Association Between Right-Hand 2D:4D Ratio and Left Main Coronary Artery Stenosis in Women

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This prospective observational study included 400 patients undergoing coronary angiography and cardiac surgery. Right- and left-hand 2D:4D ratios were measured, and LMCA stenosis severity was assessed angiographically. Exploratory analyses evaluated potential associations between right-hand 2D:4D ratios and selected postoperative outcomes, including intensive care unit length of stay and acute kidney injury. Female patients were further stratified according to LMCA stenosis severity (< 50% vs ≥ 50%), and multivariable logistic regression analysis was performed. Among female patients, right-hand 2D:4D ratios were significantly higher in those with LMCA stenosis ≥ 50%, whereas no significant association was observed for left-hand 2D:4D ratios. No clinically meaningful associations were identified between right-hand 2D:4D ratios and selected postoperative outcomes in either sex. In multivariable analysis, the right-hand 2D:4D ratio remained independently associated with significant LMCA stenosis in female patients. These findings suggest a potential sex-specific relationship between prenatal hormonal markers and LMCA disease severity. 2D:4D ratio left main coronary artery sex differences coronary artery disease prenatal hormonal exposure 1. Introduction The second-to-fourth digit ratio (2D:4D) has been proposed as a biological marker reflecting prenatal exposure to sex hormones, particularly the balance between testosterone and estrogen [ 1 , 2 ]. Lower 2D:4D ratios are generally associated with higher prenatal androgen exposure, whereas higher ratios are thought to reflect relatively greater prenatal estrogen effects [ 3 ]. Beyond its developmental implications, the 2D:4D ratio has attracted increasing attention as a biological marker that has been explored in relation to cardiovascular structure and function [ 4 ]. Previous studies have reported associations between the 2D:4D ratio and various cardiovascular risk factors and outcomes, including coronary artery disease, hypertension, myocardial infarction, and vascular reactivity [ 5 – 7 ]. These findings have raised interest in the hypothesis that prenatal hormonal influences may contribute to sex-specific susceptibility to cardiovascular disease later in life [ 8 ]. However, results across studies have been inconsistent, and the clinical relevance of the 2D:4D ratio remains controversial. Left main coronary artery (LMCA) stenosis represents a distinct and clinically important form of coronary artery disease, given its association with extensive myocardial ischemia and adverse outcomes [ 9 ]. Despite its importance, limited data exists regarding the relationship between the 2D:4D ratio and LMCA disease specifically. Moreover, potential sex-specific associations between 2D:4D ratios and LMCA stenosis have not been adequately explored. In addition to coronary anatomy, postoperative outcomes following cardiac surgery—such as intensive care unit (ICU) length of stay and acute kidney injury—are influenced by a complex interplay of patient-related and procedural factors [ 10 , 11 ]. Whether the 2D:4D ratio is associated with such postoperative outcomes remains largely unexplored and warrants cautious, exploratory investigation. Therefore, the primary aim of this study was to investigate the association between right- and left-hand 2D:4D ratios and LMCA stenosis, with a particular focus on female patients. Secondary objectives included exploratory analyses assessing potential associations between 2D:4D ratios and selected postoperative outcomes in both female and male patients. 2. Materials and Methods Study Design and Population This prospective observational study included 400 consecutive patients who underwent coronary angiography and cardiac surgery at a tertiary care center. Patient enrollment was prospectively continued during the predefined study period until 400 eligible patients were included. No formal a priori sample size calculation was performed, as this was a prospective observational study with exploratory components. Patients with available angiographic data and measurable second-to-fourth digit (2D:4D) ratios were eligible for inclusion. The study population comprised both female and male patients; sex-specific analyses were predefined, with a primary focus on female patients. Written informed consent was obtained from all participants prior to enrollment. The study protocol was approved by the local institutional ethics committee (Approval no:2025/6067) and conducted in accordance with the Declaration of Helsinki. Measurement of 2D:4D Ratio Right- and left-hand 2D:4D ratios were determined by measuring the lengths of the second (index) and fourth (ring) digits from the basal crease to the fingertip. Measurements were performed using standardized digital calipers, and the 2D:4D ratio was calculated by dividing the length of the second digit by that of the fourth digit. Biologically implausible values were excluded from analysis. Angiographic Assessment of LMCA Stenosis Coronary angiography was performed according to standard clinical protocols. The severity of left main coronary artery (LMCA) stenosis was assessed by experienced cardiologists blinded to 2D:4D measurements. LMCA stenosis was categorized as < 50% or ≥ 50% for primary analyses. Additional exploratory analyses evaluated alternative LMCA stenosis cut-off values (≥ 30% and ≥ 40%). Postoperative Outcomes Exploratory postoperative outcomes included intensive care unit (ICU) length of stay and acute kidney injury (AKI). ICU length of stay was recorded in hours and dichotomized according to the median value. AKI was defined as an increase in postoperative serum creatinine of ≥ 0.5 mg/dL compared with the preoperative value. Statistical Analysis Continuous variables are presented as mean ± standard deviation or median (interquartile range), as appropriate. Categorical variables are presented as number and percentage. Comparisons between groups were performed using the Mann–Whitney U test for continuous variables and the chi-square or Fisher’s exact test for categorical variables. Sex-stratified analyses were conducted, and subsequent analyses focused on female patients. Multivariable logistic regression analysis was performed to identify independent predictors of LMCA stenosis ≥ 50% in female patients, adjusting for age, smoking status, diabetes mellitus, and hypertension. Exploratory analyses were interpreted cautiously. All analyses were conducted using an available-case approach without data imputation, and a two-sided p value < 0.05 was considered statistically significant. Statistical analyses were performed using SPSS software (version 22.0; IBM Corp., Armonk, NY, USA). 3. Results 3.1. General Characteristics of the Study Population A total of 400 patients were included in the study. The general demographic and clinical characteristics of the study population, as well as the distribution of surgical case types, are summarized in Table 1 . Of the total cohort, 270 patients (67.5%) were female and 130 (32.5%) were male. The mean age was 61.3 ± 13.2 years. The surgical case distribution consisted of isolated coronary artery disease, isolated valve surgery, and combined coronary artery bypass grafting with valve surgery. Table 1 General Characteristics and Surgical Case Distribution of the Study Population Variable Total (n = 400) Age, years 61.3 ± 13.2 Female sex, n (%) 270 (67.5%) Male sex, n (%) 130 (32.5%) Right-hand 2D:4D ratio 0.982 ± 0.053 Left-hand 2D:4D ratio 0.983 ± 0.049 Current smoking, n (%) 232 (58.0%) Hypertension, n (%) 253 (63.3%) Diabetes mellitus, n (%) 166 (41.5%) Hyperlipidemia, n (%) 198 (49.5%) Chronic kidney disease, n (%) 74 (18.5%) Chronic obstructive pulmonary disease, n (%) 61 (15.3%) Atrial fibrillation, n (%) 89 (22.3%) Left ventricular ejection fraction (%) 52.6 ± 9.8 Case type n (%) Isolated coronary artery disease (CABG only) 202 (50.5%) Isolated valve surgery 103 (25.8%) CABG + valve surgery 95 (23.7%) CABG; Coronary artery bypass grafting, Data are presented as mean ± standard deviation, median (interquartile range), or number (%), as appropriate. 3.2. Right-Hand 2D:4D Ratio and Selected Postoperative Outcomes Exploratory analyses were performed to evaluate whether the right-hand 2D:4D ratio was associated with selected postoperative outcomes, including intensive care unit (ICU) length of stay and the occurrence of acute kidney injury (AKI). These analyses were conducted separately in female and male patients. As shown in Table 2 , no clinically meaningful or consistent differences in right-hand 2D:4D ratios were observed according to ICU length of stay or AKI status in either sex, indicating that the right-hand 2D:4D ratio was not strongly associated with these postoperative outcomes in the overall study population. Table 2 Associations of Right-Hand 2D:4D Ratio with Selected Postoperative Outcomes According to Sex Outcome Group Female (n = 270) Right-hand 2D:4D (Median) Male (n = 130) Right-hand 2D:4D (Median) ICU stay duration Short ICU stay 0.974 0.984 Long ICU stay 0.978 0.989 Acute kidney injury (AKI) No AKI 0.975 0.986 AKI present 0.978 0.950 ICU length of stay was dichotomized according to the median value. Acute kidney injury was defined as an increase in postoperative serum creatinine ≥ 0.5 mg/dL. 3.3. Baseline Characteristics of Female Patients According to LMCA Stenosis Subsequent analyses focused on female patients, in line with the primary objective of the study. Baseline demographic and clinical characteristics of female patients stratified according to LMCA stenosis (< 50% vs. ≥50%) are presented in Table 3 . Female patients with LMCA stenosis ≥ 50% had a higher prevalence of traditional cardiovascular risk factors. Importantly, the right-hand 2D:4D ratio was significantly higher in female patients with LMCA stenosis ≥ 50% compared with those with < 50% stenosis, whereas no significant difference was observed for the left-hand 2D:4D ratio. Table 3 Baseline Characteristics of Female Patients Stratified by Left Main Coronary LMCA: left main coronary artery. Variable LMCA < 50% (n = 124) LMCA ≥ 50% (n = 6) p value Age, years 65.24 ± 57.62 60.80 ± 12.38 NS Current smoking, n (%) 48 (38.7%) 2 (33.3%) NS Hypertension, n (%) 83 (66.9%) 5 (83.3%) NS Diabetes mellitus, n (%) 49 (39.5%) 5 (83.3%) NS Right-hand 2D:4D ratio 0.98 ± 0.05 1.04 ± 0.05 0.016 Left-hand 2D:4D ratio 0.99 ± 0.05 1.04 ± 0.04 NS LMCA stenosis ≥50% had a higher prevalence of traditional cardiovascular risk factors. Importantly, the right-hand 2D:4D ratio was significantly higher in female patients with LMCA stenosis ≥50% compared with those with <50% stenosis, whereas no significant difference was observed for the left-hand 2D:4D ratio. 3.4. Right- and Left-Hand 2D:4D Ratios According to LMCA Stenosis Cut-Off Values To assess the robustness of this association, right- and left-hand 2D:4D ratios were further analyzed according to different LMCA stenosis cut-off values (≥ 30%, ≥ 40%, and ≥ 50%). As summarized in Table 4 , the right-hand 2D:4D ratio demonstrated a progressive increase with higher LMCA stenosis thresholds, reaching statistical significance at the ≥ 40% and ≥ 50% cut-off levels. In contrast, left-hand 2D:4D ratios did not show a consistent association with LMCA stenosis severity. Table 4 Right- and Left-Hand 2D:4D Ratios According to Different LMCA Stenosis Cut-Off Values in Female Patients LMCA Cut-off Variable LMCA Below Cut-off LMCA Above Cut-off p value ≥ 30% Right-hand 2D:4D 0.98 ± 0.05 (n = 116) 1.01 ± 0.04 (n = 12) 0.056 Left-hand 2D:4D 0.99 ± 0.05 1.01 ± 0.05 NS ≥ 40% Right-hand 2D:4D 0.98 ± 0.05 (n = 120) 1.03 ± 0.05 (n = 9) 0.028 Left-hand 2D:4D 0.99 ± 0.05 1.02 ± 0.04 NS ≥ 50% (Primary) Right-hand 2D:4D 0.98 ± 0.05 (n = 124) 1.04 ± 0.05 (n = 6) 0.016 Left-hand 2D:4D 0.99 ± 0.05 1.04 ± 0.04 NS 2D:4D ratios are presented as median (interquartile range). 3.5. Multivariable Logistic Regression Analysis for LMCA Stenosis ≥ 50% Multivariable logistic regression analysis was performed to identify independent predictors of LMCA stenosis ≥ 50% in female patients. As shown in Table 5 , the right-hand 2D:4D ratio remained independently associated with LMCA stenosis ≥ 50% after adjustment for age, smoking status, diabetes mellitus, and hypertension. None of the traditional cardiovascular risk factors demonstrated a statistically significant independent association in the adjusted model. Table 5 Multivariable Logistic Regression Analysis for Left Main Coronary Artery Stenosis ≥ 50% in Female Patients Variable Odds Ratio (OR) 95% Confidence Interval p value Right-hand 2D:4D ratio 1.87 1.12–3.14 0.018 Age (years) 1.04 0.98–1.10 0.17 Current smoking 1.21 0.58–2.54 0.60 Diabetes mellitus 1.34 0.61–2.93 0.46 Hypertension 1.41 0.68–2.89 0.35 The model was adjusted for age, smoking status, diabetes mellitus, and hypertension. 4. Discussion In this study, we investigated the association between right- and left-hand 2D:4D ratios and left main coronary artery (LMCA) stenosis, with a primary focus on female patients. The main finding was that higher right-hand 2D:4D ratios were independently associated with significant LMCA stenosis (≥ 50%) in female patients, even after adjustment for traditional cardiovascular risk factors. This association was not observed in male patients and was not consistently present for the left-hand 2D:4D ratio. The 2D:4D ratio is widely regarded as a surrogate marker of prenatal sex hormone exposure, reflecting the balance between testosterone and estrogen during fetal development [ 12 – 14 ]. Experimental and epidemiological evidence suggests that prenatal hormonal milieu may exert long-term effects on vascular development, endothelial function, and inflammatory pathways, potentially influencing cardiovascular risk later in life [ 15 – 17 ]. Our findings are consistent with this concept, demonstrating a sex-specific association between a prenatal biomarker and a clinically important coronary phenotype. Previous studies examining the relationship between 2D:4D ratios and coronary artery disease have reported inconsistent results [ 18 – 20 ]. While some studies suggested associations between 2D:4D ratios and the presence or severity of coronary atherosclerosis, others failed to confirm such relationships. Importantly, most prior investigations focused on generalized coronary artery disease rather than LMCA involvement specifically. Given the unique anatomical and prognostic significance of LMCA stenosis [ 21 ], the present study extends existing literature by highlighting a potential association between the right-hand 2D:4D ratio and LMCA disease severity in female patients. The predominance of the right-hand 2D:4D ratio observed in this study is consistent with previous reports indicating that the right hand may more sensitively reflect prenatal androgen exposure compared with the left hand [ 22 ]. This lateralization effect has been described in several physiological and pathological contexts and may partly explain the absence of a consistent association for left-hand 2D:4D ratios in our analyses. Sex-specific differences in cardiovascular disease presentation and outcomes are well recognized [ 23 ]. Differences in hormonal profiles, plaque composition, endothelial function, and inflammatory responses have been proposed as potential mechanisms underlying these disparities [ 24 , 25 ]. The present findings align with this framework by suggesting that prenatal hormonal influences, as reflected by the 2D:4D ratio, may contribute to sex-specific susceptibility to LMCA disease. In addition to coronary anatomy, we explored potential associations between right-hand 2D:4D ratios and selected postoperative outcomes, including intensive care unit length of stay and acute kidney injury. These exploratory analyses did not demonstrate clinically meaningful or consistent associations in either female or male patients. This observation suggests that the relationship between the 2D:4D ratio and cardiovascular disease may be more closely related to disease susceptibility or anatomical severity rather than postoperative recovery or complication risk. These analyses were exploratory and should be interpreted with caution. Several limitations of this study should be acknowledged. First, the retrospective and observational design precludes causal inference. Second, the number of patients with significant LMCA stenosis was relatively limited, which may have reduced statistical power. Third, although standardized methods were used for 2D:4D measurements, inter-observer variability was not formally assessed. Fourth, adjustment for multiple comparisons was not performed, given the exploratory nature of several analyses. Finally, the study population consisted of patients undergoing coronary angiography and cardiac surgery, which may limit the generalizability of the findings to broader populations. Despite these limitations, the present study has several strengths. It focuses on a clinically important and underexplored coronary phenotype, incorporates predefined sex-specific analyses, and evaluates the robustness of findings across different LMCA stenosis thresholds. Furthermore, the inclusion of exploratory postoperative outcome analyses provides additional clinical context while maintaining appropriate interpretive caution. 5. Conclusions Higher right-hand 2D:4D ratios were independently associated with significant LMCA stenosis in female patients. This association was not observed in male patients and was not consistently related to selected postoperative outcomes. These findings suggest a potential sex-specific relationship between prenatal hormonal markers and LMCA disease severity and warrant further investigation in prospective studies. Abbreviations 2D 4D:Second-to-fourth digit ratio AKI Acute kidney injury CABG Coronary artery bypass grafting CAD Coronary artery disease ICU Intensive care unit LMCA Left main coronary artery OR Odds ratio SD Standard deviation Declarations Author Contributions: Conceptualization, S.Y. and N.G.; methodology, S.Y.; software, S.Y.; validation, S.Y., E.E., H.F.Ö. and Y.G.; formal analysis, S.Y.; investigation, S.Y., H.F.Ö. and M.I.; resources, N.G. and Y.D.; data curation, S.Y.; writing—original draft preparation, S.Y.; writing—review and editing, S.Y., E.E., Ö.T. and N.G.; visualization, S.Y.; supervision, N.G.; project administration, S.Y.; funding acquisition, N.G. All authors have read and agreed to the published version of the manuscript. Funding: This research received no external funding. Institutional Review Board Statement: The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Ethics Committee of Necmettin Erbakan Ethics Committee (protocol number 2025/6067 and date of approval 24.10.2024). Informed Consent Statement: Informed consent was obtained from all subjects involved in the study. Written informed consent has been obtained from the patient(s) to publish this paper. Data Availability Statement: We encourage all authors of articles published in MDPI journals to share their research data. In this section, please provide details regarding where data supporting reported results can be found, including links to publicly archived datasets analyzed or generated during the study. Where no new data were created, or where data is unavailable due to privacy or ethical restrictions, a statement is still required. Acknowledgments: None Conflicts of Interest: The authors declare no conflicts of interest. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8544199","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":585982660,"identity":"465e7546-ce8a-4a7c-a33a-9f7cb859452e","order_by":0,"name":"Serkan Yildirim","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2ElEQVRIiWNgGAWjYHACZjDJxt4AJA0sSNDCx3MApEWCBC1yEgkgiggt8u29jw1+7rCRY5N8fnXDjwIJBv727gS8WgzOHDdO7D2TZswmnVN2swfoMIkzZzfg1yKRxnyAt+1wYpt0TtoNHqAWA4lc/Frk5z9jPvi37X9im+SZtJt/iNHCcIONOZm37UBimwT7sdtE2WJwJo3ZWLYt2ZiNJ4fttoyBBA9Bv8i3H2OWfNtmJyfffvzZzTd/bOT423sJOAwBeAzAJLHKQYD9ASmqR8EoGAWjYAQBAAc1QY9HqcHzAAAAAElFTkSuQmCC","orcid":"","institution":"Necmettin Erbakan University","correspondingAuthor":true,"prefix":"","firstName":"Serkan","middleName":"","lastName":"Yildirim","suffix":""},{"id":585982661,"identity":"97d2e4a6-9bc2-43b2-8fc3-9924913ddb3c","order_by":1,"name":"Hanefi Furkan Öz","email":"","orcid":"","institution":"Necmettin Erbakan University","correspondingAuthor":false,"prefix":"","firstName":"Hanefi","middleName":"Furkan","lastName":"Öz","suffix":""},{"id":585982662,"identity":"1a8bcf04-a9b4-48da-90b4-f78f651ee1cc","order_by":2,"name":"Yalçın Günerhan","email":"","orcid":"","institution":"Necmettin Erbakan University","correspondingAuthor":false,"prefix":"","firstName":"Yalçın","middleName":"","lastName":"Günerhan","suffix":""},{"id":585982663,"identity":"ebe7cca4-c504-44f9-b348-b7c2ae603877","order_by":3,"name":"Mehmet Işık","email":"","orcid":"","institution":"Necmettin Erbakan University","correspondingAuthor":false,"prefix":"","firstName":"Mehmet","middleName":"","lastName":"Işık","suffix":""},{"id":585982665,"identity":"13481675-a8be-4413-b23f-f7ad4e91246c","order_by":4,"name":"Ömer Tanyeli","email":"","orcid":"","institution":"Necmettin Erbakan University","correspondingAuthor":false,"prefix":"","firstName":"Ömer","middleName":"","lastName":"Tanyeli","suffix":""},{"id":585982667,"identity":"a80d97ec-ec09-4922-aea5-9e941a32aa21","order_by":5,"name":"Yüksel Dereli","email":"","orcid":"","institution":"Necmettin Erbakan University","correspondingAuthor":false,"prefix":"","firstName":"Yüksel","middleName":"","lastName":"Dereli","suffix":""},{"id":585982668,"identity":"4de430ea-ceea-4876-addc-b870b9b65a69","order_by":6,"name":"Erdal EGE","email":"","orcid":"","institution":"Necmettin Erbakan University","correspondingAuthor":false,"prefix":"","firstName":"Erdal","middleName":"","lastName":"EGE","suffix":""},{"id":585982671,"identity":"3dbac1e0-dc2f-49d3-b0e4-af673bb6181d","order_by":7,"name":"Niyazi Görmüş","email":"","orcid":"","institution":"Necmettin Erbakan University","correspondingAuthor":false,"prefix":"","firstName":"Niyazi","middleName":"","lastName":"Görmüş","suffix":""}],"badges":[],"createdAt":"2026-01-07 17:38:24","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8544199/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8544199/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12872-026-05786-w","type":"published","date":"2026-03-26T16:08:42+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":105755943,"identity":"0907e105-8019-4352-bac4-36a698cf5f16","added_by":"auto","created_at":"2026-03-30 16:33:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1112603,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8544199/v1/5de32f0c-c779-4da2-a4ce-426f8749f668.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Association Between Right-Hand 2D:4D Ratio and Left Main Coronary Artery Stenosis in Women","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eThe second-to-fourth digit ratio (2D:4D) has been proposed as a biological marker reflecting prenatal exposure to sex hormones, particularly the balance between testosterone and estrogen [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Lower 2D:4D ratios are generally associated with higher prenatal androgen exposure, whereas higher ratios are thought to reflect relatively greater prenatal estrogen effects [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Beyond its developmental implications, the 2D:4D ratio has attracted increasing attention as a biological marker that has been explored in relation to cardiovascular structure and function [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePrevious studies have reported associations between the 2D:4D ratio and various cardiovascular risk factors and outcomes, including coronary artery disease, hypertension, myocardial infarction, and vascular reactivity [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. These findings have raised interest in the hypothesis that prenatal hormonal influences may contribute to sex-specific susceptibility to cardiovascular disease later in life [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. However, results across studies have been inconsistent, and the clinical relevance of the 2D:4D ratio remains controversial.\u003c/p\u003e \u003cp\u003eLeft main coronary artery (LMCA) stenosis represents a distinct and clinically important form of coronary artery disease, given its association with extensive myocardial ischemia and adverse outcomes [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Despite its importance, limited data exists regarding the relationship between the 2D:4D ratio and LMCA disease specifically. Moreover, potential sex-specific associations between 2D:4D ratios and LMCA stenosis have not been adequately explored.\u003c/p\u003e \u003cp\u003eIn addition to coronary anatomy, postoperative outcomes following cardiac surgery\u0026mdash;such as intensive care unit (ICU) length of stay and acute kidney injury\u0026mdash;are influenced by a complex interplay of patient-related and procedural factors [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Whether the 2D:4D ratio is associated with such postoperative outcomes remains largely unexplored and warrants cautious, exploratory investigation.\u003c/p\u003e \u003cp\u003eTherefore, the primary aim of this study was to investigate the association between right- and left-hand 2D:4D ratios and LMCA stenosis, with a particular focus on female patients. Secondary objectives included exploratory analyses assessing potential associations between 2D:4D ratios and selected postoperative outcomes in both female and male patients.\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cp\u003e \u003cb\u003eStudy Design and Population\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThis prospective observational study included 400 consecutive patients who underwent coronary angiography and cardiac surgery at a tertiary care center. Patient enrollment was prospectively continued during the predefined study period until 400 eligible patients were included. No formal a priori sample size calculation was performed, as this was a prospective observational study with exploratory components. Patients with available angiographic data and measurable second-to-fourth digit (2D:4D) ratios were eligible for inclusion. The study population comprised both female and male patients; sex-specific analyses were predefined, with a primary focus on female patients. Written informed consent was obtained from all participants prior to enrollment. The study protocol was approved by the local institutional ethics committee (Approval no:2025/6067) and conducted in accordance with the Declaration of Helsinki.\u003c/p\u003e \u003cp\u003e \u003cb\u003eMeasurement of 2D:4D Ratio\u003c/b\u003e \u003c/p\u003e \u003cp\u003eRight- and left-hand 2D:4D ratios were determined by measuring the lengths of the second (index) and fourth (ring) digits from the basal crease to the fingertip. Measurements were performed using standardized digital calipers, and the 2D:4D ratio was calculated by dividing the length of the second digit by that of the fourth digit. Biologically implausible values were excluded from analysis.\u003c/p\u003e \u003cp\u003e \u003cb\u003eAngiographic Assessment of LMCA Stenosis\u003c/b\u003e \u003c/p\u003e \u003cp\u003eCoronary angiography was performed according to standard clinical protocols. The severity of left main coronary artery (LMCA) stenosis was assessed by experienced cardiologists blinded to 2D:4D measurements. LMCA stenosis was categorized as \u0026lt;\u0026thinsp;50% or \u0026ge;\u0026thinsp;50% for primary analyses. Additional exploratory analyses evaluated alternative LMCA stenosis cut-off values (\u0026ge;\u0026thinsp;30% and \u0026ge;\u0026thinsp;40%).\u003c/p\u003e \u003cp\u003e \u003cb\u003ePostoperative Outcomes\u003c/b\u003e \u003c/p\u003e \u003cp\u003eExploratory postoperative outcomes included intensive care unit (ICU) length of stay and acute kidney injury (AKI). ICU length of stay was recorded in hours and dichotomized according to the median value. AKI was defined as an increase in postoperative serum creatinine of \u0026ge;\u0026thinsp;0.5 mg/dL compared with the preoperative value.\u003c/p\u003e \u003cp\u003e \u003cb\u003eStatistical Analysis\u003c/b\u003e \u003c/p\u003e \u003cp\u003eContinuous variables are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or median (interquartile range), as appropriate. Categorical variables are presented as number and percentage. Comparisons between groups were performed using the Mann\u0026ndash;Whitney U test for continuous variables and the chi-square or Fisher\u0026rsquo;s exact test for categorical variables.\u003c/p\u003e \u003cp\u003eSex-stratified analyses were conducted, and subsequent analyses focused on female patients. Multivariable logistic regression analysis was performed to identify independent predictors of LMCA stenosis\u0026thinsp;\u0026ge;\u0026thinsp;50% in female patients, adjusting for age, smoking status, diabetes mellitus, and hypertension. Exploratory analyses were interpreted cautiously. All analyses were conducted using an available-case approach without data imputation, and a two-sided p value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003cp\u003eStatistical analyses were performed using SPSS software (version 22.0; IBM Corp., Armonk, NY, USA).\u003c/p\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e3.1. General Characteristics of the Study Population\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eA total of 400 patients were included in the study. The general demographic and clinical characteristics of the study population, as well as the distribution of surgical case types, are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Of the total cohort, 270 patients (67.5%) were female and 130 (32.5%) were male. The mean age was 61.3\u0026thinsp;\u0026plusmn;\u0026thinsp;13.2 years. The surgical case distribution consisted of isolated coronary artery disease, isolated valve surgery, and combined coronary artery bypass grafting with valve surgery.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eGeneral Characteristics and Surgical Case Distribution of the Study Population\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal (n\u0026thinsp;=\u0026thinsp;400)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge, years\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61.3\u0026thinsp;\u0026plusmn;\u0026thinsp;13.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFemale sex, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e270 (67.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMale sex, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e130 (32.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRight-hand 2D:4D ratio\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.982\u0026thinsp;\u0026plusmn;\u0026thinsp;0.053\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLeft-hand 2D:4D ratio\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.983\u0026thinsp;\u0026plusmn;\u0026thinsp;0.049\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCurrent smoking, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e232 (58.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHypertension, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e253 (63.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDiabetes mellitus, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e166 (41.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHyperlipidemia, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e198 (49.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eChronic kidney disease, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74 (18.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eChronic obstructive pulmonary disease, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61 (15.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAtrial fibrillation, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e89 (22.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLeft ventricular ejection fraction (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52.6\u0026thinsp;\u0026plusmn;\u0026thinsp;9.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCase type\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIsolated coronary artery disease (CABG only)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e202 (50.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIsolated valve surgery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e103 (25.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCABG\u0026thinsp;+\u0026thinsp;valve surgery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95 (23.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eCABG; Coronary artery bypass grafting, Data are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, median (interquartile range), or number (%), as appropriate.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e3.2. Right-Hand 2D:4D Ratio and Selected Postoperative Outcomes\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eExploratory analyses were performed to evaluate whether the right-hand 2D:4D ratio was associated with selected postoperative outcomes, including intensive care unit (ICU) length of stay and the occurrence of acute kidney injury (AKI). These analyses were conducted separately in female and male patients. As shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, no clinically meaningful or consistent differences in right-hand 2D:4D ratios were observed according to ICU length of stay or AKI status in either sex, indicating that the right-hand 2D:4D ratio was not strongly associated with these postoperative outcomes in the overall study population.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssociations of Right-Hand 2D:4D Ratio with Selected Postoperative Outcomes According to Sex\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemale (n\u0026thinsp;=\u0026thinsp;270) Right-hand 2D:4D (Median)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMale (n\u0026thinsp;=\u0026thinsp;130) Right-hand 2D:4D (Median)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eICU stay duration\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eShort ICU stay\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.974\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.984\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLong ICU stay\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.978\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.989\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAcute kidney injury (AKI)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo AKI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.975\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.986\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAKI present\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.978\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.950\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eICU length of stay was dichotomized according to the median value. Acute kidney injury was defined as an increase in postoperative serum creatinine\u0026thinsp;\u0026ge;\u0026thinsp;0.5 mg/dL.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e3.3. Baseline Characteristics of Female Patients According to LMCA Stenosis\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eSubsequent analyses focused on female patients, in line with the primary objective of the study. Baseline demographic and clinical characteristics of female patients stratified according to LMCA stenosis (\u0026lt;\u0026thinsp;50% vs. \u0026ge;50%) are presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Female patients with LMCA stenosis\u0026thinsp;\u0026ge;\u0026thinsp;50% had a higher prevalence of traditional cardiovascular risk factors. Importantly, the right-hand 2D:4D ratio was significantly higher in female patients with LMCA stenosis\u0026thinsp;\u0026ge;\u0026thinsp;50% compared with those with \u0026lt;\u0026thinsp;50% stenosis, whereas no significant difference was observed for the left-hand 2D:4D ratio.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline Characteristics of Female Patients Stratified by Left Main Coronary LMCA: left main coronary artery.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLMCA\u0026thinsp;\u0026lt;\u0026thinsp;50% (n\u0026thinsp;=\u0026thinsp;124)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLMCA\u0026thinsp;\u0026ge;\u0026thinsp;50% (n\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge, years\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65.24\u0026thinsp;\u0026plusmn;\u0026thinsp;57.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60.80\u0026thinsp;\u0026plusmn;\u0026thinsp;12.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCurrent smoking, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48 (38.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHypertension, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e83 (66.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (83.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDiabetes mellitus, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49 (39.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (83.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRight-hand 2D:4D ratio\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e0.98\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e1.04\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.016\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLeft-hand 2D:4D ratio\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.99\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.04\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\u003cp\u003eLMCA stenosis \u0026ge;50% had a higher prevalence of traditional cardiovascular risk factors. Importantly, the right-hand 2D:4D ratio was significantly higher in female patients with LMCA stenosis \u0026ge;50% compared with those with \u0026lt;50% stenosis, whereas no significant difference was observed for the left-hand 2D:4D ratio.\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e3.4. Right- and Left-Hand 2D:4D Ratios According to LMCA Stenosis Cut-Off Values\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eTo assess the robustness of this association, right- and left-hand 2D:4D ratios were further analyzed according to different LMCA stenosis cut-off values (\u0026ge;\u0026thinsp;30%, \u0026ge;\u0026thinsp;40%, and \u0026ge;\u0026thinsp;50%). As summarized in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, the right-hand 2D:4D ratio demonstrated a progressive increase with higher LMCA stenosis thresholds, reaching statistical significance at the \u0026ge;\u0026thinsp;40% and \u0026ge;\u0026thinsp;50% cut-off levels. In contrast, left-hand 2D:4D ratios did not show a consistent association with LMCA stenosis severity.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRight- and Left-Hand 2D:4D Ratios According to Different LMCA Stenosis Cut-Off Values in Female Patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLMCA Cut-off\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLMCA Below Cut-off\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLMCA Above Cut-off\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e\u0026ge;\u0026thinsp;30%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRight-hand 2D:4D\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.98\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05 (n\u0026thinsp;=\u0026thinsp;116)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04 (n\u0026thinsp;=\u0026thinsp;12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.056\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLeft-hand 2D:4D\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.99\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e\u0026ge;\u0026thinsp;40%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRight-hand 2D:4D\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.98\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05 (n\u0026thinsp;=\u0026thinsp;120)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.03\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05 (n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.028\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLeft-hand 2D:4D\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.99\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e\u0026ge;\u0026thinsp;50%\u003c/b\u003e \u003cem\u003e(Primary)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRight-hand 2D:4D\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.98\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05 (n\u0026thinsp;=\u0026thinsp;124)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e1.04\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05 (n\u0026thinsp;=\u0026thinsp;6)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.016\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLeft-hand 2D:4D\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.99\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.04\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003e2D:4D ratios are presented as median (interquartile range).\u003c/h3\u003e\n\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.5. Multivariable Logistic Regression Analysis for LMCA Stenosis\u0026thinsp;\u0026ge;\u0026thinsp;50%\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eMultivariable logistic regression analysis was performed to identify independent predictors of LMCA stenosis\u0026thinsp;\u0026ge;\u0026thinsp;50% in female patients. As shown in Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e, the right-hand 2D:4D ratio remained independently associated with LMCA stenosis\u0026thinsp;\u0026ge;\u0026thinsp;50% after adjustment for age, smoking status, diabetes mellitus, and hypertension. None of the traditional cardiovascular risk factors demonstrated a statistically significant independent association in the adjusted model.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariable Logistic Regression Analysis for Left Main Coronary Artery Stenosis\u0026thinsp;\u0026ge;\u0026thinsp;50% in Female Patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOdds Ratio (OR)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% Confidence Interval\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRight-hand 2D:4D ratio\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.87\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.12\u0026ndash;3.14\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.018\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.98\u0026ndash;1.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCurrent smoking\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.58\u0026ndash;2.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.60\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.61\u0026ndash;2.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.68\u0026ndash;2.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eThe model was adjusted for age, smoking status, diabetes mellitus, and hypertension.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eIn this study, we investigated the association between right- and left-hand 2D:4D ratios and left main coronary artery (LMCA) stenosis, with a primary focus on female patients. The main finding was that higher right-hand 2D:4D ratios were independently associated with significant LMCA stenosis (\u0026ge;\u0026thinsp;50%) in female patients, even after adjustment for traditional cardiovascular risk factors. This association was not observed in male patients and was not consistently present for the left-hand 2D:4D ratio.\u003c/p\u003e \u003cp\u003eThe 2D:4D ratio is widely regarded as a surrogate marker of prenatal sex hormone exposure, reflecting the balance between testosterone and estrogen during fetal development [\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Experimental and epidemiological evidence suggests that prenatal hormonal milieu may exert long-term effects on vascular development, endothelial function, and inflammatory pathways, potentially influencing cardiovascular risk later in life [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Our findings are consistent with this concept, demonstrating a sex-specific association between a prenatal biomarker and a clinically important coronary phenotype.\u003c/p\u003e \u003cp\u003ePrevious studies examining the relationship between 2D:4D ratios and coronary artery disease have reported inconsistent results [\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. While some studies suggested associations between 2D:4D ratios and the presence or severity of coronary atherosclerosis, others failed to confirm such relationships. Importantly, most prior investigations focused on generalized coronary artery disease rather than LMCA involvement specifically. Given the unique anatomical and prognostic significance of LMCA stenosis [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], the present study extends existing literature by highlighting a potential association between the right-hand 2D:4D ratio and LMCA disease severity in female patients.\u003c/p\u003e \u003cp\u003eThe predominance of the right-hand 2D:4D ratio observed in this study is consistent with previous reports indicating that the right hand may more sensitively reflect prenatal androgen exposure compared with the left hand [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. This lateralization effect has been described in several physiological and pathological contexts and may partly explain the absence of a consistent association for left-hand 2D:4D ratios in our analyses.\u003c/p\u003e \u003cp\u003eSex-specific differences in cardiovascular disease presentation and outcomes are well recognized [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Differences in hormonal profiles, plaque composition, endothelial function, and inflammatory responses have been proposed as potential mechanisms underlying these disparities [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. The present findings align with this framework by suggesting that prenatal hormonal influences, as reflected by the 2D:4D ratio, may contribute to sex-specific susceptibility to LMCA disease.\u003c/p\u003e \u003cp\u003eIn addition to coronary anatomy, we explored potential associations between right-hand 2D:4D ratios and selected postoperative outcomes, including intensive care unit length of stay and acute kidney injury. These exploratory analyses did not demonstrate clinically meaningful or consistent associations in either female or male patients. This observation suggests that the relationship between the 2D:4D ratio and cardiovascular disease may be more closely related to disease susceptibility or anatomical severity rather than postoperative recovery or complication risk. These analyses were exploratory and should be interpreted with caution.\u003c/p\u003e \u003cp\u003eSeveral limitations of this study should be acknowledged. First, the retrospective and observational design precludes causal inference. Second, the number of patients with significant LMCA stenosis was relatively limited, which may have reduced statistical power. Third, although standardized methods were used for 2D:4D measurements, inter-observer variability was not formally assessed. Fourth, adjustment for multiple comparisons was not performed, given the exploratory nature of several analyses. Finally, the study population consisted of patients undergoing coronary angiography and cardiac surgery, which may limit the generalizability of the findings to broader populations.\u003c/p\u003e \u003cp\u003eDespite these limitations, the present study has several strengths. It focuses on a clinically important and underexplored coronary phenotype, incorporates predefined sex-specific analyses, and evaluates the robustness of findings across different LMCA stenosis thresholds. Furthermore, the inclusion of exploratory postoperative outcome analyses provides additional clinical context while maintaining appropriate interpretive caution.\u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eHigher right-hand 2D:4D ratios were independently associated with significant LMCA stenosis in female patients. This association was not observed in male patients and was not consistently related to selected postoperative outcomes. These findings suggest a potential sex-specific relationship between prenatal hormonal markers and LMCA disease severity and warrant further investigation in prospective studies.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e2D\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003e4D:Second-to-fourth digit ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAKI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAcute kidney injury\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCABG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCoronary artery bypass grafting\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCAD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCoronary artery disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eICU\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIntensive care unit\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLMCA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLeft main coronary artery\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOdds ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eStandard deviation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u003c/strong\u003e Conceptualization, S.Y. and N.G.; methodology, S.Y.; software, S.Y.; validation, S.Y., E.E., H.F.\u0026Ouml;. and Y.G.; formal analysis, S.Y.; investigation, S.Y., H.F.\u0026Ouml;. and M.I.; resources, N.G. and Y.D.; data curation, S.Y.; writing\u0026mdash;original draft preparation, S.Y.; writing\u0026mdash;review and editing, S.Y., E.E., \u0026Ouml;.T. and N.G.; visualization, S.Y.; supervision, N.G.; project administration, S.Y.; funding acquisition, N.G.\u003cbr\u003e\u0026nbsp;All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e This research received no external funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInstitutional Review Board Statement:\u0026nbsp;\u003c/strong\u003eThe study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Ethics Committee of Necmettin Erbakan Ethics Committee (protocol number 2025/6067 and date of approval 24.10.2024).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed Consent Statement:\u0026nbsp;\u003c/strong\u003eInformed consent was obtained from all subjects involved in the study. Written informed consent has been obtained from the patient(s) to publish this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement:\u003c/strong\u003e We encourage all authors of articles published in MDPI journals to share their research data. In this section, please provide details regarding where data supporting reported results can be found, including links to publicly archived datasets analyzed or generated during the study. Where no new data were created, or where data is unavailable due to privacy or ethical restrictions, a statement is still required.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u003c/strong\u003e None\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest:\u003c/strong\u003e The authors declare no conflicts of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eManning JT, Scutt D, Wilson J, Lewis-Jones DI. The ratio of 2nd to 4th digit length: a predictor of sperm numbers and concentrations of testosterone, luteinizing hormone and oestrogen. Hum Reprod. 1998;13(11):3000\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eManning JT. Digit ratio: a pointer to fertility, behavior, and health. Rutgers University Press; 2002.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZheng Z, Cohn MJ. Developmental basis of sexually dimorphic digit ratios. Proc Natl Acad Sci U S A. 2011;108(39):16289\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLutchmaya S, Baron-Cohen S, Raggatt P, Knickmeyer R, Manning JT. 2nd to 4th digit ratios, fetal testosterone and estradiol. Early Hum Dev. 2004;77(1\u0026ndash;2):23\u0026ndash;28.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eH\u0026ouml;nekopp J, Manning JT, M\u0026uuml;ller C. Digit ratio (2D:4D) and physical fitness in males and females. Am J Hum Biol. 2006;18(4):509\u0026ndash;19.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKyriakidis I, Papaioannidou P, Pantelidou V, Kalles V, Gemitzis K. Digit ratios and cardiovascular disease risk factors. Angiology. 2010;61(4):344\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFink B, Manning JT, Neave N. Second to fourth digit ratio and the \u0026lsquo;big five\u0026rsquo; personality factors. Pers Individ Dif. 2004;37(3):495\u0026ndash;503.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMuller DC, Giles GG, Bassett J, Morris HA, Manning JT, Hopper JL, et al. Second to fourth digit ratio (2D:4D) and coronary heart disease risk factors in men. Am J Hum Biol. 2012;24(3):393\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBagepally BS, Majumder J, Kotadiya F. Digit ratio (2D:4D) and coronary artery disease: a systematic review and meta-analysis. Early Hum Dev. 2020;140:104916.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNeumann FJ, Sousa-Uva M, Ahlsson A, et al. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J. 2019;40(2):87\u0026ndash;165.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eManning JT, Fink B. Is low digit ratio linked with late onset disease? Evidence from cancer, cardiovascular disease, and osteoarthritis. Int J Androl. 2008;31(5):518\u0026ndash;25.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRegitz-Zagrosek V, Kararigas G. Mechanistic pathways of sex differences in cardiovascular disease. Physiol Rev. 2017;97(1):1\u0026ndash;37.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVaccarino V, Badimon L, Corti R, et al. Presentation, management, and outcomes of ischemic heart disease in women. Nat Rev Cardiol. 2013;10(9):508\u0026ndash;18.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShaw LJ, Bugiardini R, Merz CNB. Women and ischemic heart disease: evolving knowledge. J Am Coll Cardiol. 2009;54(17):1561\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarker DJP. The developmental origins of adult disease. J Am Coll Nutr. 2004;23(6 Suppl):S588\u0026ndash;95.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEriksson JG, Fors\u0026eacute;n T, Tuomilehto J, Osmond C, Barker DJP. Early growth and coronary heart disease in later life. BMJ. 2001;322(7292):949\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThornburg KL, Marshall N. The placenta is the center of the chronic disease universe. Am J Obstet Gynecol. 2015;213(4 Suppl):S14\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHampson E, Ellis CL, Tenk CM. On the relation between digit ratio (2D:4D) and coronary heart disease. Am J Hum Biol. 2008;20(3):344\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang W, Chen Y, Liu J, et al. Digit ratio (2D:4D) and atherosclerosis risk: a population-based study. Atherosclerosis. 2019;287:14\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang L, Chen X, Li J, et al. Digit ratio (2D:4D) and risk of coronary artery disease in a Chinese population. Atherosclerosis. 2018;278:1\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStone GW, Sabik JF, Serruys PW, et al. Everolimus-eluting stents or bypass surgery for left main coronary artery disease. N Engl J Med. 2016;375(23):2223\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eH\u0026ouml;nekopp J, Watson S. Meta-analysis of digit ratio 2D:4D shows greater sex difference in the right hand. Am J Hum Biol. 2010;22(5):619\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaas AHEM, Appelman YEA. Gender differences in coronary heart disease. Neth Heart J. 2010;18(12):598\u0026ndash;602.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePepine CJ, Ferdinand KC, Shaw LJ, et al. Emergence of nonobstructive coronary artery disease: a woman\u0026rsquo;s problem and need for change in definition on angiography. J Am Coll Cardiol. 2015;66(17):1918\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMehta LS, Beckie TM, DeVon HA, et al. Acute myocardial infarction in women: a scientific statement from the American Heart Association. Circulation. 2016;133(9):916\u0026ndash;47.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"2D:4D ratio, left main coronary artery, sex differences, coronary artery disease, prenatal hormonal exposure","lastPublishedDoi":"10.21203/rs.3.rs-8544199/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8544199/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe second-to-fourth digit ratio (2D:4D) has been explored as a marker of prenatal hormonal exposure, but its association with left main coronary artery (LMCA) stenosis, particularly in women, remains unclear. This prospective observational study included 400 patients undergoing coronary angiography and cardiac surgery. Right- and left-hand 2D:4D ratios were measured, and LMCA stenosis severity was assessed angiographically. Exploratory analyses evaluated potential associations between right-hand 2D:4D ratios and selected postoperative outcomes, including intensive care unit length of stay and acute kidney injury. Female patients were further stratified according to LMCA stenosis severity (\u0026lt;\u0026thinsp;50% vs\u0026thinsp;\u0026ge;\u0026thinsp;50%), and multivariable logistic regression analysis was performed. Among female patients, right-hand 2D:4D ratios were significantly higher in those with LMCA stenosis\u0026thinsp;\u0026ge;\u0026thinsp;50%, whereas no significant association was observed for left-hand 2D:4D ratios. No clinically meaningful associations were identified between right-hand 2D:4D ratios and selected postoperative outcomes in either sex. In multivariable analysis, the right-hand 2D:4D ratio remained independently associated with significant LMCA stenosis in female patients. These findings suggest a potential sex-specific relationship between prenatal hormonal markers and LMCA disease severity.\u003c/p\u003e","manuscriptTitle":"Association Between Right-Hand 2D:4D Ratio and Left Main Coronary Artery Stenosis in Women","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-07 01:05:31","doi":"10.21203/rs.3.rs-8544199/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-03T07:36:14+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-18T19:35:29+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-15T17:30:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"117075696483397527532110564476445125219","date":"2026-02-12T19:38:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"113281654101859871588423640399448284277","date":"2026-02-11T13:04:40+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"328668099804000099060719159328229734523","date":"2026-02-10T16:28:53+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-04T11:48:51+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-09T08:08:38+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-08T13:01:38+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-08T12:58:21+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cardiovascular Disorders","date":"2026-01-07T17:30:40+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0e0d41fe-5fc5-4334-9393-5224800a8512","owner":[],"postedDate":"February 7th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-30T16:30:18+00:00","versionOfRecord":{"articleIdentity":"rs-8544199","link":"https://doi.org/10.1186/s12872-026-05786-w","journal":{"identity":"bmc-cardiovascular-disorders","isVorOnly":false,"title":"BMC Cardiovascular Disorders"},"publishedOn":"2026-03-26 16:08:42","publishedOnDateReadable":"March 26th, 2026"},"versionCreatedAt":"2026-02-07 01:05:31","video":"","vorDoi":"10.1186/s12872-026-05786-w","vorDoiUrl":"https://doi.org/10.1186/s12872-026-05786-w","workflowStages":[]},"version":"v1","identity":"rs-8544199","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8544199","identity":"rs-8544199","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}