Inflammatory proteins are associated with mortality in a middle-aged diverse cohort.

BACKGROUND: Recent data indicate a decline in overall longevity in the United States. Even prior to the COVID-19 pandemic, an increase in midlife mortality rates had been reported. Life expectancy disparities have persisted in the United States for racial and ethnic groups and for individuals living at low socioeconomic status. These continued trends in mortality indicate the importance of examining biomarkers of mortality at midlife in at-risk populations. Circulating levels of cytokines and inflammatory markers reflect systemic chronic inflammation, which is a well-known driver of many age-related diseases. METHODS: In this study, we examined the relationship of nine different inflammatory proteins with mortality in a middle-aged socioeconomically diverse cohort of African-American and White men and women (n = 1122; mean age = 47.8 years). RESULTS: We found significant differences in inflammatory-related protein serum levels between African-American and White middle-aged adults. E-selectin and fibrinogen were significantly higher in African-American adults. IFN-γ, TNF-α trimer, monocyte chemoattractant protein-1 (MCP-1), soluble receptor for advanced glycation end-products (sRAGE) and P-selectin were significantly higher in White participants compared to African-American participants. Higher levels of E-selectin, MCP-1 and P-selectin were associated with a higher mortality risk. Furthermore, there was a significant interaction between sex and IL-6 with mortality. IL-6 levels were associated with an increased risk of mortality, an association that was significantly greater in women than men. In addition, White participants with high levels of sRAGE had significantly higher survival probability than White participants with low levels of sRAGE, while African-American participants had similar survival probabilities across sRAGE levels. CONCLUSIONS: These results suggest that circulating inflammatory markers can be utilized as indicators of midlife mortality risk in a socioeconomically diverse cohort of African-American and White individuals.

Association of extracellular vesicle inflammatory proteins and mortality.

Even before the COVID-19 pandemic declines in life expectancy in the United States were attributed to increased mortality rates in midlife adults across racial and ethnic groups, indicating a need for markers to identify individuals at risk for early mortality. Extracellular vesicles (EVs) are small, lipid-bound vesicles capable of shuttling functional proteins, nucleic acids, and lipids. Given their role as intercellular communicators and potential biomarkers of disease, we explored whether circulating EVs may be markers of mortality in a prospective, racially, and socioeconomically diverse middle-aged cohort. We isolated plasma EVs from 76 individuals (mean age = 59.6 years) who died within a 5 year period and 76 surviving individuals matched by age, race, and poverty status. There were no significant differences in EV concentration, size, or EV-associated mitochondrial DNA levels associated with mortality. We found that several EV-associated inflammatory proteins including CCL23, CSF-1, CXCL9, GDNF, MCP-1, STAMBP, and 4E-BP1 were significantly associated with mortality. IL-10RB and CDCP1 were more likely to be present in plasma EVs from deceased individuals than in their alive counterparts. We also report differences in EV-associated inflammatory proteins with poverty status, race, and sex. Our results suggest that plasma EV-associated inflammatory proteins are promising potential clinical biomarkers of mortality.

Race-specific alterations in DNA methylation among middle-aged African Americans and Whites with metabolic syndrome.

Metabolic syndrome (MetS) is a cluster of cardiometabolic risk factors for all-cause mortality, cardiovascular disease, and cancer. Identifying epigenetic alterations associated with MetS in African Americans (AAs) and Whites may provide insight into genes that influence its differential health outcomes. We examined DNA methylation (DNAm) and performed an epigenome-wide association study (EWAS) of MetS among AAs and Whites with and without MetS. We assessed age, race and poverty status associated DNAm among AAs (n = 225) and White (n = 233) adults using NCEP-ATP III guidelines. Genome-wide DNAm measurement was assessed using Illumina Infinium Methylation EPIC BeadChip. Differentially methylated positions (DMPs) and differentially methylated regions (DMRs) were identified using dmpFinder and bumphunter. EWAS was performed using CpGassoc. We found significant DMPs associated with age, poverty status and MetS in each race. GSTT1(Glutathione S-Transferase Theta 1) was one of the top-hypermethylated genes and MIPEP (Mitochondrial Intermediate Peptidase) was one of the most hypomethylated genes when comparing AAs with and without MetS. PPP1R13L (Protein Phosphatase 1 Regulatory Subunit 13 Like) was the top hypermethylated and SCD (stearoyl-CoA desaturase-1) was one of the most hypomethylated genes for Whites with and without MetS. EWAS results showed that DNAm differences might contribute to MetS risk among Whites and AAs since different genes were identified in AAs and Whites. We replicated previously identified MetS associated genes and found that Thioredoxin-interacting protein (TXN1P) was statistically significantly differentially expressed only in Whites. Our results may be useful in further studies of genes underlying differences in MetS among AAs and Whites.

E-cigarette Product Use, or Vaping, Among Persons with Associated Lung Injury - Illinois and Wisconsin, April-September 2019.

In July 2019, the Illinois Department of Public Health and the Wisconsin Department of Health Services launched a coordinated epidemiologic investigation after receiving reports of several cases of lung injury in previously healthy persons who reported electronic cigarette (e-cigarette) use, or vaping (1). This report describes features of e-cigarette product use by patients in Illinois and Wisconsin. Detailed patient interviews were conducted by telephone, in person, or via the Internet with 86 (68%) of 127 patients. Overall, 75 (87%) of 86 interviewed patients reported using e-cigarette products containing tetrahydrocannabinol (THC), and 61 (71%) reported using nicotine-containing products. Numerous products and brand names were identified by patients. Nearly all (96%) THC-containing products reported were packaged, prefilled cartridges, and 89% were primarily acquired from informal sources (e.g., friends, family members, illicit dealers, or off the street). In contrast, 77% of nicotine-containing products were sold as prefilled cartridges, and 83% were obtained from commercial vendors. The precise source of this outbreak is currently unknown (2); however, the predominant use of prefilled THC-containing cartridges among patients with lung injury associated with e-cigarette use suggests that they play an important role. While this investigation is ongoing, CDC recommends that persons consider refraining from using e-cigarette, or vaping, products, particularly those containing THC. Given the diversity of products reported and frequency of patients using both THC- and nicotine-containing e-cigarette products, additional methods such as product testing and traceback could help identify the specific cause of this outbreak.