Letter by Čulić and Fabijanić Regarding Article, “Visible Age-Related Signs and Risk of Ischemic Heart Disease in the General Population: A Prospective Cohort Study”
To the Editor:
Christoffersen and coworkers1 reported that earlobe crease, xantelasmata, and crown top and frontoparietal baldness are associated with the increased risk of ischemic heart disease, myocardial infarction, and total death independently of several cardiovascular, socioeconomic, and lifestyle risk factors. Crude estimates and estimates adjusted for age suggested that moderate to complete graying of hair, facial wrinkles, and arcus corneae are also associated with the end points; gray hair remained a predictor after age and sex adjustments, but became nonsignificant after multifactorial adjustments.1
Although Christoffersen and coworkers1 stated that no other study associates gray hair with the risk of myocardial infarction, we have found such an association in men <45 years of age.2 In the present context, it is important that we have also analyzed the occurrence of pairs of dermatologic signs and have found a significantly frequent copresence of hair graying and earlobe crease.2 If these 2 or other signs correlated in the present study,1 this would be an important source of bias.
Our case–control study published in 19982 and the present study1 are 2 studies simultaneously investigating the associations of age-related dermatologic signs with cardiovascular end points. Although “the rule of 50” (50% of 50-year-olds have ≈50% gray hairs) is not quite accurate,3 the question is how many people without gray hair or other age-related signs can be found at a certain age. The same applies to cardiovascular risk factors. For this reason, we limited the age of our male participants to 60 years.2 In a setting where multiple correlations among factors are present, even if multivariate analysis is done with caution, a significant bias still may occur. The present study included a wide age range (20–90 years) of participants.1 Because of strong age-related correlations among cardiovascular end points, correspondent risk factors and dermatologic signs, some true associations, possibly including hair graying, might have been blurred in the multivariate models.
Previous studies on this issue, other than the 2 abovementioned,1,2 had methodological limitations in the determination of cardiovascular disease or quantification of hair graying, and investigated only this single sign. However, premature hair whitening has been associated with carotid intima-media thickness independently of chronobiological age and conventional cardiovascular risk factors in men <55 years of age.4 Adverse effects of risk factors, such as cell dysfunction and apoptosis, on follicular epithelium and resident stem cells, and simultaneously on vascular endothelium and progenitor stem cells, have been proposed as possible mechanism linking hair whitening with vascular aging and atherosclerotic changes.4
Age-related dermatologic signs, proportionally to their number, probably associate with higher cardiovascular risk. We have also reported an association of thoracic hairiness,2 a sign which was not explored in the present study,1 with an increased risk of myocardial infarction. Because of all these reasons, we think that dermatologic signs should be more thoroughly explored at the age when they are less common, particularly in the younger and middle-aged male population, as surrogate indicators of subclinical atherosclerosis regardless of conventional risk factors.
Viktor Čulić, MD, PhD
Damir Fabijanić, MD, PhD
Division of Cardiology
Department of Internal Medicine
University Hospital Center Split
University of Split School of Medicine
- © 2014 American Heart Association, Inc.