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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.

Background Evidence of the cardiovascular benefits of adherence to quality indicators in diabetes care over a period of years is lacking. Methods and Results We conducted a population-based, historical cohort study of 105 656 people aged 45 to 80 with pharmacologically treated diabetes and who were free of cardiac disease in 2010. Data were retrieved from electronic medical records of the 4 Israeli health maintenance organizations. The association between level of adherence to national quality indicators (2006-2010: adherence assessment) and incidence of cardiac outcome; ischemic heart disease or heart failure (2011-2016: outcome assessment) was estimated using Cox proportional hazards models. During 529 551 person-years of follow-up, 19 246 patients experienced cardiac disease. An inverse dose-response association between the level of adherence and risk of cardiac morbidity was shown for most of the quality indicators. The associations were modified by age, with stronger associations among younger patients (<65 years). Low adherence to low-density lipoprotein cholesterol testing (≤2 years) during the first 5 years was associated with 41% increased risk of cardiac morbidity among younger patients. Patients who had uncontrolled low-density lipoprotein cholesterol in all first 5 years had hazard ratios of 1.60 (95% CI, 1.49-1.72) and 1.23 (95% CI, 1.14-1.32), among patients aged <65 and ≥65 years, respectively, compared with those who achieved target level. Patients who failed to achieve target levels of glycated hemoglobin or blood pressure had an increased risk (hazard ratios, 1.50-1.69) for cardiac outcomes. Conclusions Longitudinal adherence to quality indicators in diabetes care is associated with reduced risk of cardiac morbidity. Implementation of programs that measure and enhance quality of care may improve the health outcomes of people with diabetes.

Introduction: Scarce research is available regarding the association between interbirth intervals (IBI) and long-term maternal health outcomes, particularly cardiovascular disease (CVD) mortality. We aimed to assess whether IBIs were associated with all-cause, CVD-related and cancer-related mortality., Methods: We conducted a cohort study in the setting of the Jerusalem Perinatal Study. Women with at least two consecutive singleton live births in 1964-1976 (N=18 294) were followed through 2016. IBIs were calculated as the interval between women's first and second cohort birth. We estimated associations between IBIs and mortality using Cox's proportional hazards models, adjusting for age, parity, maternal education, maternal origin and paternal socioeconomic status. Date of last menstrual period was available for a subset of women. We assessed the interpregnancy interval (IPI) for these women and compared the models using IPI and IBI., Results: During 868 079 years of follow up (median follow-up: 49.0 years), 3337 women died. Women with IBIs <15 months had higher all-cause mortality rates (HR 1.18; 95% CI 1.05 to 1.33) compared to women with 33-month to 68-month IBIs (reference category). IBI and CVD mortality appeared to have a J-shaped association; IBIs of <15, 15-20, 21-2626-2632, 33-68 and ≥69 months had HRs of 1.44, 1.40, 1.33, 1.14, 1.00 and 1.30, respectively. No substantial association was found with cancer mortality. Models using IPIs and those using IBI were similar., Conclusion: Our results support the WHO recommendations for IPIs of ≥24 months and add additional evidence regarding long-term CVD mortality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

Background: Several stages in the life course have been identified as important to the development of cardiovascular disease. This study aimed to assess the associations of childhood and adulthood socioeconomic position (SEP) and social mobility with cardiometabolic risk factors (CMRs) later in life., Methods: We conducted follow-up examinations of 1132 offspring, aged 32, within a population-based cohort of all births in Jerusalem from 1974 to 1976. SEP was indicated by parents' occupation and education, and adulthood SEP was based on offspring's occupation and education recorded at age 32. Linear regression models were used to investigate the associations of SEP and social mobility with CMRs., Results: Childhood-occupational SEP was negatively associated with body mass index (BMI; β=-0.29, p=0.031), fat percentage (fat%; β=-0.58, p=0.005), insulin (β=-0.01, p=0.031), triglycerides (β=-0.02, p=0.024) and low-density lipoprotein cholesterol (LDL-C; β=-1.91, p=0.015), independent of adulthood SEP. Adulthood-occupational SEP was negatively associated with waist-to-hip ratio (WHR; β=-0.01, p=0.002), and positively with high-density lipoprotein cholesterol (HDL-C; β=0.87, p=0.030). Results remained similar after adjustment for smoking and inactivity. Childhood-educational SEP was associated with decreased WHR and LDL-C level (p=0.0002), and adulthood-educational SEP was inversely associated with BMI (p=0.001), waist circumference (p=0.008), WHR (p=0.001) and fat% (p=0.0002) and positively associated with HDL-C (p=0.030). Additionally, social mobility (mainly upward) was shown to have adverse cardiometabolic outcomes., Conclusions: Both childhood and adulthood SEP contribute independently to CMR. The match-mismatch hypothesis may explain the elevated CMRs among participants experiencing social mobility. Identification of life-course SEP-related aspects that translate into social inequality in cardiovascular risk may facilitate efforts for improving health and for reducing disparities in cardiovascular disease., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Accumulating evidence demonstrates that both maternal prepregnancy body mass index (mppBMI) and gestational weight gain (GWG) are associated with adult offspring adiposity. However, whether these maternal attributes are related to other cardiometabolic risk factors in adulthood has not been comprehensively studied., Methods and Results: We used a birth cohort of 1400 young adults born in Jerusalem who had extensive archival data and clinical information at 32 years of age to prospectively examine the associations of mppBMI and GWG with adiposity and related cardiometabolic outcomes. Greater mppBMI, independently of GWG and confounders, was significantly associated with higher offspring BMI, waist circumference, systolic and diastolic blood pressures, insulin, and triglycerides and with lower high-density lipoprotein cholesterol. For example, the effect sizes were translated to nearly 5 kg/m(2) higher mean BMI, 8.4 cm higher waist circumference, 0.13 mmol/L (11.4 mg/dL) higher triglycerides, and 0.10 mmol/L (3.8 mg/dL) lower high-density lipoprotein cholesterol among offspring of mothers within the upper mppBMI quartile (mppBMI >26.4 kg/m(2)) compared with the lower quartile (mppBMI <21.0 kg/m(2)). GWG, independently of mppBMI, was positively associated with offspring adiposity; differences of 1.6 kg/m(2) in BMI and 2.4 cm in waist were observed when offspring of mothers in the upper (GWG >14 kg) and lower (GWG <9 kg) quartiles of GWG were compared. Further adjustment for offspring adiposity attenuated the observed associations to the null., Conclusions: Maternal size both before and during pregnancy is associated with cardiometabolic risk factors in young adult offspring. The associations appear to be driven mainly by offspring adiposity. Future studies that explore mechanisms underlying the intergenerational cycle of obesity are warranted to identify potentially novel targets for cardiometabolic risk-reduction interventions.

Context: The role of endogenous androgens and SHBG in the development of cardiovascular disease in young adult women is unclear., Objective: Our objective was to study the prospective association of serum androgens and SHBG with subclinical coronary and carotid disease among young to middle-aged women., Design and Setting: This was an ancillary study to the Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based multicenter cohort study with 20 yr of follow-up., Participants: Participants included 1629 women with measurements of serum testosterone and SHBG from yr 2, 10, or 16 and subclinical disease assessment at yr 20 (ages 37-52 yr)., Main Outcome Measures: Coronary artery calcified plaques (CAC) and carotid artery intima-media thickness (IMT) were assessed at yr 20. The IMT measure incorporated the common carotid arteries, bifurcations, and internal carotid arteries., Results: SHBG (mean of yr 2, 10, and 16) was inversely associated with the presence of CAC (multivariable adjusted odds ratio for women with SHBG levels above the median = 0.59; 95% confidence interval = 0.40-0.87; P = 0.008). SHBG was also inversely associated with the highest quartile of carotid-IMT (odds ratio for women with SHBG levels in the highest quartile = 0.56; 95% confidence interval = 0.37-0.84; P for linear trend across quartiles = 0.005). No associations were observed for total or free testosterone with either CAC or IMT., Conclusion: SHBG levels were inversely associated with subclinical cardiovascular disease in young to middle-aged women. The extent to which low SHBG is a risk marker or has its own independent effects on atherosclerosis is yet to be determined.

Objective: To assess whether women who experienced stillbirths have an excess risk of long-term mortality., Methods: We conducted a cohort study in the setting of the Jerusalem Perinatal Study, a population-based database of all births to West Jerusalem residents. Through data linkage with the Israeli Population Registry, we followed mothers who gave birth at least twice between 1964 and 1976 and compared the survival of women who had at least one stillbirth (n=595) with that of women who had only live births (n=24,523), using Cox proportional hazards models., Results: During the study period, 78 (13.1%) mothers with stillbirths died, compared with 1,518 (6.2%) women without stillbirth (crude hazard ratio 2.08, 95% confidence interval [CI] 1.65-2.61). The mortality risk remained significantly increased after adjustments for sociodemographic variables, maternal diseases at pregnancy, placental abruption, and preeclampsia (hazard ratio 1.40, 95% CI 1.11-1.77). Stillbirth was associated with an increased risk of death from coronary heart disease (adjusted hazard ratio 2.00, 95% CI 1.02-3.93), all circulatory (adjusted hazard ratio 1.70, 95% CI 1.02-2.84) and renal (adjusted hazard ratio 4.70, 95% CI 1.47-15.0) causes. Stratifying by country of origin, an increased risk was evident particularly among women of North African origin (all-cause mortality, adjusted hazard ratio 2.47, 95% CI 1.69-3.63)., Conclusion: Stillbirth may be a risk marker for premature mortality among parous women.