Metabolic score for insulin resistance predicts major adverse cardiovascular event in premature coronary artery disease.

BACKGROUND: The Metabolic Score for Insulin Resistance (METS-IR) index serves as a simple surrogate marker for insulin resistance (IR) and is associated with the presence and severity of coronary artery disease (CAD). However, the prognostic significance of METS-IR in patients with premature CAD remains unclear. This study aims to investigate the prognostic value of METS-IR in premature CAD. METHODS: This retrospective study included 582 patients diagnosed with premature CAD between December 2012 and July 2019. The median follow-up duration was 63 months (interquartile range, 44-81 months). The primary endpoint was Major Adverse Cardiovascular Events (MACE), defined as a composite of all-cause death, non-fatal myocardial infarction (MI), repeat coronary artery revascularization, and non-fatal stroke. RESULTS: Patients with MACE had significantly higher METS-IR levels than those without MACE (44.88±8.11 vs. 41.68±6.87, p<0.001). Kaplan-Meier survival curves based on METS-IR tertiles demonstrated a statistically significant difference (log-rank test, p<0.001). In the fully adjusted model, the Hazard Ratio (95% CI) for MACE was 1.41 (1.16-1.72) per SD increase in METS-IR, and the P for trend based on METS-IR tertiles was 0.001 for MACE. Time-dependent Receiver Operator Characteristic (ROC) analysis of METS-IR yielded an Area Under the Curve (AUC) of 0.74 at 2 years, 0.69 at 4 years, and 0.63 at 6 years. CONCLUSIONS: METS-IR serves as a reliable prognostic predictor of MACE in patients with premature CAD. Therefore, METS-IR may be considered a novel, cost-effective, and dependable indicator for risk stratification and early intervention in premature CAD.

Cardiovascular health metrics defined by Life's Essential 8 scores and subsequent macrovascular and microvascular complications in individuals with type 2 diabetes: A prospective cohort study.

AIM: To investigate the association between cardiovascular health metrics defined by Life's Essential 8 (LE8) scores and vascular complications among individuals with type 2 diabetes (T2D). MATERIALS AND METHODS: This prospective study included 11 033 participants with T2D, all devoid of macrovascular diseases (including cardiovascular and peripheral artery disease) and microvascular complications (e.g. diabetic retinopathy, neuropathy and nephropathy) at baseline from the UK Biobank. The LE8 score comprised eight metrics: smoking, body mass index, physical activity, non-high-density lipoprotein cholesterol, blood pressure, glycated haemoglobin, diet and sleep duration. Cox proportional hazards models were established to assess the associations of LE8 scores with incident macrovascular and microvascular complications. RESULTS: During a median follow-up of 12.1 years, we identified 1975 cases of incident macrovascular diseases and 1797 cases of incident microvascular complications. After adjusting for potential confounders, each 10-point increase in the LE8 score was associated with an 18% lower risk of macrovascular diseases and a 15% lower risk of microvascular complications. Comparing individuals in the highest and lowest quartiles of LE8 scores revealed hazard ratios of 0.55 (95% confidence interval 0.47-0.62) for incident macrovascular diseases, and 0.61 (95% confidence interval 0.53-0.70) for incident microvascular complications. This association remained robust across a series of sensitivity analyses and nearly all subgroups. CONCLUSION: Higher LE8 scores were associated with a lower risk of incident macrovascular and microvascular complications among individuals with T2D. These findings underscore the significance of adopting fundamental strategies to maintain optimal cardiovascular health and curtail the risk of developing diabetic vascular complications.

The association between tinnitus and risk of cardiovascular events and all-cause mortality: insight from the UK Biobank.

BACKGROUND: The potential influence of tinnitus on cardiovascular disease (CVD) and all-cause mortality has yet to be explored. We aim to examine the correlations between tinnitus and the risk of cardiovascular events and all-cause mortality. METHODS: We conducted a prospective cohort study utilising data from the UK Biobank. The presence of tinnitus was evaluated through a questionnaire. The primary outcome was defined as a composition of cardiovascular events, including myocardial infarction (MI), stroke, and mortality from CVD, as well as all-cause mortality. Cox proportional hazard models were employed to examine the associations between tinnitus and both the primary outcome and its individual components. Sensitivity analyses were conducted to evaluate the robustness of the primary analysis. RESULTS: A total of 140,146 participants were included in the study. The presence of tinnitus was found to be associated with a higher incident rate of the primary outcome (HR = 1.057, 95%CI: 1.017-1.099, p = 0.005), MI (HR = 1.139, 95%CI: 1.061-1.222, p < 0.001) and all-cause mortality (HR = 1.053, 95%CI: 1.003-1.105, p = 0.038) after adjusting for confounders. However, there was no significant association between tinnitus and stroke or mortality from CVD. Subgroup analysis revealed that the association between tinnitus and the primary outcome was significant in females, participants with abnormal BMI, and those without hearing difficulty, depression or anxiety. Sensitivity analyses yielded consistent results. CONCLUSION: The findings from this study contribute to the existing body of evidence suggesting an association between tinnitus and an increased risk of cardiovascular events and all-cause mortality.

Association between daytime napping and incident arrhythmias: A prospective cohort study and mendelian randomization analysis.

BACKGROUND: Emerging evidence has linked daytime napping with the risk of cardiovascular events. Cardiac arrhythmias are considered an early clinical stage for cardiovascular diseases. However, whether napping frequency is associated with incident arrhythmias remains unknown. OBJECTIVE: This study aimed to prospectively investigate the association between napping frequency and cardiac arrhythmias. METHODS: Daytime napping frequency was self-reported in response to touchscreen questionnaires. The primary outcomes were incident arrhythmias including atrial fibrillation/flutter (AF/Af), ventricular arrhythmia, and bradyarrhythmia. Cox regression analysis was conducted on the basis of 491,117 participants free of cardiac arrhythmias from the UK Biobank. The 2-sample mendelian randomization (MR) and 1-sample MR were used to ensure a causal effect of genetically predicted daytime napping on the risk of arrhythmias. RESULTS: During a median follow-up of 11.91 years, 28,801 incident AF/Af cases, 4132 incident ventricular arrhythmias, and 11,616 incident bradyarrhythmias were documented. Compared with never/rarely napping, usually napping was significantly associated with higher risks of AF/Af (hazard ratio, 1.141; 95% CI, 1.083-1.203) and bradyarrhythmia (hazard ratio, 1.138; 95% CI, 1.049-1.235) but not ventricular arrhythmia after adjustment for various covariates. The 2-sample MR and 1-sample MR analysis showed that increased daytime napping frequency was likely to be a potential causal risk factor for AF/Af in FinnGen (odds ratio, 1.626; 95% CI, 1.061-2.943) and bradyarrhythmia in the UK Biobank (odds ratio, 1.005; 95% CI, 1.002-1.008). CONCLUSION: The results of this study add to the burgeoning evidence of an association between daytime napping frequency and an increased risk of cardiac arrhythmias including AF/Af, ventricular arrhythmia, and bradyarrhythmia.

Association between the triglyceride-glucose index and impaired cardiovascular fitness in non-diabetic young population.

BACKGROUND: The triglyceride-glucose (TyG) index has been linked to the onset, progression, and prognosis of cardiovascular disease (CVD) in middle-aged and elderly individuals. Nevertheless, the relationship between the TyG index and impaired cardiovascular fitness (CVF) remains unexplored in non-diabetic young population. METHODS: We used data from the National Health and Nutrition Examination Survey (NHANES) study (1999-2004) to conduct a cross-sectional study of 3364 participants who completed an examination of CVF. Impaired CVF was defined as low and moderate CVF levels determined by estimated maximal oxygen consumption (Vo2max), based on sex- and age-specific criteria. The TyG index was calculated by [Formula: see text]. RESULTS: The age (median with interquartile range) of the study population was 28 (19-37) years, and the TyG index (median ± standard deviation) was 8.36 ± 0.52. A significant association between the TyG index and impaired CVF was found in multivariable logistical regression analysis (per 1-unit increase in the TyG index: OR, 1.46; 95% Cl 1.13-1.90). A dose‒response relationship between the TyG index and impaired CVF was presented by restricted cubic splines (RCS). A significant interaction (p = 0.027) between sex and the TyG index for impaired CVF was found in the population aged < 20 years. CONCLUSIONS: In non-diabetic young population, individuals with higher TyG index values are at an increased likelihood of encountering impaired CVF. Furthermore, sex may exert an impact on CVF, as males tend to be more susceptible to impaired CVF under comparable TyG index conditions.

Remnant cholesterol and risk of incident hypertension: a population-based prospective cohort study.

Remnant cholesterol (RC) has been associated with atherosclerotic cardiovascular disease, but its relationship with hypertension remains unclear. This prospective cohort study aimed to investigate the association between RC and subsequent hypertension risk. Data from the UK Biobank, comprising 295,062 participants initially free of hypertension, were analyzed. Cox proportional hazards regression assessed the association between RC quartiles and hypertension risk. Discordance analysis evaluated the risk of hypertension in discordant/concordant groups of RC and low-density lipoprotein cholesterol (LDL-C) using the difference in percentile units (>10 units). Restricted cubic spline curves were used to model the relationship between RC and hypertension risk. The mean ± SD age of participants was 55.1 ± 8.1 years, with 40.6% being men and 94.7% White. During a median follow-up of 12.8 years, 39,038 participants developed hypertension. Comparing extreme quartiles of RC, the hazard ratio (HR) for incident hypertension was 1.20 (95% CI: 1.17-1.24). After adjusting for traditional risk factors, each 1 mmol/L increase in RC levels was associated with a 27% higher risk of incident hypertension (HR: 1.27; 95% CI: 1.23-1.31). The discordant group with high RC/low LDL-C exhibited a higher risk of incident hypertension compared to the concordant group (HR: 1.06; 95% CI: 1.03-1.09). Spline curves further demonstrated a positive association between RC and the risk of incident hypertension. We concluded that elevated RC emerged as an independent risk factor of incident hypertension, extending beyond traditional risk factors. Monitoring RC levels and implementing interventions to lower RC may have potential benefits in preventing hypertension.

Prevalence, characteristics and significant predictors for cardiovascular disease of patients with preserved ratio impaired spirometry: A 10-year prospective cohort study in China.

BACKGROUND AND OBJECTIVE: Patients with preserved ratio impaired spirometry (PRIsm) have higher incidence rate of cardiovascular disease (CVD). However, few studies focused on PRIsm in China. We determined the prevalence and characteristics of patients with PRIsm in Chinese population. We also aimed to investigate the significant predictive factors of CVD in PRIsm patients. METHODS: In total, 6994 subjects aged from 35 to 70 years old and free of CVD at baseline were categorized into normal (n = 3895), PRIsm (the ratio of forced expired volume in the first second (FEV1) to forced vital capacity (FVC) ≥0.7 and FEV1 <80 % predicted; n = 1997) and obstructive spirometry (FEV1:FVC<0.7; n = 1102). Cox proportional hazards multivariable regression was performed to investigate how baseline characteristics impact CVD incidence. RESULTS: In participants with PRIsm, men had a 0.68-fold higher risk of CVD incidence than women (HR, 1.68; 95%CI, 1.09-2.59; p = 0.020). Our study showed that the rate of CVD incidence increased by 6.0 % with every year's increase in age (HR, 1.06; 95%CI, 1.04-1.09; p < 0.001). A 0.1 increase in FEV1/FVC was significantly associated with a 23.0 % decrease in CVD incidence (HR, 0.77; 95%CI, 0.61-0.97; p = 0.028). Family history of CVD greatly increased the risk of cardiovascular disease incidence (HR, 1.83; 95%CI, 1.18-2.83; p = 0.007). Higher BMI was also a significant risk factor of CVD incidence (HR, 1.06; 95%CI, 1.01-1.10; p = 0.013). CONCLUSION: The prevalence of PRIsm in China was high. PRIsm subjects should be monitored carefully, especially for the older, male, those with higher BMI, lower FEV1/FVC and family history of CVD.

AHA Life's Essential 8 and new-onset CKD: a prospective cohort study from the UK Biobank.

BACKGROUND: The AHA has recently introduced a novel metric, Life's Essential 8, to assess cardiovascular health (CVH). Nevertheless, the association between varying levels of LE8 and the propensity for CKD is still unclear from a large prospective cohort. Our objective is to meticulously examine the relationship between LE8 and its associated susceptibilities to CKD. METHODS: A total of 251,825 participants free of CKD from the UK Biobank were included. Cardiovascular health was scored using LE8 and categorized as low, moderate, and high. Cox proportional hazard models were employed to evaluate the associations of LE8 scores with new-onset CKD. The genetic risk score for CKD was calculated by a weighted method. RESULTS: Over a median follow-up of 12.8 years, we meticulously documented 10,124 incident cases of CKD. Remarkably, an increased LE8 score correlated with a significant reduction of risk in new-onset CKD (high LE8 score vs. low LE8 score: HR = 0.300, 95% CI 0.270-0.330, p < 0.001; median LE8 score vs. low LE8 score: HR = 0.531, 95% CI 0.487-0.580, p < 0.001). This strong LE8-CKD association remained robust in extensive subgroup assessments and sensitivity analysis. Additionally, these noteworthy associations between LE8 scores and CKD remained unaffected by genetic predispositions to CKD. CONCLUSIONS: An elevated degree of CVH, as delineated by the discerning metric LE8, exhibited a pronounced and statistically significant correlation with a marked reduction in the likelihood of CKD occurrence.

Age at job initiation and risk of coronary heart disease: findings from the UK biobank cohort study.

BACKGROUND: Commencing work at an early age has been linked to various risk factors for coronary heart disease (CHD), such as shift work and intensive job strain. However, the relationship between starting work too early and CHD risk remains largely unclear. We examined the association between age at job initiation and the risk of CHD. METHODS: UK Biobank participants aged 38 to 70 years without cardiovascular disease who provided data on their age at job initiation were included. The primary outcome was CHD, which was ascertained using hospital and death records. The hazard ratios (HRs) and 95% confidence interval (CIs) for the association between age at job initiation and CHD were calculated using multivariable Cox regression. RESULTS: Of the 501,971 participants, 114,418 eligible participants were included in the final analysis. The median age at job initiation was 19.0 years. During the mean follow-up of 12.6 years, 6,130 (5.4%) first CHD events occurred. We observed that age at job initiation was inversely associated with CHD (HR 0.98, 95% CI 0.97-0.99), and the association was potentially J-shaped. The HRs for the < 17-year, 17-18-year, and 19-21-year age groups were 1.29 (95%CI 1.18-1.41), 1.12 (95% CI 1.03-1.22) and 1.05 (95% CI 0.97-1.14), respectively, compared with those of the ≥ 22-year group. CONCLUSIONS: Age at job initiation was associated with incident CHD, which was independent of socioeconomic status. Participants who commenced employment before the age of 19 years exhibited a higher risk of developing CHD later in adulthood.

Combination of the triglyceride-glucose index and EuroSCORE II improves the prediction of long-term adverse outcomes in patients undergoing coronary artery bypass grafting.

AIMS: We aimed to investigate the independent and combined association of the triglyceride-glucose (TyG) index and EuroSCORE II with major adverse cardiovascular event (MACE) after coronary artery bypass grafting (CABG), and examine whether the addition of the TyG index improves the predictive performance of the EuroSCORE II. MATERIALS AND METHODS: This study included 1013 patients who underwent CABG. The primary endpoint was MACE, which was defined as the composite of all-cause death, repeat coronary artery revascularisation, non-fatal myocardial infarction and non-fatal stroke. The patients were grouped by the TyG index and EuroSCORE II tertiles and the combination of these risk indicators. RESULTS: During the follow-up, 211 individuals developed MACE. Elevated levels of the TyG index and EuroSCORE II were associated with an increased risk of MACE. The hazard ratio [95% confidence interval (CI)] was 3.66 (2.34-5.73) in patients with the highest tertile of the TyG index and EuroSCORE II. Compared with the EuroSCORE II alone, combining the TyG index with EuroSCORE II achieved a better predictive performance [C-statistic increased 0.032, p < 0.001; continuous net reclassification improvement (NRI) (95% CI): 0.364 (0.215-0.514), p < 0.001; integrated discrimination improvement (IDI) (95% CI): 0.015 (0.007-0.023), p < 0.001, Akaike's information criteria (AIC) and Bayesian information criterion (BIC) decreased, and the likelihood ratio test, p < 0.001]. CONCLUSIONS: The TyG index and EuroSCORE II are independently associated with poor prognosis. Furthermore, the TyG index is an important adjunct to the EuroSCORE II for improving risk stratification and guiding early intervention among post-CABG patients.

Triglyceride-glucose index in the prediction of adverse cardiovascular events in patients without diabetes mellitus after coronary artery bypass grafting: a multicenter retrospective cohort study.

BACKGROUND: The triglyceride-glucose (TyG) index has been evaluated as a reliable surrogate for insulin resistance (IR) and has been proven to be a predictor of poor outcomes in patients with cardiovascular diseases. However, data are lacking on the relationship of the TyG index with prognosis in nondiabetic patients who underwent coronary artery bypass grafting (CABG). Thus, the purpose of our current study was to investigate the potential value of the TyG index as a prognostic indicator in patients without diabetes mellitus (DM) after CABG. METHODS: This multicenter, retrospective cohort study involving 830 nondiabetic patients after CABG from 3 tertiary public hospitals from 2014 to 2018. Kaplan-Meier survival curve analysis was conducted followed by the log-rank test. Cox proportional hazards regression models were used to explore the association between the TyG index and major adverse cardiovascular events (MACEs). The incremental predictive power of the TyG index was evaluated with C-statistics, continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: An incrementally higher TyG index was associated with an increasingly higher cumulative incidence of MACEs (log-rank test, p < 0.001). The hazard ratio (95% CI) of MACEs was 2.22 (1.46-3.38) in tertile 3 of the TyG index and 1.38 (1.18-1.62) per SD increase in the TyG index. The addition of the TyG index yielded a significant improvement in the global performance of the baseline model [C-statistic increased from 0.656 to 0.680, p < 0.001; continuous NRI (95% CI) 0.269 (0.100-0.438), p = 0.002; IDI (95% CI) 0.014 (0.003-0.025), p = 0.014]. CONCLUSIONS: The TyG index may be an independent factor for predicting adverse cardiovascular events in nondiabetic patients after CABG.

The metabolic score for insulin resistance in the prediction of major adverse cardiovascular events in patients after coronary artery bypass surgery: a multicenter retrospective cohort study.

BACKGROUND: The metabolic score for insulin resistance (METS-IR) is a simple, convenient, and reliable marker for resistance insulin (IR), which has been regarded as a predictor of cardiovascular disease (CVD) and cardiovascular events. However, few studies examined the relationship between METS-IR and prognosis after coronary artery bypass graft (CABG). This study aimed to investigate the potential value of METS-IR as a prognostic indicator for the major adverse cardiovascular events (MACE) in patients after CABG. METHOD: 1100 CABG patients were enrolled in the study, including 760 men (69.1%) and 340 women (30.9%). The METS-IR was calculated as Ln [(2 × FPG (mg/dL) + fasting TG (mg/dL)] × BMI (kg/m2)/Ln [HDL-C (mg/dL)]. The primary endpoint of this study was the occurrence of major adverse cardiovascular events (MACE), including a composite of all-cause death, non-fatal myocardial infarction (MI), coronary artery revascularization, and stroke. RESULT: The following-up time of this study was 49-101 months (median, 70 months; interquartile range, 62-78 months). During the follow-up period, there were 243 MACEs (22.1%). The probability of cumulative incidence of MACE increased incrementally across the quartiles of METS-IR (log-rank test, p < 0.001). Multivariate Cox regression analysis demonstrated a hazard ratio (95% CI) of 1.97 (1.36-2.86) for MACE in quartile 4 compared with participants in quartile 1. The addition of the METS-IR to the model with fully adjusting variables significantly improved its predictive value [C-statistic increased from 0.702 to 0.720, p < 0.001, continuous net reclassification improvement (NRI) = 0.305, < 0.001, integrated discrimination improvement (IDI) = 0.021, p < 0.001]. CONCLUSION: METS-IR is an independent and favorable risk factor for predicting the occurrence of MACE and can be used as a simple and reliable indicator that can be used for risk stratification and early intervention in patients after CABG.

The synergistic effect of the triglyceride-glucose index and serum uric acid on the prediction of major adverse cardiovascular events after coronary artery bypass grafting: a multicenter retrospective cohort study.

BACKGROUND: Elevated serum uric acid (SUA) is regarded as a risk factor for the development of cardiovascular diseases. Triglyceride-glucose (TyG) index, a novel surrogate for insulin resistance (IR), has been proven to be an independent predictor for adverse cardiac events. However, no study has specifically focused on the interaction between the two metabolic risk factors. Whether combining the TyG index and SUA could achieve more accurate prognostic prediction in patients undergoing coronary artery bypass grafting (CABG) remains unknown. METHODS: This was a multicenter, retrospective cohort study. A total of 1225 patients who underwent CABG were included in the final analysis. The patients were grouped based on the cut-off value of the TyG index and the sex-specific criteria of hyperuricemia (HUA). Cox regression analysis was conducted. The interaction between the TyG index and SUA was estimated using relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). The improvement of model performance yielded by the inclusion of the TyG index and SUA was examined by C-statistics, net reclassification improvement (NRI) and integrated discrimination improvement (IDI). The goodness-of-fit of models was evaluated using the Akaike information criterion (AIC), Bayesian information criterion (BIC) and χ2 likelihood ratio test. RESULTS: During follow-up, 263 patients developed major adverse cardiovascular events (MACE). The independent and joint associations of the TyG index and SUA with adverse events were significant. Patients with higher TyG index and HUA were at higher risk of MACE (Kaplan-Meier analysis: log-rank P < 0.001; Cox regression: HR = 4.10; 95% CI 2.80-6.00, P < 0.001). A significant synergistic interaction was found between the TyG index and SUA [RERI (95% CI): 1.83 (0.32-3.34), P = 0.017; AP (95% CI): 0.41 (0.17-0.66), P = 0.001; SI (95% CI): 2.13 (1.13-4.00), P = 0.019]. The addition of the TyG index and SUA yielded a significant improvement in prognostic prediction and model fit [change in C-statistic: 0.038, P < 0.001; continuous NRI (95% CI): 0.336 (0.201-0.471), P < 0.001; IDI (95% CI): 0.031 (0.019-0.044), P < 0.001; AIC: 3534.29; BIC: 3616.45; likelihood ratio test: P < 0.001). CONCLUSIONS: The TyG index interacts synergistically with SUA to increase the risk of MACE in patients undergoing CABG, which emphasizes the need to use both measures concurrently when assessing cardiovascular risk.

Hyperglycemia newly detected by glycated hemoglobin affects all-cause mortality in coronary artery disease patients: a retrospective cohort study.

AIMS: We aim to assess the relationship between hyperglycemia and long-term prognosis in CAD patients without known diabetes. METHODS: In this retrospective observational study, we enrolled 11,384 CAD patients without known diabetes. Newly detected diabetes was defined as HbA1c ≥ 6.5 %, and prediabetes was defined as HbA1c ranging from 5.7 to 6.4 %.The association between hyperglycemia and long-term all-cause mortality was examined using Cox proportional hazards regression analysis. RESULTS: According to HbA1c level, 8207 (72.1 %) patients had hyperglycemia, including 13.0 % with diabetes and 59.1 % with prediabetes. During a median follow-up of 4.9 years, 1157(10.2 %) patients died. Compared with normoglycemia, hyperglycemia was associated with increased risk for long-term mortality (adjusted hazard ratio for diabetes and prediabetes: 1.23 [95 % confidence interval (CI): 1.00 to 1.51] and 1.17 [95 % CI: 1.01 to 1.36], respectively). CONCLUSIONS: Hyperglycemia detected by HbA1c was common in CAD patients without known diabetes and was associated with increased long-term mortality. It is necessary to routinely use HbA1c to assess glucose metabolic status in CAD patients and treat hyperglycemia as early as possible to reduce the risk of adverse outcomes.

Elevation of Preprocedural Systemic Immune Inflammation Level Increases the Risk of Contrast-Associated Acute Kidney Injury Following Coronary Angiography: A Multicenter Cohort Study.

Background: Inflammation and immune responses play an important role in the pathophysiology of contrast-associated acute kidney injury (CA-AKI), and systemic immune inflammation index (SII) has recently emerged as a new parameter for immune and inflammatory response evaluation. However, limited research has been undertaken to explore the relationship between SII and CA-AKI following coronary angiography (CAG). Patients and Methods: From January 2007 to December 2020, 46,333 patients undergoing CAG were included from 5 Chinese tertiary hospitals. SII was calculated as total peripheral platelets count × neutrophil-to-lymphocyte ratio. Patients were categorized by preprocedural SII quartiles: Q1 ≤404.5, Q2 >404.5 and ≤631.7, Q3 >631.7 and ≤1082.8, Q4 >1082.8. Univariable and multivariable logistic regression were used to reveal the link between preprocedural SII and CA-AKI. Results: A total of the 46,333 patients (62.9 ± 11.5 years, female 28.1%) were included in the study. The incidence of CA-AKI was 8.4% in Q1 group, 8.7% in Q2 group, 9.4% in Q3 group, 15.1% in Q4 group. In the multivariable model, comparing the highest (Q4 group) to lowest (Q1 group) SII level categories, preprocedural SII was related to a higher risk of CA-AKI after fully adjusting for well-known confounders, and there was no statistically difference in the other two SII level categories (Q2 and Q3 groups) compared with Q1 group (adjusted model 3: Q2 group: OR: 0.98, 95% CI: 0.87-1.11, P = 0.771; Q3 group: OR: 1.04, 95% CI: 0.92-1.18, P = 0.553; Q4: OR: 1.65, 95% CI: 1.45-1.88, p < 0.001; P for trend < 0.001). Similar results were found for all the subgroups analysis except for patients undergoing PCI, and the interaction analyses for age, PCI and AMI were significant. In addition, Kaplan-Meier curves demonstrated that the lowest quartile group showed the worst all-cause mortality in a significant SII level-dependent manner among the four groups (Log rank test; p < 0.0001). Conclusion: Elevated preprocedural SII level was a significant and independent risk factor for CA-AKI following CAG. Higher-quality prospective studies are needed to validate the predictive value of SII for CA-AKI.

Chronic Kidney Disease Increases Risk of Incident HFrEF Following Percutaneous Coronary Intervention.

Background: Chronic kidney disease (CKD) is very common in patients who are at a high risk of developing incident heart failure with reduced ejection fraction (HFrEF). However, the harmful effect of CKD on incident HFrEF has not yet been examined among patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). Methods: Patients undergoing PCI with baseline left ventricular ejection fraction (LVEF) ≥ 40% were included from January 2007 to December 2018 (ClinicalTrials.gov NCT04407936). We defined incident HFrEF as a follow-up LVEF of <40% within 3-12 months after discharge. Multivariable logistical regression was performed to examine the association of CKD with incident HFrEF. Results: Overall, of 2,356 patients (mean age 62.4 ± 10.7 years, 22.2% women), 435 (18.5%) had CKD, and 83 (3.5%) developed incident HFrEF following PCI. The rate of incident HFrEF in the CKD group was higher than that in the non-CKD group (6.9 vs. 2.8%; p < 0.001). Multivariate logistic regression analysis indicated that CKD was an independent risk factor of incident HFrEF [adjusted odds ratio (aOR) = 1.75; 95% CI, 1.03-2.92; p = 0.035] after adjustment for confounders including age, gender, diabetes, hypertension, atrial fibrillation, congestive heart failure (CHF), baseline LVEF, ACEI/ARB, and statins. Furthermore, patients with incident HFrEF have a higher ratio of all-cause mortality compared to those without HFrEF (26.5 vs. 8.1%; p < 0.001). Conclusions: Our results suggested that CKD was associated with increased risk of incident HFrEF, which was related to higher all-cause mortality in patients with CAD undergoing PCI. On this basis, more aggressive measures should be taken to prevent patients with CKD undergoing PCI from developing HFrEF.

Sodium Glucose Cotransporter Type 2 Inhibitors Improve Cardiorenal Outcome of Patients With Coronary Artery Disease: A Meta-Analysis.

Objective: Sodium glucose cotransporter type 2 inhibitors (SGLT-2i) are beneficial for cardiorenal outcomes in patients with type 2 diabetes mellitus (T2DM), heart failure (HF) or chronic kidney disease (CKD). However, whether or not the patients with coronary artery disease (CAD) have prognostic benefit from SGLT-2i treatment has not been fully studied. The purpose of this meta-analysis is to determine the prognostic benefit of SGLT-2i administration in CAD patients. Methods: We searched the PubMed, Embase and Cochrane Library from inception until October 15, 2021. We included randomized controlled trials (RCTs) reporting the effect of SGLT-2i on major adverse cardiovascular event (MACE), hospitalization for heart failure (HHF), cardiovascular (CV) death and cardiorenal parameters in CAD patients. Hazard ratio (HR) with 95% confidence interval (CI) and mean difference (MD) from trials were meta-analyzed using fixed-effects models. Results: Nine trials enrolling 15,301 patients with CAD were included in the analyses. Overall, SGLT2i were associated with a reduced risk of MACE (HR: 0.84; 95% CI 0.74-0.95; I2 = 0%), HHF (HR: 0.69; 95% CI 0.58-0.83; I2 = 0%) and a composite of CV death or HHF (HR: 0.78; 95% CI 0.71-0.86; I2 = 37%) in CAD patients. Compared with control group, estimated glomerular filtration rate (eGFR) level decreased less in SGLT-2i group (mean difference [MD] = -3.60, 95% CI, -5.90 to -1.30, p = 0.002; I2 = 0%). Conclusions: SGLT-2i can improve cardiorenal outcomes in CAD patients. Further RCTs and real world studies are need to investigate the effect of SGLT2i on CAD patients. Systematic Review Registration: PROSPERO, CRD42021258237.

Glycolysis Inhibition Alleviates Cardiac Fibrosis After Myocardial Infarction by Suppressing Cardiac Fibroblast Activation.

Objective: To explore the role of glycolysis in cardiac fibroblast (CF) activation and cardiac fibrosis after myocardial infarction (MI). Method: In vivo: 2-Deoxy-D-glucose (2-DG), a glycolysis inhibitor, was injected into the abdominal cavity of the MI or sham mice every day. On the 28th day, cardiac function was measured by ultrasonic cardiography, and the hearts were harvested. Masson staining and immunofluorescence (IF) were used to evaluate the fibrosis area, and western blot was used to identify the glycolytic level. In vitro, we isolated the CF from the sham, MI and MI with 2-DG treatment mice, and we also activated normal CF with transforming growth factor-ß1 (TGF-ß1) and block glycolysis with 2-DG. We then detected the glycolytic proteins, fibrotic proteins, and the concentrations of lactate and glucose in the culture medium. At last, we further detected the fibrotic and glycolytic markers in human fibrotic and non-fibrotic heart tissues with masson staining, IF and western blot. Result: More collagen and glycolytic protein expressions were observed in the MI mice hearts. The mortality increased when mice were treated with 2-DG (100 mg/kg/d) after the MI surgery (Log-rank test, P < 0.05). When the dosage of 2-DG declined to 50 mg/kg/d, and the treatment was started on the 4th day after MI, no statistical difference of mortality between the two groups was observed (Log-rank test, P = 0.98). The collagen volume fraction was smaller and the fluorescence signal of α-smooth muscle actin (α-SMA) was weaker in mice treated with 2-DG than PBS. In vitro, 2-DG could significantly inhibit the increased expression of both the glycolytic and fibrotic proteins in the activated CF. Conclusion: Cardiac fibrosis is along with the enhancement of CF activation and glycolysis. Glycolysis inhibition can alleviate cardiac fibroblast activation and cardiac fibrosis after myocardial infarction.

Protein Structural Ensembles Visualized by Solvent Paramagnetic Relaxation Enhancement.

A protein can be in different conformations when fulfilling its function. Yet depiction of protein structural ensembles remains difficult. Here we show that the accurate measurement of solvent paramagnetic relaxation enhancement (sPRE) in the presence of an inert paramagnetic cosolute allows the assessment of protein dynamics. Demonstrated with two multi-domain proteins, we present a method to characterize protein microsecond-millisecond dynamics based on the analysis of the sPRE. Provided with the known structures of a protein, our method uncovers an ensemble of structures that fully accounts for the observed sPRE. In conjunction with molecular dynamics simulations, our method can identify protein alternative conformation that has only been theorized before. Together, our method expands the application of sPRE beyond structural characterization of rigid proteins and complements the established PRE NMR technique.