The cardioprotective effects of long-chain n-3 polyunsaturated fatty acids (PUFAs) and fish consumption have been observed. However, data on the specific associations of these dietary factors with ...inflammation and endothelial activation are sparse. A cross-sectional study was conducted of 5,677 men and women from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, including African Americans, Caucasians, Chinese, and Hispanics aged 45 to 84 years and free of clinical cardiovascular disease. Dietary information was collected using a self-administered food frequency questionnaire. Multivariate linear regression analyses were used to examine relations between the intake of long-chain n-3 PUFAs, nonfried fish, and fried fish and biomarkers of inflammation and endothelial activation. Long-chain n-3 PUFA intake was inversely associated with plasma concentrations of interleukin-6 (p = 0.01) and matrix metalloproteinase–3 (p = 0.03) independent of age, body mass index, physical activity, smoking, alcohol consumption, and dietary variables. Nonfried fish consumption was inversely related to C-reactive protein (p = 0.045) and interleukin-6 (p <0.01), and fried fish consumption was inversely related to soluble intercellular adhesion molecule–1 (p <0.01) but was not associated with other biomarkers after adjustment for potential confounders. In conclusion, the results of this study suggest that the dietary intake of long-chain n-3 PUFAs and fish is inversely associated with concentrations of some biomarkers, reflecting lower levels of inflammation and endothelial activation. These results may partially explain the cardioprotective effects of fish consumption.
Adaptive immunity has been implicated in atherosclerosis in animal models and small clinical studies. Whether chronic immune activation is associated with atherosclerosis in otherwise healthy ...individuals remains underexplored. We hypothesized that activation of adaptive immune responses, as reflected by higher proportions of circulating CD4(+) memory cells and lower proportions of naive cells, would be associated with subclinical atherosclerosis.
We examined cross-sectional relationships of circulating CD4(+) naive and memory T cells with biomarkers of inflammation, serologies, and subclinical atherosclerosis in 912 participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Circulating CD4(+) naive cells were higher in women than men and decreased with age (all p-values <0.0001). European-Americans had higher levels of naive cells and lower levels of memory cells compared with African-Americans and Hispanic-Americans (all p-values ≤0.0005). Lower naive/higher memory cells were associated with interleukin-6 levels. In multivariate models, cytomegalovirus (CMV) and H. Pylori titers were strongly associated with higher memory and lower naive cells (all p-values <0.05). Higher memory cells were associated with coronary artery calcification (CAC) level in the overall population β-Coefficient (95% confidence interval (CI)) = 0.20 (0.03, 0.37). Memory and naive (inversely) cells were associated with common carotid artery intimal media thickness (CC IMT) in European-Americans memory: β = 0.02 (0.006, 0.04); naive: β = -0.02 (-0.004, -0.03).
These results demonstrate that the degree of chronic adaptive immune activation is associated with both CAC and CC IMT in otherwise healthy individuals, consistent with the known role of CD4(+) T cells, and with innate immunity (inflammation), in atherosclerosis. These data are also consistent with the hypothesis that immunosenescence accelerates chronic diseases by putting a greater burden on the innate immune system, and suggest the importance of prospective studies and research into strategies to modulate adaptive immune activation in chronic disease states such as atherosclerosis.
Background Left ventricular (LV) hypertrophy (LVH) is associated with chronic kidney disease, but the association of LVH with a mild decrease in kidney function is not known. We hypothesized that ...mild and moderate decreases in kidney function, reflected in greater serum cystatin C concentrations, would be linearly associated with a greater prevalence of LVH. Study Design Cross-sectional observational study. Settings & Participants Participants in baseline examinations in the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based study with several sites in the United States. Predictors Cystatin C–based estimated glomerular filtration rate (eGFRcysC ) and creatinine-based eGFR. Outcomes LVH and LV mass index. Measurements Serum cystatin C and creatinine, LV mass obtained by using magnetic resonance imaging. LVH cutoff values for men and women were defined by the upper 95th percentile of LV mass index of all MESA participants without hypertension. Results Of the 4,971 participants analyzed, mean creatinine-based eGFR was 81 ± 17 (SD) mL/min/1.73 m2 and mean eGFRcysC was 94 ± 32 mL/min/1.73 m2 . LVH was distinctly more prevalent (>12%) in only the lowest 2 deciles of eGFRcysC (<75 mL/min/1.73 m2 ). When 435 participants (9%) with stage 3 or higher chronic kidney disease (creatinine-based eGFR < 60 mL/min/1.73 m2 ) were excluded, the odds for LVH increased for each lower category of eGFRcysC less than 75 mL/min/1.73 m2 : odds ratio 1.6 for LVH with eGFRcysC of 60 to 75 mL/min/1.73 m2 (95% confidence interval, 1.20 to 2.07; P = 0.001), and odds ratio 2.0 for eGFRcysC less than 60 mL/min/1.73 m2 (95% confidence interval, 1.03 to 3.75; P = 0.04) after adjustment for demographic factors, study site, diabetes, and smoking. The association of lower eGFRcysC with LVH was attenuated after further adjustment for hypertension. Limitations Cross-sectional rather than longitudinal design, lack of participants with more advanced kidney disease, lack of a direct measurement of glomerular filtration rate. Conclusions In participants without chronic kidney disease, eGFRcysC of 75 mL/min/1.73 m2 or less was associated with a greater odds of LVH.
Abstract Objective Cross-sectional and prospective studies have linked cardiovascular events and traditional risk factors (TRFs) with higher plasma fibrinogen levels. In a young cohort, we sought to ...determine longitudinal associations between changes in/development of TRFs and fibrinogen levels over 13 years. Methods We included 2525 adults from the CARDIA study, aged 25–37 with fibrinogen and TRFs measured at year 7 (study baseline; 1992–1993); and year 20 (follow-up). Multiple linear regressions were used to compare mean changes in fibrinogen to TRFs. Results Mean fibrinogen increased by 71 mg/dL vs. 70 mg/dL ( p = NS) in black vs. white men, and 78 mg/dL vs. 68 mg/dL ( p < 0.05) in black vs. white women, respectively over 13 years. After multivariable adjustments, fibrinogen generally rose with increasing BMI ( p < 0.001; all sex/race groups), LDL cholesterol, log triglycerides and diastolic blood pressure; and fell with increasing HDL cholesterol and physical activity. 13-year increase in fibrinogen for persons who quit smoking or became non-obese were comparable ( p = NS) to that of never-smokers and never-obese persons. Conclusions Among young black and white men and women with few baseline cardiovascular risk factors, fibrinogen tracked longitudinally with changes in TRFs over 13 years through middle age. There was a strong inverse longitudinal relationship between modifiable risk factors (weight loss/smoking cessation) and 13-year change in fibrinogen. Our study helps provide some insight into the role of fibrinogen as a disease marker in the associations between fibrinogen and CVD.
Telomere length (TL) is considered as a marker of cell senescence, but factors influencing the rate of TL attrition are not well understood. While one previous study reported the association of ...occupation and TL, many subsequent studies have failed to find the association. This may be due to heterogeneity within the samples and cross-sectional designs. This longitudinal study examines two occupational characteristics, occupational complexity and hazardous conditions, as predictors of TL attrition in gender- and race/ethnicity-stratified analysis. Leukocyte TL (expressed as T/S ratio) was measured twice over a 10-year period in a multi-racial sample (n = 914). Linear mixed effect models were used to estimate TL attrition associated with occupational complexity and hazardous conditions. Analysis was stratified by gender and race/ethnicity (white, African American, and Latino) and controlled for baseline age, baseline TL, and time since baseline. Higher occupational complexity was associated with slower rates of TL attrition only among white men. Hazardous conditions were not associated with TL attrition for any gender-and-race/ethnicity stratified group. Occupational complexity may influence TL attrition, but the different findings for white men and other groups suggest that a more comprehensive framework is needed to better understand the potential link between occupational characteristics and biological aging.
Background Monocytes/macrophages participate in cardiovascular disease. CD163 (cluster of differentiation 163) is a monocyte/macrophage receptor, and the shed sCD163 (soluble CD163) reflects ...monocyte/macrophage activation. We examined the association of sCD163 with incident cardiovascular disease events and performed a genome-wide association study to identify sCD163-associated variants. Methods and Results We measured plasma sCD163 in 5214 adults (aged ≥65 years, 58.7% women, 16.2% Black) of the CHS (Cardiovascular Health Study). We used Cox regression models (associations of sCD163 with incident events and mortality); median follow-up was 26 years. Genome-wide association study analyses were stratified on race. Adjusted for age, sex, and race and ethnicity, sCD163 levels were associated with all-cause mortality (hazard ratio HR, 1.08 95% CI, 1.04-1.12 per SD increase), cardiovascular disease mortality (HR, 1.15 95% CI, 1.09-1.21), incident coronary heart disease (HR, 1.10 95% CI, 1.04-1.16), and incident heart failure (HR, 1.18 95% CI, 1.12-1.25). When further adjusted (eg, cardiovascular disease risk factors), only incident coronary heart disease lost significance. In European American individuals, genome-wide association studies identified 38 variants on chromosome 2 near
(top result rs62165726,
=3.3×10
),19 variants near chromosome 17 gene
(rs55714927,
=1.5×10
), and 18 variants near chromosome 11 gene
. These regions replicated in the European ancestry ADDITION-PRO cohort, a longitudinal cohort study nested in the Danish arm of the Anglo-Danish-Dutch study of Intensive Treatment Intensive Treatment In peOple with screeNdetcted Diabetes in Primary Care. In Black individuals, we identified 9 variants on chromosome 6 (rs3129781
=7.1×10
) in the
region, and 3 variants (rs115391969
=4.3×10
) near the chromosome 16 gene
Conclusions Monocyte function, as measured by sCD163, may be predictive of overall and cardiovascular-specific mortality and incident heart failure.
Distinct lymphocyte subpopulations have been implicated in the regulation of glucose homeostasis and obesity-associated inflammation in mouse models of insulin resistance. Information on the ...relationships of lymphocyte subpopulations with type 2 diabetes remain limited in human population-based cohort studies.
Circulating levels of innate (γδ T, natural killer (NK)) and adaptive immune (CD4+ naive, CD4+ memory, Th1, and Th2) lymphocyte subpopulations were measured by flow cytometry in the peripheral blood of 929 free-living participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Cross-sectional relationships of lymphocyte subpopulations with type 2 diabetes (n = 154) and fasting glucose and insulin concentrations were evaluated by generalized linear models.
Each standard deviation (SD) higher CD4+ memory cells was associated with a 21% higher odds of type 2 diabetes (95% CI: 1-47%) and each SD higher naive cells was associated with a 22% lower odds (95% CI: 4-36%) (adjusted for age, gender, race/ethnicity, and BMI). Among participants not using diabetes medication, higher memory and lower naive CD4+ cells were associated with higher fasting glucose concentrations (p<0.05, adjusted for age, sex, and race/ethnicity). There were no associations of γδ T, NK, Th1, or Th2 cells with type 2 diabetes, glucose, or insulin.
A higher degree of chronic adaptive immune activation, reflected by higher memory and lower naive CD4+ cells, was positively associated with type 2 diabetes. These results are consistent with a role of chronic immune activation and exhaustion augmenting chronic inflammatory diseases, and support the importance of prospective studies evaluating adaptive immune activation and type 2 diabetes.
BackgroundThe association between physical activity (PA), sedentary behavior, and incident diabetes has been assessed in whites but is less well investigated in multiethnic populations.ObjectiveTo ...assess the association between PA, sedentary behavior, and incident diabetes in the Multi-Ethnic Study of Atherosclerosis.Research design and methodsIncident diabetes was assessed among adults without prevalent baseline diabetes (2000–2002) at 5 in-person examinations between 2002 and 2012. Baseline PA (moderate, vigorous, and exercise-specific; metabolic equivalents of task-hours/week) and sedentary behaviors (television watching, reading; hours/day) were assessed by questionnaire. HRs were estimated using Cox proportional hazard models.ResultsAmong 5829 adults (mean age 61.8 years, 54% female, 42% white, 12% Chinese-American, 26% African-American, 21% Hispanic-American), there were 655 incident diabetes cases (median follow-up 11.1 years). After adjustment, diabetes risk was lower in those with brisk or striding compared with none or casual walking pace (HR 0.67; 95% CI 0.54 to 0.84), higher levels of exercise PA (HR for highest vs lowest quartile 0.79; 95% CI 0.63 to 0.98), and any compared with no vigorous PA (HR 0.79; 95% CI 0.66 to 0.95). Race/ethnicity influenced the association of walking pace, exercise PA, and any vigorous PA on diabetes risk, which was only significant among whites. Total leisure sedentary behaviors (HR for highest vs lowest quartile 1.65; 95% CI 1.26 to 2.14) and television watching (HR for highest vs lowest quartile 2.68; 95% CI 1.38 to 5.21) were significantly associated with diabetes risk in multiethnic analyses and were influenced by race/ethnicity.ConclusionsThese results confirm the importance of PA and sedentary behavior on diabetes risk in a multiethnic population and demonstrate potential variations across race/ethnic groups.
Chronic kidney disease is associated with a higher risk for cardiovascular mortality, as well as all-cause mortality. Whether chronic kidney disease is a predictor of noncardiovascular mortality is ...less clear. To further explore the latter, the association of kidney function with total noncardiovascular mortality and cause-specific mortality was assessed in the Cardiovascular Health Study, a community-based cohort of older individuals. Kidney disease was assessed using cystatin C and estimated GFR in 4637 participants in 1992 to 1993. Participants were followed until June 30, 2001. Deaths were adjudicated as cardiovascular or noncardiovascular disease by committee, and an underlying cause of death was assigned. The associations of kidney function with total noncardiovascular mortality and cause-specific mortality were analyzed by proportional hazards regression. Noncardiovascular mortality rates increased with higher cystatin C quartiles (16.8, 17.1, 21.6, and 50.0 per 1000 person-years). The association of cystatin C with noncardiovascular mortality persisted after adjustment for demographic factors; the presence of diabetes, C-reactive protein, hemoglobin, and prevalent cardiovascular disease; and measures of atherosclerosis (hazard ratio 1.69; 95% confidence interval 1.33 to 2.15, for the fourth quartile versus the first quartile). Results for estimated GFR were similar. The risk for noncardiac deaths attributed to pulmonary disease, infection, cancer, and other causes was similarly associated with cystatin C levels. Kidney function predicts noncardiovascular mortality from multiple causes in the elderly. Further research is needed to understand the mechanisms and evaluate interventions to reduce the high mortality rate in chronic kidney disease.
We examined associations of pentraxin 3 (PTX3), a vascular inflammation marker, with incident cardiovascular disease (CVD) and all-cause death.
1583 Cardiovascular Health Study participants free of ...prevalent CVD were included. Nonexclusive case groups were angina (n=476), myocardial infarction (MI; n=237), stroke (n=310), CVD death (n=282), and all-cause death (n=772). 535 participants had no events. PTX3 levels were higher in those with subclinical CVD (1.90+/-1.89 ng/mL) than those without (1.71+/-1.88 ng/mL; P=0.001). Using Cox regression adjusted for age, sex, and ethnicity, a standard deviation increase in PTX3 (1.89 ng/mL) was associated with CVD death (hazard ratio 1.11; 95% confidence interval 1.02 to 1.21) and all-cause death (1.08; 1.02 to 1.15). PTX3 was not associated with angina (1.09; 0.98 to 1.20), MI (0.96; 0.81 to 1.12), or stroke (1.06; 0.95 to 1.18). Adding C-reactive protein (CRP) or CVD risk factors to the models had no significant effects on associations.
In these older adults, PTX3 was associated with CVD and all-cause death independent of CRP and CVD risk factors. PTX3 likely reflects different aspects of inflammation than CRP and may provide insight into vascular health in aging and chronic diseases of aging that lead to death.
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