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.

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.

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.

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.

Effects of cumulative cognitive function within 1-year of discharge on subsequent mortality among patients hospitalized for acute heart failure: A nationwide prospective cohort study.

BACKGROUNDS: To examine the association between cumulative cognitive function and subsequent mortality among patients hospitalized for acute heart failure (AHF). METHODS: Based on a prospective cohort of patients hospitalized for AHF, cognitive function was measured by using Mini-Cog test at admission, 1- and 12-month following discharge. Cumulative cognitive function was interpreted by cumulative Mini-Cog score and cumulative times of cognitive impairment. Outcomes included subsequent all-cause and cardiovascular mortality. RESULTS: 1454 patients hospitalized for AHF with median follow-up of 4.76 (interquartile range [IQR]: 4.18-5.07) years were included. Tertile 1 of cumulative Mini-Cog score had the highest risk of all-cause (hazard ratio [HR]: 1.52, 95% confidence interval [CI]: 1.14-2.03) and cardiovascular mortality (HR: 1.40, 95% CI: 1.02-1.93) compared with Tertile 3; patients with ≥ 2 times of cognitive impairment had the highest risk of all-cause (HR: 1.34, 95% CI: 1.03-1.73) and cardiovascular mortality (HR: 1.25, 95% CI: 0.93-1.67) compared with patients without any cognitive impairment. Cumulative Mini-Cog score provided the highest incremental prognostic ability in predicting all-cause (C-statistics: 0.64, 95% CI: 0.61-0.66) and cardiovascular mortality (C-statistics: 0.63, 95% CI: 0.60-0.67) risk on the basis of Get With The Guidelines-Heart Failure score. CONCLUSION: Poor cumulative cognitive function was associated with increased risk of subsequent mortality and provided incremental prognostic ability for the outcomes among patients with AHF. Longitudinal assessment and monitoring of cognitive function among patients with AHF would be of great importance in identifying patients at greater risk of self-care absence for optimizing personal disease management in clinical practice.

Associations of remnant cholesterol with cardiovascular and cancer mortality in a nationwide cohort.

The health significance of triglyceride-rich lipoproteins, also known as remnant cholesterol, has been increasingly recognized. However, evidence of their associations with cause-specific mortality in the general population was previously insufficient. To explore these associations and their heterogeneities across subgroups, a prospective cohort study was conducted including 3,403,414 community-based participants from ChinaHEART, an ongoing government-funded public health program throughout China, from November 2014 through December 2022. The study assessed mortality risk of all-cause mortality, cardiovascular disease (CVD) mortality (including mortality from ischemic heart diseases (IHD), ischemic stroke (IS), and hemorrhagic stroke (HS), separately), and cancer mortality (including lung cancer, stomach cancer, and liver cancer, separately). During the 4-year follow-up, 23,646 individuals died from CVD (including 8807 from IHD, 3067 from IS, and 5190 from HS), and 20,318 from cancer (including 6208 from lung cancer, 3013 from liver cancer, and 2174 from stomach cancer). Compared with individuals with remnant cholesterol <17.9 mg/dL, multivariable-adjusted mortality hazard ratios (HRs) for individuals with remnant cholesterol ≥27.7 mg/dL were 1.03 (1.00-1.05) for all-cause mortality, 1.17 (1.12-1.21) for CVD (1.19 (1.12-1.27) for IHD mortality, and 1.22 (1.09-1.36) for IS mortality), and 0.90 (0.87-0.94) for all-cancer mortality (0.94 (0.87-1.02) for lung cancer, 0.59 (0.53-0.66) for liver cancer, and 0.73 (0.64-0.83) for stomach cancer). In summary, this study revealed a correlation between increased remnant cholesterol levels and an elevated risk of cardiovascular disease mortality, as well as a reduced risk of mortality for certain types of cancer.

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.

Lipoprotein(a) and Benefit of PCSK9 Inhibition in Emergency Complex Higher-risk and Indicated Patients.

OBJECTIVE: There is a large population of patients classified as complex higher-risk and indicated patients (CHIPs) in China with a poor prognosis. The treatment of these patients is complex and challenging, especially when acute cardiac events occur, such as acute coronary syndrome (ACS) or heart failure. Pharmacotherapy and some mechanical circulatory support (MCS) therapeutic devices can provide stable hemodynamic support for CHIPs-percutaneous coronary intervention (PCI). LDL-C is an important pathogenic factor in atherosclerosis, and the target of blood lipid control. Recent studies have revealed that lipoprotein(a) [Lp(a)], which is formed when a covalent bond between apolipoprotein(a) and apolipoprotein B-100 is made, produces an LDL-like particle. This particle is an independent risk factor for the development of atherosclerosis, and is closely correlated to stent thrombosis and restenosis. Furthermore, this requires active intervention. PCSK9 inhibitors have been used in lipid-lowering treatment, and preventing atherosclerosis. The present study explores the efficacy of PCSK9 inhibitors in CHIPs-ACS, and the association between the change in Lp(a) and survival after 2 years of follow-up. METHODS: The present real-world, prospective control study enrolled 321 CHIPs-ACS who underwent emergency PCI from August 2019 to November 2020, and these patients were followed up for 2 years. These patients were divided into two groups: PCSK9 group (n=161) given the combined PCSK9 inhibitor (140 mg of evolocumab every 2 weeks) and statins-based therapy, and SOC group (n=160) treated with statin-based lipid-lowering therapy alone. Then, the change in lipid index was measured, and the cardiovascular (CV) event recurrence rate was evaluated after one month and 2 years. Afterwards, the contribution of serum lipid parameters, especially the Lp(a) alteration, in patients with earlier initiation of the PCSK9 inhibitor to the CV outcome was analyzed. RESULTS: The LDL-C level was significantly reduced in both groups: 52.3% in the PCSK9 group and 32.3% (P<0.001) in the SOC group. It is noteworthy that the Lp(a) level decreased by 13.2% in the PCSK9 group, but increased by 30.3% in the SOC group (P<0.001). Furthermore, the number of CV events was not significantly different between the PCSK9 and SOC groups after the 2-year follow-up period. In the PCSK9 group, the Lp(a) reduction was associated with the baseline Lp(a) levels of the patients (r2 =-0.315, P<0.001). Moreover, the decrease in Lp(a) contributed to the decline in CV events in patients who received ACS CHIPs-PCI, and the decrease in Lp(a) level was independent of the LDL-C level reduction. CONCLUSION: The early initiation of PCSK9 inhibitors can significantly reduce the LDL-C and Lp(a) levels in ACS CHIPs-PCI. However, further studies are needed to confirm whether PCSK9 inhibitors can reduce the incidence of CV disease in CHIPs.

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.

Corrigendum: The value of HDL subfractions in predicting cardiovascular outcomes in untreated, diabetic patients with stable coronary artery disease: an age- and gender-matched case-control study.

[This corrects the article DOI: 10.3389/fendo.2022.1041555.].

Different clinical phenotypes of a pair of siblings with familial hypercholesterolemia: a case report and literature review.

BACKGROUND: Familial hypercholesterolemia (FH) leads to high plasma low-density lipoprotein cholesterol (LDL-C) levels and early cardiovascular morbidity and mortality. We treated a pair of siblings with FH. The cardiovascular manifestations in the proband were more severe than those in his elder sister, although they had almost similar LDL-C levels, ages, and lifestyles. Herein, we report the cases of this family to explore the possible causes of clinical phenotypic differences within the same genetic background. CASE PRESENTATION: We treated a 27-year-old male patient and his 30-year-old sister, both with FH. The coronary angiogram in the male patient revealed 80, 70, and 100% stenosis of the initial, distal right coronary artery branch, and left anterior descending branch, respectively, whereas his sister had almost no coronary stenosis. We treated them accordingly and performed family screening. We found that the LDL-C/particle discordance of the proband is much greater than that of his elder sister. In addition, the average size of LDL-C particle in the proband was smaller than that in his sister. CONCLUSIONS: Patients with FH have a much higher risk of premature atherosclerotic cardiovascular disease, but the clinical manifestations are heterogeneous. The smaller LDL particle size may be the underlying cause for different clinical outcomes in this pair of FH cases and be a potential novel indicator for predicting the prognosis of FH.

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.

Association between remnant cholesterol and verbal learning and memory function in the elderly in the US.

BACKGROUND: The relationship between remnant cholesterol (RC) and atherosclerotic cardiovascular risk has been given increasing attention in recent years. However, its association with verbal learning and memory performance has not been reported. METHODS: Data were extracted from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 database. Participants aged ≥60 years with available fasting lipid data were included. Verbal learning and memory performance were evaluated using the Consortium to Establish a Registry for Alzheimer's Disease Word List Memory Task (CERAD-WL) subtest. The CERAD total score was calculated as the mean of three immediate recalls and a delayed recall. RC was calculated as total cholesterol (TC) minus the sum of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). Multivariate ordinal logistic regression was performed to evaluate the association between RC, as well as its derived marker, the TC/RC ratio, and age-stratified quartiles of the CERAD total score. RESULTS: A total of 1377 participants were analysed. On a continuous scale, per 1 mmol/L increase in RC and per 1 unit increase in the TC/RC ratio were associated with multivariable adjusted odds ratios (95% CI) of 0.74 (0.58-0.94) and 1.45 (1.13-1.87), respectively, for having a CERAD total score in a higher quartile. On a categorical scale, higher RC quartiles were associated with a CERAD total score in a lower quartile; in contrast, the higher TC/RC quartile was associated with a CERAD total score in a higher quartile (all P for trend < 0.05). CONCLUSIONS: The current study suggests that lower RC levels and a higher TC/RC ratio are associated with better verbal learning and memory function, which indicates that lowering RC levels could be beneficial for preventing cognitive impairment in elderly individuals. Further research is needed to validate the causal roles of RC and the TC/RC ratio in cognition.

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.

Lipoprotein(a) and Cardiovascular Outcomes in Patients With Coronary Artery Disease and Different Metabolic Phenotypes.

Background: The positive relationship between metabolic healthy obesity (MHO) and cardiovascular risk has been under debate in recent years. Previously, strong evidence supported the causal role of increased plasma lipoprotein(a) [Lp(a)] levels in cardiovascular disease (CVD). The current study aimed to investigate the different associations of Lp(a) and cardiovascular events (CVEs) in patients with coronary artery disease (CAD) and different metabolic phenotypes. Methods: A total of 5,089 patients who were angiography-proven CAD were consecutively included and followed up for CVEs. Obesity was defined as a body mass index (BMI) ≥25 kg/m2 according to Asia-specific BMI criteria. Patients were divided into four groups according to metabolic phenotypes, namely metabolically healthy/unhealthy non-obese and metabolically healthy/unhealthy obese [metabolically healthy non-obese (MHN), MHO, metabolically unhealthy non-obese (MUN), and metabolically unhealthy obesity (MUO)]. Comparisons of CAD severity and outcomes were performed among four groups. Cox regression analyses and cubic spline models were used to examine the relationship between Lp(a) and CVEs in patients with different metabolic phenotypes. Results: During a median of 7.5 years' follow-up, 540 (10.6%) CVEs occurred. MUN and MUO populations had more severe coronary stenosis than MHN ones, while no significant difference in the Gensini score (GS) was observed between MHN and MHO. Patients with MUN and MUO presented a higher risk of CVEs than patients with MHN (hazard ratio [HR]: 1.414, 95% CI: 1.024-1.953-1.556 and HR: 1.747, 95% CI: 1.295-1.363, p < 0.05). In subgroup analysis, restricted cubic spline models showed that there was no association between Lp(a) and CVEs in patients in MHN and MHO, while the MUN and MUO groups presented increasing associations between Lp(a) and CVEs and such association was stronger in the MUO group. In Cox regression analysis, Lp(a) >50 mg/dl was associated with a 2.032- and 2.206-fold higher risk of subsequent CVEs in the MUO and MUN subgroups, respectively. Conclusion: Among patients with angiography-proven stable CAD, Lp(a) had a more significant prognostic value in both MUO and MUN individuals regardless of obesity, suggesting the importance of screening for cardiovascular risk with Lp(a) in metabolically unhealthy patients.

Current Guideline Risk Stratification and Cardiovascular Outcomes in Chinese Patients Suffered From Atherosclerotic Cardiovascular Disease.

Background and Aims: Heterogeneity exists among patients with atherosclerotic cardiovascular disease (ASCVD) with regard to the risk of recurrent events. Current guidelines have definitely refined the disease and we aimed to examine the practicability in Chinese population. Methods: A cohort of 9944 patients with ASCVD was recruited. Recurrent events occurred during an average of 38.5 months' follow-up were collected. The respective and combinative roles of major ASCVD (mASCVD) events and high-risk conditions, being defined by 2018 AHA/ACC guideline, in coronary severity and outcome were studied. Results: The number of high-risk conditions was increased with increasing number of mASCVD events (1.95 ± 1.08 vs. 2.16 ± 1.10 vs. 2.42 ± 1.22). Trends toward the higher to the highest frequency of multi-vessel coronary lesions were found in patients with 1- (71.1%) or ≥2 mASCVD events (82.8%) when compared to those without (67.9%) and in patients with 2- (70.5%) or ≥3 high-risk conditions (77.4%) when compared to those with 0-1 high-risk condition (61.9%). The survival rate was decreased by 6.2% between none- and ≥2 mASCVD events or by 3.5% between 0-1 and ≥3 high-risk conditions. Interestingly, diabetes was independently associated with outcome in patients with 1- [1.54(1.06-2.24)] and ≥2 mASCVD events [1.71(1.03-2.84)]. The positive predictive values were increased among groups with number of mASCVD event increasing (1.10 vs. 1.54 vs. 1.71). Conclusion: Propitious refinement of ASCVD might be reasonable to improve the survival. Concomitant diabetes was differently associated with the incremental risk among different ASCVD categories, suggesting the need of an appropriate estimate rather than a 'blanket' approach in risk stratification.

Molecular Cytogenetic Identification of the Wheat-Dasypyrum villosum T3DL·3V#3S Translocation Line with Resistance against Stripe Rust.

The annual species Dasypyrum villosum possesses several potentially valuable genes for the improvement of common wheat. Previously, we identified a new stripe rust-resistant line, the Chinese Spring (CS)-D. villosum 3V#3 (3D) substitution line (named CD-3), and mapped its potential rust resistance gene (designated as YrCD-3) on the 3V#3 chromosome originating from D. villosum. The objective of the present study was to further narrow down the YrCD-3 locus to a physical region and develop wheat-3V#3 introgression lines with strong stripe rust resistance. By treating CD-3 seeds with 60Co γ-irradiation, two CS-3V#3 translocation lines, T3V#3S.3DL and T3DS.3V#3L (termed 22-12 and 24-20, respectively), were identified from the M4 generation through a combination of non-denaturing fluorescence in situ hybridization (ND-FISH) and functional molecular markers. Stripe rust resistance tests showed that the line 22-12 exhibited strong stripe rust resistance similarly to CD-3, whereas 24-20 was susceptible to stripe rust similarly to CS, indicating that YrCD-3 is located on the short arm of 3V#3. The line 22-12 can potentially be used for further wheat improvement. Additionally, to trace 3V#3 in the wheat genetic background, we produced 30 3V#3-specific sequence tag (EST) markers, among which, 11 markers could identify 3V#3S. These markers could be valuable in fine-mapping YrCD-3.

SORBS2 as a molecular target for atherosclerosis in patients with familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is a metabolic disease in which patients are prone to develop premature atherosclerosis (AS). Sorbin and SH3 Domain Containing 2 (SORBS2) is known to play a role in coronary heart disease (CHD). However, the mechanism underlying SORBS2 involvement in the development of hypercholesterolemia remains unknown. Here, we investigated the effects of SORBS2 on inflammation and foam cell formation and its underlying mechanisms. METHODS: Using Bioinformatics analysis, we established that SORBS2 is upregulated in patients with FH. Circulating concentrations of SORBS2 were measured using ELISA kit (n = 30). The association between circulating SORBS2 levels and inflammatory factors or lipid indexes were conducted using Spearman correlation analysis. We further conducted in vitro experiments that the expression of SORBS2 were analyzed, and SORBS2 siRNA were transfected into oxidized LDL (OxLDL)-induced macrophages, followed by western blot and immunofluorescence. RESULTS: Circulating SORBS2 levels were positively associated with inflammatory factors and lipid indexes. We also observed that high in vitro expression of SORBS2 in OxLDL-induced macrophages. After SORBS2 silencing, Nod like receptor family pyrin domain-containing 3 protein(NLRP3)-Caspase1 activation and NF-κB activation were attenuated, and secretion of pro-inflammatory cytokines (IL-1ß and IL-18) was decreased. Moreover, SORBS2 silencing blocked reactive oxygen species (ROS) production and lipid accumulation, and promoted cholesterol efflux through ABCG1-PPARγ pathway. CONCLUSIONS: SORBS2 regulates lipid-induced inflammation and foam cell formation, and is a potential therapeutic target for hypercholesterolemia.