Lipid Level Increases Could Indicate Cardiovascular Risk in ANCA Vasculitis Subsets, Study Reports

Patients with ANCA-associated vasculitis (AAV) experience significant increases in serum lipid levels during remission induction, particularly those who are newly diagnosed or have anti-PR3 antibodies, according to new research.

The findings also indicated that disease phase and antibody type are associated with differential levels of inflammation and could help stratify the risk of cardiovascular disease for these patients, the researchers said.

The study, “Disease Activity, ANCA-Type, and Lipid Levels in ANCA-Associated Vasculitis,” appeared in the journal Arthritis & Rheumatology.

Periodic assessments of lipid (fat) levels is recommended in AAV patients, given their higher risk of cardiovascular disease than the general population. However, data remain scarce on the link between disease activity and lipid levels in these patients — data that could help determine who is at greater risk of cardiovascular disease.

The team evaluated serum lipid levels at baseline and at month six among participants of the RAVE Phase 2/3 trial (NCT00104299), who had granulomatosis with polyangiitis or microscopic polyangiitis.

The 142 patients, with a mean age of 52.3 years, had severe disease at baseline and received methylprednisolone over 1–3 days followed by prednisone, and discontinued at six months if they achieved stable remission. Seventy-two participants (51%) were newly diagnosed, and 95 had antibodies against the proteinase 3 (PR3) protein.

While 53% were treated with Rituxan (rituximab) followed by a placebo, the remaining patients received cyclophosphamide followed by azathioprine, which are both immunosuppressants.

Most participants had normal amounts of total cholesterol, low density lipoprotein (LDL) and high density lipoprotein (HDL). Those with a new AAV diagnosis had lower total cholesterol, HDL, and LDL levels than patients with relapsing disease.

Newly diagnosed patients had greater increases in lipid levels at month six than at the beginning of the study, including total cholesterol (12.4mg/dL increase), LDL (10.3 mg/dL), and apolipoprotein B (3.5 mg/dL) — implicated in lipid transport and metabolism — than in those with relapsing disease.

A similar increase was also more marked in patients with anti-PR3 antibodies compared with patients with anti-MPO antibodies.

Patients on Rituxan or cyclophosphamide followed by azathioprine did not differ in their lipid levels. Also, the data showed that altered lipid amounts correlated with changes in erythrocyte sedimentation rate (ESR) — a way to assess inflammation — but not with other inflammatory markers or glucocorticoid exposure.

The data further revealed that increases in total cholesterol, LDL, HDL, and apolipoprotein A1 — also involved in lipid transport and metabolism — were associated with increases in the BVAS-WG score of disease activity. Newly diagnosed patients experienced significantly greater decreases in ESR and C-reactive protein — also an inflammatory marker — than participants with relapsing disease.

“These differences suggest that lipid metabolism differs across AAV disease subsets,” the scientists wrote. “Disease activity and timing during the period of treatment should be considered when screening for lipid disorders in AAV patients and assessing (cardiovascular disease) risk.”