Not so long ago, when doctors saw a patient with the inflammatory skin condition psoriasis, their first line of attack was to address the signs they could see—red, itchy, scaly patches, mostly on the knees, elbows, trunk and scalp. But research over the last several years is forcing a rethinking of the very nature of this common disease. Rather than viewing it as a contained cosmetic condition, studies now show that psoriasis poses risks to the entire body, and links between it and heart disease continue to emerge.
Much of this groundbreaking research is being led by Nehal N. Mehta, M.D., a cardiologist and head of the Lab of Inflammation and Cardiometabolic Diseases at the National Heart, Lung, and Blood Institute (NHLBI). Just last year he and his team found that biologic therapies that both reduce inflammation throughout the body and minimize skin lesions could also reduce the buildup of a potentially deadly plaque in the heart arteries of people with psoriasis. The finding may have implications not just for the 7 million Americans who have psoriasis, but potentially for those with other chronic inflammatory disease such as lupus and rheumatoid arthritis—conditions all known to increase the risk of heart disease.
Since the study was published, Mehta and his team have tackled a myriad of other questions related to the development of atherosclerosis in people with psoriasis—for example, whether a powerful imaging tool called coronary computed tomography angiography (CCTA) can be used to study why high-risk coronary plaques, which are especially prone to rupturing and triggering heart attacks, form so early and fast in psoriasis. Further, they are using it to track how a coronary plaque might heal after being treated with biologic therapy for the skin. Now, two newly-published NHLBI-funded studies that Mehta led are offering some answers.
Serial CCTA scanning over one-year worked to identify high-risk plaques, Mehta said. This identification permitted his lab to study certain proteins that promote inflammation in parallel, and he found two proteins in particular that promote the early development of these high-risk dangerous plaques. These discoveries, he added, give critical new support to his earlier findings.
“This current work demonstrates that when systemic inflammation in moderate to severe psoriasis is present, there is more early coronary plaque development without symptoms. And when we treat psoriasis with biologic therapy, we see an improvement in the most dangerous features of coronary plaque,” Mehta said. The findings, he added, provide strong evidence of potentially treating both psoriasis and coronary heart disease with biologic therapy.
The current studies build on Mehta’s past research. He has shown that psoriasis is associated with the development of high-risk plaques, and that improvement in the severity of the disease is linked to a reduction in coronary non-calcified burden. In addition to his finding about the plaque-reducing benefits of biologic therapy, he also showed how using a novel imaging biomarker called the perivascular fat attenuation index (FAI) can measure the effect of that therapy in reducing inflammation. The index, Mehta said, could be particularly helpful in predicting the risk of future cardiac events for individual patients.
In the latest study, published in the Sept. 2020 issue of Circulation: Cardiovascular Imaging, Mehta and his team used CCTA on 209 middle-aged patients with psoriasis before they started therapy, then again one year later. Of these participants, 124 received a biologic therapy, while 85 (the control group) used topical creams and light therapy to treat psoriasis.
At the start of the study, Mehta and his colleagues characterized patients with psoriasis by skin disease severity, and examined body mass index, systemic inflammation, and coronary artery plaque necrotic-core made up of fat, dead cells, and cell debris. All participants enrolled in the study had a low risk of getting heart disease in the five years that followed.
After one year of treatment, participants who received biologic therapy had an 8% reduction in lipid-rich necrotic core in the coronary plaque, while those in the control group had a slight increase in the progression in coronary plaques, even after the researchers accounted for traditional cardiovascular risk factors and the severity of a participant’s psoriasis. This result, Mehta said, suggests that biologic therapy might provide benefit similar to low-dose statins—drugs commonly used to reduce cholesterol in the blood.
“Previous studies have suggested that the inflammation in psoriasis reduces the body’s ability to handle cholesterol, which can impact the formation of early coronary plaque,” Mehta said. “By treating the skin disease and reducing inflammation, we may be able to improve other factors involved in development of coronary plaque including improving cholesterol removal from the body.”
In the second study, published in September in the journal EBioMedicine, Mehta and his team gained insight into why this risky plaque develops so early and aggressively in the first place. By studying endothelial cells, the most inner layer of coronary blood vessels, Mehta found that the increasing concentrations of the same inflammatory proteins that biologic therapy inhibits, promotes storage of “bad” cholesterol. This results in crystals forming inside endothelial cells. And these crystals, he said, eventually drive an immune response within the coronary plaque, which inflames the lining of the blood vessel and allows cholesterol to enter the plaque.
This cholesterol crystal formation inside endothelial cells manifests within the coronary plaque as the lipid-rich necrotic. Recent findings of this lipid-rich necrotic core detected on CCTA suggest that the presence of this high-risk feature poses a four-fold elevation in future heart attack risk.
“Our findings in both the clinic and in cells suggest that the lipid-rich necrotic core inside the coronary plaque may be favorably modulated over one-year of anti-inflammatory treatment,” Mehta said. “There are potentially large implications of being able to modify this type of plaque on future cardiovascular events in psoriasis, but we need large outcome studies to follow patients with these CCTA findings over time.”
While the data from his studies are still observational, Mehta said that the results could pave the way for randomized controlled clinical trials. These trials, he added, can help researchers better understand how changes in coronary plaque might lead to fewer heart attacks and strokes in people with psoriasis.