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Dermatological indicators of coronary risk: a case-control study
International Journal of Cardiology 67 (1998) 251–255
Dermatological indicators of coronary risk: a case-control study ˇ ´ a , Ivo Bozic ˇ ´ a, Dinko Miric´ a , *, Damir Fabijanic´ a , Lovel Giunio a , Davor Eterovic´ b , Viktor Culic a Izet Hozo b
a ˇ´ 1, 21000 Split, Croatia Department of Medicine, Clinical Hospital Split, Spinciceva ˇ´ 1, 21000 Split, Croatia Department of Nuclear Medicine, Clinical Hospital Split, Spinciceva
Received 25 August 1998; accepted 30 September 1998
Abstract Objective: We examined the association of dermatological signs such as baldness, thoracic hairiness, hair greying and diagonal earlobe crease with the risk of myocardial infarction in men under the age of 60 years. Methods: A hospital-based, case-control study included 842 men admitted for the first non-fatal myocardial infarction, the controls were 712 men admitted with noncardiac diagnoses, without clinical signs of coronary disease. The relative risks were estimated as odds ratios. Logistic regression was used to control for the confounding variables. Results: Baldness, thoracic hairiness and earlobe crease were |40% more prevalent in cases (P,10 26 in each case). In both cases and controls, baldness and thoracic hairiness were frequently coexistent, as well as hair greying and earlobe crease (P,10 24 in each case). After allowing for age and other established coronary risk factors, the relative risk of myocardial infarction for fronto-parietal baldness compared with no hair loss was 1.77 (95% CI 1.27–2.45) and it was 1.83 (95 CI 1.4–2.3) for men with thick, extended thoracic hairiness. The presence of a diagonal earlobe crease yielded a relative risk of 1.37 (95% CI 1.25–1.5), while hair greying was associated with myocardial infarction only in men under the age of 50 years. Conclusion: It appears that baldness, thoracic hairiness and diagonal earlobe crease indicate an additional risk of myocardial infarction in men under the age of 60 years, independently of age and other established coronary risk factors. 1998 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Dermatological signs; Coronary risk; Myocardial infarction
1. Introduction The most important coronary risk factor is age. With advancing age, baldness, hair greying and wrinkling of the skin are increasingly common. Theoretically, the premature or extensive occurrence of these dermatological signs could identify a person with an accelerated aging process and consequent increased coronary risk. Another hypothesis is that increased levels of androgens is the common denominator of both the atherosclerotic process and dermatological signs like baldness and thoracic hairiness. The studies that have already addressed this *Corresponding author, Poljana stare gimnazije 1, 21000 Split, Croatia.
issue confirmed that male pattern baldness, grey hair, facial wrinkling and diagonal earlobe crease indicate increased coronary risk [1–8]. In most of these reports the age and other established risk factors were controlled for. However, the coexistence of several dermatological signs, though common in practice, was not properly accounted for. We are also unaware of any study of thoracic hairiness in relation to risk of myocardial infarction (MI). This study addresses these unresolved issues.
2. Patients and methods Data were collected from January 1991 to
0167-5273 / 98 / $ – see front matter 1998 Elsevier Science Ireland Ltd. All rights reserved. PII: S0167-5273( 98 )00313-1
252
D. Miric´ et al. / International Journal of Cardiology 67 (1998) 251 – 255
November 1997 from men under the age of 60 years who were admitted to two hospitals in Split, Croatia, at the Departments of cardiology, gastroenterology or traumatology. Cases were 842 men admitted for the first non-fatal MI and who had no history of rheumatic heart disease, cardiomyopathy or cardiac surgery. Controls were 712 men admitted for acute peptic ulcer (N5417) or injures acquired in traffic accident (N5295), who had normal ECG at rest and negative history of MI, angina pectoris, rheumatic heart disease, cardiomyopathy or cardiac surgery. Subjects with history of prior treatment of baldness were not included as cases or controls. Aside from these inclusion criteria and consent to participate in the study, the subjects were the consecutive groups of patients admitted to the respective departments. An acute MI was diagnosed according to World Health Organization criteria, that is if two of the following three criteria were fulfilled: (1) a typical chest pain lasting more than 30 min; (2) an ECG with pathologic Q waves with evolution; (3) an increase in at least one of the cardiac enzymes to over twice the upper limit of normal. The variable baldness was categorized as: (1) no baldness, (2) frontal baldness; (3) parietal baldness, i.e. baldness involving the vertex scalp; and (4) combined, fronto-parietal baldness. Hairiness of the thorax was categorized as: (1) mild or absent, when there were none or few sparse hairs on the limited area of the chest; (2) moderate, when a larger area of the chest was hairy; and (3) intensive, when the hairiness of the chest spread to the back and (or) shoulders. Hair greying was described as: (1) mild or absent, when there were none or single grey hairs diffusely over the scalp; (2) moderate, when grey sideburns were present; and (3) intensive, when the hair was completely grey / white. Presence of a diagonal earlobe crease was assigned to a person with a crease stretching obliquely from the outer ear canal towards the border of the earlobe of at least one ear. The collection of data on history of coronary or non-coronary cardiac disease and coronary risk factors (age, family history of MI, arterial hypertension, hypercholesterolemia, body mass index, diabetes and smoking), as well as assessment of dermatological signs were done by the residents during their internships at the respective departments. Smoking was quantified in terms of pack-years, i.e. as a product of
years of smoking and the packs of cigarettes consumed daily.
2.1. Data analyses Prevalences of categorical variables in cases and 2 controls were compared by x test. The same test was used to evaluate the associations of pairs of dermatological signs. The odds ratio was used to estimate the relative risk for MI for men with a particular dermatological sign, compared with men without that sign (category 1, as described above). The confidence intervals of these unadjusted (not controlled for age and other confounders) risk ratios were calculated by the Miettinen’s formula [9]. The adjusted risk ratios were obtained from the regression coefficients of the unconditional logistic regression. In each of those analyses the criterion variable was the presence of MI, the explanatory variables comprised one of the dermatological signs (or its single category) and the following set of covariates: age, family history of MI, arterial hypertension, hypercholesterolemia, body mass index, diabetes and smoking. In this way the relative risks of MI related to a particular dermatological sign were controlled for the established risk factors, but not for the dermatological signs other than the analyzed one. In order to account for the coexistence of several dermatological signs, the combinations of interaction variables (baldness3 hairiness, baldness3hairiness3earlobe crease, etc.) were used instead of a single dermatological sign in the above analyses. P values less than 0.05 were considered significant.
3. Results
3.1. Anthropometry: cases versus controls Table 1 summarizes the anthropometric parameters of the study subjects.
3.2. Prevalences of dermatological signs All dermatological signs were more common among cases compared to controls (Table 2). The differences ranged from 19% vs. 10% in case of
D. Miric´ et al. / International Journal of Cardiology 67 (1998) 251 – 255 Table 1 Clinical comparison between 842 cases of myocardial infarction and 712 non-cardiac control patients
Age (years) ,45 46–49 $50 Body mass index (kg / m 2 ) ,25 26–28 .29 Hypercholesterolemia Hypertension Family history of MI Smoking Diabetes
Cases
Controls
P value
194 (23%) 295 (35%) 353 (42%)
171 (24%) 223 (31%) 318 (45%)
NS NS NS
281 (31%) 362 (43%) 199 (26%) 109 (13%) 126 (15%) 261 (31%) 471 (56%) 42 (5%)
270 (38%) 292 (41%) 150 (21%) 58 (8%) 67 (9%) 175 (24%) 328 (46%) 14 (2%)
NS NS NS 0.004 0.001 0.006 0.001 0.003
253
parietal baldness, to 88% vs. 80% in case of any hair greying.
3.3. Risk ratios (raw and adjusted) The relative risk ratios for MI are given in Table 3. Control for the possible confounding effect of the established risk factors produced only slight changes in risk ratios. The strongest predictors of MI appeared to be parietal baldness and the diagonal earlobe crease. Hair greying yielded a significant risk ratio only in men younger then 45 years; this risk was 1.5 (95% CI 1–2.3) for moderately grey hair, while completely grey hair was approximately equally rare (around 3%) both in cases and controls.
3.4. Mutual association of dermatological signs Table 2 Prevalences of dermatological signs in 842 cases of myocardial infarction and 712 non-cardiac control patients
Baldness any frontal parietal fronto-parietal Thoracic hairiness any moderate intensive Hair greying any moderate intensive Earlobe crease
Cases
Controls
P value
50.5% 20% 19% 11.5%
35.5% 18.5% 10.5% 6.5%
4310 29 0.52 5310 26 8310 24
46.5% 25.5% 21%
32% 20.5% 11.5%
8310 29 0.02 8310 27
36.5% 32% 4.5% 62.9%
34.5% 30% 4.5% 46%
0.7 0.45 1 4310 211
Baldness and thoracic hairiness were frequently coexistent (or commonly absent), as well as hair greying and diagonal earlobe crease both in cases and controls (Table 4). Other combinations of pairs of dermatological signs were not significantly associated.
3.5. Combined risk ratios Table 5 presents the estimates of the relative risk ratios of MI for all combinations of common presence of baldness, thoracic hairiness and earlobe crease. Only the categories ‘any baldness’ and ‘any thoracic hairiness’ were analyzed. Inclusion of thoracic hairiness, in case of baldness, did not
Table 3 The relative risk ratio (95% CI) of myocardial infarction for men with a particular dermatological sign
Baldness any frontal parietal fronto-parietal Thoracic hairiness any moderate intensive Earlobe crease a
Unadjusted
Adjusted for standard risk factors a
1.42 (1.26–1.59) 1.08 (0.85–1.37) 1.81 (1.40–2.30) 1.77 (1.27–2.45)
1.40 0.90 1.90 1.68
(1.19–1.63) (0.71–1.42) (1.42–2.20) (1.20–2.50)
1.45 (1.28–1.64) 1.22 (1.03–1.45) 1.83 (1.44–2.32) 1.37 (1.25–1.5)
1.48 1.20 1.70 1.30
(1.33–1.77) (0.95–1.50) (1.40–2.55) (1.22–1.42)
Age, family history of MI, arterial hypertension, hypercholesterolemia, body mass index, diabetes and smoking.
D. Miric´ et al. / International Journal of Cardiology 67 (1998) 251 – 255
254
Table 4 Significances of associations of pairs of dermatological signs in cases of myocardial infarction and control non-cardiac patients Sign
Coexistence of Thoracic hairiness
Baldness Thoracic hairiness Hair greying
Hair greying
Earlobe crease
Cases
Controls
Cases
Controls
Cases
Controls
0.02 / N.S.
0.02 / N.S.
N.S. N.S. /
N.S. N.S. /
N.S. N.S. 0.04
N.S. N.S. 0.03
Significances are expressed as P values, obtained by x 2 test. Table 5 The relative risk ratios (95% C.I.) of myocardial infarction for men with several dermatological signs Cumulative presence of
Sign Baldness
Thoracic hairiness Earlobe crease
Baldness 1.42 (1.26–1.59) 1.40 (1.22–1.65) 1.66 (1.35–1.81) Thoracic hairiness / 1.45 (1.28–1.64) 1.60 (1.30–1.95) Earlobe crease and baldness / 1.65 (1.31–1.77) /
increase the original risk ratio. In other cases, the coexistence of an extra dermatological sign increased the relative risk ratio.
4. Discussion This case-control study demonstrated the associations of several dermatological signs: male pattern baldness, thoracic hairiness and diagonal earlobe crease with the risk of MI in men under the age of 60 years. Rather large samples were analyzed and statistical control for age and other established risk factors for ischemic heart disease was performed. Common occurrences of baldness and thoracic hairiness as well as greyness of hair and diagonal earlobe crease were noted too.
4.1. Male pattern baldness Two large studies [7,8] and eight smaller studies (for review, see Herrera and Lynch [10]) have already dealt with this issue. The smaller studies reported inconsistent relation between male pattern baldness and ischemic heart disease. Our study and both previous large studies found that in men, baldness is associated with increased risk of MI and that this association is independent of age and other risk factors. In our study and the other large case-
control study [7] this association was significant for parietal, but not frontal baldness, while the opposite results were obtained in the cohort study of Shnohr et al. [8]. The reason for this discrepancy is unclear to us.
4.2. Thoracic hairiness To our knowledge this is the first report of an association of thoracic hairiness with the risk of MI. In our subjects (both cases and controls) the thoracic hairiness and baldness were frequently coexistent. Also, the relative risk of MI for men with both baldness and thoracic hairiness did not exceed the relative risk for baldness alone. These findings may suggest that baldness and thoracic hairiness are associated with the same factor that increases the risk of MI. It is known that testosterone stimulates the growth of hair in several regions, including thorax, but suppresses follicles of the scalp. On the other hand, there are data suggesting an atherogenic effect of testosterone [11]. Thus, it is tempting to speculate that men with increased level of testosterone have an increased risk of MI and incline to baldness and thoracic hairiness, as well. This hypothesis fits to our data, but is an indirect one, since it rests on another hypothesis. Namely, the atherogenic effect of testosterone, i.e. of its active metabolite dihydrotestosterone, was suggested in some [12–14], but not all studies addressing this issue [15,16].
4.3. Hair greying Completely grey hair was a significant predictor of MI in the cohort study of Schnohr et al. [8]. In our study moderately grey hair yielded a significant relative risk of MI, but only in men under the age of 45 years.
D. Miric´ et al. / International Journal of Cardiology 67 (1998) 251 – 255
4.4. Diagonal earlobe crease The association of this dermatological sign with MI was already reported by several groups [2,3,5]. We have noted the frequent common occurrence of hair greying and diagonal earlobe crease. This may suggest a common cause of these dermatological signs, which also increases the risk of MI. The diagonal earlobe crease may reflect the local vascular insufficiency with consequent skin atrophy. Since earlobe crease, hair greying and MI are associated, they could all be indicators of atherosclerosis.
255
In conclusion, we have demonstrated the association of baldness, hair greying, thoracic hairiness and diagonal earlobe crease with the risk of myocardial infarction in men under the age of 60. These associations were independent of age and other established risk factors, but not mutually. Baldness and thoracic hairiness, as well as grey hair and diagonal earlobe crease were mutually associated, pointing to common, yet unknown denominators of these pairs of dermatological signs and coronary heart disease.
References
4.5. Coexistence of several dermatological indicators With one exception [8] all previous studies have dealt with a single dermatological indicator of coronary risk. Schnohr et al. [8] studied baldness, hair greying and facial wrinkling, but did not assess the respective combined relative risks of MI. We have noted an often common occurrence of several dermatological signs and provided the estimates of their combined relative risk of MI. Moreover, the magnitudes of the relative risks for combination of dermatological indicators may reflect their mutual associations, as discussed above. As an epidemiologic case-control study, our study may suffer from selection biases and insufficient control for confounders. Yet, we think that large samples and adequate data reduction algorithms minimized those potential sources of error. On the other hand, it remains uncertain whether our results can be extrapolated to populations that differ in prevalences of the studied dermatological signs. It appears that the studied dermatological signs are as predictive of coronary heart disease as some established risk factors, like smoking and the presence of diabetes mellitus. However, it is not likely that these signs have more than indirect relationship with MI. Thus, they could only be used as indicators of increased risk of MI and any possible intervention should relate to the established risk factors that can be influenced (smoking, cholesterol, hypertension, etc.). Future research on the genetic or environmental factors that influence the studied dermatological signs might provide new data on the pathogenesis of coronary heart disease.
[1] Cotton SG, Nixon JH, Carpenter RG, Evans DW. Factors discriminating men with coronary heart disease from healthy controls. Br Heart J 1972;34:458–64. [2] Frank ST. Aural sign of coronary artery disease. N Engl J Med 1973;9:327–8. [3] Lichstein MD, Chadda MD, Naik MD, et al. Diagonal earlobe crease: prevalence and implications as a coronary risk factor. N Engl J Med 1974;290:615–6. [4] Cooke NT. Male pattern alopecia and coronary artery disease in men. Br J Dermatol 1979;34:458–64. [5] Kirham N, Murrels T, Melcher DH, Morrison EA. Diagonal earlobe creases and fatal cardiovascular disease: a necropsy study. Br Heart J 1989;61:361–4. [6] Trevisan M, Jassa F, Kragh V, et al. Baldness and coronary heart disease risk factors. Circulation 1990;81:18. [7] Lesko SM, Rosenberg L, Shapiro SA. Case-control study of baldness in relation to myocardial infarction in men. J Am Med Assoc 1993;269:998–1003. [8] Schnohr P, Lange P, Nyboe J, Appleyard M, Jansen G. Grey hair, baldness and wrinkles in relation to myocardial infarction: the Copenhagen City Heart Study. Am Heart J 1995;130:1003–10. [9] Dawson-Sanders B, Trapp RG. Basic and clinical biostatistics. East Norwalk, CT: Appleton and Lange, 1990. [10] Herrera CR, Lynch C. Is baldness a risk factor for coronary artery disease? A review of the literature. J Clin Epidemiol 1990;43:1255– 60. [11] Heller RF, Jacobs HS, Vermeulen A, Deslypere JP. Androgens, oestrogens and coronary heart disease. Br Med J 1981;282:438–9. [12] Sheridon PJ, McGill HC, Aufdemarte TB, Triplett RG, Holt RG. Heart contains receptors for dihydrotestosterone but not testosterone: possible role in the sex differential in coronary heart disease. Anat Rec 1989;223:414–9. [13] McGill HC, Anseelmo VO, Buchanon JH, Sheridon PJ. The heart is a target organ for androgen. Science 1980;207:775–7. [14] Hamalainen E, Adlercreutz H, Ehnholm C, Puska P. Relationships of serum lipoproteins and apoproteins to sex hormones and to the binding capacity of sex hormone binding globulin in healthy Finnish men. Metabolism 1986;35:535–41. [15] Vermeulen A, Deslypere JP. Long-term transdermal dihydrotestosterone therapy: effects on pituitary gonadal axis and plasma lipoproteins. Maturitas 1985;7:281–7. [16] Gormley GJ, Stoner E, Rittmaster RS, et al. Effects of finasteride (MK-906), a 5-alpha-reductase inhibitor on circulating androgens in male volunteers. J Clin Endocrinol Metab 1990;70:136–41.
Dermatological indicators of coronary risk: a case-control study ˇ ´ a , Ivo Bozic ˇ ´ a, Dinko Miric´ a , *, Damir Fabijanic´ a , Lovel Giunio a , Davor Eterovic´ b , Viktor Culic a Izet Hozo b
a ˇ´ 1, 21000 Split, Croatia Department of Medicine, Clinical Hospital Split, Spinciceva ˇ´ 1, 21000 Split, Croatia Department of Nuclear Medicine, Clinical Hospital Split, Spinciceva
Received 25 August 1998; accepted 30 September 1998
Abstract Objective: We examined the association of dermatological signs such as baldness, thoracic hairiness, hair greying and diagonal earlobe crease with the risk of myocardial infarction in men under the age of 60 years. Methods: A hospital-based, case-control study included 842 men admitted for the first non-fatal myocardial infarction, the controls were 712 men admitted with noncardiac diagnoses, without clinical signs of coronary disease. The relative risks were estimated as odds ratios. Logistic regression was used to control for the confounding variables. Results: Baldness, thoracic hairiness and earlobe crease were |40% more prevalent in cases (P,10 26 in each case). In both cases and controls, baldness and thoracic hairiness were frequently coexistent, as well as hair greying and earlobe crease (P,10 24 in each case). After allowing for age and other established coronary risk factors, the relative risk of myocardial infarction for fronto-parietal baldness compared with no hair loss was 1.77 (95% CI 1.27–2.45) and it was 1.83 (95 CI 1.4–2.3) for men with thick, extended thoracic hairiness. The presence of a diagonal earlobe crease yielded a relative risk of 1.37 (95% CI 1.25–1.5), while hair greying was associated with myocardial infarction only in men under the age of 50 years. Conclusion: It appears that baldness, thoracic hairiness and diagonal earlobe crease indicate an additional risk of myocardial infarction in men under the age of 60 years, independently of age and other established coronary risk factors. 1998 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Dermatological signs; Coronary risk; Myocardial infarction
1. Introduction The most important coronary risk factor is age. With advancing age, baldness, hair greying and wrinkling of the skin are increasingly common. Theoretically, the premature or extensive occurrence of these dermatological signs could identify a person with an accelerated aging process and consequent increased coronary risk. Another hypothesis is that increased levels of androgens is the common denominator of both the atherosclerotic process and dermatological signs like baldness and thoracic hairiness. The studies that have already addressed this *Corresponding author, Poljana stare gimnazije 1, 21000 Split, Croatia.
issue confirmed that male pattern baldness, grey hair, facial wrinkling and diagonal earlobe crease indicate increased coronary risk [1–8]. In most of these reports the age and other established risk factors were controlled for. However, the coexistence of several dermatological signs, though common in practice, was not properly accounted for. We are also unaware of any study of thoracic hairiness in relation to risk of myocardial infarction (MI). This study addresses these unresolved issues.
2. Patients and methods Data were collected from January 1991 to
0167-5273 / 98 / $ – see front matter 1998 Elsevier Science Ireland Ltd. All rights reserved. PII: S0167-5273( 98 )00313-1
252
D. Miric´ et al. / International Journal of Cardiology 67 (1998) 251 – 255
November 1997 from men under the age of 60 years who were admitted to two hospitals in Split, Croatia, at the Departments of cardiology, gastroenterology or traumatology. Cases were 842 men admitted for the first non-fatal MI and who had no history of rheumatic heart disease, cardiomyopathy or cardiac surgery. Controls were 712 men admitted for acute peptic ulcer (N5417) or injures acquired in traffic accident (N5295), who had normal ECG at rest and negative history of MI, angina pectoris, rheumatic heart disease, cardiomyopathy or cardiac surgery. Subjects with history of prior treatment of baldness were not included as cases or controls. Aside from these inclusion criteria and consent to participate in the study, the subjects were the consecutive groups of patients admitted to the respective departments. An acute MI was diagnosed according to World Health Organization criteria, that is if two of the following three criteria were fulfilled: (1) a typical chest pain lasting more than 30 min; (2) an ECG with pathologic Q waves with evolution; (3) an increase in at least one of the cardiac enzymes to over twice the upper limit of normal. The variable baldness was categorized as: (1) no baldness, (2) frontal baldness; (3) parietal baldness, i.e. baldness involving the vertex scalp; and (4) combined, fronto-parietal baldness. Hairiness of the thorax was categorized as: (1) mild or absent, when there were none or few sparse hairs on the limited area of the chest; (2) moderate, when a larger area of the chest was hairy; and (3) intensive, when the hairiness of the chest spread to the back and (or) shoulders. Hair greying was described as: (1) mild or absent, when there were none or single grey hairs diffusely over the scalp; (2) moderate, when grey sideburns were present; and (3) intensive, when the hair was completely grey / white. Presence of a diagonal earlobe crease was assigned to a person with a crease stretching obliquely from the outer ear canal towards the border of the earlobe of at least one ear. The collection of data on history of coronary or non-coronary cardiac disease and coronary risk factors (age, family history of MI, arterial hypertension, hypercholesterolemia, body mass index, diabetes and smoking), as well as assessment of dermatological signs were done by the residents during their internships at the respective departments. Smoking was quantified in terms of pack-years, i.e. as a product of
years of smoking and the packs of cigarettes consumed daily.
2.1. Data analyses Prevalences of categorical variables in cases and 2 controls were compared by x test. The same test was used to evaluate the associations of pairs of dermatological signs. The odds ratio was used to estimate the relative risk for MI for men with a particular dermatological sign, compared with men without that sign (category 1, as described above). The confidence intervals of these unadjusted (not controlled for age and other confounders) risk ratios were calculated by the Miettinen’s formula [9]. The adjusted risk ratios were obtained from the regression coefficients of the unconditional logistic regression. In each of those analyses the criterion variable was the presence of MI, the explanatory variables comprised one of the dermatological signs (or its single category) and the following set of covariates: age, family history of MI, arterial hypertension, hypercholesterolemia, body mass index, diabetes and smoking. In this way the relative risks of MI related to a particular dermatological sign were controlled for the established risk factors, but not for the dermatological signs other than the analyzed one. In order to account for the coexistence of several dermatological signs, the combinations of interaction variables (baldness3 hairiness, baldness3hairiness3earlobe crease, etc.) were used instead of a single dermatological sign in the above analyses. P values less than 0.05 were considered significant.
3. Results
3.1. Anthropometry: cases versus controls Table 1 summarizes the anthropometric parameters of the study subjects.
3.2. Prevalences of dermatological signs All dermatological signs were more common among cases compared to controls (Table 2). The differences ranged from 19% vs. 10% in case of
D. Miric´ et al. / International Journal of Cardiology 67 (1998) 251 – 255 Table 1 Clinical comparison between 842 cases of myocardial infarction and 712 non-cardiac control patients
Age (years) ,45 46–49 $50 Body mass index (kg / m 2 ) ,25 26–28 .29 Hypercholesterolemia Hypertension Family history of MI Smoking Diabetes
Cases
Controls
P value
194 (23%) 295 (35%) 353 (42%)
171 (24%) 223 (31%) 318 (45%)
NS NS NS
281 (31%) 362 (43%) 199 (26%) 109 (13%) 126 (15%) 261 (31%) 471 (56%) 42 (5%)
270 (38%) 292 (41%) 150 (21%) 58 (8%) 67 (9%) 175 (24%) 328 (46%) 14 (2%)
NS NS NS 0.004 0.001 0.006 0.001 0.003
253
parietal baldness, to 88% vs. 80% in case of any hair greying.
3.3. Risk ratios (raw and adjusted) The relative risk ratios for MI are given in Table 3. Control for the possible confounding effect of the established risk factors produced only slight changes in risk ratios. The strongest predictors of MI appeared to be parietal baldness and the diagonal earlobe crease. Hair greying yielded a significant risk ratio only in men younger then 45 years; this risk was 1.5 (95% CI 1–2.3) for moderately grey hair, while completely grey hair was approximately equally rare (around 3%) both in cases and controls.
3.4. Mutual association of dermatological signs Table 2 Prevalences of dermatological signs in 842 cases of myocardial infarction and 712 non-cardiac control patients
Baldness any frontal parietal fronto-parietal Thoracic hairiness any moderate intensive Hair greying any moderate intensive Earlobe crease
Cases
Controls
P value
50.5% 20% 19% 11.5%
35.5% 18.5% 10.5% 6.5%
4310 29 0.52 5310 26 8310 24
46.5% 25.5% 21%
32% 20.5% 11.5%
8310 29 0.02 8310 27
36.5% 32% 4.5% 62.9%
34.5% 30% 4.5% 46%
0.7 0.45 1 4310 211
Baldness and thoracic hairiness were frequently coexistent (or commonly absent), as well as hair greying and diagonal earlobe crease both in cases and controls (Table 4). Other combinations of pairs of dermatological signs were not significantly associated.
3.5. Combined risk ratios Table 5 presents the estimates of the relative risk ratios of MI for all combinations of common presence of baldness, thoracic hairiness and earlobe crease. Only the categories ‘any baldness’ and ‘any thoracic hairiness’ were analyzed. Inclusion of thoracic hairiness, in case of baldness, did not
Table 3 The relative risk ratio (95% CI) of myocardial infarction for men with a particular dermatological sign
Baldness any frontal parietal fronto-parietal Thoracic hairiness any moderate intensive Earlobe crease a
Unadjusted
Adjusted for standard risk factors a
1.42 (1.26–1.59) 1.08 (0.85–1.37) 1.81 (1.40–2.30) 1.77 (1.27–2.45)
1.40 0.90 1.90 1.68
(1.19–1.63) (0.71–1.42) (1.42–2.20) (1.20–2.50)
1.45 (1.28–1.64) 1.22 (1.03–1.45) 1.83 (1.44–2.32) 1.37 (1.25–1.5)
1.48 1.20 1.70 1.30
(1.33–1.77) (0.95–1.50) (1.40–2.55) (1.22–1.42)
Age, family history of MI, arterial hypertension, hypercholesterolemia, body mass index, diabetes and smoking.
D. Miric´ et al. / International Journal of Cardiology 67 (1998) 251 – 255
254
Table 4 Significances of associations of pairs of dermatological signs in cases of myocardial infarction and control non-cardiac patients Sign
Coexistence of Thoracic hairiness
Baldness Thoracic hairiness Hair greying
Hair greying
Earlobe crease
Cases
Controls
Cases
Controls
Cases
Controls
0.02 / N.S.
0.02 / N.S.
N.S. N.S. /
N.S. N.S. /
N.S. N.S. 0.04
N.S. N.S. 0.03
Significances are expressed as P values, obtained by x 2 test. Table 5 The relative risk ratios (95% C.I.) of myocardial infarction for men with several dermatological signs Cumulative presence of
Sign Baldness
Thoracic hairiness Earlobe crease
Baldness 1.42 (1.26–1.59) 1.40 (1.22–1.65) 1.66 (1.35–1.81) Thoracic hairiness / 1.45 (1.28–1.64) 1.60 (1.30–1.95) Earlobe crease and baldness / 1.65 (1.31–1.77) /
increase the original risk ratio. In other cases, the coexistence of an extra dermatological sign increased the relative risk ratio.
4. Discussion This case-control study demonstrated the associations of several dermatological signs: male pattern baldness, thoracic hairiness and diagonal earlobe crease with the risk of MI in men under the age of 60 years. Rather large samples were analyzed and statistical control for age and other established risk factors for ischemic heart disease was performed. Common occurrences of baldness and thoracic hairiness as well as greyness of hair and diagonal earlobe crease were noted too.
4.1. Male pattern baldness Two large studies [7,8] and eight smaller studies (for review, see Herrera and Lynch [10]) have already dealt with this issue. The smaller studies reported inconsistent relation between male pattern baldness and ischemic heart disease. Our study and both previous large studies found that in men, baldness is associated with increased risk of MI and that this association is independent of age and other risk factors. In our study and the other large case-
control study [7] this association was significant for parietal, but not frontal baldness, while the opposite results were obtained in the cohort study of Shnohr et al. [8]. The reason for this discrepancy is unclear to us.
4.2. Thoracic hairiness To our knowledge this is the first report of an association of thoracic hairiness with the risk of MI. In our subjects (both cases and controls) the thoracic hairiness and baldness were frequently coexistent. Also, the relative risk of MI for men with both baldness and thoracic hairiness did not exceed the relative risk for baldness alone. These findings may suggest that baldness and thoracic hairiness are associated with the same factor that increases the risk of MI. It is known that testosterone stimulates the growth of hair in several regions, including thorax, but suppresses follicles of the scalp. On the other hand, there are data suggesting an atherogenic effect of testosterone [11]. Thus, it is tempting to speculate that men with increased level of testosterone have an increased risk of MI and incline to baldness and thoracic hairiness, as well. This hypothesis fits to our data, but is an indirect one, since it rests on another hypothesis. Namely, the atherogenic effect of testosterone, i.e. of its active metabolite dihydrotestosterone, was suggested in some [12–14], but not all studies addressing this issue [15,16].
4.3. Hair greying Completely grey hair was a significant predictor of MI in the cohort study of Schnohr et al. [8]. In our study moderately grey hair yielded a significant relative risk of MI, but only in men under the age of 45 years.
D. Miric´ et al. / International Journal of Cardiology 67 (1998) 251 – 255
4.4. Diagonal earlobe crease The association of this dermatological sign with MI was already reported by several groups [2,3,5]. We have noted the frequent common occurrence of hair greying and diagonal earlobe crease. This may suggest a common cause of these dermatological signs, which also increases the risk of MI. The diagonal earlobe crease may reflect the local vascular insufficiency with consequent skin atrophy. Since earlobe crease, hair greying and MI are associated, they could all be indicators of atherosclerosis.
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In conclusion, we have demonstrated the association of baldness, hair greying, thoracic hairiness and diagonal earlobe crease with the risk of myocardial infarction in men under the age of 60. These associations were independent of age and other established risk factors, but not mutually. Baldness and thoracic hairiness, as well as grey hair and diagonal earlobe crease were mutually associated, pointing to common, yet unknown denominators of these pairs of dermatological signs and coronary heart disease.
References
4.5. Coexistence of several dermatological indicators With one exception [8] all previous studies have dealt with a single dermatological indicator of coronary risk. Schnohr et al. [8] studied baldness, hair greying and facial wrinkling, but did not assess the respective combined relative risks of MI. We have noted an often common occurrence of several dermatological signs and provided the estimates of their combined relative risk of MI. Moreover, the magnitudes of the relative risks for combination of dermatological indicators may reflect their mutual associations, as discussed above. As an epidemiologic case-control study, our study may suffer from selection biases and insufficient control for confounders. Yet, we think that large samples and adequate data reduction algorithms minimized those potential sources of error. On the other hand, it remains uncertain whether our results can be extrapolated to populations that differ in prevalences of the studied dermatological signs. It appears that the studied dermatological signs are as predictive of coronary heart disease as some established risk factors, like smoking and the presence of diabetes mellitus. However, it is not likely that these signs have more than indirect relationship with MI. Thus, they could only be used as indicators of increased risk of MI and any possible intervention should relate to the established risk factors that can be influenced (smoking, cholesterol, hypertension, etc.). Future research on the genetic or environmental factors that influence the studied dermatological signs might provide new data on the pathogenesis of coronary heart disease.
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