Personalizing Risk Assessments and Treatments for Complex Cardiovascular Disease

Abstract

The term “cardiovascular disease” encompasses a number of different conditions that affect different aspects of the circulatory system. Family history is often very useful in predicting one’s risk for cardiovascular disease, and this chapter includes a list of several Internet websites that will analyze family and personal data and estimate one’s level of risk. The development of predictive genetic tests has been difficult for several reasons, including the likelihood that there is more than one molecular subtype present in any group of patients with the same clinical diagnosis. Most of the risk-increasing alleles that have been discovered have low penetrance; it may require hundreds of individual genetic tests to provide the critical genetic data to predict one’s risk. The list of candidate genes is growing rapidly, however. The list includes genes whose proteins are integral to the cardiac musculature, as well as genes that influence aspects of metabolism that may predispose one to cardiovascular disease, including blood lipid and sugar levels, blood pressure, cardiac ion channel function, inflammation, oxidative stress and blood homocysteine levels. The chapter includes a discussion of these low-penetrance gene variants, as well as a discussion of two examples of cardiovascular diseases for which highly penetrant risk-increasing alleles have been reported: familial hypercholesterolemia and hypertrophic cardiomyopathy. The chapter also includes a discussion of the pharmacogenetic tests that can influence the choice of treatment for patients with cardiovascular disease, and a case report that illustrates both the benefits and limitations of genetic testing in a patient with type 2 diabetes and a family history of myocardial infarction.