HDL May Predict Lupus Atherosclerosis

BIRMINGHAM, ENGLAND — Patients with lupus who have high levels of proinflammatory high-density lipoprotein may be at particular risk for atherosclerosis and therefore could be suitable candidates for prophylactic treatment, Bevra Hahn, M.D., said at a joint meeting of the British Society for Rheumatology and the German Society for Rheumatology.

Recognition of the prevalence and lethality of atherosclerosis in systemic lupus erythematosus (SLE) has led to increased interest in strategies to prevent its onset and progression, such as with statin therapy.

“We know that 30%–40% of lupus patients have carotid plaque, coronary artery calcifications, or some other manifestation of atherosclerosis, but we found that only 15% of patients in our cohort had any lipid abnormalities, so it didn't seem very reasonable to just put them all on statins,” said Dr. Hahn, professor of medicine and chief of rheumatology, at the University of California, Los Angeles.

Caution also is needed because the statin drugs have been reported to induce lupus-like syndromes with the development of antinuclear antibodies in an increasing number of patients. Statins also might aggravate lupus itself, possibly through enhancing the shift from a Th1 to Th2 immune response, which heightens B cell reactivity and increases the production of pathogenic autoantibodies (Lupus 2005;14:192–6).

So Dr. Hahn and her colleagues began looking for a new biomarker that might provide a more targeted population for statin therapy. “We reasoned that people with a chronic inflammatory disease like lupus might have a lot of proinflammatory HDL. That turned out to be right,” Dr. Hahn said.

Proinflammatory HDL particles contain inadequate amounts of antioxidant enzymes such as paraoxonase. These components are replaced by serum amyloid and oxidation products, rendering the HDL particle incapable of its vital function of protecting LDL particles from becoming oxidized. Once oxidized, LDL contributes to the early development of carotid plaque.

In a study at her center that included 153 patients with lupus, 45% were found to have proinflammatory HDL, as did 21% of a group of 44 patients with rheumatoid arthritis.

Fewer than 5% of a healthy control group had the abnormal HDL, Dr. Hahn said.

On multivariate analysis, the presence of proinflammatory HDL was highly correlated with increases in oxidized LDL, and was also correlated with coronary artery events, hypertension, and high erythrocyte sedimentation rate (ESR).

“So it looks like we might have one biomarker that would tell us which people are predisposed to atherosclerosis and should be treated for it,” she said.

The next question is what that treatment should be. In patients who have had a myocardial infarction and have high levels of proinflammatory HDL, statins do lower the levels, but not even close to the normal range, Dr. Hahnsaid.

“My personal opinion is that statins may be helpful but, if we are right about what is important in lupus atherogenesis, they won't be enough. I think the most effective therapy will be one that actually suppresses SLE activity,” she said.

BIRMINGHAM, ENGLAND — Patients with lupus who have high levels of proinflammatory high-density lipoprotein may be at particular risk for atherosclerosis and therefore could be suitable candidates for prophylactic treatment, Bevra Hahn, M.D., said at a joint meeting of the British Society for Rheumatology and the German Society for Rheumatology.

Recognition of the prevalence and lethality of atherosclerosis in systemic lupus erythematosus (SLE) has led to increased interest in strategies to prevent its onset and progression, such as with statin therapy.

“We know that 30%–40% of lupus patients have carotid plaque, coronary artery calcifications, or some other manifestation of atherosclerosis, but we found that only 15% of patients in our cohort had any lipid abnormalities, so it didn't seem very reasonable to just put them all on statins,” said Dr. Hahn, professor of medicine and chief of rheumatology, at the University of California, Los Angeles.

Caution also is needed because the statin drugs have been reported to induce lupus-like syndromes with the development of antinuclear antibodies in an increasing number of patients. Statins also might aggravate lupus itself, possibly through enhancing the shift from a Th1 to Th2 immune response, which heightens B cell reactivity and increases the production of pathogenic autoantibodies (Lupus 2005;14:192–6).

So Dr. Hahn and her colleagues began looking for a new biomarker that might provide a more targeted population for statin therapy. “We reasoned that people with a chronic inflammatory disease like lupus might have a lot of proinflammatory HDL. That turned out to be right,” Dr. Hahn said.

Proinflammatory HDL particles contain inadequate amounts of antioxidant enzymes such as paraoxonase. These components are replaced by serum amyloid and oxidation products, rendering the HDL particle incapable of its vital function of protecting LDL particles from becoming oxidized. Once oxidized, LDL contributes to the early development of carotid plaque.

In a study at her center that included 153 patients with lupus, 45% were found to have proinflammatory HDL, as did 21% of a group of 44 patients with rheumatoid arthritis.

Fewer than 5% of a healthy control group had the abnormal HDL, Dr. Hahn said.

On multivariate analysis, the presence of proinflammatory HDL was highly correlated with increases in oxidized LDL, and was also correlated with coronary artery events, hypertension, and high erythrocyte sedimentation rate (ESR).

“So it looks like we might have one biomarker that would tell us which people are predisposed to atherosclerosis and should be treated for it,” she said.

The next question is what that treatment should be. In patients who have had a myocardial infarction and have high levels of proinflammatory HDL, statins do lower the levels, but not even close to the normal range, Dr. Hahnsaid.

“My personal opinion is that statins may be helpful but, if we are right about what is important in lupus atherogenesis, they won't be enough. I think the most effective therapy will be one that actually suppresses SLE activity,” she said.

BIRMINGHAM, ENGLAND — Patients with lupus who have high levels of proinflammatory high-density lipoprotein may be at particular risk for atherosclerosis and therefore could be suitable candidates for prophylactic treatment, Bevra Hahn, M.D., said at a joint meeting of the British Society for Rheumatology and the German Society for Rheumatology.

Recognition of the prevalence and lethality of atherosclerosis in systemic lupus erythematosus (SLE) has led to increased interest in strategies to prevent its onset and progression, such as with statin therapy.

“We know that 30%–40% of lupus patients have carotid plaque, coronary artery calcifications, or some other manifestation of atherosclerosis, but we found that only 15% of patients in our cohort had any lipid abnormalities, so it didn't seem very reasonable to just put them all on statins,” said Dr. Hahn, professor of medicine and chief of rheumatology, at the University of California, Los Angeles.

Caution also is needed because the statin drugs have been reported to induce lupus-like syndromes with the development of antinuclear antibodies in an increasing number of patients. Statins also might aggravate lupus itself, possibly through enhancing the shift from a Th1 to Th2 immune response, which heightens B cell reactivity and increases the production of pathogenic autoantibodies (Lupus 2005;14:192–6).

So Dr. Hahn and her colleagues began looking for a new biomarker that might provide a more targeted population for statin therapy. “We reasoned that people with a chronic inflammatory disease like lupus might have a lot of proinflammatory HDL. That turned out to be right,” Dr. Hahn said.

Proinflammatory HDL particles contain inadequate amounts of antioxidant enzymes such as paraoxonase. These components are replaced by serum amyloid and oxidation products, rendering the HDL particle incapable of its vital function of protecting LDL particles from becoming oxidized. Once oxidized, LDL contributes to the early development of carotid plaque.

In a study at her center that included 153 patients with lupus, 45% were found to have proinflammatory HDL, as did 21% of a group of 44 patients with rheumatoid arthritis.

Fewer than 5% of a healthy control group had the abnormal HDL, Dr. Hahn said.

On multivariate analysis, the presence of proinflammatory HDL was highly correlated with increases in oxidized LDL, and was also correlated with coronary artery events, hypertension, and high erythrocyte sedimentation rate (ESR).

“So it looks like we might have one biomarker that would tell us which people are predisposed to atherosclerosis and should be treated for it,” she said.

The next question is what that treatment should be. In patients who have had a myocardial infarction and have high levels of proinflammatory HDL, statins do lower the levels, but not even close to the normal range, Dr. Hahnsaid.

“My personal opinion is that statins may be helpful but, if we are right about what is important in lupus atherogenesis, they won't be enough. I think the most effective therapy will be one that actually suppresses SLE activity,” she said.