INTRODUCTION
The human ratio of the second finger (index finger) to the fourth finger (ring finger) length (2D:4D) is smaller in males compared to females (1). Previous studies revealed that fetal testosterone and estrogen exposure may affect this ratio (1,2). Higher 2D:4D is associated with increased intrauterine exposure to luteinizing hormone, prolactin, and estrogen levels, and decreased testosterone exposure (3-5). The fetal testosterone/estrogen ratio in the amniotic fluid was negatively correlated with the 2D:4D ratio. Moreover, patients with Klinefelter’s syndrome had a higher 2D:4D ratio compared to their normal counterparts (1-3) The 2D:4D ratio in humans also varies between ethnic groups, for example, Afro-Caribbean Jamaicans had a lower ratio compared to Caucasian Uygurs (4). Its relationship with various physiological, behavioral, and pathological conditions, such as obesity and metabolic syndrome, has been demonstrated in various studies (5-9). Patients with female congenital adrenal hyperplasia had a higher 2D:4D ratio compared to controls (6).
Traditional coronary artery disease (CAD) risk factors are clearly-defined, whereas the effect of different risk factors, such as genetic predisposition and inflammatory markers, are still evaluated (10). Myocardial infarction (MI) prevalence is higher in males than females in the pre-menopausal period; however, the difference decreases at later ages (11). Additionally, low endogenous testosterone levels are related to MI in males (12). Moreover, a high 2D:4D ratio might be a predisposing factor for MI history at an early age in males (7,8,13). Ozdogmus et al. (9) conducted a study on the autopsy of 100 male patients and revealed that the right-hand ratio was related to atherosclerotic plaque burden in the right coronary arteries.
A small number of studies evaluated the association between 2D:4D and CAD; however, the link between this ratio and age or MI localization has not yet been reported in the literature. Thus, this study aimed to compare 2D:4D ratios according to age, other CAD risk factors, and MI localization in Turkish male patients with MI history.
METHODS
This cross-sectional, single-center, and retrospective study included 140 male patients with previous MI. All patients were from the Turkish ethnic group. Data regarding the demographic characteristics of patients were obtained from hospital registries. Age, presence of diabetes mellitus (DM), hypertension (HT), hyperlipidemia (HL), history and quantity of smoking, MI localization, and family history were recorded. Acute MI was defined by the criteria of the related guidelines (14). HT was defined as a systolic blood pressure of ≥140 mmHg or a diastolic blood pressure of ≥90 mmHg at presentation, previous diagnosis of HT, or antihypertensive usage. DM was described as a fasting blood glucose level of ≥126 mg/dL or antidiabetic medication usage. The use of antilipemic agents or serum low-density lipoproteins-cholesterol concentration of >70 mg/dL was described as HL. Patients with hand deformities, thyroid dysfunction, hormonal disorders, genetic diseases, using hormonal therapies, and left-hand users were excluded. Our Hospital Local Ethics Committee University of Health Sciences Istanbul, Turkey Bakırköy Dr. Sadi Konuk Training and Research Hospital approved the study and informed consent was obtained from all participants. The study was conducted in accordance with the principles of the Declaration of Helsinki (ethical approval number: 2018-12-04, date: 06. 25.2018).
Measurement of Finger Lengths
The index and ring finger lengths of both hands were measured using a ruler in the palmar surface, starting from the proximal palm’s basal crease to the tip of the finger. An independent examiner blinded to the study measured the finger lengths and calculated the 2D:4D ratio.
Statistical Analysis
Data were statistically analyzed using the Number Cruncher Statistical System 2007 (Kaysville, Utah, USA). Data were expressed as mean, standard deviation, median, frequency, percentage, minimum, and maximum. Normal distribution conformity of quantitative data has been tested with the Shapiro-Wilk test and graphical examinations. Comparison of quantitative variables of two groups with normal distribution was made by the Student’s t-test. One-Way analysis of variance and Kruskal-Wallis test was used for the comparison of parametric and non-parametric variables of more than two groups, respectively.
RESULTS
The group average age was 57.56±11.27 years, wherein13.6% (n=19) of patients were aged 30-45, 32.1% (n=45) were 46-55, 28.6% (n=40) were 56-65 years, and 25.7% (n=36) were over 65 years. Inferior MI was determined in 48.6% (n=68) of patients, anterior MI in 32.9% (n=46), septal MI in 3.6% (n=5), posterior MI in 2.9% (n=4), and lateral MI in 12.1% (n=17). Table 1 shows the demographic characteristics of the study population. Finger length measurements of the total group are summarized in Table 2. The average right-hand finger ratio was 0.98±0.05 cm and left hand was 0.96±0.04 cm. Table 3 demonstrates the comparison of left-right 2D:4D according to age subgroups, CAD risk factors, and MI localization. The right versus left 2D:4D was not statistically different according to any age groups, CAD risk factors, or MI localization (p>0.05).
DISCUSSION
This study revealed no statistically significant differences in the 2D:4D ratio of both hands according to age groups, presence of DM, HT, smoking, family history, or MI localization. To the best of our knowledge, the present study was the first one that evaluates the association between the 2D:4D ratio and MI in different age groups, CAD risk factors, and MI localization.
Prenatal exposure to androgenic hormones has been shown to affect the digit ratio of humans. Malas et al. (15) revealed that female fetuses have higher 2D:4D digit ratios than males. A study conducted by Lutchmaya et al. (1) revealed that 2D:4D ratios of 2-year-old children were associated with high fetal testosterone levels in the amniotic fluid with estradiol. Additionally, the right hand was more sensitive to the effect of sex steroids than the left. Other studies also showed that testosterone exposure is more effective in the development of the right side of the body than the left side (16,17). The 2D:4D ratio of the right hand and waist-body circumference, which is a predictor for metabolic syndrome, was demonstrated to be statistically significantly higher than the left hand (5). Although statistically insignificant, the 2D:4D ratio of the right hand was also higher than the left hand in our study.
The changes of the 2D:4D after birth are controversial. Studies on this topic have found conflicting findings. Some research found lower 2D:4D ratios in the prenatal period compared to childhood and adulthood, which indicates that the digit ratio increases after birth (18). A longitudinal study reported that an increased 2D:4D was less marked in the right hand, which is more likely to be affected by prenatal steroid levels (19). Contrarily, some data indicate relatively stable values of 2D:4D ratios during lifetime (20). Similarly, our study revealed that the right and left-hand 2D:4D ratios were not different among the age groups.
Previous studies revealed that the 2D:4D ratio was a predictor of CAD (7,8,21,22). Chinese females with CAD had a lower 2D:4D ratio compared to control subjects (23). Viveka et al. (24) revealed a strong association between finger ratio and diagonal ear lobe crease, which is also considered as an indicator of atherosclerosis. Ozdogmus et al. (9) demonstrated that males who had atherosclerotic plaque in the right coronary arteries had a higher right-hand 2D:4D ratio than males without plaques. Wu et al. (21) revealed a higher 2D:4D ratio in males with CAD than females with CAD, as well as a positive correlation between the 2D:4D ratio and CAD in males, but not in females. Additionally, the right-hand 2D:4D ratio had higher discriminative power for CAD. Another study showed that males with a high right-hand digit ratio had MI at a younger age compared to subjects with a low digit ratio (13). The right side of the body is more androgen-sensitive during the prenatal period and the low right-hand digit ratio is correlated with high prenatal and adult testosterone levels. High testosterone levels are is known to be protective against CAD and MI in males. The right and left sides of the body react differently to androgenic stimulation, thus an association between MI localization with the right and left-hand 2D:4D ratios was investigated. Our study revealed that MI localization was not different between the right and left-hand measurements. Similarly, the 2D:4D ratio has been linked to CAD risk factors, including HT, DM, and metabolic syndrome (5,25). Our results revealed that the right and left-hand digit ratios were not different in our study group in their CAD risk factors.
Study Limitations
The present study was a single-center study with a relatively small sample size, which may limit the generalization of our results. Only the 2D:4D ratio in male patients with MI history was measured without a control group that included subjects without MI history. However, studies are reported in the literature, which compared the 2D:4D ratio in MI versus healthy patients (19). Hence, our study aimed to evaluate the 2D:4D ratio in different age subgroups, CAD risk factors, and MI localization to add new findings to the current literature.
CONCLUSIONS
In male patients with MI history, the 2D:4D ratio is not associated with CAD risk factors and MI localization.
ETHICS
Ethics Committee Approval: Our Hospital Local Ethics Committee University of Health Sciences Turkey, Bakırköy Dr. Sadi Konuk Training and Research Hospital approved the study. The study was conducted in accordance with the principles of the Declaration of Helsinki (ethical approval number: 2018-12-04, date: 06. 25.2018).
Informed Consent: Informed consent was obtained from all participants.
Authorship Contributions
Surgical and Medical Practices: E.Ç.C., Concept: F.N.T.Ç., Design: F.N.T.Ç., E.Ç.C., Data Collection or Processing: E.Ç.C., Analysis or Interpretation: C.Y., Literature Search: C.Y., Writing: F.N.T.Ç.
Conflict of Interest: No conflict of interest was declared by the authors.
Financial Disclosure: The authors declared that this study received no financial support.