Authors:

Amoateng R*, Choi J and Caplice N

Department of Cardiology, Cork University Hospital, Wilton, Cork, Ireland

Source:

Journal of Cardiovascular Diseases & Diagnosis

Abstract
 

Objective:

Investigate the association of diagonal earlobe crease (DELC) and coronary artery disease (CAD) in men under 60.

Design:

A prospective case-control study.

Setting:

Male patients aged 60 and under, admitted to cardiology wards at Cork University Hospital.

Participants: 94 male patients were recruited from January 2018 to January 2019. 45 patients acutely presenting at the cardiology wards with an acute coronary syndrome event were included in the study. 49 patients without a history of CAD on the same wards were used as controls. Patients with visible trauma to the earlobe were excluded from the study.

Interventions: Subjects’ earlobes were inspected for the presence or absence of DELC and images were captured to be reviewed by two blinded observers.

Primary and secondary outcome measures: Primary goal was to establish the prevalence of DELC among male cardiac patients under 60. Secondary goal was to investigate the association of DELC with the traditional risk factors: smoking, hypertension, dyslipidaemia, diabetes.

Results:

Mean age (in years) of patients with DELC was 51.9 ± 7.33 (p<0.015). The prevalence of DELC among cardiac patients was 80% compared to 51% in the control group (p<0.003). Sensitivity and specificity of DELC to detect CAD was 80% and 49.0% and an odds ratio of 3.84 (95% confidence interval of 1.53-9.64, p<0.001). DELC was independently associated with CAD (p<0.001). Smoking history was associated with DELC (p<0.046). Hypertension, dyslipidaemia and diabetes were not associated with DELC (p<0.241, p<0.478, p=1.000 respectively).

Conclusion:

DELC was independently associated CAD and smoking history. DELC could be used as a simple clinical tool to risk-stratify patients for CAD.

Keywords:

Coronary artery disease; Coronary angiography study; NSTEMI; STEMI

Introduction

Coronary artery disease (CAD) is one of the leading causes of mortality and morbidity in the developed world. CAD is becoming increasingly prevalent due to our aging population [1]. There are well established risk factors of CAD. Some of these risk factors require specific investigations: lipid profiles, serum glucose, HbA1c.

Identification of simple clinical signs is thus very important in reducing the burden of disease. Xanthelasma, cornus arcus, male pattern baldness are all physical markers that have been associated with CAD [2]. Diagonal earlobe crease (DELC) (Figure 1) is another potential clinical sign for coronary artery disease (CAD). The association of DELC and CAD has been widely debated since its first description by Frank in 1973 [3]. DELC has been defined as a wrinkle-like line or crease that runs obliquely from the tragus of the ear to the outer ear [3,4] . Since Frank's publication, there have been several studies that have expanded on his work. Over the period of four decades, the association between DELC and CAD is very much still a controversial topic in cardiology.

Several studies have found a positive correlation between DELC and CAD. However, there are a substantial number of studies that couldn’t establish an association, most of which attributed DELC to an age-related change [5]. Some of these studies only found DELC to be statistically significant in patients older than 60 years [4,6-9]. The association between DELC and the other risk factors of CAD has also been studied extensively. Smoking, hyperlipidaemia, diabetes and hypertension have all been shown to be associated with DELC [5]. Though the sensitivity of DELC has been quite low, as evidenced in previous studies, DELC when combined with the other risk factors may aid to better detect the disease [5]. We could find only two published studies investigating the association between DELC and CAD in Ireland. Among those studies, the evidence is again conflicting - one found an association while the other did not [10,11].

The aim of this study was to investigate the association of DELC and CAD in high-risk cardiac but younger patients i.e., male patients aged 60 and below in an Irish hospital. Secondary goals were to determine its association with other risk factors and CAD.

Methods

Patients and inclusion criteria

The current study was designed as a prospective case-control. Male patients not older than 60 presenting with acute coronary syndrome at Cork University Hospital (CUH) from January 2018 to January 2019 were prospectively recruited. Male patients aged 60 and under without a history of CAD hospitalized over the same period were used as controls. Patients presenting to the hospital with an acute coronary syndrome: unstable angina, Non-ST Elevation Myocardial Infarction (NSTEMI) or a ST Elevated Myocardial Infarction (STEMI) who were undergoing a Coronary Angiography Study were used as the interventional group. Male subjects on the ward who were admitted for non-cardiac reasons and had no history of a cardiac event were also included in the study. Patients were examined for the presence of DELC in the sitting position. Images of the ear were captured to be cross-examined by two independent observers who were blinded to the study. Patients who had visible trauma or prior history of trauma to the ear including piercing were excluded from the study. Out of the 498 male patients screened, only of 94 patients met the inclusion criteria.

Consequently, patients were divided into two groups: one group was the CAD group (n=45) and the non-CAD group (n=49). Cardiovascular risk factors and medical history were obtained from a brief bedside history and the medical charts. Current medications for subjects in the CAD group prior to their hospital admission were recorded. The Ethics Committee of Cork University Hospital reviewed and approved the study protocol. Informed Consent was obtained from all study participants.

Risk factors for cardiovascular disease

Cigarette smoking, diabetes mellitus, hypertension and dyslipidaemia were collected. Smoking was defined as being a current smoker or significant heavy smoker in the past (>20 pack-years). Hypertension was defined as having systolic blood pressure ≥ 140 mmHg and diastolic blood pressure ≥ 90 mmHg or previously diagnosed hypertension. Diabetes Mellitus was defined as fasting glucose ≥ 7.0 mmol/L or HbA1c ≥ 6.5% according to the guidelines of Irish College of General Practitioners [12]. Patients previously diagnosed with diabetes mellitus and on anti-diabetic medications were also classified as diabetic. Dyslipidaemia was defined as a fasting LDL >140 mg/dl or triglyceride >150 mg/dl and all patients with a previous diagnosis of hyperlipidaemia and on medical management.

Statistical Analysis

All data were analyzed using Statistical Package for the Social Sciences (SPSS) version 25 for Windows. Bivariate statistical analysis was performed. Student’s t-test and Mann-Whitney U test were used for quantitative variables such as age. Chi-Square and Fischer-Exact test were used for categorical variables; the presence or absence of DELC or a risk factor. The sensitivity, specificity and predictive values for DELC and the cardiovascular risk factors were computed from four-fold tables. A receiver operating characteristic curve (ROC) was generated for DELC. A multivariate regression analysis was performed to rule out any mutual association between the traditional cardiovascular risk factors and CAD. A p<0.05 was considered as statistically significant. Data are expressed as mean ± standard deviation.

Results

Baseline characteristics

Patient demographic characteristics of the 94 subjects are outlined in Table 1. Prevalence of CAD was 47.9%. 61 patients had DELC present (67%). 36 out of the 45 patients with CAD had DELC compared to 25 out of 49 for patients without CAD (80% vs 51%, p=0.003) (Table 1). The overall inter-observer agreement for DELC was 97%. All the traditional risk factors: age, smoking, hypertension, dyslipidaemia, were significantly associated with CAD except diabetes (p=0.010, p=0.003, p=0.000, p=0.000, p=0.642 respectively).

The sensitivity, specificity, positive predict value (PPV) and negative predictive value (NPV) of DELC to diagnose CAD were 80.0%, 49.0%, 59.0%, 72.7% respectively and an area under the receiver operator characteristic curve of 0.645 (95% confidence interval of 0.533 to 0.757, p=0.016) (Figure 2). DELC had a similar sensitivity, specificity, PPV and NPV to smoking. The values for the other traditional risk factors are included in Table 4.

Multiple regression analysis: DELC as an independent risk factor for CAD

Multivariate regression analysis revealed that there was no mutual association between DELC and the other risk factors (p=0.001) (Table 2). The odds ratio (OR) for DELC was 3.84 (95% confidence interval from 1.53-9.64). Dyslipidaemia had the highest OR for DELC, 11 (95% confidence interval from 3.676-32.916). The other traditional risk factors: smoking, hypertension, dyslipidaemia and age were also independently associated with CAD (p=0.001, p=0.000, p=0.000, p=0.001 respectively). Only diabetes was not independently associated with CAD (p=0.323).

Association between DELC and the other risk factors

Smoking was found to be associated with the presence of DELC. 72.1% of patients with DELC had a smoking history (p=0.046). Age was also associated with the presence of DELC. The mean age in years of patients with DELC was 51.9 ± 7.33 and the mean age (in years) of patients with DELC absent was 46 ± 11.4 (p=0.015). Hypertension, dyslipidaemia and diabetes were not found to be associated with DELC (p=0.241, p=0.478, p=1.000 respectively) 

Discussion

Our study successfully demonstrated that DELC is an independent risk factor of CAD and is associated with smoking history. We showed that DELC is a useful marker for CAD in patients under 60 years of age. DELC may be used to help risk-stratify patients for CAD. It is a simple non-invasive marker that could be used in conjunction with conventional risk factors.

Association between DELC and CAD

Smoking, hypertension, dyslipidaemia, diabetes and advanced age are all well-known risk factors of coronary vessel disease. These risk factors except diabetes were all shown to be associated with coronary artery disease in our study population. Only 13 patients had diabetes; the low number of diabetic patients may explain why no statistical significance was detected. A most recent study found an association though many others did not find the usefulness of DELC in diabetes [13-15]. Most notably, DELC was also associated with CAD (p=0.003). The prevalence of diagonal earlobe crease among the interventional group was very high at 80%. This finding concurs with a number of international studies that found an association [1,4-7,11,16-20]. In this study, DELC had a high sensitivity to detect CAD but a low specificity. Similar findings were reported by Shimlovich et al. [7]. However, a recent meta-analysis showed a pooled sensitivity and specificity from 37 studies to be 62% and 67% respectively [20]. These values suggest that DELC cannot be used alone to detect CAD. The current Atherosclerotic Cardiovascular Disease (ASCVD) 10-year risk assessment includes all the conventional risk factors. DELC when included in this assessment may improve its accuracy in predicting CAD. The pathogenesis of CAD, atherosclerosis, is as a result of the combination of multiple risk factors. Though this study didn’t address the pathogenesis of DELC, it has not been fully understood. Very few studies have attempted to investigate its aetiology [1,21,22]. Given its low specificity, perhaps DELC is not exclusive to CAD and may be linked to several other pathologies.

A multivariate regression analysis demonstrated that DELC was independently associated with CAD. We were able to show that the other risk factors were not confounding in our study population. The odds ratio of DELC for CAD was found to be 3.84 (95% CI 1.53-9.64 (p=0.001). Wu et al. found a much similar OR in their study but with a much narrower confidence interval [8].

Age and DELC

The mean age of patients with DELC was slightly higher than patients without DELC (51.9 ± 7.33 vs 46.2 ± 11.4, p=0.015). Though DELC may be associated with advancing age, this study showed that DELC can be associated in patients younger than 60. A number of studies reported the association of DELC in much older patients thus attributing the finding to advanced age [1,4,6-8,23]. These studies did not find the association of DELC with CAD to be statistically significant when age was adjusted. However, we have demonstrated that DELC could possibly be used clinically to assess patients who are much younger.

Association of DELC with other risk factors

Smoking history was found to be associated with DELC in our study population. Smoking history was also found to be associated with DELC by Toyosaki, Doering and Montazeri et al. [6,24,25]. However, several studies could not find a similar association. [1,22,26-29]. The risk factors associated with DELC seem to differ from one study to another [5]. Different study population demographics and sample sizes may contribute to the varying study results. A large-scale study with a more diverse population should be conducted for more clarity. Even though the pathogenesis of DELC isn’t fully understood, DELC has been showed by this study and several other publications to be associated with one or more of the conventional cardiovascular risk factors.

Strengths

This is the second study to confirm the association of DELC and CAD in Ireland to the best of our knowledge. It is also one of the only few studies to link DELC to smoking history and patients aged 60 and below. The case-control set up enabled us to generate odd ratios and also to show that DELC is an independent risk factor. The design was very cost effective. No patients were lost to follow-up as it was not required. CAD has a very long latency period; thus, this design was very appropriate.

Future Directions

Future work could focus on clarifying the association with the traditional risk factors with a much larger and more diverse study population. It has been nearly half a century since DELC was first described. Several studies have shown and confirmed its significance as a clinical marker. A robust study needs to be conducted to resolve the ambiguity surrounding DELC. A prospective cohort study should investigate the timeline of DELC and the onset of CAD. Furthermore, absence of CAD in the control population with DELC doesn’t exclude the possibility of CAD later in life. It would be interesting to follow-up these patients to determine whether or not they develop CAD.

Conclusion

Diagonal earlobe crease is significantly and independently associated with CAD and smoking. It could be used in the clinical assessment of patients suspected of coronary artery disease, especially in patients who are high-risk or possess one or more of the conventional risk factors.

Limitation of the Study

This study is limited by several factors. The study population is not representative of the general population. It is only based on male patients and only 2 of the study subjects were non-Caucasian. The results may not be applicable to other ethnic groups or females. There is potential bias for identifying DELC since a universal grading system is not available. Absolute risk and incidence could not be calculated based on this study design. The strict inclusion criteria, only male patients aged 60 or less, limited the sample size. Finally, a few subjects were excluded from the study because they had a remote history of CAD. It was uncertain which group applied to these patients.

Acknowledgement

A special thanks to Professor Noel Caplice who came up with the research topic and aided in identifying diagonal earlobe crease. I am honoured to have worked on this project with him. My gratitude to Janet Choi, who helped set up my project and also for being a blinded observer. I appreciate the CUH cardiology nursing staff whose tremendous efforts aided me in recruiting study subjects. Finally, I would like to thank all the patients who agreed to participate in this research.

Copyright: 

© 2019 Amoateng R, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.