Mette Christoffersen and colleagues found that periocular macules may be a new clue for clinicians to identify individuals at high risk for myocardial infarction and severe atherosclerosis. “Macular tumors of the eyelids may be a cutaneous marker of atherosclerosis independent of lipid concentrations and should be considered as a risk factor for myocardial infarction and ischemic heart disease in clinical practice.” The study was published online in the British Medical Journal (BMJ 2011;343:d5497). The data for this study came from the Copenhagen City Heart Study, a prospective cardiovascular study of the general Danish population with follow-up examinations from 1976 to 1978. A total of 19,329 whites were randomly selected from the Copenhagen Central Population Registry for inclusion in the study, and data were collected by self-assessment scales, physical examination, and blood tests. The presence of lid macular tumors and corneal arches was determined by careful examination of the eyelids and cornea by a trained nurse or laboratory technician. Wang Junt, Critical Care Unit, Nanping First Hospital eyelid macular tumors are well-defined flat yellow plaques that occur in the upper or lower eyelid, most often located around the inner canthus. Eyelid macular tumors suggest a large number of lipid-laden macrophages in the area. The corneal arch is a grayish-yellowish opaque object that lies around the cornea but is separate from the edge of the corneal region. The corneal arch suggests a large deposit of cholesteryl ester-rich lipid particles in this region. Previous studies suggest that macular tumors of the eyelids and corneal arches may be markers of proatherosclerotic changes in blood vessels.Christoffersen et al. included 12,745 subjects with complete data at baseline from the City of Copenhagen Heart Study and followed up from baseline until May 2009. Patients with ischemic cerebrovascular disease (including ischemic stroke) were selected from the Danish National Patient Registry and Cause of Death Registry. Hospitalization records were analyzed by an experienced neurologist. Ankle-brachial index was determined by examination of 2,773 subjects from the Copenhagen City Heart Study from 2001 to 2003, who also participated in the baseline examination and had complete information. Total cholesterol, triglyceride, and HDL cholesterol concentrations were determined enzymatically in fresh plasma samples. Results showed that 4.4% of subjects had macular tumors of the eyelids, a similar proportion of men and women, and 24.8% had corneal arches, but they were relatively uncommon in women (20.1% vs. 30.2%). At a median follow-up of 22 years, a total of 1,872 subjects had myocardial infarction, 3,699 had ischemic heart disease, 1,498 had ischemic stroke, 1,815 had ischemic cerebrovascular disease, and 8,507 had died. The presence of corneal macular tumors predicted myocardial infarction [hazard ratio (HR), 1.48], ischemic heart disease (HR, 1.39), severe atherosclerosis (as determined by the ankle-brachial index; HR, 1.39), and death (HR, 1.14). However, after multifactorial correction for corneal arches (including age, sex, total cholesterol, triglycerides, body mass index, hypertension, diabetes mellitus, smoking, alcohol consumption, physical activity, menopausal status, hormone therapy, education, income, and family history of ischemic vascular disease), the HRs were no longer significant. If both eyelid macular tumor and corneal arch were present, they still predicted ischemic heart disease (HR, 1.56), even after multifactorial correction, but not other endpoints. The investigators concluded that the presence of eyelid macular tumors predicted myocardial infarction, ischemic heart disease, severe atherosclerosis, and death for the general population and was independent of known cardiovascular risk factors such as plasma cholesterol and triglyceride concentrations; whereas corneal arches were not an independent predictor of risk. This finding is particularly relevant for people who have difficulty undergoing lipid screening: the presence of macular tumors of the eyelids, combined with age and sex, can help determine the risk of myocardial infarction and ischemic heart disease and ensure that those at risk receive lifestyle interventions and medications to lower LDL cholesterol. In an accompanying journal review, cardiovascular pathologist Antonio B. Fernandez of Alpert Medical School at Brown University and Paul D Thompson, chief of cardiology at Hartford Hospital, noted that there is reason to suspect that eyelid macular tumors and/or corneal arches are associated with ischemic vascular disease and death (BMJ 2011;343:d5304). “Both eyelid macular tumors and corneal arches are composed of cholesterol esters similar to those found in serum LDL cholesterol and very low density lipoprotein cholesterol. They share similar risk factors and pathophysiological mechanisms with atherosclerosis.” They concluded that these findings confirm that “macular tumors of the eyelids are not only associated with hyperlipidemia, but are also important predictors of cardiovascular events and death.” The implications for clinical practice are that they highlight the importance of a thorough physical examination and suggest that macular tumors of the eyelids may help identify individuals at high risk for cardiovascular disease who may have a biological predisposition for cholesterol deposition in blood vessels and soft tissues that is not fully reflected by fasting lipid tests. Those with eyelid macular tumors may need more aggressive intervention for risk factors.