Prospective associations of circulating thrombospondin-2 level with heart failure hospitalization, left ventricular remodeling and diastolic function in type 2 diabetes.

BACKGROUND: Circulating thrombospondin-2 (TSP2) levels were associated with the development of heart failure (HF) in recent studies. However, these studies included only a minority of patients with type 2 diabetes, which is associated with an increased HF risk. As hyperglycemia induces TSP2 expression and its tissue expression increases in type 2 diabetes, we investigated the prospective association of circulating TSP2 with incident HF hospitalization (HHF), and its associations with longitudinal changes of echocardiographic parameters in type 2 diabetes. METHODS: Baseline serum TSP2 levels were measured in 4949 patients with type 2 diabetes to determine its association with incident HHF using multivariable Cox regression analysis. In the echocardiographic study, baseline serum TSP2 levels were measured in another 146 patients with type 2 diabetes but without cardiovascular diseases who underwent detailed transthoracic echocardiography at baseline and after 1 year. RESULTS: Over a median follow-up of 7.8 years, 330 of 4949 patients (6.7%) developed incident HHF. Baseline serum TSP2 levels were independently associated with the development of HHF (HR 1.31, 95%CI 1.06-1.62, p = 0.014) after adjustments for baseline conventional cardiovascular risk factors, atrial fibrillation, estimated glomerular filtration rate, albuminuria and high-sensitivity C-reactive protein level, use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, loop-diuretics, aspirin, insulin, metformin and sodium-glucose co-transporter 2 inhibitors. Moreover, baseline serum TSP2 levels were independently associated with increase in average E/e' and left atrial volume index (p = 0.04 and < 0.01, respectively). CONCLUSION: Serum TSP2 levels were independently associated with both incident HHF and deterioration in diastolic function in type 2 diabetes. TRIAL REGISTRATION: Not Applicable.

Age-specific reference ranges of serum anti-müllerian hormone in healthy women and its application in diagnosis of polycystic ovary syndrome: a population study.

OBJECTIVE: To establish the age-specific centiles of serum anti-müllerian hormone (AMH) levels in Chinese women, and to explore the use of multiples of median (MoM) AMH levels for the diagnosis of polycystic ovary syndrome (PCOS). DESIGN: An observational study. SETTING: University-affiliated hospitals and community clinics. POPULATION: We included 3137 healthy women aged 20-44 years recruited prospectively or who had archived serum samples from previous research projects. Another validation cohort of 751 women with PCOS as well as ovulatory controls, which was a convenient sample of women attending for infertility or menstrual disorders, was also studied. METHODS: The serum samples were assayed for AMH by the automated Access AMH assay. MAIN OUTCOME MEASURES: Age-specific reference ranges were constructed on the primary cohort with the Lambda-Mu-Sigma method. The MoM AMH of each subject in the validation cohort was calculated. RESULTS: Centile curves of serum AMH level against age were established. MoM AMH was significantly higher in women with PCOS than in controls (P < 0.05). The area under the ROC curve was 0.852 (95% confidence interval [CI] 0.825-0.877) (P < 0.0001) for discriminating women with PCOS from ovulatory controls by MoM AMH. CONCLUSIONS: We established a set of year-by-year age-specific reference ranges of serum AMH levels in Chinese women. The MoM AMH derived from this set of reference ranges is a promising tool to replace antral follicle count in the diagnosis of PCOS. TWEETABLE ABSTRACT: A set of age-specific reference ranges of AMH levels was established in Chinese women. Multiples of median AMH may be used to diagnose PCOS.