Cath Lab Digest

Introduction
Stroke is the third leading cause of death in the United States with an annual incidence of 700,000, resulting in 150,000 deaths.¹ Extracranial atherosclerotic disease of the carotid arteries and aortic arch vessels account for more than 50% of all strokes.² Since an estimated two million people over the age of fifty have asymptomatic carotid stenosis of at least 50%, identifying these patients, modifying their risk factors, and monitoring disease progression prior to a stroke remains a paramount concern for clinicians.³

The events involved in progression of a benign carotid plaque to the point of rupture, and ultimately symptomatic disease, are an area of intense research. While the exact process remains a matter of debate, in addition to an atherosclerotic component, compelling evidence suggests a significant role for inflammation in the development and progression of carotid artery stenosis.^4–6 A recent review article summarizes the role of inflammation in the development of atherosclerotic vascular disease.⁵ Secondary serum markers of inflammation, such as C-reactive protein (CRP) and serum amyloid A (SAA), are elevated in patients with significant carotid artery stenosis.⁶ Clinically, signs of inflammation, such as increased carotid intima-medial thickness (IMT) are visualized on duplex ultrasonography. Previous authors have shown an association between increased IMT with elevated levels of CRP, suggesting a strong correlation between inflammation and carotid artery stenosis.⁷ Considering these findings, the development of screening tools and medications that interact with the inflammatory component of atherosclerotic plaques is an area of intense research. We report the case of a 55-year-old male with documented bilateral carotid artery stenosis, who following a course of high dose steroids for a separate medical condition, had incidental and almost complete regression of his carotid disease.

Case Report
A 55-year-old male presented to the vascular clinic following a suspected transient ischemic attack (TIA). He had two prior strokes, each over 15 years ago. At that time, work-up demonstrated an absence of carotid artery disease (CAD). On presentation, the patient’s neurological exam was normal and the remaining part of his physical exam was unremarkable. Carotid duplex examination revealed a right carotid bulb with 50–59% stenosis and left carotid bulb with 60–69% stenosis and a correlating systolic velocity of 287 cm/sec and diastolic velocity of 120cm/sec (Figure 1). A brain CT and an MRI demonstrated no acute abnormalities. A subsequent arteriogram (Figure 2) confirmed the duplex results, and he was scheduled to undergo a left carotid endarterectomy.

Shortly thereafter, however, he developed a pruritic rash on his lower extremities with progression to his trunk and upper extremities. Dermatological and rheumatological evaluations were consistent with an allergic reaction to the contrast dye. Skin biopsies demonstrated a leukocytoclastic vasculitis, and laboratory examination was significant for an elevated CRP of 4.61 (0–0.8 mg/dl) and an Erythrocyte sedimentation rate (ESR) of 83 (0–20 mm/h). He was started on high-dose prednisone by his rheumatologist, thus delaying surgery. He was re-examined four months later at the end of a course of tapering dose steroids and found to have complete clinical recovery from his vasculitis. Repeat duplex revealed a decrease bilaterally in the degree of stenosis at the carotid bulbs, both now in the 16–49% range of stenosis and systolic and diastolic velocities of 80 cm/sec and 23 cm/sec, respectively (Figure 3). CRP and ESR at this time were decreased to 0.25 ng/dl and 39 mm/h, respectively. We elected to cancel surgery and follow him with serial examinations and duplex ultrasonography. Over the next two years, his disease remained stable with low-grade carotid stenosis.

Subsequently, he had two additional follow-up visits and duplex scans that revealed gradually progressive carotid stenosis on the left, though he remains clinically asymptomatic. At nine months, his left common carotid had a maximal velocity of 138 cm/s consistent with a 50–59% stenosis. CRP drawn at that time was 0.40 mg/dl. At twelve months, the left carotid bulb velocity increased to 203 cm/s consistent with 50–79% stenosis and a CRP of 18.8 mg/dl.

Discussion
Recent reports have indicated an inflammatory component in the development and progression of carotid artery stenosis.^8,9 While markers such as CRP, SAA, interleukin 6 and soluble CD40 ligand appear to be associated with asymptomatic carotid lesions, the degree to which these markers play a role in symptomatic disease remain unclear.¹⁰ As in the present case, different markers of inflammation, including high-sensitivity CRP and ESR, have been shown to be elevated in patients with narrowing of the carotid vessels.^7,11 Similarly, intima-medial thickness as seen on ultrasound correlates with not only the degree of stenosis, but also with elevated CRP levels.^5,7,8 In the present case, duplex ultrasonography demonstrated increased IMT with elevated CRP and ESR, only to have both the serum inflammatory markers and IMT both return to normal levels following the course of steroids. One study suggested that underlying inflammation, as demonstrated by elevations in CRP, may promote atherogenesis via its effect on other conventional risk factors, especially obesity.¹¹ However, there remains no consensus on the definitive role of inflammation, or the value of monitoring inflammatory markers such as CRP in the evaluation of CAD.