Background

Cross-sectional analyses suggest that total and low-density lipoprotein cholesterol (LDL-c) trends that had been declining are now reversing. We examined longitudinal data from the Coronary Artery Risk Development in Young Adults (CARDIA) study to examine secular trends in total cholesterol, LDL-c, high-density lipoprotein cholesterol (HDL-c), and triglycerides over 25 years. We also assessed whether modifiable lifestyle factors (body mass index, physical activity, alcohol consumption, smoking, and lipid-lowering medications) are associated with these trends.

Methods and results

CARDIA recruited 5115 black and white men and women ages 18 to 30 years from 4 US communities in 1985-1986, and re-examined them 5, 10, 15, 20, and 25 years later. Secular trends, modeled as age-matched time trends, were estimated using repeated-measures regression stratified on race and sex. Total cholesterol and LDL-c initially decreased ≈5 to 8 mg/dL between visits before plateauing and moving toward adverse trends in all groups, except black women, by year 25. HDL-c showed an upward secular trend of 1 to 3 mg/dL between visits starting at year 15 in all groups; triglyceride trends were largely flat. Obesity and use of lipid-lowering medications, which both increased over follow-up, had strong independent, but opposite, associations with lipid trends over time. In aggregate, associations of modifiable lifestyle factors counterbalanced one another, minimally influencing secular trends.

Conclusions

Over 25 years, initially favorable trends in total cholesterol and LDL-c have leveled off and may be reversing, persisting after control for modifiable risk factors. Factors such as dietary changes over 25 years and poor adherence to medications are candidates for additional investigation.

Background

Higher levels of intra-abdominal adipose tissue (IAAT) comprising visceral adipose tissue (VAT), intermuscular adipose tissue (IMAT), and liver fat are posited drivers of obesity-related chronic disease risk. Fast food is hypothesized to contribute to IAAT patterns.

Objectives

We quantified levels of abdominal subcutaneous adipose tissue (SAT), IAAT, and odds of metabolic-associated fatty liver disease (MAFLD) in middle age according to average fast-food intake over the preceding 25 y.

Methods

We analyzed data from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants underwent 6 clinical exams and measurements over 25 y with computed tomography-measured VAT, SAT, and IMAT (n = 3156), plus MAFLD defined by liver attenuation (≤40 Hounsfield units) and 1 metabolic abnormality at year 25 (2010, n = 3001, n cases = 302). We estimated means of VAT, SAT, IMAT, and liver attenuation at the year 25 exam according to categories of average fast-food intake over the previous 25 y adjusted for sociodemographic and lifestyle factors and logistic regression to estimate the odds ratio of MAFLD at year 25.

Results

With higher average fast-food intake over 25 y (categorized as follows: never-1×/mo, >1×-3×/mo, 1-<2×/wk, 2-<3×/wk, ≥3×/wk), there were monotonic higher levels of VAT (98.5, 127.6, 134.5, 142.0, 145.5 cm3), P-trend < 0.0001, which were consistent across anthropometrically classified obesity categories. There was a similar pattern with liver fat. There were higher levels of IMAT and SAT with higher fast-food intake (P-trend = 0.003, 0.0002, respectively), with amounts leveling off at ≥2×/wk. In addition, compared with participants who ate fast food never-1×/mo, there were monotonic higher odds of having MAFLD at year 25 with higher average fast-food intake, with participants who ate fast food ≥3×/wk having an OR of MAFLD = 5.18 (95% CI: 2.87, 9.37).

Conclusions

There were monotonic higher levels of VAT, liver fat, and odds of having MAFLD in middle age according to higher average fast-food intake over the preceding 25 y.

Objectives

Substantial evidence associates persistent organic pollutants (POP) with metabolic disturbances related to diabetes, but longitudinal studies with repeated measures are scarce. We aimed to characterize the association between background exposures to POPs with repeated measures of glucose homeostasis over 23-years.

Methods

Within the Coronary Artery Risk Development in Young Adults study (year 0 ages: 18-30 years), we measured POPs in serum obtained in 1987-88 (follow-up year 2) in 90 non-diabetic controls and 90 cases diabetes-free at year 2 who became diabetic by year 20. We analyzed 32 POPs detectable in ≥75% of participants and created summary scores for 32 POPs, 23 polychlorinated biphenyls (PCB), and 8 organochlorine pesticides (OCP). Dependent variables were measures of glucose homeostasis at years 0-25 (up to 8 examinations). We explored associations using repeated measures regression adjusted for race, sex, concurrent body mass index (BMI), examination center and period, separately for cases and controls.

Results

The associations between the three summary scores and measures of glucose homeostasis were present for observations at ages 40-55 years, and particularly between 48-55 years: the 23 PCB summary was associated with HbA1c (never-diabetics: slope [value per unit of summary score], β=0.008, p=0.02; diabetics: β=0.03, p=0.07), fasting glucose (never-diabetics: β=0.24, p=0.003; diabetics: β=1.10, p=0.03), and insulin sensitivity% (never-diabetics: β=-2.82, p<0.001, diabetics: β=-0.31, p=0.30). No associations were observed at younger ages.

Conclusions

Glucose homeostasis may worsen after decades of exposure to PCBs and OCPs at background environmental levels, independent of BMI and after participants reached the 5th decade of life.

Background

Although microvascular dysfunction is known to result from diabetes, it might also lead to diabetes. Lower values of C2, a derivative of the radial artery pressure waveform, indicate microvascular dysfunction and predict hypertension and cardiovascular disease (CVD). We studied the association of C2 with incident diabetes in subjects free of overt CVD.

Methods

Among multi-ethnic participants (n = 5214), aged 45-84 years with no diabetes, C2 was derived from the radial artery pressure waveform. Incident diabetes (N = 651) was diagnosed as new fasting glucose ≥ 126 mg/dL or antidiabetic medicine over ~ 10 years. The relative incidence density (RID) for incident diabetes per standard deviation (SD) of C2 was studied during ~ 10 years follow-up using four levels of adjustment.

Results

Mean C2 at baseline was 4.58 ± 2.85 mL/mmHg × 100. The RID for incident diabetes per SD of C2 was 0.90 (95% CI 0.82-0.99, P = 0.03). After adjustment for demographics plus body size, the corresponding RID was 0.81 (95% CI 0.73-0.89, P < 0.0001); body mass index (BMI) was the dominant covariate here. After adjustment for demographics plus cardiovascular risk factors, the RID was 0.98 (95% CI 0.89, 1.07, P = 0.63). After adjustment for all the parameters in the previous models, the RID was 0.87 (95% CI 0.78, 0.96, P = 0.006).

Conclusions

In a multi-ethnic sample free of overt CVD and diabetes at baseline, C2 predicted incident diabetes after adjustment for demographics, BMI and CVD risk factors. Differences in arterial blood pressure wave morphology may indicate a long-term risk trajectory for diabetes, independently of body size and the classical risk factors.

Conflicting results have been reported concerning a relationship between smoking and serum PTH. Our study objective was to examine whether smoking was associated with serum PTH independent of correlates of PTH among young adults, and explore potential mechanisms. This was a cross-sectional study of healthy individuals, 24-36 years old, examined during 1992 through 1993 in California, USA (a subset of Coronary Artery Risk Development in Young Adults study). Linear regression was used to obtain adjusted means of PTH according to smoking habit (current, former, never). Biomarkers for calcium metabolism and bone turnover (including serum concentrations of osteocalcin, bone-specific alkaline phosphatase, and 24-hour urinary excretion of calcium) and bone mineral density were similarly compared by smoking. 376 participants were analyzed (171 women, 181 black). Over half reported never smoking. We observed lower PTH in current smokers compared to non-smokers and found no evidence of an interaction by race and sex. PTH was lowest in current smokers, intermediate in former smokers, and highest in never smokers (geometric mean PTH: 23.6, 26.7, 27.4 pg/mL, respectively: P for trend, 0.006) after adjusting for potential confounders including calcium intake. Among the biomarkers, serum osteocalcin concentration and 24-hour urinary excretion of calcium were lowest in current smokers. We observed no smoking-related difference in bone mineral density. In this community-based sample of young adult men and women, smoking was associated with significantly lower PTH concentration. The mechanism and clinical implication of the finding, however, remains uncertain.

The purpose of this study was to investigate whether long-term television viewing patterns, a common sedentary behavior, in early to mid-adulthood is associated with gray matter brain volume in midlife and if this is independent of physical activity. We evaluated 599 participants (51% female, 44% black, mean age 30.3 ± 3.5 at baseline and 50.2 ± 3.5 years at follow-up and MRI) from the prospective Coronary Artery Risk Development in Young Adults (CARDIA) study. We assessed television patterns with repeated interviewer-administered questionnaire spanning 20 years. Structural MRI (3T) measures of frontal cortex, entorhinal cortex, hippocampal, and total gray matter volumes were assessed at midlife. Over the 20 years, participants reported viewing an average of 2.5 ± 1.7 h of television per day (range: 0-10 h). After multivariable adjustment, greater television viewing was negatively associated with gray matter volume in the frontal (β = - 0.77; p = 0.01) and entorhinal cortex (β = - 23.83; p = 0.05) as well as total gray matter (β = - 2.09; p = 0.003) but not hippocampus. These results remained unchanged after additional adjustment for physical activity. For each one standard deviation increase in television viewing, the difference in gray matter volume z-score was approximately 0.06 less for each of the three regions (p < 0.05). Among middle-aged adults, greater television viewing in early to mid-adulthood was associated with lower gray matter volume. Sedentariness or other facets of television viewing may be important for brain aging even in middle age.

Background

Exposures to cholinesterase inhibitor pesticides (e.g. organophosphates) have been associated with children's neurobehavioral alterations, including attention deficit and impulsivity. Animal studies have observed transient alterations in neurobehavioral performance in relation to cholinesterase inhibitor pesticide exposures; however, limited evidence exists regarding transient effects in humans.

Methods

We estimated the associations between neurobehavioral performance and time after Mother's Day flower harvest (the end of a heightened pesticide usage period) among 308 4-to 9-year-old children living in floricultural communities in Ecuador in 2008 who participated in the ESPINA study. Children's neurobehavior was examined once (NEPSY-II: 11 subtests covering 5 domains), between 63 and 100days (SD: 10.8days) after Mother's Day harvest (blood acetylcholinesterase activity levels can take 82days to normalize after irreversible inhibition with organophosphates).

Results

The mean (SD) neurobehavioral scaled scores across domains ranged from 6.6 (2.4) to 9.9 (3.3); higher values reflect greater performance. Children examined sooner after Mother's Day had lower neurobehavioral scores than children examined later, in the domains of (score difference per 10.8days, 95%CI): Attention/Inhibitory Control (0.38, 0.10-0.65), Visuospatial Processing (0.60, 0.25-0.95) and Sensorimotor (0.43, 0.10-0.77). Scores were higher with longer time post-harvest among girls (vs. boys) in Attention/Inhibitory Control.

Conclusions

Our findings, although cross-sectional, are among the first in non-worker children to suggest that a peak pesticide use period may transiently affect neurobehavioral performance, as children examined sooner after the flower harvest had lower neurobehavioral performance than children examined later. Studies assessing pre- and post-exposure measures are needed.

Background

Organophosphate exposures can affect children's neurodevelopment, possibly due to neurotoxicity induced by acetylcholinesterase (AChE) inhibition, and may affect boys more than girls. We tested the hypothesis that lower AChE activity is associated with lower neurobehavioral development among children living in Ecuadorian floricultural communities.

Methods

In 2008, we examined 307 children (age: 4-9 years; 52% male) and quantified AChE activity and neurodevelopment in 5 domains: attention/executive functioning, language, memory/learning, visuospatial processing, and sensorimotor (NEPSY-II test). Associations were adjusted for demographic and socioeconomic characteristics and height-for-age, flower worker cohabitation, and hemoglobin concentration.

Results

Mean ± standard deviation AChE activity was 3.14 ± 0.49 U/mL (similar for both genders). The range of scores among neurodevelopment subtests was 5.9 to 10.7 U (standard deviation: 2.6-4.9 U). Girls had a greater mean attention/executive functioning domain score than boys. In boys only, there were increased odds ratios of low (<9th percentile) neurodevelopment among those in the lowest tertile versus the highest tertile of AChE activity (odds ratios: total neurodevelopment: 5.14 [95% confidence interval (CI): 0.84 to 31.48]; attention/executive functioning domain: 4.55 [95% CI: 1.19 to 17.38], memory/learning domain: 6.03 [95% CI: 1.17 to 31.05]) after adjustment for socioeconomic and demographic factors, height-for-age, and hemoglobin. Within these domains, attention, inhibition and long-term memory subtests were most affected.

Conclusions

Low AChE activity was associated with deficits in neurodevelopment, particularly in attention, inhibition, and memory in boys but not in girls. These critical cognitive skills affect learning and academic performance. Added precautions regarding secondary occupational pesticide exposure would be prudent.

Background and purpose

The relationship between carotid artery intima-media thickness (IMT) and cognitive function in midlife remains relatively unexplored. We examined the association between IMT and cognitive function in a middle-aged epidemiological cohort of 2618 stroke-free participants.

Methods

At the year 20 visit (our study baseline), participants from the Coronary Artery Risk Development in Young Adults study had IMT measured by ultrasound at the common carotid artery. Five years later, participants completed a cognitive battery consisting of the Rey Auditory-Verbal Learning Test of verbal memory, the Digit Symbol Substitution Test of processing speed, and the Stroop test of executive function. We transformed cognitive scores into standardized z scores, with negative values indicating worse performance.

Results

Mean age at baseline was 45.3 years (SD, 3.6). Greater IMT (per 1 SD difference of 0.12 mm) was significantly associated with worse performance on all cognitive tests (z scores) in unadjusted linear regression models (verbal memory, -0.16; 95% confidence interval [CI], -0.20 to -0.13; processing speed, -0.23; 95% CI, -0.27 to -0.19; and executive function, -0.17; 95% CI, -0.20 to -0.13). In models adjusted for sociodemographics and vascular risk factors that lie earlier in the causal pathway, greater IMT remained negatively associated with processing speed (-0.06; 95% CI, -0.09 to -0.02; P, 0.003) and borderline associated with executive function (-0.03; 95% CI, -0.07 to 0.00; P, 0.07) but not with verbal memory.

Conclusions

We observed an association between greater IMT and worse processing speed-a key component of cognitive functioning-at middle age above and beyond traditional vascular risk factors. Efforts targeted at preventing early stages of atherosclerosis may modify the course of cognitive aging.

Purpose

We examined whether sedentary lifestyle habits and physical activity level are associated with abdominal visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), intermuscular adipose tissue (IMAT), and liver attenuation, independently of one another and potential confounders.

Methods

This study analyzed 3010 African American and Caucasian men and women, 42-59 yr old, from the Coronary Artery Risk Development in Young Adults (CARDIA) study, who completed multiple-slice abdominal computed tomography in 2010-2011. Participants reported average hours per day sitting (television, computing, paperwork, music, telephone, and car). Physical activity was assessed with the CARDIA physical activity history. VAT, SAT, IMAT, and liver attenuation were estimated from computed tomography. Multivariable general linear regression models regressed means of fat depots on total sedentary time, task-specific sedentary time, and total physical activity.

Results

Television viewing was positively, and physical activity inversely, associated with fat depots. For each 1 SD increment in television viewing (1.5 h·d), VAT, SAT, and IMAT were greater by 3.5, 3.4, and 3.9 cm, respectively (P < 0.03 for all). For each 1 SD increment in physical activity (275 exercise units), VAT, SAT, and IMAT were lower by 7.6, 6.7, and 8.1 cm, respectively, and liver attenuation was greater (indicating more liver fat) by 0.5 Hounsfield units (P < 0.01 for all). Total sedentary time was associated with VAT, IMAT, and liver attenuation in White men only after controlling for physical activity, SAT, and other potential confounders (P ≤ 0.01 for all). No other task-specific sedentary behaviors were associated with fat depots.

Conclusions

Sedentary behaviors, particularly television viewing, and physical activity levels have distinct, independent associations with fat deposition.