Kaplan Discusses Link Between Lupus and Early Cardiovascular Disease Risk
People with autoimmune conditions like lupus are at higher risk of developing cardiovascular disease (CVD) at a young age, but researchers are uncovering clues that could lead to better treatments.
Dr. Mariana Kaplan, deputy scientific director of the National Institute of Arthritis and Musculoskeletal Diseases (NIAMS), discussed the link between autoimmune disorders and CVD risk at the recent Astute Clinician Lecture. The lecture honors U.S. scientists who have observed unusual clinical occurrences and, by investigating them, have opened important new avenues of research.
When someone has an autoimmune disorder, the person’s immune system mistakenly attacks healthy tissues. These conditions often cause uncontrolled inflammation in different parts of the body. Clinicians have long observed that many people with autoimmune diseases are more likely to have heart attacks and strokes. This finding led to the realization that inflammation is important in CVD.
To understand how inflammation contributes to early CVD risk, Kapan and colleagues turned their attention to lupus. Previous studies revealed up to a 50-fold increased risk for heart attack in young women with lupus compared to age-matched healthy women.
“I became interested in studying lupus when I was in medical school, and I remember very vividly how a couple of patients developed heart attacks in their 20s and 30s,” recalled Kaplan.
Researchers also saw that young people with lupus often had the vascular health of much older patients. Vascular damage and atherosclerosis—the hardening of blood vessels due to plaque buildup—were also more prevalent in young people with lupus compared to healthy controls. Kaplan emphasized that the vascular damage appears to begin early during the course of the disease.
But how does inflammation drive vascular events and CVD risk in lupus? Kaplan and others have uncovered several suspected culprits.
For instance, Kaplan and her colleagues found an imbalance between vascular repair and vascular damage in lupus. People with lupus have elevated levels of a class of signaling proteins called type I interferons, and these proteins negatively affect cells and other factors involved in vascular repair.
Kaplan also suspects that a class of white blood cells called neutrophils contribute to CVD risk in autoimmune diseases. In lupus, neutrophils form structures called neutrophil extracellular traps (NETs), which can damage blood vessel cells. These NETs can also become trapped in blood vessels and may trigger other vascular complications.
Another culprit may be an abnormality with cholesterol. In the general population, low-density lipoprotein—also known as “bad” cholesterol—is linked to the development of atherosclerosis. But in lupus, an abnormality with high-density lipoprotein—“good” cholesterol—may be to blame.
“Good” cholesterol has potent anti-inflammatory properties and helps to remove “bad” cholesterol from blood vessels. But in lupus, it becomes oxidized, and its protective properties are greatly reduced. Kaplan believes the NETs generated by lupus patients produce factors that oxidize “good” cholesterol and contribute to CVD.
“We’re hoping that these discoveries on the role of the immune system and other pathways may help us come up with more targeted strategies. At the end, what we really want are personalized approaches to treat complex autoimmune conditions,” Kaplan concluded.