Priya Palta | PubMed Health

PubMed2026

Proteomic pathways mediating low socioeconomic status and cardiovascular events in older adults in CHS and ARIC.

BACKGROUND AND AIMS: Many studies have linked socioeconomic status (SES) and cardiovascular outcomes, yet the biologic mechanisms mediating these associations are only partially understood. The objective of this study was to identify molecular mediators of the association of low SES with coronary heart disease (CHD) and stroke. METHODS: This research was conducted in 2942 Black and White adults in the Cardiovascular Health Study (mean age 76.2 years) and 10,689 Black and White adults in the Atherosclerosis Risk in Communities Study (mean age 60.0 years). We used factor analysis to create a composite measure of low educational attainment, low-income, and blue-collar occupation. Approximately 5000 proteins were measured with an aptamer-based method, and CHD and stroke events were adjudicated. Results were stratified by race, which was conceptualized as a social factor. RESULTS: Low SES was associated with 44 and 262 proteins, in Black and White adults, respectively. No protein met the Bonferroni adjusted threshold for statistically significantly mediation among Black participants. Among White participants, 23 proteins mediated the association between SES adversity and CHD and 5 mediated the association between SES adversity and stroke. The strongest mediating associations for CHD included PTPRS, SCG3, and MMP12. The strongest mediating associations for stroke included NCAN, FAM20B, and APLP1. SPARCL1 and CDCP1 remained the strongest mediators of the association between SES adversity and CHD, after adjusting for potential confounders and traditional cardiovascular risk factors. CONCLUSION: We identified several biomarkers that characterize the biologic risk of SES adversity on CHD and stroke.

Aged↗

PubMed2024

Urinary Metal Levels, Cognitive Test Performance, and Dementia in the Multi-Ethnic Study of Atherosclerosis.

IMPORTANCE: Metals are established neurotoxicants, but evidence of their association with cognitive performance at low chronic exposure levels is limited. OBJECTIVE: To investigate the association of urinary metal levels, individually and as a mixture, with cognitive tests and dementia diagnosis, including effect modification by apolipoprotein ε4 allele (APOE4). DESIGN, SETTING, AND PARTICIPANTS: The multicenter prospective cohort Multi-Ethnic Study of Atherosclerosis (MESA) was started from July 2000 to August 2002, with follow-up through 2018. A total of 6303 MESA participants were included. Data analysis was performed from October 12, 2023, to June 13, 2024. EXPOSURE: Urine samples were collected at baseline (2000-2002), and arsenic, cadmium, cobalt, copper, lead, manganese, tungsten, uranium, and zinc levels were measured in 2020-2022. MAIN OUTCOMES AND MEASURES: Digit Symbol Coding (DSC) (n = 3819) (possible score range, 0-133), Cognitive Abilities Screening Instrument (CASI) (n = 3918) (possible score range, 0-100), and Digit Span (DS) (n = 4176) (possible score range, 0-30) cognitive tests were administered in 2010-2012; higher scores of each test indicate increasing levels of positive response. RESULTS: A total of 6303 participants were followed up for dementia diagnosis through 2018. The median age at baseline was 60 (IQR, 53-70) years, and 3303 participants (52.4%) were female. The median cognitive scores were 51 (IQR, 38-64) for DSC, 90 (IQR, 84-95) for CASI, and 15 (IQR, 12-18) for DS. There were 559 cases of dementia through the follow-up period. Inverse associations with DSC were identified: mean differences in z scores per IQR increase in metal levels were -0.03 (95% CI, -0.07 to 0.00) for arsenic, -0.05 (95% CI, -0.09 to -0.004) for cobalt, -0.05 (95% CI, -0.07 to -0.02) for copper, -0.04 (95% CI, -0.08 to -0.001) for uranium, and -0.03 (95% CI, -0.06 to -0.01) for zinc. Among 1058 APOE4 carriers, manganese was also inversely associated with DSC. The joint mean difference of DSC comparing percentile 95th with the 25th of the 9-metal mixture was -0.30 (95% CI, -0.47 to -0.14) for APOE4 carriers and -0.10 (95% CI, -0.19 to -0.01) for noncarriers. Arsenic, cadmium, cobalt, copper, tungsten, uranium, and zinc were individually associated with dementia, with hazard ratios per IQR of metal ranging from 1.15 (95% CI, 1.03-1.29) for tungsten to 1.46 (95% CI, 1.06-2.02) for uranium. The joint hazard ratio of dementia comparing percentiles 95th with the 25th of the 9-metal mixture was 1.71 (95% CI, 1.24-3.89), with no significant difference by APOE4 status. CONCLUSIONS AND RELEVANCE: In this study, participants with higher concentrations of metals in their urine, compared with those with lower concentrations, had worse performance on cognitive tests and greater likelihood of developing dementia. The findings of this multicenter multiethnic cohort study might inform screening and potential interventions for prevention of dementia based on individuals' metal exposure levels and genetic profiles.

Humans↗