Early-onset Coronary Artery Disease Clinical and Hereditary Aspects

A family history of coronary artery disease (CAD) is an important risk factor for adverse coronary events, in particular if the disease has an early onset. The risk of CAD is influenced by genetic and environmental factors with a greater genetic contribution earlier in life. Through recent years the advances in genetic techniques has led to an increased understanding of the genetic background of CAD, which may potentially be translated into clinical use. The studies of this thesis aimed to investigate the burden of conventional risk factors and control in early-onset CAD (i.e. < 40 years), and to characterize and quantify subclinical atherosclerosis in their relatives. Furthermore, the aim was to explore the impact of common genetic risk variants on the age of onset, familial clustering and disease severity. In study I, 143 patients with early-onset CAD were recruited from the Western Denmark Heart Registry and risk factor control was evaluated. The study revealed that risk factors are common in early-onset CAD and that a large room for risk factor improvement remains. In study II, we used coronary computed tomography angiography to compare the coronary plaque burden and characteristics between 88 first-degree relatives of patients with early-onset CAD and 88 controls with no familial predisposition. Relatives had a significantly increased coronary plaque burden, which displayed characteristics associated with myocardial ischemia and adverse coronary events. In study III, 134 patients with early-onset CAD, a cohort of 446 late-onset CAD patients (onset > 55/65 years in males/females), and 89 healthy controls were genotyped for 45 common genetic risk variants and a genetic risk score was calculated as a measure of the polygenetic burden. Early-onset CAD patients had a modestly increased genetic burden compared with late-onset CAD patients and healthy controls; however, the burden did not associate with familial clustering of CAD. Additionally, familial clustering seemed to be stronger associated with CAD disease severity than the polygenetic burden. Our findings emphasize the hereditary component of coronary atherosclerosis and underpin the need for risk factor optimization in early-onset CAD. Furthermore, our data support that yet identified common risk variants may have little clinical relevance in the clinical setting of early-onset CAD.