Xanthelasmata, arcus corneae, and ischaemic vascular disease and death in general population: prospective cohort study

Abstract

Objective: To test the hypothesis that xanthelasmata and arcus corneae, individually and combined, predict risk of ischaemic vascular disease and death in the general population.

Design: Prospective population based cohort study.

Setting: The Copenhagen City Heart Study.

Participants: 12,745 people aged 20-93 years free of ischaemic vascular disease at baseline and followed from 1976-8 until May 2009 with 100% complete follow-up.

Main outcome measures: Hazard ratios for myocardial infarction, ischaemic heart disease, ischaemic stroke, ischaemic cerebrovascular disease, and death; odds ratios for severe atherosclerosis.

Results: 563 (4.4%) of participants had xanthelasmata and 3159 (24.8%) had arcus corneae at baseline. During 33 years' follow-up (mean 22 years), 1872 developed myocardial infarction, 3699 developed ischaemic heart disease, 1498 developed ischaemic stroke, 1815 developed ischaemic cerebrovascular disease, and 8507 died. Multifactorially adjusted hazard/odds ratios for people with versus those without xanthelasmata were 1.48 (95% confidence interval 1.23 to 1.79) for myocardial infarction, 1.39 (1.20 to 1.60) for ischaemic heart disease, 0.94 (0.73 to 1.21) for ischaemic stroke, 0.91 (0.72 to 1.15) for ischaemic cerebrovascular disease, 1.69 (1.03 to 2.79) for severe atherosclerosis, and 1.14 (1.04 to 1.26) for death. The corresponding hazard/odds ratios for people with versus those without arcus corneae were non-significant. In people with versus those without both xanthelasmata and arcus corneae, hazard/odds ratios were 1.47 (1.09 to 1.99) for myocardial infarction, 1.56 (1.25 to 1.94) for ischaemic heart disease, 0.87 (0.57 to 1.31) for ischaemic stroke, 0.86 (0.58 to 1.26) for ischaemic cerebrovascular disease, 2.75 (0.75 to 10.1) for severe atherosclerosis, and 1.09 (0.93 to 1.28) for death. In all age groups in both women and men, absolute 10 year risk of myocardial infarction, ischaemic heart disease, and death increased in the presence of xanthelasmata. The highest absolute 10 year risks of ischaemic heart disease of 53% and 41% were found in men aged 70-79 years with and without xanthelasmata. Corresponding values in women were 35% and 27%.

Conclusion: Xanthelasmata predict risk of myocardial infarction, ischaemic heart disease, severe atherosclerosis, and death in the general population, independently of well known cardiovascular risk factors, including plasma cholesterol and triglyceride concentrations. In contrast, arcus corneae is not an important independent predictor of risk.

Fig 1 Mean plasma concentrations of lipids, lipoproteins, and apolipoproteins in people with or without baseline xanthelasmata at the 1976-8, 1981-3, 1991-3, and 2001-3 examinations of Copenhagen City Heart Study. Error bars represent standard errors of the mean. HDL=high density lipoprotein; LDL=low density lipoprotein.

Fig 2 Mean plasma concentrations of lipids, lipoproteins, and apolipoproteins in people with or without baseline arcus corneae at the 1976-8, 1981-3, 1991-3, and 2001-3 examinations of Copenhagen City Heart Study. Error bars represent standard errors of the mean. HDL=high density lipoprotein; LDL=low density lipoprotein.

Fig 3 Cumulative incidences of myocardial infarction, ischaemic heart disease, and total death in Copenhagen City Heart Study in people with or without xanthelasmata. Dotted lines indicate median survival time in people with and without xanthelasmata

Fig 4 Risk of myocardial infarction, ischaemic heart disease, and total death in Copenhagen City Heart Study in people with versus those without xanthelasmata stratified by cardiovascular risk factors. Hazard ratios are from 1976-8 examination (n=12 745; follow-up up to 33 years, mean follow-up 22 years). Adjustment was for age, sex, total cholesterol, triglycerides, body mass index, hypertension, diabetes, pack years’ smoking, alcohol consumption, physical inactivity, education, income, family history of ischaemic vascular disease, and in women also for postmenopausal status and hormonal replacement therapy. P values are for interaction between presence or absence of xanthelasmata and cardiovascular risk factors on risk of myocardial infarction, ischaemic heart disease, and total death. Within strata of risk factors, people without xanthelasmata (reference group) have hazard ratio=1 and are not shown