Non-Invasive Assessment of Atherosclerosis in Patients With CGD and Other Disorders of the Immune System

Atherosclerosis, Chronic Granulomatous Disease (CGD)

CAT SCAN, Heart Disease, Magnetic Resonance Imaging, Electrocardiogram, Superoxide

Background: * Atherosclerosis, the arterial plaques or blockages that cause heart disease, develops in many people by the time they are in their mid-20s. The rate of atherosclerosis in patients with immune system disorders has not been well studied, but it may be very different from the general population. * Patients with chronic granulomatous disease (CGD) produce less of a group of molecules known as free radicals, which help to fight infection and may play a role in the development of atherosclerosis. Patients with CGD may develop atherosclerosis much more slowly than people without CGD. On the other hand, carrier mothers of children with genetically-linked CGD often have problems with autoimmune problems in addition to a problem with making free radicals. Patients with other immune system disorders also have very different responses to infection, and many of them also have autoimmune-like problems that may change the risk of developing atherosclerosis. Objectives: \- To study the prevalence of atherosclerosis in patients with immune system disorders, compared with healthy individuals. Eligibility: \- Individuals at least 18 years of age who either have been diagnosed with an immune system disorder or are healthy volunteers. Design: * The active part of the study involves one or two visits to the National Institutes of Health Clinical Center for a series of imaging tests and scans. * Participants will have the following tests during the active part of the study: * (1) CAT scan to obtain images of the chest arteries and measure the amount of calcium in the artery walls. * (2) Magnetic resonance imaging scan to obtain images of the coronary and carotid arteries in the chest and neck. * (3) Electrocardiogram to provide data on current heart function. * (4) Blood samples to provide data on heart, kidney, and immune system function. * Participants will be contacted every 2 years in the future for up to 30 years to determine whether they have developed heart disease. Researchers will ask participants to provide contact information for two other people who may likely know how to get in touch with the participant in the future.

Heart disease kills more than half a million people in the U.S. each year. Atherosclerosis, the major cause of heart disease, is thought to relate to dysregulated inflammation in the cardiovascular system and possibly results from over production of reactive oxygen species (ROS). The rate of atherosclerosis in patients with disorders of the immune system has not been well characterized but is likely to be dramatically different than that seen in the general population. Specifically, patients with Chronic Granulomatous Disease (CGD) may be protected from developing atherosclerosis due to reduced superoxide and other ROS production by phagocytic cells. We hypothesize that patients with CGD are at decreased risk of developing atherosclerosis. The primary objective of this study is to determine the prevalence of atherosclerosis and it s inflammatory characteristics in these and other patients with in-born disorders of immune function. The primary objective will be assessed using carotid studies and other imaging techniques to measure coronary artery calcium scores and the presence or absence of soft plaque. Secondary endpoints include physiologic characteristics such as blood pressure as well as circulating biomarkers associated with heart disease such as C-reactive protein and lipid profile. This study may lead to improved understanding of the pathophysiology of atherosclerosis, specifically the role of free radical stress, and could lead to novel therapies for atherosclerosis that may benefit patients with immune disorders and the general population.

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United States