Abstract
Background:
Ischemic heart disease (IHD) is among the most important and top ranked causes of death in the world. An early and accurate diagnosis of IHD is necessary to improve outcomes.Objectives:
We assessed the prevalence of dermatologic signs associate with the risk of ischemic heart disease among the hospitalized IHD patients.Materials and Methods:
This descriptive-analytic and cross-sectional study was conducted on IHD patients during 6 months in Kamkar Hospital in Qom and Shaheed Beheshti Hospital in Kashan. Participants were assessed for the presence of male pattern baldness, hair graying, diagonal earlobe crease (DELC), and xanthoma.Results:
A total of 366 patients with IHD (52.5% male and 47.5% female) with a mean age of 58.5 ± 7.5 years were evaluated. IHD was more prevalent between people 60-69 years old. Prevalence and occurrence of alopecia, hair whitening, DELC, and xanthoma were 79.2%, 78.7%, 34.1%, and 18.6%, respectively. Hyperlipidemia was seen in 70.5% of individuals with xanthoma. Alopecia was more prevalent in subjects with family history of baldness (P < 0.0001). Family history of hair whitening had a significant effect on its prevalence (P < 0.0001). Bilateral DELC was more prevalent than unilateral one (22.4% vs 12.5%).Conclusions:
Male pattern baldness, hair graying, xanthoma, and earlobe crease are associated with increased risk of ischemic heart disease. These dermatologic signs can be considered as CVD risk factors for screening.Keywords
Myocardial Ischemia Alopecia Graying of Hair Precocious Xanthomatosis
1. Background
Today, cardiovascular disease (CVD) is the most common cause of death, disability, and serious illness. Ischemic heart disease (IHD) is caused by inadequate oxygen delivery to supply the metabolic demands of the heart muscle. IHD can be the result of a failure to sufficiently perfuse myocytes with oxygenated blood, to increase myocyte oxygen need, or a collection of acute and chronic conditions such as coronary artery spasm, anemia, arrhythmia, coronary embolism, hypertension, or hypotension (1). In IHD, atherosclerosis usually causes progressive obstruction of one or more of the three main coronary arteries supplying oxygen and nutrients to the heart muscle. Acute myocardial necrosis, fatal arrhythmia, stable angina pectoris or heart failure can occur consequently (2). IHD was the leading cause of deaths in 2010, which affects adults of working age and is a growing problem in low- and middle-income countries (3-5). In terms of disability, ischemic heart disease problems include chest pain (angina) accompanying with physical or emotional stress, heart failure, and fear of engaging in normal activities. Early detection of ischemia is extremely important to prevent sudden death. The term IHD, often used synonymously with coronary heart disease (CHD), or coronary artery disease, which is most often due to atherosclerosis of coronary arteries.
The common clinical manifestations of IHD are myocardial infarction (MI), angina, and sudden death. CHD can be asymptomatic and its screening may fail to prevent cardiovascular events (6, 7). Several recent studies have shown that some hair and skin features are associated with the risk of CHD. These features include male pattern baldness or androgenic alopecia, hair graying, diagonal ear lobe crease (DELC), and xanthoma. As some individuals are free of classical risk factors such as hypertension, hyperlipidemia, diabetes, tobacco use, obesity, or sedentary a lifestyle (8), elucidating the relationship between hair and dermal signs and CHD could lead to the early detection of cardiac disease. Accordingly, it might let physicians identify persons at risk, thereby applying the most appropriate therapy to improve patients' prognosis.
2. Objectives
This study was undertaken to test whether androgenic alopecia, hair graying, DELC, and xanthoma are more prevalent in subjects with IHD.
3. Patients and Methods
3.1. Participants
This study had a descriptive-analytic cross-sectional design and was conducted on middle-aged and elderly men and women (≥ 40 year age) at Kamkar Hospital in Qom and Shaheed Beheshti Hospital in Kashan. We used easy nonrandomized method for sampling in which all patients with IHD diagnosis referred at Kamkar and Shaheed Beheshti hospitals were enrolled. Informed consent was obtained from all patients prior to conducting the study. The study was performed in accordance with the principles stated in the Declaration of Helsinki and approved by the Isfahan University of Medical Sciences Ethics Committee. Patients were diagnosed by residents of internal medicine based on IHD history and clinical examination. Electrocardiogram and biochemical tests were used to confirm the diagnosis and a cardiologist verified them. The patients were evaluated in terms of age, history of hypertension, hyperlipidemia, and diabetes mellitus, and smoking habits. Hypertension was defined by a systolic and diastolic blood pressure over 140 and 90 mm Hg, respectively. Patients under drug therapy for hypertension were considered as hypertensive. Hyperlipidemia was defined by history of abnormal values of cholesterol or triglycerides.
3.2. Dermatologic Features Assessment
Norwood’s androgenic alopecia classification was used to collect standardized information (9). We used a gray/white-hair proportion (more than 50% and less than 50%) to determine the percentage of hair whitening. The presence of a diagonal ear lobe crease was assigned to a person with a crease stretching obliquely from the outer ear canal towards the border of the ear lobe of both the ears; examiners were guided to diagnose the ELC, by comparing the features with the standard photograph provided to them. Xanthoma was determined by careful visual examination.
3.3. Statistical Analysis
Statistical analyses were conducted using SPSS 15.0 (SPSS Inc, Chicago, IL, USA). The chi-square and Fisher exact test were used for categorical variables. P values < 0.05 were considered as significant.
4. Results
A total of 366 patients with IHD were studied (192 men and 174 women). IHD was more prevalent between 60-69 year old cases. Table 1 shows the prevalence of androgenic alopecia, hair graying, DELC, and xanthoma in IHD patients. There were no meaningful differences between age, sex, underlying disease and the prevalence of dermatologic signs (P > 0.05). Prevalence of diseases such as diabetes mellitus, hypertension, and hyperlipidemia were 36.0%, 55.7%, and 43.1%, respectively. Smoking was seen in 29.5% of patients. Sex differences were found between hypertensive and smoker subjects (P < 0.0001). Alopecia was more prevalent in subjects with family history of baldness (P < 0.0001). Hair loss progression was less than 6 years in 38.1% and more than 6 years in 61.8% of patients (Data are not shown). Hyperlipidemia was seen in 70.5% of individuals with xanthoma. Family history of hair whitening had a significant effect on its prevalence (P < 0.0001). Bilateral DELC was more prevalent than unilateral (22.4% vs 12.5%) (Data are not shown). Table 2 illustrates joint prevalence of IHD risk factors based on dermatological indicators. As it shows, there is no difference in joint prevalence of IHD risk factors based on dermatologic signs (P > 0.05).
| Sign | Sex | Total | P Value | |
|---|---|---|---|---|
| Male | Female | |||
| Male pattern baldness | NS | |||
| with | 152 (79.2) | - | 152 (79.2) | |
| without | 40 (20.8) | - | 40 (20.8) | |
| Xanthoma | NS | |||
| with | 40 (20.8) | 28 (16.1) | 68 (18.6) | |
| without | 152 (79.2) | 146 (83.9) | 298 (81.4) | |
| Gray hair | NS | |||
| with | 152 (79.2) | 136 (78.2) | 288 (78.7) | |
| without | 40 (20.8) | 38 (21.8) | 78 (21.3) | |
| DELC c | ||||
| with | 68 (35.4) | 60 (34.5) | 128 (34.1) | NS |
| without | 124 (64.6) | 114 (65.5) | 238 (65.9) | |
| Risk factors | Male Pattern Baldness | Hair Graying | DELCN | Xanthoma | P Value |
|---|---|---|---|---|---|
| Hypertension and hyperlipidemia | 46 (23.9) | 88 (24.0) | 44 (12.0) | 34 (9.3) | NS |
| Hypertension and diabetes mellitus | 20 (10.4) | 66 (18.0) | 28 (7.6) | 20 (5.5) | NS |
| Hypertension and smoking | 40 (20.8) | 44 (12.0) | 24 (6.6) | 16 (4.4) | NS |
| Hyperlipidemia and diabetes mellitus | 30 (15.6) | 82 (22.4) | 38 (10.3) | 22 (6.0) | NS |
| Hyperlipidemia and smoking | 32 (16.7) | 44 (12.0) | 20 (5.5) | 12 (3.3) | NS |
| Diabetes mellitus and smoking | 28 (14.6) | 40 (10.9) | 20 (5.5) | 8 (2.2) | NS |
5. Discussion
This study was conducted to evaluate the prevalence of androgenic alopecia, hair graying, DELC, and xanthoma in 366 IHD patients admitted to Kamkar and Shaheed Beheshti hospitals. Our findings suggest that these dermatological signs, especially baldness and hair whitening can be considered as CVD risk factors. Male pattern baldness in the study showed a high prevalence of 79.2% in men. Positive association between heart diseases and baldness has been demonstrated in some previous studies too (10, 11). In a retrospective cohort study among 22071 male physicians relative risk (RR) CHD was 1.36 for severe vertex baldness, which remained unchanged after adjustment for risk factors such as age, diabetes mellitus, hypertension, and hyperlipidemia (12). A meta-analysis on risk of CHD and alopecia in observational studies confirmed this association but only for vertex baldness (13). Nevertheless, this relationship was not seen in some case-control and cross-sectional studies, which can be related to their design, selection and information biases. Cardiometabolic risk factors like hypertension, hyperlipidemia, fibrinogen, CRP, and insulin are higher in bald individuals (10, 12, 14-16), which are in contrast with our results. This discrepancy can be attributed to small sample size. As hormones like aldosterone and testosterone are greater in this group, peripheral sensitivity to androgens can explain the elevated levels of risk factors like blood pressure (14).
Several studies have shown an association between premature hair whitening and CHD (17-20). In the present study, prevalence of this indicator was noticeably high. Schnohr et al. found RR of 1.9 for myocardial infarction (MI) in men with completely gray hair in comparison with men who had no gray hair; in women there was a similar but non-significant weak relationship (17). It has also shown a positive relationship between risk factors that can be involved in this phenomenon through mechanisms like impaired DNA repair, inflammatory processes, and antioxidant reactions (21-26). However, some researchers could not find a correlation (27), which can be explained by their poor methodology and lack of determination of diseases severity.
When disturbance in lipoprotein metabolism exists, lipid containing foam cells appear in dermis or tendons which led to premature detection of atherosclerosis (28). In our study, the prevalence of xanthoma in IHD patients was 18.6%. Elevated levels of serum lipids, especially total cholesterol (TC) and LDL-c has been shown in patients with xanthomas (29-31). Even normolipidemic individuals with xanthelasma may have abnormal lipoprotein composition (32). There is a relationship between this sign and IHD or MI even after adjustment for other CVD risk factors (33). A meta-analysis showed that xanthoma in persons with familial hypercholesterolemia is associated with CVD risk (34). Hazard/odds ratio of MI, IHD, and ischemic cerebrovascular disease was respectively 1.48, 1.39, and 1.69 in participants with xanthelasma irregardless of plasma lipids (35). It can be explained by cholesterol leakage from vessels, its deposition in connective tissues, and its uptake by macrophages (36). Civeira et al. also found that tendon xanthoma (TX) is associated with hypertension (37).
There are numerous studies, which have demonstrated the very strong relationship between DELC and coronary artery atherosclerosis (CAA) (38-42). We found a 34.1% prevalence of DELC among our patients. Lichstein et al. showed that unilateral or bilateral DELC was significantly more common (47%) among patients hospitalized in an USA coronary-care unit than among age-matched control subjects (30%) (39). There was a relationship between DELC, arterial hypertension, and hypercholesterolemia (43). Degeneration of elastin, supplying ear lobe and heart by end arteries, skin aging, and shortened telomeres are some proposed mechanisms (44). In conclusion, male pattern baldness, hair graying, xanthoma, and earlobe crease are associated with increased risk of ischemic heart disease. These dermatologic signs can be considered as CVD risk factors for screening.
References
-
1.
Tehrani DM, Seto AH. Third universal definition of myocardial infarction: update, caveats, differential diagnoses. Cleve Clin J Med. 2013;80(12):777-86. [PubMed ID: 24307162]. https://doi.org/10.3949/ccjm.80a.12158.
-
2.
Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, et al. Third universal definition of myocardial infarction. Circulation. 2012;126(16):2020-35. [PubMed ID: 22923432]. https://doi.org/10.1161/CIR.0b013e31826e1058.
-
3.
Murray CJ, Vos T, Lozano R, Naghavi M, Flaxman AD, Michaud C, et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2197-223. [PubMed ID: 23245608]. https://doi.org/10.1016/S0140-6736(12)61689-4.
-
4.
Murray CJ, Lopez AD. Mortality by cause for eight regions of the world: Global Burden of Disease Study. Lancet. 1997;349(9061):1269-76. [PubMed ID: 9142060]. https://doi.org/10.1016/S0140-6736(96)07493-4.
-
5.
Abegunde DO, Mathers CD, Adam T, Ortegon M, Strong K. The burden and costs of chronic diseases in low-income and middle-income countries. Lancet. 2007;370(9603):1929-38. [PubMed ID: 18063029]. https://doi.org/10.1016/S0140-6736(07)61696-1.
-
6.
Pyorala K. Relationship of glucose tolerance and plasma insulin to the incidence of coronary heart disease: results from two population studies in Finland. Diabetes Care. 1979;2(2):131-41. [PubMed ID: 520116].
-
7.
Welborn TA, Wearne K. Coronary heart disease incidence and cardiovascular mortality in Busselton with reference to glucose and insulin concentrations. Diabetes Care. 1979;2(2):154-60. [PubMed ID: 520119].
-
8.
Despres JP, Lamarche B, Mauriege P, Cantin B, Dagenais GR, Moorjani S, et al. Hyperinsulinemia as an independent risk factor for ischemic heart disease. N Engl J Med. 1996;334(15):952-7. [PubMed ID: 8596596]. https://doi.org/10.1056/NEJM199604113341504.
-
9.
Norwood OT. Male pattern baldness: classification and incidence. South Med J. 1975;68(11):1359-65. [PubMed ID: 1188424].
-
10.
Trevisan M, Farinaro E, Krogh V, Jossa F, Giumetti D, Fusco G, et al. Baldness and coronary heart disease risk factors. J Clin Epidemiol. 1993;46(10):1213-8. [PubMed ID: 8410106].
-
11.
Ford ES, Freedman DS, Byers T. Baldness and ischemic heart disease in a national sample of men. Am J Epidemiol. 1996;143(7):651-7. [PubMed ID: 8651226].
-
12.
Lotufo PA, Chae CU, Ajani UA, Hennekens CH, Manson JE. Male pattern baldness and coronary heart disease: the Physicians' Health Study. Arch Intern Med. 2000;160(2):165-71. [PubMed ID: 10647754].
-
13.
Yamada T, Hara K, Umematsu H, Kadowaki T. Male pattern baldness and its association with coronary heart disease: a meta-analysis. BMJ Open. 2013;3(4). [PubMed ID: 23554099]. https://doi.org/10.1136/bmjopen-2012-002537.
-
14.
Arias-Santiago S, Gutierrez-Salmeron MT, Castellote-Caballero L, Buendia-Eisman A, Naranjo-Sintes R. Androgenetic alopecia and cardiovascular risk factors in men and women: a comparative study. J Am Acad Dermatol. 2010;63(3):420-9. [PubMed ID: 20619491]. https://doi.org/10.1016/j.jaad.2009.10.018.
-
15.
Ellis JA, Stebbing M, Harrap SB. Male pattern baldness is not associated with established cardiovascular risk factors in the general population. Clin Sci (Lond). 2001;100(4):401-4. [PubMed ID: 11256978].
-
16.
Arias-Santiago S, Gutierrez-Salmeron MT, Buendia-Eisman A, Giron-Prieto MS, Naranjo-Sintes R. A comparative study of dyslipidaemia in men and woman with androgenic alopecia. Acta Derm Venereol. 2010;90(5):485-7. [PubMed ID: 20814623]. https://doi.org/10.2340/00015555-0926.
-
17.
Schnohr P, Lange P, Nyboe J, Appleyard M, Jensen G. Gray hair, baldness, and wrinkles in relation to myocardial infarction: the Copenhagen City Heart Study. Am Heart J. 1995;130(5):1003-10. [PubMed ID: 7484729].
-
18.
Pomerantz HZ. The relationship between coronary heart disease and the presence of certain physical characteristics. Can Med Assoc J. 1962;86:57-60. [PubMed ID: 14487723].
-
19.
Gould L, Reddy CV, Oh KC, Kim SG, Becker W. Premature hair graying: a probable coronary risk factor. Angiology. 1978;29(11):800-3. [PubMed ID: 727561].
-
20.
Eisenstein I, Edelstein J. Gray hair in black males a possible risk factor in coronary artery disease. Angiology. 1982;33(10):652-4. [PubMed ID: 7125292].
-
21.
Van Neste D, Tobin DJ. Hair cycle and hair pigmentation: dynamic interactions and changes associated with aging. Micron. 2004;35(3):193-200. [PubMed ID: 15036274]. https://doi.org/10.1016/j.micron.2003.11.006.
-
22.
Tobin DJ, Paus R. Graying: gerontobiology of the hair follicle pigmentary unit. Exp Gerontol. 2001;36(1):29-54. [PubMed ID: 11162910].
-
23.
Kauser S, Thody AJ, Schallreuter KU, Gummer CL, Tobin DJ. A fully functional proopiomelanocortin/melanocortin-1 receptor system regulates the differentiation of human scalp hair follicle melanocytes. Endocrinology. 2005;146(2):532-43. [PubMed ID: 15498881]. https://doi.org/10.1210/en.2004-1145.
-
24.
Slominski A, Tobin DJ, Shibahara S, Wortsman J. Melanin pigmentation in mammalian skin and its hormonal regulation. Physiol Rev. 2004;84(4):1155-228. [PubMed ID: 15383650]. https://doi.org/10.1152/physrev.00044.2003.
-
25.
Lindner G, Botchkarev VA, Botchkareva NV, Ling G, van der Veen C, Paus R. Analysis of apoptosis during hair follicle regression (catagen). Am J Pathol. 1997;151(6):1601-17. [PubMed ID: 9403711].
-
26.
Mecklenburg L, Tobin DJ, Muller-Rover S, Handjiski B, Wendt G, Peters EM, et al. Active hair growth (anagen) is associated with angiogenesis. J Invest Dermatol. 2000;114(5):909-16. [PubMed ID: 10771470]. https://doi.org/10.1046/j.1523-1747.2000.00954.x.
-
27.
Glasser M. Is early onset of gray hair a risk factor? Med Hypotheses. 1991;36(4):404-11. [PubMed ID: 1809864].
-
28.
Parker F. Xanthomas and hyperlipidemias. J Am Acad Dermatol. 1985;13(1):1-30. [PubMed ID: 4031142].
-
29.
Gagne C, Moorjani S, Brun D, Toussaint M, Lupien PJ. Heterozygous familial hypercholesterolemia. Relationship between plasma lipids, lipoproteins, clinical manifestations and ischaemic heart disease in men and women. Atherosclerosis. 1979;34(1):13-24. [PubMed ID: 227426].
-
30.
van Aalst-Cohen ES, Jansen AC, Tanck MW, Defesche JC, Trip MD, Lansberg PJ, et al. Diagnosing familial hypercholesterolaemia: the relevance of genetic testing. Eur Heart J. 2006;27(18):2240-6. [PubMed ID: 16825289]. https://doi.org/10.1093/eurheartj/ehl113.
-
31.
Humphries SE, Cranston T, Allen M, Middleton-Price H, Fernandez MC, Senior V, et al. Mutational analysis in UK patients with a clinical diagnosis of familial hypercholesterolaemia: relationship with plasma lipid traits, heart disease risk and utility in relative tracing. J Mol Med (Berl). 2006;84(3):203-14. [PubMed ID: 16389549]. https://doi.org/10.1007/s00109-005-0019-z.
-
32.
Watanabe A, Yoshimura A, Wakasugi T, Tatami R, Ueda K, Ueda R, et al. Serum lipids, lipoprotein lipids and coronary heart disease in patients with xanthelasma palpebrarum. Atherosclerosis. 1981;38(3-4):283-90. [PubMed ID: 7225167].
-
33.
Christoffersen M, Frikke-Schmidt R, Schnohr P, Jensen GB, Nordestgaard BG, Tybjaerg-Hansen A. Visible age-related signs and risk of ischemic heart disease in the general population: a prospective cohort study. Circulation. 2014;129(9):990-8. [PubMed ID: 24334176]. https://doi.org/10.1161/CIRCULATIONAHA.113.001696.
-
34.
Oosterveer DM, Versmissen J, Yazdanpanah M, Hamza TH, Sijbrands EJ. Differences in characteristics and risk of cardiovascular disease in familial hypercholesterolemia patients with and without tendon xanthomas: a systematic review and meta-analysis. Atherosclerosis. 2009;207(2):311-7. [PubMed ID: 19439299]. https://doi.org/10.1016/j.atherosclerosis.2009.04.009.
-
35.
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;343:d5497. [PubMed ID: 21920887]. https://doi.org/10.1136/bmj.d5497.
-
36.
Bergman R. The pathogenesis and clinical significance of xanthelasma palpebrarum. J Am Acad Dermatol. 1994;30(2 Pt 1):236-42. [PubMed ID: 8288783].
-
37.
Civeira F, Castillo S, Alonso R, Merino-Ibarra E, Cenarro A, Artied M, et al. Tendon xanthomas in familial hypercholesterolemia are associated with cardiovascular risk independently of the low-density lipoprotein receptor gene mutation. Arterioscler Thromb Vasc Biol. 2005;25(9):1960-5. [PubMed ID: 16020744]. https://doi.org/10.1161/01.ATV.0000177811.14176.2b.
-
38.
Friedlander AH, Scully C. Diagonal ear lobe crease and atherosclerosis: a review of the medical literature and oral and maxillofacial implications. J Oral Maxillofac Surg. 2010;68(12):3043-50. [PubMed ID: 20970909]. https://doi.org/10.1016/j.joms.2010.07.009.
-
39.
Lichstein E, Chadda KD, Naik D, Gupta PK. Diagonal ear-lobe crease: prevalence and implications as a coronary risk factor. N Engl J Med. 1974;290(11):615-6. [PubMed ID: 4812503]. https://doi.org/10.1056/NEJM197403142901109.
-
40.
Kaukola S. The diagonal ear-lobe crease, a physical sign associated with coronary heart disease. Acta Med Scand Suppl. 1978;619:1-49. [PubMed ID: 279228].
-
41.
Kaukola S, Manninen V, Valle M, Halonen PI. Ear-lobe crease and coronary atherosclerosis. Lancet. 1979;2(8156-8157):1377. [PubMed ID: 92726].
-
42.
Shmilovich H, Cheng VY, Rajani R, Dey D, Tamarappoo BK, Nakazato R, et al. Relation of diagonal ear lobe crease to the presence, extent, and severity of coronary artery disease determined by coronary computed tomography angiography. Am J Cardiol. 2012;109(9):1283-7. [PubMed ID: 22335855]. https://doi.org/10.1016/j.amjcard.2011.12.024.
-
43.
Gutiu I, el Rifai C, Mallozi M. Relation between diagonal ear lobe crease and ischemic chronic heart disease and the factors of coronary risk. Med Interne. 1986;24(2):111-6. [PubMed ID: 3726421].
-
44.
Friedlander AH, Lopez-Lopez J, Velasco-Ortega E. Diagonal ear lobe crease and atherosclerosis: a review of the medical literature and dental implications. Med Oral Patol Oral Cir Bucal. 2012;17(1):e153-9. [PubMed ID: 21743392].