Association between genetics of diabetes, coronary artery disease, and macrovascular complications: exploring a common ground hypothesis

Type 2 diabetes and coronary artery disease (CAD) are conditions that cause a substantial public health burden. Since both conditions often coexist in the same individual, it has been hypothesized that they have a common effector. Insulin and hyperglycemia are assumed to play critical roles in this scenario. In recent years, many genetic risk factors for both diabetes and CAD have been discovered, mainly through genome-wide association studies. Genetic aspects of diabetes, diabetic macrovascular complications, and CAD are assumed to have intersections leading to the common effector hypothesis. However, only a few genetic risk factors could be identified that modulate the risk for both conditions. Polymorphisms in TCF7L2 and near the CDKN2A/B genes seem to be of great importance in this regard since they appear to modulate both conditions, and they are not necessarily related to insulinism, or hyperglycemia, for CAD development. Other issues related to this hypothesis, such as the problems of phenotype heterogeneity, are also of interest. Recent studies have contributed to a better understanding of the complex genetics of diabetic macrovascular complications. Much effort is still needed to clarify the associations in the genetics of diabetes, and cardiovascular disease. At present, there is little genetic evidence to support a common effector hypothesis, other than insulin or hyperglycemia, for the association between these conditions.     

Susceptibility genes for coronary heart disease and myocardial infarction

Coronary heart disease and its main complication, myocardial infarction is leading cause of death worldwide. Over the past years, much progress has been made in the pharmacotherapy of major risk factors like dyslipidemias, diabetes mellitus and hypertension. The targeting of coronary risk factors coupled with advances in the management of coronary artery disease has improved patient survival. However, the incidence of cardiovascular disease is projected to continue to rise and the identification of individuals at risk should improve beyond the traditional models of global risk factor scoring. In the past few years, important progresses have been made in the area of genomics, especially with the completion of the human genome-sequencing Consortium of 2004, proteomics and imaging. This progress will promote a better understanding of cardiovascular risk assessments and disease prediction, thus allowing earlier preventive strategies to prevent and improve cardiovascular outcomes. These genomic advances have improved characterization of disease pathology especially at the molecular level with the discovery and introduction of genetic markers, single nucleotide polymorphisms (SNPs), and haplotype blocks.     

Obstructive coronary artery disease with a coronary artery calcium score of 0: A case report

Coronary artery calcium (CAC) scoring has emerged as a useful tool in identifying patients who may benefit from more aggressive risk factor modification and for prognostication. Although a CAC score of 0 is associated with a very low prevalence of obstructive epicardial coronary artery disease and low event rates, it can also provide a false sense of reassurance. We present a case of a 39-year-old woman with a CAC score of 0 obtained as part of a coronary computerized tomography angiography study that was ultimately found to have significant left anterior descending artery disease requiring percutaneous coronary intervention and a stent.     

Ostial renal artery stent placement for atherosclerotic renal artery stenosis in patients with coronary artery disease

To test the utility of endoprosthetic treatment for ostial renal artery stenosis, and to examine blood pressure and its treatment, serum creatinine, and restenosis rate, 44 ostial renal stent placements were performed in 30 patients with concomitant coronary artery disease, arterial hypertension, and the indication for angiotensin converting enzyme (ACE) therapy. There was a marked decrease in systolic and diastolic blood pressure (163 ± 30 to 145 ± 17 and 93 ± 18 to 83 ± 10 mm Hg; P < 0.008) with a decrease in number of medication (3.2 ± 0.9 to 2.8 ± 1.0; P = 0.005). In 5 out of 8 patients not receiving an ACE inhibitor, this drug could be added. Serum creatinine changed from 1.46 ± 0.7 mg/dl to 1.39 ± 0.58 mg/dl (P = ns). Three patients showed restenosis (12.5%). Ostial stenting lowers blood pressure, decreases antihypertensive drugs and increases medication flexibility. Cathet. Cardiovasc. Diagn. 45:1–8, 1998. © 1998 Wiley-Liss, Inc.     

ICAM-1基因K469E多态性与冠心病关联的荟萃分析

目的 探讨细胞间黏附分子-1(Intercellular adhesion molecule-1,ICAM-1)基因K469E多态性与冠心病的关联性.方法 全面检索中英文数据库关于K469E多态性与冠心病遗传易感性关系的病例对照研究,采用Meta分析方法合并K469E与冠心病关联的OR值,结合95％CI作为每个研究结果...     

Integration of summary data from GWAS and eQTL studies identified novel risk genes for coronary artery disease

Several genetic loci have been reported to be significantly associated with coronary artery disease (CAD) by multiple genome-wide association studies (GWAS). Nevertheless, the biological and functional effects of these genetic variants on CAD remain largely equivocal. In the current study, we performed an integrative genomics analysis by integrating large-scale GWAS data (N = 459,534) and 2 independent expression quantitative trait loci (eQTL) datasets (N = 1890) to determine whether CAD-associated risk single nucleotide polymorphisms (SNPs) exert regulatory effects on gene expression. By using Sherlock Bayesian, MAGMA gene-based, multidimensional scaling (MDS), functional enrichment, and in silico permutation analyses for independent technical and biological replications, we highlighted 4 susceptible genes (CHCHD1, TUBG1, LY6G6C, and MRPS17) associated with CAD risk. Based on the protein–protein interaction (PPI) network analysis, these 4 genes were found to interact with each other. We detected a remarkably altered co-expression pattern among these 4 genes between CAD patients and controls. In addition, 3 genes of CHCHD1 (P = .0013), TUBG1 (P = .004), and LY6G6C (P = .038) showed significantly different expressions between CAD patients and controls. Together, we provide evidence to support that these identified genes such as CHCHD1 and TUBG1 are indicative factors of CAD.     

Anomalous origin of the right coronary artery from the left anterior descending coronary artery

A 77-year-old male presented with a recent posterior myocardial infarction for coronary angiography. This angiogram revealed a rare, previously unreported anomalous origin of the right coronary artery from the proximal left anterior descending coronary artery distal to the first major diagonal branch. Cathet. Cardiovasc. Diagn. 42:308–309, 1997. © 1997 Wiley-Liss, Inc.     

Peripheral atherosclerosis evaluation through ultrasound: A promising diagnostic tool for coronary artery disease

Effective treatment, but also proper diagnosis of cardiovascular diseases, remains a major challenge in everyday practice. A quick, safe, and economically acceptable non-invasive procedure should play a leading role in cardiovascular risk assessment before invasive diagnostics is performed. The staging of subclinical atherosclerosis may help in further clinical decisions. Safe, widely available, and relatively inexpensive, ultrasonography is a promising examination that should find wider application in clinical practice. The latest ESC guidelines emphasize the usefulness of carotid ultrasound in the diagnosis of coronary artery disease (CAD) and subclinical assessment of atherosclerosis, which help to determine the level of cardiovascular risk. Ultrasound examination of peripheral arteries, especially superficial vessels such as the femoral arteries, is quite easy, quick, and accurate. Other vascular beds, such as iliac and renal, are more demanding to examine, but can also provide valuable information. This review summarizes important studies comparing the severity of atherosclerosis in ultrasound-visible vascular beds in patients with established CAD. We especially emphasize the benefits of the combined assessment of atherosclerosis features, which were characterized by high sensitivity and specificity in the diagnosis of CAD and other serious cardiovascular diseases.     

Genetics of coronary artery disease in the post-GWAS era

During the past decade, genome-wide association studies (GWAS) have transformed our understanding of many heritable traits. Three recent large-scale GWAS meta-analyses now further markedly expand the knowledge on coronary artery disease (CAD) genetics in doubling the number of loci with genome-wide significant signals. Here, we review the unprecedented discoveries of CAD GWAS on low-frequency variants, underrepresented populations, sex differences and integrated polygenic risk. We present the milestones of CAD GWAS and post-GWAS studies from 2007 to 2021, and the trend in identification of variants with smaller odds ratio by year due to the increasing sample size. We compile the 321 CAD loci discovered thus far and classify candidate genes as well as distinct functional pathways on the road to indepth biological investigation and identification of novel treatment targets. We draw attention to systems genetics in integrating these loci into gene regulatory networks within and across tissues. We review the traits, biomarkers and diseases scrutinized by Mendelian randomization studies for CAD. Finally, we discuss the potentials and concerns of polygenic scores in predicting CAD risk in patient care as well as future directions of GWAS and post-GWAS studies in the field of precision medicine.     

Angiotensin-converting enzyme and apolipoproteins genes polymorphism in coronary artery disease

BACKGROUND: Association between angiotensin-converting enzyme (ACE) as well as apolipoprotein (apo) AI, B, and E polymorphisms and dyslipidemia and coronary artery disease (CAD) is controversial. HYPOTHESIS: This study assessed the distribution of ACE insertion/deletion, apo AI A/G mutation, apo B signal peptide insertion/deletion, apo B XbaI restriction fragment length, and apo E polymorphisms in 388 nondiabetic patients. METHODS: The study population included 112 patients with stable CAD, 139 patients with acute myocardial infarction (AMI), and 137 age-matched control subjects. RESULTS: Univariate analysis showed higher prevalence of XbaI X+/X+ genotype in patients with CAD (p = 0.02). Angiotensin-converting enzyme and apo polymorphisms were not associated with lipid levels or severity of CAD. When all genotypes known to be related to CAD; such as ACE DD, apo AI GG, apo B del/del, and XbaI X+X+, and E4 allele of apo E, were pooled, again no significant differences among groups were seen. Multivariate regression analysis disclosed traditional risk factors and elevated levels of apo B for men and reduced levels of apo AI for women as independent variables for CAD. CONCLUSIONS: In addition to traditional coronary risk factors, apo B and AI could be considered predictors of CAD. No association between either form of CAD and polymorphisms was noted.     

Anomalous origin of the right coronary artery from the left anterior descending: Angiographic diagnosis in a patient with coronary artery disease

The coronary angiographic findings of an individual whose right coronary artery originates from the proximal left anterior descending coronary artery are described.     

Electron beam computed tomography: screening for coronary artery disease.

The need to detect coronary atherosclerosis early in its course has been well recognized by clinicians and epidemiologists for decades. The ability to identify populations with a greater prevalence of coronary disease prior to manifestation of illness would greatly reduce cardiac morbidity and mortality. Electron beam computed tomography (EBCT) uniquely combines the characteristics of speed and excellent density resolution that have led to a rebirth of interest in detecting coronary calcium as a means of screening asymptomatic populations for coronary atherosclerosis. Electron beam computed tomography is noninvasive and widely applicable. It can both detect and quantitate the presence of coronary atherosclerosis. A positive test has diagnostic and prognostic significance, predicting future cardiac events and the extent of atherosclerosis, including the probability of obstructive coronary artery disease (CAD). Multiple studies demonstrate a 6- to 35-fold increased risk of developing a cardiac event with elevated calcium scores. A negative test is highly predictive for excluding obstructive CAD. The cost ranges from $300 to $400, similar to that of an exercise treadmill test. Moreover, scanning for coronary calcium does not require injection of contrast medium, requiring no patient preparation or exercise; therefore, a CT technician can perform the study without supervision. The entire procedure takes < 10 min to perform. These features make EBCT a potential screening test for occult CAD in symptomatic and asymptomatic persons.     

冠状动脉钙化的影响因素

冠状动脉钙化是冠状动脉粥样硬化性心脏病的特异性标志和独立预测因子,其形成机制复杂,与基因、年龄、性别、性格、吸烟、睡眠、高血压、高血糖、高脂血症、肾脏疾病等多种因素密切相关。早期预测和延缓冠状动脉钙化进展将是未来冠状动脉粥样硬化性心脏病诊治中一项任重道远的工作。     

HO-1基因启动子区多态性与客家人群糖尿病个体冠心病患病风险关联

目的:通过检测客家人群冠心病患者HO-1基因启动子区GT重复多态性,旨在阐明HO-1基因多态性与冠心病易感性的关联.方法:选择广东梅州客家地区确诊的冠心病患者100例为病例组,经冠状动脉造影或无创检查排除冠心病的个体100例为对照组.采用荧光标记PCR和毛细管电泳相结合技术检测HO-1启动子区(GT)n多态性并进行基因...     

Prevalence and predictors of renal artery stenosis in Chinese patients with coronary artery disease

Abstract
Background:  Ischaemic nephropathy is currently a major public health issue in atherosclerotic populations. Although atherosclerotic cardiovascular disease in Asia has reached epidemic proportions over the last two decades, there is little published data on the prevalence of atherosclerotic renal artery stenosis (ARAS) in Oriental subjects. Because ARAS may be clinically silent until end-stage renal failure sets in, it is important to identify patients with significant but clinically unsuspected ARAS. ARAS and coronary artery disease (CAD) often coexist.
Aims:  The purpose of the present study was to evaluate the prevalence and predictors of ARAS among Chinese patients with CAD.
Methods:  A total of 230 consecutive Chinese patients with CAD confirmed by coronary angiography underwent an abdominal aortogram in the same sitting to screen for ARAS. Patient demographics and comorbid­ities were analysed for any association with ARAS.
Results:  A total of 34 (14.8%) patients was found to have significant ARAS. Age and multivessel CAD were independent predictors of ARAS. Hypertension, renal insufficiency, extracranial cerebrovascular disease and female gender were also associated with a higher risk of ARAS but did not independently predict ARAS.
Conclusion:  Clinically silent yet angiographically significant ARAS is common among CAD patients. The prevalence and predictors of ARAS among Chinese patients with CAD are similar to those reported for Caucasian subjects. Underlying ARAS should be suspected in CAD patients with such comorbidities as hypertension, renal insufficiency, extracranial cerebrovascular disease, and more so in the elderly and those with multivessel disease. (Intern Med J 2003; 33: 280−285)     

伴有慢性支气管炎症老年患者颈动脉硬化病变与冠状动脉病变有相关性

目的:应用多普勒超声分析伴有慢性支气管炎的心绞痛患者颈动脉病变,并分析与冠心病病变的相关性。方法: 选择因心绞痛行冠状动脉造影的患者328例,根据造影结果分为对照组80例、单支病变组102例、2支病变组62例和多支病变组84例。测量颈总动脉内膜中层厚度（IMT）及颈动脉分叉处IMT,记录颈动脉斑块的位置、数量。结果: 颈总动脉IMT、分叉部IMT、斑块积分组间差异有统计学意义（P<0.05,P<0.01）。颈总动脉 IMT多支病变组与对照组（P<0.01）、2支病变组与对照组（P<0.05）、单支病变组与多支病变组（P<0.01）差异有统计学意义,其余组间两两比较无统计学差异。分叉部IMT,单支病变组与对照组差异无统计学意义,其余各组两两之间比较均有统计学差异(P<0.01,P<0.05)。斑块积分,多支病变组与2支病变组间差异无统计学意义,其余组间两两比较均有统计学差异(P<0.01,P<0.05)。颈动脉IMT、分叉部IMT、斑块积分相关系数均有统计学意义（P<0.05）。结论: 伴有慢性支气管炎的老年颈动脉粥样硬化与其冠状动脉病变有相关性。     

Accelerated coronary artery disease after heart transplantation: the role of enhanced platelet aggregation and thrombosis

Abstract. The present study is a prospective examination of the relationship between platelet aggregation and the occurrence of graft failure in a single cohort of heart transplantation (HT) recipients. One-hundred-and-twenty-four patients underwent platelet function study and were then followed for 1 to 24 months (mean 6.7 months). There were nine re-transplantations and 13 deaths (11 related to ischaemic events, and two others). In 15 patients, pathologic examination confirmed or revealed that recent acute myocardial infarction was the obvious cause of the graft failure. In five patients, myocardial fibrosis related to severe and diffuse coronary disease was the only microscopic finding. In the last two patients, the cause of the heart failure was not clearly identified. In recent myocardial infarction there was a high incidence (14/15) of coronary thrombi. Thrombi were multiple, disseminated in the coronary tree end of different age. Their presence at autopsy or after explantation was associated with an enhanced ex vivo platelet aggregability as compared with patients without coronary thrombi (n = 8): 43.3 ± 1.7% of maximal aggregation vs. 34.4 ± 2.4 (P = 0.006) and 48.4 ± 5.2 vs. 22.6 ± 4.9 (P = 0.003) for the primary and secondary waves of ADP-induced aggregation. These results suggest that thrombosis and platelets may play a major role in the process of accelerated coronary artery disease after HT.     

Triple origin of left coronary arteries from right coronary artery: Unusual case of single coronary artery

A rare case of coronary anomaly is presented: all of the coronary arteries originated from a single ostium located in the right coronary cusp. No clinical evidence of coronary pathology was recognized until the age of 57 years when the patient was found to have coronary obstructive disease. The single coronary artery had a main branch corresponding to the usual dominant right coronary artery. Three other branches separated from this and vascularized the areas normally receiving the circumflex and ramus medianus, the left anterior descending, and a large septal branch.