Earlobe crease (ELC) is a wrinkle-line in the skin that surrounds the ear approximately one third of the length between the tragus and the posteroinferior edge of the earlobe. Since the first study in 1973, the relationship between ELC and coronary heart disease (CHD) remains unclear. In addition, the pathogenesis of ELC has not well described, yet. This review aimed to evaluate the relationship between CHD and the presence of ELC using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) protocol. Eligible studies obtained from PubMed and Google Scholar using relevant keywords were collected. The assessment of quality of the studies was carried out based on the National Heart Lung and Blood Institute. Among 21 studies collected, 19 studies reported a correlation between the ELC and CHD indicating that ELC as a potential marker of CHD. Seven studies reported a significant association of ELC with CHD after adjusting confounding variables such as age, sex and other risk factors for atherosclerosis in analysis. Seven studies reported that subjects with ELC had more significantly severe CHD based on coronary angiography. The sensitivity of the ELC was reported between 30-98% and the specificity between 43-91%. Two studies reported no relationship between ELC and CHD after adjustment of age in analysis. Earlobe crease is a dermatological sign which was reported to have potential as a marker of CHD. Further study with large sample in population from various ethnics is needed in order to obtain a robust conclusion regarding the clinical importance of ELC in predicting CHD.

1. Agouridis AP, Elisaf MS, Nair DR, Mikhailidis DP. Ear lobe crease: a marker of coronary artery disease? Arch Med Sci 2015; 11(6):1145-55. https://doi.org/10.5114/aoms.2015.56340.
2. Study Quality Assessment Tools | NHLBI, NIH [Internet]. [cited 2020 Oct 7]. Available from: https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools
3. Mishra V, Khanra D, Himanshu K, Jain B, Tripathi S, Anggarwal P, et al. Correlation between earlobe crease and coronary artery disease in Indian population-A multicentre experience. J Clin Prev Cardiol 2020; 9(2):67-72. https://doi.org/10.4103/JCPC.JCPC_10_20
4. Suen LKP, Lau Y, Ma HC, Lai KW, Holtoyd E. Predictive value of auricular diagnosis on coronary heart disease. Evid Based Complement Alternat Med 2012; 2021:706249. https://doi.org/10.1155/2012/706249.
5. Shmilovich H, Cheng VY, Rajani R, Dey D, Tamaroppo 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. https://doi.org/10.1016/j.amjcard.2011.12.024
6. Wu XL, Yang DY, Zhao YS, Chai WH, Jin ML. Diagonal earlobe crease and coronary artery disease in a Chinese population. BMC Cardiovasc Disord 2014; 14:43. https://doi.org/10.1186/1471-2261-14-43
7. Wang Y, Mao LH, Jia EZ, Li ZY, Ding XQ, Ge PC, et al. Relationship between diagonal earlobe creases and coronary artery disease as determined via angiography. BMJ Open 2016; 6(2):008558. https://doi.org/10.1136/bmjopen-2015-008558
8. Sousa ED, Fernandes VLG, Goel HC, Naik K, Pinto NMG. A study on the prevalence of diagonal earlobe crease in patients with cardiovascular disease and diabetes mellitus. Indian J Otol 2020; 26(1):9-14. https://doi.org/10.4103/indianjotol.INDIANJOTOL_117_18
9. Kumar A. Frank’s sign and coronary artery disease in Indian population. Med Hear India. 2016. https://doi.org/10.4103/2321-449x.196285
10. Viveka S, Sagar TV, Kumar JA. Evaluation of 2D:4D digit ratio and diagonal earlobe crease as markers of coronary artery disease. J Anat Soc India 2016; 65(2):148-51. https://doi.org/10.1016/j.jasi.2017.02.004
11. Bawaskar HS, Bawaskar PH, Bawaskar PH. Diagonal ear lobe crease: A premonitory diagnostic sign of impeding ischemic heart disease. J Fam Med Prim care. 2018; 7(6):1361-7. https://doi.org/10.4103/jfmpc.jfmpc_181_18
12. Hou X, Jiang Y, Wang N, Shen Y, Wang X, Zhong Y, et al. The combined effect of ear lobe crease and conventional risk factor in the diagnosis of angiographically diagnosed coronary artery disease and the short-term prognosis in patients who underwent coronary stents. Medicine (Baltimore). 2015; 94(26):815. https://doi.org/10.1097/MD.0000000000000815.
13. Montazeri M, Montazeri M, Rashidi N, Montazeri M, Montazeri M. Diagonal earlobe crease and coronary artery disease in Iranian population: A marker for evaluating coronary risk. Indian J Otol 2014; 20(4):208-10. https://doi.org/ 10.4103/0971-7749.146941
14. Sharma RK, Pulimood S, Peter D, George L. Association of The Cutaneous Markers with Coronary Artery Disease: A Case-control Study. Indian J Clin Dermatology 2018; 1(1):6-11.
15. Kumar A, Kumar A, Kumar P, Kachhap S. Study to evaluate the frequency of diagonal earlobe crease as a marker of coronary artery disease and its risk factors in tertiary hospital of east india. Int J Sci Res 2018; 7(1):13-4.
16. Montazeri M, Rashidi N, Montazeri M, Melaki A, Motazeri M, Motazeri M. Is diagonal earlobe crease a marker for coronary artery disease? Hear India. 2014; 2(4):104-6. https://doi.org/10.4103/2321-449X.146614
17. López CR, Díaz HG, Mariscal RM, Cervilla PJS, Graciani A, Sendón JLL, et al. Earlobe crease shapes and cardiovascular events. Am J Cardiol 2015; 15;116(2):286-93. https://doi.org/10.1016/j.amjcard.2015.04.02
18. Christoffersen M, Frikke-Schmidt R, Schnohr P, Jensen GB, Nordestgaard BG, Tybjærg-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. https://doi.org/ 10.1161/CIRCULATIONAHA.113.001696
19. Aligisakis M, Vidal PM, Guessous I, Vollenweider P. Did Dumbo suffer a heart attack? independent association between earlobe crease and cardiovascular disease. BMC Cardiovasc Disord 2016; 16:17. https://doi.org/10.1186/s12872-016-0193-7
20. Wakasugi M, Nagai M, Yokota S, Omori K, Fujikawa H, Aoike I, et al. The association between earlobe creases and cardiovascular events in Japanese hemodialysis patients: a prospective cohort study. Intern Med 2020; 59(7):927-32. https://doi.org/10.2169/internalmedicine.3943-19
21. Ramdurg P, Srinivas N, Puranik S, Sande1 A. “Frank Sign”–A clinical indicator in the detection of coronary heart disease among dental patients: A case control study. J Indian Acad Oral Med Radiol 2018; 30(3):241-6. https://doi.org/10.4103/jiaomr.jiaomr_90_18
22. Kamal R, Kausar K, Qavi AH, Minto MH, Ilyas F, Assad S, et al. Diagonal earlobe crease as a significant marker for coronary artery disease: a case-control study. Cureus 2017; 9(2):e1013. https://doi.org/10.7759/cureus.1013
23. Wakasugi M, Kazama JJ, Kawamura K, Yamamoto S, Nagai M, Omori K, et al. Prevalence of earlobe creases and their association with history of cardiovascular disease in patients undergoing hemodialysis: a cross-sectional study. Ther Apher Dial 2017; 21(5):478-84. https://doi.org/10.1111/1744-9987.12567
24. Lucenteforte E, Romoli M, Zagli G, Gensini GF, Mugelli A, Vannacci A. Ear lobe crease as a marker of coronary artery disease: a meta-analysis. Int J Cardiol 2014; 175(1):171-5. https://doi.org/10.1016/j.ijcard.2014.04.025
25. Oda N, Maruhashi T, Kishimoto S, Kajikawa M, Iwamoto Y, Iwamoto A, et al. Relation of the Bilateral Earlobe Crease to Endothelial Dysfunction. Am J Cardiol 2017; 119(12):1983-8. https://doi.org/10.1016/j.amjcard.2017.03.029
26. Koyama T, Watanabe H, Ito H. The association of circulating inflammatory and oxidative stress biomarker levels with diagonal earlobe crease in patients with atherosclerotic diseases. J Cardiol 2016; 67(4):347-51. https://doi.org/10.1016/j.jjcc.2015.06.002
27. Stoyanov GS, Dzhenkov D, Petkova L, Sapundzhiev N, Georgiev S. The Histological Basis of Frank’s Sign. Head Neck Pathol 2020; 15(2):402-7. https://doi.org/10.1007/s12105-020-01205-4