Coronary artery disease and the thrombospondin single nucleotide polymorphisms

GeneQuest was a high throughput, large-scale analysis of single nucleotide polymorphisms (SNPs) to identify gene associated with familial, premature coronary artery disease and myocardial infarction. The three SNPs showing the highest and most significant associations with disease were all members of the thrombospondin gene family, thrombospondin-1, thrombospondin-2 and thrombospondin-4. These unanticipated associations have kindled efforts to understand how the three SNPs influence the structures and functions of the thrombospondins. The SNP in thrombospondin-1 and thrombospondin-4 reside in their coding regions and result in single amino acid changes: in thrombospondin-1, the predominant asparagine at position 700 is changed to a serine while, in thrombospondin-4, it is a change of an alanine to a proline at position 387. The SNP in thrombospondin-2 is a base change in the 3'-untranslated region of the mRNA. At this early stage of investigation, predictive analyses suggest that the substitutions in thrombospondin-2 and thrombospondin-4 should alter structure, and there is direct evidence to indicate that the thrombospondin-1 SNP alters conformational stability. In addition, profound differences in the function of the thrombospondin-4 SNP variants have been identified with respect to their capacity to support endothelial cell adhesion and proliferation. While substantial additional information is needed to understand if and how the polymorphic forms of the thrombospondins affect coronary artery disease, the data assembled to date suggest marked effects of these SNPs on the structures and functions of the thrombospondins, which are consistent with induction of a proatherogenic and prothrombotic phenotype.     

Coronary artery disease: Part 1. Epidemiology and diagnosis

Coronary artery disease (CAD) is the leading cause of death in Americans, accounting for about 500,000 deaths every year. The annual incidence of myocardial infarction (MI) is about 1.5 million. As many as 2 million middle-aged men may have silent myocardial ischemia. (1)     

Coronary artery fistulas

The aetiology of congenital coronary artery fistulas remains a challenging issue. Coronary arteries with an anatomically normal origin may, for obscure reasons, terminate abnormally and communicate with different single or multiple cardiac chambers or great vessels. When this occurs, the angiographic morphological appearance may vary greatly from discrete channels to plexiform network of vessels. Coronary arteriovenous fistulas (CAVFs) have neither specific signs nor pathognomonic symptoms; the spectrum of clinical features varies considerably. The clinical presentation of symptomatic cases can include angina pectoris, myocardial infarction, fatigue, dyspnoea, CHF, SBE, ventricular and supraventricular tachyarrhythmias or even sudden cardiac death. CAVFs may, however, be a coincidental finding during diagnostic coronary angiography (CAG). CAG is considered the gold standard for diagnosing and delineating the morphological anatomy and pathway of CAVFs. There are various tailored therapeutic modalities for the wide spectrum of clinical manifestations of CAVFs, including conservative pharmacological strategy, percutaneous transluminal embolisation and surgical ligation.     

Coronary artery calcium findings in asymptomatic subjects with family history of premature coronary artery disease

ABSTRACT: BACKGROUND: To evaluate the frequency of positive coronary arteries calcium (CAC) scores in a unique population of asymptomatic first degree relatives (FDRs) of patients with angiographically confirmed early onset of coronary artery disease (CAD) and to assess their association with carotid ultrasound findings and other cardiovascular risk factors. Method and Results: We scanned, using 64-slice multi-detector computed tomography, 57 asymptomatic FDRs (47+9 years old; 44% male, 56% female), out of the 111 FDRs previously phenotyped for cardiovascular (CV) risk factors. The controls were 616 individuals (57+10 years old; 76% male, 24% female) with no family history of cardiovascular disease, chest pain or diabetes selected out of the 3500 subjects scanned between 2002 and 2007. FDRs had higher risk of abnormal CAC scores compared to controls; odds ratio (OR) for the 75th percentile was 1.96 (95%CI 1.04 - 3.67, p<0.05). CONCLUSION: The frequency of abnormal CAC scores is two-fold higher in asymptomatic FDRs than in controls. CAC scan provides additional information on CV risk assessment in asymptomatic FDRs, particularly for those in the intermediate risk category. Clinical Trial Registration: NCT00387595.     

Coronary artery surgery.

Coronary artery disease has been described as the largest public health problem in Western society. In spite of the many advances in recent years in its medical management, many patients remain disabled even after optimal medical therapy. The aortocoronary bypass operation, introduced in the mid-1960s, has been shown to have consistent subjective and objective effects on the course of the disease in a large proportion of patients. The procedure consists of inserting a portion of the saphenous vein into both the aorta and a coronary artery to bypass the obstruction. It is usual now to bypass obstructions in several coronary arteries at the same operation if necessary. The prognosis for patients with ischemic heart disease with medical management depends on the extent of the disease. Patients with obstruction of only one coronary artery have a prognosis very little different from normal. On the other hand, obstruction of several arteries is consistently associated with a mortality approaching or exceeding 10% per year.