Objective To evaluate the association between body mass index and mortality from overall cardiovascular disease and specific subtypes of cardiovascular disease in east and south Asians.Design Pooled analyses of 20 prospective cohorts in Asia, including data from 835 082 east Asians and 289 815 south Asians. Cohorts were identified through a systematic search of the literature in early 2008, followed by a survey that was sent to each cohort to assess data availability.

Lipodystrophies are a group of disorders characterized by absence or loss of adipose tissue and abnormal fat distribution, commonly accompanied by metabolic dysregulation. Although considered rare disorders, their prevalence in the general population is not well understood. We aimed to evaluate the clinical and genetic prevalence of lipodystrophy disorders in a large clinical care cohort. We interrogated the electronic health record (EHR) information of >1.3 million adults from the Geisinger Health System for lipodystrophy diagnostic codes. We estimate a clinical prevalence of disease of 1 in 20,000 individuals. We performed genetic analyses in individuals with available genomic data to identify variants associated with inherited lipodystrophies and examined their EHR for comorbidities associated with lipodystrophy. We identified 16 individuals carrying the p.R482Q pathogenic variant in LMNA associated with Dunnigan familial partial lipodystrophy. Four had a clinical diagnosis of lipodystrophy, whereas the remaining had no documented clinical diagnosis despite having accompanying metabolic abnormalities. We observed a lipodystrophy-associated variant carrier frequency of 1 in 3,082 individuals in our cohort with substantial burden of metabolic dysregulation. We estimate a genetic prevalence of disease of ∼1 in 7,000 in the general population. Partial lipodystrophy is an underdiagnosed condition. and its prevalence, as defined molecularly, is higher than previously reported. Genetically guided stratification of patients with common metabolic disorders, like diabetes and dyslipidemia, is an important step toward precision medicine.

A strong positive association has been observed between circulating anti-Müllerian hormone (AMH), a biomarker of ovarian reserve, and breast cancer risk in three prospective studies. Confirming this association is important because of the paucity of biomarkers of breast cancer risk in premenopausal women. We conducted a consortium study including ten prospective cohorts that had collected blood from premenopausal women. A nested case-control design was implemented within each cohort. A total of 2,835 invasive (80%) and in situ (20%) breast cancer cases were individually matched to controls (n = 3,122) on age at blood donation. AMH was measured using a high sensitivity enzyme-linked immunoabsorbent assay. Conditional logistic regression was applied to the aggregated dataset. There was a statistically significant trend of increasing breast cancer risk with increasing AMH concentration (p across quartiles <0.0001) after adjusting for breast cancer risk factors. The odds ratio (OR) for breast cancer in the top vs. bottom quartile of AMH was 1.60 (95% CI = 1.31-1.94). Though the test for interaction was not statistically significant (p = 0.15), the trend was statistically significant only for tumors positive for both estrogen receptor (ER) and progesterone receptor (PR): ER+/PR+: OR = 1.96, 95% CI = 1.46-2.64, p <0.0001; ER+/PR-: OR = 0.82, 95% CI = 0.40-1.68, p = 0.51; ER-/PR+: OR = 3.23, 95% CI = 0.48-21.9, p = 0.26; ER-/PR-: OR = 1.15, 95% CI = 0.63-2.09, p = 0.60. The association was observed for both pre- (OR = 1.35, 95% CI = 1.05-1.73) and post-menopausal (OR = 1.61, 95% CI = 1.03-2.53) breast cancer (p = 0.34). In this large consortium study, we confirmed that AMH is associated with breast cancer risk, with a 60% increase in risk for women in the top vs. bottom quartile of AMH.

Background Anthropometric measures such as waist-hip-ratio (WHR), waist-height-ratio (WHtR), waist circumference, Mid-upper arm circumference (MUAC), and upper thigh circumference, have been linked to the risk of cardiovascular disease (CVD). However, their relationships with subclinical atherosclerosis are unclear. Studies in normal-weight populations, especially in Asian countries where leanness is prevalent, are lacking. Methods We conducted a cross-sectional study to assess the associations of WHR, WHtR, waist circumference, hip circumference, body mass index (BMI), MUAC and upper thigh circumference with carotid intima-media thickness (cIMT) among 562 middle-aged participants free of CVD in rural Bangladesh. Results After adjusting for age and sex, WHR and waist circumference but not BMI showed a positive significant association with cIMT. In multivariate analysis, each standard deviation (SD) increase of WHR (0.08) or WHtR (0.07) was associated with an 8.96 μm (95% CI, 1.12–16.81) or 11.45 μm (95%CI, 0.86–22.04) difference in cIMT, respectively, after controlling for age, sex, BMI, smoking status, education level, and systolic blood pressure (SBP). The associations of WHR and WHtR with cIMT were independent of the influence of other anthropometric measures. The associations of other anthropometric measures and cIMT were not apparent. Conclusions In our relatively lean, healthy Asian population, WHR and WHtR appear to be better predictors of early atherosclerosis than other common surrogates of adiposity.

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Our results suggested that the disrupted arginine and proline metabolism associated with phthalate exposure might contribute to the development of overweight and obesity in school-age children, providing insights into the pathophysiological changes and molecular mechanisms involved in childhood obesity.

BackgroundModels that accurately predict risk of breast cancer are needed to help younger women make decisions about when to begin screening. Premenopausal concentrations of circulating anti-Müllerian hormone (AMH), a biomarker of ovarian reserve, and testosterone have been positively associated with breast cancer risk in prospective studies. We assessed whether adding AMH and/or testosterone to the Gail model improves its prediction performance for women aged 35–50.MethodsIn a nested case-control study including ten prospective cohorts (1762 invasive cases/1890 matched controls) with pre-diagnostic serum/plasma samples, we estimated relative risks (RR) for the biomarkers and Gail risk factors using conditional logistic regression and random-effects meta-analysis. Absolute risk models were developed using these RR estimates, attributable risk fractions calculated using the distributions of the risk factors in the cases from the consortium, and population-based incidence and mortality rates. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminatory accuracy of the models with and without biomarkers.ResultsThe AUC for invasive breast cancer including only the Gail risk factor variables was 55.3 (95% CI 53.4, 57.1). The AUC increased moderately with the addition of AMH (AUC 57.6, 95% CI 55.7, 59.5), testosterone (AUC 56.2, 95% CI 54.4, 58.1), or both (AUC 58.1, 95% CI 56.2, 59.9). The largest AUC improvement (4.0) was among women without a family history of breast cancer.ConclusionsAMH and testosterone moderately increase the discriminatory accuracy of the Gail model among women aged 35–50. We observed the largest AUC increase for women without a family history of breast cancer, the group that would benefit most from improved risk prediction because early screening is already recommended for women with a family history.Electronic supplementary materialThe online version of this article (10.1186/s13058-019-1126-z) contains supplementary material, which is available to authorized users.

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