To the Editor:
A recent publication entitled “The evaluation of endothelial function with flow mediated dilatation and carotid intima media thickness in young nonobese polycystic ovary syndrome patients: existence of insulin resistance alone may not represent an adequate condition for deterioration of endothelial function” (1) has shown that flow mediated dilatation (FMD) was not different between polycystic ovary syndrome (PCOS) and ovulatory women. The FMD in PCOS women was 24.88±9.63% and 22.35±9.40% in the control group. Comparing the values for basal brachial arterial diameter (3.54±0.37 mm and 3.81±0.66 mm; PCOS and control group, respectively) and stimulated brachial arterial diameter (4.41±0.39 mm and 4.65±0.77 mm) the observed dilation was really larger than 20% for both groups. However, the expected FMD in healthy people is 7% to 10%, while the expected FMD in patients with cardiovascular disease is 0 to 5% (2). Furthermore, the great majority of studies evaluating healthy people reported mean FMD between 3% and 15% (3).
The authors did not explain why the results for FMD observed in this study were awkwardly high. As far as we know, the highest value for FMD reported in the literature for PCOS women was 13.7±2.7% (4). However, in this study the authors have used upper arm compression, which is related to FMD, up to 4.4% larger than when compressing the forearm (3). Actually, the highest value we found for FMD in PCOS women using forearm compression was 8.17±1.26%, observed after 6 months of metformin treatment (5); before treatment, the observed FMD was 3.24±0.71%. Since the compression to induce hyperemia was performed in the right forearm in the study by Arikan et al. (1), we expect maximum values for mean FMD both PCOS and ovulatory women between 6% and 14%, but not 24%.
Wellington P Martins, M.D
Carolina O. Nastri, MD
Carolina S.Vieira, PhD
Rui A Ferriani, PhD
Departamento de Ginecologia e Obstetrícia da Faculdade de Medicina de Ribeirão Preto
Universidade de São Paulo
Sao Paulo, Brazil
1. Arikan S, Akay H, Bahceci M, Tuzcu A, Gokalp D. The evaluation of endothelial function with flow-mediated dilatation and carotid intima media thickness in young nonobese polycystic ovary syndrom patients; existence of insulin resistance alone may not represent an adequate condition for deterioration of endothelial function. Fertil Steril 2008.2. Moens AL, Goovaerts I, Claeys MJ, Vrints CJ. Flow-mediated vasodilation: a diagnostic instrument, or an experimental tool? Chest 2005;127:2254-63.
3. Bots ML, Westerink J, Rabelink TJ, de Koning EJ. Assessment of flow-mediated vasodilatation (FMD) of the brachial artery: effects of technical aspects of the FMD measurement on the FMD response. Eur Heart J 2005;26:363-8.
4. Cascella T, Palomba S, De Sio I, Manguso F, Giallauria F, De Simone B et al. Visceral fat is associated with cardiovascular risk in women with polycystic ovary syndrome. Hum Reprod 2008;23:153-9.
5. Diamanti-Kandarakis E, Alexandraki K, Protogerou A, Piperi C, Papamichael C, Aessopos A et al. Metformin administration improves endothelial function in women with polycystic ovary syndrome. Eur J Endocrinol 2005;152:749-56.
Published online in Fertility and Sterility doi: 10.1016/j.fertnstert.2008.12.105
The Authors Respond:
Although Wellington P. Martins et al. claimed that “the expected FMD in healthy people is 7% to 10%, while the expected FMD in patients with cardiovascular disease is 0 to 5%. Furthermore, the great majority of studies evaluating healthy people reported mean FMD between 3% and 15%,” this issue is controversial. There is a wide variety in measured mean FMD levels among populations (1). Bots et al (2) demonstrated that the mean FMD values varied from 0.20 to 19.2% for the healthy populations. In the same meta-analysis authors showed that for the CVD patients, mean FMD ranged from 21.3 to 14%. For subjects with diabetes mellitus mean FMD ranged from 0.75 to 12% (2). Again we reported that FMD values of patients with Sheehan syndrome was 13.42±6.5% baseline, 20.8± 10.2% after hormone replacement treatment, 18.9±5.6% in healthy women previously. Therefore, this issue needs further investigations (3).
Lack of a standardized method to measure brachial artery reactivity may contribute to these different results. In our method, the average of all the measurements for each time period was calculated and FMD was estimated as the percentage increase in vessel diameter from baseline conditions to maximum vessel diameter during hyperemia. This method may be influenced by operator and subject variability. Again, a longer duration of the ischemic trigger and increased occlusion pressure may also lead to a higher absolute value of FMD (4). In this manner, Peretz et al. (5) showed a significantly greater and delayed FMD following proximal occlusion (16.2% and 107.2 seconds, respectively), compared to when distal occlusion (7.3% and 67.8 seconds) was present (5).
On the other hand, FMD values may be affected by age and BMI variability. Many studies addressing this issue have been performed in various populations in terms of age and BMI (elderly, young, obese and non-obese patients). Our study population was made up of young non-obese women (mean age 22.82±5.53 yr; range 17–30 yr; and body mass index (BMI): 21.48±6.50 kg/m2). This study population may also be responsible for these results. As a result, standardization of the FMD measurements and patient population will establish prevention of the different results among with studies.Senay Arikan, MDa
Hatice Akay, MDb
Mithat Bahceci, MDa
Alpaslan Tuzcu, MDa
Deniz Gokalp, MDa
aDepartment of Endocrinology
bDepartment of Radiology
University of Dicle School of Medicine
1. Al-Qaisi M, Kharbanda RK, Mittal TK, Donald AE. Measurement of endothelial function and its clinical utility for cardiovascular risk. Vasc Health Risk Manag. 2008;4(3):647-52.
2. Bots ML, Westerink J, Rabelink TJ, de Koning EJ. Assessment of flow-mediated vasodilatation (FMD) of the brachial artery: effects of technical aspects of the FMD measurement on the FMD response. Eur Heart J. 2005 Feb;26(4):363-8.
3. Bahceci M, Pasa S, Akay HO, Tuzcu A, Tumer C, Gokalp D. Serum nitric oxide levels and flow-mediated dilatation in patients with Sheehan syndrome and the effect of combination therapy consisting of L-thyroxine, prednisolone, and conjugated estrogen/medroxyprogesterone acetate.Fertil Steril. 2008 Apr;89(4):995-7. Epub 2007 Jun 19.
4. Corretti MC, Plotnick GD, Vogel RA. Technical aspects of evaluating brachial artery vasodilatation using high-frequency ultrasound. Am J Physiol 1995;268:H1397–H1404.
5. Peretz A, Leotta DF, Sullivan JH, Trenga CA, Sands FN, Aulet MR, Paun M, Gill EA, Kaufman JD. Flow mediated dilation of the brachial artery: an investigation of methods requiring further standardization. BMC Cardiovasc Disord. 2007 Mar 21;7:11.
Published online in Fertility and Sterility doi: 10.1016/j.fertnstert.2008.12.104