A risk analysis of alpelisib-induced hyperglycemia in patients with advanced solid tumors and breast cancer.

BACKGROUND: Hyperglycemia is an on-target effect of PI3Kα inhibitors. Early identification and intervention of treatment-induced hyperglycemia is important for improving management of patients receiving a PI3Kα inhibitor like alpelisib. Here, we characterize incidence of grade 3/4 alpelisib-related hyperglycemia, along with time to event, management, and outcomes using a machine learning model. METHODS: Data for the risk model were pooled from patients receiving alpelisib ± fulvestrant in the open-label, phase 1 X2101 trial and the randomized, double-blind, phase 3 SOLAR-1 trial. The pooled population (n = 505) included patients with advanced solid tumors (X2101, n = 221) or HR+/HER2- advanced breast cancer (SOLAR-1, n = 284). External validation was performed using BYLieve trial patient data (n = 340). Hyperglycemia incidence and management were analyzed for SOLAR-1. RESULTS: A random forest model identified 5 baseline characteristics most associated with risk of developing grade 3/4 hyperglycemia (fasting plasma glucose, body mass index, HbA1c, monocytes, age). This model was used to derive a score to classify patients as high or low risk for developing grade 3/4 hyperglycemia. Applying the model to patients treated with alpelisib and fulvestrant in SOLAR-1 showed higher incidence of hyperglycemia (all grade and grade 3/4), increased use of antihyperglycemic medications, and more discontinuations due to hyperglycemia (16.7% vs. 2.6% of discontinuations) in the high- versus low-risk group. Among patients in SOLAR-1 (alpelisib + fulvestrant arm) with PIK3CA mutations, median progression-free survival was similar between the high- and low-risk groups (11.0 vs. 10.9 months). For external validation, the model was applied to the BYLieve trial, for which successful classification into high- and low-risk groups with shorter time to grade 3/4 hyperglycemia in the high-risk group was observed. CONCLUSIONS: A risk model using 5 clinically relevant baseline characteristics was able to identify patients at higher or lower probability for developing alpelisib-induced hyperglycemia. Early identification of patients who may be at higher risk for hyperglycemia may improve management (including monitoring and early intervention) and potentially lead to improved outcomes. REGISTRATION: ClinicalTrials.gov: NCT01219699 (registration date: October 13, 2010; retrospectively registered), ClinicalTrials.gov: NCT02437318 (registration date: May 7, 2015); ClinicalTrials.gov: NCT03056755 (registration date: February 17, 2017).

Factors associated with self-report of polycystic ovary syndrome in the Coronary Artery Risk Development in Young Adults study (CARDIA).

BACKGROUND: Polycystic ovary syndrome (PCOS) is underdiagnosed, but factors associated with women's report of diagnosis are not well-understood, particularly social determinants of health. Therefore, in a population-based cohort, we compared the characteristics of women with self-reported PCOS vs. women who have unrecognized PCOS vs. women without PCOS. METHODS: We performed a secondary data analysis of the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a population-based, prospective cohort of Black and White women. Participants were women (n = 2028) who responded to the question, "Did a doctor or nurse ever tell you that you had polycystic ovarian syndrome or polycystic ovarian disease?" at the year 15 examination. Women who answered "yes" were defined as having self-reported PCOS. Women who answered "no or not sure" were defined as having unrecognized PCOS if they also had irregular menses and hyperandrogenemia between 20 and 30 years of age. Exposures of interest included social determinants of health, symptoms including irregular menses and hirsutism, and comorbid conditions. RESULTS: Forty-three (2.1%) of women had self-reported PCOS, 135 (6.7%) had unrecognized PCOS, and 1850 (91%) women were without PCOS. In logistic regression models adjusting for age, race, and center, women with self-reported PCOS were more likely to have obesity (OR 1.83, 95% CI 1.22, 2.75) and diabetes (OR 2.37, 95% CI 1.05, 5.33) compared to women without PCOS. Women with unrecognized PCOS were more likely to have hypertension (OR 1.68, 95% CI 1.03, 2.74) and food insecurity (OR 1.94, 95% CI 1.25, 3.01) compared to women without PCOS. CONCLUSIONS: Unrecognized PCOS is common. Self-report of PCOS is not associated with access to healthcare. Women who report PCOS are more often obese and comorbidities may contribute to recognition of PCOS.

The prospective association of hyperandrogenism, oligomenorrhea and polycystic ovary syndrome with incident gestational diabetes: The coronary artery risk development in young adults women's study.

In this 28-year prospective study of 455 women (mean age: 26 years), polycystic ovary syndrome (PCOS) was associated with a 2.6-fold elevated risk of gestational diabetes (GDM). However, hyperandrogenism or oligomenorrhea in the absence of PCOS was not associated with GDM.

Antimüllerian hormone and leukocyte aging markers in the Coronary Artery Risk Development in Young Adults study.

OBJECTIVE: To examine whether premenopausal reproductive age, as indicated by serum antimüllerian hormone (AMH), is associated with leukocyte aging biomarkers. DESIGN: Prospective cohort analysis. SETTING: The Coronary Artery Risk Development in Young Adults study, a population-based study of Black and White adults from four US communities (Birmingham, AL; Chicago, IL; Minneapolis, MN; Oakland, CA). PATIENT(S): Premenopausal women with serum AMH measures at examination year 15 as well as leukocyte aging markers. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Telomere length, mitochondrial deoxyribonucleic acid (mtDNA) copy number, and intrinsic and extrinsic epigenetic age acceleration (EAA) at examination years 15, 20, and 25 as well as change between examination years. RESULT(S): Women were 40.2 (standard deviation, 3.7) years of age at examination year 15 when the AMH and initial measures of telomere length and mtDNA copy number (n = 386) were obtained and EAA occurred. After adjustment for chronological age, race, and smoking history, AMH quartile at examination year 15 was not associated with telomere length at examination years 15 and 25 or telomere length change between these years, mtDNA copy number at examination years 15 and 25 or change between these years, or intrinsic EAA at examination years 15 and 20 or change between these years. Women in the second AMH quartile had faster extrinsic EAA than women in the lowest AMH quartile (ß-coefficient, 1.84; 95% confidence interval, 0.20-3.49). CONCLUSION(S): In a population-based cohort, AMH did not have associations with leukocyte telomere length, mtDNA copy number, or intrinsic EAA.

Antimüllerian hormone and F2-isoprostanes in the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

OBJECTIVE: To examine whether F2-isoprostanes, a marker of systematic oxidative stress, are associated with antimüllerian hormone (AMH), an indicator of ovarian reserve, in a population-based cohort of women of black and white ethnicities. DESIGN: Cross-sectional analysis. SETTING: Not applicable. PATIENTS: The CARDIA Women's Study, a population-based cohort. Black (n = 398) and white (n = 432) late reproductive-aged women (mean age 40 ± 3.6 years) without histories of gynecologic surgery. MAIN OUTCOME MEASURES: Log-transformed serum AMH concentrations. RESULTS: Linear regression models evaluated whether plasma F2-isoprostanes were associated with log-transformed AMH after adjustment for age, race, smoking, body mass index, and oral contraceptive pill use. Higher levels of F2-isoprostanes were associated with lower AMH levels (ß -0.048 per standard deviation, 95% confidence interval -0.087, -0.01). The observed associations were stronger at younger ages (P=.04 for interaction between levels of age and F2-isoprostanes). Indicators of other steps in the oxidative stress pathway (superoxide dismutase, paraoxonase activity, oxidized low-density lipoprotein cholesterol, and carotenoids) were not associated with AMH, although lower phospholipase A2 activity (ß 0.036 per standard deviation, 95% confidence interval 0.001, 0.071) was associated with lower AMH across all ages. CONCLUSION: In a population-based cohort, higher levels of F2-isoprostanes were associated with lower ovarian reserve, particularly at younger ages.

Association of smoking with abdominal adipose deposition and muscle composition in Coronary Artery Risk Development in Young Adults (CARDIA) participants at mid-life: A population-based cohort study.

BACKGROUND: Smokers have lower risk of obesity, which some consider a "beneficial" side effect of smoking. However, some studies suggest that smoking is simultaneously associated with higher central adiposity and, more specifically, ectopic adipose deposition. Little is known about the association of smoking with intermuscular adipose tissue (IMAT), an ectopic adipose depot associated with cardiovascular disease (CVD) risk and a key determinant of muscle quality and function. We tested the hypothesis that smokers have higher abdominal IMAT and lower lean muscle quality than never smokers. METHODS AND FINDINGS: We measured abdominal muscle total, lean, and adipose volumes (in cubic centimeters) and attenuation (in Hounsfield units [HU]) along with subcutaneous (SAT) and visceral adipose tissue (VAT) volumes using computed tomography (CT) in 3,020 middle-aged Coronary Artery Risk Development in Young Adults (CARDIA) participants (age 42-58, 56.3% women, 52.6% white race) at the year 25 (Y25) visit. The longitudinal CARDIA study was initiated in 1985 with the recruitment of young adult participants (aged 18-30 years) equally balanced by female and male sex and black and white race at 4 field centers located in Birmingham, AL, Chicago, IL, Minneapolis, MN, and Oakland, CA. Multivariable linear models included potential confounders such as physical activity and dietary habits along with traditional CVD risk factors. Current smokers had lower BMI than never smokers. Nevertheless, in the fully adjusted multivariable model with potential confounders, including BMI and CVD risk factors, adjusted mean (95% CI) IMAT volume was 2.66 (2.55-2.76) cm3 in current smokers (n = 524), 2.36 (2.29-2.43) cm3 in former smokers (n = 944), and 2.23 (2.18-2.29) cm3 in never smokers (n = 1,552) (p = 0.007 for comparison of former versus never smoker, and p < 0.001 for comparison of current smoker versus never and former smoker). Moreover, compared to participants who never smoked throughout life (41.6 [41.3-41.9] HU), current smokers (40.4 [39.9-40.9] HU) and former smokers (40.8 [40.5-41.2] HU) had lower lean muscle attenuation suggesting lower muscle quality in the fully adjusted model (p < 0.001 for comparison of never smokers with either of the other two strata). Among participants who had ever smoked, pack-years of smoking exposure were directly associated with IMAT volume (ß [95% CI]: 0.017 [0.010-0.025]) (p < 0.001). Despite having less SAT, current smokers also had higher VAT/SAT ratio than never smokers. These findings must be viewed with caution as residual confounding and/or reverse causation may contribute to these associations. CONCLUSIONS: We found that, compared to those who never smoked, current and former smokers had abdominal muscle composition that was higher in adipose tissue volume, a finding consistent with higher CVD risk and age-related physical deconditioning. These findings challenge the belief that smoking-associated weight loss or maintenance confers a health benefit.

Depression Over the Lifespan in a Population-Based Cohort of Women With Polycystic Ovary Syndrome: Longitudinal Analysis.

OBJECTIVE: To (i) determine whether women with polycystic ovary syndrome (PCOS) from a population-based cohort experience elevated depression symptoms and (ii) characterize the trajectory of symptoms over the lifespan. DESIGN: The association between PCOS and longitudinal depression scores was investigated among 1127 black and white women participating in Coronary Artery Risk Development in Young Adults study. PCOS was ascertained at baseline (ages 20 to 32) by U.S. National Institutes of Health (NIH) criteria, incorporating androgens and symptoms of oligomenorrhea and hirsutism. The Center for Epidemiologic Studies-Depression (CES-D) scale was repeated prospectively in 5-year intervals over 25 years. Mixed-effects models evaluated the association between depression scores and PCOS after adjustment for confounders and characterized the trajectory of scores. The impact of race was explored. RESULTS: Eighty-three of 1127 (7.4%) participants met NIH PCOS criteria. Of these, 33 (40%) were black and 50 (60%) were white. CES-D scores were higher among women with PCOS [coefficient (coef) 2.51; 95% CI 1.49, 3.54; P < 0.01] across the lifespan. Scores decreased across the lifespan in women with and without PCOS (coef -0.1 point per year; P < 0.001). Black women experienced higher depression burden than white women (coef 1.80; 95% CI 1.20, 2.41; P < 0.001); however, an interaction was not detected between PCOS and race (P = 0.68). CONCLUSIONS: Women with PCOS-NIH from a population-based cohort are at risk for higher depression scores across the lifespan. Depression scores decline over time in women with PCOS in a trajectory similar to that in women without PCOS. Racial differences in depression risk should be acknowledged clinically and further explored.

Uterine Fibroids and the Risk of Cardiovascular Disease in the Coronary Artery Risk Development in Young Adult Women's Study.

BACKGROUND: Uterine fibroids, the most common reproductive tract tumor in women, have been associated with hypertension and atherosclerotic cardiovascular disease (CVD). Prior studies of fibroids and CVD have examined the subset of women with symptomatic fibroids who undergo hysterectomy, itself a risk factor for CVD. We aimed to study the risk of subclinical CVD, as determined by coronary artery calcification (CAC), carotid intima media thickness (CIMT), and left ventricular (LV) mass, in women with ultrasound-diagnosed uterine fibroids. MATERIALS AND METHODS: Participants were 972 women from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a cohort recruited in 1985-1986. CARDIA screened black and white women aged 35-49 years by ultrasound for fibroids at 16 years of follow-up (2002-2004). Demographics and CVD risk factors were collected in 2000-2001 at 15 years of follow-up (baseline for this analysis). Women were tested at years 15, 20, and 25 for CAC, at year 20 for CIMT, and at year 25 for echocardiographic LV mass. Multivariable logistic regression was used to estimate the odds of CAC, CIMT, and LV mass. RESULTS: Fifty-two percent of women had fibroids (61.7% in black, 38.3% in white women). Most CVD risk factors were more common in women with fibroids. Adjusted odds of subclinical CVD, such as elevated CIMT and elevated LV mass, were not different for women with fibroids compared with those without (CIMT odds ratio [OR] = 1.03; confidence interval [95% CI] 0.7-1.5 and LV mass OR = 1.14; 95% CI 0.77-1.68), when adjusted for confounders. CONCLUSIONS: Although women with fibroids had more CVD risk factors, presence of fibroids was not associated with subclinical CVD.

Transethnic and race-stratified genome-wide association study of fibroid characteristics in African American and European American women.

OBJECTIVE: To identify, through genome-wide association studies, genetic loci that associate with differences in fibroid size and number in a population of African American and European American women. DESIGN: Cross-sectional study. SETTING: Not applicable. PATIENT(S): Using BioVU, a clinical population from the Vanderbilt University Medical Center, and the Coronary Artery Risk Development in Young Adults cohort, a prospective cohort, we identified 1520 women (609 African American and 911 European American) with documented fibroid characteristics. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Outcome measurements include volume of largest fibroid, largest fibroid dimension, and number of fibroids (single vs. multiple). RESULT(S): In race-stratified analyses we achieved genome-wide significance at a variant located between MAT2B and TENM2 (rs57542984, ß = 0.13; 95% confidence interval 0.09, 0.17) for analyses of largest fibroid dimension in African Americans. The strongest signal for transethnic analyses was at a variant on 1q31.1 located between PLA2G4A and BRINP3 (rs6605005, ß = 0.24; 95% confidence interval 0.15, 0.33) for fibroid volume. Results from MetaXcan identified an association between predicted expression of the gene ER degradation enhancing alpha-mannosidase like protein 2 (EDEM2) in the thyroid and number of fibroids (Z score = -4.51). CONCLUSION(S): This study identified many novel associations between genetic loci and fibroid size and number in both race-stratified and transethnic analyses. Future studies are necessary to further validate our study findings and to better understand the mechanisms underlying these associations.

Admixture mapping of uterine fibroid size and number in African American women.

OBJECTIVE: To evaluate the relationship between genetic ancestry and uterine fibroid characteristics. DESIGN: Cross-sectional study. SETTING: Not applicable. PATIENT(S): A total of 609 African American participants with image- or surgery-confirmed fibroids in a biorepository at Vanderbilt University electronic health record biorepository and the Coronary Artery Risk Development in Young Adults studies were included. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Outcome measures include fibroid number (single vs. multiple), volume of largest fibroid, and largest fibroid dimension of all fibroid measurements. RESULT(S): Global ancestry meta-analyses revealed a significant inverse association between percentage of European ancestry and risk of multiple fibroids (odds ratio: 0.78; 95% confidence interval 0.66, 0.93; P=6.05 × 10-3). Local ancestry meta-analyses revealed five suggestive (P<4.80 × 10-3) admixture mapping peaks in 2q14.3-2q21.1, 3p14.2-3p14.1, 7q32.2-7q33, 10q21.1, 14q24.2-14q24.3, for number of fibroids and one suggestive admixture mapping peak (P<1.97 × 10-3) in 10q24.1-10q24.32 for volume of largest fibroid. Single variant association meta-analyses of the strongest associated region from admixture mapping of fibroid number (10q21.1) revealed a strong association at single nucleotide polymorphism variant rs12219990 (odds ratio: 0.41; 95% confidence interval 0.28, 0.60; P=3.82 × 10-6) that was significant after correction for multiple testing. CONCLUSION(S): Increasing African ancestry is associated with multiple fibroids but not with fibroid size. Local ancestry analyses identified several novel genomic regions not previously associated with fibroid number and increasing volume. Future studies are needed to explore the genetic impact that ancestry plays into the development of fibroid characteristics.

The association of surgical versus natural menopause with future left ventricular structure and function: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

OBJECTIVE: To evaluate the association between surgical menopause (SM) versus natural menopause (NM) in relation to later left ventricular (LV) structure and function, while taking into account the LV parameters and other cardiovascular disease risk factor (CVDRF) levels that predate the menopausal transition. METHODS: We studied 825 premenopausal women from the Coronary Artery Risk Development in Young Adults study in 1990 to 1991 (baseline, mean age 32 years) who later reached menopause by 2010 to 2011 and had echocardiograms at these two time points. RESULTS: During 20 years of follow-up, 508 women reached NM, whereas 317 underwent SM (34% had bilateral oophorectomy). At baseline, women who later underwent SM were more likely to be black, younger, have greater parity, and higher mean values of systolic blood pressure, body mass index, and also lower mean high-density lipoprotein cholesterol and physical activity than women who reached NM. No significant differences in LV structure/function were found between groups. In 2010 to 2011, SM women had significantly higher LV mass, LV mass/volume ratio, E/e' ratio, and impaired longitudinal and circumferential strain than NM women. SM women with bilateral oophorectomy had adverse LV measures than women with hysterectomy with ovarian conservation. Controlling for baseline echocardiographic parameters and CVDRF in linear regression models eliminated these differences between groups. Further adjustment for age at menopause/surgery and hormone therapy use did not change these results. CONCLUSION: In this study, the adverse LV structure and function observed among women with SM compared with NM were explained by their unfavorable presurgical CVDRF profiles, suggesting that premenopausal CVDRF rather than gynecologic surgery predispose SM women to elevated future cardiovascular disease risk.

Prospective association of polycystic ovary syndrome with coronary artery calcification and carotid-intima-media thickness: the Coronary Artery Risk Development in Young Adults Women's study.

OBJECTIVE: To study the independent associations of polycystic ovary syndrome (PCOS), and its 2 components, hyperandrogenism and anovulation, with coronary artery calcification (CAC) and carotid artery intima-media thickness (IMT). APPROACH AND RESULTS: At the year 20 of the Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based multicenter cohort of young adults, women (mean age, 45 years) with information on menses and hirsutism in their twenties were assessed for CAC (n=982) and IMT (n=988). We defined PCOS as women who had both irregular menses and hyperandrogenism (n=55); isolated oligomenorrhea (n=103) as women who only had irregular menses; and isolated hyperandrogenism (n=156) as women who had either hirsutism or increased testosterone levels. Logistic regressions and general linear models were used to estimate the associations between components of PCOS and subclinical CVD. The prevalence of CAC was 10.3% overall. Women with PCOS had a multivariable adjusted odds ratio of 2.70 (95% confidence interval, 1.31-5.60) for CAC. Women with either isolated oligomenorrhea or isolated hyperandrogenism had no increased risk of CAC when compared with unexposed women. Women with PCOS had significantly increased bulb and internal carotid-IMT measurements; however, no significant differences were noted in bulb or internal carotid artery IMT among women with either isolated oligomenorrhea or isolated hyperandrogenism when compared with unexposed women. There were no differences in common carotid-IMT among the 4 study groups. CONCLUSIONS: In this study, women with PCOS, manifested as both anovulation and hyperandrogenism, but not women with one of these manifestations alone, were at increased risk for the development of subclinical CVD.

Birth weight and subsequent risk of cancer.

BACKGROUND: We aimed to determine the association between self-reported birth weight and incident cancer in the Women's Health Initiative Observational Study cohort, a large multiethnic cohort of postmenopausal women. METHODS: 65,850 women reported their birth weight by category (<6 lbs, 6-7 lbs 15 oz, 8-9 lbs 15 oz, and ≥10 lbs). All self-reported, incident cancers were adjudicated by study staff. We used Cox proportional hazards regression to estimate crude and adjusted hazard ratios (aHR) for associations between birth weight and: (1) all cancer sites combined, (2) gynecologic cancers, and (3) several site-specific cancer sites. RESULTS: After adjustments, birth weight was positively associated with the risk of lung cancer (p=0.01), and colon cancer (p=0.04). An inverse trend was observed between birth weight and risk for leukemia (p=0.04). A significant trend was not observed with breast cancer risk (p=0.67); however, women born weighing ≥10 lbs were less likely to develop breast cancer compared to women born between 6 lbs-7 lbs 15 oz (aHR 0.77, 95% CI 0.63, 0.94). CONCLUSION: Birth weight category appears to be significantly associated with the risk of any postmenopausal incident cancer, though the direction of the association varies by cancer type.

Assessing the utility of methods for menopausal transition classification in a population-based cohort: the CARDIA Study.

OBJECTIVES: Perimenopause significantly impacts women's health, but is under-researched due to challenges in assessing perimenopause status. Using CARDIA data, we compared the validity of six approaches for classifying perimenopause status in order to better understand the performance of classification techniques which can be applied to general cohort data. Specifically, we examined the validity of a self-reported question concerning changes in menstrual cycle length and two full prediction models using all available data concerning menstrual cycles as potential indicators of perimenopause. The validity of these three novel methods of perimenopause classification were compared to three previously established classification methods. METHODS: For each method, women were classified as pre- or peri-menopausal at Year 15 of follow-up (ages 32-46). Year 15 perimenopause status was then used to predict Year 20 post-menopausal status (yes/no) to estimate measures of validity and area under the curve. RESULTS: The validity of the methods varied greatly, with four having an area under the curve greater than 0.8. CONCLUSIONS: When designing studies, researchers should collect the data required to construct a prediction model for classifying perimenopause status that includes age, smoking status, vasomotor symptoms, and cycle irregularities as predictors. The inclusion of additional data regarding menstrual cycles can be used to construct a full prediction model which may offer improved validity. Valid classification methods that use readily available data are needed to improve the scientific accuracy of research regarding perimenopause, promote research on this topic, and inform clinical practices.

Cardiometabolic risk factors among HIV patients on antiretroviral therapy.

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.

Antral follicle count predicts natural menopause in a population-based sample: the Coronary Artery Risk Development in Young Adults Women's Study.

OBJECTIVE: The timing of menopause is associated with multiple chronic diseases. Tools that predict this milestone have relevance for clinical and research purposes. Among infertile women, a positive relationship exists between antral follicle count (AFC) and response to controlled ovarian hyperstimulation, a marker of ovarian reserve. However, an age-independent relationship between AFC and menopause has not been demonstrated. Thus, our objective was to evaluate the relationship between AFC measured in women aged 34 to 49 years and incident natural menopause during 7 years of follow-up. METHODS: The Coronary Artery Risk Development in Young Adults Study is a longitudinal community-based study (Chicago, IL; Birmingham, AL; Minneapolis, MN; and Oakland, CA) begun in 1985-1986. In 2002-2003, the Coronary Artery Risk Development in Young Adults Women's Study measured follicle-stimulating hormone (FSH) levels and performed a transvaginal ultrasound protocol that included AFC (2-10 mm follicles on both ovaries). Incident natural menopause was assessed by surveys in 2005-2006 and 2009-2010. RESULTS: In our sample (n = 456), the median (interquartile range) AFC and FSH level were 5 (2-9) and 7.8 (5.6-11.0) mIU/mL, respectively, at a mean (range) age of 42 (34-49) years in 2002-2003. One hundred one women reported natural menopause by 2009-2010. In Cox models, current smoking, stable menses, FSH level higher than 13 mIU/mL, and AFC of 4 or less were independently associated with incident natural menopause. Compared with AFC higher than 4, those with an AFC of 4 or less were nearly twice as likely to have undergone menopause during 7 years of follow-up (hazard ratio, 1.89; 95% CI, 1.19-3.02) after adjustment for covariates. CONCLUSIONS: AFC has been found to be independently associated with natural menopause during 7 years of follow-up after controlling for other markers of ovarian aging.

Preterm birth and future maternal blood pressure, inflammation, and intimal-medial thickness: the CARDIA study.

Preterm birth (PTB, <37 weeks) may be a marker of endothelial dysfunction and a proinflammatory phenotype; both are risk factors for cardiovascular disease. We studied 916 women (46% black) with 1181 live births between enrollment in the Coronary Artery Risk Development in Young Adults study (age 18-30 years) and 20 years later. C-reactive protein was measured at years 7, 15, and 20. Interleukin-6 and carotid intima-media thickness, which incorporated the common carotid arteries, bifurcations, and internal carotid arteries, were measured at year 20. Blood pressure, lipids, anthropometrics, and pregnancy events were assessed at all visits. Change in risk factors and differences in inflammatory markers and intima-media thickness according to PTB were evaluated. Women with PTBs (n=226) had higher mean systolic blood pressures before pregnancy (106 versus 105 mm Hg, respectively; P=0.03). Systolic and diastolic blood pressure increased more rapidly over 20 years compared with women with term births (P<0.01 time interaction), even after removing women with self-reported hypertension in pregnancy. Women with PTB versus term births had similar mean intima-media thickness adjusted for age, body mass index, race, lifestyle, and cardiovascular risk factors. C-reactive protein and interleukin-6 did not differ according to PTB. Women with PTB, regardless of hypertension during pregnancy, had higher blood pressure after pregnancy compared with women with term births. In the United States, where rates of PTB are high and race disparities persist, PTB may identify women with higher blood pressure in the years after pregnancy.

Optimizing natural fertility: the role of lifestyle modification.

Preconception counseling provides an opportunity for health care providers to promote maternal and neonatal health, and to make recommendations regarding the optimization of natural fertility. While educating patients on the negative impact of maternal obesity on fertility and maternal and neonatal health; many health care providers recommend weight loss to reduce these negative outcomes. The recommendations start with lifestyle modifications, including diet and exercise. This article focuses on the available evidence regarding lifestyle modifications and fertility, and on the type of lifestyle modifications that health care providers should recommend to patients seeking to optimize their natural fertility.

Racial differences in self-reported infertility and risk factors for infertility in a cohort of black and white women: the CARDIA Women's Study.

OBJECTIVE: To determine racial differences in self-reported infertility and in risk factors for infertility in a cohort of black and white women. DESIGN: A cross-sectional analysis of data from the longitudinal Coronary Artery Risk Development in Young Adults (CARDIA) Study, a prospective, epidemiologic investigation of the determinants and evolution of cardiovascular risk factors among black and white young adults and from the ancillary CARDIA Women's Study (CWS). SETTING: Population-based sample from four US communities (Birmingham, AL; Chicago, IL; Minneapolis, MN; Oakland, CA). PATIENT(S): Women aged 33-44 years who had complete data (n = 764). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Self-report of ever having unprotected sexual intercourse for at least 12 months without becoming pregnant. RESULT(S): Among nonsurgically sterile women, blacks had a twofold increased odds (95% confidence interval [CI] 1.3-3.1) of infertility compared with whites after adjustment for socioeconomic position (education and ability to pay for basics), correlates of pregnancy intent (marital status and hormonal contraceptive use), and risk factors for infertility (age, smoking, T, fibroid presence, and ovarian volume). The corresponding odds ratio among all women was 1.5 (95% CI 1.0-2.2). Difficulty paying for basics and ovarian volume were associated with infertility among black but not white women. CONCLUSION(S): In this population-based sample, black women were more likely to have experienced infertility. This disparity is not explained by common risk factors for infertility, such as smoking and obesity, and among nonsurgically sterile women, it is not explained by gynecologic risk factors such as fibroids and ovarian volume.