More Work Needed to Make Progress Against CVD Risk in SLE

People with systemic lupus erythematosus (SLE) face a higher risk of cardiovascular disease (CVD) based on a mix of traditional and nontraditional risk factors, but careful management and assessment of risk factors can help physicians better treat patients with SLE and potentially lower the risk of CVD, according to a new review in Journal of Internal Medicine.

SLE is a difficult disease to treat because it can present in many ways and involve many organs, and the study author said the development of immunosuppressant therapies helped to improve outcomes for patients while sparking a need for a greater emphasis on addressing comorbidities.

“After that, it became clear that CVD was important as a later complication of SLE,” said the study author, Johan Forstegård, PhD, Karolinka Institutet. One critical question then became figuring out exactly which risk factors are predictive of CVD complications, he said. The existing research lays out a mix of factors.

Dyslipidemia is one important risk factor, Frostegård said. However, dyslipidemia in SLE looks different than in the general population, with low high-density lipoprotein (HDL) and raised triglycerides, but not raised low-density lipoprotein (LDL). Some patients also have pro-inflammatory HDL. In addition, Frostegård said studies of other traditional CVD risk factors have led to mixed results.

“Other traditional risk factors such as smoking, blood pressure, and diabetes were not associated with CVD,” he said. “Both cortisone treatment and osteoporosis were associated with CVD.”

Frostegård said people with SLE have increased rates of atherosclerosis; in particular, atherosclerotic plaques. He noted there are important characteristics of SLE that align with atherosclerosis.

“Atherosclerosis is an inflammatory condition, where immunity plays an important role,” he wrote. “Interestingly, oxidized LDL, defective clearance of dead cells, and inflammation, with a pro-inflammatory T-cell profile are characteristics of both atherosclerosis and SLE.”

However, he said there are several other mechanisms that can increase CVD risk, including antiphospholipid antibodies (aPL), which can cause antiphospholipid antibody syndrome (APS). APS is characterized by venous and arterial thrombosis, as well as pregnancy complications.

“aPL can cause direct pro-inflammatory and prothrombotic effects on endothelial and other cells and also interfere with the coagulation, for example, by inhibiting annexin A5 from its antithrombotic and protective effects,” he wrote.

Still, Frostegård said improvements in treatment have improved outcomes for patients with aPL, APS, and SLE. He added that antiphosphorylcholine antibodies and other natural antibodies are negatively associated with the risk of CVD and atherosclerosis in SLE.

He said given the latest research, the high rates of CVD-related morbidity and mortality in SLE, and the advancements in treatment, physicians should focus first on managing and treating traditional risk factors for CVD. Statins have been the subject of significant research in patients with SLE, but Frostegård said the current evidence is conflicting and warrants more investigation. He said hydroxychloroquine, the widely used SLE therapy, has been shown to reduce the risk of thromboembolic events significantly. However, hydroxychloroquine also has potential to affect statins effectiveness.

While many questions require more study, he said physicians have tools to help manage CVD risk.

“Close monitoring of both traditional risk factors and nontraditional ones, including treatment of disease manifestations, not least renal disease in SLE, is warranted,” he concluded.

Reference

Frostegård J. Systemic lupus erythematosus and cardiovascular disease. J Intern Med. Published online August 18, 2022. doi:10.1111/joim.13557