabbit Atherosclerotic Plaques: a Preclinical PET/CT Study.

AIM: Atherosclerosis remains the pathological basis of myocardial infarction and ischemic stroke. Early and accurate identification of plauqes is crucial to improve clinical outcomes of atherosclerosis patients. Our study aims to evaluate the potential value of fibroblast activation protein inhibitor (FAPI)-04 PET/CT in identifying plaques via a preclinical rabbit model of atherosclerosis. METHODS: New Zealand white rabbits were fed high-fat diet (HFD), and randomly divided into the model group injured by the balloon, and the sham group only with incisions. Ultrasound was performed to detect plaques, and FAPI-avid was determined through Al18F-NOTA-FAPI-04 PET/CT. Mean standardized uptake values (SUVmean) in lesions were compared, and biodistribution of Al18F-NOTA-FAPI-04 and target-to-background ratios (TBRs) were calculated. Histological staining was performed to display arterial plaques, and autoradiography (ARG) was employed to measure the in vitro intensity of Al18F-NOTA-FAPI-04. At last, the correlation among FAP levels, plaque area, SUVmean values and fibrous cap thickness was assessed. RESULTS: The rabbit carotid and abdominal atherosclerosis model was established. Al18F-NOTA-FAPI-04 showed a higher uptake in carotid plaques (SUVmean 1.32 ± 0.11) and abdominal plaques (SUVmean 0.73 ± 0.13) compared to corresponding controls (SUVmean 1.07 ± 0.06; 0.46 ± 0.03) (P < 0.05). Biodistribution analysis of Al18F-NOTA-FAPI-04 revealed that the bigger plaques were delineated with higher TBRs. Pathological staining showed the formation of arterial plaques, and ARG staining exhibited a higher intensity of Al18F-NOTA-FAPI-04 in the bigger plaques. Lastly, plaque area was found to be positively correlated to FAP expression and SUVmean, while FAP expression was negatively correlated to fibrous cap thickness of plaques. CONCLUSIONS: We successfully achieve molecular imaging of fibroblast activation in atherosclerotic lesions of rabbits, suggesting Al18F-NOTA-FAPI-04 PET/CT may be a potentially valuable tool to identify plaques.

Association of acute glycemic parameters at admission with cardiovascular mortality in the oldest old with acute myocardial infarction.

OBJECTIVES: Stress-related glycemic indicators, including admission blood glucose (ABG), stress-hyperglycemia ratio (SHR), and glycemic gap (GG), have been associated with worse outcomes after acute myocardial infarction (AMI). However, data regarding their prognostic value in the oldest old with AMI are unavailable. Therefore, this study aimed to investigate the association of stress-related glycemic indicators with short- and long-term cardiovascular mortality (CVM) in the oldest old (≥ 80 years) with AMI. METHODS: In this prospective study, a total of 933 consecutive old patients with AMI admitted to FuWai hospital (Beijing, China) were enrolled. On admission, ABG, SHR, and GG were assessed and all participants were classified according to their quartiles. Kaplan-Meier, restricted cubic splines (RCS), and multivariate Cox regression analyses were performed to evaluate the association between these glycemic indicators and CVM within 30 days and long-term follow-up. RESULTS: During an average of 1954 patient-years of follow-up, a total of 250 cardiovascular deaths were recorded. Kaplan-Meier analyses showed the lowest CVM in quartile 1 of ABG and in quartile 2 of SHR and GG. After adjusting for potential covariates, patients in quartile 4 of ABG, SHR, and GG had a respective 1.67-fold (95% CI: 1.03-2.69; P = 0.036), 1.80-fold (95% CI: 1.16-2.79; P = 0.009), and 1.78-fold (95% CI: 1.14-2.79; P = 0.011) higher risk of long-term CVM risk compared to those in the reference groups (quartile 1 of ABG and quartile 2 of SHR and GG). Furthermore, RCS suggested a J-shaped relationship of ABG and a U-shaped association of SHR and GG with long-term CVM. Additionally, we observed similar associations of these acute glycemic parameters with 30-day CVM. CONCLUSIONS: Our data first indicated that SHR and GG consistently had a U-shaped association with both 30-day and long-term CVM among the oldest old with AMI, suggesting that they may be useful for risk stratification in this special population.