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1.  13-Year Long-Term Associations between Changes in Traditional Cardiovascular Risk Factors and Changes in Fibrinogen Levels: The Coronary Artery Risk Development in Young Adults (CARDIA) Study 
Atherosclerosis  2012;226(1):214-219.
Objective
Cross-sectional and prospective studies have linked cardiovascular events and traditional risk factors (TRFs) with higher plasma fibrinogen levels. In a young cohort, we sought to determine longitudinal associations between changes in/development of TRFs and fibrinogen levels over 13 years.
Methods
We included 2525 adults from the CARDIA study, aged 25-37 with fibrinogen and TRFs measured at year 7 (study baseline; 1992-1993); and year 20 (follow-up). Multiple linear regressions were used to compare mean changes in fibrinogen to TRFs.
Results
Mean fibrinogen increased by 71mg/dL vs. 70mg/dL (p=NS) in black vs. white men, and 78mg/dL vs. 68mg/dL (p<0.05) in black vs. white women, respectively over 13 years. After multivariable adjustments, fibrinogen generally rose with increasing BMI (p<0.001; all sex/race groups), LDL-cholesterol, log triglycerides and diastolic blood pressure; and fell with increasing HDL-cholesterol and physical activity. 13-year increase in fibrinogen for persons who quit smoking or became non-obese were comparable (p=NS) to that of never-smokers and never-obese persons.
Conclusions
Among young black and white men and women with few baseline cardiovascular risk factors, fibrinogen tracked longitudinally with changes in TRFs over 13 years through middle-age. There was a strong inverse longitudinal relationship between modifiable risk factors (weight loss/smoking cessation) and 13-year change in fibrinogen. Our study helps provide some insight into the role of fibrinogen as a disease marker in the associations between fibrinogen and CVD.
doi:10.1016/j.atherosclerosis.2012.10.043
PMCID: PMC3529787  PMID: 23177973
Fibrinogen; risk factors; cardiovascular disease prevention; obesity; smoking; sex; race
2.  Relationship of Body Mass Index in Young Adulthood and Health-Related Quality of Life Two Decades Later: The Coronary Artery Risk Development in Young Adults (CARDIA) Study 
International journal of obesity (2005)  2010;35(1):10.1038/ijo.2010.120.
Objective
The expanding overweight and obesity epidemic notwithstanding, little is known about their long-term effect on health-related quality of life (HRQoL). The main objective of this study was to investigate whether overweight (body mass index [BMI] 25–<30 kg/m2) and obese (BMI ≥ 30 kg/m2) young adults have poorer HRQoL 20 years later.
Methods
The authors studied 3014 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a longitudinal, community-dwelling, biracial cohort from four cities. BMI was measured at baseline and 20 years later. HRQoL was assessed via the physical component summary (PCS) and the mental component summary (MCS) scores of the Medical Outcomes Study 12-Item Short Form Health Survey at year 20. Higher PCS or MCS scores indicate better HRQoL.
Results
Mean year 20 PCS score was 52.2 for normal weight participants at baseline, 50.3 for overweight, and 46.4 for obese (P-trend <0.001). This relation persisted after adjustment for baseline demographics, general health, and physical and behavioral risk factors and after further adjustment for 20-year changes in risk factors. No association was observed for MCS scores (P-trend 0.43).
Conclusion
Overweight and obesity in early adulthood are adversely associated with self-reported physical HRQoL, but not mental HRQoL 20 years later.
doi:10.1038/ijo.2010.120
PMCID: PMC3875360  PMID: 20548305
3.  Associations of Non-Invasive Measures of Arterial Compliance and Ankle-Brachial Index: The Multi-Ethnic Study of Atherosclerosis (MESA) 
American journal of hypertension  2012;25(5):535-541.
Background
The association between measures of arterial compliance and peripheral arterial disease (PAD) is unclear. Early changes in arterial wall compliance could be a useful marker of patients at high risk for developing lower extremity atherosclerosis.
Methods
We used linear and logistic regression models on baseline data from 2803 female and 2558 male participants in the Multi-Ethnic Study of Atherosclerosis (MESA) to study associations between tonometry-derived baseline measures of arterial compliance (large artery compliance [C1] and small artery compliance [C2]) and the baseline ankle-brachial index (ABI), as well as change in the ABI over approximately 3 years of follow up.
Results
In cross-sectional analyses, lower C1 and C2 values, indicating poorer arterial compliance, were associated with lower ABI. There were significant linear trends across strata of ABI, especially in C2 which ranged from 3.7ml/mmHg × 100 (95% confidence interval (CI) 3.3 to 4.2) in women with an ABI < 0.90 to 4.2ml/mmHg × 100 (95% CI 4.1 to 4.3 p<0.001) in women with ABI 1.10 - <1.40. Similar significant trends (p<0.001) were seen in men. In prospective analyses, those with the lowest tertile of C2 values at baseline had a greater multivariable-adjusted odds for decline in ABI of ≥ 0.15 over 3 years compared to those with the highest C2 values at baseline (OR 1.80 95% CI 1.23–2.64).
Conclusions
We observed that less compliant arteries were significantly associated with low ABI in cross-sectional analysis and with greater decline in ABI over time.
doi:10.1038/ajh.2012.13
PMCID: PMC3748962  PMID: 22357412
Ankle-Brachial Index; Arterial Compliance; Peripheral Arterial Disease
4.  Long-term change in alcohol-consumption status and variations in fibrinogen levels: the coronary artery risk development in young adults (CARDIA) study 
BMJ Open  2013;3(7):e002944.
Objective
To examine long-term associations between change in alcohol-consumption status and cessation of alcohol use, and fibrinogen levels in a large, young, biracial cohort.
Design
Analysis of covariance models were used to analyse participants within the Coronary Artery Risk Development in Young Adults Study (CARDIA) cohort who had fibrinogen and alcohol use data at year 7 (1992–1993; ages 25–37) and year 20 examinations.
Setting
4 urban US cities.
Patients
2520 men and women within the CARDIA cohort.
Main outcome measures
13-year changes in alcohol use related to changes in fibrinogen.
Results
Over 13 years, mean fibrinogen increased by 71 vs 70 mg/dL (p=NS) in black men (BM) versus white men (WM), and 78 vs 68 mg/dL (p<0.05) in black women (BW) versus white women (WW), respectively. Compared with never-drinkers, there were smaller longitudinal increases in fibrinogen for BM, BW and WW (but a larger increase in WM) who became or stayed drinkers, after multivariable adjustment. For BM, WM and WW, fibrinogen increased the most among persons who quit drinking over 13 years (p<0.001 for WM (fibrinogen increase=86.5 (7.1) (mean (SE))), compared with never-drinkers (fibrinogen increase=53.1 (5.4)).
Conclusions
In this young cohort, compared with the participants who never drank, those who became/stayed drinkers had smaller increases, while those who quit drinking had the highest increase in fibrinogen over 13 years of follow-up. The results provide a novel insight into the mechanism for the established protective effect of moderate alcohol intake on cardiovascular disease outcomes.
doi:10.1136/bmjopen-2013-002944
PMCID: PMC3710982  PMID: 23847267
Epidemiology; Preventive Medicine
5.  Lower Extremity Fat Mass Is Associated With Insulin Resistance in Overweight and Obese Individuals: The CARDIA Study 
Obesity (Silver Spring, Md.)  2011;19(11):2248-2253.
Lower extremity fat mass (LEFM) has been shown to be favorably associated with glucose metabolism. However, it is not clear whether this relationship is similar across varying levels of obesity. We hypothesized that lower amounts of LEFM is associated with higher insulin resistance (IR) and this association may vary according to weight status. Participants with available measures were examined from the Coronary Artery Risk Development in Young Adults study (CARDIA), a multi-center longitudinal study of the etiology of atherosclerosis in black and white men and women aged 38–50 years old in 2005–2006 (n = 1,579). The homeostasis model assessment of IR (HOMAIR) was calculated to estimate IR, regional adiposity was measured using dual energy X-ray absorptiometry (DXA), and weight status was defined according to BMI categories. Obese and overweight participants exhibited higher IR, total fat mass (FM), trunk FM (TFM), and LEFM compared to normal weight participants. After controlling for age, height, race, study center, education, smoking, and cardiorespiratory fitness (CRF), greater LEFM was significantly associated with higher IR only in normal weight men and women. Further adjustment for TFM revealed that lower LEFM was significantly associated with higher IR in overweight and obese men and women and the positive association in normal weight individuals was attenuated. These results suggest that excess adiposity in the lower extremities may attenuate the metabolic risk observed at a given level of abdominal adiposity in overweight and obese individuals. Weight status presents additional complexity since the metabolic influence of adipose tissue may not be homogenous across anatomic regions or level of obesity.
doi:10.1038/oby.2011.113
PMCID: PMC3203327  PMID: 21617639
6.  An Association between Clotting Factor VII and Carotid Intima-Media Thickness: The CARDIA Study 
Purpose
To investigate associations of procoagulants (FVII, FVIII, von Willebrand factor [vWF]) with subclinical atherosclerosis, we examined participants in The Coronary Artery Risk Development in Young Adults (CARDIA) Study.
Methods
Clotting factor assays were performed in 1254 participants ages 23–37 (baseline) and repeated at ages 38–50 (follow-up). Carotid intima-media thickness (IMT) was measured at follow-up.
Results
Baseline levels of procoagulants (%): mean (SD) were: FVII: 76(18), FVIII: 102(38), and vWF: 108(47). At follow-up, all had increased by 40%–55%. After age adjustment, mean common carotid (CC) IMT increased from the lowest to the highest tertile of FVII in the total group (0.787 to 0.801, P=0.007), in whites (0.772 to 0.790, P=0.002), and in men (0.807 to 0.827, P=0.015). All associations were attenuated by multivariable adjustment. However, participants with FVII values in the highest tertile at one or both examinations, as compared with those in the lowest tertile, had greater CC-IMT after age and multivariable adjustment (0.806 versus 0.778, P<0.05). Baseline FVIII was associated with greater internal carotid (IC) IMT in the total group, in whites, and in women after age but not multivariable adjustment. No associations were seen for vWF.
Conclusions
FVII is associated with CC-IMT in young adults, but the strength of the association is modified by other cardiovascular disease risk factors, such as body mass index. FVIII is associated with IC IMT only in age-adjusted analyses, and no associations were observed for vWF.
doi:10.1161/STROKEAHA.110.580100
PMCID: PMC2894290  PMID: 20466994
Factor VII; Carotid Thickening; Atherosclerosis; Factor VIII
7.  PREVALENCE AND PROGRESSION OF SUBCLINICAL ATHEROSCLEROSIS IN YOUNGER ADULTS WITH LOW SHORT-TERM BUT HIGH LIFETIME ESTIMATED RISK FOR CARDIOVASCULAR DISEASE: THE CARDIA AND MESA STUDIES 
Circulation  2009;119(3):382-389.
Background
We hypothesized that individuals with low 10-year but high lifetime cardiovascular disease (CVD) risk would have a greater burden of subclinical atherosclerosis than those with low 10-year but low lifetime risk.
Methods and Results
We included 2988 individuals age ≤50 at exam year 15 from the Coronary Artery Risk Development in Young Adults (CARDIA) study and 1076 individuals age ≤50 at study entry from the Multi-Ethnic Study of Atherosclerosis (MESA). The 10-year risk and lifetime risk for CVD were estimated for each participant, permitting stratification into three groups: low 10-year (<10%)/low lifetime (<39%) risk, low 10-year (<10%)/high lifetime risk (≥39%), and high 10-year risk (≥10%) or diagnosed diabetes. Baseline levels and change in levels of subclinical atherosclerosis (coronary artery calcium [CAC] or carotid intima-media thickness [IMT]) were compared across risk strata. Among participants with low 10-year risk (91% of all participants) in CARDIA, those with a high lifetime risk compared to low lifetime risk had significantly greater common (0.83 vs 0.80 mm in men; 0.79 vs 0.75 mm in women) and internal (0.85 vs 0.80 mm; 0.80 vs 0.76 mm) carotid IMT, higher CAC prevalence (16.6 vs 9.8%; 7.1 vs 2.3%), and significantly greater incidence of CAC progression (22.3 vs 15.4%; 8.7 vs 5.3%). Similar results were observed in MESA.
Conclusions
Individuals with low 10-year but high lifetime risk have a greater subclinical disease burden and greater incidence of atherosclerotic progression compared to individuals with low 10-year and low lifetime risk, even at younger ages.
doi:10.1161/CIRCULATIONAHA.108.800235
PMCID: PMC2836265  PMID: 19139385
epidemiology; risk estimation; prevention
8.  Elevated Fibrinogen Levels and Subsequent Subclinical Atherosclerosis: The CARDIA Study 
Atherosclerosis  2008;202(2):623-631.
Objective
To determine whether elevated levels of hemostatic factors are associated with the subsequent development of subclinical cardiovascular disease.
Methods
Fibrinogen, factors VII (FVII) and VIII (FVIII), and von Willebrand factor (vWF) were measured in 1396 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Coronary artery calcification (CAC) and carotid intimal/medial thickness (CIMT) were determined 13 years later. The adjusted prevalence of CAC and mean CIMT across the quartiles of each hemostatic factor was computed for the total sample and for each race and gender group.
Results
The age, race, and gender-adjusted prevalences of CAC with increasing quartiles of fibrinogen were 14.4%, 15.2%, 20.0%, and 29.1% (p<0.001 for trend). This trend persisted after further adjustment for body mass index (BMI), smoking, educational level, center, systolic blood pressure (BP), diabetes, antihypertensive medication use, total and high density lipoprotein (HDL) cholesterol, and CRP. A similar trend was observed for CIMT (age, race and gender-adjusted, p<0.001; multivariable-adjusted, p=0.014). Further analyses of race and gender subgroups showed that increasing quartiles of fibrinogen were associated with CAC and CIMT in all subgroups except black men. The prevalence of CAC was not associated with increasing quartiles of FVII, FVIII or vWF, suggesting they may be less involved in plaque progression.
Conclusion
An elevated fibrinogen concentration in persons aged 25 to 37 is independently associated with subclinical cardiovascular disease in the subsequent decade.
doi:10.1016/j.atherosclerosis.2008.05.039
PMCID: PMC2662501  PMID: 18602107
hemostatic factors; coronary calcium; carotid thickness; fibrinogen; atherosclerosis
9.  Association of Acculturation Levels and Prevalence of Diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA)  
Diabetes Care  2008;31(8):1621-1628.
OBJECTIVE—The prevalence of type 2 diabetes among Hispanic and Asian Americans is increasing. These groups are largely comprised of immigrants who may be undergoing behavioral and lifestyle changes associated with development of diabetes. We studied the association between acculturation and diabetes in a population sample of 708 Mexican-origin Hispanics, 547 non–Mexican-origin Hispanics, and 737 Chinese participants in the Multi-Ethnic Study of Atherosclerosis (MESA).
RESEARCH DESIGN AND METHODS—Diabetes was defined as fasting glucose ≥126 mg/dl and/or use of antidiabetic medications. An acculturation score was calculated for all participants using nativity, years living in the U.S., and language spoken at home. The score ranged from 0 to 5 (0 = least acculturated and 5 = most acculturated). Relative risk regression was used to estimate the association between acculturation and diabetes.
RESULTS—For non–Mexican-origin Hispanics, the prevalence of diabetes was positively associated with acculturation score, after adjustment for sociodemographics. The prevalence of diabetes was significantly higher among the most acculturated versus the least acculturated non–Mexican-origin Hispanics (prevalence ratio 2.49 [95% CI 1.14−5.44]); the higher the acculturation score is, the higher the prevalence of diabetes (P for trend 0.059). This relationship between acculturation and diabetes was partly attenuated after adjustment for BMI or diet. Diabetes prevalence was not related to acculturation among Chinese or Mexican-origin Hispanics.
CONCLUSIONS—Among non–Mexican-origin Hispanics in MESA, greater acculturation is associated with higher diabetes prevalence. The relation is at least partly mediated by BMI and diet. Acculturation is a factor that should be considered when predictors of diabetes in racial/ethnic groups are examined.
doi:10.2337/dc07-2182
PMCID: PMC2494621  PMID: 18458142
10.  The association of heart rate recovery immediately after exercise with coronary artery calcium: the coronary artery risk development in young adults study 
Clinical Autonomic Research  2007;17(1):46-49.
We tested whether slower heart rate recovery (HRR) following graded exercise treadmill testing (GXT) was associated with the presence of coronary artery calcium (CAC). Participants (n = 2,648) ages 18–30 years at baseline examination underwent GXT, followed by CAC screening 15 years later. Slow HRR was not associated with higher odds of testing positive (yes/no) for CAC at year 15 (OR = 0.99, p = 0.91 per standard deviation change in HRR). Slow HRR in young adulthood is not associated with the presence of CAC at middle age.
doi:10.1007/s10286-006-0391-y
PMCID: PMC1797060  PMID: 17264979
sudden cardiac death; atherosclerosis; heart rate; heart rate recovery; autonomic nervous system; coronary artery calcium
11.  Depressive Symptoms and Lower Extremity Functioning in Men and Women with Peripheral Arterial Disease 
OBJECTIVE
Factors associated with impaired functioning in patients with lower extremity peripheral arterial disease (PAD) are not fully understood. The purpose of this study was to determine the relationship between depressive symptoms and objective measures of lower extremity functioning in persons with PAD.
DESIGN
Cross-sectional.
PATIENTS/PARTICIPANTS
Four hundred twenty-three men and women with PAD identified from 3 Chicago area medical centers.
MEASUREMENTS AND MAIN RESULTS
PAD was defined as ankle brachial index (ABI) <0.90. The Geriatric Depression Scale short form (GDS-S) (0–15 scale, 15 = worst) was completed by all participants. A clinically significant number of depressive symptoms was defined as a GDS-S score ≥6. Six-minute walk distance and usual-and fast-pace walking velocity were determined for all participants. A GDS-S score ≥6 was present in 21.7% of participants with PAD. Adjusting for age, increasing numbers of depressive symptoms were associated with an increasing prevalence of leg pain on exertion and rest (P = .004). Adjusting for age, sex, race, ABI, number of comorbidities, current smoking, and antidepressant medications, increasing numbers of depressive symptoms were associated with shorter 6-minute walk distance (P < .001), slower usual-pace walking velocity (P = .005), and slower fast-pace walking velocity (P = .005). These relationships were attenuated slightly after additional adjustment for presence versus absence of leg pain on exertion and rest and severity of exertional leg symptoms.
CONCLUSIONS
Among men and women with PAD, the prevalence of a clinically significant number of depressive symptoms is high. Greater numbers of depressive symptoms are associated with greater impairment in lower extremity functioning. Further study is needed to determine whether identifying and treating depressive symptoms in PAD is associated with improved lower extremity functioning.
doi:10.1046/j.1525-1497.2003.20527.x
PMCID: PMC1494875  PMID: 12823653
depression; peripheral vascular disease; physical functioning

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