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

Background: Triglyceride glucose (TyG) and TyG-body mass index (TyG-BMI) are reliable surrogate indexes 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 indexes 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.

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.

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 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.

Diagnostic performance of intravascular ultrasound-based fractional flow reserve in evaluating of intermediate left main stenosis.

BACKGROUND: The recently introduced ultrasonic flow ratio (UFR), is a novel fast computational method to derive fractional flow reserve (FFR) from intravascular ultrasound (IVUS) images. In the present study, we evaluate the diagnostic performance of UFR in patients with intermediate left main (LM) stenosis. METHODS: This is a prospective, single center study enrolling consecutive patients with presence of intermediated LM lesions (diameter stenosis of 30%-80% by visual estimation) underwent IVUS and FFR measurement. An independent core laboratory assessed offline UFR and IVUS-derived minimal lumen area (MLA) in a blinded fashion. RESULTS: Both UFR and FFR were successfully achieved in 41 LM patients (mean age, 62.0 ± 9.9 years, 46.3% diabetes). An acceptable correlation between UFR and FFR was identified (r = 0.688, P < 0.0001), with an absolute numerical difference of 0.03 (standard difference: 0.01). The area under the curve (AUC) in diagnosis of physiologically significant coronary stenosis for UFR was 0.94 (95% CI: 0.87-1.01), which was significantly higher than angiographic identified stenosis > 50% (AUC = 0.66, P < 0.001) and numerically higher than IVUS-derived MLA (AUC = 0.82; P = 0.09). Patient level diagnostic accuracy, sensitivity and specificity for UFR to identify FFR ≤ 0.80 was 82.9% (95% CI: 70.2-95.7), 93.1% (95% CI: 82.2-100.0), 58.3% (95% CI: 26.3-90.4), respectively. CONCLUSION: In patients with intermediate LM diseases, UFR was proved to be associated with acceptable correlation and high accuracy with pressure wire-based FFR as standard reference. The present study supports the use of UFR for functional evaluation of intermediate LM stenosis.

Chinese Expert Consensus on the Clinical Diagnosis and Management of Statin Intolerance.

The clinical benefits of statins have well-established and recognized worldwide. Although statins are well-tolerated generally, however, the report of statin-related adverse event and statin intolerance are common in China, which results in insufficient use of statins and poor adherence. The main reason may be attributed to confusions or misconceptions in the clinical diagnosis and management in China, including the lack of unified definitions and diagnostic standards, broad grasp of diagnosis, and unscientific management strategies. Based on that, this consensus carefully summarized the statin-related gene polymorphism and statin usage issue among Chinese population, and comprehensively reviewed global research data on statin intolerance, referenced guidelines, and consensus literature on statin intolerance in foreign and different regions, proposes an appropriate and easy to implement statin intolerance definition as well as corresponding diagnostic criteria and management strategies for Chinese clinicians, in order to improve the clinical application of statin drugs and enhance the prevention and treatment level of atherosclerotic cardiovascular disease in China.

Monoclonal antibodies for dyslipidemia in adults: a focus on vulnerable patients groups.

INTRODUCTION: Dyslipidemia significantly contributes to atherosclerotic cardiovascular disease (ASCVD). Patients with lipid-rich vulnerable plaques are particularly susceptible to cardiovascular complications. Despite available lipid-lowering therapies (LLTs), challenges in effective lipid management remain. AREAS COVERED: This article reviews monoclonal antibody (mAb) therapy in dyslipidemia, particularly focusing on vulnerable plaques and patients. We have reviewed the definitions of vulnerable plaques and patients, outlined the efficacy of traditional LLTs, and discussed in-depth the mAbs targeting PCSK9. We extensively discuss the potential mechanisms, intracoronary imaging, and clinical evidence of PCSK9mAbs in vulnerable plaques and patients. A brief overview of promising mAbs targeting other targets such as ANGPTL3 is also provided. EXPERT OPINION: Research consistently supports the potential of mAb therapies in treating adult dyslipidemia, particularly in vulnerable patients. PCSK9mAbs are effective in regulating lipid parameters, such as LDL-C and Lp(a), and exhibit anti-inflammatory and anti-thrombotic properties. These antibodies also maintain endothelial and smooth muscle health, contributing to the stabilization of vulnerable plaques and reduction in adverse cardiovascular events. Future research aims to further understand PCSK9 and other targets like ANGPTL3, focusing on vulnerable groups. Overall, mAbs are emerging as a promising and superior approach in dyslipidemia management and cardiovascular disease prevention.

Synergetic impact of lipoprotein(a) and fibrinogen on stroke in coronary artery disease patients.

BACKGROUND: Emerging data suggested that lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease. Previous studies indicated fibrinogen (Fib) had synergetic effect on Lp(a)-induced events. However, combined impact of Fib and Lp(a) on ischemic stroke has not been elucidated. METHODS: In this prospective study, we consecutively enrolled 8263 patients with stable coronary artery diseases (CAD) from 2011 to 2017. Patients were categorized into three groups according to tertiles of Lp(a) levels [Lp(a)-low, Lp(a)-medium, and Lp(a)-high] and further divided into nine groups by Lp(a) and Fib levels. All subjects were followed up for the occurrence of ischemic stroke. RESULTS: During a median follow-up of 37.7 months, 157 (1.9%) ischemic strokes occurred. Stroke incidence increased by Lp(a) (1.1 vs. 2.1 vs. 2.5%, Cochran-Armitage p < .001) and Fib (1.1 vs. 2.0 vs. 2.6%, Cochran-Armitage p < .001) categories. When further classified into nine groups by Lp(a) and Fib levels, the incidence of ischemic stroke in group 9 [Lp(a)-high and Fib-high] was significantly higher than that in group 1 [Lp(a)-low and Fib-low] (3.1 vs. 6%, p < .001). The group 9 was associated with a highest risk for ischemic stroke (adjusted HR 4.907, 95% CI: 2.154-11.18, p < .001), compared with individuals in the Lp(a)-high (adjusted HR 2.290, 95% CI: 1.483-3.537, p < .001) or Fib-high (adjusted HR 1.184, 95% CI: 1.399-3.410, p = .001). Furthermore, combining Lp(a) with Fib increased C-statistics by .045 (p = .004). CONCLUSIONS: Current study first demonstrated that elevated Lp(a) combining with Fib evaluation enhanced the risk of ischemic stroke in patients with CAD beyond Lp(a) or Fib alone.

Rationale and design of a randomized controlled trial: The effect of intensive lipid-lowering therapy with PCSK9 inhibitor on endothelial-coverage of stent strut after percutaneous coronary intervention (PCI) for patients with acute coronary syndrome (ACS): Optical coherence tomography (OCT) study (PIECES-OCT study).

Background: For the patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), dual antiplatelet therapy (DAPT) for at least 1 year is recommended in the guidelines to minimize the risk of stent thrombosis. Persistently uncovered stent strut means delayed neointima formation and extend the window of time in which the stent is prone to thrombosis. Previous studies showed that statins could improve post-stenting strut endothelial coverage for patients undergoing PCI. However, there are lack of evidences on whether early initiation of proprotein convertase subtilisin/Kexin type 9 monoclonal antibody (PCSK9mAb) after PCI in ACS patients can further improve the rate of stent strut coverage on the background of oral lipid-lowering therapy (LLT). Methods: This is a single-center, randomized trial to enroll 36 patients undergoing PCI with a clinical diagnosis of non-ST-segment elevation ACS. The baseline level of low-density lipoprotein cholesterol (LDL-C) of these patients are between 1.4 mmol/L and 3.4 mmol/L. Patients will be assigned to intensive lipid-lowering therapy (LLT) with PCSK9mAb group and conventional LLT without PCSK9mAb group for 12 weeks in a clinical follow-up setting according to 1: 1 randomization. the rate of stent strut endothelial coverage by optical coherence tomography (OCT) examination at 12 weeks after enrollment between the groups will be compared. Conclusion: This will be the first study to investigate changes in the rate of stent strut endothelial coverage under intensive LLT with PCSK9mAb by OCT examination in ACS patients undergoing PCI. The finding of this study will provide clinical evidence for future research about the hypothesis of a novel strategy of "intensive LLT (PCSK9mAb + statin ± ezetimibe) combined with shortened DAPT duration" for ACS patients undergoing PCI.Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: ChiCTR2200063395.

Low-density lipoprotein triglyceride predicts outcomes in patients with chronic coronary syndrome following percutaneous coronary intervention according to inflammatory status.

BACKGROUND: Low-density lipoprotein-triglyceride (LDL-TG), a novel lipid marker, has been reported to be associated with cardiovascular events (CVEs). However, whether inflammatory status has a combined effect with LDL-TG on CVEs in patients with chronic coronary syndrome (CCS) receiving percutaneous coronary intervention (PCI) remains uncertain. METHODS: A total of 4,415 patient with coronary angiography were primarily enrolled. Among them, 2,215 patients undergoing PCI were finally classified into subgroups according to LDL-TG and high-sensitivity C-reactive protein (hs-CRP) concentrations. Patients were followed up for up to 7 y for CVEs. The associations between LDL-TG, hs-CRP and CVEs were analyzed. RESULTS: Patients with CVEs showed higher concentrations of LDL-TG compared to those without. In Cox regression analysis, LDL-TG was independently associated with CVEs (hazard ratio [HR]: 2.003, 95 % confidence intervals [CI]: 1.365-2.940, p < 0.001). Interestingly, when patients were further categorized into six subgroups according to hs-CRP and LDL-TG concentrations, LDL-TG was correlated with increased events only in patients with high hs-CRP concentrations (HR: 1.726, 95 %CI: 1.055-2.826, p = 0.030). Moreover, the Kaplan-Meier survival curves indicated that patients in the higher plasma concentrations of hs-CRP in combination with the highest LDL-TG concentrations were associated with the highest risk of CVEs. CONCLUSIONS: LDL-TG was associated with increased CVEs among patients receiving PCI with increased hs-CRP concentrations, suggesting that measurement of LDL-TG combined with hs-CRP facilitates prognostic utility for cardiovascular risks.

2023 China Guidelines for Lipid Management.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death among urban and rural residents in China, and elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for ASCVD. Considering the increasing burden of ASCVD, lipid management is of the utmost importance. In recent years, research on blood lipids has made breakthroughs around the world, hence a revision of China guidelines for lipid management is imperative, especially since the target lipid levels in the general population vary in respect to the risk of ASCVD. The level of LDL-C, which can be regarded as appropriate in a population without frisk factors, can be considered abnormal in people at high risk of developing ASCVD. As a result, the "Guidelines for the prevention and treatment of dyslipidemia" were adapted into the "China Guidelines for Lipid Management" (henceforth referred to as the new guidelines) by an Experts' committee after careful deliberation. The new guidelines still recommend LDL-C as the primary target for lipid control, with CVD risk stratification to determine its target value. These guidelines recommend that moderate intensity statin therapy in adjunct with a heart-healthy lifestyle, be used as an initial line of treatment, followed by cholesterol absorption inhibitors or/and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, as necessary. The new guidelines provide guidance for lipid management across various age groups, from children to the elderly. The aim of these guidelines is to comprehensively improve the management of lipids and promote the prevention and treatment of ASCVD by guiding clinical practice.

The Effects of Sacubitril/Valsartan Compared to Olmesartan on the Blood Pressure and Glucolipid Metabolism in DM Patients with Primary Hypertension.

PURPOSE: Given the beneficial effects of sacubitril/valsartan on blood pressure generally, this study investigates its antihypertension effects in diabetes mellitus (DM) patients with primary hypertension specifically, and the effect of sacubitril/valsartan on glycolipid metabolism. METHODS: We conducted a randomized, open-label, active-controlled study to compare the antihypertension effects of sacubitril/valsartan in DM individuals with primary hypertension. The primary end point was reduction in mean systolic blood pressure (SBP) from baseline with sacubitril/valsartan vs. olmesartan at week 8. The secondary endpoints included the changes in diastolic blood pressure (DBP), daytime SBP/DBP, nighttime SBP/DBP, BP achievement (office sitting BP < 130/80 mmHg), and lipid profile. The trial was registered with chictr.org.cn (ChiCTR2200066428) on Dec 22, 2022. RESULTS: A total of 124 patients were included in the final analysis. SBP decreased to a greater extent in the sacubitril/valsartan group from baseline to 8 weeks [between-treatment difference: 3.51 mm Hg, 95% confidence interval (95% CI) 0.41 to 6.62 mm Hg, P = 0.03]. Furthermore, more patients achieved the blood pressure goal with sacubitril/valasartan (74.60% vs. 54.70%, P = 0.03). Multiple logistical regression analysis showed that sacubitril/valsartan was associated with BP achievement [odds ratio (OR) 0.33, 95% CI 0.14-0.73, P = 0.007], but the difference in SBP, DBP, day time SBP/DBP, and night time SBP/DBP reduction did not approach statistical significance. HbA1C1, total cholesterol, and low-density lipoprotein-cholesterol were lower than baseline in both groups (P < 0.05); however, there was no difference in the effects on glucose and lipid metabolism from sacubitril/valsartan compared to olmesartan. CONCLUSIONS: Sacubitril/valsartan not only provided superior BP reduction compared to olmesartan, it did so without adverse effects on glycemic control and lipid parameters in DM patients with primary hypertension.

2023 Chinese guideline for lipid management.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death among urban and rural residents in China, and elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for ASCVD. Considering the increasing burden of ASCVD, lipid management is of the utmost importance. In recent years, research on blood lipids has made breakthroughs around the world, hence a revision of Chinese guideline for lipid management is imperative, especially since the target lipid levels in the general population vary in respect to the risk of ASCVD. The level of LDL-C, which can be regarded as appropriate in a population without frisk factors, can be considered abnormal in people at high risk of developing ASCVD. As a result, the "Guidelines for the prevention and treatment of dyslipidemia" were adapted into the "Chinese guideline for Lipid Management" (henceforth referred to as the new guidelines) by an Experts' committee after careful deliberation. The new guidelines still recommend LDL-C as the primary target for lipid control, with cardiovascular disease (CVD) risk stratification to determine its target value. These guidelines recommend that moderate intensity statin therapy in adjunct with a heart-healthy lifestyle, be used as an initial line of treatment, followed by cholesterol absorption inhibitors or/and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, as necessary. The new guidelines provide guidance for lipid management across various age groups, from children to the elderly. The aim of these guidelines is to comprehensively improve the management of lipids and promote the prevention and treatment of ASCVD by guiding clinical practice.

Intracranial Hemorrhage in Hospitalized Patients Following Percutaneous Coronary Intervention: A Large Cohort Analysis from a Single Center.

BACKGROUND: There are several reports on the prevalence and characteristics of intracranial hemorrhage (ICH) following percutaneous coronary intervention (PCI), which is a rare but severe complication with high mortality. However, the clinical landscapes of computed tomography (CT)-confirmed, symptomatic ICH in hospitalized patients are not fully characterized. METHODS: Among 121,066 patients receiving PCI treatment in the Fu Wai Hospital between 2013 and 2022, there were 18 CT-defined, symptomatic patients with ICH occurring during post-PCI hospitalization. Symptomatic ICH was defined as clinical suspicion of hemorrhage and/or new focal neurological signs. We analyzed ICH timing, clinical and imaging features, and subsequent outcomes. RESULTS: Overall, in this retrospective analysis, the incidence of CT-defined, symptomatic ICH was 0.015% (18/121,066). More than half of the cases (55.6%) occurred within the first 12 h following PCI. The most common initial manifestation of ICH patients was disturbance of consciousness. Thirteen patients (72.2%) had a hematoma volume ≥ 30 cm3. Additionally, the ICH was observed in the cerebral lobe (66.7%), cerebellum (22.2%), and the basal ganglia and thalamus (11.1%). The 90-day mortality of ICH patients undergoing PCI was very high (72.2%). Consciousness disturbance (p = 0.036), intracerebral hemorrhage volume > 30 mm3 (p = 0.001), and intracerebral hemorrhage originating from the infratentorial origin (p = 0.044) were significantly higher in patients who died. CONCLUSIONS: Symptomatic ICH events occur with a rate of around 0.015%, with significantly higher short-term mortality risk in our cohort receiving PCI, which has not yet been demonstrated in other cohorts.

Circulating Total Bilirubin and Long-Term Prognosis in Patients With Previous Myocardial Infarction.

Background: Although experimental studies have demonstrated the protective role of total bilirubin (TBil) in cardiovascular diseases, several previous clinical observations are controversial. More importantly, no data are currently available regarding the relation of TBil to major adverse cardiovascular events (MACE) in patients with previous myocardial infarction (MI). Objectives: This study sought to explore the association between TBil and long-term clinical outcomes in patients with previous MI. Methods: A total of 3,809 patients who are post-MI were consecutively enrolled in this prospective study. Cox regression models using HRs and CIs were applied to investigate associations between the TBil concentration category (group 1: bottom to median tertiles within the reference range; group 2: top tertile; group 3: above reference range) and main outcome (recurrent MACE) as well as secondary outcomes (hard endpoints and all-cause mortality). Results: During the 4-year follow-up period, 440 patients (11.6%) suffered from recurrent MACE. Kaplan-Meier survival analysis showed the lowest MACE incidence in group 2 (P < 0.001). When compared with the reference group (group 1) in multivariable analysis, a J-shaped association was apparent for MACE, with decreased risk in group 2 (HR: 0.76; 95% CI: 0.59-0.96) and elevated risk in group 3 (HR: 1.29; 95% CI: 1.03-1.61). Similar associations were identified regarding hard endpoints and all-cause mortality. Moreover, TBil demonstrated incremental discriminatory strength when added to the predictive model. Conclusions: In this prospective cohort study with long-term follow-up, higher TBil levels within the physiological range reduced the incidence of long-term cardiovascular events in patients who are post-MI.

Long-term clinical outcomes of percutaneous coronary intervention for ostial left main coronary artery disease.

BACKGROUND: There are limited data regarding the long-term prognosis of percutaneous coronary intervention treatment for left main (LM) ostial stenosis. AIMS: The present study sought to investigate the long-term clinical outcomes and risk factors for adverse events in LM ostial lesions following drug-eluting stent implantation (DES) in a large cohort of an LM registry database. METHODS: Patients presenting with LM coronary disease from January 2004 to December 2016 at Fuwai Hospital were included. The primary endpoint was target vessel failure (TVF), a composite endpoint of cardiac death, target vessel myocardial infarction and target vessel revascularisation. Cox proportional hazards models were constructed to identify independent predictors. RESULTS: Among 4,625 LM patients, 627 (13.6%) patients were identified with LM ostial lesions. There were more female patients in the ostial group (31.3%), compared with the shaft (18.1%) and bifurcation groups (19.9%) (p<0.0001). Among patients with DES implantation, 3-year TVF occurred in 44 patients (7.5%) in the ostial group, which is comparable with the other two groups. Myocardial infarction (MI) was significantly lower in the ostial group (2.0%) compared with the bifurcation group (4.2%) (p=0.02), especially for MI events originating in the LM vessel (p=0.02). For patients with ostial LM disease who received percutaneous coronary intervention (PCI) treatment, procedural complications were an independent risk factor for long-term cardiac death or MI, while a more recent PCI proved to be a protective factor. CONCLUSIONS: PCI treatment for ostial LM lesions achieved favourable long-term outcomes, with a similar MI risk compared with the mid-shaft group but a significantly lower risk of MI compared with the distal group.

Coronary artery disease risk factors affected by RNA modification-related genetic variants.

Background: Single nucleotide polymorphisms that affect RNA modification (RNAm-SNPs) may have functional roles in coronary artery disease (CAD). The aim of this study was to identify RNAm-SNPs in CAD susceptibility loci and highlight potential risk factors. Methods: CAD-associated RNAm-SNPs were identified in the CARDIoGRAMplusC4D and UK Biobank genome-wide association studies. Gene expression and circulating protein levels affected by the RNAm-SNPs were identified by QTL analyses. Cell experiments and Mendelian randomization (MR) methods were applied to test whether the gene expression levels were associated with CAD. Results: We identified 81 RNAm-SNPs that were associated with CAD or acute myocardial infarction (AMI), including m6A-, m1A-, m5C-, A-to-I- and m7G-related SNPs. The m6A-SNPs rs3739998 in JCAD, rs148172130 in RPL14 and rs12190287 in TCF21 and the m7G-SNP rs186643756 in PVT1 were genome-wide significant. The RNAm-SNPs were associated with gene expression (e.g., MRAS, DHX36, TCF21, JCAD and SH2B3), and the expression levels were associated with CAD. Differential m6A methylation and differential expression in FTO-overexpressing human aorta smooth muscle cells and peripheral blood mononuclear cells of CAD patients and controls were detected. The RNAm-SNPs were associated with circulating levels of proteins with specific biological functions, such as blood coagulation, and the proteins (e.g., cardiotrophin-1) were confirmed to be associated with CAD and AMI in MR analyses. Conclusion: The present study identified RNAm-SNPs in CAD susceptibility genes, gene expression and circulating proteins as risk factors for CAD and suggested that RNA modification may play a role in the pathogenesis of CAD.

Long Noncoding RNA TPRG1-AS1 Suppresses Migration of Vascular Smooth Muscle Cells and Attenuates Atherogenesis via Interacting With MYH9 Protein.

BACKGROUND: Migration of human aortic smooth muscle cells (HASMCs) contributes to the pathogenesis of atherosclerosis. This study aims to functionally characterize long noncoding RNA TPRG1-AS1 (tumor protein p63 regulated 1, antisense 1) in HASMCs and reveal the underlying mechanism of TPRG1-AS1 in HASMCs migration, neointima formation, and subsequent atherosclerosis. METHODS: The expression of TPRG1-AS1 in atherosclerotic plaques was verified a series of in silico analysis and quantitative real-time polymerase chain reaction analysis. Northern blot, rapid amplification of cDNA ends and Sanger sequencing were used to determine its full length. In vitro transcription-translation assay was used to investigate the protein-coding capacity of TPRG1-AS1. RNA fluorescent in situ hybridization was used to confirm its subcellular localization. Loss- and gain-of-function studies were used to investigate the function of TPRG1-AS1. Furthermore, the effect of TPRG1-AS1 on the pathological response was evaluated in carotid balloon injury model, wire injury model, and atherosclerosis model, respectively. RESULTS: TPRG1-AS1 was significantly increased in atherosclerotic plaques. TPRG1-AS1 did not encode any proteins and its full length was 1279nt, which was bona fide a long noncoding RNA. TPRG1-AS1 was mainly localized in cytoplasmic and perinuclear regions in HASMCs. TPRG1-AS1 directly interacted with MYH9 (myosin heavy chain 9) protein in HASMCs, promoted MYH9 protein degradation through the proteasome pathway, hindered F-actin stress fiber formation, and finally inhibited HASMCs migration. Vascular smooth muscle cell-specific transgenic overexpression of TPRG1-AS1 significantly reduced neointima formation, and attenuated atherosclerosis in apolipoprotein E knockout (Apoe-/-) mice. CONCLUSIONS: This study demonstrated that TPRG1-AS1 inhibited HASMCs migration through interacting with MYH9 protein and consequently suppressed neointima formation and atherosclerosis.

Hypertension and clinical outcomes in patients with familial hypercholesterolemia.

BACKGROUND: Hypertension is a known risk factor for cardiovascular disease; however, its impact on clinical outcomes in patients with heterozygous familial hypercholesterolemia (HeFH) is unclear. Hence, we aimed to investigate the effects of hypertension on severity of coronary artery atherosclerosis and cardiovascular outcomes in patients with HeFH. METHODS: A total of 480 patients with clinical or molecular diagnosis of definite or probable familial hypercholesterolemia according to Dutch Lipid Clinic Network criteria (DLCN score ≥6) were included in the study. They were divided into the two groups according to their blood pressure status: hypertension group and normotension group. The severity of coronary stenosis was assessed by a number of diseased vessels, Gensini, Syntax, and Jeopardy scores. All individuals were followed up for cardiovascular events (CVEs) and cox proportion hazard models were used to evaluate the association of hypertension with cardiovascular outcomes. RESULTS: Patients with hypertension had more severe coronary stenosis and a higher incidence of CVEs compared with the ones with normotension (log-rank P < 0.001). After multivariable adjustment, there was a 2.1-fold increased risk of CVEs among patients with hypertension compared with patients with normotension (adjusted hazard ratio 2.06, 95% confidential interval 1.17-3.65, P < 0.01). Hypertension control status was also associated with CVEs even after adjustment of multiple variables. However, no combined effect on increased cardiovascular risks was detected in this HeFH cohort. CONCLUSION: In patients with HeFH, hypertension is an independent risk factor for cardiovascular events. Moreover, blood pressure control status in patients with hypertension is associated with the worse outcomes.