Biomedical subjects

Teresa E Seeman

Publications and source records attributed to Teresa E Seeman.

At least 19 recordsLinked to original sources

PubMed2025

GWAS of CRP response to statins further supports the role of APOE in statin response: A GIST consortium study.

Statins are first-line treatments in the primary and secondary prevention of cardiovascular disease. Clinical studies show statins act independently of lipid-lowering mechanisms to decrease C-reactive protein (CRP), an inflammation marker. We aim to elucidate genetic loci associated with CRP statin response. CRP statin response is the change in log-CRP between off-treatment and on-treatment measurements. Cohort-level Genome-Wide Association Studies (GWAS) of CRP response were performed using 1000 Genomes imputed data, testing ∼10 million common genetic variants. GWAS meta-analysis combined results from seven cohorts and clinical trials totalling 14,070 statin-treated individuals of European ancestry within the GIST consortium. Secondary analyses included statin-by-placebo interaction analyses, and lookups in African ancestry cohorts. Our GWAS identified two genome-wide significant (P < 5e-8) loci: APOE and HNF1A for CRP statin response corrected for baseline CRP. The missense lead variant rs429358 at APOE, contributing to the APOE-E4 haplotype, is a risk locus for dyslipidaemia, Alzheimer's and coronary artery disease (CAD). The HNF1A locus is associated with diabetes, cholesterol levels, and CAD. Both loci are also associated with baseline CRP levels, and neither locus achieved a significant (P < 0.05) result from the statin v. placebo interaction meta-analysis using randomized clinical trial data. However, the interaction result (P-int=0.09) for APOE was suggestive and possibly underpowered. The APOE-E4 signal may therefore be associated with both CRP and LDL-cholesterol statin response. Combined with suggestions in the literature that APOE also leads to differential statin benefit in Alzheimer's, the APOE locus warrants further investigation for potential genetic effects on healthcare with statin treatment.

Humans↗

PubMed2006

The associations between socioeconomic status, allostatic load and measures of health in older Taiwanese persons: Taiwan social environment and biomarkers of aging study.

Data from a national representative sample of 1023 elderly and near-elderly Taiwanese were used to explore whether allostatic load is associated with health outcomes and mediates the association between socioeconomic status and health in a non-Western population. The information collected included: demographic characteristics; allostatic load scores; socioeconomic status, measured by education and income; health behaviours; health-related variables, including self-rated health, basic activities of daily living difficulties, instrumental activities of daily living difficulties, and physical activity difficulties. The adjusted prevalent odds ratios of higher allostatic load level were 1.25 (95% CI: 1.00, 1.56) for reporting one level worse in self-rated health and 1.43 (95% CI: 1.14, 1.82) for reporting one more physical activity difficulty. There were significant associations of lower education or less income with worse self-rated health and more difficulties with physical functioning. The associations between education, income and health status are not mediated by the conventional ten-point measure of allostatic load in older Taiwanese adults.

Age Factors↗

PubMed2006

Combinations of biomarkers predictive of later life mortality.

A wide range of biomarkers, reflecting activity in a number of biological systems (e.g., neuroendocrine, immune, cardiovascular, and metabolic), have been found to prospectively predict disability, morbidity, and mortality outcomes in older adult populations. Levels of these biomarkers, singly or in combination, may serve as an early warning system of risk for future adverse health outcomes. In the current investigation, 13 biomarkers were examined as predictors of mortality occurrence over a 12-year period in a sample of men and women (n = 1,189) 70-79 years of age at enrollment into the study. Biomarkers examined in analyses included markers of neuroendocrine functioning (epinephrine, norepinephrine, cortisol, and dehydroepiandrosterone), immune activity (C-reactive protein, fibrinogen, IL-6, and albumin), cardiovascular functioning (systolic and diastolic blood pressure), and metabolic activity [high-density lipoprotein (HDL) cholesterol, total to HDL cholesterol ratio, and glycosylated hemoglobin]. Recursive partitioning techniques were used to identify a set of pathways, composed of combinations of different biomarkers, that were associated with a high-risk of mortality over the 12-year period. Of the 13 biomarkers examined, almost all entered into one or more high-risk pathways although combinations of neuroendocrine and immune markers appeared frequently in high-risk male pathways, and systolic blood pressure was present in combination with other biomarkers in all high-risk female pathways. These findings illustrate the utility of recursive partitioning techniques in identifying biomarker combinations predictive of mortal outcomes in older adults, as well as the multiplicity of biological pathways to mortality in elderly populations.

Age Factors↗

PubMed2006

Relationship of early life stress and psychological functioning to adult C-reactive protein in the coronary artery risk development in young adults study.

BACKGROUND: Low socioeconomic status (SES) and a harsh family environment in childhood have been linked to mental and physical health disorders in adulthood. The objective of the present investigation was to evaluate a developmental model of pathways that may help explain these links and to relate them to C-reactive protein (CRP) in the Coronary Artery Risk Development in Young Adults (CARDIA) dataset. METHODS: Participants (n = 3248) in the CARDIA study, age 32 to 47 years, completed measures of childhood SES (CSES), early family environment (risky families [RF]), adult psychosocial functioning (PsyF, a latent factor measured by depression, mastery, and positive and negative social contacts), body mass index (BMI), and C-reactive protein. RESULTS: Structural equation modeling indicated that CSES and RF are associated with C-reactive protein via their association with PsyF (standardized path coefficients: CSES to RF, RF to PsyF, PsyF to CRP, CSES to CRP, all p < .05), with good overall model fit. The association between PsyF and CRP was partially mediated by BMI (PsyF to BMI, BMI to CRP, both p < .05). CONCLUSIONS: Low childhood SES and a harsh early family environment appear to be related to elevated C-reactive protein in adulthood through pathways involving psychosocial dysfunction and high body mass index.

Adult↗

PubMed2006

Urban neighborhood context, educational attainment, and cognitive function among older adults.

Existing research has not addressed the potential impact of neighborhood context--educational attainment of neighbors in particular--on individual-level cognition among older adults. Using hierarchical linear modeling, the authors analyzed data from the 1993 Study of Assets and Health Dynamics Among the Oldest Old (AHEAD), a large, nationally representative sample of US adults born before 1924. Data from participants residing in urban neighborhoods (n = 3,442) were linked with 1990 US Census tract data. Findings indicate that 1) average cognitive function varies significantly across US Census tracts; 2) older adults living in low-education areas fare less well cognitively than those living in high-education areas, net of individual characteristics, including their own education; 3) this association is sustained when controlling for contextual-level median household income; and 4) the effect of individual-level educational attainment differs across neighborhoods of varying educational profiles. Promoting educational attainment among the general population living in disadvantaged neighborhoods may prove cognitively beneficial to its aging residents because it may lead to meliorations in stressful life conditions and coping deficiencies.

Aged↗

PubMed2006

Relation of social integration to inflammatory marker concentrations in men and women 70 to 79 years.

The lack of social integration has predicted coronary heart disease morbidity and mortality in prospective observational studies; however, the biologic mechanisms by which this may occur are not well understood. The objective of this study was to determine whether social integration is associated with inflammatory risk factors for coronary heart disease, specifically C-reactive protein (CRP) and interleukin-6. The study participants (aged 70 to 79 years; 380 men and 425 women) were from the MacArthur Successful Aging Study, a longitudinal study of 3 community-based cohorts in the United States of older adults with relatively high physical and cognitive functioning at baseline (1988 to 1989). The plasma concentrations of interleukin-6 and CRP were assessed using a high-sensitivity enzyme-linked immunosorbent assay. Cross-sectional logistic regression analyses were performed. Multivariate adjusted analyses indicated that social integration was significantly inversely associated with CRP concentration in men after adjusting for age, race/ethnicity, smoking, alcohol consumption, physical activity, body mass index, cardiovascular disease, other major or chronic conditions, physical functioning, socioeconomic status, and depression (odds ratio 2.23, 95% confidence interval 1.05 to 4.76, for elevated CRP [>3.19 mg/L] in the least socially integrated quartile vs the most socially integrated quartile). No significant associations were found between social integration and interleukin-6 in men or either inflammatory marker in women. In conclusion, social integration was negatively associated with the plasma CRP concentration in men. These findings suggest a potential biologic mechanism for the observed associations between social integration and coronary heart disease in prospective studies. Differences may exist between women and men in the biologic pathways associated with social integration.

Age Factors↗

PubMed2006

Cognitive functioning and sex steroid hormone gene polymorphisms in women at midlife.

Single nucleotide polymorphism (SNP) genotype frequencies were examined to determine whether variation in 6 estrogen-related genes was associated with differences in cognitive functioning in women at midlife. DNA from a multiracial/multiethnic sample of 875 African American, Caucasian, Chinese, and Japanese women aged 45 to 56 years participating in the Study of Women's Health Across the Nation (SWAN) was genotyped. Gene markers from the sex steroid hormone pathway were linked to measures of cognitive functioning including the Digit Span Backward Test (DSB), a measure of working memory; the Symbol Digit Modalities Test (SDMT), a measure of perceptual speed; and the East Boston Memory Test (EBMT), a measure of episodic memory. Statistical models were fit using logistic regression and general linear models to estimate the strength of association of estrogen-related polymorphisms with DSB, SDMT, and EBMT scores. On the EBMT, African American women and Caucasian women with ESR1 rs9340799 GG genotypes had about 1.5 to 2.0 times greater odds of remembering story elements on the EBMT-immediate recall test. Caucasian women with ESR1 rs2234693 CC genotypes had 1.3 to 1.5 times greater odds of remembering story elements on the EBMT-delayed recall test. Chinese women with 17HSD rs615942 GG genotypes, 17HSD rs592389 TT genotypes, and 17HSD rs2830 GG genotypes had about 1.7 times greater odds of remembering story elements on the EBMT-immediate recall test. African American women with CYP 19 rs936306 CC genotypes had about 0.25 to 0.40 lower odds of remembering story elements on the EBMT-immediate recall test, whereas Chinese women with CYP 19 rs936306 CC genotypes had about 2.3 times greater odds of remembering story elements on both the EBMT-immediate and -delayed recall tests. On the DSB, African American women with CYP 19 rs749292 GG genotype had a higher mean score. On the SDMT, Japanese women with ESR1 rs728524 GG genotypes had a higher mean score. On the 3 tests of cognitive functioning, there was 1 significant finding for CYP1A1 and none for the CYP1B1 or ESR2 SNPs. We conclude that selected genes involved in estrogen synthesis and metabolism may be associated with performance differences on cognitive function tests. Also, the relevant estrogen-related polymorphisms may vary by race/ethnicity.

17-Hydroxysteroid Dehydrogenases↗

PubMed2006

Association between serum beta-carotene levels and decline of cognitive function in high-functioning older persons with or without apolipoprotein E 4 alleles: MacArthur studies of successful aging.

BACKGROUND: Growing evidence from animal studies suggests an interaction between antioxidants and apolipoprotein E (APOE) alleles on cognitive functioning. We used data from a 7-year cohort study of high-functioning older persons to explore whether the associations between serum beta-carotene level and subsequent decline of cognitive function differed by APOE 4 genotype. METHODS: Baseline information on sociodemographic characteristics, serum beta-carotene level, inflammation markers, APOE genotype, and cognitive functioning measured by a 9-item Short Portable Mental Status Questionnaire (SPMSQ) was obtained in 455 survivors. Multivariable logistic regression analyses were used to examine the relation between high serum beta-carotene level and risk of SPMSQ score decline in participants with or without APOE 4 alleles, while adjusting for age, sex, race, baseline SPMSQ score, and other covariates. RESULTS: Nine (2%) study participants had homozygous and 97 (21%) had heterozygous APOE 4 alleles. Two hundred forty-nine (55%) had decline of SPMSQ scores during the follow-up. The presence of an APOE 4 allele was associated with higher risk and larger magnitude of SPMSQ score decline. The adjusted odds ratio of high beta-carotene level for cognitive decline was 0.11 (95% confidence interval, 0.02-0.57) in participants with at least one APOE 4 allele and 0.89 (95% confidence interval, 0.54-1.47) among those who were APOE 4 negative. CONCLUSION: Among high-functioning older persons, antioxidants and beta-carotene in particular may offer protection from cognitive decline in persons with greater genetic susceptibility as evidenced by the presence of the APOE 4 allele.

Activities of Daily Living↗

PubMed2005

Socioeconomic status and C-reactive protein levels in the US population: NHANES IV.

C-reactive protein (CRP), a marker of inflammation, has been identified as a risk factor for cardiovascular disease and mortality. Using data on adults aged 20 and over from the fourth National Health and Nutrition Examination Survey, a nationally representative cross-sectional survey, we examined the association between socioeconomic status and CRP in US adults (N=7634). Socioeconomic variation in CRP occurred only at very high levels of CRP (>10.0 mg/L). There was no significant difference in the prevalence of moderate (1.1-3.0 mg/L) or high values of CRP (3.1-10.0mg/L) by socioeconomic status; however, among those with family income at or below the poverty level, 15.7% had very high levels of CRP (greater than 10.0 mg/L), compared to only 9.1% of those in families above the poverty level. Logistic regression results indicate that acute illness, chronic conditions, and differential health behaviors account for about two-thirds of this association. African Americans, Hispanics, and women were more likely to have high levels of CRP. Obesity was the largest risk factor for every level of CRP above normal. Results suggest that differences in very high CRP may be due to factors beyond acute illness and may also reflect chronic health, behavioral and disease processes associated with low socioeconomic status.

Adult↗

PubMed2005

Urinary cortisol excretion as a predictor of incident cognitive impairment.

Elevated glucocorticoid levels have been associated with cognitive impairment, including dementia. However, few longitudinal studies have examined the association between resting cortisol levels and the incidence of cognitive impairment. We measured overnight urinary excretion of cortisol in 538 high-functioning men and women, 70-79 years of age, in 1988, and assessed their cognitive functioning in 1988, 1991, and 1995 using the short portable mental status questionnaire (SPMSQ). Compared to participants in the bottom quartile of urinary cortisol at baseline, those in the top three quartiles had higher risk of incident cognitive impairment over the 7-year follow up (i.e., decline in SPMSQ score to below six out of nine). This association was not affected by adjustment for age, gender, education level, ethnicity, smoking, prevalent cardiovascular disease, and blood pressure (adjusted odds ratio for the highest quartile 2.34, 95% confidence interval, 1.07-5.14). There was no effect modification by gender; the association was equally strong in men and women. We conclude that urinary excretion of cortisol predicts incident cognitive impairment in older men and women.

Aged↗

PubMed2005

Homocysteine versus the vitamins folate, B6, and B12 as predictors of cognitive function and decline in older high-functioning adults: MacArthur Studies of Successful Aging.

BACKGROUND: Elevated plasma total homocysteine concentration may be a risk factor for cognitive decline and Alzheimer disease, but data from prospective studies are limited. Further, high homocysteine levels are associated with low vitamin status, and it is unknown whether it is homocysteine toxicity or vitamin insufficiency that is responsible for the observed cognitive dysfunction. METHODS: We performed cross-sectional and longitudinal analyses of a cohort of 499 high-functioning community-dwelling persons aged 70 to 79 years to determine the effect of homocysteine and related vitamin plasma concentrations on cognitive function and cognitive decline. Nonfasting plasma concentrations of homocysteine, folate, vitamin B(6), and vitamin B(12) were measured at baseline. Summary measures of cognitive function were created from tests of multiple cognitive domains administered at baseline and again after 7 years. RESULTS: In cross-sectional analyses investigating each variable separately, subjects with elevated homocysteine levels, or low levels of folate or vitamin B(6), demonstrated worse baseline cognitive function. In longitudinal analyses, after adjusting for multiple covariates, including homocysteine, those in the bottom quartile of folate had a 1.6-fold increased risk (95% confidence interval: 1.01 to 2.31; P =0.04) of being in the worst quartile of 7-year cognitive decline. Low folate levels largely accounted for a trend towards greater cognitive decline with elevated homocysteine level. CONCLUSION: In high-functioning older adults, low folate levels appear to be a risk factor for cognitive decline. The risk of developing cognitive decline might be reduced through dietary folate intake.

Aged↗

PubMed2005

Increase in epinephrine excretion is associated with cognitive decline in elderly men: MacArthur studies of successful aging.

BACKGROUND: High stress hormone levels are associated with increased risk of cognitive decline in elderly individuals. However, the effect of late-life changes in stress hormone levels on cognitive decline risk has not been examined. Our objective was to investigate whether increase over time in urinary epinephrine excretion in older adults was associated with subsequent cognitive decline. METHODS: Measurements were made on 154 high-functioning men and women, 70-79 years of age, in 1988, 1991, and 1995. Twelve-hour overnight urinary excretion of epinephrine (normalized by creatinine excretion to adjust for body size) was recorded in 1988 and 1991. Cognitive functioning was assessed in 1991 and 1995 by summary scores based on standard tests of language, memory, abstraction, spatial recognition, and spatial construction. RESULTS: Compared to individuals whose epinephrine excretion decreased between 1988 and 1991, the individuals whose epinephrine excretion increased over the same period had greater subsequent declines in summary cognitive scores between 1991 and 1995. After adjusting for baseline epinephrine, baseline cognitive function, and relevant covariates, and stratifying by gender, increases in urine epinephrine were positively associated with cognitive decline only in men. CONCLUSIONS: We conclude that increase in urinary excretion of epinephrine predicts subsequent cognitive decline in older men.

Aged↗

PubMed2005

Impact of socioeconomic status on longitudinal accumulation of cardiovascular risk in young adults: the CARDIA Study (USA).

Our objectives were to describe the trajectories of biological risk factors of cardiovascular disease in young adults, and to study the association of socioeconomic status (SES) with aggregate risk scores that summarize longitudinal risk accumulation from multiple risk factors. We used data from a prospective, bi-racial, cohort study of 18-30-year-old adults in the USA, initiated in 1985, with 10-year follow-up. SES was measured by parental education level, financial hardship during the study, and the participant's education level by the end of the study. We studied growth patterns of seven biological risk factors for cardiovascular disease using a semi-parametric, class-mixture model to identify clusters of individuals with distinct growth trajectories. Risk scores that summarize risk from all seven risk factors were created to reflect risk at baseline, longitudinal risk change over 10 years, and total accumulated risk. Multivariable regression was used to study their associations with SES within each race/gender group. We found tracking of all seven risk factors: in each case, the cluster with the highest baseline value maintained its position as the highest-risk cluster over the next 10 years. After adjustment for age, lifestyle, and healthcare access, SES was associated inversely with baseline risk score in women (black and white), with risk change score in all four race/gender groups, and with accumulated risk score in women (black and white) and in white men. Our findings suggest that individuals with high overall cardiovascular risk in midlife can be identified by their relatively higher values of risk factors in younger ages and that socioeconomic differences in cardiovascular risk start accumulating early in life.

Adolescent↗

PubMed2005

Education and APOE-e4 in longitudinal cognitive decline: MacArthur Studies of Successful Aging.

Longitudinal data from the MacArthur Study of Successful Aging were used to test for interactions between education and apolipoprotein E (APOE) genotype with respect to time trends in cognitive performance. Interactions between education, APOE-e4 status, and time were found for overall cognitive function, and for subscales measuring memory and naming: The presence of the e4 allele was associated with steeper declines in cognition for those with a greater than eighth-grade education. For those with an eighth-grade education or less, time trends did not differ by APOE genotype. A measure of cognitive impairment (i.e., scores of < or = 7 on the Short Portable Mental Status Questionnaire) yielded parallel though weaker evidence for a similar interaction with respect to risk of cognitive impairment. These findings suggest that the presence of at least one e4 allele appears to reduce the protective effects of education for those with at least a ninth-grade education or more, resulting in steeper cognitive declines with age.

Aged↗

PubMed2005

Relationship between subjective social status and measures of health in older Taiwanese persons.

OBJECTIVES: To compare the association between subjective ladder ranking and health measures with the association between objective indices and health measures in older Taiwanese men and women. DESIGN: Cross-sectional study. SETTING: A population-representative sample of elderly and nearly elderly men and women in Taiwan. PARTICIPANTS: The study included 991 participants from the Social Environment and Biomarkers of Aging Study in Taiwan. MEASUREMENTS: The information collected included demographic characteristics; subjective ladder score of SES; objective measures of SES, including education, income, and occupation; health behaviors; health-related variables such as self-rated health, basic activity of daily living difficulties, instrumental activity of daily living (IADL) difficulties, and physical activity difficulties; and depression score. RESULTS: Low ladder score was associated with poorer self-rated health and more reported IADL and physical activity difficulties, even after adjustment for objective measures of SES and other covariates. The multiply adjusted odds ratio for a one-quartile difference in ladder score and worse self-rated health was 1.19 (95% confidence interval=1.06-1.33). The associations between subjective ladder ranking and health status were generally stronger in those who had 6 years or less of education than in those who received more education. CONCLUSION: A simple subjective assessment of one's ranking on the social hierarchy was associated with self-rated health and physical functional status in an older ethnic Chinese population. The associations were independent of the effects of traditional objective measures of SES, such as education, income, and occupation.

Activities of Daily Living↗

PubMed2004

Cumulative biological risk and socio-economic differences in mortality: MacArthur studies of successful aging.

Previous research has suggested that socio-economic status (SES) differences in mortality are only partially explained by differences in life-style, psychological and social factors. Seven year mortality data (1988-1995) from the MacArthur Study of Successful Aging, a longitudinal study of adults, aged 70-79, from New Haven, CT; East Boston, MA; and Durham, NC; were used to test the hypothesis that a cumulative measure of biological dysregulation ("allostatic load"), reflecting multiple regulatory systems, would serve as a further mediator of SES differences in mortality. Logistic regression analyses revealed that a cumulative index of biological risk explained 35.4% of the difference in mortality risk between those with higher versus lower SES (as measured by less than high school education versus high school or greater educational attainment). Importantly, the cumulative index provided independent explanatory power, over and above a measure of doctor-diagnosed disease, though the latter also contributed to education-related variation in mortality risks. The summary measure of biological risk also accounted for more variance than individual biological parameters, suggesting the potential value of a multi-systems view of biological pathways through which SES ultimately affects morbidity and mortality.

Adaptation, Physiological↗

PubMed2004

Refining the categorization of physical functional status: the added value of combining self-reported and performance-based measures.

BACKGROUND: When considered individually, self-reported functional status and performance-based functional status predict functional status decline and mortality. However, what additional prognostic information is gained by combining these approaches remains unknown. METHODS: The authors used three waves of three sites (5138 participants) of the Established Populations for Epidemiologic Studies of the Elderly to determine the prognostic value of individual and combined approaches. Baseline self-reported (mobility and activities of daily living [ADL] items) and performance-based (Physical Performance Score) functional status information was classified into three and four hierarchical categories, respectively. RESULTS: Based on self-reported information alone, at 1 year, 73% participants had not changed, 15% declined, 6% improved, and 6% died. At 4 years, 53% had not changed, 24% declined, 2% improved, and 22% died. Based on performance-based assessment alone, at 4 years, 33% of the sample remained stable, 37% declined, 6% improved, and 24% died. In the top two self-reported categories, functioning on the performance-based assessment varied widely. Among those who were independent in all self-reported functioning, approximately 40% scored in each of the top two performance-based categories. Among persons in the top two self-reported categories, poorer performance was associated with progressively higher 1-year and 4-year mortality rates. Among persons with impaired mobility and at least 1 ADL dependency, the mortality rate was high and was not influenced by performance-based score. CONCLUSIONS: Combining self-reported and performance-based measurements can refine prognostic information, particularly among older persons with high self-reported functioning. However, if ADL dependency is present, performance-based measures do not add prognostic value regarding mortality.

Activities of Daily Living↗

PubMed2004

The effects of serum beta-carotene concentration and burden of inflammation on all-cause mortality risk in high-functioning older persons: MacArthur studies of successful aging.

BACKGROUND: It remains unclear to what extent the associations between low serum beta-carotene concentration and increased risk for cardiovascular disease and cancers are attributable to inflammation. The objective of this study was to evaluate simultaneously the effects of serum beta-carotene concentration and inflammation on the subsequent all-cause mortality risk in high-functioning older persons. METHODS: The authors conducted a prospective cohort study using information from 672 participants from the MacArthur Studies of Successful Aging. Baseline information was obtained for serum concentrations of beta-carotene, C-reactive protein, interleukin-6, cholesterols, and albumin; body mass index; waist:hip ratio; prevalent medical conditions; health behaviors; and medications. Sex-specific univariate and multivariate logistic regression analyses were used to study the effects of low beta-carotene, high inflammation burden, or both on 7-year all-cause mortality rates while adjusting for other confounders. RESULTS: The serum beta-carotene concentration was inversely associated with C-reactive protein and interleukin-6 levels. After adjustment for inflammation markers and other covariates, the relative risks for low beta-carotene for the 7-year all-cause mortality risk were 2.30 (95% confidence interval [CI], 1.23 to 4.31) in men and 0.85 (95% CI, 0.42 to 1.75) in women. Compared with men with high beta-carotene levels and low inflammation, the multiply adjusted relative risk for low beta-carotene and high inflammation burden was 3.78 (95% CI, 1.69 to 8.47) in men. CONCLUSIONS: Low levels of serum beta-carotene are independently associated with an increased all-cause mortality risk in older men, even after adjustment for the effects of inflammation and other risk factors. In men, but not women, a synergistic effect occurs between low beta-carotene concentration and high inflammation burden in predicting higher mortality rates.

Aged↗