title: Central arterial stiffness and diastolic dysfunction are associated with insulin resistance and abdominal obesity in young women but polycystic ovary syndrome does not confer additional risk.
abstract: OBJECTIVE
  Are arterial stiffness, carotid intima-media thickness and diastolic dysfunction increased in young women with polycystic ovary syndrome (PCOS) independently of the effects of obesity?
  
  
  CONCLUSIONS
  Insulin resistance and central obesity are associated with subclinical cardiovascular dysfunction in young women, but a diagnosis of PCOS does not appear to confer additional risk at this age.
  
  
  BACKGROUND
  Some studies have shown that young women with PCOS may have increased measures of cardiovascular risk, including arterial stiffness, carotid intima-media thickness and myocardial dysfunction. However, it is difficult to establish how much of this risk is due to PCOS per se and how much is due to obesity and insulin resistance, which are common in PCOS and themselves associated with greater vascular risk.
  
  
  METHODS
  This cross-sectional study comprised 84 women with PCOS and 95 healthy volunteers, aged 16-45 years.
  
  
  METHODS
  The study was conducted in a university hospital. Subjects underwent a comprehensive assessment of body composition (including computed tomography (CT) assessment of visceral fat; VF), measurements of arterial stiffness (aortic pulse wave velocity; aPWV), common carotid intima-media thickness (ccIMT), diastolic function (longitudinal tissue velocity; e':a') and endocrinological measures. A sample size of 80 in each group gave 80% power for detecting a difference of 0.45 m/s in aPWV or a difference of 0.25 in e':a'.
  
  
  RESULTS
  After adjustment for age and body mass index (BMI), PCOS subjects had a greater insulin response (insulin area under the curve-IAUC) following glucose challenge (adjusted difference [AD] 35 900 pmol min/l, P < 0.001) and higher testosterone (AD 0.57 nmol/l, P < 0.001) and high molecular weight adiponectin than controls (AD 3.01 µg/ml, P = 0.02), but no significant differences in aPWV (AD -0.13 m/s, P = 0.33), ccIMT (AD -0.01 mm, P = 0.13), or e':a' (AD -0.01, P = 0.86) were observed. After adjustment for age, height and central pulse pressure, e':a' and aPWV were associated with logVF and IAUC. ccIMT was not related to logVF. The relationships between e':a' or aPWV and insulin resistance were only partly attenuated by adjusting for logVF. There was no significant relationship between aPWV or e':a' and either testosterone or adiponectin.
  
  
  CONCLUSIONS
  The study recruited young women meeting the Rotterdam criteria for PCOS diagnosis; hence our findings may not be generalizable to older patients or those meeting other definitions of the syndrome. Biochemical hyperandrogenism was based solely on measurement of total testosterone. Cases and controls were not matched in advance for age and BMI, although the influence of these variables on the cardiovascular outcome measures was adjusted for.
  
  
  CONCLUSIONS
  This study shows that central arterial stiffness and diastolic dysfunction are not increased in young women with PCOS, whereas they are associated with both insulin resistance and central obesity. Obesity thus represents the greatest modifiable risk factor for cardiovascular disease in young women with PCOS and lifestyle measures which target weight reduction are critical.
  
  
  BACKGROUND
  This study received no specific grant support from any funding body. The authors have no conflicts of interest to declare.
authors.affiliation: College of Human and Health Sciences, Swansea University, Swansea SA2 8PP, UK.
authors.forename: E
authors.initials: E
authors.lastname: Rees
authors.affiliation: Institute of Molecular and Experimental Medicine, Cardiff University, Cardiff CF14 4XN, UK.
authors.forename: R
authors.initials: R
authors.lastname: Coulson
authors.affiliation: Institute of Primary Care and Public Health, Cardiff University, Cardiff CF14 4XN, UK.
authors.forename: F
authors.initials: F
authors.lastname: Dunstan
authors.affiliation: Department of Medical Physics, University Hospital of Wales, Cardiff CF14 4XW, UK.
authors.forename: W D
authors.initials: WD
authors.lastname: Evans
authors.affiliation: Department of Medical Physics, University Hospital of Wales, Cardiff CF14 4XW, UK.
authors.forename: H L
authors.initials: HL
authors.lastname: Blundell
authors.affiliation: Institute of Life Science, College of Medicine, Swansea University, Swansea SA2 8PP, UK.
authors.forename: S D
authors.initials: SD
authors.lastname: Luzio
authors.affiliation: Institute of Life Science, College of Medicine, Swansea University, Swansea SA2 8PP, UK.
authors.forename: G
authors.initials: G
authors.lastname: Dunseath
authors.affiliation: Institute of Life Science, College of Medicine, Swansea University, Swansea SA2 8PP, UK.
authors.forename: J P
authors.initials: JP
authors.lastname: Halcox
authors.affiliation: Institute of Molecular and Experimental Medicine, Cardiff University, Cardiff CF14 4XN, UK.
authors.forename: A G
authors.initials: AG
authors.lastname: Fraser
authors.affiliation: Institute of Molecular and Experimental Medicine, Cardiff University, Cardiff CF14 4XN, UK reesda@cf.ac.uk.
authors.forename: D A
authors.initials: DA
authors.lastname: Rees
mesh_terms: D000293:Adolescent; D000328:Adult; D001823:Body Composition; D002318:Cardiovascular Diseases / Q000150:complications*; D005260:Female; D006334:Heart Function Tests; D006801:Humans; D007333:Insulin Resistance; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000150:complications*; D011085:Polycystic Ovary Syndrome / Q000150:complications*; D018570:Risk Assessment; D059289:Vascular Stiffness
keywords: PCOS; cardiovascular; insulin resistance; obesity; polycystic ovary syndrome