Single Nucleotide Polymorphism of B-Type Natriuretic Peptide and Carotid Ultrasound Imaging as Biomarkers to Determine the Severity of Atherosclerosis
Cardiovascular disease (CVD) has been the number one cause of death in the world for several decades and will continue to worsen as a global epidemic. The underlying cause of CVD is atherosclerosis: most myocardial infarctions are caused by atherosclerotic plaque build-up in the coronary arteries, also known as coronary artery disease (CAD). Even though the exact mechanism is unknown, hemodynamic disturbance is a potential precursor for atherosclerotic development. The natriuretic peptide system, especially B-type natriuretic peptide (BNP), plays an important role in hemodynamic regulation. Genetic variants, such as single nucleotide polymorphisms (SNPs), of the BNP gene affect its expression and correlate with increased circulating BNP levels. The goal of this thesis research is to determine if SNPs of the natriuretic peptide system contributes to atherosclerotic development, and if these genetic variants can help predict CVD. We recruited 513 patients from Kingston General Hospital, who were undergoing coronary angiography, the clinical standard for detecting CAD. Blood sample was collected from each patient for genetic analysis. BNP gene SNP, rs198389, was significantly associated with severe CAD in women but not in men. It suggests that the mechanism of atherosclerosis development may differ between the sexes. In the second portion of the thesis, we investigated the role of genetic mutation in atherosclerosis in the carotid arteries, major arteries in the neck. Ultrasound was used to reveal and quantify carotid plaques, which correlated with the severity of plaques in coronary arteries. BNP genetic variant, rs198389, was associated with the extend of atherosclerosis in the carotid artery. In the final part of the thesis, we evaluated major adverse cardiovascular events such as heart attack, stroke and cardiovascular death. The SNP rs198389 was found to be a significant predictor for early cardiovascular events, as well as recurrent events. In summary, this thesis demonstrates that the BNP genetic variant rs198389 may contribute to the development of atherosclerosis in different arterial beds across the body, and it has the potential to be an important tool to predict adverse cardiovascular events.