The 2nd–4th digit ratio (2D:4D) and neck circumference: implications for risk factors in coronary heart disease

Abstract

Background:

The ratio of the lengths of the 2nd and 4th digit (2D:4D) is negatively related to prenatal and adult concentrations of testosterone (T). Testosterone appears to be a protective against myocardial infarction (MI) in men as men with low 2D:4D are older at first MI than men with high 2D:4D, and men with coronary artery disease have lower T levels than men with normal angiograms. Neck circumference (NC), a simple and time-saving screening measure to identify obesity is reported to be positively correlated with the factors of the metabolic syndrome, a complex breakdown of normal physiology characterized by obesity, insulin resistance, hyperlipidemia, and hypertension, and is therefore likely to increase the risk of coronary heart disease (CHD).

Objective:

To investigate possible associations between 2D:4D ratios and NC in men and women.

Research methods and procedures:

2D:4D ratios, NC, along with measures of waist and hip circumferences, body mass index (BMI), and waist-to-hip ratio was recorded from 127 men and 117 women.

Results:

A significant positive correlation between 2D:4D and NC and was found for men but not for women after controlling for body mass index (BMI); the higher the ratio the higher the NC.

Discussion:

This finding supports the suggestion of NC to serve as a predictor for increased risk for CHD as previously suggested. In addition, the present association suggests a predisposition for men towards CHD via 2D:4D as proxy to early sex-steroid exposure.

Introduction

There is a sex difference in the ratio of the length of the 2nd digit (the index finger) and the 4th digit (the ring finger) (digit ratio, 2D:4D) such that male subjects have lower 2D:4D than female subjects.1, 2, 3, 4 Relative finger lengths are determined before birth at around week 13 of gestation,5 the sex difference is present in children,4, 5 and sex differences in 2D:4D are robust across a number of ethnic groups and races.3, 6, 7 The sexual dimorphism in 2D:4D has been known for many years and studies now provide direct and indirect evidence for the suggestion that sex differences in 2D:4D arise from in utero concentrations of sex steroids (for a review see Manning3), with 2D:4D negatively related to prenatal testosterone and positively associated with prenatal estrogen.

With regard to direct evidence Lutchmaya et al.8 studied the relationships between 2D:4D ratios and fetal testosterone (FT) and fetal estrogen (FE) from amniotic fluid in a sample of 33 children. They reported significant negative associations between right 2D:4D ratio and FT/FE ratio – independent of sex – such that low 2D:4D was associated with higher levels of FT relative to FE, and high 2D:4D correlated with low FT relative to FE.

With regard to indirect evidence there have been a number of studies, which link the waist-to-hip ratio (WHR) with 2D:4D. Thus, the WHR in women is positively correlated with serum levels of testosterone and negatively with women's 2D:4D6 and the WHR of mothers is negatively related to the 2D:4D of their children.9 WHR in female subjects appears to be directly linked to health and fertility as it has been shown to be an accurate predictor of risk for various diseases (e.g., Singh10 and Abbott et al.11). In men, studies have shown that aging is accompanied by decreasing testosterone levels, which in turn decrease lean body mass and increase abdominal fat deposition. Testosterone supplementation in elderly male subjects, and in healthy eugonadal men decreases WHR and increases lean body mass.12, 13

This has led to the assumption that if 2D:4D ratio is associated with testosterone and estrogen levels it may correlate with risk of myocardial infarction (MI). Manning and Bundred14 and Manning et al.15 found a negative relationship between 2D:4D ratio and age at first MI, that is men with low 2D:4D ratio tended to have their first MI's later in life than men with high 2D:4D ratios. Consequently, they suggested that the formation and maintenance of the cardiovascular system is sensitive to testosterone and estrogen in men16 and that the 2D:4D ratio is a marker for in utero and adult levels of these hormones.

Body obesity and the metabolic syndrome, a cluster of conditions associated with increased risk for type 2 diabetes and hypertension is considered a major risk factor for coronary heart disease (CHD), associated with an elevated risk for stroke and early mortality. There are numerous methods of assessing obesity (e.g. Cruz and Goran17). However, Ben-Noun et al.18 tested a method of identifying overweight or obese patients solely by measuring the circumference of the neck circumference (NC). Their results indicated a significant association between NC and body mass index (BMI), age, weight, waist circumference, hip circumference, and WHR. A follow-up study19 also demonstrated that higher NC is correlated positively with the factors of the metabolic syndrome and is therefore likely to increase the risk of CHD. More recently, Ben-Noun and Laor20 examined a relationship between changes in systolic blood pressure (BP), and diastolic BP and changes in NC of the metabolic syndrome, and found changes in both to correlate positively with changes in NC.

Finally, Fink et al.21 studied 2D:4D ratio in relation to measures of body shape and body fat distribution and found some support for an early organizational effect of sex hormones through the association between indices of female body shape, male BMI, and human finger length patterns.

Based upon these findings, we hypothesized that 2D:4D ratio – a correlate of prenatal and adult T and E levels – would also correlate with NC. Given that T acts as a protective against MI and CHD, and NC is positively correlated with the risk for these diseases, we expected higher 2D:4D ratios to be associated with higher NC. We further hypothesized that correlations would be stronger in male than in female subjects. If our assumptions were right, it would (i) support the view that both 2D:4D ratio and NC are simple measures for screening of people at higher risk for CHD and metabolic syndrome, and (ii) argue that the development of those diseases may influenced by early exposure to sex-steroids.

Research methods and procedures

Sample

Our sample was 244 heterosexual, right-handed, subjects (127 men and 117 women) between the ages of 18–38 years (men: mean=22.19, s.d.=4.36; women: mean=21.75; s.d.=2.95) from mainly undergraduate courses at the University of Vienna (Austria) and Northumbria University (United Kingdom). Participants were informed of the purposes of the study and gave their written consent. Ethical approval was granted by the local Ethics Committees.

Measurements

We recorded age of the participant and measured body weight, body height, circumferences of waist, hip, and neck. Weight (kg) was measured by digital scales and body height (cm) with a portable stadiometer. Waist circumference (cm) was measured at the midpoint between the costal margin and iliac crest; hip circumference (cm) was defined as maximum circumference in the gluteal area. NC (cm) was measured at the level of the upper margin of the thyroid cartilage. In men, with a laryngeal prominence (Adam's apple), we measured below the prominence. All circumference measurements were taken at the end of expiration with a plastic tape measuring within 1 mm. WHR was calculated by dividing the waist measure by the hip measure (in cm). BMI was calculated as weight (in kg) divided by square of the height (in m).

The 2nd and 4th digits were measured on the palmar surface of the hand from the basal crease proximal to the palm to the tip of the finger using Vernier calipers measuring to 0.01 mm (for reviews see Garn et al.5, Manning et al.6). It should be noted that accurate calculation of 2D:4D is not dependent on measurement of finger lengths to 0.01 mm as sexual dimorphism in 2D:4D has been shown from measurements made to the nearest mm with a ruler or tape measure.22 Each finger was measured twice and comparisons between first and second 2D:4D ratios measurements gave an intraclass correlation coefficient of r1=0.89 for the right hand and r1=0.79 for the left. We used repeated measures ANOVA to calculate the ratio (F) between measurement error (the differences between successive measures of 2D:4D) and between-participant differences. We found that between-individual differences were significantly greater than measurement error in 2D:4D (right hand: F=26.68, P=<0.0001; left hand: F=57.33, P=<0.0001). We concluded that our calculated values of 2D:4D reflected real differences between individuals.

Statistical analysis

We used unpaired t-tests for determining possible differences between men and women in 2D:4D and body measures. Pearson correlation (r) was used for assessing the relationship between 2D:4D, NC and other body measures and partial correlations were calculated in order to remove confounding effects of body weight.

Results

Sex differences

In accordance with previous reports (for a review see Manning et al. 6), a sex difference in 2D:4D was found, as mean male 2D:4D ratio was significantly lower than mean female 2D:4D. The difference was statistically significant for left-hand 2D:4D ratio but not for the right-hand 2D:4D ratio (unpaired t-tests; right hand: t(242)=0.992, P=0.322; left hand: t(242)=2.681, P=0.008).

Table 1 shows descriptive statistics of the total sample and for men and women separately. There was no sex difference for age (t(242)=−0.909, P=0.364) and hip circumference (t(242)=0.718, P=0.473). Sex differences in body measures were found for body weight (t(242)=−12.663, P=<0.0001), body height (t(242)=−18.468, P=<0.0001), waist circumference (t(242)=−9.904, P=<0.0001), NC (t(242)=−23.307, P=<0.0001), WHR (t(242)=−14.360, P=<0.0001), and BMI (t(242)=−4.641, P=<0.0001).

Table 1 Descriptive statistics, means and standard deviations (s.d.), for age, body measures, and 2D:4D ratios

Correlations between 2D:4D ratios and body measurements

Table 2 reports correlation coefficients for the relationships between 2D:4D ratios, age, and body measures. In men, there was a significant positive association between right-hand 2D:4D with WHR. Moreover, hip circumference was found to correlate significantly negatively with right-hand 2D:4D ratio. NC correlated positively with right- and left-hand 2D:4D ratios but this was not significant (right hand 2D:4D, P=0.105, left-hand 2D:4D, P=0.150). There were no significant associations with 2D:4D and any body measures in women and in comparison to men, correlation coefficients were lower.

Table 2 Pearson correlation coefficients for the relationships between 2D:4D ratios, age, and body measures

The highest correlation coefficients between body measurements were found for NC and body weight, in both men (r=0.709, P=<0.0001) and women (r=0.648, P=<0.0001). As a result, of the apparent increase of NC with weight (see also 18) we controlled for the effect of body weight by calculating partial correlations (rp) between 2D:4D ratios and body measures. In men, there were significant positive correlations between right-hand and left-hand 2D:4D and NC (right hand: rp=0.272, P=0.006; left hand: rp=0.258, P=0.009). WHR was positively associated with mean 2D:4D ratio (rp=0.280, P=0.014) and left- and right-hand 2D:4D ratio (left hand: rp=0.253, P=0.027; right hand: rp=0.263, P=0.021). Further, NC was also found to correlate significantly positively with WHR (rp=0.366, P=0.004) when controlling for body weight. None of these correlations was found to be significant in women where the strongest correlation was found between NC and WHR, but this failed to reach significance (rp=0.175, P=0.085).

Discussion

In accord with our predictions, we found that NC was positively correlated with 2D:4D ratios when body weight was controlled for. This association was present in men but not in women. This may be due to the sexual dimorphic pattern of body fat distribution in men and women, which is known to be closely linked to sex-steroid hormones, and thus influences cardiovascular and metabolic disease processes.23 Previous studies suggested NC as a simple screening measure for identifying overweight and obese patients. Our results of positive correlations between NC and body weight, and also NC and WHR when weight was controlled, support this measure. In particular, the present data also suggest that the association is stronger in men than in women. WHR as a measure of body fat distribution has been reported to have a high predictive value for cardiovascular risk factors (see Esmaillzadeh et al.24 and also Dalton et al.25 for recent discussion). Our findings of positive associations between NC and WHR in men confirm that both measures are indicative of body fat. Also, positive associations between 2D:4D ratio (a putative marker for prenatal T) and WHR suggest that low androgen levels in men are associated with a greater risk of obesity. Moreover, this result and also the positive correlation between 2D:4D ratios and NC suggest that digit ratio is indicative for being overweight (at least in men) and may thus be an additional simple screening measure. Being overweight and/or obese is a high-risk factor for CHD associated with NC. Manning and Bundred14 and Manning et al.15 found that men with low 2D:4D ratios tend to have their first MI's later in life than men with high 2D:4D ratios. The present findings of positive correlations between 2D:4D ratios and NC in men suggest a possible predisposition towards CHD via 2D:4D as proxy to early sex-steroid exposure.

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Fink, B., Manning, J. & Neave, N. The 2nd–4th digit ratio (2D:4D) and neck circumference: implications for risk factors in coronary heart disease. Int J Obes 30, 711–714 (2006). https://doi.org/10.1038/sj.ijo.0803154

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Keywords

  • digit ratio
  • neck circumference
  • testosterone
  • coronary heart disease
  • metabolic syndrome

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