sympathetic nervous system (Muller-Wieland et al 1998; Sechi and Bartoli 1996). Insulin also stimulates the release of IGF-1 that may contribute to the development of hypertension by causing vascular smooth muscle hypertrophy. Current evidence on prevalence of hypertension in patients with PCOS are conﬂicting at present with some studies suggesting a higher prevalence in this population (Vrbikova et al 2003; Elting et al 2001; Orbetzova et al 2003; Holte et al 1996), but not by others (Cibula et al 2000; Zimmermann et al 1992; Sampson et al 1996). A large long-term follow-up study by Wild et al (2000a) suggested an increased prevalence of hypertension in patients with PCOS, but with no increased risk of mortality and morbidity from coronary heart disease. Dyslipidemia Data are conﬂicting on whether women with PCOS have a characteristic dyslipidemia. Studies have reported decreased levels of the cardioprotective high-density cholesterol lipoprotein (HDL-C), and elevated levels of triglycerides (Reaven 1988; Robinson et al 1996; Conway et al 1992; Holte et al 1994; Wild et al 1985; Legro et al 1999), although in one study HDL was elevated (Legro et al 2001). Of con- cern, dyslipidemia has been found at puberty in studies on adolescent girls with a history of premature pubarche (Kent and Legro 2002) and the metabolic disturbances can often be detected in the prepubertal period and throughout puberty (Ibanez et al 1998). This dyslipidemia is seen in both lean and obese PCOS (Yildirim et al 2003) Pro-thrombotic state Hyperinsulinemia contributes to the prothrombotic state by reducing ﬁbrinolysis and raising the level of plasminogen activator inhibitor (PAI-1) (Potter van Loon et al 1993). In patients with PCOS, the level of PAI-1 was found to be elevated (Atiomo et al 1998; Sampson et al 1996; Yildiz et al 2002), and it decreased with improvement in insulin sensitivity, either through weight loss (Andersen et al 1995) or the use of insulin sensitizing agents (Ehrmann et al 1997; Velazquez et al 1997). The increase in PAI-1 activity in PCOS was thought to be independent of body mass index since elevated levels were also observed in lean PCOS women. Moreover, the increased level of PAI activity in PCOS was directly correlated with insulin resistance, thus implicating it as a contributing cardiovascular risk factor (Tarkun et al 2004). However, other studies disagree (Atiomo et al 2000; Dahlgren et al 1994). Vascular Health and Risk Management 2007:3(1) Cardiometabolic aspects of POCS Risk of type 2 diabetes PCOS is commonly detected in a younger age group and is associated with a high risk of progression to type 2 diabetes and impaired glucose tolerance. For example, in one study, 35% of patients with PCOS had impaired glucose tolerance and 10% had type 2 diabetes by the age of 40 (Ehrmann et al 1999). A history of type 2 diabetes in a ﬁrst-degree relative appears to deﬁne a subset of PCOS subjects with a greater prevalence of insulin secretory defects. The risk of develop- ing type 2 diabetes through increased insulin resistance in PCOS may be enhanced by the defects described in insulin secretion (Ehrmann et al 1995). A unique defect in serine phosphorylation of the insulin receptor that resulted in decreased activation of the recep- tor has been identiﬁed in about 50% of women with PCOS (Zhang et al 1995). Furthermore, serine phosphorylation of CYP17 (Cytochrome P450, subfamily XVII), may also be part of the mechanism of increased adrenal androgen synthesis implicating serine phosphorylation an important process in the PCOS phenotype. The CYP17 gene encodes the cytochrome P450c17 enzyme which mediates the 17α-hydroxylation of pregnenolone and progesterone, and subsequent conversion of these 17-hydroxylated products to the estradiol precursors DHEA and androstenedione. In addition, familial PCOS has been linked to an insulin regulatory locus on chromosome 11 (Waterworth et al 1997). Whether this represents a common genetic defect in PCOS and diabetes or whether it reﬂects co-segregation of diabetes with PCOS in the tested families, remains to be determined. Sleep apnea Sleep apnea is an independent cardiovascular risk factor that has been found to be more common in PCOS, the dif- ference remained signiﬁcant even when controlled for body mass index (BMI) (Gopal et al 2002; Fogel et al 2001). It was reported that the strongest predictors for sleep apnoea were fasting plasma insulin and glucose-to-insulin ratios (Vgontzas et al 2001). Atherosclerosis The presence of cardiovascular risk factors of obesity, in- sulin resistance and dyslipidemia may predispose women with PCOS to coronary heart disease, although this remains controversial: Angiography One report evaluated 143 women age less than 60 years old undergoing cardiac catheterization for the investigation of 57