Clin Rheumatol (2007) 26:1701–1704 DOI 10.1007/s10067-007-0575-4
ORIGINAL ARTICLE
B-type natriuretic peptide (BNP) levels in female systemic lupus erythematosus patients: what is the clinical significance? Omer Karadag & Meral Calguneri & Bunyamin Yavuz & Enver Atalar & Ali Akdogan & Umut Kalyoncu & Sedat Kiraz & Serdar Aksoyek & Ferhan Ozmen & A. Ihsan Ertenli
Received: 21 December 2006 / Accepted: 26 January 2007 / Published online: 21 February 2007 # Clinical Rheumatology 2007
Abstract Cardiovascular disease is a major cause of death in patients with systemic lupus erythematosus (SLE) especially during the late phase of the disease. This study was conducted to evaluate B-type natriuretic peptide (BNP) levels in female SLE patients without cardiac symptoms and to investigate whether BNP levels correlated with echocardiographic findings. We studied 59 women with SLE and 33 healthy women. SLE patients with history of cardiac disease, diabetes mellitus, hypertension, and other inflammatory diseases were excluded from the study. All subjects had a complete history and physical examination. Overall disease activity assessment in SLE patients at the time of the study were derived by calculation of SLE disease activity index (SLEDAI). BNP levels were determined, and transthoracic echocardiography were performed in all subjects. There was no difference between SLE patients and controls in terms of age, blood pressure, smoking status, plasma glucose, creatinine levels, and lipid profiles. Nine patients had SLEDAI score greater than 5.
O. Karadag : M. Calguneri : A. Akdogan : U. Kalyoncu : S. Kiraz : A. I. Ertenli Faculty of Medicine, Department of Internal Medicine Division of Rheumatology, Hacettepe University, Ankara, Turkey B. Yavuz : E. Atalar : S. Aksoyek : F. Ozmen Faculty of Medicine, Department of Cardiology, Hacettepe University, Ankara, Turkey O. Karadag (*) Hacettepe Universitesi Tip Fakültesi Romatoloji Unitesi, 06100 Sihhiye-Ankara, Turkey e-mail:
[email protected]
All subjects had an EF greater than 55%. Diastolic dysfunction was more frequent in lupus patients than in controls (15 [25.4%] vs. 2 [6%]; p=0.022). BNP levels of SLE patients were significantly higher than controls (median 17.9 range [5–211] pg/ml vs. median 14.7 range [5–39.7] pg/ml; p=0.033). Twenty-seven of the SLE patients (46%) and seven of the controls (21%) had BNP levels greater than or equal to 20 pg/ml (p=0.019). There were no differences in BNP levels of SLE patients with and without diastolic dysfunction (median 17.8 range [5–117] pg/ml vs. median 18.5 range [5–211] pg/mL; p=NS). BNP levels were positively correlated with left atrium diameter (r2 =0.39, p=0.001). BNP levels did not correlate with erythrocyte sedimentation rate/C-reactive protein levels, SLEDAI scores, total steroid dosage used, or other echocardigraphic parameters. BNP levels were increased in female SLE patients without cardiac symptoms as compared to healthy controls. Although none of the SLE patients in our study had clinical signs of ischemic heart disease, increased levels of BNP in SLE patients might be a reflection of a ischemic myocardial tissue. Keywords B-type natriuretic peptide (BNP) . Cardiovascular diseases . Diastolic dysfunction . Novel cardiovascular risk factors . Systemic lupus erythematosus (SLE) Patients with systemic lupus erythematosus (SLE) have a five- to tenfold risk for atherosclerotic cardiovascular disease (CVD) compared to the general population [1]. CVD is a major cause of death in patients with SLE especially during the late phase of the disease. Independent of traditional cardiovascular risk factors, lupus itself may
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contribute to the development of atherosclerosis [2]. Therefore, it is prudent that early identification and treatment of lupus patients with CVD is of clinical importance to decrease morbidity and mortality in lupus [3]. B-type natriuretic peptide (BNP) and N-terminal prohormone BNP are reliable biomarkers, reflecting myocardial stress caused by various CVDs [4]. Wang et al. [5] found that, after adjusting for traditional risk factors, the level of BNP was independently predictive of the risk of death, heart failure (HF), atrial fibrillation, and stroke over a mean follow-up period of about 5 years. In a recent study, BNP was found as a potentially useful screening tool for the detection of CVD in patients with rheumatoid arthritis (RA) [6]. This study was conducted (1) to evaluate BNP levels in female SLE patients without cardiac symptoms and (2) to investigate whether BNP levels correlated with echocardiographic findings.
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disease activity index (SLEDAI) [8]. Active lupus was defined as SLEDAI less than 5 as previously described [9, 10]. Current treatment and total dose of prednisone therapy in SLE patients were also noted. Laboratory assesment Blood samples were drawn after an overnight fast. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured by routine methods. Serum glucose, creatinine, and lipid (total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], triglycerides) levels were determined by using an autoanalyzer (Hitachi P800™). BNP was determined by a commercial fluorescent immunoassay method (IBL-Hamburg) [11]. Transthoracic echocardiography
Materials and methods SLE patients and controls We studied 59 women with SLE and 33 healthy women as control group. SLE patients were selected from consecutive patients at the Rheumatology Outpatient Clinic of the Hacettepe University Hospital. Healthy control subjects were recruited from hospital staff. All patients fulfilled greater than or equal to 4 of the 1982 American College of Rheumatology classification criteria for SLE [7]. Patients with renal impairment or significant proteinuria (>1+ on dipstick analysis or >500 mg/day), HF, coronary artery disease, atrial fibrillation, diabetes mellitus (DM), hypertension (HT), and other inflammatory diseases were excluded from the study. Electrocardiography (ECG) and transthoracic echocardiography were performed in all subjects. Subjects who had ECG abnormalities or moderate/severe valvular disease or ejection fraction (EF) less than 55% or any myocardial wall motion abnormalities were also excluded from the study. All subjects gave written informed consent, and the institutional ethical committee approved the study protocol. Clinical assessments All subjects had a complete history and physical examination including resting blood pressure and body mass index [weight (kg)/height(m2)]. Smoking status was defined as smoker or nonsmoker. Family history of atherosclerotic CVD was considered with the presence a first-degree relative with the disease diagnosed before 55 years of age. Overall disease activity assessment in SLE patients at the time of the study were derived by calculation of SLE
All echocardiographic examinations were performed by the same operator using a commercially available equipment (Vivid Five, GE Vingmed, Norway) and 2.5–3.5 MHz transducers. Systolic and diastolic left ventricule (LV) dimensions, EF, and fractional shortening were measured in the parasternal view. Flow velocity indexes were obtained using pulsed and continuous wave Doppler from apical projections, and measurements were made utilizing the software of the ultrasound equipment. Mitral diastolic flow was obtained with the pulsed Doppler, and sample volume was positioned perpendicular to the tips of the mitral valve leaflets. The Doppler cursor was then moved toward the LV outflow position, and the sample volume was placed approximately 1 cm proximal to the aortic valve so that it would be adjacent to the anterior mitral valve leaflet. Isovolumic relaxation time (ms) was measured as the interval between the end of the aortic click artifact and the onset of mitral inflow waveform. The following indexes were measured from the mitral valve diastolic waveform: peak early (E) and atrial (A) diastolic flow velocities (m/s), E/A ratio, and deceleration time (ms) of the LV diastolic filling. Heart rate (beats/min) was measured from simultaneous ECG recordings. LV diastolic dysfunction was classified in three categories (impaired relaxation, pseudonormal, or restrictive) as previously described [12]. Statistical analysis We used version 11.0 of the SPSS statistical package. Values are quoted as mean (±SD) or median (range). The prevalence of each factor was compared between groups using chi-square tests. Differences between numeric variables were tested with Student’s t test or the Mann–Whitney
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U test. Correlation was tested with Spearman’s rank-order or Pearson’s correlation coefficient. A significance level was set at P
