Eye markers of cardiovascular diseaseBMJ 2011; 343 doi: https://doi.org/10.1136/bmj.d5304 (Published 15 September 2011) Cite this as: BMJ 2011;343:d5304
- 1Division of Cardiology, The Warren Alpert School of Medicine, Providence, RI, USA
- 2Cardiology Division, Hartford Hospital, Hartford, CT 06102, USA
Most clinicians are aware that arcus corneae and xanthelasmata are related to hyperlipidaemia, but results have been conflicting on whether they provide extra information compared with traditional risk factors when predicting the risk of cardiovascular disease.1 2 3 In the linked prospective cohort study (doi:10.1136/bmj.d5497), Christoffersen and colleagues assess whether xanthelasmata and arcus corneae, individually and combined, predict risk of ischaemic vascular disease and death in the general population.4
Arcus corneae and xanthelasmata are recognised signs of hyperlipidaemia when seen in younger patients.5 6 The arcus corneae associated with hyperlipidaemia, “arcus lipoides,” is a white discoloration of the peripheral cornea near the corneoscleral limbus, which is generally separated from the limbic edge by a zone of normal cornea.1 Arcus lipoides ranges from a barely visible arc in one of the poles of the cornea to a complete dense ring. In contrast, other age related peripheral corneal opacities commonly blur into the limbus.7 Arcus is more common in black people than in white people,8 and in men than in women.1
Xanthelasma palpebrarum is the most common cutaneous xanthoma. It consists of soft, yellow plaques that appear on the medial aspects of the eyelids bilaterally. It most often occurs in middle aged and older adults. Raised low density lipoprotein-cholesterol is the most common dyslipidaemia associated with xanthelasmata. Both xanthelasmata and arcus corneae are composed of cholesterylesters similar to those found in serum low density lipoprotein-cholesterol and very low density lipoprotein-cholesterol. They share similar risk factors and have pathophysiological similarities with atherosclerosis,1 9 but normolipidaemic patients can also develop arcus and xanthelasmata.6 9
Christoffersen and colleagues’ study looked at 12 745 people aged 20-93 years who were free of ischaemic vascular disease at baseline and were followed for between 31 and 33 years. After controlling for established cardiovascular disease risk factors, xanthelasmata predicted the risk of myocardial infarction (hazard ratio 1.48, 95% confidence interval 1.23 to 1.79), ischaemic heart disease (1.39, 1.20 to 1.60), severe atherosclerosis as determined by ankle brachial index (1.69, 1.03 to 2.79), and death (1.14, 1.04 to 1.26). The risk of ischaemic heart disease became stronger (1.56, 1.25 to 1.94) when xanthelasmata and arcus were both present but did not change significantly for other outcomes.
These results indicate that xanthelasmata are an important predictor of cardiovascular disease events and death beyond its known association with hyperlipidaemia. These findings are consistent with a previous case-control study that showed a higher prevalence of cardiovascular disease in patients with xanthelasmata (11%) compared with matched controls without xanthelasmata (1%).10 Likewise, a larger population cohort study found that xanthelasmata predicted all cause mortality, although mortality from cardiovascular disease was not reported.3
Christoffersen and colleagues’ results differ from those of a recent smaller study,2 however, which found similar rates of clinical cardiovascular disease events in patients with and without xanthelasmata (8% v 7%). In Christoffersen and colleagues’ study, arcus corneae did not predict outcomes in multivariate models—some,11 but not all,12 previous studies agree with these data.
As with any study, the current study has some limitations. The data are derived from a relatively homogeneous, predominantly white, population. The study did not include black people, in whom corneal arcus has historically been more prevalent. Data were collected by “trained nurses or medical laboratory technicians,” but it is not clear whether any distinction was made between arcus lipoides and other age related peripheral corneal opacities. This is a potential problem in other studies,11 and it might explain why arcus corneae was not an independent risk factor after adjustment for age in the Framingham cohort. However, these criticisms are minor and may simply reflect our personal reluctance to abandon using arcus as a possible marker of atherosclerotic risk, especially in people with low lipid values.
What do these results mean in practice? 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. These people 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. Patients with xanthelasmata may therefore require more aggressive management of risk factors.
Cite this as: BMJ 2011;343:d5304
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; in the past three years PDT has received consultancy fees from Regeneron, Furiex Pharmaceuticals, and Lupin Pharmaceuticals; payment for lectures from GlaxoSmithKline, Merck, Pfizer, Astra Zeneca, Kowa, and Abbott; his institution has received money from GlaxoSmithKline, Genomas, Novartis, Furiex Pharmaceuticals; he also stock options in Zoll Medical, JA Wiley Publishing, General Electric, Zimmer, Medtronic, Johnson and Johnson, Sanofi-Aventis, and Abbott; no other relationships or activities that could appear to have influenced the submitted work.
Provenance and peer review: Commissioned; not externally peer reviewed.