Premature aortic atherosclerosis in systemic lupus erythematosus: a controlled transesophageal echocardiographic study

Abstract

Objective: Premature carotid and coronary atherosclerosis are common in systemic lupus erythematosus (SLE), but data on aortic atherosclerosis (AA) are limited. Thus, using multiplane transesophageal echocardiography (TEE), we sought to determine the prevalence and clinical correlates of AA in patients with SLE.

Methods: Forty-seven patients with SLE (44 women, age 38 +/- 12 years) and 21 healthy controls (19 women, age 34 +/- 12 years) underwent clinical and laboratory evaluations and TEE to assess AA defined as aortic intima media thickness (IMT) > 0.86 mm or plaques as > 50% focal IMT as compared with surrounding walls. TEE studies were interpreted by an experienced observer unaware of subjects' clinical data.

Results: The prevalence of abnormal aortic IMT, plaques, or both lesions was higher in patients as compared to controls (37%, 23%, and 43% vs 14%, 0%, and 14%, respectively, all p </= 0.02). In patients, age at diagnosis of SLE was the only positive independent predictor of AA [OR 1.12 per year from diagnosis of SLE, 95% confidence interval (CI) 1.04-1.19, p = 0.001] and cyclophosphamide therapy was the only negative independent predictor of AA (OR 0.186, 95% CI 0.153-0.95, p = 0.04, equivalent to 5.4 times less likely to develop AA).

Conclusion: AA is common in young patients with SLE and is predicted by a later age at diagnosis of SLE, but is negatively correlated with cyclophosphamide therapy. Thus, early diagnosis and more aggressive immunosuppressive therapy may be required to decrease the development and progression of atherosclerosis in patients with SLE.

Figure 1. Aortic Intima-Media Thickening and Plaques by TEE

A, B. Short axis (A) and long axis (B) two-dimensional guided M-mode images of the anterior wall at the mid level (30 cm) of the descending thoracic aorta (Ao) demonstrating normal intima media thickness (IMT) of <8mm (arrows) in a 50 year old woman with SLE. C,D. Two-dimensional guided M-mode images in a 48 year old woman with SLE demonstrating a well defined aortic plaque of 3.3 mm at the proximal (C, arrow) and abnormal IMT of 1.2 mm at the distal (D, arrow) descending thoracic aorta.

Figure 2. Aortic Atherosclerosis Versus Age by Group

By multivariate analyses, age and SLE disease were the only independent predictors of AA [odds ratio (OR) 1.08 per year of age increment, 95% confidence interval (CI) 1.025 - 1.4, p = 0.004 for age effect; and OR 6.7, CI 1.28 - 35, and p = 0.02, for group (SLE) effect]. Note that the probability of AA in patients with SLE was 40% at age 40 and 80% at age 60 as compared to 10% and 40%, respectively, in controls.

Figure 3. Aortic Atherosclerosis Versus Age at Diagnosis of SLE by Cyclophosphamide Therapy

In patients with SLE and by multivariate analyses, age at diagnosis of SLE was the only independent positive predictor and cyclophosphamide (CTX) therapy was the only independent negative predictor of AA (OR = 1.118 per year from diagnosis of SLE, 95% CI 1.037 - 1.2, p = 0.004 and OR 0.186, CI 0.039 - 0.875, p = 0.03, equivalent to 5.4 times less likely to develop AA). Note that the probabilities of AA in patients with no cyclophosphamide therapy were nearly 40% at age 20, 80% at age 40, and almost 100% at age 60 as compared to nearly 10% at age 20, 40% at age 40, and 70% at nearly age 60 in patients on cyclophosphamide therapy.

Figure 4. Aortic Atherosclerosis Defined as Intima Media Thickening (>1 mm) or Plaques Versus Age by Group

By multivariate analyses, age and SLE disease were the only independent predictors of AA [odds ratio (OR) 1.08 per year of age increment, 95% confidence interval (CI) 1.025 - 1.4, p = 0.005 for age effect; and OR 6.7, CI 1.28 - 35, and p = 0.03, for group (SLE) effect]. Note that the probability of AA in patients with SLE was 40% at age 40 and 75% at age 60 as compared to 5% and nearly 35%, respectively, in controls.