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Mendelian randomization studies on atherosclerotic cardiovascular disease: evidence and limitations

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Science China(Life Sciences) 2019年第6期62卷 758-770页

作者： Qin Hu Panpan Hao Qiji Liu Mei Dong Yaoqin Gong Cheng Zhang Yun Zhang The Key Laboratory of Cardiovascular Remodeling and Function Research Ministry of Education of China Ministry of Health of China and Chinese Academy of Medical Sciences and The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine Qilu Hospital of Shandong University Jinan 250012 China Department of Medical Genetics School of Medicine Key Laboratory of Experimental Teratology Ministry of Education Shandong University Jinan 250012 China

Epidemiological research has revealed a galaxy of biomarkers, such as genes, molecules or traits, which are associated with increased risk of atherosclerotic cardiovascular diseases(ASCVD). However, the etiological basis remains poorly characterized.Mendelian randomization(MR) involves the use of observational genetic data to ascertain the roles of disease-associated risk factors and, in particular, differentiate those reflecting the presence or severity of a disease from those contributing causally to a disease. Over the past decade, MR has evolved into a fruitful approach to clarifying the causal relation of a biomarker with ASCVD and to verifying potential therapeutic targets for ASCVD. In this review, we selected high-quality MR studies on ASCVD, examined the causal relationship of a series of biomarkers with ASCVD, and elucidated the role of MR in validating biomarkers as a therapeutic target by comparing the results from MR studies and randomized clinical trials(RCTs) for the treatment of ASCVD. The good agreement between the results derived by MR and RCTs suggests that MR could be performed as a screening process before novel drug development. However, when designing and interpreting a MR study, the assumptions and limitations inherent in this approach should be taken into account. Novel methodological developments, such as sensitivity analysis, will help to strengthen the validity of MR studies.

关键词： Mendelian randomization atherosclerotic cardiovascular disease causality therapeutic target

Microstructural damage pattern of vascular cognitive impairment: a comparison between moyamoya disease and cerebrovascular atherosclerotic disease

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Neural Regeneration Research 2019年第5期14卷 858-867页

作者： Jia-Bin Su Si-Da Xi Shu-Yi Zhou Xin Zhang Shen-Hong Jiang Bin Xu Liang Chen Yu Lei Chao Gao Yu-Xiang Gu Department of Neurosurgery Huashan Hospital Fudan University Shanghai Medical College Fudan University Department of Radiology Huashan Hospital Fudan University

Moyamoya disease and cerebrovascular atherosclerotic disease are both chronic ischemic diseases with similar presentations of vascular cognitive impairment. The aim of the present study was to investigate the patterns of microstructural damage associated with vascular cognitive impairment in the two diseases. The study recruited 34 patients with moyamoya disease(age 43.9 ± 9.2 years; 20 men and 14 women, 27 patients with cerebrovascular atherosclerotic disease(age: 44.6 ± 7.6 years; 17 men and 10 women), and 31 normal controls(age 43.6 ± 7.3 years; 18 men and 13 women) from Huashan Hospital of Fudan University in China. Cognitive function was assessed using the Mini-Mental State Examination, long-term delayed recall of Auditory Verbal Learning Test, Trail Making Test Part B, and the Symbol Digit Modalities Test. Single-photon emission-computed tomography was used to examine cerebral perfusion. Voxel-based morphometry and tract-based spatial statistics were performed to identify regions of gray matter atrophy and white matter deterioration in patients and normal controls. The results demonstrated that the severity of cognitive impairment was similar between the two diseases in all tested domains. Patients with moyamoya disease and those with cerebrovascular atherosclerotic disease suffered from disturbed supratentorial hemodynamics. Gray matter atrophy in bilateral middle cingulate cortex and parts of the frontal gyrus was prominent in both diseases, but in general, was more severe and more diffuse in those with moyamoya disease. White matter deterioration was significant for both diseases in the genu and body of corpus callosum, in the anterior and superior corona radiation, and in the posterior thalamic radiation, but in moyamoya disease, it was more diffuse and more severe. Vascular cognitive impairment was associated with regional microstructural damage, with a potential link between, gray and white matter damage. Overall, these results provide insight into the pathophysiological nature of vascular cognitive i

关键词： nerve regeneration vascular cognitive impairment moyamoya disease cerebrovascular atherosclerotic disease magnetic resonance imaging diffusion tensor imaging gray matter volume tract-based spatial statistics single-photon emission computed tomography neural regeneration

Potential protective effects of red yeast rice in endothelial function against atherosclerotic cardiovascular disease

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Chinese Journal of Natural Medicines 2019年第1期17卷 50-58页

作者： FENG Shu-Jun TANG Zhi-Han WANG Ying TANG Xin-Ying LI Tao-Hua TANG Wei KUANG Ze-Min Department of Cardiology The First People's Hospital of ChenzhouUniversity of South China Institute of Cardiovascular Disease Key Lab for Arteriosclerology of Hunan ProvinceUniversity of South China Department of Biochemistry and Molecular Biology The Libin Cardiovascular Institute of AlbertaThe University of CalgaryHealth Sciences Center3330 Hospital Drive NW Department of Cardiology The Second Affiliated Hospital of Henan University of Science and Technology Class 2014 Medical CollegeUniversity of South China Department of Hypertension Beijing Anzhen Hospital of Capital Medical University

atherosclerotic cardiovascular disease(ASCVD) is the deadliest disease in the world, with endothelial injury occurring throughout the course of the disease. Therefore, improvement in endothelial function is of essential importance in the prevention of ASCVD. Red yeast rice(RYR), a healthy traditional Chinese food, has a lipid modulation function and also plays a vital role in the improvement of endothelial reactivity and cardiovascular protection; thus, it is significant in the prevention and treatment of ASCVD. This article reviews the molecular mechanisms of RYR and its related products in the improvement of endothelial function in terms of endothelial reactivity, anti-apoptosis of endothelial progenitor cells, oxidative stress alleviation and anti-inflammation.

关键词： Red yeast rice Xuezhikang atherosclerotic cardiovascular disease Endothelial cells Molecular mechanism

Value of superb micro-vascular imaging in predicting ischemic stroke in patients with carotid atherosclerotic plaques

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World Journal of Clinical Cases 2019年第7期7卷 839-848页

作者： De-Bin Yang Jie Zhou Lan Feng Rong Xu Ying-Chun Wang Department of Ultrasonic Imaging Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences

BACKGROUND Unstable carotid atherosclerotic plaques are prone to cause ischemic stroke.Contrast-enhanced ultrasound(CEUS) is the primary method of assessing plaque stability, but CEUS cannot be a method for screening for unstable plaque. The emergence of superb micro-vascular imaging(SMI) offers the possibility of clinically screening for unstable plaque AIM To investigate the value of SMI in predicting ischemic stroke in patients with carotid atherosclerotic plaques.METHODS Patients with carotid atherosclerotic plaques(luminal stenosis of 50%-70%) were enrolled into the present study. All patients received conservative medication.The patient's clinical baseline data, serological data, CEUS and SMI data were analyzed. All patients underwent a 3-year follow-up. The follow-up endpoint was the occurrence of ischemic stroke and patients were divided into stroke group and non-stroke group according to whether the prognosis occurred or not.Subsequently, the difference in clinical data was compared, the correlation of SMI and CEUS was analyzed, and multiple Cox regression and receiver operating characteristic curve were applied to investigate the value of SMI and CEUS in predicting cerebral arterial thrombosis in three years.RESULTS In this study, 43 patients were enrolled in the stroke group and 82 patients were enrolled in the non-stroke group. Cox regression revealed that SMI level(P =0.013) and enhancement intensity(P = 0.032) were the independent factors influencing ischemic stroke. There was a positive correlation between SMI level and enhancement intensity(r = 0.737, P = 0.000). The area under curve of SMI level predicting ischemic stroke was 0.878. The best diagnostic point was ≥ level Ⅱ, and its sensitivity and specificity was 86.05% and 79.27%. The area under curve of enhancement intensity predicting ischemic stroke was 0.890. The best diagnostic point was 9.92 db, and its sensitivity and specificity was 88.37% and89.02%. As the SMI level gradually increased, the incidence of ischemic stroke increased graduall

关键词： Superb micro-vascular imaging Contrast-enhanced ultrasound Carotid atherosclerotic plaques Ischemic stroke

Association between Coronary atherosclerotic Plaque Composition and Cardiovascular Disease Risk

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Biomedical and Environmental Sciences 2019年第2期32卷 75-86页

作者： LI Lin WANG Long LIU Shan Shan ZHAO Zhi Yun LI Mian WANG Tian Ge XU Min LU Jie Li CHEN Yu Hong WANG Shuang Yuan DAI Meng HOU Ya Nan WU Xue Yan MA Li Na WANG Wei Qing XU Yu BI Yu Fang National Clinical Research Center for Metabolic Diseases Shanghai Institute of Endocrine and Metabolic Diseases and Department of Endocrine and Metabolic Diseases Rui-Jin Hospital Shanghai Jiao-Tong University School of Medicine

Objective The objective of this study is to determine whether coronary atherosclerotic plaque composition is associated with cardiovascular disease(CVD) risk in Chinese adults. Methods We performed a cross-sectional analysis in 549 subjects without previous diagnosis or clinical symptoms of CVD in a community cohort of middle-aged Chinese adults. The participants underwent coronary computed tomography(CT) angiography for the evaluation of the presence and composition of coronary plaques. CVD risk was evaluated by the Framingham risk score(FRS) and the 10-year atherosclerotic cardiovascular disease(ASCVD) risk score. Results Among the 549 participants, 267(48.6%) had no coronary plaques, 201(36.6%) had noncalcified coronary plaques, and 81(14.8%) had calcified or mixed coronary plaques. The measures of CVD risk including FRS and ASCVD risk score and the likelihood of having elevated FRS significantly increased across the groups of participants without coronary plaques, with noncalcified coronary plaques, and with calcified or mixed coronary plaques. However, only calcified or mixed coronary plaques were significantly associated with an elevated ASCVD risk score [odds ratio(OR) 2.41; 95% confidence interval(CI) 1.09-5.32] compared with no coronary plaques, whereas no significant association was found for noncalcified coronary plaques and elevated ASCVD risk score(OR 1.25; 95% CI 0.71-2.21) after multivariable adjustment. Conclusion Calcified or mixed coronary plaques might be more associated with an elevated likelihood of having CVD than noncalcified coronary plaques.

关键词： Coronary plaque composition Framingham risk score 10-year atherosclerotic cardiovascular disease risk score

Characterization of coronary atherosclerotic plaques in a homozygous familial hypercholesterolemia visualized by optical coherence tomography

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Journal of Geriatric Cardiology 2018年第12期15卷 738-743页

作者： Ze-Sen LIU Jie PENG Shi-Long WANG Tao JIANG Jie LIN Kang MENG Department of Cardiology Beijing Anzhen Hospital.Capital Medical UniversityBeijingChina Department of Atherosclerosis.Beijing Anzhen Hospital Capital Medical UniversityBeijingChina Department of Radiology Beijing Anzhen HospitalCapital Medical UniversityBeijingChina

Familial hypercholesterolemia(FH)is an autosomal dominant genetic disorder,which resulted in severe elevations in low-density lipoprotein cholesterol(LDL-C)and a markedly increased risk of early-onset coronary disease.[1]t is most frequently caused by loss-of-function mutations in genes affecting the LDL receptor,which clears LDL particles from plasma.

关键词： Coronary atherosclerotic plaques Homozygous familial hypercholesterolemia Optical coherence tomography

Efficacy of Qingre Huayu Fang (清热化瘀方) on atherosclerotic vulnerable plaque in apolipoprotein E knockout mice:proteasome pathway involvement

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Journal of Traditional Chinese Medicine 2021年第3期41卷 432-437页

作者： PANG Jun CHENG Wenli PENG Jingbing LI Hong WU Qiang LI Ling LIU Chengming LIU Wei HUANG Jing De-partment of Cardiology Guizhou Provincial People's HospitalGuiyang 520000China Department of Hypertension Beijing Anzhen HospitalBeijing 100029China Institute of Clinical Medicine Beijing China-Japan Friendship HospitalBeijing 100029China Emergency Department Guizhou Provincial People's HospitalGuiyang 520000China

OBJECTIVE: To investigate the efficacy and mechanism of the Qingre Huayu Fang(清热化瘀方) on atherosclerotic vulnerable plaque in apolipoprotein E(Apo E) knockout mice through the ubiquitin proteasome pathway.METHODS: Sixty 8-week-old C57BL/6J Apo E knockout mice were fed a high-fat for 12 weeks and randomly divided into four treatment groups(n = 15 each): high-fat control, bortezomib(a proteasome inhibitor), bortezomib combined with Qingre Huayu Fang, and Qingre Huayu Fang alone. Aortic sections were examined for plaque development, inflammatory cell infiltration, type Ⅰ/Ⅲ collagen expression and immunohistochemical staining of CD40L, nuclear factor-kappa B(NF-κB)/P65 and ubiquitin.RESULTS: Mice in the high-fat control group had obvious atherosclerosis, with increased aortic plaque area. The degree of atherosclerosis of the atherosclerotic plaque was reduced in all of the treatment groups that received bortezomib and/or Duzhong(Cortex Eucommiae) Qingre Huayu. The expression of NF-?B, CD40L and ubiquitin were all reduced in the group that received combination bortezomib + Qingre Huayu Fang.CONCLUSION: The Qingre Huayu Fang inhibited aortic atherosclerosis in mice through a mechanism that may involve inhibition of the ubiquitin proteasome pathway.

关键词： atherosclerosis plaque atherosclerotic proteasome endopeptidase complex CD40 ligand NF-kappa B Qingre Huayu

Study of apolipoprotein E genetic polymorphism in patients with atherosclerotic cerebral infarction

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2003年第6期4卷 128-131页

作者：罗本燕陈智陈峰李霞潘小平 Hangzhou 310003 Department of Neurology Zhejiang University Institute of Infectious Diseases The First Affiliated Hospital Institute of Infectious Diseases Medical College China

Objective: To explore the frequency and significance of ApoE gene polymorphisms in Chinese patients with atherosclerotic cerebral infarction (ACI). Methods: Polymerase chain reaction and gene sequencing, single nucleotide polymorphisms of ApoE gene were used to analyze 33 cases of patients with ACI and 35 controls. Results: The frequencies of ApoE gene single nucleotide polymorphisms 465C/G, 462C/G and 451delC in the ACI group were significantly higher than those in the control group (P<0.05). The prevalence of polymorphism 486G/T in the control group was significantly higher than that in the ACI group ( P = 0.011) . Conclusions: 465C/G,462C/G and 451delC polymorphisms might be associated with ACI.486GT allele might have protective effect on the pathogenesis of ACI.

关键词： Cerebral infarction atherosclerotic Genetics ApoE allele Single nucleotide polymorphism

The rate of patients at high risk for cardiovascular disease with an optimal low-density cholesterol level: a multicenter study from Thailand

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Journal of Geriatric Cardiology 2019年第4期16卷 344-353页

作者： Rungroj Krittayaphong Arintaya Phrommintikul Smonporn Boonyaratvej Rapeephon Kunjara Na Ayudhya Pyatat Tatsanavivat Chulaluk Komoltri Piyamitr Sritara Division of Cardiology Department of MedicineFaculty of Medicine Siriraj HospitalMahidol UniversityBangkokThailand Division of Cardiology Department of Internal MedicineFaculty of MedicineChiang Mai UniversityChiang MaiThailand Division of Cardiology Department of MedicineFaculty of MedicineChulalongkorn UniversityBangkokThailand Department of Cardiology Vichaiyut Hospital and Medical CenterBangkokThailand Division of Cardiology Department of MedicineFaculty of MedicineKhon Kaen UniversityKhon KaenThailand Clinical Epidemiology Unit Office for Research and DevelopmentFaculty of Medicine Siriraj HospitalMahidol UniversityBangkokThailand Division of Cardiology Department of MedicineFaculty of Medicine Ramathibodi HospitalMahidol UniversityBangkokThailand

Background Hypercholesterolemia is a major risk factor for cardiovascular events in patients with established atherosclerotic disease (EAD) and in those with multiple risk factors (MRFs). This study aimed to investigate the rate of optimal low-density lipoprotein (LDL) cholesterol level in a multicenter registry of patients at high risk for cardiovascular events. Methods A multicenter registry of EAD and MRF patients was conducted. Demographic data,medical history,cardiovascular risk factors,anthropometric data,laboratory data,and medications were recorded and analyzed. We classified patients according to target LDL levels based on recommendation by the European Society of Cardiology (ESC) 2011 into Group 1 which is EAD and diabetes or chronic kidney disease (CKD)–target LDL below 70 mg/dL,and Group 2 which is MRF without diabetes or CKD–target LDL below 100 mg/dL. The rate of optimal LDL level in patients with Group 1 and Group 2 was analyzed and stratified according to the treatment pattern of lipid-lowering medications. Results A total of 3100 patients were included. Of those,51.7% were male. Average age was 65.8 ± 9.7 years. Average LDL level was 96.3 ± 32.6 mg/dL. A vast majority (92.7%) received statin and 9.3% received ezetimibe. Optimal LDL level was achieved in 20.3% of patients in Group 1 (LDL < 70 mg/dL),and in 46.6% in Group 2 (LDL < 100 mg/dL). The overall rate of optimal LDL control was 23% since 89.6% of study population belongs to Group 1. The rate of optimal LDL was not different between high and low potency statin. Factors that were associated with optimal LDL control were older age,the presence of coronary artery disease or peripheral artery disease. Conclusions The rates of optimal LDL level were unacceptably low in this study population. As such,a strategy to improve LDL control in high-risk population should be implemented.

关键词： Cardiovascular event Established atherosclerotic disease Low-density lipoprotein cholesterol Risk factors Thailand