Xanthelasmata, arcus corneae, and ischaemic vascular disease and death in general population: prospective cohort study
BMJ 2011; 343 doi: https://doi.org/10.1136/bmj.d5497 (Published 15 September 2011) Cite this as: BMJ 2011;343:d5497All rapid responses
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The otherwise fine study by Christoffersen et al (1) documenting the
association of xanthelasmata with heart disease had one significant flaw:
the lack of confirmation of the diagnosis of xanthelasmata. The authors
state that "trained nurses and laboratory technicians...determined the
presence of xanthelasmata and arcus corneae..." I have seen xanthelasmata
misdiagnosed many times in my 30 year career as a dermatology consultant
at a tertiary care medical center, and my own first year dermatology
residents could easily rattle off at least a dozen entities to be
considered in the differential diagnosis of these lesions. The study would
have been significantly strengthened by having a trained dermatologist
examine the patients.
(1) Christoffersen M, Frikke-Schmidt R, Schnohr P, Jensen GB,
Nordestgaard BG, Tybjaerg-Hansen A. Xanthelasmata, arcus corneae, and
ischaemic vascular disease and death in general population: prospective
cohort study. BMJ. 2011 Sep 15;343:d5497. doi: 10.1136/bmj.d5497
Competing interests: No competing interests
Sir,
I read with particular interest the paper by Christoffersen et
al.(1) In addition to the accurate comment of Fernandez AB and Thompson PD in
their editorial (2), I have a comment on what the authors call
"predictivity". Indeed, they concluded "xanthelasmata predict risk of
myocardial infarction [... ] arcus corneae is not an important independent
predictor of risk". However, when you calculate the overall predictivity of
xanthelasmata for myocardial infarction (for instance), using likelihood
ratio (LR, better parameter than predictive values (3), considering the
outcome as a gold standard (4,5), you found the LR+ =1.6 [1.34-1.93], with
a "pretest" probability =14.7% and a positive "posttest" probability
=21.8%. Then, although xanthelasmata for myocardial infarction is an
independent predictor statistically speaking, I feel the predictivity of xanthelasmata for myocardial infarction is low (with a probability of
myocardial infarction in study and for the practitioner at 21.8%). This
result is also similar for investigated categories (LR+ <10), except
for association of xanthelasmata and arcus corneae in predictivity of
death= "pretest" probability= 29%; positive "posttest" probability =90.5%,
LR+ =23.3 [14.16-27.13], with obviously a low negative predictivity
(negative "posttest" probability =28.1%, LR- =0.96 [0.95-0.96].
In conclusion, I feel authors might give information to the readers
on predictive values using LR and "pre/posttest" probabilities, and
soften their conclusion about predictivity, which is currently probably too strong a
statement. However, it gives valuable information for practitioners, needed
to be investigated if confirmed (what kind of surveillance and treatment
should be initiated? Does treatment modify the outcome?).
References
1. Christoffersen M, Frikke-Schmidt R, Schnohr P, Jensen GB,
Nordestgaard BG, Tybjerg-Hansen A. Xanthelasmata, arcus corneae, and
ischaemic vascular disease and death in general population: prospective
cohort study. BMJ. 2011;343:d5497.
2. Fernandez AB, Thompson PD. Eye markers of cardiovascular disease.
BMJ. 2011;343:d5304.
3. Deeks JJ, Altman DG. Diagnostic tests 4: likelihood ratios. BMJ.
2004 juill 17;329(7458):168-9.
4. Coggon D, Martyn C, Palmer KT, Evanoff B. Assessing case
definitions in the absence of a diagnostic gold standard. Int.J.Epidemiol.
2005;34(4):949-52.
5. Novotny-Baumann M, Baud FJ, Descatha A. Can the Initial Clinical
Signs Be Used for Triage of Patients with Acute H(2)S Poisoning? J
Emerg.Med [Internet]. 2009 nov 16;Available from: PM:19926436
Competing interests: No competing interests
As a relatively junior doctor studying I can still recall my medical
student days, and lectures relating to Cardiovascular disease. One of the
clinical signs that was hammered into us day in day out to look out for
was Xanthelasma. We were told that this was a marker of hyper-
cholesterolaemia and therefore, cardiovascular disease. This has been
shown in numerous studies over many years, and a literature search on
Pubmed using Xanthelasma AND heart disease found 319 articles, including
Schmidt et al1. A further 430 mention Cholesterol plaques and heart
disease. This clinical sign is also well associated with the familial
hypercholeterolaemia syndromes1, and as we know these conditions are known
to correlate with early onset cardiovascular disease and mortality if left
untreated.
I have to question what this paper adds to clinical practice
and to the way doctors approach their patients. I am studying for PACES
and if I did not mention such an obvious sign in my Cardiovascular
examination I would expect to fail, having failed to detect a well
documented, long known clinical sign. In addition. If this is NEW research
and new insightful research I question whether my lectures in medical
school were based on fact or merely assumptions.
1. Shmidt HH et al. Relation of cholesterol-year score to severity of
calcific atherosclerosis and tissue deposition in homozygous familial
hypercholesterolemia.Am J Cardiol. 20065;77(8): 575-80
2.Zech LA. Hoeg JM. Correlating corneal arcus with atherosclerosis in
familial hypercholesterolemia. Lipids Health Dis. 2008. March 10;7:7
Competing interests: No competing interests
Xanthelasmata, risk of ischemic vascular disease and death - authors' response
Dr Samuel questions what this study adds to clinical practice, while
Dr Descatha comments on our conclusions on predictivity. Though several
previous studies have reported an association between xanthelasmata and
increased plasma lipid levels, these studies have also reported that on
average 50% of individuals with xanthelasmata were normolipidemic (1).
Most of these previous studies were case-control studies, and results on
the association between xanthelasmata and risk of cardiovascular disease
have been conflicting (1,2). This is the first long term prospective study
to confirm the association between xanthelasmata and risk of ischemic
vascular disease and death. We furthermore find that this association is
independent of plasma cholesterol levels, which indicates that individuals
with xanthelasmata may have an increased biological propensity to deposit
cholesterol in the connective tissues of the body. We thank Dr Descatha
for her calculations and views on the predictive value of xanthelasmata.
While the predictive value of xanthelasmata is modest, it is still very
important for clinicians to regard xanthelasmata as an independent risk
factor for ischemic vascular disease and death. Xanthelasmata are easy to
diagnose visually, and may thus serve as a tool to help clinicians
identify patients at increased risk of cardiovascular disease, and make
sure that these individuals are managed accordingly with respect to
lifestyle changes and therapy.
As Professor Thiers describes the diagnosis of xanthelasmata was not
made by dermatologists. However, the nurses and laboratory technicians,
who performed the physical examination of the participants, were
specifically trained to recognize xanthelasmata. Furthermore, since the
prevalence corresponds very well with previous reports in the literature,
we feel relatively confident with the visual diagnostic procedure (1).
References
(1) Bergman R. The pathogenesis and clinical significance of
xanthelasma palpebrarum. J Am Acad Dermatol. 1994;30:236-242.
(2) Ozdol S, Sahin S, Tokgozoglu L. Xanthelasma palpebrarum and its
relation to atherosclerotic risk factors and lipoprotein (a). Int J
Dermatol. 2008;47:785-789.
Competing interests: No competing interests