Cholesterol Mass Efflux Capacity, Incident Cardiovascular Disease, and Progression of Carotid Plaque.

Objective- To assess the role of HDL (high-density lipoprotein)-mediated cholesterol mass efflux capacity (CMEC) in incident cardiovascular disease and carotid plaque progression. Approach and Results- We measured CMEC in 2 cohorts aged 45 to 84 years at baseline derived from the MESA (Multi-Ethnic Study of Atherosclerosis). Cohort 1 comprised 465 cases with incident cardiovascular disease events during 10 years of follow-up and 465 age- and sex-matched controls; cohort 2 comprised 407 cases with progression of carotid plaque measured by ultrasonography at 2 exams >10 years and 407 similarly matched controls. Covariates and outcome events were ascertained according to the MESA protocol. CMEC level was modestly correlated with HDL cholesterol ( R=0.13; P<0.001) but was not associated with age, sex, race/ethnicity, body mass index, diabetes mellitus, alcohol use, smoking status, or statin use. Higher CMEC level was significantly associated with lower odds of cardiovascular disease (odds ratio, 0.82 per SD of CMEC [95% CI, 0.69-0.98; P=0.031] in the fully adjusted model) in cohort 1 but higher odds of carotid plaque progression (odds ratio, 1.24 per SD of CMEC [95% CI, 1.04-1.48; P=0.018] in the fully adjusted model) in cohort 2 but without dose-response effect. In subgroup analysis within cohort 1, higher CMEC was associated with lower risk of incident coronary heart disease events (odds ratio, 0.72 per SD of CMEC (95% CI, 0.5-0.91; P=0.007) while no association was found with stroke events. Conclusions- These findings support a role for HDL-mediated cholesterol efflux in an atheroprotective mechanism for coronary heart disease but not stroke.

Job Strain and the Cortisol Diurnal Cycle in MESA: Accounting for Between- and Within-Day Variability.

Evidence of the link between job strain and cortisol levels has been inconsistent. This could be due to failure to account for cortisol variability leading to underestimated standard errors. Our objective was to model the relationship between job strain and the whole cortisol curve, accounting for sources of cortisol variability. Our functional mixed-model approach incorporated all available data-18 samples over 3 days-and uncertainty in estimated relationships. We used employed participants from the Multi-Ethnic Study of Atherosclerosis Stress I Study and data collected between 2002 and 2006. We used propensity score matching on an extensive set of variables to control for sources of confounding. We found that job strain was associated with lower salivary cortisol levels and lower total area under the curve. We found no relationship between job strain and the cortisol awakening response. Our findings differed from those of several previous studies. It is plausible that our results were unique to middle- to older-aged racially, ethnically, and occupationally diverse adults and were therefore not inconsistent with previous research among younger, mostly white samples. However, it is also plausible that previous findings were influenced by residual confounding and failure to propagate uncertainty (i.e., account for the multiple sources of variability) in estimating cortisol features.

Incidence of Age-Related Macular Degeneration in a Multi-Ethnic United States Population: The Multi-Ethnic Study of Atherosclerosis.

PURPOSE: To describe the incidence of age-related macular degeneration (AMD) and associated risk factors in 4 racial/ethnic groups (white, black, Hispanic, and Chinese) residing in the United States. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 3811 participants, aged 46 to 86 years, from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, with retinal data collected twice, on average, 8 years apart. METHODS: Fundus images, taken using a digital camera through dark-adapted pupils using a standard protocol and the same equipment at both study visits, were graded centrally for early and late AMD on the basis of drusen size, type and area, increased retinal pigment, retinal pigment epithelial depigmentation, neovascular lesions, and geographic atrophy using the modified Wisconsin Age-Related Maculopathy Grading System. Demographic, clinical, and laboratory measures were included in multivariable regression models to determine their impact on the variation in AMD incidence among racial/ethnic groups. MAIN OUTCOME MEASURES: Incident early and late AMD. RESULTS: The overall 8-year age- and sex-standardized incidence of early and late AMD were 4.1% and 2.3%, respectively, with incidence of early and late AMD highest in whites (5.3% and 4.1%, respectively), intermediate in Chinese (4.5% and 2.2%, respectively) and Hispanics (3.3% and 0.8%, respectively), and lowest in blacks (1.6% and 0.4%, respectively). By adjusting for age and sex, blacks had a 70% lower risk of developing early AMD than whites, and this decreased only slightly to a 67% lower risk after multivariable adjustment. By adjusting for age, sex, and race/ethnicity, hyperopia was associated with early AMD (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.04-2.20), as was astigmatism (OR, 1.47; 95% CI, 1.00-2.16), but not myopia (P = 0.29). Age, race/ethnicity, current smoking, hyperopia, and AMD-susceptibility genotypes Complement Factor H (CFH) RS1061170 and Age Related Maculopathy Susceptibility 2 (ARMS2) RS3793917 were independently associated with incident early AMD in multivariable models for the combined sample. However, the only statistically significant factor consistently associated with incident early AMD across the 4 racial/ethnic groups was increasing age. Risk factors for late AMD were not assessed because of its low incidence, particularly across racial/ethnic groups. CONCLUSIONS: Variation in the incidence of early AMD exists among racial/ethnic groups in the United States and is not explained by the clinical, genetic, and environmental factors included in this study.

Life course socioeconomic status and longitudinal accumulation of allostatic load in adulthood: multi-ethnic study of atherosclerosis.

OBJECTIVES: We examined the association of childhood and adult socioeconomic status with longitudinal change in allostatic load (AL), a measure of biological dysfunction. METHODS: The study sample included 6135 participants from the Multi-Ethnic Study of Atherosclerosis, aged 45 to 84 years, recruited in 2000 from 6 US counties; 3 follow-up examinations took place through September 2011. We calculated standardized scores for several metabolic and cardiovascular components relative to accepted clinical cut points for "higher risk" and then summed them to create an overall index of AL. We used mixed effects growth curve models to assess the relationship between socioeconomic status and AL as a linear function of time passed since the baseline examination; we included random effects for the intercept and slope. RESULTS: Among those with lower baseline AL (< median), high adult education was associated with a significantly slower increase in AL over time, whereas there was no significant association among those with higher baseline AL. CONCLUSIONS: The relationship between socioeconomic status and patterns of change in health parameters may vary over time and with the accumulation of biological risk.

Social determinants of health and disease in companion dogs: a cohort study from the Dog Aging Project.

Exposure to social environmental adversity is associated with health and survival across many social species, including humans. However, little is known about how these health and mortality effects vary across the lifespan and may be differentially impacted by various components of the environment. Here, we leveraged a relatively new and powerful model for human aging, the companion dog, to investigate which components of the social environment are associated with dog health and how these associations vary across the lifespan. We drew on comprehensive survey data collected on 21,410 dogs from the Dog Aging Project and identified five factors that together explained 33.7% of the variation in a dog's social environment. Factors capturing financial and household adversity were associated with poorer health and lower physical mobility in companion dogs, while factors that captured social support, such as living with other dogs, were associated with better health when controlling for dog age and weight. Notably, the effects of each environmental component were not equal: the effect of social support was 5× stronger than financial factors. The strength of these associations depended on the age of the dog, including a stronger relationship between the owner's age and the dog's health in younger as compared to older dogs. Taken together, these findings suggest the importance of income, stability and owner's age on owner-reported health outcomes in companion dogs and point to potential behavioral and/or environmental modifiers that can be used to promote healthy aging across species.

Lifetime prevalence of malignant and benign tumours in companion dogs: Cross-sectional analysis of Dog Aging Project baseline survey.

Although cancer is widely regarded as a major contributor to canine morbidity and mortality, its frequency in companion dogs has only infrequently been characterised. We analysed cross-sectional data from the baseline survey of owners of 27 541 living companion dogs enrolled in the Dog Aging Project as of 31 December 2020 to estimate the lifetime prevalence of malignant and benign tumours and several potentially-associated characteristics. Survey questions elicited information on history of 'cancer or tumors' including organ site and histologic type. Owners reported 819 malignant tumours (56% sited in the skin, muscle or other soft tissue) and 404 benign tumours (69% sited in the skin, muscle or other soft tissue). The lifetime prevalence of malignant tumours (29.7/1000 dogs) was approximately double the lifetime prevalence of benign tumours (14.7/1000 dogs). Lifetime prevalence of both malignant and benign tumours increased with dog age at survey completion. There were no statistically discernable differences in age-adjusted lifetime prevalence of malignant (prevalence ratio (PR) = 0.93 [95% confidence interval (CI) 0.82, 1.07] or benign tumours (PR = 1.10, 95% CI 0.91, 1.34) in mixed vs. purebred dogs. The lifetime prevalence of malignant tumours increased with increasing dog size class; compared to toy and small dogs, the age-adjusted PRs (95% CIs) for medium, standard, large, and giant dogs were 1.65 (1.28, 2.11), 2.92 (2.35, 3.64), 3.67 (2.92, 4.62) and 2.99 (1.23, 4.02), respectively. Similar though less pronounced patterns in relation to dog size class were observed for benign tumours. Ongoing prospective data collection will permit future studies on risk factors for canine tumour incidence.

Air Pollution and the microvasculature: a cross-sectional assessment of in vivo retinal images in the population-based multi-ethnic study of atherosclerosis (MESA).

BACKGROUND: Long- and short-term exposures to air pollution, especially fine particulate matter (PM(2.5)), have been linked to cardiovascular morbidity and mortality. One hypothesized mechanism for these associations involves microvascular effects. Retinal photography provides a novel, in vivo approach to examine the association of air pollution with changes in the human microvasculature. METHODS AND FINDINGS: Chronic and acute associations between residential air pollution concentrations and retinal vessel diameters, expressed as central retinal arteriolar equivalents (CRAE) and central retinal venular equivalents (CRVE), were examined using digital retinal images taken in Multi-Ethnic Study of Atherosclerosis (MESA) participants between 2002 and 2003. Study participants (46 to 87 years of age) were without clinical cardiovascular disease at the baseline examination (2000-2002). Long-term outdoor concentrations of PM(2.5) were estimated at each participant's home for the 2 years preceding the clinical exam using a spatio-temporal model. Short-term concentrations were assigned using outdoor measurements on the day preceding the clinical exam. Residential proximity to roadways was also used as an indicator of long-term traffic exposures. All associations were examined using linear regression models adjusted for subject-specific age, sex, race/ethnicity, education, income, smoking status, alcohol use, physical activity, body mass index, family history of cardiovascular disease, diabetes status, serum cholesterol, glucose, blood pressure, emphysema, C-reactive protein, medication use, and fellow vessel diameter. Short-term associations were further controlled for weather and seasonality. Among the 4,607 participants with complete data, CRAE were found to be narrower among persons residing in regions with increased long- and short-term levels of PM(2.5). These relationships were observed in a joint exposure model with -0.8 µm (95% confidence interval [CI] -1.1 to -0.5) and -0.4 µm (95% CI -0.8 to 0.1) decreases in CRAE per interquartile increases in long- (3 µg/m(3)) and short-term (9 µg/m(3)) PM(2.5) levels, respectively. These reductions in CRAE are equivalent to 7- and 3-year increases in age in the same cohort. Similarly, living near a major road was also associated with a -0.7 µm decrease (95% CI -1.4 to 0.1) in CRAE. Although the chronic association with CRAE was largely influenced by differences in exposure between cities, this relationship was generally robust to control for city-level covariates and no significant differences were observed between cities. Wider CRVE were associated with living in areas of higher PM(2.5) concentrations, but these findings were less robust and not supported by the presence of consistent acute associations with PM(2.5). CONCLUSIONS: Residing in regions with higher air pollution concentrations and experiencing daily increases in air pollution were each associated with narrower retinal arteriolar diameters in older individuals. These findings support the hypothesis that important vascular phenomena are associated with small increases in short-term or long-term air pollution exposures, even at current exposure levels, and further corroborate reported associations between air pollution and the development and exacerbation of clinical cardiovascular disease. Please see later in the article for the Editors' Summary.

Perceived racial/ethnic discrimination, smoking and alcohol consumption in the Multi-Ethnic Study of Atherosclerosis (MESA).

OBJECTIVE: To examine the association of perceived racial/ethnic discrimination with smoking and alcohol consumption in adults participating in the Multi-Ethnic Study of Atherosclerosis. METHODS: Data on 6680 black, Chinese, Hispanic and white adults aged 45 to 84 years of age recruited from Illinois, New York, Maryland, North Carolina, Minnesota and California during 2000 and 2002 were used for this analysis. Logistic regression was used to estimate the association of perceived racial/ethnic discrimination with smoking status and alcohol consumption for each racial/ethnic group separately. RESULTS: Blacks were more likely to experience racial/ethnic discrimination (43%) than Hispanics (19%), Chinese participants (10%) or whites (4%, P<0.0001). In the fully-adjusted model, blacks reporting racial/ethnic discrimination had 34% and 51% greater odds of reporting smoking and drinking, respectively, than blacks who did not report racial/ethnic discrimination. Hispanics reporting racial/ethnic discrimination had 62% greater odds of heavy drinking. Whites reporting racial/ethnic discrimination had 88% greater odds of reporting being current smokers than whites who did not report racial/ethnic discrimination. CONCLUSIONS: Our findings suggest that the experience of discrimination is associated with greater prevalence of unhealthy behaviors. Specifically, the use of smoking and alcohol may be patterned by experience of discrimination.

Race/ethnicity, neighborhood socioeconomic status and cardio-metabolic risk.

OBJECTIVE: To determine the association between neighborhood socioeconomic status (NSES) and cardio-metabolic risk and whether this relationship differs by race/ethnicity. METHODS: Participants in the Multi-Ethnic Study of Atherosclerosis (n = 5750), ages 45-84 years, from 6 US counties, including 5 examinations from 2000 to 2012. We calculated a modified allostatic load (AL) index, indicating cardio-metabolic risk. NSES score included census-derived measures at census tract of residence. Mixed effects growth curve models were used to assess linear and non-linear associations between NSES and AL at baseline and over time. RESULTS: Higher NSES was associated with lower AL across race/ethnic groups; considering NSES quintiles, significant associations were found only for the highest NSES quintiles (difference of -0.86 and -1.15 for white and Hispanic participants) vs. the lowest. We found no significant association between NSES and change in AL over time. DISCUSSION: Our findings suggest that the relationship between NSES and AL reflects the health benefits of living in the most advantaged neighborhoods. PUBLIC HEALTH IMPLICATIONS: Understanding the impact of higher NSES on health effects may help identify interventions to effectively target high risk neighborhoods.

Association of salivary cortisol circadian pattern with cynical hostility: multi-ethnic study of atherosclerosis.

OBJECTIVE: To determine if cynical hostility is associated with alterations in diurnal profiles of cortisol. Hostility has been linked to cardiovascular disease but the biological mechanisms mediating this association remain unknown. METHODS: Up to 18 measures of salivary cortisol taken over 3 days were obtained from each of 936 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Cynical hostility was measured using an eight-item subscale of the Cook-Medley Hostility Scale. Cortisol profiles were modeled using regression spline models that incorporated random parameters for subject-specific effects. Models were adjusted for race, sex, age, socioeconomic position, and lifestyle factors. The association of cynical hostility with key features of the cortisol diurnal profile, both in the full sample and important subsamples, was examined. RESULTS: Waking cortisol levels as well as the extent of the morning surge in cortisol levels did not differ significantly across tertiles of cynical hostility. Respondents in the lowest tertile of cynical hostility experienced a 22% sharper decline in salivary cortisol (age- and sex-adjusted slope of -0.49 microg/dL per hour) than respondents in the highest tertile (-0.40 microg/dL per hour, p for difference = .0004). Intertertile differences in these parameters remained unaltered after further adjustment for potential confounders. This pattern of differences in cortisol diurnal profile tended to be related in a dose-response way to level of cynical hostility, and persisted in stratified analyses. CONCLUSIONS: Cynical hostility is associated with the declining phase of the awakening cortisol response. The implications of this for cardiovascular and other health outcomes remain to be determined.

Life-course socioeconomic positions and subclinical atherosclerosis in the multi-ethnic study of atherosclerosis.

A major limitation of past work on the social patterning of atherosclerosis has been the reliance on measures of neighborhood or individual-level socioeconomic position (SEP) assessed at a single point in time in adulthood. Risk of chronic disease is thought to accumulate throughout the life-course, so the use of a measure for a single point in time may result in inaccurate estimates of the social patterning of subclinical disease. Using data from the US Multi-Ethnic Study of Atherosclerosis (MESA), we examined the relation between childhood SEP [CSEP] (father or caretaker's education), adulthood SEP [ASEP] (a summary score of income, education, and wealth), and 20-year average exposure to neighborhood poverty [NSEP] (residential addresses geocoded and linked to census data) and the prevalence of subclinical atherosclerosis, as assessed by common carotid intimal-medial thickness (IMT) in mid to late adulthood. Participants were 45-84 years of age at baseline and were sampled from six study sites in the United States. After adjustment for age, CSEP and ASEP were both inversely and independently associated with IMT in men. All three indicators CSEP, ASEP, and NSEP were inversely and independently associated with IMT in women. Associations were somewhat reduced after adjustment for cardiovascular risk factors, suggesting that these factors may play a mediating role. There was evidence of heterogeneity in effects of NSEP by gender, and in the effects of ASEP and NSEP by race/ethnicity. Our results contribute to the growing body of work that shows that SEP at multiple points in the life-course, and at the individual and neighborhood level, contributes to the development of atherosclerosis.

Acculturation is associated with hypertension in a multiethnic sample.

BACKGROUND: Hypertension varies in prevalence among race/ethnic groups in the United States. Within-ethnic group differences associated with acculturation have been less frequently examined. We studied the association of three measures of acculturation (language spoken at home, place of birth, and years living in the US) with hypertension in a population sample of 2619 white, 1898 African American, 1,494 Hispanic, and 803 Chinese participants in the Multiethnic Study of Atherosclerosis. METHODS: Multivariate Poisson regression was used to estimate the association between the acculturation variables and hypertension. RESULTS: Birthplace outside the US and speaking a non-English language at home were each associated with a lower prevalence of hypertension after adjustment for age, gender, and socioeconomic status (prevalence ratio [95% confidence intervals] 0.82 (0.77-0.87) for non-US born versus US born and 0.80 (0.74-0.85) for those not speaking English at home versus speakers of English at home, both P < .001). For participants born outside of the US, each 10-year increment of years in the US was associated with a higher prevalence of hypertension after adjustment for age, gender, and socioeconomic status (P for trend < .01). The associations between acculturation variables and hypertension were weakened after adjustment for race/ethnic category and risk factors for hypertension. Compared to US-born Hispanics, those born in Mexico or South America had lower prevalence of hypertension, but those born in the Caribbean and Central America had higher prevalence of hypertension. CONCLUSIONS: Acculturation and place of birth are associated with hypertension in a multiethnic sample.

Association of Sleep Duration and Quality With Alterations in the Hypothalamic-Pituitary Adrenocortical Axis: The Multi-Ethnic Study of Atherosclerosis (MESA).

CONTEXT: Short sleep duration and poor sleep quality are associated with cardiovascular outcomes. One mechanism proposed to explain this association is altered diurnal cortisol secretion. OBJECTIVE: The objective of the study was to examine the associations of sleep duration and sleep quality with diurnal salivary cortisol levels. DESIGN: This was a cross-sectional analysis using data from examination 5 (2010-2012) of the Multi-Ethnic Study of Atherosclerosis. Actigraphy-based measures of sleep duration and efficiency were collected over 7 days, and salivary cortisol samples were collected over 2 days from participants aged 54-93 years (n = 600 with analyzable data). RESULTS: Shorter average sleep duration (<6 h/night) was associated with less pronounced late decline in cortisol [2.2% difference in slope; 95% confidence interval (CI) 0.8-3.7; P ≤ .01] and less pronounced wake-to-bed slope (2.2% difference; 95% CI 1.0-3.4; P ≤ .001) compared with longer sleep duration (≥6 h/night). Lower sleep efficiency (<85%) was associated with less pronounced early decline in cortisol (29.0% difference in slope; 95% CI 4.1-59.7; P < .05) compared with higher sleep efficiency (≥85%). Subjects reporting insomnia had a flatter cortisol awakening response (-16.1% difference in slope; 95% CI -34.6 to -0.1; P < .05) compared with those not reporting insomnia. CONCLUSIONS: Shorter sleep duration, lower sleep efficiency, and insomnia are associated with alterations in diurnal cortisol levels consistent with changes in hypothalamic-pituitary-adrenal regulation.

Visual Impairment in White, Chinese, Black, and Hispanic Participants from the Multi-Ethnic Study of Atherosclerosis Cohort.

PURPOSE: To describe the prevalence of visual impairment and examine its association with demographic, socioeconomic, and health characteristics in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. METHODS: Visual acuity data were obtained from 6134 participants, aged 46-87 years at time of examination between 2002 and 2004 (mean age 64 years, 47.6% male), from six communities in the United States. Visual impairment was defined as presenting visual acuity 20/50 or worse in the better-seeing eye. Risk factors were included in multivariable logistic regression models to determine their impact on visual impairment for men and women in each racial/ethnic group. RESULTS: Among all participants, 6.6% (n = 421) had visual impairment, including 5.6% of men (n = 178) and 7.5% of women (n = 243). Prevalence of impairment ranged from 4.2% (n = 52) and 6.0% (n = 77) in white men and women, respectively, to 7.6% (n = 37) and 11.6% (n = 44) in Chinese men and women, respectively. Older age was significantly associated with visual impairment in both men and women, particularly in those with lower socioeconomic status, but the effects of increasing age were more pronounced in men. Two-thirds of participants already wore distance correction, and not unexpectedly, a lower prevalence of visual impairment was seen in this group; however, 2.4% of men and 3.5% of women with current distance correction had correctable visual impairment, most notably among seniors. CONCLUSION: Even in the U.S. where prevalence of refractive correction is high, both visual impairment and uncorrected refractive error represent current public health challenges.

Change in waist circumference with longer time in the United States among Hispanic and Chinese immigrants: the modifying role of the neighborhood built environment.

PURPOSE: We examined whether living in neighborhoods supportive of healthier diets and more active lifestyles may buffer immigrants against the unhealthy weight gain that is purported to occur with longer length of US residence. METHODS: Neighborhood data referring to a 1-mile buffer around participants' baseline home addresses were linked to longitudinal data from 877 Hispanic and 684 Chinese immigrants aged 45 to 84 years in the Multi-Ethnic Study of Atherosclerosis. We used ethnicity-stratified linear mixed models to examine whether food and activity-based neighborhood measures (healthy food stores, walkability, and recreational facilities) were associated with change in waist circumference (WC) over a 9-year follow-up. RESULTS: Among Hispanics, living in neighborhoods with more resources for healthy food and recreational activity was related to lower baseline WC. However, there was no association with change in WC over time. Among Chinese, living in more walkable neighborhoods was associated with lower baseline WC and with slower increases in WC over time, especially among the most recent immigrant arrivals. CONCLUSIONS: Where immigrants reside may have implications for health patterns that emerge with longer time in the United States.

Job Strain, Occupational Category, Systolic Blood Pressure, and Hypertension Prevalence: The Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: To assess associations of occupational categories and job characteristics with prevalent hypertension. METHODS: We analyzed 2517 Multi-Ethnic Study of Atherosclerosis participants, working 20+ hours per week, in 2002 to 2004. RESULTS: Higher job decision latitude was associated with a lower prevalence of hypertension, prevalence ratio = 0.78 (95% confidence interval 0.66 to 0.91) for the top versus bottom quartile of job decision latitude. Associations, however, differed by occupation: decision latitude was associated with a higher prevalence of hypertension in health care support occupations (interaction P = 0.02). Occupation modified associations of sex with hypertension: a higher prevalence of hypertension in women (vs men) was observed in health care support and in blue-collar occupations (interaction P = 0.03). CONCLUSIONS: Lower job decision latitude is associated with hypertension prevalence in many occupations. Further research is needed to determine reasons for differential impact of decision latitude and sex on hypertension across occupations.

Associations of socioeconomic and psychosocial factors with urinary measures of cortisol and catecholamines in the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Stress hormones have been hypothesized to contribute to the social patterning of cardiovascular disease but evidence of differences in hormone levels across social groups is scant. PURPOSE: To examine the associations of socioeconomic and psychosocial factors with urinary levels of cortisol and catecholamines and determine whether these associations are modified by race/ethnicity. METHODS: Measures of cortisol, epinephrine, norepinephrine and dopamine were obtained on 12-h overnight urine specimens from 942 White, African American and Hispanic participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Linear regression was used to examine associations of income-wealth index, education, depression, anger, anxiety and chronic stress with the four hormones after adjustment for covariates. RESULTS: Higher income-wealth index was associated with lower levels of urinary cortisol, epinephrine, norepinephrine and dopamine, after adjustment for age, sex, race/ethnicity, medication use, body mass index, smoking, and alcohol use. Education and psychosocial factors were not associated with urinary stress hormone levels in the full sample. However, there was some evidence of effect modification by race: SES factors were more strongly inversely associated with cortisol in African Americans than in other groups and anger was inversely associated with catecholamines in African Americans but not in the other groups. CONCLUSIONS: Lower SES as measured by income-wealth index in a multi-ethnic sample is associated with higher levels of urinary cortisol and catecholamines. Heterogeneity in these associations by race/ethnicity warrants further exploration.

Stability and predictors of change in salivary cortisol measures over six years: MESA.

A major challenge in characterizing features of the daily cortisol curve is variability in features over time. Few studies have examined the stability of daily features of the cortisol curve over long periods or the predictors of long term changes. Repeated salivary cortisol measures on 580 adults from the MESA Stress study were used to examine the stability of various features of the daily cortisol curve (wakeup value, the cortisol awakening response (CAR), the early and late decline slope and the area under the curve (AUC)), over short periods (several days) and long periods (approximately 6-years) and to investigate the association of demographic factors with the changes. Intraclass correlation coefficients (ICCs) were used to estimate the short and long term stability. Piecewise linear mixed models were used to assess factors associated with changes in features over time. For most features, short term stability (ICCs: 0.17-0.74) was higher than long term stability (ICCs: 0.05-0.42), and long term stability was highest when several days were averaged for each time point. The decline over the day showed the highest long term stability: when several days for each wave were averaged the stability of the daily decline slope across 6 years was similar (or higher) than the stability across short periods. AUC had high stability over short periods (ICCs: 0.65-0.74) but much lower stability across long periods (ICC: 0.05). All features of daily cortisol curve investigated changed significantly over the approximately 6 year follow-up period. The wakeup cortisol became higher; the CAR became smaller; both the early and late decline became flatter; and the AUC became larger. Hispanics experienced significantly larger increases in the wakeup value; and African-Americans and Hispanics showed less flattening over time of the early decline slope than Non-Hispanic Whites. Our findings have implications for characterization of features in studies linking cortisol to health outcomes. The presence of variability over time suggests opportunities for future investigation of the predictors of changes over time as well as the links between these changes and health outcomes.

Salivary cortisol protocol adherence and reliability by socio-demographic features: the Multi-Ethnic Study of Atherosclerosis.

Collection of salivary cortisol has become increasingly popular in large population-based studies. However, the impact of protocol compliance on day-to-day reliabilities of measures, and the extent to which reliabilities differ systematically according to socio-demographic characteristics, has not been well characterized in large-scale population-based studies to date. Using data on 935 men and women from the Multi-Ethnic Study of Atherosclerosis, we investigated whether sampling protocol compliance differs systematically according to socio-demographic factors and whether compliance was associated with cortisol estimates, as well as whether associations of cortisol with both compliance and socio-demographic characteristics were robust to adjustments for one another. We further assessed the day-to-day reliability for cortisol features and the extent to which reliabilities vary according to socio-demographic factors and sampling protocol compliance. Overall, we found higher compliance among persons with higher levels of income and education. Lower compliance was significantly associated with a less pronounced cortisol awakening response (CAR) but was not associated with any other cortisol features, and adjustment for compliance did not affect associations of socio-demographic characteristics with cortisol. Reliability was higher for area under the curve (AUC) and wake up values than for other features, but generally did not vary according to socio-demographic characteristics, with few exceptions. Our findings regarding intra-class correlation coefficients (ICCs) support prior research indicating that multiple day collection is preferable to single day collection, particularly for CAR and slopes, more so than wakeup and AUC. There were few differences in reliability by socio-demographic characteristics. Thus, it is unlikely that group-specific sampling protocols are warranted.

Diurnal salivary cortisol is associated with body mass index and waist circumference: the Multiethnic Study of Atherosclerosis.

OBJECTIVE: Neuroendocrine abnormalities, such as activation of the hypothalamic-pituitary-adrenal (HPA) axis, are associated with obesity; however, few large-scale population-based studies have examined HPA axis and markers of obesity. We examined the cross-sectional association of the cortisol awakening response (CAR) and diurnal salivary cortisol curve with obesity. DESIGN AND METHODS: The Multiethnic Study of Atherosclerosis Stress Study includes 1,002 White, Hispanic, and Black men and women (mean age 65 ± 9.8 years) who collected up to 18 salivary cortisol samples over 3 days. Cortisol profiles were modeled using regression spline models that incorporated random parameters for subject-specific effects. Cortisol curve measures included awakening cortisol, CAR (awakening to 30-min postawakening), early decline (30 min to 2-h postawakening), late decline (2-h postawakening to bedtime), and the corresponding areas under the curve (AUC). Body mass index (BMI) and waist circumference (WC) were used to estimate adiposity. RESULTS: For the entire cohort, both BMI and WC were negatively correlated with awakening cortisol (P < 0.05), AUC during awakening rise, and early decline and positively correlated to the early decline slope (P < 0.05) after adjustments for age, race/ethnicity, gender, diabetes status, socioeconomic status, ß-blockers, steroids, hormone replacement therapy, and smoking status. No heterogeneities of effects were observed by gender, age, and race/ethnicity. CONCLUSIONS: Higher BMI and WC are associated with neuroendocrine dysregulation, which is present in a large population sample, and only partially explained by other covariates.