Metabolic syndrome at baseline was not predictive to new-onset cardiovascular diseases in patients with systemic lupus erythematosus: A prospective observational registry

Abstract

Objective: It has been established that metabolic syndrome is prevalent in patients with systemic lupus erythematosus (SLE). The objective of this study was to investigate the effect of metabolic syndrome at baseline on new-onset cardiovascular disease (CVD) in patients with SLE. Methods: The demographic and lupus-related clinical variables of 229 patients with SLE were collected from the Korean Lupus Network (KORNET) registry. Metabolic syndrome was defined by the modified National Cholesterol Education Program’s Adult Treatment Panel III (NCEP ATP III) criteria. Binary logistic regression analysis was applied to identify clinical variables including metabolic syndrome related to pre-existing CVD at the time of enrollment or new-onset CVD during 3 years of follow-up.

Results: Patients with pre-existing CVD at baseline had higher rates of metabolic syndrome than those without CVD in SLE (p = .022), whereas there was no difference in the frequency of metabolic syndrome between patients with and without new-onset CVD. Logistic regression analysis revealed that metabolic syndrome and the number of its components were associated with pre-existing CVD, together with body mass index and hypertriglyceridemia. Metabolic syndrome at baseline and its components were not related with increased risk of new-onset CVD. On the contrary, anti-dsDNA antibody titer, anti-ds DNA positivity, and lower diastolic blood pressure increased the risk of new-onset CVD. Conclusion: This study demonstrated that metabolic syndrome at baseline was not predictive to new-onset CVD at 3 years of follow-up, although it was associated with pre-existing CVD in SLE.

Keywords

systemic lupus erythematosus metabolic syndrome cardiovascular diseases anti-dsDNA

Introduction

Systemic lupus erythematosus (SLE) is a multisystemic heterogeneous autoimmune disease characterized by substantial mortality and morbidity rates estimated to be about three times greater than those in the general population.¹ Cardiovascular disease (CVD) induced by accelerated premature atherosclerosis accounts for more than one-third of all-cause mortality in patients with SLE.² Both traditional and nontraditional (lupus-related) cardiovascular risk factors have been found to be responsible for atherosclerotic CVD in SLE.³ Research has focused on traditional cardiovascular risk factors correlated with vascular atherosclerosis in SLE, including metabolic syndrome, smoking, and hyperhomocysteinemia, but these risk factors do not fully explain the higher rate of ischemic vascular events in this population.

Metabolic syndrome is a set of independent risk factors associated with the development of CVD and type II diabetes mellitus, such as glucose intolerance, dyslipidemia, abdominal obesity, and hypertension.^4,5 Sufficient evidence that metabolic syndrome could increase the risk of cardiovascular outcomes and all-cause death has emerged.^6,7,8 Considering the risk of CVD in SLE patients, early detection and treatment of metabolic syndrome can be beneficial in improving clinical outcomes and prognosis. The data of clinical studies have been accumulating that metabolic syndrome may increase the risk of CVD in SLE patients. Several studies have shown that the prevalence of metabolic syndrome in SLE was higher than in the control group.^9,10,11,12 Furthermore, several cross-sectional studies revealed that there is a close association between metabolic syndrome and CVD in patients with SLE.^13,14,15 Numerous lupus-related variables such as disturbance of lipid profiles, aberrant serologic inflammatory markers, and medications for SLE were found to be associated with metabolic syndrome. Some longitudinal studies have also demonstrated that metabolic syndrome contributes to the new development of CVD or increased vascular mortality.^16,17 However, available data regarding a causal relationship between these diseases in the longitudinal study remain insufficient. This study sought to determine the effect of metabolic syndrome on pre-existing or new-onset CVD using a longitudinal prospective observational registry.

Subjects and methods

Study population

The study population was recruited from the Korean Lupus Network (KORNET) registry for SLE, which is a prospective, observational multicenter registry designed to assess clinical features and outcome in Korean patients with SLE that was annually updated from 2014 to 2018. All participants met the 1997 American College of Rheumatology criteria for the classification of SLE.¹⁸ We conducted cross-sectional, non-randomized, and observational study in KORNET registry. This study excluded patients with other autoimmune diseases such as rheumatoid arthritis, Sjogren’ syndrome, systemic sclerosis, mixed connective tissue disease, and inflammatory myositis. All study participants provided written informed consent at the time of their enrollment into the KORNET registry. This study was approved by the Institutional Review Board of Daegu Catholic University Medical Center (approval no. CR-14-123-L).

Identification of clinical information

Demographic variables, including age (years), sex, disease duration (months), body mass index (BMI) (kg/m²), systolic and diastolic blood pressures (mmHg), and smoking status (current vs non-current) were assessed. This study also identified results of relevant serologic biochemical tests, such as fasting glucose, total cholesterol (mg/dL), high-density lipoprotein (HDL) cholesterol (mg/dL), low-density lipoprotein (LDL) cholesterol (mg/dL), erythrocyte sedimentation rate (ESR, mm/hr), and C-reactive protein (CRP, mg/mL). The presence of comorbid diseases, including hypertension, diabetes mellitus, dyslipidemia, and cerebral infarction, was also assessed.

Assessment of systemic lupus erythematosus-related measures

Serologic titer and positivity for complement 3 (C3, mg/mL), complement 4 (C4, mg/mL), and anti–double-stranded DNA (anti-dsDNA) antibody were identified. Disease activity indexes, including the physician global assessment (PGA) as well as a modified version of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) developed by the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) trial, known as SELENA-SLEDAI, were adopted.¹⁹ Lupus-related organ damage was measured using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index.²⁰

Definition of metabolic syndrome

This study adapted definition of metabolic syndrome based on modified National Cholesterol Education Program’s Adult Treatment Panel III (NCEP ATP III) criteria.²¹ Patients with three or more items among five items were diagnosed as metabolic syndrome; 1) waist circumference ≥90 cm in men and ≥80 cm in women (Asian cutoff points), 2) triglyceride ≥150 mg/dL, 3) HDL cholesterol <40 mg/dL for men and <50 mg/dL for women, 4) systolic/diastolic blood pressure ≥130/85 mmHg or current use of medication for hypertension, and 5) fasting blood glucose ≥100 mg/dL or current use of medication for diabetes mellitus.

Definition of cardiovascular diseases

Patients who have been diagnosed with angina pectoris, myocardial infarction, pericardial effusion, pericarditis, or cardiomyopathy using the questionnaire of study registry or who were undergoing treatment for these cardiovascular events at baseline and during the follow-up period were defined as patients with CVD. This definition was modified from the cardiac involvement subcategory of the SLICC/ACR damage index.²⁰ Patients with pre-existing CVD were those already diagnosed and/or being treated at the time of baseline registration, while new-onset CVD refers to patients in which the disease newly developed during the follow-up period of this study after baseline.

Statistical analysis

The data were described as numbers of cases (%) for qualitative variables and median with interquartile range (IOR) values for quantitative variables. Normality of data was assessed by Kolmogorov-Smirnov test, showing no normal distribution. Comparisons between two groups (patients with and without CVD) were performed using the chi-squared or Fisher’s exact test for qualitative variables and Mann–Whitney U test for quantitative variables.

Logistic regression modeling was used to determine the association between significant variables by two-group analyses (pre-existing or new-onset CVD), which is presented using 95% confidence intervals (CIs) and odds ratio (OR) in model 1 without adjustment for confounding factors. In model 2, the relationships between significant variables identified in model 1 and pre-existing or new-onset CVD were identified after adjustment for age and sex. Statistical analyses were performed using the Statistical Package for the Social Sciences version 19.0 version program (IBM Corp. Armonk, NY, USA). p values of less than 0.05 were considered to be statistically significant.

Results

Baseline characteristics of the study population

A total of 229 patients with SLE were analyzed, as shown in Table 1. The median age of the study population was 40.2 years (IQR 35.0–51.0 years). Most of the study population was female (n = 213, 93%), and the median disease duration was 34.5 months (IQR, 93.0–164.5 months). Patients with metabolic syndrome accounted for 31.9% of the study population (n = 73). All patients had an average of 2.0 metabolic syndrome components. Other baseline characteristics, including biochemistry variables, comorbidities, SLE-specific measures, and current medications, are also listed in Table 1.

Table 1.

Baseline characteristics of enrolled subjects (n = 229).

Variables	Results
Demographic variables
Age (years)	42.0 (35.0–51.0)
Female gender	213 (93.0)
Disease duration (months)	34.5 (93.0–164.5)
Body mass index (kg/m²)	21.5 (19.7–24.1)
Systolic blood pressure	118.0 (110.0–128.0)
Diastolic blood pressure	70.0 (65.0–80.0)
Current smoking	25 (11.0)
Biochemistry variables
Fasting glucose (mg/dL)	90.0 (82.5–99.0)
Triglyceride (mg/dL)	104.0 (69.5–151.5)
Total cholesterol (mg/dL)	161.0 (140.0–184.5)
HDL cholesterol (mg/dL)	49.0 (40.0–58.0)
LDL cholesterol (mg/dL)	88.0 (72.0–103.0)
Erythrocyte sedimentation rate (mm/hr)	19.0 (9.0–32.0)
C-reactive protein (mg/L)	0.10 (0.05–0.30)
Variables for metabolic syndrome
Number of metabolic syndrome component	2.0 (1.0–3.0)
Metabolic syndrome components
Hypertension	50 (21.8)
Waist circumference	212 (92.6)
Low HDL cholesterol	115 (50.2)
Hypertriglyceridemia	58 (25.3)
Hyperglycemia	55 (24.0)
Comorbidities
Hypertension	29 (12.7)
Diabetes mellitus	4 (1.7)
Dyslipidemia	17 (7.4)
Cerebral infarction	5 (2.2)
SLE-specific markers
Complement 3 titer (mg/dL)	80.8 (66.8–96.0)
Abnormal C3	135 (59.2)
Complement 4 titer (mg/dL)	15.3 (10.4–20.6)
Abnormal C4	60 (26.3)
Anti-dsDNA titer (IU/mL)	8.3 (0.0–39.8)
Abnormal anti-dsDNA	123 (53.7)
Physician global assessment	1.0 (0.5–1.0)
SELENA-SLEDAI	4.0 (2.0–6.0)
SLICC damage index	0.0 (0.0–1.0)
Current medications
Corticosteroid	219 (95.6)
Doses of corticosteroid (mg/day)^*	7.5 (5.0–10.0)
Methotrexate	10 (4.4)
Mycophenolate mofetil	53 (23.1)
Hydroxychloroquine	227 (99.1)

Data were described as number of case (%) for qualitative variables or median (interquartile, IQR) for quantitative variables.

Abbreviation: CVD, cardiovascular diseases; HDL, high-density lipoprotein; LDL, low-density lipoprotein; SELENA-SLEDAI, Safety of estrogen in lupus erythematosus national assessment-systemic lupus erythematosus disease activity index; SLICC = Systemic Lupus International Collaborating Clinics/American College of Rheumatology.

Corticosteroid doses are calculated using prednisolone-equivalent doses per day.

Comparison of clinical variables between patients with and without pre-existing cardiovascular disease

Using the baseline data, we first assessed whether there were differences in clinical variables between patients with and without pre-existing CVD. In the study population, patients with pre-existing CVD were 13.1% (n = 30). Patients with pre-existing CVD presented with higher BMI values, triglyceride levels, numbers of metabolic syndrome components, and hypertriglyceridemia among metabolic syndrome components as well as higher PGA scores than did those without pre-existing CVD (Table 2). A significant difference in the prevalence of metabolic syndrome was noted between the two groups (29.1% vs. 50.0%, p = 0.022) (Figure 1).

Table 2.

Comparison of variable according to the presence of preexisting or new-onset cardiovascular diseases.

Demographic variables	Preexisting CVD			New-onset CVD
Demographic variables	Absence (n = 199)	Presence (n = 30)	p value	Absence (n = 211)	Presence (n = 18)	p value
Age (years)	41.0 (35.0–51.0)	43.0 (25.8–53.5)	0.587	41.0 (35.0–51.0)	45.0 (37.8–60.0)	0.198
Female gender	186 (9.35)	27 (90.0)	0.487	196 (92.9)	17 (94.4)	0.804
Disease duration (months)	91.0 (36.0–160.0)	104.5 (24.8–181.0)	0.534	91.0 (31.0–160.)	112.5 (60.5–191.5)	0.250
Body mass index (kg/m²)	21.4 (19.4–23.6)	23.2 (20.1–26.5)	0.039	21.4 (19.4–24.0)	22.4 (20.1–24.2)	0.605
Systolic blood pressure	117.0 (110.0–127.0)	122.0 (110.0–131.0)	0.135	118.0 (110.0–128.0)	111.0 (105.8–126.3)	0.334
Diastolic blood pressure	70.0 (64.0–80.0)	74.0 (68.3–81.3)	0.110	71.0 (65.0–80.0)	70.0 (60.8–71.3)	0.049
Current smoking	23 (11.6)	2 (6.7)	0.419	23 (11.0)	2 (11.1)	0.983
Biochemistry variables
Fasting glucose (mg/dL)	90.0 (82.0–99.0)	90.5 (82.5–102.5)	0.634	90.0 (82.0–99.0)	91.5 (83.8–100.3)	0.732
Triglyceride (mg/dL)	98.0 (68.0–142.0)	144.5 (89.0–193.3)	0.009	100.0 (69.0–151.0)	128.5 (91.3–155.3)	0.131
Total cholesterol (mg/dL)	162.0 (139.0–185.0)	160.5 (143.8–175.5)	0.813	162.0 (140.0–185.0)	159.0 (140.1–175.0)	0.371
HDL cholesterol (mg/dL)	50.0 (41.0–59.0)	44.0 (36.0–54.3)	0.056	49.0 (40.0–58.0)	47.0 (40.0–53.5)	0.634
LDL cholesterol (mg/dL)	88.0 (72.0–103.0)	91.0 (78.3–102.0)	0.852	88.0 (72.0–103.0)	84.5 (71.8–102.8)	0.663
Erythrocyte sedimentation rate (mm/hr)	19.0 (9.0–32.0)	18.5 (9.0–30.8)	0.887	18.0 (9.0–30.0)	25.0 (8.0–39.5)	0.322
C-reactive protein (mg/L)	0.09 (0.05–0.30)	0.18 (0.06–0.36)	0.184	0.09 (0.05–0.30)	0.14 (0.07–0.20)	0.560
Variables for metabolic syndrome
Number of metabolic syndrome component	2.0 (1.0–3.0)	2.5 (2.0–3.3)	0.007	2.0 (1.0–3.0)	2.0 (1.0–3.3)	0.887
Metabolic syndrome components
Hypertension	42 (21.1)	8 (26.7)	0.492	48 (22.7)	2 (11.1)	0.251
Waist circumference	185 (93.0)	27 (90.0)	0.564	195 (92.1)	17 (94.4)	0.753
Low HDL cholesterol	96 (48.2)	19 (63.3)	0.123	105 (49.8)	10 (55.6)	0.637
Hypertriglyceridemia	44 (22.1)	14 (46.7)	0.004	53 (25.1)	5 (27.8)	0.803
Hyperglycemia	45 (22.6)	10 (33.3)	0.200	50 (23.7)	5 (27.8)	0.697
Comorbidities
Hypertension	22 (11.1)	7 (23.3)	0.059	25 (11.8)	4 (22.2)	0.204
Diabetes mellitus	2 (1.0)	2 (6.7)	0.084	3 (1.4)	1 (5.6)	0.281
Dyslipidemia	14 (7.0)	3 (10.0)	0.564	15 (7.1)	2 (11.1)	0.534
Cerebral infarction	3 (1.5)	2 (6.7)	0.129	4 (1.9)	1 (5.6)	0.338
SLE-specific markers
Complement 3 titer (mg/dL)	78.7 (66.3–95.9)	91.3 (70.7–98.4)	0.197	80.1 (67.8–96.0)	87.1 (57.9–96.1)	0.579
Abnormal C3	122 (61.6)	13 (43.3)	0.058	126 (60.0)	9 (50.0)	0.407
Complement 4 titer (mg/dL)	15.3 (10.5–20.5)	14.5 (10.3–22.0)	0.616	15.3 (10.5–20.6)	14.5 (10.3–20.2)	0.699
Abnormal C4	52 (86.8)	30 (13.2)	0.963	56 (26.7)	4 (22.2)	0.681
Anti-dsDNA titer (IU/mL)	8.0 (0.0–39.8)	16.5 (0.0–46.1)	0.135	8.1 (0.0–38.8)	31.2 (5.9–133.3)	0.015
Abnormal anti-dsDNA	102 (51.3)	21 (70.0)	0.055	109 (51.7)	14 (77.8)	0.033
Physician global assessment	1.0 (0.5–1.0)	0.5 (0.0–1.0)	0.024	1.0 (0.5–1.0)	0.5 (0.0–1.0)	0.376
SELENA-SLEDAI	4.0 (2.0–6.0)	3.5 (0.0–5.3)	0.470	4.0 (2.0–6.0)	3.5 (0.0–6.3)	0.845
SLICC damage index	0.00 (0.0–1.0)	0.0 (0.0–1.3)	0.529	0.0 (0.0–1.0)	0.0 (0.0–0.5)	0.987
Current medications
Corticosteroid	190 (95.5)	29 (96.7)	0.766	201 (95.3)	18 (100.0)	0.345
Methotrexate	9 (4.5)	1 (3.3)	0.766	10 (4.7)	0 (0.0)	0.345
Mycophenolate mofetil	48 (24.1)	5 (16.7)	0.367	51 (24.2)	2 (11.1)	0.207
Hydroxychloroquine	197 (99.0)	30 (100.0)	0.755	209 (99.1)	18 (100.0)	0.849

Data were described as number of case (%) for qualitative variables or median (interquartile, IQR) for quantitative variables.

Figure 1.

Risk of cardiovascular diseases according to metabolic syndrome during follow-up period. Abbreviation: CVD, cardiovascular disease.

Comparison of clinical variables between patients with and without new-onset cardiovascular disease

Next, we compared clinical variables between patients with and without new-onset CVD during the 3-year follow-up period. Overall, a total of 18 patients experienced new-onset CVD (7.9%). In the comparison of clinical variables between patients with and without new-onset CVD, there were significant differences in diastolic blood pressure, anti-dsDNA positivity, and anti-dsDNA titer observed (Table 2). However, the prevalence of metabolic syndrome was not different between the two groups (p = .697) (Figure 1).

Determination of clinical variable related with pre-existing and new-onset cardiovascular disease

Logistic regression analysis was used to determine clinical variables related to pre-existing CVD. Model 1 showed that BMI, the number of metabolic syndrome components, hypertriglyceridemia, and metabolic syndrome were associated with pre-existing CVD (Table 3). Model 2, after adjusting for age and sex, also showed consistent results. We assessed the association between clinical variables and new-onset CVD. Metabolic syndrome at baseline was not associated with increased risk of new-onset CVD, whereas diastolic blood pressure, and anti-dsDNA positivity were linked to new-onset CVD in model 1 (Table 3). Further analysis after adjustment for age and sex in model 2 revealed a consistent association.

Table 3.

Logistic regression analysis of variables associated with preexisting and new-onset cardiovascular diseases.

Variables	Preexisting CVD
	Model 1 (unadjusted)			Model 2 (adjusted)
	OR	95% CI	p value	OR	95% CI	p value
Body mass index	1.142	1.022–1.277	0.019	1.140	1.013–1.282	0.030
Number of metabolic syndrome components	1.621	1.124–2.339	0.010	1.614	1.094–2.382	0.016
Hypertriglyceridemia	3.082	1.397–6.802	0.005	3.033	1.322–6.960	0.009
Physician global assessment	0.505	0.238–1.071	0.075	0.520	0.242–1.117	0.094
Metabolic syndrome	2.431	1.116–5.294	0.025	2.395	1.055–5.437	0.037
New-onset CVD
Diastolic blood pressure	0.936	0.889–0.984	0.010	0.933	0.885–0.984	0.010
Abnormal anti-dsDNA	3.275	1.044–10.277	0.042	4.048	1.246–13.155	0.020
Metabolic syndrome	0.809	0.277–2.361	0.698	0.638	0.206–1.976	0.436

Data were described as odds ratio (OR) and 95% confidence intervals (CIs).

Model 1, unadjusted; Model 2 adjusted with age and gender.

Abbreviation: CVD, cardiovascular diseases.

Discussion

This study retrospectively analyzed the association between metabolic syndrome and pre-existing or new-onset CVD using prospective observational KORNET registry data. Patients with metabolic syndrome were 31.9% of the study population at baseline, which is similar to other prevalence rates reported for different ethnic groups.¹² Pre-existing CVD at baseline and new-onset CVD during 3 years of follow-up was present in 13.1% and 7.9% of the study population, respectively. At baseline, the prevalence of metabolic syndrome in patients with pre-existing CVD was higher than that in those without pre-existing CVD. Furthermore, metabolic syndrome was significantly associated with pre-existing CVD. However, metabolic syndrome or its individual components at baseline did not predict the occurrence of new-onset CVD during 3 years of follow-up in our study population.

An increased risk of CVD and its related mortality in patients with SLE has been found to be associated with accelerated premature atherosclerosis.³ Although the exact pathogenic mechanisms of early subclinical atherosclerosis are still not clearly defined, a lupus-related inflammatory response or traditional cardiovascular risk factors have been suggested as major causes. Among the traditional risk factors, metabolic syndrome is a potent independent predictor linked to cardiovascular mortality and morbidity beyond a cluster of individual risk factors.⁴ In lupus patients, interest in the relationship between metabolic syndrome and CVD has increased. Many studies have demonstrated that metabolic syndrome in SLE patients is closely connected to the presence of CVD, together with lupus-related inflammation.^13,14,15 However, because these studies employed a cross-sectional study design, limitations in confirming the causal relationship between metabolic syndrome and CVD were noted. Recently, several studies have provided evidence to support these casual relationships. García-Villegas et al.¹⁶ demonstrated that metabolic syndrome had a potent predictive value for the cumulative incidence of CVD in a cohort of premenopausal patients with SLE. In addition, a longitudinal Chinese cohort study revealed that the presence of metabolic syndrome contributed to the development of new vascular events and mortality.¹⁷ However, they did not record a predictive effect of metabolic syndrome on cardiovascular damage (OR 3.57 95% CI, 0.99%–12.9%, p = .05). On the contrary, our study did not show a predictive value for metabolic syndrome regarding new-onset CVD during 3 years of follow-up.

Several considerations are needed to explain the difference in the role of metabolic syndrome in predicting newly emerging CVD in our study compared to previous studies. First, regional and ethical variations and different definitions of CVD among patients participating in each study might have led to the use of diverse risk factors for CVD. Second, there does not appear to be a significant level of agreement between metabolic syndrome–related clinical variables and cardiovascular risk factors. The metabolic syndrome–related factors identified at baseline of this study included age, sex, blood pressure, fasting glucose, triglycerides, HDL cholesterol, dyslipidemia as a comorbidity, and SLICC damage index (Supplementary Tables 1 and 2). Most of the risk factors related to metabolic syndrome were not present among known risk factors for pre-existing or new-onset CVD.

Considering lupus-related variables support a connection between metabolic syndrome and CVD, our present study found that anti-dsDNA was a risk factor for new-onset CVD, although anti-dsDNA antibody was not associated with metabolic syndrome (Supplementary Table 2). Recently, Patiño-Trives et al.²² demonstrated that anti-dsDNA antibody in patients with SLE is associated with endothelial dysfunction, dyslipidemia, and atherosclerosis, which suggests that the presence of anti-dsDNA antibody might increase the risk for the development of CVD. A study from Turkey assessing metabolic syndrome and CVD showed that antiphospholipid antibody positivity was correlated with CVD, together with metabolic syndrome.¹³ Our study found that there was no association between lupus activity and damage indexes, such as SLEDAI and the SLICC damage index, nor the presence of CVD, although the SLICC damage index was related with metabolic syndrome. On the contrary, higher SLICC damage index values increased the risk of the probability of developing CVD in a premenopausal cohort study.¹⁶ In our study, diastolic blood pressure was lower in patients with new-onset CVD than those without CVD, and lower diastolic blood pressure paradoxically increased the risk of new-onset CVD. The analysis of the SPRINT (Systolic Blood Pressure Intervention Trial) observed a J-shaped association between diastolic blood pressure and the composite CVD outcome.²³ The hazard ratios for CVD of diastolic blood pressure <55 mm Hg versus 55–90 mm Hg were 1.68 (p = .006). In addition, other study demonstrated that isolated diastolic hypotension might be an independent risk factor for incident heart failure.²⁴ Diastolic hypotension might cause undiagnosed CVD patients to be susceptible to an increased risk of ischemic change.

The present study has several limitations. First, the follow-up period may be relatively short to detect the occurrence of new-onset CVD in a relatively young age study group. Two longitudinal studies with more than 5 years of follow-up revealed that metabolic syndrome was a predictor of CVD in premenopausal SLE patietns.^16,17 In addition, the possibility that the incidence of new-onset CVD might be underestimated during the follow-up period cannot be excluded because some of the patients who enrolled in the present registry lost follow-up for undetermined causes. The follow-up period is considered to be an important variable in determining the relationship between the metabolic syndrome and new-onset CVD. Second, objective atherosclerosis biomarkers of CVD such as carotid intima-media thickness (cIMT) were not presented in this study. Subjects with metabolic syndrome may be vulnerable to impaired vascular function.²⁵ To further support the results of this study, it is necessary to confirm the relationship between the metabolic syndrome and cIMT, an indicator of CVD. Third, the sample size of the study subjects may not be sufficient to confirm the primary outcome of this study. Further study participating a larger study population should be needed. Fourth, various confounding factors such as antiphospholipid syndrome, lipid-lowering agents, aspirin, and cumulative corticosteroid doses that could affect cardiovascular events in SLE patients was not sufficiently considered. The possibility that these variables affect the results of this study cannot be excluded. But it is judged that the effect will be insignificant since most of the actual study subjects are young and the disease activity is not high.

Conclusion

In conclusion, metabolic syndrome at baseline was associated with pre-existing CVD. In contrast, metabolic syndrome did not predict new-onset CVD in patients with SLE after 3 years follow-up, which is consistent with the 2004 result that the presence of metabolic syndrome did not reflect newly developed CVD in a Mexican cohort followed from 2001 to 2008.¹⁶ Lower diastolic blood pressure, higher anti-dsDNA antibody titer, and anti-dsDNA positivity at baseline might be predictors for an increased risk of new-onset CVD. Although metabolic syndrome is an independent marker for CVD in the cross-sectional assessment, the predictive value of metabolic syndrome in SLE patients with newly developed CVD should be explored and further verified in prospective, longitudinal investigations.

Supplemental Material

Supplemental Material - Metabolic syndrome at baseline was not predictive to new-onset cardiovascular diseases in patients with systemic lupus erythematosus: A prospective observational registry

Supplemental Material for Metabolic syndrome at baseline was not predictive to new-onset cardiovascular diseases in patients with systemic lupus erythematosus: A prospective observational registry by Seong-Kyu Kim and Jung-Yoon Choe in European Journal of Inflammation

Footnotes

Author’s note

Electronic development of the case report form and data management for this study were performed using iCReaT (internet-based Clinical Research and Trial management system, ), a data management system established by the Centers for Disease Control and Prevention, Ministry of Health and Welfare, Republic of Korea (iCReaT Study No. C140018).

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Ethics approval

Ethical approval for this study was obtained from the Institutional Review Board (IRB No. CR -14-123-L) of Daegu Catholic University Medical Center.

Informed consent

All study participants provided written informed consent at the time of their enrollment into the KORNET registry.

ORCID iD

Seong-Kyu Kim

Supplemental Material

Supplemental material for this article is available online.

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