Increased Risk for Cardiovascular Events in Women With Systemic Lupus Erythematosus

This week, we spoke with Brian Skaggs, PhD, and Maureen McMahon, MD, to discuss the preliminary results of their study, “A Panel of Biomarkers Associates With Increased Risk for Cardiovascular Events in Women With Systemic Lupus Erythematosus.” The doctors, who are both investigators at the UCLA David Geffen School of Medicine, wanted to more fully understand the increase in cardiovascular and cerebrovascular events for patients, specifically women, with lupus. Cardiovascular disease is linked to comorbidity and mortality in this patient population. In the longitudinal study, investigators used a PREDICTS score method to ascertain any association between adverse events in this patient population. This panel of 4 inflammatory biomarkers and 2 cardiac risk factors (age and diabetes) were better able to predict outcomes when compared with individual biomarkers and risk factors. Investigators concluded that a higher PREDICTS score, as well as hypertension, increase the risk of new cardiovascular events (CVEs) for women with lupus. In addition, women with lupus had a significantly higher risk of major cardiovascular events, with 20% of the patients with lupus experiencing these adverse effects, compared with only 5.2% of the control participants. While there is more research to be done, we briefly discuss the reasons why this may be, if the investigators were surprised by the results, and how women with SLE can minimize their risk of CVEs.

Rheumatology Network: Hello, thank you for joining me today. I would like to begin by asking you to explain your initial interest in determining risk for cardiovascular events in women with lupus.

Maureen McMahon, MD: So, this is a study that we've actually started many years ago. It's been known for a while that women with lupus have an increased risk for cardiovascular disease. And certainly there's you know, a lot of treatments that we use for lupus patients such as corticosteroids that can cause complications and that are known risk factors for heart disease, such as diabetes, and hypertension. But even if you take into account all of the traditional risk factors for cardiovascular disease, we still know that women with lupus have anywhere from a 7-fold increased risk of heart attack to when you look at young women in the 35- to 44-year-old age group. We know that that risk can even be as high as 50 times higher than the general population. So, we really know that we need to be able to better identify which of our patients are at risk. But currently, there really aren't any specific lupus specific markers that we can use to help us identify that. And also to identify which patients should be targeted for earlier intervention. So that's how we became interested in this topic and trying to see if we could find any, any lupus specific panels or biomarkers that we could use to help us.

RN: Why do you think that women, specifically younger women, have an increased risk of cardiovascular events in relation to lupus?

MM: Well, that's really what we're trying to figure out. I think that we know that there must be something specific to lupus, but it's a little bit unclear if it's just general inflammation, or whether there are parts of the disease process. More specifically, that are really causing, you know, the increases that we see.

RN: Were you surprised by the results of the study?

Brian Skaggs, PhD: I don't really I don't know if we're necessarily that surprised. I mean, this this particular study that we're talking about, is a very longitudinal study where we're looking at patients over a 10 or more year period. And following these patients throughout that time, the initial panel of what we think are lupus specific biomarkers for cardiovascular disease was determined more in cross sectional studies. So to say that were surprised, I don't know if we would necessarily be surprised after, you know, 10 years that lupus patients, women with lupus have significant risk for cardiovascular or especially cerebrovascular events. It's not necessarily surprising. It's, of course, not good for the patients. But I think it's validating the need for lupus specific markers to be looked at, again to identify patients at risk before they have an event after.

RN: How do you think that these results can help you treat patients with lupus, specifically women?

MM: Well, at this point, I think that that we're still in the research phases. So you know, we, as Dr. Skaggs just mentioned, we develop these panels and based on cross sectional studies looking for patients who had thickening of their of their arteries. And over time, those markers we've shown in this most recent study not only identified the patients with thickening of the arteries, or plaques, but also with cardiovascular events. So we need to certainly take these results that we found and validate them in other populations of lupus patients to make sure that it's not just predicting events in in lupus patients at UCLA, but also events in the lupus population in general. But I hope that as we go forward, you know, these markers will not yet available to the general population of treating rheumatologists. I hope that in the short term, we'll be able to use these to identify patients who can enter into trials, so we can figure out the best strategies using the patients who are at highest risk of progression of disease. And then ultimately, we'll see if we can find a way to commercialize the panel so that physicians can check this for their patients and know if these patients are at risk and pay more attention to special risk factors.

RN: Do you have anything to add before we wrap up in regard to your study and women with lupus?

MM: I think that the thing that I would add is just that for now, while we're still trying to find the best path forward for identifying patients and treating patients. I think the best we can do now is for all of us to be aware that there have this increased risk of cardiovascular disease in patients and to pay attention to the things that we know that we can control, such as smoking, controlling high cholesterol, hypertension, if it's there, and modifying those risk factors that we know about.

RN: Thank you so much for taking the time to speak with me today. I really appreciate it.

Reference:

Skaggs BJ, Grossman J, Sahakian L, et al. A Panel of Biomarkers Associates With Increased Risk for Cardiovascular Events in Women With Systemic Lupus Erythematosus [published online ahead of print, 2021 Feb 19]. ACR Open Rheumatol. 2021;10.1002/acr2.11223. doi:10.1002/acr2.11223