Li Wei Cho et al chest pain. Polycystic ovarian morphology was present in 42% of women, and was associated with hirsutism, lower levels of HDL cholesterol, and higher concentrations of free testosterone, triglyceride, and C-peptide. The women with polycystic ovaries had more extensive coronary disease on angiography than those with normal ovaries (Birdsall et al 1997). However, this study only examined at the asso- ciation between ultrasound evidence of polycystic ovaries alone (rather than the full Rotterdam consensus deﬁnition of PCOS) and the extent of coronary disease on cardiac catheterization. Carotid ultrasound A predisposition toward atherosclerosis was suggested in an ultrasonographic study of 16 women with PCOS aged over 40 years, where carotid artery intima-media thickness (IMT) was signiﬁcantly greater than in normal controls (Guzick et al 1996). However, the mean IMT in the PCOS group was still well below that seen in patients with signiﬁcant carotid artery disease. In another study with a larger cohort of subjects, the same group of researchers reported that among women aged 45 years or above, patients with PCOS had signiﬁcantly greater mean carotid IMT than women in the control group (Talbott et al 2000). Endothelial dysfunction Endothelial dysfunction is associated with the development of atherosclerosis (Celermajer et al 1992). A positive cor- relation was demonstrated between abnormal endothelial function and testosterone levels in hyperandrogenic insulin-resistant women with PCOS, an association that was stronger than that of insulin sensitivity (Paradisi et al 2001). Conversely, others have reported no differences in surrogate markers including endothelial function for increased car- diovascular risk in PCOS compared with weight-matched controls (Bickerton et al 2005). Several mechanisms may be involved in the develop- ment of endothelial dysfunction, such as reduced synthesis and release of nitric oxide (NO) (Kawashima and Yokoyama 2004), enhanced inactivation of NO after its release from endothelial cells (Bitar et al 2005) or enhanced synthesis of vasoconstricting agents (Bhagat and Vallance 1999). It has been demonstrated that insulin exerts a direct hypertrophic effect on the vascular endothelium and the smooth muscle cells. It has been found that in the skeletal muscle circulation insulin stimulates both endothelin-1 and NO activity, and an imbalance between the release of these two substances may be involved in the pathophysiology of endothelial dysfunc- 58 tion. Recent studies suggested that CRP directly promotes the atherosclerotic processes and endothelial cell inﬂammation leading to atherothrombosis (Sjoholm and Nystrom 2005). Long-term risk In the Nurses’ Health Study, a history of menstrual cycle ir- regularity was associated with an increased risk of non-fatal and fatal coronary heart disease (Solomon et al 2002). This might be explained by a high rate of PCOS with its associ- ated metabolic disturbances in these women, although no other clinical or biochemical androgen data was available to conﬁrm that menstrual irregularity was due to PCOS. Despite the increase in cardiovascular risk factors includ- ing diabetes, hypertension, raised plasma cholesterol and BMI >30, morbidity and mortality from of coronary heart disease among women with PCOS in a long-term study has not proved to be as high as previously predicted (Wild et al 2000b). One recent observation showed no difference in surrogate markers of cardiovascular risk between PCOS and weight- matched controls (glucose, lipid, lipoprotein, sialic acid, ﬁbrino- gen, CRP, reactive hyperemic forearm blood ﬂow) (Bickerton et al 2005). However, in contrast, in another study patients with PCOS were found to have elevated triglycerides and cholesterol but no differences in CRP or 24 hour BP were observed. In addition, they also demonstrated that patients with PCOS had increased arterial stiffness measured by pulse wave velocity (PWV) and reduced brachial artery ﬂow mediated vasodilatation (FMD), a marker of endothelial function (Meyer et al 2005). Whether these differences could have been accounted for by differing patient selection is unclear. In summary, cardiovascular disease studies in PCOS have been inconclusive with some suggesting increased cardiac events among women with PCOS whilst other stud- ies suggesting no increase compared with normal cycling women. This could be due to small sample size in the stud- ies and variation in the characteristics of patients recruited. It has been suggested that patients with PCOS as deﬁned by hyperandrogenemia plus either of oligomenorrhoea or polycystic ovaries on ultrasound may have a slight increase in cardiovascular risk proﬁle as compared with those with only oligomenorrhoea and polycystic ovaries without hy- perandrogenemia. The role of adipocyte in cardiometabolic syndrome Adipose tissue has traditionally been considered an energy storage organ, but over the last decade a novel role of the Vascular Health and Risk Management 2007:3(1)