Risk Factors Identified for Atherosclerosis and Cardiovascular Events in Women With SLE

Modifiable risk factors, such as glucose and waist circumference monitoring, as well as non-use of hydroxychloroquine, may prevent women with systemic lupus erythematosus (SLE) from developing adverse cardiovascular events and atherosclerosis, according to a study published in Lupus Science & Medicine.¹

“Cardiovascular disease (CVD) is a well-established cause of morbidity and mortality in patients with SLE and is known to occur at an earlier age than the general population. Investigations into subclinical atherosclerosis in patients with SLE have been undertaken with the hope of identifying modifiable risk factors for CVD,” investigators stated. “When compared with the general population, progression of atherosclerosis has been found to be accelerated in SLE. However, studies investigating risk factors for this accelerated progression are few and have yielded varied results.”

Subclinical atherosclerosis is measured by carotid intima media thickness (IMT) and carotid plaque.

Women with SLE and their control counterparts participated in the Study of Lupus Vascular and Bone Long-term Endpoints (SOLVABLE) study. Subjects were followed for up to 5 years between 2004 and 2013, with visits scheduled at baseline, 36 months, and 60 months.

Eligible patients were aged 18 years or older, met at least 4 of the American College of Rheumatology (ACR) classification criteria for SLE, and were enrolled in the Chicago Lupus Database (CLD). Controls, taken from the general population, were matched for age, ethnicity, and zip code.

Lupus disease activity was measured by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and damage was assessed by the American College of Rheumatology Systemic Lupus International Collaborating Clinics Damage Index (ACR/SLICC-DI).

Demographics, such as age, race/ethnicity, medication, smoking status, blood pressure, and waist circumference were collected along with bloodwork, including fasting glucose, fasting lipids, lipoprotein(a), C-reactive protein, homocysteine, and fibrinogen. Occurrences of hypertension, high cholesterol, and diabetes were accounted for.

Carotid ultrasounds were performed at baseline and at the 60-month follow-up to detect carotid IMT and plaque. Ultrasound technicians were blinded to the patient’s SLE status. Linear and logistic regression models were adjusted for factors such as age, hypertension, and cholesterol to high-density lipoprotein (HDL) ratio.

A total of 149 patients with SLE and 126 matched controls were included in the study. Follow-up time was 5.35 years in patients with SLE and 5.62 years in the control group. The mean age was 43.2 years in cases of SLE and 46.6 years in controls. In the SLE group, the average disease duration was 12 years.

Cases were significantly more likely to have hypertension when compared with controls (52.3% vs 23.8%, p<0.001). Fasting glucose levels were higher in the control group when compared with their SLE counterparts (96.8±18.5 mg/dL and 91.0±18.5 mg/dL, respectfully). Approximately 38% of cases were receiving corticosteroids at baseline, with 75% taking HCQ and 35.6% taking immunosuppressants. Seven patients with SLE had at least 1 CVD during the 5-year follow-up period, compared with only 1 control. After adjusting for age, hypertension, and other factors, for those with SLE, a higher fasting glucose combined with lower fibrinogen were associated with IMT progression and a higher likelihood of developing adverse cardiovascular events. A larger waist circumference and non-use of hydroxychloroquine was a factor in plaque progression.

Mean IMT at baseline was 0.61 for patients with SLE and 0.63 for the control group. During the follow-up period, the mean IMT change per year was 0.008mm in patients with SLE and 0.005mm in controls. A total of 72.5% (n = 108) of cases showed an increase in IMT, compared with 66.7% (n = 126) of controls. A regression in IMT was seen in 27.5% (n = 41) of patients with SLE and 33.3% (n = 42) controls.

For patients with plaque at baseline, 7.9% (n = 10) controls had more plaque progression, compared with 16.1% (n = 24) of patients with SLE. However, 20.6% (n = 26) controls and 10.7% (n = 16) cases had less plaque at follow-up. A total of 31.5% of patients with SLE and 15% of patients in the control group had plaque progression. Participants with plaque at baseline were more likely to have developed more plaque at follow-up when compared with those who did not have plaque (16.1% vs 15.4% in patients with SLE, 7.9% vs 7.1% in controls).

The small number of participants, including 19% of those who did not complete the 5-year follow-up, limited the study. Additionally, follow-up time may not have been long enough to determine changes in IMT or plaque. The association between diabetes and smoking could not be determined as too few participants fit these criteria. Investigators would like to explore newly diagnosed patients to create a more similar group of patients and be able to identify risk factors as time progresses.

“While better screening for these risk factors and earlier implementation of lifestyle modifications are essential, future research is needed to examine the longitudinal efficacy and safety of interventions including HCQ use in alleviating metabolic syndrome and the progression of atherosclerosis in patients with SLE,” investigators concluded. “The implementation of an inception cohort may be a reasonable study approach to begin to answer these questions.”

Reference:

Lertratanakul A, Sun J, Wu PW, et al. Risk factors for changes in carotid intima media thickness and plaque over 5 years in women with systemic lupus erythematosus. Lupus Sci Med. 2021;8(1):e000548. doi:10.1136/lupus-2021-000548