Evaluation of pro‐atherogenic lipid profile and high atherohenic indexes in patients with Behçet's disease: A case–control study

Behçet's disease is a systemic auto‐immune and auto‐inflammatory chronic disease in which genetic and environmental factors play a role. Patients with Behçet's are at significant risk for developing many comorbidities, including cardiovascular diseases.


| INTRODUC TI ON
Behçet's disease is a chronic, recurrent, and auto-inflammatory multi-systemic disease that manifests with oral and genital aphthae, cutaneous lesions, and multiple systemic involvements. It is most often seen in young adults in the third and fourth decades and affects both genders equally. However, the clinical course in men is reported to be more serious. The onset of the disease before puberty and after the age of 50 is rare. 1 Behçet's disease is more common in countries located in the Mediterranean-especially in Turkey-Central Asia, and the Far East on the Silk Road in the northern hemisphere, such as Iran, Japan, China, and Korea, compared to Europe and North America. 2 Studies show that the highest prevalences are seen in Turkey (20-420/100000) and Iran (80/100000), followed by Saudi Arabia (20/100000), Iraq (17/100000), Italy (15.9/100000), and Israel (15.2/100000). 3 Although it is known that genetic and environmental factors are influential in the development of the disease, its etiology has not been fully elucidated. It is stated that the risk is increased in people with HLA-B51/B5, and genes related to Tumor Necrosis Factor (TNF), Heat Shock Proteins, Major Histocompatibility Complex class I (MHC-I) may also play a role as a genetic factor. 4 Infectious agents such as Streptococcus sangius, Herpes simplex virus type 1 (HSV-1), Staphylococcus aureus, and Prevotella species, and various environmental factors are stated to trigger the condition in genetically susceptible individuals. 1,4 Serum lipid levels are important in many disorders' current status and progression, especially in cardiovascular and cerebrovascular diseases. In addition, recent experimental studies indicate that lipid metabolism plays a decisive role in tumor proliferation and metastases in cancer. 5 In these diseases, most of which develop on the basis of atherosclerogenic plaque, chronic inflammation is thought to be effective in plaque formation and rupture. It is pointed out that in addition to classical markers such as CRP and ESR, IL-6, CXCL12 and hs-CRP can be used to define this inflammation in the laboratory. 6 Due to this situation, clinicians often evaluate and monitor the serum lipid values of their patients. The relationships between many auto-inflammatory diseases and serum lipid levels and atherogenic risk indexes obtained by using various serum lipid parameters have been started to be investigated in recent studies.
These indexes can be listed as the Atherogenic Index of Plasma (AIP), Castelli Risk Index I and II (CRI-I and II), and Atherogenic Coefficient (AC). 7,8 Previous studies mainly investigated the cardiovascular involvement of Behçet's Disease. 9,10 As far as we know, only one study has examined the relationship between AIP and sub-clinical atherosclerosis. 11 However, atherogenic indexes that determine the level of cardiovascular risk in Behçet's patients have not been investigated as a whole. This study aimed to evaluate the serum lipid parameters as a whole and the activity of atherogenic indexes such as AIP, CRI-I and II, and AC in patients with and without Behçet's disease and, therefore, the risk of cardiovascular events.

| Study design and sample
This study is a retrospective type case-control study. Case and control groups were formed among the patients with and without Behçet's Disease who applied to the dermatology outpatient clinic of a university hospital between 2016 and 2022. The study was carried out with 212 participants, including 106 patients in the case group and 106 individuals in the control group. The participants were over the age of 18 and did not have a significant difference in terms of age and gender. Exclusion criteria were determined as having metabolic disorders, alcoholism, pregnancy, use of oral contraceptives, being in the postmenopausal period, and taking lipid-lowering therapy. Ufuk

University Faculty of Medicine Non-interventional Clinical Research
Review Committee approved the study-Number: 12024861-95.

| Data collection and study parameters
Demographic and laboratory values of the patients were obtained from the database of the health center. Laboratory values included serum hemoglobin (g/dl), serum C-reactive protein (CRP) (mg/dl), erythrocyte sedimentation rate (ESR) (mm/h), serum cholesterol (mg/dl), serum triglyceride (mg/dl), serum HDL (mg/dl) and serum LDL (mg/dl) values. Serum hemoglobin values lower than 12 g/dl for women and 13 g/dl for men were used as cut-offs for the diagnosis of anemia. 12 Values of 10 mg/dl and above for CRP were considered high. 13 ESR value over 15 mm/h for men and over 20 mm/h for women aged 50 and under, over 20 mm/h for men, and over 30 mm/h for women over 50 was evaluated as high. 14 The following atherogenic indexes were calculated using these serum lipid values to assess the cardiovascular risk level. The atherogenic indexes in our study were calculated using the following formulas: • AC = Non-high-density lipoprotein cholesterol (NHC)/serum HDLc.
Based on previous studies, the cut-off values of atherogenic indexes were determined to assess the cardiovascular risk. AIP value < 0.1 was considered low, and ≥0.1 was regarded as high risk.

| Statistical analysis
Data in this study were analyzed using SPSS 20 (Statistical Package for Social Sciences). Descriptive statistics were given as numbers, percentages, mean and standard deviation. The t-test was used to evaluate the significance of continuous variables between the case and control groups. The Chi-square test was used for categorical variables. Risk estimates were used, and odds ratio and 95% CI were calculated. A value of p < 0.05 was considered significant.

| RE SULTS
A total of 212 people were included in the study, 106 of which constitute the case group and 106 of the control group. Case and control groups were matched for age and gender, and there was no significant difference between them. The characteristics of the study population are presented in Table 1.  Table 3 shows the atherogenic index findings of the case and control groups. Evaluated as atherogenic risk indexes; AIP, CRI-I, CRI-II and AC were found to be significantly higher in Behçet's patients than in the control group.
According to the accepted cut-off values, atherogenic index values were grouped as high and low risk, and the difference between the case and control groups is shown in Table 4  times for AIP, 9.61 times for CRI-I, 6.39 times for CRI-II and 9.62 times for AC. It is known that there is a strong relationship between atherogenic indices and coronary artery disease. In a prospective study conducted with 2676 middle-aged people in Turkey over a period of 8 years, AIP was found to be a strong risk factor for coronary artery disease. 26 In another study coronary atherosclerosis was detected with multislice computed tomography and CRI-I was found to reflect coronary plaque formation and intima thickness in young adults. 27  Our study shows that patients with Behçet's have a higher proatherogenic lipid profile and high-risk atherogenic indexes. They are at increased risk of developing cardiovascular diseases associated with atherosclerosis. To prevent morbidity and mortality that may develop, patients exposed to Behçet's disease for an extended period should be followed up more closely clinically regarding cardiovascular disease risk.

AUTH O R CO NTR I B UTI O N S
OA, GAS, HA designed the research study. GAS, DDR collected data.
OA analyzed the data. OA, GAS, DDR, HA wrote the paper.

FU N D I N G I N FO R M ATI O N
No funding was used for this study.

CO N FLI C T O F I NTE R E S T
No conflict of interest.

DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of this study are available from the corresponding author upon reasonable request.

E TH I C A L A PPROVA L
It was approved from Ufuk University Faculty of Medicine