|Year : 2019 | Volume
| Issue : 4 | Page : 863-872
|Predictive values of dyslipidemia and B-type natriuretic peptide levels in juvenile systemic lupus erythematosus: A two center-experience
Mohamed A El-Gamasy1, Mohamed Mohamed Abd Elsalam2, Amal Mohamed Abd-El Latif2, Hanaa Hossney Elsaid3
1 Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta, Egypt
2 Department of Pediatrics, Faculty of Medicine, Zagazig University, Zagazig, Egypt
3 Department of Clinical Pathology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
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|Date of Submission||04-Apr-2018|
|Date of Decision||10-May-2018|
|Date of Acceptance||02-Jul-2018|
|Date of Web Publication||27-Aug-2019|
| Abstract|| |
B-type natriuretic peptide (BNP) is a biomarker that helps in determining the diagnosis and prognosis of heart failure (HF). There is an increased risk for cardiovascular disease (CVD) in systemic lupus erythematosus (SLE) with high disease activity, demonstrated by the higher frequency of dyslipidemia and higher BNP concentrations than in healthy controls. The aim of the work was to evaluate the association between the levels of lipids and BNP in pediatric patients with SLE with HF. We classified our subjects into three groups as follows: Group 1 (active SLE group): included 38 patients who subgrouped into 16 with HF and 22 without HF; Group 2 (inactive SLE group): included 38 patients, and Group 3 (control group): included 38 apparently healthy children. All children were subjected to complete history taking, clinical examination, SLE disease activity index scoring and investigations included complete blood count, erythrocyte sedimentation rate, 24-h urinary protein, anti-double strand deoxy-ribonucleic acid and anti-nuclear antibody, lipid profile, serum albumin, protein, and BNP. There was a significantly elevated lipid level and decreased high-density lipoproteins in lupus patients than in healthy controls. The dyslipidemia was more prevalent in active SLE. There were significantly elevated BNP levels in lupus patients than in healthy controls. In this study, we found that BNP was a biomarker in determining the diagnosis and prognosis of HF. This study revealed that BNP levels were increased in SLE patients without cardiac symptoms as compared to healthy controls; furthermore, the BNP levels were higher in active SLE patients with HF. The data indicated that there is a high risk for CVD in SLE with high disease activity, as demonstrated by the higher frequency of dyslipidemia and higher BNP concentrations than in healthy controls.
|How to cite this article:|
El-Gamasy MA, Abd Elsalam MM, Abd-El Latif AM, Elsaid HH. Predictive values of dyslipidemia and B-type natriuretic peptide levels in juvenile systemic lupus erythematosus: A two center-experience. Saudi J Kidney Dis Transpl 2019;30:863-72
|How to cite this URL:|
El-Gamasy MA, Abd Elsalam MM, Abd-El Latif AM, Elsaid HH. Predictive values of dyslipidemia and B-type natriuretic peptide levels in juvenile systemic lupus erythematosus: A two center-experience. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2020 Jan 21];30:863-72. Available from: http://www.sjkdt.org/text.asp?2019/30/4/863/265462
| Introduction|| |
Various autoimmune rheumatic diseases (ARDs), including rheumatoid arthritis, spondylarthritis, vasculitis, and systemic lupus erythematosus (SLE), are associated with premature atherosclerosis. Cardiovascular disease (CVD) in ARDs is caused by traditional and nontraditional risk factors. This association is the result of the complex interaction between classic risk factors, chronic inflammation and the production of autoantibodies. SLE is a typical example of an autoimmune inflammatory disease, in which accelerated atherosclerosis and its sequelae are recognized as one of the most frequent causes of morbidity and mortality.
CVD is a major cause of death in patients with SLE, especially during the late phase of the disease. Abnormal plasma concentration of lipids is common in patients with SLE. Dyslipidemia usually refers to elevated total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and decreased high-density lipoprotein (HDL) levels.
B-type natriuretic peptide (BNP) is the gold standard biomarker in determining the diagnosis and prognosis of heart failure (HF). Patients with HF often present with signs and symptoms that are nonspecific and with a wide differential diagnosis, making diagnosis by clinical presentation alone challenging. Although lipids are a major risk factor for CVD and are routinely measured for risk stratification, the association between dyslipidemia and BNP in SLE patients remains unclear. Establishing the association between lipid levels and BNP in SLE patients is critical for understanding the role of lipids in the CVD risk among SLE patients. The present study was designed to evaluate the presence of dyslipidemia and the plasma concentrations of BNP in patients with active SLE.
| Aim of the study|| |
The aim of the work was to measure lipid profile and BNP and to evaluate their association in patients with SLE and to assess the value of BNP as early marker for HF in SLE patients.
| Subjects and Methods|| |
Our case–control study was performed on 76 cases collected from the lupus clinic in the Pediatric Nephrology Units of Pediatric Departments of Hospitals of Tanta and Zagazig Universities. During the period from April 2017 to April 2018, 76 patients with SLE and 38 age- and sex-matched healthy controls taken as a control group were studied.
Approval was obtained from the Local Ethics Committee of Tanta and Zagazig Faculties of Medicine, Egypt.
Children fulfilling the revised criteria of the American College of Rheumatology for SLE were included in the study.
Children with congenital or rheumatic heart diseases or diabetes mellitus were excluded from the study. The included children were classified into the following three groups:
- Group 1 (active SLE group): included 38 patients with age-group ranging from 9 to 18 years, and there were four males and 34 females who had manifestations or complications of SLE. Disease activity was evaluated according to the SLE disease activity index (SLEDAI) score which is a validated disease activity measure for childhood-onset SLE with a total score of 0–100. The tool consists of 24 weighted items grouped into the following nine domains: central nervous system (CNS), vascular, renal, musculoskeletal, mucosal, dermal, immunological, constitutional, and hematological diseases. If the SLEDAI score is 4 or more, the disease is active. If the SLEDAI score is <4, the disease is inactive. Subgroups taken from the active group included 16 patients with HF and 22 patients without HF
- Group 2 (inactive SLE group): included 38 patients with age-group ranging from 9 to 18 years and there were four males and 34 females, who had no manifestations or complications of SLE
- Group 3 (control group): included 38 patients with age-group ranging from 9 to 18 years and there were 12 males and 26 females. They were apparently healthy children.
All subjects were subjected to:
- Full history taking including age, sex and clinical presentation (fever, arthralgia, change in the color of urine, headache), and history of similar attacks
- Clinical examination included general examination such as measuring arterial blood pressure and local examination (involvement of the skin, joints, renal, pulmonary, cardiovascular, and CNS)
- Disease activity was evaluated according to the SLEDAI score
- Laboratory investigations which included: complete blood picture, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), anti-nuclear antibody (ANA), anti-double strand deoxyribonucleic acid, TC, TG, HDL-cholesterol (HDL-C), LDL–cholesterol (LDL-C), serum albumin, and proteinuria were performed
- BNP was measured using enzyme-linked immunosorbent assay
- Echocardiographic examination using M-mode, two-dimensional conventional Echo, and Doppler echocardiography color coding character was performed using a Vivid 7 dimensions (General Electric machine equipped with a multi-frequency M3S and a 7s transducers with simultaneous electrocardiogram recording
- To detect asymptomatic heart diseases, examination was performed by a pediatric cardiologist after feeding to calm the baby. Mild oral sedative (chloral hydrate) was used for a crying child
- The following standard windows were used:
- Long- and short-axis para-sternal
- Long- and short-axis supra-sternal.
The views were used for assessing:
- Cardiac anatomy
- Associated anomalies
- Evaluation of cardiac dimensions
- Evaluation of cardiac function.
| Statistical Analysis|| |
Data were collected and submitted to statistical analysis. The following statistical tests and parameters were used.
Data collected from history, basic clinical examination, laboratory investigations, and outcome measures were coded, entered, and analyzed using Microsoft Excel software. Data were then imported into Statistical Package for the Social Sciences version 20.0 software for analysis (IBM Corp., Armonk, NY, USA). According to the type of data, qualitative data were presented as number and percentage, and quantitative data were presented as a mean ± standard deviation (SD). The following tests were used to test differences for significance. Differences between frequencies (qualitative variables) and percentages in groups were compared using the Chi-square test, differences between parametric quantitative independent groups by t-test and nonparametric by Mann-Whitney, correlation by Pearson’s correlation. P value was set at <0.05 for significant results and <0.001 for highly significant result.
| Results|| |
The total number of patients with SLE in this study was 76, eight of them (10.5 %) were males and 68 were females (89.5%). The total number of controls was 38, including 12 males (31.6%) and 26 females (68.4%). Prevalence of the disease was higher in females with a female-to-male ratio of 8.5:1. The age in studied patients ranged from 9 to 18 years with a mean ± SD of 12.22 ± 2.02 years, whereas in controls, the mean ± SD age was 11.70 ± 2.75 years. There was no statistically significant difference between studied patients and controls regarding age and sex (P >0.05).
Clinical manifestations of SLE were significantly higher in active (A1 and A2) than in inactive patients (A3) (P <0.05) except for CNS manifestations which were present only in active patients but did not show statistical significance (P >0.05) as shown in [Table 1].
|Table 1: Lipid profile and BNP results of the studied patients and controls at diagnosis.|
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There was a significant difference between patients’ subgroups regarding their SLEDAI score (P <0.05). The SLEDAI score was the highest in active SLE patients and lowest in inactive SLE patients.
There was a significant increase in white blood cells in cases compared to controls; there were was no statistically significant difference in other hematological parameters between active and inactive SLE cases.
There was a statistically significant increase in ESR in active SLE compared to the inactive group. Furthermore, there was a statistically significant increase in CRP levels in cases compared to controls.
There was a statistically significant increase in blood urea nitrogen and significant decrease in serum albumin in cases compared to controls and in the active group when compared to the inactive group.
There were statistically significant increase in ANA and anti-DNA levels in cases compared to controls and in active SLE patients when compared to inactive cases.
Table 1 and [Table 2] show statistically significant increase in TC, TG, and LDL-C and highly significant decrease in HDL-C in cases when compared to controls, and in active cases when compared with inactive cases.
|Table 2: Comparison of lipid profile and BNP levels in active systemic lupus erythematosus and inactive cases of systemic lupus erythematosus at diagnosis.|
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Table 1 and [Table 2] also show that there was statistically significant increase in BNP in cases when compared to controls, and in active SLE when compared to inactive cases. [Table 3] shows that there was a statistically significant increase in BNP in active SLE cases with HF when compared to active SLE cases without HF; all active SLE cases with HF had peri-cardial effusion.
|Table 3: Laboratory results of active systemic lupus erythematosus patients with or without heart failure.|
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[Table 4] and [Table 5] summarize the echocardio- graphic data of the studied patients and controls. There was a statistically significant decrease in fractional shortening (FS) in cases compared to controls, but other echocardio-graphic parameters did not show any significant difference.
|Table 4: Comparison between echocardiographic dimensions of the studied patients and controls at diagnosis.|
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|Table 5: Comparison between echocardiographic dimensions of active and inactive cases at diagnosis.|
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There was statistically, a highly significant decrease in FS and statistically significant decrease in ejection fraction (EF) and statistically highly significant increase in left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) in active cases compared to inactive cases [Table 5].
[Table 6] summarizes correlations between lipid profile and BNP and other studied parameters. There was a significant negative correlation between BNP and age [Figure 1] and HDL-C, and a significant positive correlation between BNP with SLEDAI [Figure 2], CRP [Figure 3], and TC.
|Table 6: Correlation between lipid profile and BNP levels and different studied parameters in patient group.|
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|Figure 1: Scatter plot with regression line showing negative correlation between age and BNP. |
BNP: B-type natriuretic peptide.
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|Figure 2: Scatter plot with regression line showing the positive correlation BNP and SLEDAI.|
BNP: B-type natriuretic peptide, SLEDAI: Systemic lupus erythematosus disease activity index.
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|Figure 3: Scatter plot with regression line showing positive correlation between BNP and CRP. |
BNP: B-type natriuretic peptide, CRP: C- reactive protein.
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| Discussion|| |
Patients with SLE have a higher prevalence of subclinical atherosclerosis and a higher risk of cardiovascular events compared to the general population. The estimated prevalence of cardiovascular complications in the SLE population is between 6% and 10%, with an annual incidence of 1.3%–1.5%. Cardiovascular complications have now become a major cause of morbidity and mortality in SLE as the treatment of other complications have improved. Patients with inflammatory diseases are now considered to have an increased risk of CVD. Systemic inflammation and autoimmune reactions lead to monocyte and lymphocyte recruitment and activation. Increased lipid deposition and augmented inflammation in vascular intima have been suggested to underlie the pathogenesis of accelerated atherosclerosis in various ARDs. Early identification of cardiovascular risk in pediatric patients is a major challenge, particularly in patients with SLE.
The female-to-male ratio in this study was 8.5:1 showing female predominance, similar to reports from other countries, emphasizing the importance of hormonal factors in the clinical expression of the disease.
In the current study, we found that during SLE activity, proteinuria was significantly higher than in inactive SLE. In contrast, Christopher-Stine et al, reported that protei-nuria was a poor indicator of underlying disease severity or activity.
In our study, abnormal lipid profile was also confirmed in SLE patients compared with healthy controls. This was similar to studies reported by Toloza et al and Urowitz et al.
Our results were also in agreement with Tyrrell et al who reported that lipid abnormalities were present in two-thirds of their pediatric patients with SLE at diagnosis. Another study by Szabó et al reported that inflammatory mediators were proved to decrease HDL and increase TG levels. LDL activity was reduced by TNF-α and IL-6 and antibodies against LDL.
In our study, abnormal lipid profile was aggravated by disease activity (detected by SLEDAI), and there was a statistically highly significant increase in TC, LDL and TG levels and decrease in HDL level in active patients when compared to inactive patients. Similar results were reported by Tyrrell et al, Borba and Bonfó, and Cardoso et al. These findings show that adequate control of activity of SLE helps to improve the lipid abnormalities thus, decreasing cardiovascular risks in these patients.
In contrast, Szabo et al, reported that in inactive SLE, the dyslipidemia was more prevalent than during activity and attributed this to significant changes, which have been observed in inactive lupus patients suggesting that inflammation itself cannot fully explain the changes in lipid metabolism.
Our study revealed that BNP levels were increased in SLE patients without cardiac symptoms as compared to healthy controls. These results were in agreement with Yuan et al and Karadag et al. Similarly, Gaggin and Januzzi revealed that elevated BNP levels were also predictors of future HF or other CV events in asymptomatic patients without evident HF. Hunt et al reported that BNP production in normal healthy individuals is minimal, with a level of ~10 pg/mL.
In our study, we classified the active SLE patients into two sub-groups; with HF and without HF and we found significantly higher concentrations of BNP in the active SLE patients with HF when compared with those without HF. Similar results were recently reported by Yuan et al.
Our results were in agreement with McCullough who reported that measuring BNP provided additional diagnostic and prognostic information about HF and added that BNP level above 100 pg/mL has been suggested as a confirmatory test for the diagnosis of HF in these patients. Harney et al suggested BNP to be a useful test for screening for CVD in patients with SLE.
Gaggin and Januzzi reported that elevated BNP level was a predictor of cardiovascular risk events such as HF in their SLE patients and recommended that BNP should be considered as the gold standard biomarker for determining the diagnosis and prognosis of HF.
Conventional echocardiography was the most widely used technique for the assessment of cardiac function in SLE patients.
Measurement of LVEDD, LVESD, FS, and LV EF are considered as routine screening parameters for cardiac enlargement and function. In this study, on conventional echocar-diographic evaluation, LVEDD and LVESD were higher and LVFR and FS were lower in SLE patients than in the controls (but statistically not significant). These findings were in agreement with previously published reports.,
In a study on adolescents, Barsalou et al reported that LVEDD and LVESD were significantly higher in their SLE patients when compared to controls. Nevertheless, EF values of SLE patients were within normal range and preserved within normal range at short-term follow-up of these patients.
In the current study, we reported that during disease activity, LVEDD and LVESD were significantly higher and LVEF and FS were significantly lower than in the inactive group. These findings were in agreement with Roman et al who reported that during SLE activity, patients may have experienced subclinical myocarditis which may result in a slight enlargement of the heart chambers.
In this study, we found that SLE patients had significantly higher risk of pericardial effusion detected by echocardiography, This is in agreement with a study done by Sugiura et al, who showed that pericarditis is a risk factor for the development of pericardial effusion in SLE patients and in agreement also with Omdal et al, who reported that pericardial effusion was an early cardiac involvement with acute and chronic pericarditis in their SLE patients.
Our results were in accordance also with Doria et al who reported that pericardial effusion was a common finding in active SLE patients. In this study, pericardial effusion was reported in 23 (31.9%) of the studied patients. Similarly, Hameed et al reported pericardial effusion in 57% of their SLE patients.
Regarding correlations, the present study showed significant negative correlation between serum levels of HDL-C in SLE patients and BNP (spearman correlation coefficient = 0.3) and P ≤0.05.
Disease activity was positively correlated with the TC (r = 0.3, P <0.04). This was in agreement with a study done by Yuan et al. The present study also showed significant positive correlation between CRP level and BNP (Spearman correlation coefficient = 0.4) and P <0.05. No statistically significant associations were identified between the BNP level and other demographic, clinical manifestations, or laboratory parameters in the studied patients with SLE. This was in agreement with a study done by Yuan et al.
| Conclusions|| |
Our results indicated the presence of cardiovascular risk factors in children and adolescents with SLE, especially in patients with high SLEDAI, evidenced by the higher frequency of dyslipidemia and higher BNP concentrations in these patients when compared to healthy controls.
| Recommendations|| |
To determine the prognosis of pediatric SLE patients, serial measurement of lipid profile and serum BNP levels are important during the follow-up period.
Conflict of interest: None declared.
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Mohamed A El-Gamasy
Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]
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