Xanthelasmata Identified as Independent CV Risk Factor Reply

A large new study from Denmark finds that xanthelasmata (raised yellow patches around the eyelids) but not arcus cornae (white or grey rings around the cornea) is an independent risk factor for cardiovascular disease.

In a paper in BMJ, Mette Christoffersen and colleagues report on 12,745 adults in Copenhagen without cardiovascular disease at baseline who were followed for a mean of 22 years. At baseline 4.4% had xanthelasmata and 24.8% had arcus corneae. Here are the main results, comparing the group without xanthelasmata to the group with xanthelasmata:

  • MI: 65 events versus 121 events  per 10,000 person years (multifactorial adjusted HR for xanthelasmata: 1.48, CI 1.23-1.79).
  • Ischemic heart disease: 134 versus 226 events per 10,000 person years (multifactorial adjusted HR for xanthelasmata: 1.39, CI 1.20-1.60)
  • Ischemic stroke: 53 versus 64 events per 10,000 person years (multifactorial adjusted HR for xanthelasmata: 0.94, CI 0.73-1.21)
  • Ischemic cerebrovascular disease: 65 versus 74 events per 10,000 person years (multifactorial adjusted HR for xanthelasmata: 0.91, CI 0.72-1.15)
  • Total deaths: 293 versus 414 events per 10,000 person years (multifactorial adjusted HR for xanthelasmata: 1.14, CI 1.04-1.26)

The authors write that their results “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.” They say the findings may be especially useful in places with limited access to laboratories.

In an accompanying editorial, Antonio Fernandez and Paul Thompson write that people with xanthelasmata “may have an enhanced biological propensity to deposition of cholesterol in vascular and soft tissue, which is not fully represented by their fasting lipid profiles. Because xanthelasmata are composed of foam cells similar to those present in atherosclerotic plaque, they may be a better marker than arcus corneae of the intra-arterial atherosclerotic process.” Therefore, they conclude, these patients “may therefore require more aggressive management of risk factors.”

Here is the press release from the BMJ:

Yellow patches around eyelids predict risk of heart problems

Research: Xanthelasmata, arcus corneae, and ischaemic vascular disease and death in general population: prospective cohort study
Editorial: Eye markers of cardiovascular disease

Raised yellow patches of skin (xanthelasmata) around the upper or lower eyelids are markers of an individual’s increased risk of having a heart attack or suffering from heart disease, finds research published on bmj.com today.

The study, led by Professor Anne Tybjærg-Hansen at the University of Copenhagen, also concludes that white or grey rings around the cornea (arcus corneae) are not linked to an increased risk.

Previous research has established that both xanthelasmata and arcus corneae are deposits of cholesterol. However, around half of the individuals who have either or both condition will not test positively for high cholesterol in a blood test.

The researchers wanted to investigate links between xanthelasmata and/or arcus corneae and an increased risk of heart attack, heart disease, stroke, severe thickening of the arteries or premature death in the general population, as the evidence in this area is lacking.

Indeed, many patients are referred to dermatologists so that xanthelasmata can be removed, they add.

They surveyed 12,745 individuals who had participated in the Copenhagen City Heart Study. The participants were aged between 20 and 93 and were free of heart disease when the study began. They were followed from 1976-8 until May 2009 with 100% complete follow-up.

At the beginning of the study 563 (4.4%) of participants had xanthelasmata and 3,159 (24.8%) had arcus corneae.

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. This increased risk is independent of other well-known risk factors such as 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%.

In contrast, the results show that arcus corneae is not a significant independent risk predictor for heart attack or heart disease.

The authors conclude that the presence of xanthelasmata could help clinicians when they diagnose heart disease and associated conditions. And they add that their findings “could be of particular value in societies where access to laboratory facilities and thus lipid profile measurement is difficult.”

An accompanying editorial concludes that, overall, the evidence highlights the importance of a comprehensive physical examination and suggests that xanthelasmata could be used by general clinicians to help identify people at higher risk of cardiovascular disease.

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