Plaque occurring around the eyelids may offer clinicians a new way of identifying patients at an increased risk for myocardial infarction and severe atherosclerosis, a study has shown.
"The results from this study suggest that xanthelasmata are a cutaneous marker of atherosclerosis independent of lipid concentrations and thus should be considered in clinical practice as an independent and additional risk factor for myocardial infarction and ischemic heart disease," Mette Christoffersen and her coinvestigators wrote in a study published online (BMJ 2011;343:d5497).
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Xanthelasmata and arcus corneae may be markers of proatherogenic changes in the vessels and thus markers of atherosclerosis.
The presence of xanthelasmata predicted MI (hazard ratio, 1.48); ischemic heart disease (HR, 1.39); severe atherosclerosis determined by ankle brachial index (HR, 1.69); and death (HR, 1.14), in a Danish population-based study of 12,745 patients. However, on multifactorial adjustment for arcus corneae, no hazard ratios remained significant. The presence of both xanthelasmata and arcus corneae significantly increased the risk of ischemic heart disease (HR, 1.56) but not any other outcomes after multifactorial adjustment.
Xanthelasmata palpebrarum are sharply demarcated, yellowish flat plaques that appear on the upper or lower eyelids, most often near the inner canthus. Xanthelasmata represent areas of macrophages containing lipids. Arcus corneae (or arcus senilis) is a grey-white-yellowish opacity that is located near the periphery of the cornea, though separated from the limbic margin by a clear corneal zone. Arcus corneae represents deposits of cholesteryl ester–rich lipid particles. It has been suggested that xanthelasmata and arcus corneae may be markers of proatherogenic changes in the vessels and thus markers of atherosclerosis.
"The findings from our study could be of particular value in societies where access to laboratory facilities, and thus lipid profile measurement, is difficult. In this setting, presence of xanthelasmata may be a useful predictor of underlying atherosclerotic disease. An easy registration of presence of xanthelasmata along with age and sex makes it possible to assess the risk of myocardial infarction and ischemic heart disease and thus to make sure that people at increased risk are managed accordingly with lifestyle changes and treatment to reduce low-density lipoprotein cholesterol," wrote Ms. Christoffersen, a clinical biochemistry PhD student at Rigshospitalet in Copenhagen, and his colleagues.
They used data from the Copenhagen City Heart Study, which is a prospective cardiovascular study of the Danish general population that started in 1976-1978 with follow-up examinations. A total of 19,329 white women and men of Danish descent were drawn randomly from the Copenhagen Central Person Registry and invited to participate. Data came from a self-administered questionnaire, a physical examination, and blood samples.
For this analysis, the researchers included 12,745 people, for whom complete information on all relevant variables, including xanthelasmata and arcus corneae, were available at baseline. The patients were followed from baseline at the 1976-1978 examination to the end of May 2009 through the use of their unique Central Person Register number. No participants were lost to follow-up.
Trained nurses or medical laboratory technicians determined the presence of xanthelasmata and arcus corneae by careful visual inspection of the eyelids and the cornea during the physical examination. The investigators collected and verified diagnoses of MI and ischemic heart disease using ICD-8 and ICD-10 codes by reviewing all hospital admissions, diagnoses entered in the national Danish Patient Registry, all causes of death entered in the national Danish Causes of Death Registry, and medical records from hospitals and general practitioners. The prevalence of xanthelasmata was 4.4% and similar in women and men. The prevalence of arcus corneae was 24.8% overall, but was lower in women than in men (20.1% vs. 30.2%).
Potential patients with ischemic cerebrovascular disease, including ischemic stroke, were collected from the national Danish Patient Registry and the national Danish Causes of Death Registry. Hospital records were reviewed by experienced neurologists. Ankle brachial index, a drop in blood pressure in the legs that predicts severe atherosclerosis, was determined in the 2001-2003 examination of the Copenhagen City Heart Study in 2,773 participants, who had also participated in the baseline examination and had complete information on all relevant variables, including xanthelasmata and arcus corneae.
Enzymatic methods were used on fresh plasma samples to measure plasma concentrations of total cholesterol, triglycerides, and high-density lipoprotein cholesterol, the last after precipitation of lipoproteins containing apolipoprotein B.
The median follow-up was 22 years. In all, 1,872 participants developed MI, 3,699 developed ischemic heart disease, 1,498 developed ischemic strokes, 1,815 developed ischemic cerebrovascular disease, and 8,507 died. The models were adjusted for age, sex, total cholesterol, triglycerides, body mass index, hypertension, diabetes, pack-years' smoking, alcohol consumption, physical activity, postmenopausal status, hormone therapy, education, income, and family history of ischemic vascular disease.