Subclinical Carotid Atherosclerosis in a Patient with Systemic Lupus Erythematosus

Deborah Alpert; Adrienne Davis; Doruk Erkan; Mary J Roman; Jane E Salmon

Nat Clin Pract Rheumatol. 2007;3(8):473-478.

Discussion of Diagnosis

Following the patient's diagnosis of SLE and her initial treatment, her early disease course was uneventful; however, she later suffered recurrent SLE flares in the setting of poor medical compliance, and developed new carotid atherosclerotic plaque.

Over the last half century, the prognosis of patients with SLE has dramatically improved as a result of early diagnosis, aggressive immunomodulatory therapy and improved infection control.^[1] In this setting, atherosclerosis has increasingly contributed to the morbidity and mortality of these patients. Observational studies of patients with SLE have demonstrated a prevalence of 6-20% for symptomatic coronary artery disease (CAD), and 2-15% for stroke.^[2] These findings highlight the importance of identifying markers of subclinical atherosclerosis in patients with SLE, which could potentially allow for prevention of future ischemic events.

The prevalence of subclinical atherosclerosis in patients with SLE over a broad age range is estimated to be 30-40%.^[1] Carotid plaque is a manifestation of systemic atherosclerosis; although it is an indication of cerebrovascular disease, carotid plaque is actually a stronger predictor of myocardial infarction than stroke.^[3] Notably, the observational study that the patient was enrolled in found a significantly increased prevalence of carotid plaque in patients with SLE compared with controls (37.1% versus 15.2%, P <0.001), and also demonstrated that patients with plaque were more likely to have pre-existing CAD.^[4]

Noninvasive imaging techniques that assess definite or presumptive subclinical atherosclerosis in patients with SLE are described in Table 2 ;^[1,2] however, the use of such techniques to screen for subclinical atherosclerosis in individual patients is currently experimental, and not yet recommended for clinical practice. It is unclear which patients with SLE should be screened, or which tests are most useful for predicting the risk of cardiovascular events. At present, treating physicians should be vigilant for symptoms of CAD, and have a low threshold for initiating standard diagnostic evaluations. In patients with SLE without overt CAD symptoms, such as the case patient, appropriate detection and management of atherosclerotic risk factors are warranted.

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Written consent was obtained from this patient to participate in the Hospital for Special Surgery Autoimmune Disease Registry and Accelerated Atherosclerosis in SLE study. Both these protocols were approved by the Hospital for Special Surgery Institutional Review Board.

Cite this: Subclinical Carotid Atherosclerosis in a Patient with Systemic Lupus Erythematosus - Medscape - May 18, 2007.

Table 1. Patient's Serial Laboratory Evaluations and Disease Scores at the Initial Clinic Visit and Each Study Visit, Compared With Normal Values
Laboratory evaluation or disease score	Initial clinic visit (0 years)	First study visit (1.2 years)	Second study visit (5.6 years)	Final clinic visit (7.1 years)	Normal ranges
Hemoglobin (g/dl)	10.6	10.4	8.8	8.6	11.5-16.0
WBC count (× 10^[9] cells/l)	4.1	2.4	2.9	3.0	3.5-10.7
Platelet count (× 10⁹ cells/l)	329	299	283	296	160-400
Creatinine (μmol/l)	53.0	61.9	61.9	79.6	35.4-106.1
Glucose (mmol/l)	5.8	4.8	4.3	5.2	3.9-5.8
Urinalysis	Normal	Normal	2+ protein, 1+ blood, 0-3 WBCs, 5-8 RBCs	3+ protein, 1+ blood, 18 WBCs, 12 RBCs	No protein, no blood, 0-3 WBCs, 0-3 RBCs
Total cholesterol (mmol/l)	6.1	4.2	3.4	ND	<5.2
LDL cholesterol (mmol/l)	ND	2.3	1.6	ND	<3.4
HDL cholesterol (mmol/l)	ND	1.6	1.3	ND	>1.0
Triglycerides (mmol/l)	ND	0.6	1.1	ND	<2.3
Lipoprotein(a) (μmol/l)	ND	3.2	4.0	ND	0.0-0.7
Homocysteine (μmol/l)	ND	5.6	ND	ND	<15.0
ESR (mm/h)	39	8	124	106	<27
C-reactive protein (mg/dl)	ND	0.5	2.9	ND	<0.5
anti-dsDNA^a	Negative	3+	4+	4+	Negative
C3 complement (mg/dl)	86.9	108.0	43.6	51.4	79.0-152.0
C4 complement (mg/dl)	21.3	22.3	4.2	6.1	16.0-38.0
Total protein (g/dl)	7.7	8.3	9.4	7.9	6.0-8.0
Albumin (g/dl)	4.3	4.2	4.2	3.3	3.5-5.0
SLEDAI score^b	0	3	17	24	0
SDI score^c	0	0	2	2	0

^aAnti-dsDNA determined by immunofluorescence on Crithidia luciliae.

^bScores can range from 0 to 105, with higher scores indicating greater disease activity.

^cScores can range from 0 to 46, with higher scores indicating greater disease-related damage.

Abbreviations: dsDNA = double-stranded DNA; ESR = erythrocyte sedimentation rate; ND = not determined; RBC = red blood cell; SDI = systemic lupus erythematosus damage index; SLEDAI = systemic lupus erythematosus disease activity index; WBC = white blood cell.

Table 1. Patient's Serial Laboratory Evaluations and Disease Scores at the Initial Clinic Visit and Each Study Visit, Compared With Normal Values
Laboratory evaluation or disease score	Initial clinic visit (0 years)	First study visit (1.2 years)	Second study visit (5.6 years)	Final clinic visit (7.1 years)	Normal ranges
Hemoglobin (g/dl)	10.6	10.4	8.8	8.6	11.5-16.0
WBC count (× 10^[9] cells/l)	4.1	2.4	2.9	3.0	3.5-10.7
Platelet count (× 10⁹ cells/l)	329	299	283	296	160-400
Creatinine (μmol/l)	53.0	61.9	61.9	79.6	35.4-106.1
Glucose (mmol/l)	5.8	4.8	4.3	5.2	3.9-5.8
Urinalysis	Normal	Normal	2+ protein, 1+ blood, 0-3 WBCs, 5-8 RBCs	3+ protein, 1+ blood, 18 WBCs, 12 RBCs	No protein, no blood, 0-3 WBCs, 0-3 RBCs
Total cholesterol (mmol/l)	6.1	4.2	3.4	ND	<5.2
LDL cholesterol (mmol/l)	ND	2.3	1.6	ND	<3.4
HDL cholesterol (mmol/l)	ND	1.6	1.3	ND	>1.0
Triglycerides (mmol/l)	ND	0.6	1.1	ND	<2.3
Lipoprotein(a) (μmol/l)	ND	3.2	4.0	ND	0.0-0.7
Homocysteine (μmol/l)	ND	5.6	ND	ND	<15.0
ESR (mm/h)	39	8	124	106	<27
C-reactive protein (mg/dl)	ND	0.5	2.9	ND	<0.5
anti-dsDNA^a	Negative	3+	4+	4+	Negative
C3 complement (mg/dl)	86.9	108.0	43.6	51.4	79.0-152.0
C4 complement (mg/dl)	21.3	22.3	4.2	6.1	16.0-38.0
Total protein (g/dl)	7.7	8.3	9.4	7.9	6.0-8.0
Albumin (g/dl)	4.3	4.2	4.2	3.3	3.5-5.0
SLEDAI score^b	0	3	17	24	0
SDI score^c	0	0	2	2	0

Table 1. Patient's Serial Laboratory Evaluations and Disease Scores at the Initial Clinic Visit and Each Study Visit, Compared With Normal Values
Laboratory evaluation or disease score	Initial clinic visit (0 years)	First study visit (1.2 years)	Second study visit (5.6 years)	Final clinic visit (7.1 years)	Normal ranges
Hemoglobin (g/dl)	10.6	10.4	8.8	8.6	11.5-16.0
WBC count (× 10^[9] cells/l)	4.1	2.4	2.9	3.0	3.5-10.7
Platelet count (× 10⁹ cells/l)	329	299	283	296	160-400
Creatinine (μmol/l)	53.0	61.9	61.9	79.6	35.4-106.1
Glucose (mmol/l)	5.8	4.8	4.3	5.2	3.9-5.8
Urinalysis	Normal	Normal	2+ protein, 1+ blood, 0-3 WBCs, 5-8 RBCs	3+ protein, 1+ blood, 18 WBCs, 12 RBCs	No protein, no blood, 0-3 WBCs, 0-3 RBCs
Total cholesterol (mmol/l)	6.1	4.2	3.4	ND	<5.2
LDL cholesterol (mmol/l)	ND	2.3	1.6	ND	<3.4
HDL cholesterol (mmol/l)	ND	1.6	1.3	ND	>1.0
Triglycerides (mmol/l)	ND	0.6	1.1	ND	<2.3
Lipoprotein(a) (μmol/l)	ND	3.2	4.0	ND	0.0-0.7
Homocysteine (μmol/l)	ND	5.6	ND	ND	<15.0
ESR (mm/h)	39	8	124	106	<27
C-reactive protein (mg/dl)	ND	0.5	2.9	ND	<0.5
anti-dsDNA^a	Negative	3+	4+	4+	Negative
C3 complement (mg/dl)	86.9	108.0	43.6	51.4	79.0-152.0
C4 complement (mg/dl)	21.3	22.3	4.2	6.1	16.0-38.0
Total protein (g/dl)	7.7	8.3	9.4	7.9	6.0-8.0
Albumin (g/dl)	4.3	4.2	4.2	3.3	3.5-5.0
SLEDAI score^b	0	3	17	24	0
SDI score^c	0	0	2	2	0

Table 1. Patient's Serial Laboratory Evaluations and Disease Scores at the Initial Clinic Visit and Each Study Visit, Compared With Normal Values
Laboratory evaluation or disease score	Initial clinic visit (0 years)	First study visit (1.2 years)	Second study visit (5.6 years)	Final clinic visit (7.1 years)	Normal ranges
Hemoglobin (g/dl)	10.6	10.4	8.8	8.6	11.5-16.0
WBC count (× 10^[9] cells/l)	4.1	2.4	2.9	3.0	3.5-10.7
Platelet count (× 10⁹ cells/l)	329	299	283	296	160-400
Creatinine (μmol/l)	53.0	61.9	61.9	79.6	35.4-106.1
Glucose (mmol/l)	5.8	4.8	4.3	5.2	3.9-5.8
Urinalysis	Normal	Normal	2+ protein, 1+ blood, 0-3 WBCs, 5-8 RBCs	3+ protein, 1+ blood, 18 WBCs, 12 RBCs	No protein, no blood, 0-3 WBCs, 0-3 RBCs
Total cholesterol (mmol/l)	6.1	4.2	3.4	ND	<5.2
LDL cholesterol (mmol/l)	ND	2.3	1.6	ND	<3.4
HDL cholesterol (mmol/l)	ND	1.6	1.3	ND	>1.0
Triglycerides (mmol/l)	ND	0.6	1.1	ND	<2.3
Lipoprotein(a) (μmol/l)	ND	3.2	4.0	ND	0.0-0.7
Homocysteine (μmol/l)	ND	5.6	ND	ND	<15.0
ESR (mm/h)	39	8	124	106	<27
C-reactive protein (mg/dl)	ND	0.5	2.9	ND	<0.5
anti-dsDNA^a	Negative	3+	4+	4+	Negative
C3 complement (mg/dl)	86.9	108.0	43.6	51.4	79.0-152.0
C4 complement (mg/dl)	21.3	22.3	4.2	6.1	16.0-38.0
Total protein (g/dl)	7.7	8.3	9.4	7.9	6.0-8.0
Albumin (g/dl)	4.3	4.2	4.2	3.3	3.5-5.0
SLEDAI score^b	0	3	17	24	0
SDI score^c	0	0	2	2	0

Table 1. Patient's Serial Laboratory Evaluations and Disease Scores at the Initial Clinic Visit and Each Study Visit, Compared With Normal Values
Laboratory evaluation or disease score	Initial clinic visit (0 years)	First study visit (1.2 years)	Second study visit (5.6 years)	Final clinic visit (7.1 years)	Normal ranges
Hemoglobin (g/dl)	10.6	10.4	8.8	8.6	11.5-16.0
WBC count (× 10^[9] cells/l)	4.1	2.4	2.9	3.0	3.5-10.7
Platelet count (× 10⁹ cells/l)	329	299	283	296	160-400
Creatinine (μmol/l)	53.0	61.9	61.9	79.6	35.4-106.1
Glucose (mmol/l)	5.8	4.8	4.3	5.2	3.9-5.8
Urinalysis	Normal	Normal	2+ protein, 1+ blood, 0-3 WBCs, 5-8 RBCs	3+ protein, 1+ blood, 18 WBCs, 12 RBCs	No protein, no blood, 0-3 WBCs, 0-3 RBCs
Total cholesterol (mmol/l)	6.1	4.2	3.4	ND	<5.2
LDL cholesterol (mmol/l)	ND	2.3	1.6	ND	<3.4
HDL cholesterol (mmol/l)	ND	1.6	1.3	ND	>1.0
Triglycerides (mmol/l)	ND	0.6	1.1	ND	<2.3
Lipoprotein(a) (μmol/l)	ND	3.2	4.0	ND	0.0-0.7
Homocysteine (μmol/l)	ND	5.6	ND	ND	<15.0
ESR (mm/h)	39	8	124	106	<27
C-reactive protein (mg/dl)	ND	0.5	2.9	ND	<0.5
anti-dsDNA^a	Negative	3+	4+	4+	Negative
C3 complement (mg/dl)	86.9	108.0	43.6	51.4	79.0-152.0
C4 complement (mg/dl)	21.3	22.3	4.2	6.1	16.0-38.0
Total protein (g/dl)	7.7	8.3	9.4	7.9	6.0-8.0
Albumin (g/dl)	4.3	4.2	4.2	3.3	3.5-5.0
SLEDAI score^b	0	3	17	24	0
SDI score^c	0	0	2	2	0

Table 2. Noninvasive Techniques for Investigating the Presence of Subclinical Atherosclerosis in Patients With SLE ^[1,2]
Technique	Measurement description
Carotid ultrasonography	Carotid artery plaque Carotid artery intimal-medial thickness
Electron beam CT	Coronary artery calcification
Myocardial perfusion scintigraphy	Exercise or pharmacologic-induced myocardial perfusion defects
Brachial artery flow-mediated vasodilatation	Endothelial dysfunction Endothelium-dependent, nitric oxide-mediated, brachial artery vasodilation in response to post-ischemic reperfusion

Table 3. Risk Factors That Potentially Contribute to Accelerated Atherosclerosis in Patients With SLE ^[1,2,4,18]
Demographic risk factors	Traditional risk factors	SLE-related factors
Age Males ≥45 years Females ≥55 years Male sex Ethnicity (see references for details)	Hypertension Diabetes mellitus Dyslipidemia Elevated total and LDL cholesterol Decreased HDL cholesterol Elevated homocysteine Smoking Obesity Sedentary lifestyle Early menopause Family history of premature coronary artery disease	Age at diagnosis (increasing age at diagnosis is associated with increasing risk) Cumulative disease activity Disease damage Disease duration Less immunosuppressive therapy Corticosteroid use Renal disease Vasculitis Verrucous endocarditis Antiphospholipid antibodies Elevated C-reactive protein levels

Table 3. Risk Factors That Potentially Contribute to Accelerated Atherosclerosis in Patients With SLE ^[1,2,4,18]
Demographic risk factors	Traditional risk factors	SLE-related factors
Age Males ≥45 years Females ≥55 years Male sex Ethnicity (see references for details)	Hypertension Diabetes mellitus Dyslipidemia Elevated total and LDL cholesterol Decreased HDL cholesterol Elevated homocysteine Smoking Obesity Sedentary lifestyle Early menopause Family history of premature coronary artery disease	Age at diagnosis (increasing age at diagnosis is associated with increasing risk) Cumulative disease activity Disease damage Disease duration Less immunosuppressive therapy Corticosteroid use Renal disease Vasculitis Verrucous endocarditis Antiphospholipid antibodies Elevated C-reactive protein levels

Table 1. Patient's Serial Laboratory Evaluations and Disease Scores at the Initial Clinic Visit and Each Study Visit, Compared With Normal Values
Laboratory evaluation or disease score	Initial clinic visit (0 years)	First study visit (1.2 years)	Second study visit (5.6 years)	Final clinic visit (7.1 years)	Normal ranges
Hemoglobin (g/dl)	10.6	10.4	8.8	8.6	11.5-16.0
WBC count (× 10^[9] cells/l)	4.1	2.4	2.9	3.0	3.5-10.7
Platelet count (× 10⁹ cells/l)	329	299	283	296	160-400
Creatinine (μmol/l)	53.0	61.9	61.9	79.6	35.4-106.1
Glucose (mmol/l)	5.8	4.8	4.3	5.2	3.9-5.8
Urinalysis	Normal	Normal	2+ protein, 1+ blood, 0-3 WBCs, 5-8 RBCs	3+ protein, 1+ blood, 18 WBCs, 12 RBCs	No protein, no blood, 0-3 WBCs, 0-3 RBCs
Total cholesterol (mmol/l)	6.1	4.2	3.4	ND	<5.2
LDL cholesterol (mmol/l)	ND	2.3	1.6	ND	<3.4
HDL cholesterol (mmol/l)	ND	1.6	1.3	ND	>1.0
Triglycerides (mmol/l)	ND	0.6	1.1	ND	<2.3
Lipoprotein(a) (μmol/l)	ND	3.2	4.0	ND	0.0-0.7
Homocysteine (μmol/l)	ND	5.6	ND	ND	<15.0
ESR (mm/h)	39	8	124	106	<27
C-reactive protein (mg/dl)	ND	0.5	2.9	ND	<0.5
anti-dsDNA^a	Negative	3+	4+	4+	Negative
C3 complement (mg/dl)	86.9	108.0	43.6	51.4	79.0-152.0
C4 complement (mg/dl)	21.3	22.3	4.2	6.1	16.0-38.0
Total protein (g/dl)	7.7	8.3	9.4	7.9	6.0-8.0
Albumin (g/dl)	4.3	4.2	4.2	3.3	3.5-5.0
SLEDAI score^b	0	3	17	24	0
SDI score^c	0	0	2	2	0

Authors and Disclosures

Dr Deborah Alpert is a Senior Rheumatology Fellow at the Hospital for Special Surgery. She earned an MD and a PhD from New York University School of Medicine, and trained in internal medicine at New York Presbyterian Hospital. Dr Alpert's research interests include systemic lupus erythematosus, the antiphospholipid syndrome, and vasculitis.

Ms Adrienne Davis is a third-year Medical Student at Weill Cornell Medical College. She earned her Bachelor's degree at Barnard College and then coordinated a clinical research study at the Hospital for Special Surgery, evaluating preclinical atherosclerosis in patients with systemic lupus erythematosus. Ms Davis's interests include women's health, pediatrics and chronic disease.

Dr Doruk Erkan is an Associate PhysicianScientist at the Barbara Volcker Center for Women and Rheumatic Disease; Assistant Attending Rheumatologist and Clinical Researcher at the Hospital for Special Surgery; and Assistant Professor of Medicine at the Weill Medical College of Cornell University in New York. Dr Erkan has a long-term research interest in the field of autoimmune diseases, with particular focus on the antiphospholipid syndrome and systemic lupus erythematosus.

Dr Mary J Roman is Professor of Medicine in the Division of Cardiology at Weill College of Medicine of Cornell University. She earned her medical degree at Columbia University College of Physicians and Surgeons, trained in internal medicine at the Harlem Hospital, and cardiology at the New York Presbyterian Hospital. Dr Roman's research interests include the Marfan syndrome, familial aortic aneurysm, valvular heart disease, and cardiovascular involvement in rheumatologic diseases, particularly systemic lupus erythematosus.

Dr Jane E Salmon is Professor of Medicine and Obstetrics-Gynecology at Weill College of Medicine of Cornell University, Collette Kean Research Professor at Hospital for Special Surgery, and a Director of The Mary Kirkland Center for Lupus Research. She earned a medical degree from the College of Physicians and Surgeons of Columbia University, trained in internal medicine at the New York Presbyterian Hospital, and rheumatology at the Hospital for Special Surgery. Dr Salmon's research focuses on elucidating mechanisms of tissue injury in systemic lupus erythematosus and other autoimmune diseases. Her basic and clinical studies have expanded our understanding of pregnancy loss and organ damage in patients with systemic lupus erythematosus, and the determinants of disease in patients with cardiovascular disease.

Disclosure: JE Salmon is the recipient of an investigator-initiated grant from Genentech to study a biomarker of atherosclerosis in lupus. JE Salmon is also on the Advisory Boards of Amgen, Centocor, Roche and Wyeth. The other authors declared no competing interests.

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Subclinical Carotid Atherosclerosis in a Patient with Systemic Lupus Erythematosus

Discussion of Diagnosis

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