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.

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.

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.

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.

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.

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.

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.