Relationship between plasma atherogenic index and xanthelasma palpebrarum

ABSTRACT


INTRODUCTION
Xanthelasma is a common form of skin xanthoma, characterized by yellowish plaques, and generally occurs on the upper eyelid (xanthelasma palpebrarum / XP).It is due to abnormal lipid deposition in the eyelid skin. 1,2In the world, the incidence is 0.56-1.5%,with the age of onset 15-73 years.Most cases occur in the fourth and fifth decades of life, with most cases in women. 3,4In Padang from 2013-2017, as many as ten new xanthelasma patients, with two male patients and eight female patients. 57][8] Xanthelasma is thought to be a sign of dyslipidemia, one of the important risk factors in developing atherosclerotic cardiovascular disease.Xanthelasmata can be found in soft, semisolid, or calcareous forms.Generally, xanthemata appear bilaterally and involve the entire eyelid.Progressive xanthelasmata tend to coalesce and become permanent.Xanthelasmata represent lipid areas containing macrophages, but their pathogenesis is still not fully understood. 9ther article showed that xanthelasma and atherogenic formation correlated with the same mechanism, namely upregulation of T cells, macrophages, and the inflammatory mediator iNOS, COX, and this mechanism was also found in the early stages of atherosclerotic plaque formation. 10e risk of atherosclerotic disease can be determined by using the atherogenic index of plasma (AIP) parameters obtained by looking at the triglyceride (TG) and high-density lipid (HDL) profiles.Xanthelasma is a marker of dyslipidemia, a major factor causing cardiovascular disease and is often assessed from the lipid profile level.

ORIGINAL ARTICLE
age, lipid profile values (cholesterol, HDL, LDL, and Triglycerides), and Atherogenic Index of Plasma (AIP) values.Laboratory tests measured assessment atherogenic index of plasma to determine levels of triglycerides (TG) and high-density lipids (HDL) using the Cobas 6000 C501 device.The formula to calculate the AIP was log (TG/HDL-C).
The results were analyzed by descriptive analysis, and an independent t-test was performed to assess the relationship between the research variables, which were declared significant with p < 0.001.

RESULTS
In this study, the dominant female sex characteristics in xanthelasma palpebrarum subjects were 47 people (94%), and subjects aged 50-59 years dominated the xanthelasma palpebrarum group as many as 21 people (42%).Characteristics by sex and age are described in Table 1.
Based on cholesterol levels, the mean value of total cholesterol in the subjects with xanthelasma palpebrarum with an average of 220.63 mg/dL.Based on HDL levels, the mean HDL value in the group of subjects with xanthelasma palpebrarum was 49.41 mg/dL.Based on LDL levels, the mean LDL value in the group of subjects with xanthelasma palpebrarum was 168.28 mg/dL.Based on triglyceride levels, the mean value of the group of subjects with xanthelasma palpebrarum was seen with an average of 204.25 mg/dL.The lipid profile values of the subjects are depicted in Table 2.
The results of the categorization of an atherogenic index of plasma values in this study showed that in the group of subjects with xanthelasma palpebrarum, the highest proportion was subjects with an atherogenic index of plasma values > 0.21 (high risk) with a total of 27 people (54%).In the control group, the highest proportion of subjects was with an atherogenic index of plasma value also found hyperlipidemia with high triglyceride values by 45 (55.6%) and low HDL values in both xanthelasma patients and controls. 18The Atherogenic index of plasma which is a specific predictor to assess the risk of atherosclerosis, is supported by several studies such as Onat et al., who concluded that high AIP is associated with cardiometabolic disorders. 13 Karniawati et al. showed that an increase in the AIP value had a 4.472 times greater risk for atherosclerosis. 14Based on the description of the background above, the atherogenic index of plasma makes it easier to predict the risk of atherosclerosis by looking at TG and HDL levels, especially in xanthelasma palpebrarum patients.It has prompted research on the relationship between plasma atherogenic index and xanthelasma palpebrarum.

METHOD
This study is an observational analytic study with a cross-sectional approach consisting of 50 patients with xanthelasma palpebrarum and 50 controls aged 20 years at the Dermatology and Venereology Polyclinic, Universitas Sumatera Utara Hospital.Each research subject has signed informed consent in this study.Exclusion criteria were subjects diagnosed with cardiovascular disease based on anamnesis and who had consumed certain drugs for a maximum of the last one month, as well as xanthelasma palpebrarum subjects who were pregnant or pregnant or breastfeeding. This

ORIGINAL ARTICLE
<0.11 (low risk) with a total of 36 people (72%).The atherogenic index of plasma values is shown in Table 3 and Figure 1.
The results obtained using logistic regression showed a significant relationship between the atherogenic index of plasma values and xanthelasma palpebrarum (p < 0.001).The OR value obtained was 7.714 (95% CI 2.822 -21.087), which means that subjects who have an IAP > 0.21 (high risk) have a risk of experiencing xanthelasma palpebrarum by 7.714 times greater than subjects who have an IAP < 0.11 (low risk).Subjects with IAP between 0.11 -0.21 were not significantly associated with palpebral xanthelasma when compared with subjects with IAP < 0.11 (p = 0.585).

DISCUSSION
Subjects with dominant female sex on xanthelasma palpebrarum subjects were 47 people (94%).It is in line with a study conducted by Gondane in 2020, which found the highest prevalence of xanthelasma palpebrarum was in women (82.2%) compared to men (17.8%). 19The same thing was also found in a study conducted by Ghimire in 2017; the prevalence of xanthelasma palpebrarum was the highest in women (78.6%). 20Research conducted by Chaudhary also found that xanthelasma palpebrarum was most common in women (81%).It can be caused because women pay more attention to the cosmetic side than men. 21bjects aged 50-59 years were dominant in the xanthelasma palpebrarum group as many as 21 people (42%).It is in line with the research conducted by Gondane.The results showed that the age group with the highest prevalence of xanthelasma palpebrarum was the 40-50 year age group (33%).The study did not find a significant difference between the two groups based on age with a p-value = 0.6299.Xanthelasma formation begins with increased local extravasation of lipids through the vascular wall into the interstitial spaces of connective tissue.The accumulation of monocytes and macrophages is taken up by lipid particles (specific receptors) to phagocytize LDL and lipid aggregation complexes with antibodies; then foam cells are formed.Lipoproteins do not induce cell formation directly.Intracellular LDL catabolism by LDL receptors is slow, and cholesterol homeostasis is effectively regulated.Free cholesterol is released from LDL after internalization, which inhibits its synthesis.In addition, free cholesterol inhibits the synthesis of LDL receptors, thereby reducing the endocytosis of LDL by cells. 22ased on LDL levels, the mean LDL value in the group of subjects with xanthelasma palpebrarum was 168.28 mg/dL.Research conducted by Gondane found an increase in LDL values in 52 cases (71.2%) with a mean value of 137.3 mg/dL. 19Research conducted by Chaudhary also obtained similar results with LDL values in the xanthelasma palpebrarum group of 135.2 mg/dL. 21Research conducted by Sankar also found a significantly increased LDL cholesterol value in 82% of cases. 23ccording to the HDL levels, the mean HDL value in subjects with xanthelasma palpebrarum was 49.41 mg/dL.Research conducted by Chaudhary found that the mean HDL value in the case group was 41.7 mg/dL. 21In Gondane's study, HDL levels decreased in 34 cases (46.6%) with a mean HDL value of 41.33 mg/dL. 19The results of Kavoussi et al. 's study also found something similar with the HDL value in the case group of 36.2 mg/dL. 6Low HDL cholesterol levels are also another factor that plays a role in the pathogenesis of xanthelasma palpebrarum.It is because HDL can get rid of excess cholesterol in the tissues and low levels indicate a malfunction.
Cholesterol levels also change.The mean value of total cholesterol in the group of subjects with xanthelasma palpebrarum with an average of 220.63 mg/dL, Gondane et al. report an enhancement of total cholesterol in most cases (46 cases or 63.01%), with the average total cholesterol value being 212.6 mg/dL. 19Several research also found similar findings, such as research conducted by Chaudhary with the mean cholesterol value in the case group of 218.5 mg/dl. 21The same thing was also found in a study conducted by Kavoussi et al., which found the total cholesterol value in patients was 221.51 mg/dL. 6Research conducted by Sankar in 2015 also found a significant increase in total cholesterol in xanthelasma palpebrarum patients with p = 0.009. 23Thus, we can conclude that xanthelasma palpebrarum could be a sign of enhancement of cholesterol level.
In addition, another lipid that changed besides HDL, LDL, and cholesterol was triglyceride levels; the mean value of the group of subjects with xanthelasma palpebrarum was seen with an average of 204.25 mg/dL.It is in line with Gondane's study with an increase in triglyceride values in 29 cases (39.7%) with an average triglyceride value of 152.29 mg/ dL. 19Research conducted by Chaudhary found triglyceride values of 171.4 mg/dL in the group of xanthelasma palpebrarum cases. 21Research by Kavoussi et al. found the mean triglyceride value of 185.98 mg/ dL. 6he OR value obtained was 7.714 (95% CI 2.822 -21.087), which means that subjects who have an IAP > 0.21 (high risk) are at risk of experiencing xanthelasma palpebrarum by 7.714 times greater than subjects who have an AIP < 0.11 (low risk).Subjects with IAP between 0.11 -0.21 were not significantly associated with palpebral xanthelasma when compared with subjects with AIP < 0.11 (p = 0.585).A study conducted by Dey stated that patients with xanthelasma palpebrarum had a significantly higher thickness of the carotid intima-media because there was a significant increase in atherogenic apolipoproteins in xanthelasma palpebrarum patients, as well as an increase in mean serum cholesterol, LDL cholesterol, and triglycerides.The researchers concluded that patients with xanthelasma palpebrarum with any lesion size and serum lipid value should be screened for carotid intima-media thickness screening for early detection of subclinical atherosclerosis. 9The limitation of this study was only conducted in one center, did not assess a grading of xanthelasma, other factors that contribute to xanthelasma formation.

CONCLUSION
There is a relationship between the atherogenic index of plasma and xanthelasma palpebrarum.Based on an atherogenic index of plasma values in the group of subjects with xanthelasma palpebrarum, the highest proportion were subjects with an atherogenic index of plasma values > 0.21 (high risk) and 7.714 times greater risk of experiencing xanthelasma palpebrarum than subjects with AIP < 0.11 (risk of low).

Figure 1 .
Figure 1.Histogram graph of differences in the proportion of atherogenic index of plasma values between the xanthelasma palpebrarum subject and the control groups.

7,13-18 This
17 in line with the research finding that hyperlipidemia significantly increased in XP patients in as many as 64 cases and controls in 40 cases where (p = 0.001) and triglyceride values.17Sumanet al.