- Mette Christoffersen, PhD student1,
- Ruth Frikke-Schmidt, consultant1,
- Peter Schnohr, consultant2,
- Gorm B Jensen, professor23,
- Børge G Nordestgaard, professor24,
- Anne Tybjærg-Hansen, professor12
- 1Department of Clinical Biochemistry, Rigshospitalet, DK-2100 Copenhagen, Denmark
- 2Copenhagen City Heart Study, Bispebjerg Hospital, DK-2400 Copenhagen
- 3Department of Cardiology, Hvidovre Hospital, DK-2650 Hvidovre, Denmark
- 4Department of Clinical Biochemistry, Herlev Hospital, DK-2730 Herlev, Denmark
- Correspondence to: A Tybjærg-Hansen, Department of Clinical Biochemistry KB 3011, Section for Molecular Genetics KB 4111, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark
- Accepted 14 July 2011
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.
We thank the staff and participants from the Copenhagen City Heart Study for their important contributions to our study.
Contributors: All authors contributed to the study design and had full access to all the data in the study. MC, RF-S, BGN, and AT-H analysed and interpreted the data. PS and GBJ contributed to the collection of data, through initiation of the Copenhagen City Heart Study. MC and AT-H drafted the report (with significant contributions from all other authors). All authors have seen and approved the final version of the report. MC and AT-H are the guarantors.
Funding: This study was funded by the Research Fund at Rigshospitalet, the Lundbeck Foundation, the Danish Medical Research Council, and the Danish Heart Foundation. The sponsors had no role in the design of the study; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. The views expressed in this paper are those of the authors and not those of any funding body or others whose support is acknowledged.
Competing interests: All authors have completed the Unified Competing Interest 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; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: The study was approved by institutional review boards and by Danish ethical committees (the Copenhagen and Frederiksberg committee and the Copenhagen County committee; KF-100.2039/91, KF-01-144/01, H-KF-01-144/01). Participants gave written informed consent.
Data sharing: No additional data available.
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