Premature Coronary Artery Disease in Systemic Lupus Erythematosus with Extensive Reocclusion Following Coronary Artery Bypass Su
- Volume 15 - Issue 5 - May, 2003
- Posted on: 8/1/08
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Advances in medical therapy and a better understanding of systemic lupus erythematosus (SLE) have contributed to a dramatic improvement in the long-term survival of patients. However, despite the overall long-term improvement, coronary artery disease remains a major cause of morbidity and mortality1 (Table 1) with an incidence that is approximately nine-fold greater than would be expected for this population.2 Following active lupus, coronary artery disease is the second most common cause of hospitalization for SLE patients.3 Manzi et al. found that, when controlled for age and gender, women with SLE who are 35–44 years old have a 50-times higher risk of myocardial infarction (MI).4 Previous autopsy studies have observed that severe coronary artery disease is present in as many as 40% of patients with SLE compared with only 2% of age-matched controls at the time of death.5,6 Etiologies of myocardial damage in SLE patients include premature atherosclerotic disease,7 antiphospholipid antibody syndrome,8 coronary artery spasm,9 coronary artery vasculitis10 and restenosis after percutaneous revascularization procedures. The present case illustrates the importance and challenge of differentiating among these etiologies, especially since the therapies used are different in each situation. The following discussion will focus on the diagnosis and pathogenesis of coronary artery disease with an emphasis on premature atherosclerosis and coronary vasculitis in patients with SLE.
Case Report. A 21-year-old woman presented to the emergency room with a chief complaint of substernal chest pain. The pain was scaled a 9/10, was non-radiating and not associated with diaphoresis, dizziness, nausea or vomiting. The patient had a history of SLE, with a positive ANA and double-stranded DNA antibodies seven years ago. Clinical manifestations included a malar rash and joint swelling. Subsequently, the patient was only treated with hydroxychloroquine. As a child she had several hospitalizations for lupus flares for which she was treated with short courses of steroids. She had no history of pregnancy, deep venous thrombosis, pulmonary embolus or migraine headaches. She had undergone a four-vessel coronary artery bypass graft operation in June of 2000 with separate saphenous vein grafts to the left anterior descending (LAD), obtuse marginal (OM) 1 and 2, and distal right coronary arteries (RCA) 4 months prior to admission. At that time, a biopsy was taken of the internal mammary artery that reported a chronic mural inflammatory infiltrate composed of lymphocytes and occasional eosinophils (Figure 1). Her medications included enteric-coated aspirin 325 mg QD, metoprolol 25 mg BID, omeprazole 30 mg QD and hydroxychloroquine 200 mg QD. She reported allergies to sulfonamides, clarithromycin, metronidazole, nifedipine and ranitidine. The patient denied any family history of hypercholesterolemia or coronary artery disease. She reported a history of tobacco use of one pack per day for 2 years, but this was discontinued one month prior to admission. There was no history of drug or alcohol use.
Physical exam revealed a well-developed young female who was alert and in no acute distress. Vital signs showed arterial pressure of 117/66 mmHg, pulse rate of 85 bpm, respiratory rate of 16/minute, and temperature of 99 °F. The patient had no rash, oral ulcers, alopecia or adenopathy. Her chest had a sternotomy scar and her lungs were clear bilaterally. Auscultation of the heart revealed a regular rate and rhythm with normal heart sounds without murmur, gallop or rub. Her abdominal exam was benign. Extremity examination did not show clubbing, cyanosis or edema. Joint examination revealed mild erythema of the metacarpophalangeal joints bilaterally without associated swelling. Laboratory evaluation: white blood count, 7,700/mm3 with a mild lymphopenia; hematocrit, 36%; mean corpuscular volume, 76 µm3; and platelets, 188,000/mm3. Erythrocyte sedimentation rate (ESR) was 55 mm/hour and C-reactive protein (CRP) was 0.2 mg/dl. A chemistry panel was normal including a BUN/Cr of 17/0.9 mg/dl, respectively. Creatine phosphokinase (CPK) was 740 IU/L; MB was 112.6 IU/L; troponin I was 10.9 ng/ml (all positive for myocardial infarction). A lipid profile showed total cholesterol of 157 mg/dl, high-density lipoprotein of 58 mg/dl and low-density lipoprotein of 86 mg/dl. Lipoprotein (a) was 15 mg/dl (0–30 mg/dl) and homocysteine level was 10 µmol/L (5–15 µmol/L). Immunologic studies revealed the following: ANA titer of 1:320; anti-DS DNA titer < 10; anti-Sm negative; anti-ribonucleoproteins (RNP) negative; C3 = 55 mg/dl (normal range, 60–143 mg/dl); C4 = 5 mg/dL (normal range 14-42 mg/dL); anticardiolipin antibody levels of IgG = 17.7 mg/dl and IgM <= 15 mg/dl (both normal); and lupus anticoagulant was negative. Beta 2 glycoprotein levels were: IgG <= 5 mg/dl (normal); IgA = 30 mg/dl (high); and IgM = 9 mg/dl (normal). The urinalysis was normal. Electrocardiogram showed inverted T-waves in leads I, aVL, V4–V6 and Q-waves in leads III and aVF (Figure 2).
The patient was initially stabilized with aspirin, enoxaparin (1 mg/kg sq BID), metoprolol, intravenous nitroglycerin and eptifibatide infusion. Medications prior to admission were also continued. Coronary angiography showed severe diffuse disease with a long, 90% narrowing of the saphenous vein bypass graft to the LAD and occluded saphenous vein grafts to the obtuse marginal branches (OM1 and OM2). The RCA graft showed diffuse disease. On echocardiography, the ejection fraction was approximately 54%; the basal inferior septal, mid inferior septal and apical anterior walls were mildly hypokinetic with normal wall motion in all other segments. An intervention was performed in which the LAD was stented in two sequential lesion locations with final TIMI 3 flow. For the management of her vasculitis, the patient was treated with pulse dose cytoxan (1,200 mg) in addition to hydroxychloroquine (500 QD).11–13