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1.  Association of Race and Sex With Risk of Incident Acute Coronary Heart Disease Events 
It is unknown whether long-standing disparities in incidence of coronary heart disease (CHD) among US blacks and whites persist.
To examine incident CHD by black and white race and by sex.
Prospective cohort study of 24 443 participants without CHD at baseline from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, who resided in the continental United States and were enrolled between 2003 and 2007 with follow-up through December 31, 2009.
Expert-adjudicated total (fatal and nonfatal) CHD, fatal CHD, and nonfatal CHD (definite or probable myocardial infarction [MI]; very small non–ST-elevation MI [NSTEMI] had peak troponin level <0.5 µg/L).
Over a mean (SD) of 4.2 (1.5) years of follow-up, 659 incident CHD events occurred (153 in black men, 138 in black women, 254 in white men, and 114 in white women). Among men, the age-standardized incidence rate per 1000 person-years for total CHD was 9.0 (95% CI, 7.5–10.8) for blacks vs 8.1 (95% CI, 6.9–9.4) for whites; fatal CHD: 4.0 (95% CI, 2.9–5.3) vs 1.9 (95% CI, 1.4–2.6), respectively; and nonfatal CHD: 4.9 (95% CI, 3.8–6.2) vs 6.2 (95% CI, 5.2–7.4). Among women, the age-standardized incidence rate per 1000 person-years for total CHD was 5.0 (95% CI, 4.2–6.1) for blacks vs 3.4 (95% CI, 2.8–4.2) for whites; fatal CHD: 2.0 (95% CI, 1.5–2.7) vs 1.0 (95% CI, 0.7–1.5), respectively; and nonfatal CHD: 2.8 (95% CI, 2.2–3.7) vs 2.2 (95% CI, 1.7–2.9). Age- and region-adjusted hazard ratios for fatal CHD among blacks vs whites was near 2.0 for both men and women and became statistically nonsignificant after multivariable adjustment. The multivariable-adjusted hazard ratio for incident nonfatal CHD for blacks vs whites was 0.68 (95% CI, 0.51–0.91) for men and 0.81 (95% CI, 0.58–1.15) for women. Of the 444 nonfatal CHD events, 139 participants (31.3%) had very small NSTEMIs.
The higher risk of fatal CHD among blacks compared with whites was associated with cardiovascular disease risk factor burden. These relationships may differ by sex.
PMCID: PMC3772637  PMID: 23117777
coronary heart disease; epidemiology; racial disparities; disease incidence; cohort study
2.  Relation of Left Ventricular Mass at Age 23 to 35 years to Global Left Ventricular Systolic Function 20 Years Later (From the Coronary Artery Risk Development in Young Adults Study) 
The American journal of cardiology  2013;113(2):377-383.
Left ventricular (LV) mass and LV ejection fraction (EF) are major independent predictors of future cardiovascular disease. The association of LV mass with future LVEF in younger populations has not been studied. We investigated the relation of LV mass index (LVMI) at age 23 to 35 years to LV function after 20 years of follow-up in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. CARDIA is a longitudinal study that enrolled young adults in 1985–1986. We included participants with echocardiographic examinations at both years-5 and -25. LVMI and LVEF were assessed using M-mode echocardiography at year-5 and using both M-mode and 2-dimensional images at year-25. Statistical analytic models assessed the correlation between LVMI and LV functional parameters both cross-sectionally and longitudinally. A total of 2,339 participants were included. The mean LVEF at year-25 was 62%. Although there was no cross-sectional correlation between LVMI and LVEF at year-5, there was a small, but statistically significant negative correlation between LVMI at year-5 and LVEF 20 years later (r = −0.10, p < 0.0001); this inverse association persisted for LVMI in the multivariable model. High LVMI was an independent predictor of systolic dysfunction (LVEF < 50%) 20 years later (odds ratio 1.46, p = 0.0018). In conclusion, we have shown that LVMI in young adulthood in association with chronic risk exposure impacts systolic function in middle age; the antecedents of heart failure may occur at younger ages than previously thought.
PMCID: PMC3901209  PMID: 24176073
left ventricular mass; left ventricular ejection fraction; echocardiography; left ventricular remodeling
3.  Estimated GFR and Risk of Hip Fracture in Older Men: Comparison of Associations Using Cystatin C and Creatinine 
Higher serum cystatin C is associated with an increased risk of hip fracture in postmenopausal white women, but there is a paucity of data in men. Whether an estimated GFR (eGFR) based on cystatin C (eGFRcys) is superior in predicting hip fracture risk to an eGFR based on creatinine (eGFRcr) or the combination (eGFRcr-cys) is also uncertain.
Study Design
Nested case-cohort.
Setting & Participants
Participants enrolled in the Osteoporotic Fractures in Men (MrOS) Study (5,994 men aged ≥65 years from six U.S. centers) including a random subcohort of 1602 men and 168 men with incident hip fractures (51 of whom were in the subcohort).
eGFRcys, eGFRcr and eGFRcr-cys computed using the CKD-EPI equations and expressed in categories of <60, 60–74, and ≥75 mL/min/l.73 m2 (referent group).
Incident hip fracture ascertained by participant contacts every 4 months and confirmed with radiographic reports.
Median eGFRcys was 72.9 (IQR, 60.5–85.7) mL/min/1.73 m2. In unadjusted models, all measures of eGFR were associated with increased hip fracture risk. However, after adjustment for age, race, site and BMI, the association of lower eGFRcys (but not lower eGFRcr or lower eGFRcr-cys) with higher hip fracture risk remained: for <60 vs. ≥75 mL/min/l.73 m2, HRs were 1.96 [95% CI, 1.25–3.09], 0.84 [95% CI, 0.52–1.37], and 1.08 [95% CI, 0.66–1.77] for eGFRcys, eGFRcr, and eGFRcr-cys, respectively. Similarly, after adjustment for age, race, site and BMI, eGFR of <60 ml/min/1.73 m2 defined by eGFRcys but not eGFRcr or eGFRcr-cys, was associated with higher hip fracture risk. The association between eGFRcys and hip fracture was not explained by levels of calcitropic hormones or inflammatory markers, but the relationship was attenuated and no longer reached significance (for <60 vs. ≥75 mL/min/l.73 m2: HR, 1.43; 95% CI, 0.88–2.34) after consideration of additional clinical risk factors and bone mineral density.
Findings not generalizable other populations; residual confounding may exist.
Older community-dwelling men with lower eGFRcys have an increased risk of hip fracture that is explained in large part by greater burden of risk factors among men with lower eGFRcys. In contrast, lower eGFRcr or lower eGFRcr-cys were not associated with a higher age-adjusted hip fracture risk.
PMCID: PMC3833961  PMID: 23890927
kidney function; cystatin C; creatinine; hip fracture; elderly; men
4.  Evaluating the Framingham Hypertension Risk Prediction Model in Young Adults: The Coronary Artery Risk Development in Young Adults (CARDIA) Study 
Hypertension  2013;62(6):1015-1020.
A prediction model was developed in the Framingham Heart Study (FHS) to evaluate short-term risk of hypertension. Our goal was to determine the predictive ability of the FHS hypertension model in a cohort of young adults advancing into middle age and compare it with the predictive ability of prehypertension, and individual components of the FHS model. We studied 4,388 participants, age 18-30 years without hypertension at baseline, enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) Study who participated in 2 consecutive exams occurring 5 years apart between the baseline (1985-1986) and Year 25 examination (2010-2011). Weibull regression was used to assess the association of the FHS model overall, individual components of the FHS model, and prehypertension with incident hypertension. Over the 25 year follow-up period, 1179 participants developed incident hypertension. The FHS hypertension model (c-index=0.84, 95% CI=0.83, 0.85) performed well in discriminating those who did and did not develop hypertension and was better than prehypertension alone (c-index=0.71, 95% CI=0.70, 0.73). The predicted risk from the FHS hypertension model was systematically lower than the observed hypertension incidence initially (χ2= 249.4; p<0.001), but demonstrated a good fit after recalibration (χ2= 14.6; p=0.067). In summary, the FHS model performed better than prehypertension and may be a useful tool for identifying young adults with a high risk for developing hypertension.
PMCID: PMC4019674  PMID: 24041951
hypertension; prehypertension; epidemiology; risk
5.  Association Between Duration of Overall and Abdominal Obesity Beginning in Young Adulthood and Coronary Artery Calcification in Middle Age 
JAMA  2013;310(3):280-288.
Younger individuals are experiencing a greater cumulative exposure to excess adiposity over their lifetime. However, few studies have determined the consequences of long-term obesity.
To examine whether the duration of overall and abdominal obesity was associated with the presence and 10-year progression of coronary artery calcification (CAC), a subclinical predictor of coronary heart disease.
Prospective study of 3275 white and black adults aged 18 to 30 years at baseline in 1985–1986 who did not initially have overall obesity (body mass index [BMI] ≥30) or abdominal obesity (men: waist circumference [WC] >102 cm; women: >88 cm) in the multicenter, community-based Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants completed computed tomography scanning for the presence of CAC during the 15-, 20-, or 25-year follow-up examinations. Duration of overall and abdominal obesity was calculated using repeat measurements of BMI and WC, respectively, performed 2, 5, 7, 10, 15, 20, and 25 years after baseline.
Presence of CAC was measured by computed tomography at the year 15 (2000–2001), year 20 (2005–2006), or year 25 (2010–2011) follow-up examinations. Ten-year progression of CAC (2000–2001 to 2010–2011) was defined as incident CAC in 2010–2011 or an increase in CAC score of 20 Agatston units or greater.
During follow-up, 40.4% and 41.0% developed overall and abdominal obesity, respectively. Rates of CAC per 1000 person-years were higher for those who experienced more than 20 years vs 0 years of overall obesity (16.0 vs 11.0, respectively) and abdominal obesity (16.7 vs 11.0). Approximately 25.2% and 27.7% of those with more than 20 years of overall and abdominal obesity, respectively, experienced progression of CAC vs 20.2% and 19.5% of those with 0 years. After adjustment for BMI or WC and potential confounders, the hazard ratios for CAC for each additional year of overall or abdominal obesity were 1.02 (95% CI, 1.01–1.03) and 1.03 (95% CI, 1.02–1.05), respectively. The adjusted odds ratios for CAC progression were 1.04 (95% CI, 1.01–1.06) and 1.04 (95% CI, 1.01–1.07), respectively. Associations were attenuated but largely persisted following additional adjustment for potential intermediate metabolic factors during follow-up.
Longer duration of overall and abdominal obesity was associated with subclinical coronary heart disease and its progression through midlife independent of the degree of adiposity. Preventing or at least delaying the onset of obesity in young adulthood may lower the risk of developing atherosclerosis through middle age.
PMCID: PMC4226407  PMID: 23860986
7.  The Women’s Health Initiative Hormone Therapy Trials: Update and Overview of Health Outcomes During the Intervention and Post-Stopping Phases 
Menopausal hormone therapy continues in clinical use but questions remain regarding its risks and benefits for chronic disease prevention.
To provide a comprehensive, integrated overview of findings from the two Women’s Health Initiative (WHI) hormone therapy (HT) trials with extended post-intervention follow up.
27,347 postmenopausal women, age 50–79 years, were enrolled at 40 US centers. Interventions were conjugated equine estrogens (CEE, 0.625 mg/day) with medroxyprogesterone acetate (MPA, 2.5 mg/day) for women with an intact uterus (N = 16,608) and CEE alone for women with hysterectomy (N= 10,739), or their placebos. Intervention continued for 5.6 and 7.2 years (median), respectively, with cumulative follow-up of 13 years through September 30, 2010.
The primary efficacy and safety outcomes were coronary heart disease (CHD) and invasive breast cancer, respectively. A global index also included stroke, pulmonary embolism, colorectal cancer, endometrial cancer, hip fracture, and deaths. Secondary and quality-of-life outcomes were also assessed.
During the intervention phase for CEE+MPA, the hazard ratio (HR) for CHD was 1.18 (95% confidence interval [CI] 0.95–1.45) and overall risks outweighed benefits, with increases in invasive breast cancer, stroke, pulmonary embolism, and the global index. Other risks included increased dementia (in women >65 years), gallbladder disease, and urinary incontinence, while benefits included decreased hip fractures, diabetes, and vasomotor symptoms. Post-intervention, most risks and benefits dissipated, although some elevation in breast cancer risk persisted (cumulative hazard ratio [HR] =1.28; 95% confidence interval, 1.11–1.48). During intervention for CEE alone, risks and benefits were more balanced, with a HR for CHD of 0.94 (0.78–1.14), increased stroke and venous thrombosis, decreased hip fractures and diabetes, and over cumulative follow-up, decreased breast cancer (HR=0.79 [0.65–0.97]). Neither regimen affected all-cause mortality. With CEE, younger women (50–59 years) had more favorable results for all-cause mortality, myocardial infarction, and the global index (nominal P values for trend by age <0.05), but not for stroke and venous thrombosis. Absolute risks of adverse events (measured by the global index) per 10,000 women per year on CEE+MPA ranged from 12 excess cases for age 50–59 to 38 for age 70–79 and, for CEE, from 19 fewer cases for age 50–59 to 51 excess cases for age 70–79. Results for quality of life outcomes in both trials were mixed.
Menopausal hormone therapy has a complex pattern of risks and benefits. While appropriate for symptom management in some women, its use for chronic disease prevention is not supported by the WHI randomized trials.
clinical Identifier: NCT00000611
PMCID: PMC3963523  PMID: 24084921
8.  Impact of Weight Loss on Ankle-Brachial Index and Inter-Artery Blood Pressures in Overweight and Obese Adults with Diabetes 
Obesity (Silver Spring, Md.)  2014;22(4):1032-1041.
To assess whether weight loss improves markers of peripheral artery disease and vascular stenosis.
Design and Methods
The Action for Health in Diabetes randomized clinical trial compared intensive lifestyle intervention (ILI) for weight loss to a control condition of diabetes support and education (DSE) in overweight or obese adults with type 2 diabetes. Annual ankle and brachial blood pressures over four years were used compute ankle-brachial indices (ABIs) and to assess inter-artery blood pressure differences in 5018 participants.
ILI, compared to DSE, produced 7.8% (Year 1) to 3.6% (Year 4) greater weight losses. These did not affect prevalence of low (<0.90) ABI (3.60% in DSE versus 3.14% in ILI; p=0.20) or elevated (>1.40) ABI (7.52% in DSE versus 7.59% in ILI: p=0.90), but produced smaller mean (SE) maximum inter-artery systolic blood pressure differences among ankle sites [19.7 (0.2) mmHg for ILI versus 20.6 (0.2) mmHg for DSE (p<0.001)] and between arms [5.8 (0.1) mmHg for ILI versus 6.1 (0.1) mmHg for DSE (p=0.01)].
Four years of intensive behavioral weight loss intervention did not significantly alter prevalence of abnormal ABI, however it did reduce differences in systolic blood pressures among arterial sites.
PMCID: PMC3968218  PMID: 24174392
Peripheral artery disease; Weight loss; Diabetes
9.  Effect of Intensive Lifestyle Intervention on Sexual Dysfunction in Women With Type 2 Diabetes 
Diabetes Care  2013;36(10):2937-2944.
Sexual dysfunction is a prevalent problem in obese women with type 2 diabetes. This study examined the effects of intensive lifestyle intervention (ILI) in these women.
Look AHEAD is a 16-center, randomized, controlled trial evaluating the health effects of ILI compared with a control group (diabetes support and education [DSE]). The Look AHEAD Sexual Function Ancillary study included 375 female participants at five Look AHEAD sites. Participants completed the Female Sexual Function Inventory (FSFI) and Beck Depression Inventory (BDI), and assessments of weight and cardiovascular risk factors at baseline and 1 year were made.
At baseline, 50% of the 229 participants who reported being sexually active met criteria for female sexual dysfunction (FSD); only BDI score was related to FSD. One-year weight losses were greater in the ILI group than in the DSE group (7.6 vs. 0.45 kg; P < 0.001). Among women with FSD at baseline, those in the ILI group (N = 60) compared with those in the DSE group (N = 53) were significantly more likely to remain sexually active (83 vs. 64%; P < 0.008), reported greater improvement in total FSFI scores and in most FSFI domains (P < 0.05), and were more likely to experience remission of FSD (28 vs. 11%; P < 0.04) at 1 year. No significant differences between ILI and DSE were seen in women who did not have FSD at baseline.
Participation in ILI appeared to have beneficial effects on sexual functioning among obese women with diabetes, particularly in those who had FSD at baseline.
PMCID: PMC3781524  PMID: 23757437
10.  The Diagnostic Performance of Anterior Knee Pain and Activity-related Pain in Identifying Knees with Structural Damage in the Patellofemoral Joint: The Multicenter Osteoarthritis Study 
The Journal of rheumatology  2014;41(8):1695-1702.
To determine the diagnostic test performance of location of pain and activity-related pain in identifying knees with patellofemoral joint (PFJ) structural damage.
The Multicenter Osteoarthritis Study is a US National Institutes of Health-funded cohort study of older adults with or at risk of knee osteoarthritis. Subjects identified painful areas around the knee on a knee pain map and the Western Ontario and McMaster Universities Osteoarthritis Index was used to assess pain with stairs and walking on level ground. Cartilage damage and bone marrow lesions were assessed from knee magnetic resonance imaging. We determined the sensitivity, specificity, positive and negative predictive values for presence of anterior knee pain (AKP), pain with stairs, absence of pain while walking on level ground, and combinations of tests in discriminating knees with isolated PFJ structural damage from those with isolated tibiofemoral joint (TFJ) or no structural damage. Knees with mixed PFJ/TFJ damage were removed from our analyses because of the inability to determine which compartment was causing pain.
There were 407 knees that met our inclusion criteria. “Any” AKP had a sensitivity of 60% and specificity of 53%; and if AKP was the only area of pain, the sensitivity dropped to 27% but specificity rose to 81%. Absence of moderate pain with walking on level ground had the greatest sensitivity (93%) but poor specificity (13%). The combination of “isolated” AKP and moderate pain with stairs had poor sensitivity (9%) but the greatest specificity (97%) of strategies tested.
Commonly used questions purported to identify knees with PFJ structural damage do not identify this condition with great accuracy.
PMCID: PMC4182011  PMID: 24931959
11.  Racial Differences in Self-Reported Infertility and Risk Factors for Infertility in a Cohort of Black and White Women: The CARDIA Women’s Study 
Fertility and sterility  2008;90(5):1640-1648.
To determine racial differences in self-reported infertility and in risk factors for infertility in a cohort of black and white women.
A cross-sectional analyses 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).
Population-based sample from 4 US communities (Birmingham, AL; Chicago, IL, Minneapolis, MN; and Oakland, CA).
Women ages 33–44 who had complete data (n=764).
Main Outcome Measure
Self-report of ever having unprotected sexual intercourse for at least 12 months without becoming pregnant.
Among non-surgically sterile women, blacks had a two-fold increased odds (95% CI = 1.3–3.1) of infertility as 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, testosterone, fibroid presence, and ovarian volume). The corresponding OR 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.
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 non-surgically sterile women, it is not explained by gynecologic risk factors such as fibroids and ovarian volume.
PMCID: PMC2592196  PMID: 18321499
Infertility; race; ethnicity; disparity; fibroids; ovarian volume
12.  Blood Pressure Trajectories in Early Adulthood and Subclinical Atherosclerosis in Middle Age 
Single measures of blood pressure (BP) levels are associated with the development of atherosclerosis; however, long-term patterns in BP and their impact on CVD risk are poorly characterized.
To identify common BP trajectories throughout early adulthood and to determine their association with presence of coronary artery calcification (CAC) during middle age.
We used data from the CARDIA study from baseline in 1985-1986 through 25 years of follow-up (2010-2011).
Prospective cohort study
CARDIA participants were Black and White men and women aged 18-30 years at baseline.
We examined systolic BP, diastolic BP, and mid-BP [calculated as (SBP+DBP)/2 and an important marker of CHD risk among younger populations] at baseline and years 2, 5, 7, 10, 15, 20, and 25. Latent mixture modeling was used to identify trajectories in SBP, DBP and mid-BP over time.
Main Outcome Measure
Coronary artery calcification greater than or equal to Agatston score of 100 Agatston units at year 25.
Among 4,681 participants, we identified 5 distinct mid-BP trajectories: Low-Stable (22% [95% CI 19.9-23.7], n=987), Moderate-Stable (42% [40.3-44.3], n=2,085), Moderate-Increasing (12% [10.4-14.0], n=489), Elevated-Stable (19% [17.1-20.0], n=903) and Elevated-Increasing (5% [4.0-5.5], n=217). As compared to the Low-Stable group, trajectories with elevated BP levels had greater odds of having CAC >100. Adjusted odds ratios (95% CI) were 1.44 (0.83-2.49) for Moderate-Stable, 1.86 (0.91-3.82) for Moderate-Increasing, 2.28 (1.24-3.70) for Elevated-Stable, and 3.70 (1.66-8.20) for Elevated-Increasing groups. The adjusted prevalence of CAC ≥ 100 was 5.8% in the Low-Stable group. These ORs represent an absolute increase of 2.7%, 5%, 6.3% and 12.9% for the prevalence of CAC ≥100 for the Moderate-Stable, Moderate-Increasing, Elevated Stable and Elevated Increasing groups respectively as compared to the Low-Stable Group. Associations were not altered after adjustment for baseline and year 25 BP. Findings were similar for trajectories of isolated systolic BP trajectories, but were attenuated for diastolic BP trajectories.
Conclusions and Relevance
BP trajectories throughout young adulthood vary and higher BP trajectories were associated with an increased risk of CAC in middle age. Long-term trajectories in BP may assist in more accurate identification of individuals with subclinical atherosclerosis.
PMCID: PMC4122296  PMID: 24496536
blood pressure; calcium; epidemiology; risk factors
13.  The Multicenter Osteoarthritis Study (MOST): Opportunities for Rehabilitation Research 
PM & R : the journal of injury, function, and rehabilitation  2013;5(8):10.1016/j.pmrj.2013.04.014.
The Multicenter Osteoarthritis Study (MOST) is a longitudinal observational study of the effects of biomechanical, bone and joint structural, and nutritional factors on the incidence and progression of knee symptoms and radiographic and symptomatic knee osteoarthritis (OA). It is the first large-scale epidemiologic study to focus on symptomatic knee OA in a community-based sample of adultswith or at high risk for knee OA, based on thepresence of knee symptoms, history of knee injury or surgery or being overweight. Beginning in 2003, 3026 individuals (60.1% women) age 50-79 years were enrolled. Examinations at baseline, and 15, 30, 60, 72 and 84 months later included assessment of risk factors, disease characteristics, body functions and structure, and measures of physical activity and participation. The wealth of data from this longitudinal cohort of community-dwelling older adults affords valuable opportunities for rehabilitation researchers.
PMCID: PMC3867287  PMID: 23953013
14.  Antral Follicle Count Predicts Natural Menopause in a Population-Based Sample: The CARDIA Women’s Study 
Menopause (New York, N.Y.)  2013;20(8):825-830.
The timing of menopause is associated with multiple chronic diseases. Tools to 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, a relationship between AFC and menopause that is age-independent has not been demonstrated. Thus, our objective was to evaluate the relationship between AFC measured in women at ages 34–49 and incident natural menopause over 7-years of follow-up.
The Coronary Artery Risk Development in Young Adults (CARDIA) study is a longitudinal community-based study (Chicago, Illinois; Birmingham, Alabama; Minneapolis, Minnesota; and Oakland, California) begun in 1985–1986. In 2002–03, the CARDIA Women’s Study measured FSH levels and performed a transvaginal ultrasound protocol that included AFC (2mm–10mm follicles on both ovaries). Incident natural menopause was assessed by survey in 2005–06 and 2009–10.
In our sample (n=456), median AFC and FSH were 5 (IQR 2–9) and 7.8 mIU/mL (IQR 5.6–11.0), respectively, at a mean age of 42 (range 34–49) in 2002–03. 101 women reported natural menopause by 2009–10. In Cox models, current smoking, stable menses, FSH>13, and AFC ≤4 were independently associated with incident natural menopause. Compared to AFC >4, those with AFC ≤4 were nearly twice as likely to have undergone menopause over 7-years of follow-up (HR 1.89, 95% CI 1.19–3.02) after adjustment for covariates.
AFC is independently associated with natural menopause over 7-years of follow-up after controlling for other markers of ovarian aging.
PMCID: PMC3675173  PMID: 23422869
Antral Follicle Count; Menopause; Ovarian Aging; Ovarian Reserve; FSH
15.  Perceived weight discrimination in the CARDIA study: Differences by race, sex, and weight status 
Obesity (Silver Spring, Md.)  2013;22(2):530-536.
To examine self-reported weight discrimination and differences based on race, sex, and BMI in a biracial cohort of community-based middle-aged adults.
Design and Methods
We report on 3,466 participants (mean age=50 years, mean BMI=30 kg/m2) of the Coronary Artery Risk Development in Young Adults (CARDIA) Study who completed the 25-year examination of this epidemiological investigation in 2010–11. The sample included normal weight, overweight, and obese participants. CARDIA participants are distributed into four race-sex groups, with about half being African-American and half White. Participants completed a self-reported measure of weight discrimination.
Among overweight/obese participants, weight discrimination was lowest for White men (12.0%) and highest for White women (30.2%). The adjusted odds ratio (95% CI) for weight discrimination in those with class 2/3 obesity (BMI≥35 kg/m2) versus the normal-weight was most pronounced: African American men, 4.59(1.71–12.34); African American women, 7.82(3.57–17.13); White men, 6.99(2.27–21.49); and White women, 18.60(8.97–38.54). Being overweight (BMI=25–29.9 kg/m2) vs. normal weight was associated with increased discrimination in White women only: 2.10(1.11–3.96).
We provide novel evidence for a race-sex interaction on perceived weight discrimination, with White women more likely to report discrimination at all levels of overweight and obesity. Pychosocial mechanisms responsible for these differences deserve exploration.
PMCID: PMC3695009  PMID: 23512948
discrimination; obesity; weight; sex; race
16.  Long-term Plasma Lipid Changes Associated with a First Birth The Coronary Artery Risk Development in Young Adults Study 
American journal of epidemiology  2004;159(11):1028-1039.
Previous studies have reported declines in high density lipoprotein (HDL) cholesterol 1–2 years after pregnancy. In 1986–1996, the authors prospectively examined the association between childbearing and changes in fasting plasma lipids (low density lipoprotein, HDL, and total cholesterol; triglycerides) among 1,952 US women (980 Black, 972 White) in the Coronary Artery Risk Development in Young Adults study. Repeated-measures multiple linear regression was used to examine lipid changes over three time intervals (baseline to years 5, 7, and 10) in time-dependent follow-up groups: P0 (0 pregnancies), P1 (≥1 miscarriages/abortions), B1 (1 birth), and B2 (≥2 births). Means stratified by race and baseline parity (nulliparous or parous) were fully adjusted for study center, time, height, baseline diet, and other baseline and time-dependent covariates (age, smoking, education, weight, waist circumference, alcohol intake, oral contraceptive use, physical activity, short pregnancies). For both races, fully adjusted HDL cholesterol declines of −3 to −4 mg/dl were associated with a first birth versus no pregnancies during follow-up (p < 0.001). Higher-order births were not associated with greater declines in HDL cholesterol (B2 similar to B1, no association among women parous at baseline). In Whites, total and low density lipoprotein cholesterol declines were associated with follow-up births. HDL cholesterol declines of −3 to −4 mg/dl after a first birth persisted during the 10 years of follow-up independent of weight, central adiposity, and selected behavior changes.
PMCID: PMC4107869  PMID: 15155287
ethnic groups; lipids; lipoproteins; HDL cholesterol; parity; pregnancy
17.  The Effect of Non-surgical Periodontal Therapy on Hemoglobin A1c Levels in Persons with Type 2 Diabetes and Chronic Periodontitis: A Randomized Clinical Trial 
Chronic periodontitis, a destructive inflammatory disorder of the supporting structures of the teeth, is prevalent in patients with diabetes. Limited evidence suggests that periodontal therapy may improve glycemic control.
To determine if non-surgical periodontal treatment reduces hemoglobin A1c (HbA1c) in persons with type 2 diabetes (DM) and moderate to advanced chronic periodontitis.
Design, Setting and Participants
The Diabetes and Periodontal Therapy Trial (DPTT) is a 6-month, single-masked, randomized, multi-center clinical trial. Participants had DM, were taking stable doses of medications, had HbA1c ≥7% and <9%, and untreated periodontitis. Five hundred fourteen participants were enrolled between November 2009 and March 2012 from diabetes and dental clinics and communities affiliated with five academic medical centers.
The treatment group (n=257) received scaling and root planing plus chlorhexidine oral rinse at baseline, and supportive periodontal therapy at three and six months. The control group (n=257) received no treatment for six months.
Main Outcome Measure
Difference in HbA1c change from baseline between groups at six months. Secondary outcomes included changes in probing pocket depths, clinical attachment loss, bleeding on probing, gingival index, fasting glucose, and the Homeostasis Model Assessment (HOMA2).
Enrollment was stopped early due to futility. At 6 months, the periodontal therapy group increased HbA1c 0.17% (1.0) (mean (SD)) compared to 0.11% (1.0) in the control group, with no significant difference between groups based on a linear regression model adjusting for clinical site (mean difference = -0.05%; 95% Confidence Interval (CI): -0.23%, 0.12%; p=0.55). Probing depth, clinical attachment loss, bleeding on probing and gingival index measures improved in the treatment group compared to the control group at six months with adjusted between-group differences of 0.33mm (95% CI: 0.26, 0.39), 0.31mm (95% CI: 0.23, 0.39), 16.5% (95% CI: 12.9, 20.0) and 0.28 (95% CI: 0.21, 0.35), respectively; all p values <0.0001).
Conclusions and Relevance
Non-surgical periodontal therapy did not improve glycemic control in patients with DM and moderate to advanced chronic periodontitis. These findings do not support the use of nonsurgical periodontal treatment in patients with diabetes for the purpose of lowering HbA1c.
PMCID: PMC4089989  PMID: 24346989
Diabetes; Diabetes Mellitus; Type 2; Periodontal Disease; Periodontitis; Glycated Hemoglobin; HbA1c
18.  The association between meniscal damage of the posterior horns and localized posterior synovitis detected on T1-weighted contrast-enhanced MRI—the MOST study 
Synovitis is thought to be a secondary phenomenon in the osteoarthritis (OA) process and the menisci might be triggers of localized synovitis. The aim was to assess the cross-sectional associations of posterior horn meniscal damage with perimeniscal synovitis, and with synovitis posterior to the posterior cruciate ligament (PCL) using contrast enhanced (CE) MRI.
The Multicenter Osteoarthritis (MOST) Study is a longitudinal observational study of subjects with or at risk for knee OA. Subjects are a subset of MOST who were examined with 1.5 T CE MRI and had semiquantitative synovitis (scored from 0–2 at 11 locations) and meniscal readings (scored with WORMS from 0–4 ) available. Logistic regression was used to assess the association of posterior meniscal damage and perimeniscal synovitis in the same compartment, and between posterior meniscal damage and synovitis posterior to the PCL.
Three hundred and seventy seven knees were included (mean age 61.1 years ± 6.9, mean BMI 29.6 ± 4.9, 44.3% women). The odds for ipsi-compartmental perimeniscal synovitis were increased for knees with medial posterior horn meniscal damage (adjusted odds ratio [aOR] 2.5, 95% confidence intervals [95% CI] 1.3,4.8), but not for lateral damage (aOR 1.7, 95% CI 0.4,6.6). No positive associations were found for meniscal damage and presence of synovitis posterior to the PCL (aOR 0.9, 95% CI 0.6,1.5).
Meniscal damage of the posterior horns is associated with ipsi-compartmental perimensical synovitis. No associations were found for posterior horn meniscal damage with synovitis posterior to the PCL, which suggests that synovitis posterior to the PCL is likely to be triggered by different pathomechanisms.
PMCID: PMC3640766  PMID: 23270763
Osteoarthritis; Magnetic resonance imaging; Synovitis; Meniscal damage
19.  Randomized controlled trial of the Medifast 5 & 1 Plan for weight loss 
International journal of obesity (2005)  2013;37(12):10.1038/ijo.2013.43.
The Medifast 5 & 1 Plan (MD) is a portion-controlled, nutritionally-balanced, low-fat weight-loss plan. We studied the effects of MD compared with a reduced-energy, food-based diet (FB) on body weight, waist circumference, fat mass, and other measures in adults.
We conducted a 2 parallel-arm, randomized, controlled trial comparing MD to FB over 52 weeks. A total of 120 men and women aged 19-65 years with BMI ≥35 and ≤50 kg/m2 were randomized to MD (n = 60) or FB (n = 60). Follow-up included a 26-week weight-loss phase and 26-week weight-maintenance phase. Anthropometric, body composition, biochemical, and appetite/satiety measures were performed at baseline, 26 and 52 weeks. An intention-to-treat, linear mixed models analysis was the primary analysis.
Fifty MD subjects (83.3%) and 45 FB subjects (75.0%) completed the study on assigned treatment. At 26 weeks, race-adjusted mean weight loss was 7.5 kg in MD subjects vs. 3.8 kg in FB subjects (P = 0.0002 for difference); reduction in waist circumference was 5.7 cm in MD vs. 3.7 cm in FB (P = 0.0064); and fat mass loss was 6.4 kg in MD vs. 3.7 kg in FB (P = 0.0011). At 52 weeks, the corresponding reductions were 4.7 vs. 1.9 kg (P = 0.0004); 5.0 vs. 3.6 cm (P = 0.0082); and 4.1 vs. 1.9 kg (P = 0.0019) in MD and FB subjects, respectively.
In obese adults, MD resulted in significantly greater reductions in body weight and fat compared with an FB diet for one year after randomization.
PMCID: PMC3836833  PMID: 23567927
Meal replacements; obesity; weight-loss diets; weight maintenance
20.  Association of Comorbidity Burden With Abnormal Cardiac Mechanics: Findings From the HyperGEN Study 
Comorbidities are common in heart failure (HF), and the number of comorbidities has been associated with poor outcomes in HF patients. However, little is known about the effect of multiple comorbidities on cardiac mechanics, which could impact the pathogenesis of HF. We sought to determine the relationship between comorbidity burden and adverse cardiac mechanics.
Methods and Results
We performed speckle‐tracking analysis on echocardiograms from the HyperGEN study (n=2150). Global longitudinal, circumferential, and radial strain, and early diastolic (e') tissue velocities were measured. We evaluated the association between comorbidity number and cardiac mechanics using linear mixed effects models to account for relatedness among subjects. The mean age was 51±14 years, 58% were female, and 47% were African American. Dyslipidemia and hypertension were the most common comorbidities (61% and 58%, respectively). After adjusting for left ventricular (LV) mass index, ejection fraction, and several potential confounders, the number of comorbidities remained associated with all indices of cardiac mechanics except global circumferential strain (eg, β=−0.32 [95% CI −0.44, −0.20] per 1‐unit increase in number of comorbidities for global longitudinal strain; β=−0.16 [95% CI −0.20, −0.11] for e' velocity; P≤0.0001 for both comparisons). Results were similar after excluding participants with abnormal LV geometry (P<0.05 for all comparisons).
Higher comorbidity burden is associated with worse cardiac mechanics, even in the presence of normal LV geometry. The deleterious effect of multiple comorbidities on cardiac mechanics may explain both the high comorbidity burden and adverse outcomes in patients who ultimately develop HF.
PMCID: PMC4309045  PMID: 24780206
cardiac mechanics; comorbidities; echocardiography; risk factors; strain
21.  Breaking the Law of Valgus: the surprising and unexplained prevalence of medial patellofemoral cartilage damage 
Annals of the rheumatic diseases  2012;71(11):1827-1832.
To compare the prevalence of medial and lateral patellofemoral (PF) cartilage damage in three large osteoarthritis (OA) studies and determine the relationship of this damage to varus, neutral, and valgus knee alignment.
In the Boston OA of the Knee (BOKS), Framingham OA (FOA), and Multicenter OA (MOST) studies, MRIs were read for cartilage morphology at the medial and lateral patella and trochlea femoris using Whole-Organ MRI Scores (WORMS). WORMS scores ≥ 2 (any cartilage defect), ≥ 3 (areas of partial thickness loss), ≥ 4 (diffuse partial thickness loss), and ≥ 5 (extensive full thickness loss) were all variously considered as thresholds to identify damage that may indicate OA. Full-limb radiographs were measured for mechanical alignment, and varus (< −2°), neutral (−2° to 2°), and valgus (> 2°) knees were identified.
The prevalence of medial PF cartilage damage exceeded that of lateral damage in all three OA studies and according to nearly every threshold. Only among severely involved knees (WORMS ≥ 4 or ≥ 5) did the prevalence of lateral PF cartilage damage approximate that of medial damage. The high prevalence of medial PF damage persisted in all strata of knee alignment. Even among knees with valgus malalignment, the prevalence of lateral PF cartilage damage equaled or surpassed that of medial PF damage only when the threshold was specific to severely involved knees.
Medial PF cartilage damage is at least as prevalent among older adults as lateral PF cartilage damage.
PMCID: PMC4011177  PMID: 22534825
Osteoarthritis; Knee; Patellofemoral Joint; Prevalence; Articular Cartilage
22.  Duration of Abdominal Obesity Beginning in Young Adulthood and Incident Diabetes Through Middle Age 
Diabetes Care  2013;36(5):1241-1247.
To examine whether the duration of abdominal obesity determined prospectively using measured waist circumference (WC) is associated with the development of new-onset diabetes independent of the degree of abdominal adiposity.
The Coronary Artery Risk Development in Young Adults Study is a multicenter, community-based, longitudinal cohort study of 5,115 white and black adults aged 18–30 years in 1985 to 1986. Years spent abdominally obese were calculated for participants without abdominal obesity (WC >102 cm in men and >88 cm in women) or diabetes at baseline (n = 4,092) and was based upon repeat measurements conducted 2, 5, 7, 10, 15, 20, and 25 years later.
Over 25 years, 392 participants developed incident diabetes. Overall, following adjustment for demographics, family history of diabetes, study center, and time varying WC, energy intake, physical activity, smoking, and alcohol, each additional year of abdominal obesity was associated with a 4% higher risk of developing diabetes [hazard ratio (HR) 1.04 (95% CI 1.02–1.07)]. However, a quadratic model best represented the data. HRs for 0, 1–5, 6–10, 11–15, 16–20, and >20 years of abdominal obesity were 1.00 (referent), 2.06 (1.43–2.98), 3.45 (2.28–5.22), 3.43 (2.28–5.22), 2.80 (1.73–4.54), and 2.91 (1.60–5.29), respectively; P-quadratic < 0.001.
Longer duration of abdominal obesity was associated with substantially higher risk for diabetes independent of the degree of abdominal adiposity. Preventing or at least delaying the onset of abdominal obesity in young adulthood may lower the risk of developing diabetes through middle age.
PMCID: PMC3631861  PMID: 23248193
23.  Walking to meet physical activity guidelines in knee osteoarthritis: Is 10,000 steps enough? 
To study if step goals (e.g. walking 10,000 steps/day) approximate meeting 2008 Physical Activity Guidelines for Americans among adults with or at high risk of knee OA.
Cross-sectional observational cohort
People with or at high risk of knee OA
Main Outcome Measures
Objective physical activity data were collected over 7 consecutive days from people with or at high risk of knee (OA) participating in the Multicenter Osteoarthritis Study. Using activity monitor data, we determined the proportion that 1) walked ≥10,000 steps/day, 2) met the 2008 Physical Activity Guidelines, and 3) achieved both recommendations.
Of 1788 subjects studied (age 67 ± 8 yrs, BMI 31 ± 6 kg/m2, 60% women), 16.7% of men and 12.6% of women walked ≥10,000 steps/day, while 6% of men and 5% of women met the 2008 Physical Activity Guidelines for Americans. Of those walking ≥10,000 steps/day, 16.7% and 26.7% of men and women also met the 2008 Physical Activity Guidelines.
Among this sample of older adults with or at high risk of knee OA, walking ≥10,000 steps/day did not translate into meeting public health guidelines. These findings highlight the disparity between number of steps/day believed to be needed and recommended time-intensity guidelines to achieve positive health benefits.
PMCID: PMC3608824  PMID: 23228625
Physical Activity; knee osteoarthritis; pedometer; Public Health Guidelines; Walking
24.  History of Gestational Diabetes Mellitus and Future Risk of Atherosclerosis in Mid‐life: The Coronary Artery Risk Development in Young Adults Study 
History of gestational diabetes mellitus (GDM) increases lifetime risk of type 2 diabetes (DM) and the metabolic syndrome (MetS), which increase risk of cardiovascular disease. It is unclear, however, whether GDM increases risk of early atherosclerosis independent of pre‐pregnancy obesity and subsequent metabolic disease.
Methods and Results
Of 2787 women (18 to 30 years) enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study, we studied 898 (47% black) who were free of DM and heart disease at baseline (1985‐1986), delivered ≥1 post‐baseline births, reported GDM history, and had common carotid intima media thickness (ccIMT, mm) measured in 2005‐2006. We used multivariable linear regression to assess associations between GDM and ccIMT adjusted for race, age, parity, and pre‐pregnancy cardiometabolic risk factors. We assessed mediators (weight gain, insulin resistance, blood pressure), and effect modification by incident DM or MetS during the 20‐year period. Of the 898 women, 119 (13%) reported GDM (7.6 per 100 deliveries). Average age was 31 at last birth and 44 at ccIMT measurement for GDM and non‐GDM groups. Unadjusted mean ccIMT was 0.023 mm higher for GDM than non‐GDM groups (P=0.029), but pre‐pregnancy BMI attenuated the difference to 0.016 mm (P=0.109). In 777 women without subsequent DM or the MetS, mean ccIMT was 0.023 mm higher for GDM versus non‐GDM groups controlling for race, age, parity, and pre‐pregnancy BMI (0.784 versus 0.761, P=0.039). Addition of pre‐pregnancy insulin resistance index had minimal impact on adjusted mean net ccIMT difference (0.22 mm). Mean ccIMT did not differ by GDM status among 121 women who developed DM or the MetS (P=0.58).
History of GDM may be a marker for early atherosclerosis independent of pre‐pregnancy obesity among women who have not developed type 2 diabetes or the metabolic syndrome.
PMCID: PMC4187501  PMID: 24622610
atherosclerosis; gestational diabetes mellitus; pregnancy; prospective cohort studies; women
To assess the diagnostic performance of signal changes in Hoffa's fat pad (HFP) assessed on non-contrast-enhanced (CE) MRI in detecting synovitis, and the association of pain with signal changes in Hoffa’s fat pad on non-CE MRI and peripatellar synovial thickness on CE MRI.
The Multicenter Osteoarthritis (MOST) Study is an observational study of individuals who have or are at high risk for knee OA. All subjects with available non-CE and CE MRIs were included. Signal changes in HFP were scored from 0 to 3 in 2 regions using non-CE MRI. Synovial thickness was scored from 0 to 2 on CE MRI in 5 peripatellar regions. Sensitivity, specificity and accuracy of HFP signal changes were calculated considering synovial thickness on CE MRI as the reference standard. We used logistic regression to assess the associations of HFP changes (non-CE MRI) and synovial thickness (CE MRI) with pain from walking up or down stairs, after adjusting for potential confounders.
A total of 393 subjects were included. Sensitivity of infrapatellar and intercondylar signal changes in HFP was high (71% and 88%), but specificity was low (55% and 30%). No significant associations were found between HFP changes on non-CE MRI and pain. Grade 2 synovial thickness assessed on CE MRI was significantly associated with pain after adjustments for potential confounders.
Signal changes in HFP detected on non-CE MRI are a sensitive but non-specific surrogate for the assessment of synovitis. CE MRI identifies associations with pain better than non-CE MRI.
PMCID: PMC3578385  PMID: 23277189
Knee osteoarthritis; synovitis; magnetic resonance imaging; knee pain

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