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1.  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
2.  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
3.  Blood Pressure and the Risk of Developing Diabetes in African Americans and Whites 
Diabetes Care  2011;34(4):873-879.
We examined the association between high blood pressure and incident type 2 diabetes in African Americans and whites aged 35–54 years at baseline.
We combined data from the Atherosclerosis Risk in Communities (ARIC) study, the Coronary Artery Risk Development in Young Adults (CARDIA) study, and the Framingham Heart Study offspring cohort. Overall, 10,893 participants (57% women; 23% African American) were categorized by baseline blood pressure (normal, prehypertension, hypertension) and examined for incident diabetes (median follow-up 8.9 years).
Overall, 14.6% of African Americans and 7.9% of whites developed diabetes. Age-adjusted incidence was increasingly higher across increasing blood pressure groups (P values for trend: <0.05 for African American men; <0.001 for other race-sex groups). After adjustment for age, sex, BMI, fasting glucose, HDL cholesterol, and triglycerides, prehypertension or hypertension (compared with normal blood pressure) was associated with greater risks of diabetes in whites (hazard ratio [HR] for prehypertension: 1.32 [95% CI 1.09–1.61]; for hypertension: 1.25 [1.03–1.53]), but not African Americans (HR for prehypertension: 0.86 [0.63–1.17]; for hypertension: 0.92 [0.70–1.21]). HRs for developing diabetes among normotensive, prehypertensive, and hypertensive African Americans versus normotensive whites were: 2.75, 2.28, and 2.36, respectively (P values <0.001).
In African Americans, higher diabetes incidence among hypertensive individuals may be explained by BMI, fasting glucose, triglyceride, and HDL cholesterol. In whites, prehypertension and hypertension are associated with greater risk of diabetes, beyond that explained by other risk factors. African Americans, regardless of blood pressure, have greater risks of developing diabetes than whites.
PMCID: PMC3064044  PMID: 21346180
4.  Segment-Specific Associations of Carotid IMT with Cardiovascular Risk Factors: The Coronary Artery Risk Development in Young Adults (CARDIA) Study 
Background and Purpose
We propose to study possible differences in the associations between risk factors for cardiovascular disease (myocardial infarction and stroke) and Carotid Intima-Media thickness (IMT) measurements made at three different levels of the carotid bifurcation. Methods: Cross-sectional study of a cohort of Whites and African Americans of both genders with mean age 45 years. Traditional cardiovascular risk factors were determined in cohort members. Carotid IMT was measured from high-resolution B-mode ultrasound images at three levels: the common carotid artery (CCA), the carotid artery bulb (Bulb) and the internal carotid artery (ICA). Associations with risk factors were evaluated by multivariate linear regression analyses.
Of 3258 who underwent carotid IMT measurements, CCA, Bulb, and ICA IMT were measured at all three separate levels in 3023 (92.7%). A large proportion of the variability of CCA IMT was explained by cardiovascular risk factors (26.8%) but less so for the Bulb (11.2%) and ICA (8.0%). Carotid IMT was consistently associated with age, LDL-cholesterol, smoking and hypertension in all segments. Associations with fasting glucose and diastolic blood pressure were stronger for CCA than for the other segments. Hypertension, diabetes and current smoking had qualitatively stronger associations with Bulb IMT, and LDL cholesterol with ICA IMT. Conclusion: In our cohort of relatively young white and African-American men and women, a greater proportion of the variability in common carotid IMT can be explained by traditional cardiovascular risk factors than for the carotid artery bulb and internal carotid arteries.
PMCID: PMC3163306  PMID: 19910544
Carotid Intimal Medial Thickness; Risk Factors; Carotid Ultrasound
5.  Lactation and Changes in Maternal Metabolic Risk Factors 
Obstetrics and gynecology  2007;109(3):729-738.
To examine the relationship between duration of lactation and changes in maternal metabolic risk factors.
This 3-year prospective study examined changes in metabolic risk factors among lactating women from preconception to postweaning and among nonlactating women from preconception to postdelivery, in comparison with nongravid women. Of 1,051 (490 black, 561 white) women who attended two consecutive study visits in years 7 (1992–1993) and 10 (1995–1996), 942 were nongravid and 109 had one interim birth. Of parous women, 48 (45%) did not lactate, and 61 (55%) lactated and weaned before year 10. The lactated and weaned women were subdivided by duration of lactation into less than 3 months and 3 months or more. Multiple linear regression models estimated mean 3-year changes in metabolic risk factors adjusted for age, race, parity, education, and behavioral covariates.
Both parous women who did not lactate and parous women who lactated and weaned gained more weight (+5.6, +4.4 kg) and waist girth (+5.3, +4.9 cm) than nongravid women over the 3-year interval; P<.001. Low-density lipoprotein cholesterol (+6.7 mg/dL, P<.05) and fasting insulin (+2.6 microunits, P= .06) increased more for parous women who did not lactate than for nongravid and parous women who lactated and weaned. High-density lipoprotein cholesterol decrements for both parous women who did not lactate and parous women who lactated and weaned were 4.0 mg/dL greater than for nongravid women (P<.001). Among parous, lactated and weaned women, lactation for 3 months or longer was associated with a smaller decrement in high-density lipoprotein cholesterol (−1.3 mg/dL versus −7.3 mg/dL for less than 3 months; P<.01).
Lactation may attenuate unfavorable metabolic risk factor changes that occur with pregnancy, with effects apparent after weaning. As a modifiable behavior, lactation may affect women’s future risk of cardiovascular and metabolic diseases.
PMCID: PMC2930880  PMID: 17329527
6.  Long-Term Blood Pressure Changes Measured From Before to After Pregnancy Relative to Nonparous Women 
Obstetrics and gynecology  2008;112(6):1294-1302.
To prospectively examine whether blood pressure changes persist after pregnancy among women of reproductive age.
Prospective, population-based, observational cohort of 2,304 (1,167 black, 1,137 white) women (aged 18–30) who were free of hypertension at baseline (1985–86) and reexamined up to six times at 2, 5, 7, 10, or 20 years later (2005–2006). We obtained standardized blood pressure measurements before and after pregnancies, and categorized women into time-dependent groups by the cumulative number of births since baseline within each time interval [0 births (referent); 1 interim birth and 2 or more interim births; non-hypertensive pregnancies]. The study assessed differences in systolic and diastolic blood pressures among interim birth groups using multivarible, repeated measures linear regression models stratified by baseline parity (nulliparous and parous) adjusted for time, age, race, baseline covariates (blood pressure, BMI, education, oral contraceptive use), and follow-up covariates (smoking, anti-hypertensive medications, oral contraceptive use, weight gain).
Among nulliparas at baseline, mean (95%CI) fully adjusted systolic and diastolic blood pressures (mm Hg), respectively, were lower by −2.06 (−2.72 to −1.41) and −1.50 (−2.08 to −0.92) after one interim birth, and lower by −1.89 (−2.63 to −1.15) and −1.29 (−1.96 to −0.63) after 2 or more interim births compared with no births (all p-value <0.001). Among women already parous at baseline, adjusted mean blood pressure changes did not differ by number of subsequent births.
A first birth is accompanied by persistent lowering of blood pressure from preconception to years after delivery. Although the biologic mechanism is unclear, pregnancy may create enduring alterations in vascular endothelial function.
PMCID: PMC2930887  PMID: 19037039
7.  Longitudinal Association of PCSK9 Sequence Variations with LDL-Cholesterol Levels: The Coronary Artery Risk Development in Young Adults (CARDIA) Study 
Mutations of PCSK9 are associated cross-sectionally with plasma LDL cholesterol (LDL-C) levels, but, little is known about their longitudinal association with LDL-C levels from young adulthood to middle age.
Methods and Results
We investigated the associations of 6 PCSK9 variants with LDL-C over 20 years in 1750 African Americans and 1828 whites from the CARDIA study. Generalized estimating equations were used to assess longitudinal differences in LDL-C levels between genotype categories. For African Americans, LDL-C levels at age 18 were significantly lower (p<0.001) among those with 3 genetic variants (L253F, C679X, and Y142X; 81.5 mg/dL) and A443T (95.5 mg/dL) compared with non-carriers (109.6 mg/dL). The difference in LDL-C levels from non-carriers tended to widen for those with the 3 variants only, by 0.24 mg/dl per year of age (p=0.14). For whites with the R46L variant, compared with non-carriers, LDL-C levels at age 18 were significantly lower (84.4 vs 100.9 mg/dL, p<0.001), and the increase in LDL-C with age was similar to non-carriers. The 3 genetic variants and the A443T variant in African American men were associated with lower carotid intima-media thickness and lower prevalence of coronary calcification measured at ages 38~50.
Our results suggest that participants with several genetic variants of PCSK9 have persistently lower serum LDL-C levels than non-carriers from ages 18–50. Such long-term reduction in LDL-C levels is associated with reduced subclinical atherosclerosis burden in African-American men.
PMCID: PMC2810147  PMID: 20031607
PCSK9; LDL-C; genetic variant; longitudinal study
8.  The Relation Between Body Size Perception and Change in Body Mass Index Over 13 Years 
American Journal of Epidemiology  2009;169(7):857-866.
The authors assessed associations of body size perception and weight change over 13 years in black men and women and white men and women from the Coronary Artery Risk Development in Young Adults (CARDIA) Study (1992–2005). The perceptions of self and ideal body size were measured by using the Stunkard 9-figure scale at the year 7 examination (1992–1993). Figures were classified into underweight, normal weight, overweight, and obese. Self-ideal discrepancy yielded 4 body size satisfaction categories. Body mass index (BMI) (measured at years 7, 10, 15, and 20) was the dependent variable in gender-specific adjusted multiple regression models stratified by year 7 BMI. Obese women who perceived themselves as obese lost 0.09 BMI units annually, while those who perceived themselves as normal weight gained 0.31 units annually (P = 0.0005); obese women who considered their body size much too large had less annual weight gain than did those who considered their body size a bit too large (0.21 vs. 0.38 BMI units; P = 0.009). Obese women with overweight ideal body size gained less weight annually than did those with normal weight ideal body size (0.12 vs. 0.27 BMI units; P = 0.04). Results for men showed fewer and weaker associations. When obese women perceive themselves as obese and feel that their body size is too large, they gain less weight over time.
PMCID: PMC2727220  PMID: 19221119
body image; body mass index; health status disparities; obesity; psychology; weight gain
9.  Prehypertension During Young Adulthood and Coronary Calcium Later in Life: The Coronary Artery Risk Development in Young Adults Study 
Annals of internal medicine  2008;149(2):91-99.
High blood pressure in middle age is a well-established risk factor for cardiovascular disease, but the consequences of low-level elevations during young adulthood are unknown.
To measure the association between prehypertension exposure before age 35 and coronary calcium later in life
Prospective cohort study
Four U.S. communities
Black and white men and women recruited at age 18–30 for the Coronary Artery Risk Development in Young Adults (CARDIA) Study in 1985–6, and without hypertension before age 35
We estimated blood pressure trajectories for each participant using measurements from 7 examinations over the course of 20 years. Cumulative exposure to blood pressure in the prehypertension range (systolic 120–139 and/or diastolic 80–89 mmHg) from age 20–35 was calculated in units of “mmHg-years” (similar to “pack-years” of tobacco exposure) and related to presence of coronary calcium measured at each participant’s last examination (age 44±4).
Among 3560 participants, the 635 (18%) who developed prehypertension before age 35 were more often black, male, overweight and of lower socioeconomic status. Exposure to prehypertension before age 35, especially systolic prehypertension, showed a graded association with coronary calcium later in life (coronary calcium prevalence 15%, 24% and 38% for 0, 1–30, and >30 mmHg-years of exposure, respectively, p<.001). This association remained strong after adjusting for blood pressure elevation after age 35 and other coronary risk factors and participant characteristics.
Coronary calcium, though a strong predictor of future coronary heart disease, is not a clinical outcome.
Prehypertension during young adulthood is common and associated with coronary atherosclerosis 20 years later. Keeping systolic pressure below 120 mmHg before age 35 may provide important health benefits later in life.
PMCID: PMC2587255  PMID: 18626048

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