The stress associated with providing care for a spouse diagnosed with Alzheimer’s disease can have adverse effects on cardiovascular health. One potential explanation is that chronic caregiving stress may contribute to the development of atherosclerosis. The purpose of this study was to determine if the duration that one has provided care is associated with degree of atherosclerotic burden, as measured by carotid artery intima-media thickness (IMT). One hundred and ten Alzheimer caregivers (mean age 74 ± 8 years, 69% female) underwent in-home assessment of carotid artery IMT via B-mode ultrasonography. Data regarding medical history, blood pressure, and multiple indicators of caregiving stress were also collected. Multiple regression indicated that duration of care was positively associated with IMT measured in the internal/bifurcation segments of the carotid artery (β = 0.202, p = 0.044) independent of risk factors such as age, gender, body mass index, smoking history, sleep quality, hypertension status, and caregiving stressors. Duration of care was positively associated with IMT in the common carotid artery, but the relationship was not significant. These findings provide more evidence of the link between chronic caregiving stress and cardiovascular disease and suggest that enduring the experience of caregiving over a period of years might be associated with atherosclerotic burden.
Alzheimer’s disease; Atherosclerosis; Caregiving; Chronic Stress; Coronary Heart Disease; Intima-media thickness
Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based cohorts.
Methods and Results
Continuous ABI and PAD (ABI≤0.9) phenotypes adjusted for age and sex were examined. Each study conducted genotyping and imputed data to the ~2.5 million SNPs in HapMap. Linear and logistic regression models were used to test each SNP for association with ABI and PAD using additive genetic models. Study-specific data were combined using fixed-effects inverse variance weighted meta-analyses. There were a total of 41,692 participants of European ancestry (~60% women, mean ABI 1.02 to 1.19), including 3,409 participants with PAD and with GWAS data available. In the discovery meta-analysis, rs10757269 on chromosome 9 near CDKN2B had the strongest association with ABI (β= −0.006, p=2.46x10−8). We sought replication of the 6 strongest SNP associations in 5 population-based studies and 3 clinical samples (n=16,717). The association for rs10757269 strengthened in the combined discovery and replication analysis (p=2.65x10−9). No other SNP associations for ABI or PAD achieved genome-wide significance. However, two previously reported candidate genes for PAD and one SNP associated with coronary artery disease (CAD) were associated with ABI : DAB21P (rs13290547, p=3.6x10−5); CYBA (rs3794624, p=6.3x10−5); and rs1122608 (LDLR, p=0.0026).
GWAS in more than 40,000 individuals identified one genome-wide significant association on chromosome 9p21 with ABI. Two candidate genes for PAD and 1 SNP for CAD are associated with ABI.
cohort study; genetic association; genome-wide association study; meta-analysis; peripheral vascular disease
To estimate the glomerular filtration rate (GFR) in relation to the chronic stress of dementia caregiving and major transitions in the caregiving situation.
We longitudinally assessed 119 elderly spousal Alzheimer’s disease (AD) caregivers and 58 non-caregiving controls for a period of up to three years (mean of 2.8 assessments per participant). Random regression models with fixed and time-variant effects for psychosocial factors, risk factors of chronic kidney disease, and caregiving transitions were used to evaluate changes over time in estimated GFR.
The change in GFR did not differ between caregivers and controls during follow-up (p=.77). Further analyses revealed that GFR declined disproportionately following placement of the spouse in a nursing home at 3 months post-placement (−4.9±2.2 mL/min/1.73m2; p=.03). Post hoc analyses showed that this effect was stronger in caregivers with hypertension compared to those without hypertension (−5.7±3.1 vs. −2.4±3.4 mL/min), as well as in caregivers with diastolic BP levels at 1 standard deviation above the mean than in those with diastolic BP levels at 1 standard deviation below the mean (−8.3±2.9 vs. −1.4±2.7 mL/min).
Kidney function did not differ between caregivers and controls over time. However, GFR had impaired at 3 months after a major caregiving transition. As the effect of placement of the AD spouse on the decline in GFR was moderated by BP, it might be confined to caregivers who experience increased sympathetic activation post-placement.
Blood pressure; caregivers; dementia; kidney disease; psychological stress
Sedentary behavior is associated with adiposity and cardiometabolic risk.
To determine the associations between sedentary behavior and measures of adiposity-associated inflammation.
Between 2002 and 2005, a total of 1543 Multi-Ethnic Study of Atherosclerosis participants completed detailed health history questionnaires, underwent physical measurements and had blood assayed for adiponectin, leptin, tumor necrosis factor – alpha (TNF - α) and resistin. Analyses included linear regression completed in 2010. The mean age was 64.3 years and nearly 50% were female. Forty-one percent were non-Hispanic white, 24% Hispanic-American, 20% African-American, and 14% Chinese-American.
In linear regression analyses and with adjustment for age, gender, ethnicity, education, BMI, smoking, alcohol consumption, hypertension, diabetes mellitus, dyslipidemia, hormone therapy and waist circumference, sedentary behavior was associated with higher natural log (“ln”) of leptin and ln TNF - α but a lower ln adiponectin-to-leptin ratio (β = 0.07, β = 0.03 and –0.07, p < 0.05 for all). Compared to the first tertile, and after the same adjustment, the second and third tertiles of sedentary behavior were associated with higher levels of ln leptin (β = 0.11and β = 0.12, respectively; p < 0.05 for both) but lower levels of the adiponectin-to-leptin ratio (β = –0.09 and –0.11, respectively; p < 0.05 for both).
Sedentary behavior is associated with unfavorable levels of adiposity-associated inflammation.
In randomized trials, the effect of vitamin D supplementation on blood pressure has been equivocal, while most prospective cohort studies have shown that the risk of incident hypertension is lower in people with higher levels of 25-hydroxyvitamin D (25(OH)D). The authors examined the association between levels of 25(OH)D and changes in blood pressure and incident hypertension in 4,863 postmenopausal women recruited into the Women’s Health Initiative between 1993 and 1998. Over 7 years, there were no significant differences in the adjusted mean change in systolic or diastolic blood pressure by quartile of 25(OH)D. The covariate-adjusted risk of incident hypertension was slightly lower in the upper 3 quartiles of 25(OH)D compared with the lowest quartile, but this was statistically significant only in the third quartile (hazard ratio = 0.67, 95% confidence interval: 0.46, 0.96). There was no significant linear or nonlinear trend in the risk of incident hypertension by untransformed or log-transformed continuous values of 25(OH)D. In postmenopausal women in this study, serum levels of 25(OH)D were not related to changes in blood pressure, and evidence for an association with lower risk of incident hypertension was weak.
blood pressure; calcifediol; hypertension; prospective studies; vitamin D
Providing care to a spouse with Alzheimer’s disease (AD) may contribute to cardiovascular disease (CVD). The acute phase reactant C-reactive protein is a well-established biomarker of an increased CVD risk.
To investigate the hypothesis that dementia caregiving is associated with elevated circulating levels of CRP and possibly other biomarkers of CVD risk.
We examined 118 elderly spousal Alzheimer caregivers and 51 non-caregiving controls about once a year for up to three years. Random regression models with fixed and time-variant effects for a range of covariates known to affect biomarker levels were used to evaluate changes in CRP and in twelve additional measures of inflammation, cellular adhesion, endothelial function, and hemostasis in relation to caregiving status, years of caregiving, and major transitions in the caregiving situation.
During the study period longer duration of caregiving was associated with elevated CRP levels (p=0.040) and caregivers showed greater tumor necrosis factor alpha (TNF-α) levels than controls (p=0.048). Additionally, three months after the death of the AD spouse, caregivers showed a significant drop in CRP levels (p=0.003) and also in levels of soluble intercellular adhesion molecule (sICAM)-1 (p=0.008).
Duration of caregiving, and being a caregiver per se, were both associated with chronic low-grade inflammation as indicated by elevated CRP and TNF-α levels, respectively. Conversely, death of the AD spouse was associated with lower CRP and sICAM-1 levels. The findings indicate that chronic caregiving of those with dementia may result in increased inflammation and thereby, possibly increased CVD risk.
Alzheimer disease; biomarkers; cardiovascular disease; caregiver; cytokines; inflammation; psychological stress
This study examined differences in the frequency of leisure activity participation and relationships to depressive symptom burden and cognition in Latino and Caucasian women. Cross-sectional data were obtained from a demographically matched subsample of Latino and Caucasian (n = 113 each) post-menopausal women (age ≥60), interviewed in 2004–06 for a multi-ethnic cohort study of successful aging in San Diego County. Frequencies of engagement in 16 leisure activities and associations between objective cognitive performance and depressive symptom burden by ethnicity were identified using bivariate and linear regression, adjusted for physical functioning and demographic covariates. Compared to Caucasian women, Latinas were significantly more likely to be caregivers and used computers less often. Engaging in organized social activity was associated with fewer depressive symptoms in both groups. Listening to the radio was positively correlated with lower depressive symptom burden for Latinas, and better cognitive functioning in Caucasians. Cognitive functioning was better in Latinas who read and did puzzles. Housework was negatively associated with Latinas’ emotional health and Caucasians’ cognitive functioning. Latino and Caucasian women participate in different patterns of leisure activities. Additionally, ethnicity significantly affects the relationship between leisure activities and both emotional and cognitive health.
Alzheimer’s Disease (AD) caregiving stress may contribute to increased cardiovascular disease risk in spousal caregiving through physiological changes characteristic of the metabolic syndrome (MetS).
We tested the hypothesis that cardiometabolic risk is attenuated when caregivers are relieved from caregiving stress when the caregiving recipient transitions out of the home.
One hundred and nineteen spousal caregivers of a patient with AD and 55 non-caregiving controls (mean age 75±8 years of entire sample, 68% women).
Participants underwent up to three yearly assessments of MetS factors related to adiposity, dyslipidemia, hypertension, and hyperglycemia. Changes in the total number of MetS factors (range 0–5) at 3 months after caregiver transitions were evaluated using random regression models with fixed and time-variant effects for sociodemographic and health-related covariates.
Compared to non-caregivers, caregivers had a greater number of MetS factors over time (1.78±0.13 vs. 1.36±0.18, p=0.008), which, after the death of the spouse, dropped by 0.46±0.16 (p=0.003) being no longer different from non-caregivers; this effect was most prominently related to decreases in triglycerides (−22.2±11.0 mg/dl, p=0.032), systolic BP (−6.2±2.6 mmHg, p=0.019), and diastolic BP (−3.4±1.5 mmHg, p=0.026). Placement of the spouse decreased the number of MetS factors only in caregivers with lower levels of depressive symptoms (−0.48±0.18, p=0.010) and sleeping difficulties (−0.42±0.18, p=0.021), but not in caregivers with higher levels in these measures at post-placement.
Elevated cardiometabolic risk in caregivers decreased to the level of non-caregivers within three months of death of the AD spouse. Placement, a transition in the course of dementia caregiving, however, did not benefit cardiovascular health in highly distressed caregivers.
Cardiovascular disease; caregivers; dementia; metabolic syndrome; psychological stress
To determine the association of family history of peripheral artery disease (PAD) with PAD prevalence and severity.
PAD is a significant public health problem. Shared genetic and environmental factors may play an important role in the development of PAD. However, family history of PAD has not been adequately investigated.
The San Diego Population Study (SDPS) enrolled 2404 ethnically diverse men and women aged 29–91 who attended a baseline visit from 1994–98 to assess PAD and venous disease. Ankle brachial index (ABI) measurement was performed at the baseline clinic examination and family history of PAD was obtained via questionnaire. Family history of PAD was primarily defined as having any 1st degree relative with PAD. Prevalent PAD was defined as ABI ≤ 0.90 and severe prevalent PAD as ABI ≤ 0.70, with both definitions also including any previous leg revascularization. Logistic regression was used to evaluate the association of family history of PAD with prevalent PAD.
The mean (SD) age was 59 (11) years, 66% were women, and 58% were Caucasian with 42% comprising other racial/ethnic groups. Prevalence of PAD was 3.6%, and severe prevalent PAD was 1.9%. In fully adjusted models, family history of PAD was associated with a 1.83-fold higher odds of PAD (95% CI (1.03, 3.26), p=0.04), an association which was stronger for severe prevalent PAD (OR 2.42, 95% CI (1.13, 5.23), p=0.02).
Family history of PAD is independently strongly associated with PAD prevalence and severity. This indicates a role for genetic factors and/or other shared environmental factors contributing to PAD.
family history; peripheral artery disease; ankle brachial index
To investigate whether differences in admixture in African American (AFA) and Hispanic American (HA) adult women are associated with adiposity and adipose distribution.
The proportion of European, sub– Saharan African and Amerindian admixture was estimated for AFA and HA women in the Women's Heath Initiative using 92 ancestry informative markers. Analyses assessed the relationship between admixture and adiposity indices.
11712 AFA and 5088 HA self– identified post– menopausal women.
There was a significant positive association between body mass index (BMI) and African admixture when BMI was considered as a continuous variable, and age, education, physical activity, parity, family income and smoking were included covariates (p < 10− 4). A dichotomous model (upper and lower BMI quartiles) showed that African admixture was associated with a high odds ratio [OR = 3.27 (for 100% admixture compared to 0% admixture), 95% confidence interval (CI) 2.08 – 5.15]. For HA there was no association between BMI and admixture. In contrast, when waist to hip ratio (WHR) was used as a measure of adipose distribution, there was no significant association between WHR and admixture in AFA but there was a strong association in HA (p<10− 4; OR Amerindian admixture = 5.93, CI = 3.52 – 9.97).
These studies show that 1) African admixture is associated with BMI in AFA women; 2) Amerindian admixture is associated with WHR but not BMI in HA women; and 3) it may be important to consider different measurements of adiposity and adipose distribution in different ethnic population groups.
European admixture; African admixture; Amerindian admixture; post–menopausal women; waist to hip ratio; body mass index
Objective. To investigate the relationship between coping and atherothrombotic biomarkers of an increased cardiovascular disease (CVD) risk in the elderly. Methods. We studied 136 elderly caregiving and noncaregiving men and women who completed the Ways of Coping Checklist to assess problem-focused coping, seeking social support (SSS), blamed self, wishful thinking, and avoidance coping. They had circulating levels of 12 biomarkers measured. We also probed for potential mediator and moderator variables (chronic stress, affect, health behavior, autonomic activity) for the relation between coping and biomarkers. Results. After controlling for demographic and CVD risk factors, greater use of SSS was associated with elevated levels of serum amyloid A (P = 0.001), C-reactive protein (CRP) (P = 0.002), vascular cellular adhesion molecule (VCAM)-1 (P = 0.021), and D-dimer (P = 0.032). There were several moderator effects. For instance, greater use of SSS was associated with elevated VCAM-1 (P < 0.001) and CRP (P = 0.001) levels in subjects with low levels of perceived social support and positive affect, respectively. The other coping styles were not significantly associated with any biomarker. Conclusions. Greater use of SSS might compromise cardiovascular health through atherothrombotic mechanisms, including elevated inflammation (i.e., serum amyloid A, CRP, VCAM-1) and coagulation (i.e., D-dimer) activity. Moderating variables need to be considered in this relationship.
Emerging evidence suggests that women with menopausal vasomotor symptoms (VMS) have increased cardiovascular disease (CVD) risk as measured by surrogate markers. We investigated the relationships between VMS and clinical CVD events and all-cause mortality in the Women's Health Initiative Observational Study (WHI-OS).
We compared the risk of incident CVD events and all-cause mortality between four groups of women (total N=60,027): (1) No VMS at menopause onset and no VMS at WHI-OS enrollment (no VMS [referent group]); (2) VMS at menopause onset, but not at WHI-OS enrollment (early VMS); (3) VMS at both menopause onset and WHI-OS enrollment (persistent VMS [early and late]); and (4) VMS at WHI-OS enrollment, but not at menopause onset (late VMS).
For women with early VMS (N=24,753), compared to no VMS (N=18,799), hazard ratios (HRs) and 95% confidence intervals (CIs) in fully-adjusted models were: major CHD, 0.94 (0.84, 1.06); stroke, 0.83 (0.72, 0.96); total CVD, 0.89 (0.81, 0.97); and all-cause mortality, 0.92 (0.85, 0.99). For women with persistent VMS (N=15,084), there was no significant association with clinical events. For women with late VMS (N=1,391) compared to no VMS, HRs and 95% CIs were: major CHD, 1.32 (1.01, 1.71); stroke, 1.14 (0.82, 1.59); total CVD, 1.23 (1.00, 1.52); and all-cause mortality, 1.29 (1.08, 1.54).
Early VMS were not associated with increased CVD risk. Rather, early VMS were associated with decreased risk of stroke, total CVD events, and all-cause mortality. Late VMS were associated with increased CHD risk and all-cause mortality. The predictive value of VMS for clinical CVD events may vary with onset of VMS at different stages of menopause. Further research examining the mechanisms underlying these associations is needed. Future studies will also be necessary to investigate whether VMS that develop for the first time in the later postmenopausal years represent a pathophysiologic process distinct from classical perimenopausal VMS.
Vasomotor symptoms; Hot flashes; Cardiovascular disease; Women's health
Pericardial fat is a localized fat depot associated with coronary artery calcium and myocardial infarction. We hypothesized that genetic loci would be associated with pericardial fat independent of other body fat depots. Pericardial fat was quantified in 5,487 individuals of European ancestry from the Framingham Heart Study (FHS) and the Multi-Ethnic Study of Atherosclerosis (MESA). Genotyping was performed using standard arrays and imputed to ∼2.5 million Hapmap SNPs. Each study performed a genome-wide association analysis of pericardial fat adjusted for age, sex, weight, and height. A weighted z-score meta-analysis was conducted, and validation was obtained in an additional 3,602 multi-ethnic individuals from the MESA study. We identified a genome-wide significant signal in our primary meta-analysis at rs10198628 near TRIB2 (MAF 0.49, p = 2.7×10-08). This SNP was not associated with visceral fat (p = 0.17) or body mass index (p = 0.38), although we observed direction-consistent, nominal significance with visceral fat adjusted for BMI (p = 0.01) in the Framingham Heart Study. Our findings were robust among African ancestry (n = 1,442, p = 0.001), Hispanic (n = 1,399, p = 0.004), and Chinese (n = 761, p = 0.007) participants from the MESA study, with a combined p-value of 5.4E-14. We observed TRIB2 gene expression in the pericardial fat of mice. rs10198628 near TRIB2 is associated with pericardial fat but not measures of generalized or visceral adiposity, reinforcing the concept that there are unique genetic underpinnings to ectopic fat distribution.
Pericardial fat is a localized fat depot associated with coronary artery calcium and myocardial infarction. To test whether genetic loci are associated with pericardial fat independent of other body fat depots, we measured pericardial fat in 5,487 individuals of European ancestry. After performing an unbiased screen using genome-wide association, we identified a genome-wide significant signal in our primary meta-analysis at rs10198628 near TRIB2 (MAF 0.49, p = 2.7×10-08). This SNP was not associated with visceral fat (p = 0.17) or body mass index (p = 0.38). Our findings were robust among multi-ethnic participants from the MESA study, with a combined p-value of 5.4E-14. We observed TRIB2 gene expression in the pericardial fat of mice. rs10198628 near TRIB2 is associated with pericardial fat but not measures of generalized or visceral adiposity, reinforcing the concept that there are unique genetic underpinnings to ectopic fat distribution.
An abnormally high ankle brachial index (ABI) is associated with increased all-cause and cardiovascular mortality. The relationship of obesity to incident high-ABI has not been characterized. We investigated the hypothesis that increased obesity—quantified by body weight, BMI, waist circumference, and waist-to-hip-ratio—is positively associated with a high-ABI (ABI ≥ 1.3) and with mean ABI increases over a four year follow-up. Prevalence and incidence ratios for a high-ABI were obtained for 6540 and 5045 participants respectively in the Multi-Ethnic Study of Atherosclerosis (MESA), using log-binomial regression models adjusted for demographic, cardiovascular, and inflammatory/novel risk factors. Linear regression was used to analyze mean ABI change. Both prevalence and incidence of a high-ABI were significantly higher for the highest versus the lowest quartile of every baseline measure of obesity, with weight and BMI demonstrating the highest incidence ratios (2.7 and 2.4, respectively). All prevalence and incidence ratios were positive and graded across obesity quartiles, and were persistent in the subpopulation without diabetes. Among those with normal baseline ABI values, one MESA-standard deviation increase in every baseline measure of obesity was associated with significant increases in mean ABI values. In conclusion, we observed an independent, positive and graded association of increasing obesity to both prevalent and incident high-ABI, and to mean increases in ABI values over time. Weight and BMI seemed to be at least as strongly, if not more strongly, associated with a high-ABI than were measures of abdominal obesity.
obesity; anthropometric measures; peripheral vascular disease; ankle-brachial index; epidemiology
To test the hypothesis of a significant association between resting heart rate (RHR) and coronary artery calcium (CAC).
This is a cross-sectional study of a subset of women enrolled in the estrogen-alone clinical trial of the Women's Health Initiative (WHI). We used a longitudinal study that enrolled 998 postmenopausal women with a history of hysterectomy between the ages of 50 and 59 at enrollment at 40 different clinical centers. RHR was measured at enrollment and throughout the study, and CAC was determined approximately 7 years after the baseline clinic visit.
The mean (standard deviation [SD]) age was 55 (2.8) years. With adjustment for age and ethnicity, a 10-unit increment in RHR was significantly associated with CAC (SD 1.18, 95% confidence interval [CI] 1.01-1.38), but this was no longer significant after adjustment for body mass index (BMI), income, education, dyslipidemia, diabetes, smoking, and hypertension (SD 1.06, 95% CI 0.90-1.25). In a fully adjusted multivariable model, however, there was a significant interaction (p=0.03) between baseline RHR and systolic blood pressure (SBP) for the presence of any CAC. Compared to women with an RHR < 80 beats per minute (BPM) and an SBP < 140 mm Hg, those who had an RHR ≥ 80 BPM and an SBP ≥ 140 mm Hg had 2.66-fold higher odds (1.08-6.57) for the presence of any CAC.
Compared to those with normal BP and RHR, postmenopausal, hysterectomized women with an elevated SBP and RHR have a significantly higher odds for the presence of calcified coronary artery disease.
To gain insight into early mechanisms of aortic widening, we examined associations between the diameter of the abdominal aorta (AD) and cardiovascular disease (CVD) risk factors and biomarkers, as well as measures of subclinical atherosclerosis, in a multi-ethnic population.
A total of 1926 participants (mean age 62, 50% women) underwent chest and abdomen scanning by computed tomography, ultrasound of the carotid arteries, and CVD risk factor assessment. AD was measured 5 cm above and at the bifurcation.
In a model containing traditional CVD risk factors, biomarkers and ethnicity, only age (standardized β=0.97), male sex (β=1.88), body surface area (standardized β=0.92), current smoking (β=0.42), D-dimer levels (β=0.19) and hypertension (β=0.53) were independently and significantly associated with increasing AD (in mm) at the bifurcation; use of cholesterol-lowering medications predicted smaller AD (β=-0.70) (P<.01 for all). These findings were similar for AD 5 cm above the bifurcation with one exception: compared to Caucasian-Americans, Americans of Chinese, African and Hispanic descent had significantly smaller AD 5 cm above the bifurcation (β's= -0.59, -0.49, and -0.52, respectively, all P<.01), whereas AD at the bifurcation did not differ by ethnicity. Physical activity, alcohol consumption, diabetes and levels of IL-6, CRP and homocysteine were not independently associated with AD. Higher aortic and coronary artery calcium burden, but not common carotid artery intima-media thickness, were independently, but modestly (β=0.11 to 0.19), associated with larger AD.
Incremental widening of the aortic diameter shared some, but not all, risk factors for occlusive vascular disease.
aorta; aneurysm; atherosclerosis; ethnicity; epidemiology
The initiation and acceleration of atherosclerosis is hypothesized as a physiologic mechanism underlying associations between air pollution and cardiovascular effects. Despite toxicologic evidence, epidemiologic data are limited.
In this cross-sectional analysis we investigated exposure to fine particulate matter (PM2.5) and residential proximity to major roads in relation to abdominal aortic calcification a sensitive indicator of systemic atherosclerosis. Aortic calcification was measured by computed tomography among 1147 persons, in 5 U.S. metropolitan areas, enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA). The presence and quantity of aortic calcification were modeled using relative risk regression and linear regression, respectively, with adjustment for potential confounders.
We observed a slightly elevated risk of aortic calcification (RR = 1.06; 95% confidence interval = 0.96–1.16) with a 10-μg/m3 contrast in PM2.5. The PM2.5-associated risk of aortic calcification was stronger among participants with long-term residence near a PM2.5 monitor (RR = 1.11; 1.00–1.24) and among participants not recently employed outside the home (RR = 1.10; 1.00–1.22). PM2.5 was not associated with an increase in the quantity of aortic calcification (Agatston score) and no roadway proximity effects were noted. There was indication of PM2.5 effect modification by lipid-lowering medication use, with greater effects among users, and PM2.5 associations were observed most consistently among Hispanics.
Although we did not find persuasive associations across our full study population, associations were stronger among participants with less exposure misclassification. These findings support the hypothesis of a relationship between particulate air pollution and systemic atherosclerosis.
To examine whether lower serum levels of serum 25-hydroxyvitamin (OH) D [25(OH)D] are associated with increased risk of developing type 2 diabetes.
RESEARCH DESIGN AND METHODS
A post hoc analysis of three nested case-control studies of fractures, colon cancer, and breast cancer that measured serum 25(OH)D levels in women participating in the Women’s Health Initiative (WHI) Clinical Trials and Observational Study who were free of prevalent diabetes at baseline. Diabetes was defined as self-report of physician diagnosis or receiving insulin or oral hypoglycemic medication. We used inverse probability weighting to make the study population representative of the WHI population as a whole. Weighted logistic regression models compared 25(OH)D levels (divided into quartiles, clinical cut points [<50, 50–<75, ≥75 nmol/L], or as a continuous variable) using the distribution of control subjects and adjusted for multiple confounding factors.
Of 5,140 women (mean age 66 years) followed for an average of 7.3 years, 317 (6.2%) developed diabetes. Regardless of the cut points used or as a continuous variable, 25(OH)D levels were not associated with diabetes incidence in either age or fully adjusted models. Nor was any relationship found between 25(OH)D and incident diabetes when evaluated by strata of BMI, race/ethnicity, or randomization status in the Calcium Vitamin D trial.
Lower serum 25(OH)D levels were not associated with increased risk of developing type 2 diabetes in this racially and ethnically diverse population of postmenopausal women.
Attitudes toward own aging (ATOA) refers to expectations about the personal experience of aging. As of now, there is limited literature that addresses the impact of ATOA on indicators of psychological, physical, and social health. In this study, we examine associations between ATOA and several measures associated with successful aging.
A detailed cross-sectional survey questionnaire on successful aging was completed by 1,973 older women enrolled in the San Diego site of the Women's Health Initiative study. ATOA was measured using the Philadelphia Geriatric Morale Scale (PGMS)
The final sample consisted of 1151 women. The mean ATOA score was 3.8 indicating generally positive ATOA. Positive ATOA score was significantly associated with younger age, lower income, being married, higher SF-36 Physical Composite scores, higher SF-36 Mental composite scores, lower depression scores, and higher resilience scores. Approximately 40% of variance in ATOA scores was explained by successful aging-related domain scores.
Better physical and emotional functioning, greater resilience and lower depression are associated with more positive ATOA. Associations with sociodemographic traits are complex. Modifying ATOA may have potential to impact a broad range of health and successful aging related outcomes.
Attitude toward aging; Depression; Health; Social status; Spirituality; Personal mastery; Optimism
Excessive non-subcutaneous fat deposition may impair the functions of surrounding tissues and organs through the release of inflammatory cytokines and free fatty acids.
We examined the cross-sectional association between non-subcutaneous adiposity and calcified coronary plaque, a non-invasive measure of coronary artery disease burden.
Participants in the Multi-Ethnic Study of Atherosclerosis underwent CT assessment of calcified coronary plaque. We measured multiple fat depots in 398 white and black participants (47% men and 43% black), ages 47–86 years, from Forsyth County, NC during 2002–2005, using cardiac and abdominal CT scans. In addition to examining each depot separately, we also created a non-subcutaneous fat index using the standard scores of non-subcutaneous fat depots.
A total of 219 participants (55%) were found to have calcified coronary plaque. After adjusting for demographics, lifestyle factors and height, calcified coronary plaque was associated with a one standard deviation increment in the non-subcutaneous fat index (OR = 1.41; 95% CI: 1.08, 1.84), pericardial fat (OR = 1.38; 95% CI: 1.04, 1.84), abdominal visceral fat (OR = 1.35; 95% CI: 1.03, 1.76), but not with fat content in the liver, intermuscular fat, or abdominal subcutaneous fat. The relation between non-subcutaneous fat index and calcified coronary plaque remained after further adjustment for abdominal subcutaneous fat (OR = 1.40; 95% CI: 1.00, 1.94). The relation did not differ by gender and ethnicity.
The overall burden of non-subcutaneous fat deposition, but not abdominal subcutaneous fat, may be a correlate of coronary atherosclerosis.
Abdominal aortic calcification (AAC) is a measure of subclinical cardiovascular disease (CVD). Data are limited regarding its relation to other measures of atherosclerosis.
Among 1,812 subjects (49% female, 21% black, 14% Chinese, and 25% Hispanic) within the population-based Multiethnic Study of Atherosclerosis, we examined the cross-sectional relation of AAC with coronary artery calcium (CAC), ankle brachial index (ABI), and carotid intimal medial thickness (CIMT), as well as multiple measures of subclinical CVD.
AAC prevalence ranged from 34% in those aged 45–54 to 94% in those aged 75–84 (p<0.0001), was highest in Caucasians (79%) and lowest in blacks (62%) (p<0.0001). CAC prevalence, mean maximum CIMT ≥ 1 mm, and ABI<0.9 was greater in those with vs. without AAC: CAC 60% vs 16%, CIMT 38% vs 7%, and ABI 5% vs 1% for women and CAC 80% vs 37%, CIMT 43% vs 16%, and ABI 4% vs 2% for men (p<0.01 for all except p<0.05 for ABI in men). The presence of multi-site atherosclerosis (≥ 3 of the above) ranged from 20% in women and 30% in men (p<0.001), was highest in Caucasians (28%) and lowest in Chinese (16%) and ranged from 5% in those aged 45–54 to 53% in those aged 75–84 (p<0.01 to p<0.001). Finally, increased AAC was associated with 2 to 3-fold relative risks for the presence of increased CIMT, low ABI, or CAC.
AAC is associated with an increased likelihood of other vascular atherosclerosis. Its additive prognostic value to these other measures is of further interest.
atherosclerosis; calcification; cardiovascular disease; epidemiology
Providing care for a spouse diagnosed with Alzheimer's disease has been associated with an increased risk of coronary heart disease, potentially due to the impact of caregiving stress on the atherosclerotic disease process. We hypothesized that Alzheimer caregivers would have increased prevalence of carotid artery plaque compared to non-caregiving controls and that prolonged sympatho-adrenal arousal to acute stress would relate to this difference.
Participants were 111 spousal caregivers (74±8 years of age, 69% women) to patients with Alzheimer’s disease and 51 non-caregiving controls (75±6 years of age, 69% women). In-home assessment of carotid artery plaque via B-mode ultrasonography was conducted. Plasma catecholamine response to an acute speech stressor task was also measured.
Logistic regression indicated that caregiving status (i.e., caregiver vs. non-caregiver) was significantly associated with a 2.2 times greater odds for the presence of plaque independent of other risk factors of atherosclerosis (95% CI=1.01–4.73, p=.048). Decreased recovery to basal levels of epinephrine after a psychological stress task was significantly associated with the presence of plaque in caregivers, but not in non-caregivers. Norepinephrine recovery post-stressor was not associated with plaque in either group.
Caregivers had a higher prevalence of carotid plaque compared to non-caregivers. Poorer epinephrine recovery after acute stress was associated with the presence of plaque in caregivers but not in non-caregivers. A prolonged sympatho-adrenal response to acute stress might enhance the development of atherosclerosis in chronically stressed Alzheimer caregivers.
caregiving; stress; Alzheimer’s disease; carotid artery plaque; atherosclerosis; catecholamines
To examine how chronic stress in major life domains [relationship, work, sympathetic-caregiving, financial] relates to CVD risk, operationalized using the inflammatory marker C-Reactive Protein (CRP), and whether gender differences exist.
Participants were 6583 individuals aged 45 to 84 years, recruited as part of the Multi-Ethnic Study of Atherosclerosis (MESA). Demographic and behavioral factors, health history, and chronic stress were self-reported. CRP was obtained through venous blood draw.
In aggregate, gender by chronic stress interaction effects accounted for a significant, albeit small, amount of variance in CRP (p<.01). The sympathetic-caregiving stress by gender interaction was significant (p<.01); the work stress by gender effect approached significance (p=.05). Women with sympathetic-caregiving stress had higher CRP than those without, whereas no difference in CRP by stress group was observed for men.
Findings underscore the importance of considering gender as an effect modifier in analyses of stress – CVD risk relationships.
Cardiovascular disease; C-reactive Protein; chronic stress; gender; inflammation; stress domains
The pro-inflammatory cytokine interleukin (IL)-6 has been linked with health morbidity, particularly risk for cardiovascular disease. The purpose of this study was to investigate the potential protective role of coping self-efficacy on the relationship between caregiving stress and circulating concentrations of IL-6.
A total of 62 elderly Alzheimer’s caregivers (mean age = 74 years) were assessed for plasma concentrations of IL-6, caregiving-related overload, and coping self-efficacy. Multiple regression was used to examined the main effects of stress and self-efficacy, as well as the interaction between stress and self-efficacy, in predicting plasma IL-6 after controlling for age, gender, resting blood pressure, and obesity.
There was a significant interaction between stress and self-efficacy in predicting IL-6. Post-hoc examination indicated that when self-efficacy was low, stress was significantly related to IL-6 (β = .43). However, when self-efficacy was high, stress was not significantly related to IL-6 (β = -.10).
Caregiving stress in combination with low coping self-efficacy is significantly related to IL-6, a known risk marker for health morbidity, particularly CVD. However, stress was not associated with IL-6 with high self-efficacy. While limited and preliminary, these results point to a potential protective effect of self-efficacy on caregiver health that can be tested in longitudinal studies.
Coping; Personal Control; Cardiovascular Disease; Inflammation; Elderly
The role of spirituality in the context of mental health and successful aging is not well understood. In a sample of community-dwelling older women enrolled at the San Diego site of the Women's Health Initiative study, we examined the association between spirituality and a range of variables associated with successful cognitive and emotional aging, including optimism, resilience, depression, and health-related quality of life (HRQoL).
A detailed cross-sectional survey questionnaire on successful aging was completed by 1,973 older women. It included multiple self-reported measures of positive psychological functioning (e.g., resilience, optimism,), as well as depression and HRQoL. Spirituality was measured using a 5-item self report scale constructed using two items from the Brief Multidimensional Measure of Religiosity/Spirituality and three items from Hoge's Intrinsic Religious Motivation Scale
Overall, 40% women reported regular attendance in organized religious practice, and 53% reported engaging in private spiritual practices. Several variables were significantly related to spirituality in bivariate associations; however, using model testing, spirituality was significantly associated only with higher resilience, lower income, lower education, and lower likelihood of being in a marital or committed relationship.
Our findings point to a role for spirituality in promoting resilience to stressors, possibly to a greater degree in persons with lower income and education level. Future longitudinal studies are needed to confirm these associations.
Spirituality; religiosity; elderly; successful aging; resilience