Xanthelasmata increase risk of cardiovascular disease or death

GPs should be on the lookout for raised yellow patches of skin around the upper or lower eyelids, as new research published in the BMJ suggests these are important markers of increased risk of heart attack or heart disease.

A study by Danish researchers found the patches – known clinically as xanthelasmata – raised the absolute risk of an ischaemic vascular disease and death by 12% compared with those without the condition.

Xanthelasmata are deposits of cholesterol, but their significance in heart disease has been unclear as around half of patients who have either or both condition will not test positively for high cholesterol in a blood test.

Researchers surveyed 12,745 individuals who had participated in the Copenhagen City Heart Study aged between 20 and 93 who were free of heart disease when the study began. They were followed from 1976 until May 2009 with 100% complete follow-up.

At the beginning of the study 4.4% of participants had xanthelasmata. During the follow-up 1,872 of the participants had a heart attack, 3,699 developed heart disease, 1,498 had a stroke, 1,815 developed cerebrovascular disease and 8,507 died.

The results show that in all age groups for both men and women, the risk of having a heart attack, developing heart disease or dying within a ten year period increased in individuals with xanthelasmata. The risk was independent of gender, smoking, obesity or high blood pressure and cholesterol levels.

The highest risks were found in men between the ages of 70 and 79. Those with xanthelasmata had a 53% increased risk compared to the 41% risk for men without the condition - an absolute increase of 12%. The corresponding figures for women were 35% and 27%.

There was also a 69% increased risk in severe atherosclerosis in people with xanthelasmata compared with those without, independent of cardiovascular risk factors including plasma cholesterol and triglyceride concentrations.

But arcus corneae – white or grey rings around the cornea, which was seen in 24.8% of the study population – were not found to be linked to a significantly increased risk.

Professor Anne Tybjærg-Hansen, professor of clinical biochemistry and chief physician at Righospitalet in Copenhagen, concluded: ‘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 ischaemic heart disease.'

‘A possible explanation may be an increased propensity of these people to deposit cholesterol in connective tissues of the body. This could be due to increased leakage of cholesterol from the vessels, increased retention of cholesterol in connective tissue, or increased uptake of cholesterol in macrophages.'

In an accompanying editorial, Dr Paul Thompson, director of the cardiology division at the Hartford Hospital, said: ‘The evidence highlights the importance of a comprehensive physical examination and suggests that xanthelasmata could be used by GPs to help identify people at higher risk of cardiovascular disease. Patients with xanthelasmata may therefore require more aggressive management of risk factors.'

BMJ 2011, online 15 September