Relationship Between Frank's Sign and Cardiovascular Disease: An Autopsy-Based Study

Frank's sign, defined as a diagonal crease on the earlobe extending from the tragus to the outer edge, has been proposed as a potential external marker for cardiovascular (CV) mortality. While previous autopsy studies have linked it to fatal outcomes of coronary artery disease, this study was designed to compare its prevalence in CV versus non-CV deaths. A cross-sectional study of autopsy cases was conducted at Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia, from September 2023 to December 2024, examining 51 CV deaths and 51 matched non-CV deaths. The presence and severity of Frank's sign in both ears were assessed from photographs and correlated with critical coronary artery stenosis. Data were analyzed using IBM SPSS Statistics for Windows, Version 29.0 (Released 2022; IBM Corp., Armonk, NY, USA). Descriptive statistics were applied, chi-square tests were used to assess associations, and multivariable logistic regression controlled for confounders. The study population (N = 102) had a mean age of 46.5 years and was predominantly male (83.3%). The analysis revealed a significantly higher prevalence of Frank's sign in CV deaths compared to non-CV deaths (χ² = 18.21, p < 0.001). Furthermore, a strong association was found between the sign and critical atherosclerotic coronary artery occlusion at autopsy (χ² = 19.79, p < 0.001). Even after adjusting for age, sex, and ethnicity, Frank's sign remained a strong independent predictor of critical coronary occlusion, with an adjusted odds ratio of 7.77 (p < 0.001). The diagnostic performance, measured by Youden's index, was moderate, at 0.39 for predicting CV death and 0.42 for predicting critical occlusion, indicating a moderate discriminative ability. In summary, this study confirms a significant association between Frank's sign and CV mortality due to coronary artery atherosclerosis occlusion, suggesting its potential utility as a supportive, external clinical marker.