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 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.

Joint Association of Lipoprotein(a) and a Family History of Coronary Artery Disease with the Cardiovascular Outcomes in Patients with Chronic Coronary Syndrome.

AIM: No data are currently available regarding the association between Lp(a) and the cardiovascular outcomes in patients with coronary artery disease (CAD) according to their family history (FHx) of CAD. This study aimed to evaluate the significance of Lp(a) in predicting major adverse cardiovascular events (MACEs) in patients with chronic coronary syndrome (CCS) with or without FHx. METHODS: A total of 6056 patients with CCS were enrolled. Information on FHx was collected, and the plasma Lp(a) levels were measured. All patients were followed up regularly. The independent and joint associations of Lp(a) and FHx with the risk of MACEs, including cardiovascular death, nonfatal myocardial infarction, and stroke, were analyzed. RESULTS: With over an average of 50.35±18.58 months follow-up, 378 MACEs were recorded. A Cox regression analysis showed an elevated Lp(a) level to be an independent predictor for MACEs in patients with [hazard ratio (HR): 2.77, 95% confidence interval (CI): 1.38-5.54] or without FHx (HR: 1.35, 95% CI: 1.02-1.77). In comparison to subjects with non-elevated Lp(a) and negative FHx, patients with elevated Lp(a) alone were at a nominally higher risk of MACEs (HR: 1.26, 95% CI: 0.96-1.67), while those with both had the highest risk (HR: 1.93, 95% CI: 1.14-3.28). Moreover, adding Lp(a) to the original model increased the C-statistic by 0.048 in subjects with FHx (p=0.004) and by 0.004 in those without FHx (p=0.391). CONCLUSIONS: The present study is the first to suggest that Lp(a) could be used to predict MACEs in CCS patients with or without FHx; however, its prognostic significance was more noteworthy in patients with FHx.

Association between red blood cell distribution width-to-albumin ratio and prognosis in non-ischaemic heart failure.

AIMS: Red blood cell distribution width-to-albumin ratio (RAR), an innovate biomarker of inflammation, can independently predict adverse cardiovascular outcomes. However, the association between RAR and prognosis in patients with non-ischaemic heart failure (NIHF) remains unclear. METHODS AND RESULTS: A total of 2077 NIHF patients admitted to the Heart Failure Care Unit, Fuwai Hospital, were consecutively enrolled from December 2006 to October 2017 in this retrospective study. The primary endpoint was a composite outcome of all-cause mortality and heart transplantation. The correlation between RAR and the composite outcome was assessed by the Kaplan-Meier survival analysis and the Cox regression analysis. Incremental predictive values and the clinical performance of RAR for all-cause mortality or heart transplantation were also assessed based on a 12-variable traditional risk model. The median follow-up time in this study was 1433 (1341, 1525) days. As the gender no longer satisfied the Cox proportional risk assumption after 1150 days, we set 1095 days as the follow-up time for analysis. A total of 500 patients reached the composite outcome. Multivariable Cox regression showed that per log2 increase of RAR was significantly associated with a 132.9% [hazard ratio 2.329, 95% confidence interval (CI) 1.677-3.237, P < 0.001] increased risk of all-cause mortality or heart transplantation. Better model discrimination [concordance index: 0.766 (95% CI 0.754-0.778) vs. 0.758 (95% CI 0.746-0.770), P < 0.001], calibration (Akaike information criterion: 1487.3 vs. 1495.74; Bayesian information criterion: 1566.25 vs. 1569.43; Brier score: 1569.43 vs. 1569.43; likelihood ratio test P < 0.001), and reclassification (integrated discrimination improvement: 1.35%, 95% CI 0.63-2.07%, P < 0.001; net reclassification improvement: 13.73%, 95% CI 2.05-27.18%, P = 0.034) were improved after adding RAR to the traditional model (P < 0.001 for all). A higher overall net benefit was also obtained in the threshold risk probability of 20-55%. CONCLUSIONS: High level of RAR was an independent risk factor of poor outcome in NIHF.

Application of improved GalNAc conjugation in development of cost-effective siRNA therapies targeting cardiovascular diseases.

N-Acetylgalactosamine (GalNAc)-conjugated small interfering RNA (siRNA) therapies have received approval for treating both orphan and prevalent diseases. To improve in vivo efficacy and streamline the chemical synthesis process for efficient and cost-effective manufacturing, we conducted this study to identify better designs of GalNAc-siRNA conjugates for therapeutic development. Here, we present data on redesigned GalNAc-based ligands conjugated with siRNAs against angiopoietin-like 3 (ANGPTL3) and lipoprotein (a) (Lp(a)), two target molecules with the potential to address large unmet medical needs in atherosclerotic cardiovascular diseases. By attaching a novel pyran-derived scaffold to serial monovalent GalNAc units before solid-phase oligonucleotide synthesis, we achieved increased GalNAc-siRNA production efficiency with fewer synthesis steps compared to the standard triantennary GalNAc construct L96. The improved GalNAc-siRNA conjugates demonstrated equivalent or superior in vivo efficacy compared to triantennary GalNAc-conjugated siRNAs.

Association of ß-blocker use at discharge and prognosis of oldest old with acute myocardial infarction: a prospective cohort study.

PURPOSE: It is uncertain whether ß-blockers are beneficial for long-term prognosis in older patients following acute myocardial infarction (AMI). Thus, this study sought to examine the effect of ß-blockers on long-term cardiovascular mortality (CVM) in the oldest old (≥ 80 years) with AMI. METHODS: In this prospective, consecutive, non-randomized study, a total of 1156 patients with AMI admitted within 24 h after onset of symptoms were enrolled from January 2012 to February 2020. Univariate and multivariate Cox regression analyses were performed to examine the impact of ß-blocker use on prognosis. Furthermore, one-to-one propensity score matching (PSM) and inverse probability treatment weighting (IPTW) analyses were used to control for systemic differences between groups. The primary outcome was long-term CVM. RESULTS: Among the enrolled subjects, 972 (85.9%) were prescribed with ß-blockers at discharge. Over a mean follow-up of 26.3 months, 224 cardiovascular deaths were recorded. Both univariate [hazard ratio (HR), 1.41, 95% confidence interval (CI) 0.93-2.13] and multivariate (HR, 1.29, 95% CI 0.79-2.10) Cox regression analyses showed that ß-blocker use had no significant association with the long-term CVM, which was further demonstrated by PSM (HR, 1.31, 95% CI 0.75-2.28) and IPTW (HR, 1.41, 95% CI 0.73-2.69) analyses. Subgroup analyses according to sex, heart rate, hypertension, diabetes, revascularization, left ventricular ejection fraction, and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers use showed consistent results as well. CONCLUSION: Our findings first suggested that the use of ß-blockers at discharge in oldest old with AMI was not useful for reducing post-discharge CVM, which need to be further verified by randomized controlled trials.