SLE, Cardiovascular Disease Have Complex Interplay

Cardiovascular disease (CVD) is a major complication for people with systemic lupus erythematosus (SLE), but a considerable amount of research is pointing toward biomarkers for risk stratification and potential therapies to mitigate those factors.

Those are the key conclusions of a new article published in Journal of Autoimmunity.

SLE can affect various organs, including those of the cardiovascular system. Patients with SLE-related cardiovascular disease (CVD) face significantly heightened risks of morbidity and mortality, the authors said. They noted that about 1 in 5 deaths of people with SLE in the United Kingdom was found to be tied to CVD.

Exactly why and how SLE leads to CVD has been the subject of significant investigation, leading to answers to some—but not all—of the relevant questions.

“While the mechanisms underlying premature atherosclerosis and cardiovascular complications in SLE are partly clear, an interplay between profound activation of both innate and adaptive immune systems and traditional CVD risk factors has been suggested,” the study investigators said.

In the new review article, they aimed to summarize what is known so far about the mechanisms behind SLE-associated CVD, with one potential pathway of CVD being lipid abnormalities and dysfunction sparked by the systemic inflammation associated with SLE.

SLE can also create an environment conducive to vascular injury, an early sign of potential atherosclerosis, they said.

“Levels of circulating apoptotic endothelial cells are elevated in SLE and strongly linked to the vascular dysfunction and raised tissue factor levels, indicating a significant imbalance between vascular repair and endothelial cell damage in the setting of SLE,” the authors wrote.

In addition, they said several features of SLE may be responsible for accelerating CVD. Those features include excessive type 1 interferon burden, platelet and complements activation, and neutrophil dysregulation.

Several existing therapies have been investigated to see whether they might affect CVD risk in patients with SLE. Statin use, for instance, is thought by some to be protective against CVD in patients with SLE and hyperlipidemia, but the study authors said their use as an agent of CVD prevention remains controversial. Antimalarials and mycophenolate mofetil are among the other therapies studied with regard to CVD risk, they said.

They also said it may be possible to create targeted therapies to address the immune dysregulation of SLE, and therefore prevent or limit CVD. However, considerably more work needs to be done before that will be possible, the authors added.

In the meantime, they identified several biomarkers that may be helpful in identifying patients with SLE who are at the highest risk of CVD. Those include parathormone, an endogenous biomarker for 25(OH) vitamin D3 deficiency; neutrophil extracellular trap and low-density granulocyte levels; and soluble CD163 levels.

The authors said future prospective studies will be needed to find out which biomarkers might be most important in assessing SLE-associated CVD.

“While the current understanding of these complex interplays has progressed substantially, continued efforts to identify novel mechanisms and establish criteria for assessing CVD risk and CVD progression are important to improve CVD outcomes in SLE patients,” the authors concluded.

Reference

Liu Y, Yu X, Zhang W, Zhang X, Wang M, Ji F. Mechanistic insight into premature atherosclerosis and cardiovascular complications in systemic lupus erythematosus. J Autoimmun. Published online July 16, 2022. doi:10.1016/j.jaut.2022.102863