Objective: There is evidence of preclinical cardiovascular disease even in young women with polycystic ovary syndrome (PCOS). The aim of our study was to assess and compare the effects of metformin (MET) and rosiglitazone (ROSI) on endothelial function in PCOS patients. Methods: For 6 months, 26 women with PCOS received either MET or ROSI. Blood samples for assessment of androgens, lipids, and high-sensitive C-reactive protein were taken at baseline and at endpoint. Endothelium-dependent flow-mediated dilation (FMD) and glyceryl trinitrate-induced endothelium-independent dilation of brachial artery were studied before and after treatment. Homeostasis model assessment (HOMA IR ) calculation was applied as a measure of insulin resistance (IR). Results: With treatment, FMD of brachial artery improved significantly from 4.2G6.6 to 10.2G5.9% in MET group (PZ0.036) and from 2.9G3.2 to 7.6G4.9% in ROSI group (PZ0.026), MET being as effective as ROSI (PZ0.70). The endothelium-independent dilation did not change. Additionally, administration of MET was associated with a significant decrease in HOMA IR (PZ0.003), serum total and serum-free testosterone (PZ0.045 and PZ0.008 respectively) and significantly higher frequencies of menstrual bleeding (PZ0.006). Conclusions: A 6-month therapy with insulin sensitizers, MET and ROSI, resulted in marked improvement of endothelial function in young PCOS patients without clinically evident atherosclerosis who were not severely insulin resistant. Neither drug was superior to the other. We conclude that therapeutic intervention with either insulin sensitizer may reverse the atherosclerotic process in PCOS patients at its early stage.European Journal of Endocrinology 159 399-406

Background and Purpose-In our study we hypothesized that statins improve endothelial function in patients with lacunar infarctions (LI). Cerebral and systemic endothelial function was determined before and after 3-months treatment with atorvastatin. Methods-Cerebral endothelial function was determined by L-arginine reactivity and systemic endothelial function by flow-mediated dilatation (FMD) in patients with LI (18 patients, aged 61.1Ϯ7.6 years), 20 age-and gender-matched patients with similar risk factors (SR) and 19 age-and gender-matched healthy controls. The mean arterial velocity (v m ) in both middle cerebral arteries was measured by transcranial Doppler sonography before, during and after a 30-minute intravenous infusion of L-arginine. FMD of the brachial artery after hyperaemia was determined. The measurements were repeated after 3-months treatment with 40 mg of atorvastatin per day. Results-L-arginine reactivity was decreased in LI patients (13.1Ϯ8.4%) and in patients with SR compared with healthy controls (PՅ0.01). FMD was more impaired in patients with LI (0.06Ϯ4.9%) compared with patients with SR and healthy controls (PՅ0.01). After atorvastatin treatment, L-arginine reactivity and FMD improved in both patients with LI (17.1Ϯ7.6%; 7.0Ϯ5.7%) and patients with SR (PՅ0.01). Previously mildly increased cholesterol values normalized. Conclusion-The

Oral E(2), with or without NETA, produced no net activation of coagulation but improved fibrinolysis. Both modes of oral menopausal hormone therapy have a greater impact on markers of inflammation, coagulation, fibrinolysis, lipids, and lipoproteins than transdermal E(2). NETA attenuates some E(2) effects. Further studies are needed to elucidate the impact of these effects on clinical endpoints.

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SummaryThe impact of heart failure with preserved left ventricular ejection fraction (LVEF) on activated hemostasis is still unclear. We sought to compare the activation of hemostasis in patients with heart failure with preserved LVEF, with impaired LVEF, and in healthy controls. Biomarkers of coagulation and fibrinolysis (D-dimer, tPA and PAI-1) were determined in outpatients with chronic stable (NYHA I-III), optimally managed heart failure with preserved LVEF (n = 46) and with impaired LVEF (n = 52), and in healthy ageand gender-matched controls (n = 14). In comparison to healthy controls, patients with heart failure and preserved LVEF had increased median D-dimer levels (606 [330-1222] Moreover, in patients with impaired LVEF, but not in those with preserved LVEF, age and NT-proBNP emerged as independent predictors of log-transformed D-dimer levels. Heart failure with preserved LVEF is associated with a procoagulant state as determined by increased levels of D-dimer, tPA and PAI-1 antigens. D-dimer levels are significantly higher in patients with impaired LVEF, while tPA and PAI-1 levels are increased regardless of LVEF. (Int Heart J 2009; 50: 591-600)

Increased lipoprotein(a) (Lp(a)) levels are an independent predictor of coronary artery disease (CAD), degenerative aortic stenosis (DAS), and heart failure independent of CAD and DAS. Lp(a) levels are genetically determinated in an autosomal dominant mode, with great intra- and inter-ethnic diversity. Most variations in Lp(a) levels arise from genetic variations of the gene that encodes the apolipoprotein(a) component of Lp(a), the LPA gene. LPA is located on the long arm of chromosome 6, within region 6q2.6–2.7. Lp(a) levels increase cardiovascular risk through several unrelated mechanisms. Lp(a) quantitatively carries all of the atherogenic risk of low-density lipoprotein cholesterol, although it is even more prone to oxidation and penetration through endothelia to promote the production of foam cells. The thrombogenic properties of Lp(a) result from the homology between apolipoprotein(a) and plasminogen, which compete for the same binding sites on endothelial cells to inhibit fibrinolysis and promote intravascular thrombosis. LPA has up to 70% homology with the human plasminogen gene. Oxidized phospholipids promote differentiation of pro-inflammatory macrophages that secrete pro-inflammatory cytokines (e. g., interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α). The aim of this review is to define which of these mechanisms of Lp(a) is predominant in different groups of patients.

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We found that patients with LI have a diminished FMD, but a similar IMT, compared to patients with SR. Our results reveal that for a given level of atherosclerosis patients with LI have additional endothelial impairment.