A panel of six readily available biomarkers and clinical traits proved to be very good at predicting which women with systemic lupus erythematosus are at increased risk for cardiovascular events based on serial carotid artery ultrasound exams in a prospective case-control study.
Women with SLE who scored as "high risk" on the PREDICTS scale had a 28-fold increased odds of having or acquiring carotid plaque on serial ultrasound exams performed during a 2-year period than did SLE patients with lower scores. They also were at much higher risk of showing plaque progression (odds ratio, 15.5), reported Dr. Maureen McMahon of the rheumatology division at the University of California, Los Angeles (UCLA), Medical Center and her associates.
The PREDICTS (Predictors of Risk for Elevated Flares, Damage Progression, and Increased Cardiovascular Disease in Patients with SLE) score was more accurate at predicting the incidence or progression of carotid plaque than were any individual biomarkers or any panel of traditional cardiovascular risk factors in SLE patients, the investigators noted.
Longer follow-up is needed to definitively establish that carotid plaque deposition in these patients corresponds to later CVD events, and thus that the PREDICTS score predicts actual CVD events. Further study also will determine whether identifying these high-risk patients can guide preventive treatment and avert CVD events, the authors added.
Accelerated atherosclerosis is known to be more common in SLE patients than in the general population and to occur at a younger age. It causes significant morbidity and mortality and is thought to be related to the chronic inflammation underlying SLE.
Dr. McMahon and her colleagues assessed combinations of several biomarkers and risk factors, both traditional and novel, to develop a screen for identifying which SLE patients are at high CVD risk. They enrolled 210 women (mean age, 41 years) attending rheumatology practices at UCLA and Cedars Sinai medical centers who underwent a baseline ultrasound examination of the carotid artery and at least one follow-up ultrasound within a mean of 30 months, as well as 100 age-matched healthy control women who did not have SLE. Participants who had active renal disease or were taking statins were excluded from the study so as to avoid enrollment of women with known inflammation and hyperlipidemia.
The study subjects provided fasting blood samples that were tested for lipids, homocysteine, and high-sensitivity C-reactive protein. They also completed questionnaires that assessed SLE activity, organ damage, medications, and nonlaboratory CVD risk factors.
Univariate analysis showed that the presence, development, and progression of carotid plaque all were strongly associated with two traditional clinical factors – older age (48 years or older) and a history of diabetes – as well as four biomarkers of inflammation: high-density lipoprotein function (not HDL level), leptin level, homocysteine level, and soluble tumor necrosis factor–like weak inducer of apoptosis (sTWEAK) level.
HDL particles are anti-inflammatory in the basal state but become proinflammatory during an acute phase response. The chronic inflammation of SLE thus may inhibit HDL’s cardioprotective action and even promote cardiovascular damage, according to the investigators
Hyperleptinemia is associated with hypertension, oxidative stress, and endothelial dysfunction, and is known to be more common in SLE patients than in the general population. Homocysteine is a known indicator of inflammation and a predictor of cardiovascular disease. A high sTWEAK level has been linked to atherosclerosis, inflammation, angiogenesis, and apoptosis in laboratory studies, as well as to increased CVD mortality in other patient populations, Dr. McMahon and her associates said.
These six most significant independent predictors of incident or progressive carotid plaque were fashioned into the PREDICTS score, which proved to have the best overall predictive profile of any of the variables tested alone and in combination (Arthritis Rheum. 2013 Sept. 24 [doi: 10.1002/art.38204]).
For incident carotid plaque, the PREDICTS score had a sensitivity of 81%, a specificity of 79%, a positive predictive value of 40%, and a negative predictive value of 95%. SLE patients who earned a "high-risk" PREDICTS score had 28-fold higher odds of showing plaque at baseline or at follow-up ultrasound exam, compared with SLE patients whose scores didn’t indicate high risk.
In addition, SLE patients who had high-risk PREDICTS scores were significantly more likely than those who did not to show carotid plaque progression, a higher mean intima-media thickness, a higher rate of increase of intima-media thickness, and a higher mean number of new plaques per year.
In a multivariate analysis, the only variable significantly associated with carotid plaque progression over time was the PREDICTS score, with an odds ratio of 15.5.
Five participants, all of whom were SLE patients, had a documented incident cardiovascular event during follow-up, and all of them had a high PREDICTS score at baseline. In addition, 17 participants had a cerebrovascular event during follow-up, and 9 of them had high PREDICTS scores at baseline.