Ezetimibe, cardiovascular risk and atherogenic dyslipidaemia

Ezetimibe is a selective cholesterol absorption inhibitor with an excellent side-effect profile, able to reduce low-density lipoprotein (LDL) cholesterol by 15-25% from baseline in monotherapy and on top of statins and fibrates. Yet, it seems that ezetimibe produces quantitative rather than qualitative changes in LDL, with small net effects on atherogenic dyslipidaemia. This is supported by findings from the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) study on atherosclerosis progression, where the addition of ezetimibe to simvastatin in patients with heterozygous familial hypercholesterolaemia did not affect the mean change in carotid intima-media thickness, although a significant reduction in LDL cholesterol levels was observed. The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study has further shown that combination treatment with simvastatin significantly reduced LDL cholesterol levels in patients with aortic stenosis, but did not affect the primary end point of aortic valve and cardiovascular events, although a significant reduction in the risk of ischaemic events was reported. Formal cardiovascular outcome trials are underway and these will provide additional insights into the long-term effects of ezetimibe on clinical events as well as on atherogenic dyslipidaemia, beyond LDL cholesterol levels

High prevalence of polycystic ovary syndrome in women with mild hirsutism and no other significant clinical symptoms

OBJECTIVE: To verify the conclusions of the Endocrine Society Guidelines that patients with mild hirsutism and no other important clinical signs (menstrual irregularities, infertility, central obesity, acanthosis nigricans, rapid progression of the hirsutism, clitoromegaly) should not be further studied. DESIGN: Retrospective study in patients referred because of mild hirsutism and no other clinical signs. SETTING: Department of Clinical Medicine of the University of Palermo. PATIENT(S): One hundred fifty-two patients with mild hirsutism. INTERVENTION(S): Measurement of serum testosterone, dehydroepiandrosterone sulfate, 17-OH-Progesterone, assessment of ovulation by measurement of progesterone in 21 to 24 days and ovarian ultrasound. RESULT(S): In 72 (47%) patients a diagnosis of polycyctic ovarian syndrome (PCOS) was performed. Polycyctic ovarian syndrome patients included 56 patients with the mild ovulatory form (OV-PCOS) but also 16 patients with the anovulatory form (classic PCOS). Three (2%) patients had nonclassic adrenal hyperplasia. CONCLUSION(S): Because of the high prevalence of PCOS and the possibility of finding nonclassic 21-hydroxylase deficiency, patients with mild hirsutism need a diagnostic evaluation that should include 17-hydroxyprogesterone measurement plus assessment of ovulation and ovarian ultrasound

Influence of sociocultural factors on the ovulatory status of polycystic ovary syndrome.

OBJECTIVE: To evaluate the role of social and cultural differences inside the same ethnic group on the ovulatory status of women with polycystic ovary syndrome (PCOS). DESIGN: To correlate social and cultural status with the phenotypic expression (body weight and ovulation) and with androgen and insulin levels of PCOS. SETTING: University department of medicine. PATIENT(S): Two hundred and forty-four consecutive PCOS women. INTERVENTION(S): All studied patients completed a simple questionnaire to indicate their mean family income and their school education. MAIN OUTCOME MEASURE(S): Ovulation was assessed by measurement of serum progesterone on day 22 of a spontaneous or induced menstrual cycle. Levels of blood testosterone, sex hormone-binding globulin, insulin, and blood glucose were evaluated. RESULT(S): In the low to medium income group, 21% of patients had ovulatory PCOS, but the prevalence of the same PCOS phenotype was 43% in patients with high income. In patients with low education, only 12% presented with ovulatory PCOS compared with 47% of the patients with high education status. Mean family income negatively correlated with body mass index, waist circumference, insulin, and insulin resistance. Serum progesterone correlated negatively with insulin and insulin resistance. CONCLUSION(S): In an ethnically homogeneous PCOS population, high socioeconomic status was associated with a higher prevalence of the ovulatory phenotype. Differences in ovulatory status between the social classes seem to be related to differences in insulin levels and fat quantity and distribution

Circulating levels of adipose products and differences in fat distribution in the ovulatory and anovulatory phenotypes of polycystic ovary syndrome.

Central fat distribution is increased in anovulatory women with polycystic ovary syndrome (PCOS) compared with ovulatory PCOS and matched controls. Among secreted adipocytokines, this is reflected mainly in lower levels of adiponectin

Prevalence and predictors of left ventricular hypertrophy in patients with hypertension and normal electrocardiogram

Background: Electrocardiography (ECG) has low sensitivity for detecting left ventricular hypertrophy (LVH), while echocardiography cannot be routinely performed. Design/methods: In this study we evaluate the prevalence of LVH and diastolic dysfunction in hypertensive patients with normal ECG. We excluded patients with cardiovascular (CV) diseases, diabetes, chronic kidney disease, or presenting ECG-LVH or other ECG anomalies. The enrolled 440 hypertensive patients underwent echocardiographic examination (Acuson Sequoia 512); LV mass was indexed by body surface area (LVMI) and LVH was defined as LVMI >125 g/m2 in men and >110 g/m2 in women. Diastolic function was evaluated by mitral inflow and tissue Doppler imaging (TDI). Results: The prevalence of LVH was 8.18% (95% confidence interval [CI] 5.97–11.1%). Multiple regression analysis showed that the only variable independently associated with LVH was duration of hypertension (p<0.001). The receiver operating characteristic (ROC) curve showed that duration of hypertension was a powerful predictor of LVH, with an area under the curve (AUC) of 0.878 and p<0.0001. Further, in patients with LVH the mean difference of LVMI from the cut-off value for LVH was 12.3 9.19 g/m2. Diastolic dysfunction, defined as early diastolic myocardial velocity (Em) <0.08 m/s, was detected only in 3.2% of patients. Conclusions: The prevalence of LVH among hypertensive patients with normal ECG, free of diabetes and of CV diseases is low; moreover, patients with echocardiographic LVH presented LVMI values that identified mild LVH. Few cases of impaired diastolic function were registered. We suggest that in hypertensive patients with such characteristics the echocardiographic examination should be reserved to those who present with higher duration of hypertension

Activin A circulating levels in patients with bone metastasis from breast or prostate cancer

Recent studies have highlighted that Activin A, a member of the transforming growth factor-beta (TGF-beta) superfamily, may be involved in the regulation of osteoblastic activity and in osteoclast differentiation. Therefore, we have investigated the clinical significance of its circulating levels in patients with bone metastasis. Activin A serum concentrations were determined, by a commercially available enzyme-linked immunosorbent assay kit, in 72 patients with breast cancer (BC) or prostatic cancer (PC) with (BM+) or without (BM-) bone metastases, in 15 female patients with age-related osteoporosis (OP), in 20 patients with benign prostatic hypertrophy (BPH) and in 48 registered healthy blood donors (HS) of both sex (25 female and 23 male). Activin A serum concentrations were significantly increased in BC or PC patients as compared to OP (P < 0.0001) or BPH (P = 0.045), respectively, or to sex matched HS (P < 0.0001). Additionally, these levels resulted more elevated in PC patients as compared to BC patients (P = 0.032). Interestingly, Activin A was significantly higher in BM+ patients than in BM- patients (BC, P = 0.047; PC, P = 0.016). In BC patients, a significant correlation was observed only between Activin A and number of bone metastases (P = 0.0065) while, in PC patients, Activin A levels were strongly correlated with the Gleason score (P = 0.011) or PSA levels (P = 0.0001) and, to a lessen extent, with the number of bone metastases (P = 0.056). Receiver operating characteristic curve (ROC) analysis showed a fair diagnostic accuracy of Activin A to discriminate between BM+ and BM- patients (BC: AUC = 0.71 +/- 0.09, P = 0.03; PC: AUC = 0.73 +/- 0.081, P = 0.005). These findings indicate that Activin A may be implicated in the pathogenesis of bone metastasis. Therefore, this cytokine may be considered a novel potential target for a more selective therapeutic approach in the treatment of skeletal metastasis and may be also useful as additional biochemical marker of metastatic bone disease