WASHINGTON — Atherosclerosis is more likely to progress in systemic lupus erythematosus patients when lupus is diagnosed at older ages, when it has existed for a long duration, and when high homocysteine levels are present, according to new research presented at the annual meeting of the American College of Rheumatology.
Other research at the meeting suggested that the risk that women with SLE will develop carotid artery plaque may be determined by the presence of proinflammatory high-density lipoprotein (piHDL) cholesterol.
“We really don't know the rate and determinants of progression of carotid plaque in lupus,” said Dr. Mary J. Roman of Cornell University, New York.
She and her colleagues used serial ultrasound scans of the distal carotid artery and clinical assessments to evaluate the progression of atherosclerosis in 159 patients in the Hospital for Special Surgery's SLE registry.
After an average follow-up of 34 months, 28% of the patients had either developed first-time atherosclerotic plaque in the carotid since their baseline assessment or showed an increase in existing plaque since baseline. That is equivalent to progression of atherosclerosis in about 10% of SLE patients per year, Dr. Roman said.
“We may use this observed rate of atherosclerosis progression in assessing the efficacy in future intervention trials,” she said.
Compared with patients who had progressive plaque build up, those without plaque progression were significantly younger at baseline (mean age 50 years vs. 36 years) and at diagnosis (mean 36 years vs. 21 years), and had lower serum homocysteine levels at baseline. Patients without progression of atherosclerosis also tended to have more aggressive treatment of disease than those who experienced progression.
For each 10-year increase in either age at diagnosis or disease duration, patients were about three times more likely to have plaque progression than no plaque or stable plaque. Progression of atherosclerosis occurred in 56% of patients in the highest tertile of baseline serum homocysteine levels (7.9 mcmol/L or greater).
“Other than older age, traditional risk factors were not associated with progression of atherosclerosis,” Dr. Roman noted.
In a separate presentation, Dr. Maureen McMahon of the department of rheumatology at the University of California at Los Angeles reported preliminary results from an ongoing study that suggest the development of carotid artery plaque in women with SLE is associated with the presence of piHDL.
After conducting B-mode ultrasound screening of the carotid artery and taking blood samples of women with SLE and healthy control women, Dr. McMahon and her colleagues found that 42 of 95 (44%) women with SLE had piHDL, compared with 3 of 52 (6%) age-matched control women. Significantly more SLE patients with carotid plaque had piHDL than did SLE patients without plaque (93% vs. 38%). But there was no significant difference in the presence of piHDL between control patients with and without plaque.
Oxidized low-density lipoprotein (LDL cholesterol) directly and indirectly promotes the production of inflammatory cytokines, the migration of monocytes into the subepithelial space of vessels, and the formation of macrophages that take up the oxidized LDL cholesterol and form foam cells that build an atherosclerotic plaque. Normal HDL cholesterol helps to reduce the effect of oxidized LDL cholesterol by promoting cholesterol efflux from cells and by inhibiting the oxidization of LDL cholesterol. During periods of acute inflammation, HDL cholesterol may become proinflammatory and unable to perform its usual protective function, Dr. McMahon explained.
SLE patients with piHDL were 25 times more likely than control patients to have plaque after controlling for the traditional cardiovascular risk factors of hypertension, elevated LDL cholesterol, age, body mass index, diabetes, and high-sensitivity C-reactive protein.
“Measurement of piHDL may be one tool to identify [SLE] patients at risk for the development of atherosclerosis,” Dr. McMahon concluded.
The SLE patients had a mean age of about 43 years and were not selected for a history of cardiovascular disease. None of the patients was allowed to take statins within 6 months of entry into the study.