Thigh circumference and risk of heart disease and premature death: prospective cohort study

Heitmann and Frederiksen (1) in a study of 1436 men and 1380 women in
Denmark concluded that smaller thigh circumference was independently
related to total death and cardiovascular and coronary heart diseases for
men and to total death for women. The risk was stronger than that of waist
circumference or body mass index. There was also a threshold thigh size
below which the risk was greatly increased.

Ian Scott (2) asks whether this risk is biologically plausible. One
possible explanation comes from a literature review (3) which showed that
the sympathetic nervous system and the catecholamines played a major role
in the aetiology and pathogenesis of coronary heart disease.

The catecholamines are responsible for the process of
gluconeogenesis, the synthesis of blood sugar from stored glycogen in the
muscles (and liver), including the thigh muscles. This would result in
shrinking of the thigh muscles and a smaller thigh size.

A measure that might confirm this mechanism is that of resting heart
rate , a low tech and inexpensive measure of autonomic tone, which has
been shown to independently predict myocardial infarction or coronary
death in women and previously in men (4)

References

1.David L Heitmann and Peter Frederiksen. Thigh circumference and risk of
heart disease:prospective cohort study. BMJ 2009;339:b3292 (26 September)

2. Ian Scott. Thigh Circumference and risk of heart disease and
premature death. The strength of the association needs further research.
(Editorial).BMJ 2009; 339: b3302 (26 September)

3. Lee. J.A.The role of the sympathetic nervous system in ischaemic
heart disease: A review of epidemiological features and risk factors,
integration with clinical and experimental evidence and hypothesis,
Activitas Nervosa Superior 1983; 25: 110-121.

4. Women's Health Research Group. Resting heart rate as a low tech
preictor of coronary events in women: prospective cohort study. BMJ 2009;
338; b219(7March). .

Competing interests:
None declared

We read with great interest the article by Heitmann and Frederiksen1.

We want to hightlight two elements.

First, age might be the most important prognostic factor in primary2 and
secondary prevention3 and Heitmann et al. excluded age in their
statistical model; although compared with the men and women who died
during follow-up, baseline age was 20 and 10 years lower for the men and
women who survived in each case.

Second, a focus on thigh circumference might help general practitioners to
identify individuals who are at increased risk of early morbidity and
mortality. We can state that generally underweight pacient was a high risk
group4, but this fact is not taken into account in the current obesity
classification of the National Institutes of Health5.
Recently, we published a new ergoantropometric classification, which it
takes into consideration that underweight (body mass index BMI, <_18.5 kg="kg" m2="m2" is="is" an="an" increased="increased" risk="risk" especially="especially" in="in" secondary="secondary" prevention="prevention" and="and" includes="includes" assessment="assessment" of="of" waist="waist" circumference="circumference" physical="physical" fitness="fitness" addition="addition" to="to" bmi6.="bmi6." p="p"/>References

1. Heitmann BL and Frederiksen P. Thigh circumference and risk of heart
disease and premature death: prospective cohort study. BMJ 2009;339: b3292

2. Hippisley-Cox J, Coupland C, Vinogradova Y, Robson J, Minhas R, Sheikh
A, et al. Predicting cardiovascular risk in England and Wales: prospective
derivation and validation of QRISK2. BMJ 2008;336:a33

3. Nowicki ER, Birkmeyer NJ, Weintraub RW, Leavitt BJ, Sanders JH, Dacey
LJ, et al. Multivariable prediction of in-hospital mortality associated
with aortic and mitral valve surgery in Northern New England. Ann Thorac
Surg. 2004 Jun;77(6):1966-77.

4. Flegal KM, Graubard BI, Williamson DF, Gail MH. Excess Deaths
Associated With Underweight, Overweight, and Obesity JAMA. 2005;293:1861-
1867

5. Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Pi-Sunyer FX, et al.
Obesity and cardiovascular disease: pathophysiology, evaluation, and
effect of weight loss: an update of the 1997 American Heart Association
scientific statement on obesity and heart disease from the Obesity
Committee of the Council on nutrition, physical activity, and metabolism.
Circulation. 2006;113:898-91

6. Morales Salinas A, Coca A. Obesity, physical activity and
cardiovascular risk: ergo-anthropometric classification, pharmacological
variables, biomarkers and ‘‘obesity paradox’’. Med Clin(Barc).2009.
doi:10.1016/j.medcli.2009.02.038

Competing interests:
None declared

According to the abstract of their paper, Heitmann et al. [1] found
that "a threshold effect for thigh circumference was evident, with greatly
increased risk of premature death below around 60 cm". Their Table 1 shows
the median thigh circumference was around 55 cm, so this implies that more
than half the population were at greatly increased risk. In contrast to
the misleading abstract and press release[2], the staff of BMJ Best
Treatments provided a more appropriate interpretation in the “best
treatments” section of Friday’s Guardian [3]: " Having thighs larger than
60cm made no difference to people's risk. People were most at risk if they
had a thigh measurement of less than 46.5 centimetres (18 inches). This
group had roughly double the chances of getting heart and circulation
problems or dying during the study. However, only 2.5 percent of the
people fell into this category."

Particularly in men, the reported effects were modest before analyses
were adjusted for anthropometric measures such as body mass index (BMI)
and waist circumference. These adjusted estimates are hard to interpret,
because they refer to the differences in risk that would apply if an
individual changed their thigh circumference while keeping these other
anthropometric measures constant.

The sources referred to above[1-3], as well as the accompanying
editorial[4], seemed to ignore these issues in interpretation.

[1] Heitmann BL, Frederiksen P. Thigh circumference and risk of
heart disease and premature death: prospective cohort study. BMJ
2009;339:b3292.

[2] BMJ press releases Monday 31 August to Friday 4 September 2009.
<http://www.bmj.com/content/vol339/issue7720/press_release.dtl>

[3] BMJ Group. Could big thighs protect against heart disease? The
Guardian. 4 September 2009.
<http://www.guardian.co.uk/lifeandstyle/besttreatments/2009/sep/04/could
-big-thighs-protect-against-heart-disease>

[4] Scott IA. Thigh circumference and risk of heart disease and
premature death. BMJ 2009;339:b3302.

Competing interests:
None declared

The paper by Heitmann and Frederiksen1 provides a valuable
contribution in understanding the role of fat free mass and muscle mass on
health. According to their findings a low thigh circumference was
associated with an increased risk of developing heart disease or premature
health. As the authors state “The adverse effects of small thighs might be
related to too little muscle mass in the region”. The authors can only
speculate on the possible mechanism that explain the role of increased
muscle mass on decreased risk of mortality.

In one of our studies (Nassis et al., 2005) body composition was
determined with DXA and insulin sensitivity with oral glucose tolerance
test before and after 12 weeks of aerobic training in 19 overweight and
obese girls aged 9-15 years. In addition, adiponectin, CRP, IL-6, IGF-1,
sICAM-1 and sVCAM-1, blood lipids and lipoproteins concentration was
determined pre- and post-training. The major finding was a 23.3%
improvement in insulin sensitivity as shown by the smaller (compared with
pre-training levels) area under the insulin concentration curve (AUC)
after training (12781.7±7454.2 vs. 9799.0±4918.6 ìU•min/ml, before and
after intervention, respectively, P= 0.03). Insulin sensitivity was
improved in these girls without changes in body weight, percent body fat,
waist circumference and estimated visceral fat. Lower limb fat free mass
(LLFFM) increased by 6.2% (P<0.01), as a result of training. The
interesting finding was that LLFFM increase was inversely correlated with
lowering of insulin AUC (r= -0.68, P<0.01). Finally, this improvement
in insulin sensitivity was without change in serum adiponectin, IL-6 and
CRP concentrations.

These findings are in agreement with other studies in adults, which
suggest that exercise training-induced improvements in insulin sensitivity
with no change in total body and visceral fat may be due to changes in the
ability of muscles to metabolize glucose3. The increase in the LLFFM in
our study2 is in accordance with this concept.

Since skeletal muscle is the primary target tissue for insulin
action, it is tempting to suggest that the observed exercise training-
induced increase in muscle mass may, at least in part, explain the
enhanced insulin sensitivity in these studies. Conclusively, there is
evidence in the literature that exercise induced increase in fat free mass
of the legs might contribute to improved health risk factors such as
insulin resistance. This exercise-induced effect might, at least
partially, explain the lower risk for cardiovascular disease with
increased thigh circumference in Heitmann and Frederiksen’s 1 study.

George P Nassis1 and Labros S Sidossis2

1Department of Sport Medicine and Biology of Physical Activity,
Faculty of Physical Education and Sport Science, National and Kapodistrian
University of Athens, Greece

2Laboratory of Nutrition and Clinical Dietetics, Department of Nutrition
and Dietetics, Harokopio University, Athens, Greece

References

1. Heitmann BL and Frederiksen P. Thigh circumference and risk of
heart disease and premature death: prospective cohort study. BMJ 2009;339:
b3292

2. Nassis GP, Papantakou K, Skenderi K, Triandafillopoulou M,
Kavouras SA, Yannakoulia M, Chrousos GP, and Sidossis LS. Aerobic exercise
training improves insulin sensitivity without changes in body weight, body
fat, adiponectin and inflammatory markers in overweight and obese girls.
Metabolism 2005;54:1472-1479

3. Potteiger JA, Jacobsen DJ, Donnelly JE and Hill JO. Glucose and
insulin responses following 16 months of exercise training in overweight
adults: the Midwest Exercise Trial. Metabolism 2003;52:1175-1181

Competing interests:
None declared