Xanthelasma is not associated with increased risk
of carotid atherosclerosis in normolipidaemia
C.-C. Chan,
1,2,3* S.-J. Lin,
1,3* J.-J. Hwang,
4,5C.-C. Sun,
1J.-S. Jeng,
6B.-S. Hwang,
6H.-C. Chiu,
1M.-F. Chen,
5C.-S. Liau,
5H.-J. Hsu,
7T.-C. Su
5,8Introduction
Xanthelasma palpebrarum, or simply xanthelasma, is a commonly encountered cutaneous xanthoma with an unknown aetiology (1,2). They are diagnosed clin-ically with the presentation of oval or elongated
yel-lowish plaques just beneath the skin of the
periorbital region. Most commonly, they are noted near the inner canthus of the upper eyelid. About half of xanthelasma patients have been reported to have hyperlipidaemia (2), which is well known as a contributing factor of atherosclerotic vascular disease. Nevertheless, most patients, as well as medical doc-tors, put a value on cosmetic consultation without interest in the possible underlying disorders. Consid-ering the possible clinical applications in preventive
cardiology, the stigmata of xanthelasma could
become a useful sign if it is significantly associated
with serum lipids, systemic atherosclerosis or other risk factors of major cardiovascular diseases (CVD).
Cardiovascular disease and stroke have been ranked among the leading causes of death in the past decades in the USA, Western world and also in Tai-wan (3). Bodies of evidence support the importance of early detection of atherosclerosis and its associated risk factors in the prevention and treatment of ath-erosclerotic diseases. Common carotid artery (CCA), intima-media thickness (IMT) and extracranial caro-tid arteries (ECCA) atherosclerosis have been shown as having a significant association with cardiovascular risk factors, CVD and stroke (4–7). Measuring caro-tid atherosclerosis (CA) by ultrasound has been widely used for its simple and reliable detection of early preclinical atherosclerosis and for its high cor-relation between measured IMT and actual patholog-ical changes (8,9).
Linked Comment: Crook. Int J Clin Pract 2008; 62: 178–9.
S U M M A R Y
Objectives: Extracranial carotid artery (ECCA) atherosclerosis is well known to be associated with cardiovascular diseases. This study aims to investigate the differ-ence of ECCA atherosclerosis between patients with xanthelasma and control sub-jects in normolipidaemia. Methods: Carotid atherosclerosis (CA) of 41 (8 males and 33 females) patients with xanthelasma and normolipidaemia, defined as levels of cholesterol below 6.21 mmol/l and triglyceride below 2.26 mmol/l, recruited from Department of Dermatology was compared with that of 85 age- and gender-matched control subjects. The extent and severity of CA were measured by high-resolution B-mode ultrasound and expressed as the mean intima-media thickness (IMT) of the common carotid artery (CCA) and ECCA plaque score. Mixed-effects model and multivariate logistic regression analyses were used to estimate the association between xanthelasma and CA. Results: Patients with xanthelasma showed significantly higher levels of low-density lipoprotein cholesterol (LDL-C) lev-els and higher body mass index (BMI) compared with the control group. Mixed models identified age, male gender, smoking and subjects of hypertension with medication, but not the presence of xanthelasma, were associated with an increase of CCA IMT. Multivariate logistic regression analysis revealed subjects of male gen-der, and hypertension with medication, but not the presence of xanthelasma, asso-ciated with thicker IMT, defined as IMT‡ 75th percentile, or ECCA plaque score ‡ 3. Conclusions: Normolipidaemia with xanthelasma is not significantly associ-ated with CA, but did relate with adverse cardiovascular profiles, such as higher BMI, waist circumference and LDL-C levels.
What’s known
Xanthelasma associates with hyperlipidaemia. Hyperlipidaemia increases atherosclerosis. However, there is limited information regarding xanthelasma and cardiovascular disease.
What’s new
Subjects of normolipidaemia with xanthelasma are not significantly associated with carotid atherosclerosis, but did relate with adverse cardiovascular profiles, such as higher BMI, waist circumference and LDL-C levels.
1Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
2Department of Dermatology, Yu-Lin Branch of National Taiwan University Hospital, Douliu, Yulin, Taiwan 3Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan 4Department of Internal Medicine, Yu-Lin Branch of National Taiwan University Hospital, Douliu, Yu-Lin, Taiwan 5Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
6Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan 7Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
8Department of Environmental and Occupational Medicine, National Taiwan University Hospital, Taipei, Taiwan Correspondence to: Ta-Chen Su, MD, PhD, Departments of Internal Medicine, and Environmental and Occupational Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Chung-Shan S. Road, Taipei, Taiwan Tel.: + 886 2 23123456 (ext. 6719) Fax: + 886 23712361 Email: [email protected] Disclosures
The authors have declared that they have no interests which might be perceived as posing a conflict or bias.
*These two authors contributed equally to this work.
As the association between xanthelasmas and CVD is still controversial (1,2,10–12), conducting a study to evaluate the relationship between this particular sign and the well-accepted surrogate outcome of CVD by CA seems to be valuable in a clinical setting. Because hyperlipidaemia, defined as cholesterol level ‡ 6.21 mmol/l (240 mg/dl) or triglyceride levels ‡ 2.26 mmol/l (200 mg/dl), has been well known to increase the risk of atherosclerosis. In this study, we used high-resolution carotid ultrasound to evaluate the ECCA atherosclerosis and IMT in patients of xanthelasma with normolipidaemia after controlling potential associated factors. Unlike most studies of xanthelasma and its association with major CVD (1,10–12), our cases were recruited from a general dermatology clinic rather than referrals from cardio-vascular units. We investigated whether xanthelasmas provides suitable information to associate with sub-clinical atherosclerosis, as indexes by CA.
Subjects and methods
Study subjectsFrom 2001 through 2002, 63 (9 men and 54 women) consecutive patients diagnosed as xanthelasma palpe-brarum were enrolled from a general dermatology
clinic of National Taiwan University Hospital
(NTUH). One hundred and twenty age- and gender-matched controls without xanthelasma (22 men and 98 women) were randomly recruited from subjects receiving physical examination during the same per-iod in NTUH. Among 63 with xanthelasma palpe-brarum, 41 (8 men and 33 women) patients were diagnosed as normolipidaemia, defined as levels of cholesterol below 6.21 mmol/l and triglyceride below 2.26 mmol/l. And, of the 120 age- and gender-matched controls, 85 (17 men and 68 women)
ful-filled the criteria of normolipidaemia. Written
informed consent was obtained from all participants. The study has been approved by the Ethics Commit-tee of the Institutional Review Board of NTUH. Assessment of cardiovascular risk factors Blood pressure measurements were measured by a mercury sphygmomanometer in a standardised fash-ion, cuff size adjusted to the girth of the arm. Sub-jects with systolic blood pressure higher than 140 mmHg and/or diastolic blood pressure higher than 90 mmHg, receiving antihypertensive medica-tion (HTN-med), were considered hypertensive. Pre-valent diabetes mellitus (DM) was defined as fasting glucose ‡ 6.99 mmol/l and/or a history of DM with management. Patients with poor control of DM (HbA1c > 7.0%) were excluded. All participants did not have cholestasis, nephrotic syndrome or
signifi-cant evidence of familial hyperlipidaemia. Patients with cholesterol levels ‡ 6.21 mmol/l or triglyceride ‡ 2.26 mmol/l or on lipid-lowering agents were defined as hyperlipidaemia according to the criteria of the National Cholesterol Educational Program Adult Treatment Panel III (13). Body mass index (BMI) was computed from the subject’s weight (in kilograms) over the square of height (in metres). We obtained data on smoking and alcohol drinking from a detailed chart review and a self-reported question-naire for each patient.
As xanthelasma palpebrarum is a clinically diag-nosed disease characterised by the presence of yellow, soft and either macular or slightly elevated plaques on the periocular skin, numbers and locations of xanthelasma palpebrarum were recorded on inspec-tion by the same dermatologist in our study. The extent of xanthelasma status was arbitrarily classified into three categories: one single and xanthelasma size
smaller than 2 cm2, two or xanthelasma size over
2 cm2, and three or more or xanthelasma area over
3 cm2.
Overnight fasting (> 12 h) blood samples were collected for measurements of glucose, total choles-terol, high-density lipoprotein cholesterol and triglyc-eride by standard enzymatic methods with an automatic multichannel chemical analyser (Hitachi 7450, Hitachi Corp., Tokyo, Japan) in the central laboratory of NTUH. Low-density lipoprotein choles-terol (LDL-C) was calculated by Friedewald’s formula if their triglyceride levels < 4.52 mmol/l. If subjects’ triglyceride levels ‡ 4.52 mmol/l, LDL were measured directly by enzymatic method with automatic chemi-cal analyser.
ECCA ultrasonographic measurement
A Hewlett-Packard SONO 4500 ultrasound system (Andover, MA), equipped with a 3–11 MHz real-time B-mode scanner, was used for evaluation. Caro-tid end-organ disease was assessed by maximal IMT at carotid arteries and by ECCA plaque score. The measurement protocol for CA assessment has been described previously (4,5,14–18). The interobserver and intra-observer correlation coefficients were high (0.86–0.93 and 0.70–0.87 respectively) for both sides of CCA IMT measurements (16). Maximal IMT on the CCA proximal to the carotid bifurcation was obtained bilaterally. CCA1 and CCA2 are points located 0–1 and 1–2 cm, respectively, on the CCA distal from the carotid bifurcation. IMT of the pos-terior wall of the distal CCA was measured as the distance from the leading edge of the first echogenic line (interface between lumen and vascular intima) to the leading edge of the second line (interface between vascular media and adventitia). All the
caro-tid ultrasound examinations were performed by a experienced ultrasonographer (Hwang BS) and she was not aware of the health status and risk factors of the study individuals. For future and subsequent off-line analysis, all scans were recorded on super-Video Home System (VHS) videotape.
The plaque scoring quantified method has been described previously (4,5,14–18). To summarise briefly, a focal thickening of IMT with > 50% of thickness than the adjacent IMT was considered as an atherosclerotic plaque. A grade was assigned for each chosen segment: grade 0 for normal or no observable plaque, grade 1 for one small plaque with a diameter stenosis < 30%, grade 2 for one medium plaque with a 30–49% diameter stenosis or multiple small plaques, grade 3 for one large plaque with a 50–99% diameter stenosis or multiple plaques with at least one medium plaque and grade 4 for 100% occlusion. Carotid artery segments, including the proximal and distal CCA (> 20 and 0–20 mm distal to the bulb bifurcation respectively), bulb, internal carotid artery and external carotid artery, were exam-ined bilaterally. The plaque score was calculated by summing the plaque grades at 10 segments of the ECCA. Reproducibility of the plaque grade scoring showed a good agreement with a kappa value of 0.70 (17).
Statistical analyses
Clinical features and cardiovascular risk factors of the study subjects were first compared by xanthel-asma status, i.e. between patients with xanthelxanthel-asma and controls, including all subjects and those sub-groups of excluding of hyperlipidaemia respectively. Continuous variables were expressed as the mean ± 1 standard deviation. A t-test was used to make com-parisons between these groups. For categorical data, a chi-squared test was used to test for the signifi-cance level between the two groups. The average CCA IMT measurements at CCA1 and CCA2 on both sides, and ECCA plaques were compared sepa-rately by xanthelasma and control groups, and the groups of extent of xanthelasma status.
The determinants of IMT (four measurements at different locations) of CCA were analysed by
con-structing mixed-effect regression models. The
strength of associations between CA and xanthelasma and other potential risk factors was measured in terms of an odds ratio in the 95% confidence inter-val by using multivariate logistic regression analysis. A mean value of CCA IMT at or above the 75th per-centile or ECCA score ‡ 3 was regarded as an indica-tor of significant CA. The statistical significance levels of alpha and beta were set at 5% and 20% respectively. Data analysis was performed with SAS
statistical software (version 8.2, SAS Institute Inc., Cary, NC).
Results
Table 1 shows the clinical features and cardiovascular risk factors between patients with xanthelasma and controls. No significant differences in the distribu-tions of gender, age, and hypertension status, levels of blood pressure, prevalence of diabetes, and life-styles were found between xanthelasma patients and control subjects. In comparison with control subjects, patients with xanthelasma had significantly higher levels of LDL-C, fasting glucose, waist circumference and higher average BMI (p < 0.05). After excluding subjects with hypercholesterolaemia and hypertrigly-ceridaemia, the difference of cholesterol levels is dis-appeared; however, the levels of LDL-C, BMI and waist circumference are still higher and a trend of higher glucose levels in patients with xanthelasma.
In Table 2, the average IMT measurements at dif-ferent carotid locations were not significantly higher in patients with xanthelasma. There was no signifi-cant difference of ECCA score and the percentage with ECCA plaque between those patients with xan-thelasma and control subjects. The number of the xanthelasma plaques and its association to carotid IMT and ECCA scores and plaque showed no signifi-cant difference, as shown in Table 3.
Mixed-effects model identified age, male gender, HTN-med and current smoking, but not the pres-ence of xanthelasma, independent determinants of CCA IMT (Table 4). Subjects with DM and who had higher BMI or higher LDL-C had no significant asso-ciation with CCA IMT. In Table 5, multivariate logistic regression models revealed that subjects with HTN-med and older age significantly increased the risk of thicker IMT. The risk of an ECCA plaque score ‡ 3 increased significantly in conjunction with subjects with HTN-med and male gender. However, xanthelasma was not a determinant for significant CA, indexes by thicker IMT or ECCA plaque score ‡ 3.
Discussion
This study is the first to demonstrate that normolip-idaemia with xanthelasma is not significantly associ-ated with subclinical atherosclerosis, in terms of CA. Subjects with HTN-med, male gender, older age and current smoking habit would have a higher CCA IMT. HTN-med and male gender were two impor-tant factors associated with a significant ECCA pla-que scores. In this study, we found the number of xanthelasma was not related to thicker IMT at CCA,
as well as higher ECCA plaque scores. The findings of the lack of relationship between the extent of xan-thelasma and CA also supported that the presence of xanthelasma may not be at increased risk for athero-sclerosis in normolipidaemia. However, the subjects
of normolipidaemia with xanthelasma are related with adverse cardiovascular profiles, such as higher BMI, higher levels of LDL-C and glucose.
As in our previous studies, hypertension or hyper-tension with medication have been demonstrated as the major determinants of CCA IMT and significant CA (4,14,18). As our previous study (14), this study also applied a mixed regression model to associate multiple carotid IMT measures as repeated measure-ments with its risk factors, while previous studies have taken, on the whole, the average value of repeated IMT measurements (4–7). The rational use of mixed models assumes that repeated measure-ments have a random effect, which corresponds more to the bilateral measurements of IMT at a fixed specific segment for each subject. Statistically, it is generally more efficient than simply taking the mean and can possibly improve the detection power of limited study subjects. Furthermore, multivariate logistic regression analysis identified the similar risk factors (age and HTN-med) for a thicker IMT, and male gender and HTN-med for a significant ECCA plaque score.
Xanthelasma palpebrarum and its clinically signifi-cant association with hyperlipidaemia, along with impacts on atherosclerotic risk factors, have been
widely discussed (1,2,10–12,19–22). Bergman
authored two great reviews with regard to both clini-cal aspects, and ascribing the pathogenesis of this Table 1Basic characteristics of xanthelasma and matched control subjects
Characteristics Xanthelasma (n = 63) Control subjects (n = 120) p-value Xanthelasma with normolipidaemia (n = 41)
Control subjects with
normolipidaemia (n = 85) p-value Age, years 50.78 (11.51) 50.06 (10.41) 0.777 52.49 (10.85) 51.22 (9.76) 0.513 Male 14.29% 18.33% 0.488 19.73% 21.18% 0.829 HTN 22.22% 16.67% 0.359 24.39% 16.47% 0.289 HTN-Med 17.46% 13.33% 0.455 19.51% 12.94% 0.334 SBP, mmHg 122.23 (23.29) 116.75 (17.00) 0.106 120.54 (17.07) 115.55 (15.43) 0.109 DBP, mmHg 73.36 (14.10) 74.452 (10.41) 0.593 71.95 (11.28) 73.26 (10.39) 0.527 DM 7.94% 3.33% 0.111 9.76% 3.53% 0.153 Glu, mmol/l 5.74 (1.78) 5.22 (0.54) 0.027 5.70 (1.66) 5.22 (0.57) 0.080 Smoking 17.46% 18.33% 0.884 17.07% 17.65% 0.937 Alcohol 6.35% 5.83% 0.249 7.32% 5.88% 0.757 CHO, mmol/l 6.02 (1.82) 5.29 (0.77) 0.003 5.13 (0.63) 4.99 (0.65) 0.279 LDL, mmol/l 3.81 (1.40) 3.00 (0.70) < 0.000 3.24 (0.61) 2.81 (0.65) 0.001 HDL, mmol/l 1.34 (0.36) 1.42 (0.34) 0.132 1.33 (0.30) 1.39 (0.34) 0.293 TG*, mmol/l 1.12 (0.43–5.08) 1.04 (0.35–4.99) 0.266 1.03 (0.43–2.25) 0.98 (0.35–2.15) 0.450 BMI, kg/m2 24.68 (4.40) 23.05 (2.90) 0.010 24.50 (3.17) 23.12 (2.94) 0.018 Waist, cm 81.43 (10.33) 77.85 (8.79) 0.021 83.78 (9.80) 78.02 (9.19) 0.002
HTN, hypertension; HTN-Med, on antihypertensive medication; SBP and DBP, systolic and diastolic blood pressure; DM, diabetes mellitus; Glu, glucose; CHO, choles-terol; LDL and HDL, low-density and high-density lipoprotein cholescholes-terol; TG, triglyceride; BMI, body mass index. *Levels of TG were expressed as median (minimum– maximum) and analysed by two-sample paired (Wilcoxon) signed rank test.
Table 2Measurements of common carotid artery (CCA), intima-media thickness (IMT) in different locations and extracranial carotid artery (ECCA) plaque scores, by xanthelasma status
Xanthelasma (n = 41) Control (n = 85) p-value IMT Rt CCA1, mm 0.63 (0.17) 0.64 (0.13) 0.683 Rt CCA2, mm 0.59 (0.14) 0.61 (0.12) 0.587 Rt CCA, mm 0.61 (0.15) 0.63 (0.11) 0.629 Lt CCA1, mm 0.65 (0.23) 0.64 (0.14) 0.817 Lt CCA2, mm 0.64 (0.17) 0.63 (0.12) 0.915 Lt CCA, mm 0.64 (0.19) 0.64 (0.12) 0.854 CCA, mm 0.63 (0.16) 0.63 (0.11) 0.907 *ECCA score 1.00 (2.19) 0.73 (1.29) 0.909 *ECCA plaque 34.15% 34.12% 0.998 Values in IMT are mean ± SD mm. CCA indicates mean IMT of both RCCA and LCCA. Values in ECCA score are average plaque score (mean ± SD). Values in ECCA plaque are per cent, showing the prevalence of ECCA plaque. *Two-sample paired (Wilcoxon) signed rank test.
particular skin presentation of xanthelasma, conclud-ing that clinical value still could not be drawn as most investigators fail to demonstrate a study with appropriate control groups or are limited by small numbers of participants (1,2). Another important factor is due to biased patient selection, as most of the patients are collected from those who are visiting a cardiologist or had been sent for a cardiac evalua-tion, reflecting that these populations are predisposed to an association with cardiovascular morbidity and mortality (1,2,12,22).
To prevent similar limitations, our study chose xanthelasma patients from a dermatology outpatient clinic and excluded subjects of hyperlipidaemia,
which was the major confounding factor that associ-ated with atherosclerosis. Patients who visited for cosmetic consultation were less likely to be influ-enced by predisposing underlying cardiovascular
dis-orders and were more likely to show their
representatives among the general population. The control subjects were randomly selected from people visiting for a health examination and work-site health promotion programme during the same period.
Table 3Extents of xanthelasma and common carotid artery (CCA) intima-media thickness (IMT) and extracranial carotid artery (ECCA) plaque scores
Numbers of xanthelasma
p-value, v2for trend
1 2 ‡ 3 n = 6 n = 24 n = 11 IMT RCCA1, mm 0.71 (0.14) 0.62 (0.14) 0.60 (0.24) 0.4098 RCCA2, mm 0.66 (0.11) 0.60 (0.14) 0.53 (0.12) 0.1637 RCCA, mm 0.68 (0.11) 0.61 (0.14) 0.57 (0.18) 0.2846 LCCA1, mm 0.75 (0.20) 0.63 (0.12) 0.63 (0.39) 0.5123 LCCA2, mm 0.72 (0.18) 0.64 (0.13) 0.58 (0.24) 0.2562 LCCA, mm 0.74 (0.19) 0.64 (0.12) 0.61 (0.31) 0.4148 CCA, mm 0.71 (0.14) 0.62 (0.12) 0.59 (0.23) 0.3094 ECCA score 1.17 (1.47) 0.46 (0.93) 2.09 (3.75) 0.1197 ECCA plaque 50.00% 29.17% 36.36% 0.3684
Values in IMT are mean ± SD mm. RCCA indicates mean IMT of both RCCA1 and RCCA2; LCCA indicates mean IMT of both LCCA1 and LCCA2. Values in ECCA score are average plaque score. Values in ECCA plaque are per cent, showing the prevalence rate of ECCA plaque.
Table 4Determinants of common carotid artery intima-media thickness by mixed-effects model
Characteristics b(SE) mm Intercept 0.57 (0.07)à Age, years, 10)2 0.44 (0.21)* Male gender 0.05 (0.02) Systolic BP, mmHg, 10)2 0.00 (0.04) Antihypertensive medication 0.06 (0.02) Diabetes mellitus 0.00 (0.03) Smoking, current 0.06 (0.02)
Body mass index, kg/m2 0.02 (0.02) LDL-cholesterol, mmol/l )0.01 (0.01)
Xanthelasma, 10)2 1.21 (1.30)
AIC )596.0
p-value: *< 0.05, < 0.01, à< 0.005. AIC, Akaike’s informa-tion criterion; LDL, low-density lipoprotein; BP, blood pressure.
Table 5Multivariate logistic regression models for carotid atherosclerosis Characteristics IMT‡ 75th percentile OR (95% CI) ECCA score‡ 3 OR (95% CI) Age, years 1.05 (1.00–1.12)* 1.04 (0.94–1.16) Male gender 1.83 (0.56–5.98) 10.81 (1.76–66.31) Systolic BP, mmHg 1.01 (0.98–1.05) 1.01 (0.95–1.07) Antihypertensive medication 4.67 (1.18–18.47)* 9.83 (1.32–73.13)* Diabetes mellitus 0.35 (0.03–3.68) 0.69 (0.03–17.10) Smoking, current 2.98 (0.90–9.90) 4.01 (0.62–26.15) Body mass index,
kg/m2
0.89 (0.74–1.07) 0.85 (0.62–1.16) LDL-cholesterol, mmol/l0.97 (0.45–2.11) 3.33 (0.65–16.97) Xanthelasma 1.14 (0.37–3.49) 1.23 (0.17–8.72) Values are given as odds ratios (OR) (95% confidence inter-vals, CI). p-value: *< 0.05, < 0.01. LDL, low-density lipopro-tein; IMT, intima-media thickness; ECCA, extracranial carotid artery; BP, blood pressure.
Compared with the control group, subjects with xanthelasma have significantly higher levels of fasting glucose, serum LDL-C and BMI, which indicates
some biological differences between these two
groups. Elevated serum LDL-C in xanthelasma patients has been reported before (10,11,20,21). However, in this study, we are the first to report the elevated serum glucose level and higher BMI in sub-jects with xanthelasma. Higher levels of LDL and fasting glucose have been well documented as major cardiovascular risk factors (13). Obesity also was considered as a major cardiovascular risk factor by the American Heart Association (23). Although we did not show significant effects of these metabolic factors in the multivariate regression models in this study, the combination of poor metabolic profiles, higher levels of LDL, glucose and BMI in patients with xanthelasma, might contribute to adverse car-diovascular effects in the future.
This study is limited by its cross-sectional design. The fewer male participants in this study also indi-cated the cosmetic preference of women seeking for help in dermatologic clinic; however, may limit the gender inference. Although the data analysis failed to demonstrate a direct effect by xanthelasma to significant CA, other cardiovascular risk factors (age, male gender, HTN-med and smoking status) were significantly correlated with CCA IMT, and HTN-med and male gender associated with ECCA plaque score in this study, which were well in line with previous studies (4,5,13,17), which corrobo-rated this study. This indicates that our design in elucidating the association between xanthelasma and atherosclerosis, although not significant enough to draw a conclusion, deserves our greater concern. Even though some traditional risk factors have been identified in association with xanthelasma in this study, conducting further study in genetic polymor-phism for apolipoprotein E, B and other candidate genes might be necessary to answer the presentation of xanthelasma in some particular patients. All patients with xanthelasma should be reminded of the importance of regular checkup for blood choles-terol and receive HTN-med if with hypertension, and stop of smoking habit, which all have positive impacts in the emergence of atherosclerosis and long-term adverse effects on cardiovascular morbid-ity and mortalmorbid-ity.
Acknowledgement
This work was partly supported by the grants from National Science Council, Taiwan (NSC94-2314-002-300) and National Taiwan University Hospital (91– S062).
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