Cardiometabolic risk factors among HIV patients on antiretroviral therapy

Abstract: Background: HIV and combination antiretroviral therapy (cART) may increase cardiovascular disease (CVD) risk. We assessed the early effects of cART on CVD risk markers in a population with presumed low CVD risk. Methods: Adult patients (n=118) in Lusaka, Zambia were recruited at the time of initiation of cART for HIV/AIDS. Cardiometabolic risk factors were measured before and 90 days after starting cART. Participants were grouped according to cART regimens: Zidovudine + Lamivudine + Nevirapine (n=58); Stavudine + Lamivudine + Nevirapine (n=43); and ‘other’ (Zidovudine + Lamivudine + Efavirenz, Stavudine + Lamivudine + Efavirenz, Tenofovir + Emtricitabine + Efavirenz or Tenofovir + Emtricitabine + Nevirapine, n=17). ANOVA was used to test whether changes in cardiometabolic risk markers varied by cART regimen. Results: From baseline to 90 days after initiation of cART, the prevalence of low levels of high-density lipoprotein cholesterol (<1.04 mmol/L for men and <1.30 mmol/L for women) significantly decreased (78.8% vs. 34.8%, P<0.001) while elevated total cholesterol (TC ≥5.18 mmol/L, 5.1% vs. 11.9%, P=0.03) and the homeostasis model assessment of insulin resistance ≥3.0 (1.7% vs. 17.0%, P<0.001) significantly increased. The prevalence of TC:HDL-c ratio ≥5.0 significantly decreased (44.9% vs. 6.8%, P<0.001). These changes in cardiometabolic risk markers were independent of the cART regimen. Conclusion: Our results suggest that short-term cART is associated with a cardioprotective lipid profile in Zambia and a tendency towards insulin resistance regardless of the cART regimen

Erratum to: A multi-stage genome-wide association study of uterine fibroids in African Americans

The article "A multi-stage genome-wide association study of uterine fibroids in African Americans", written by Jacklyn N. Hellwege, was originally published Online First without open access. After publication in volume 136, issue 10, page 1363-1373 the author decided to opt for Open Choice and to make the article an open access publication. Therefore, the copyright of the article has been changed t

Rare coding variants and X-linked loci associated with age at menarche.

More than 100 loci have been identified for age at menarche by genome-wide association studies; however, collectively these explain only ∼3% of the trait variance. Here we test two overlooked sources of variation in 192,974 European ancestry women: low-frequency protein-coding variants and X-chromosome variants. Five missense/nonsense variants (in ALMS1/LAMB2/TNRC6A/TACR3/PRKAG1) are associated with age at menarche (minor allele frequencies 0.08-4.6%; effect sizes 0.08-1.25 years per allele; P<5 × 10(-8)). In addition, we identify common X-chromosome loci at IGSF1 (rs762080, P=9.4 × 10(-13)) and FAAH2 (rs5914101, P=4.9 × 10(-10)). Highlighted genes implicate cellular energy homeostasis, post-transcriptional gene silencing and fatty-acid amide signalling. A frequently reported mutation in TACR3 for idiopathic hypogonatrophic hypogonadism (p.W275X) is associated with 1.25-year-later menarche (P=2.8 × 10(-11)), illustrating the utility of population studies to estimate the penetrance of reportedly pathogenic mutations. Collectively, these novel variants explain ∼0.5% variance, indicating that these overlooked sources of variation do not substantially explain the 'missing heritability' of this complex trait.UK sponsors (see article for overseas ones): This work made use of data and samples generated by the 1958 Birth Cohort (NCDS). Access to these resources was enabled via the 58READIE Project funded by Wellcome Trust and Medical Research Council (grant numbers WT095219MA and G1001799). A full list of the financial, institutional and personal contributions to the development of the 1958 Birth Cohort Biomedical resource is available at http://www2.le.ac.uk/projects/birthcohort. Genotyping was undertaken as part of the Wellcome Trust Case-Control Consortium (WTCCC) under Wellcome Trust award 076113, and a full list of the investigators who contributed to the generation of the data is available at www.wtccc.org.uk ... The Fenland Study is funded by the Wellcome Trust and the Medical Research Council, as well as by the Support for Science Funding programme and CamStrad. ... SIBS - CRUK ref: C1287/A8459 SEARCH - CRUK ref: A490/A10124 EMBRACE is supported by Cancer Research UK Grants C1287/A10118, C1287/A16563 and C1287/A17523. Genotyping was supported by Cancer Research - UK grant C12292/A11174D and C8197/A16565. Gareth Evans and Fiona Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester. The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles and Elizabeth Bancroft are supported by Cancer Research UK Grant C5047/A8385. ... Generation Scotland - Scottish Executive Health Department, Chief Scientist Office, grant number CZD/16/6. Exome array genotyping for GS:SFHS was funded by the Medical Research Council UK. 23andMe - This work was supported in part by NIH Award 2R44HG006981-02 from the National Human Genome Research Institute.This is the final version of the article. It first appeared from NPG via http://dx.doi.org/10.1038/ncomms875

Prepregnancy Lipids Related to Preterm Birth Risk: The Coronary Artery Risk Development in Young Adults Study

Context: Preterm birth is associated with maternal cardiovascular risk, but mechanisms are unknown

Do women residents delay childbearing due to perceived career threats

PURPOSE: To assess gender differences among residents regarding their plans to have children during residency and determine the most influential reasons for these differences. METHOD: Using the Health Belief Model as a framework, the authors created an instrument to survey 424 residents from 11 residency programs at three academic medical institutions about their intentions to have children during residency. The authors developed a scale to assess the perceived career threats of having children during residency, evaluated its psychometric properties, and calculated the effect of the mediators. RESULTS: The response rate was 77% (328/424). Forty-one percent of men versus 27% of women planned to have children during residency (P = .01). The instrument measured four career threats-extended training, loss of fellowship positions, pregnancy complications, and interference with career plans-on a five-point Likert scale. The scale had a Cronbach alpha of 0.84 and an eigenvalue of 2.2. Compared with men, women had higher scores for each item and a higher mean score (2.9 versus 2.1, P = .001), signifying greater belief in the potential of pregnancy to threaten careers. After adjusting for age, institution, postgraduate year, and knowledge of parental leave policies, women were less likely to plan to have children during residency (odds ratio 0.46 [95% confidence interval 0.25-0.84]). In mediation analysis, threats to career explained 67% of the gender variance. CONCLUSIONS: Women residents intentionally postpone pregnancy because of perceived threats to their careers. Medical educators should be aware of these findings when counseling female trainees

Women's Reproductive Milestones and Cardiovascular Disease Risk: A Review of Reports and Opportunities From the CARDIA Study

In 1985 to 1986, the CARDIA (Coronary Artery Risk Development in Young Adults) study enrolled 5115 Black or White participants, including 2788 women, aged 18 to 30 years. Over the following 35 years, the CARDIA study amassed extensive longitudinal data on women's reproductive milestones, spanning menarche to menopause. Although not initially conceived as a study of women's health, >75 CARDIA study publications address relationships between reproductive factors and events with cardiovascular and metabolic risk factors, subclinical and clinical cardiovascular disease, and social determinants of health. The CARDIA study was one of the earliest population‐based reports to note Black‐White differences in age at menarche and associations with cardiovascular risk factors. Adverse pregnancy outcomes, particularly gestational diabetes and preterm birth, have been assessed along with postpartum behaviors, such as lactation. Existing studies have examined risk factors for adverse pregnancy outcomes and lactation, as well as their relationship to future cardiovascular and metabolic risk factors, diagnoses, and subclinical atherosclerosis. Ancillary studies examining components of polycystic ovary syndrome and ovarian biomarkers, such as anti‐Müllerian hormone, have facilitated examination of reproductive health in a population‐based cohort of young adult women. As the cohort transitioned through menopause, examination of the importance of premenopausal cardiovascular risk factors along with menopause has improved our understanding of shared mechanisms. The cohort is now aged in the 50s to mid‐60s, and women will begin to experience a greater number of cardiovascular events as well as other conditions, such as cognitive impairment. Thus, in the next decade, the CARDIA study will provide a unique resource for understanding how the women's reproductive life course epidemiology informs cardiovascular risk, as well as reproductive and chronological aging