Publication Date
10-1-2024
Journal
Journal of the American Heart Association
DOI
10.1161/JAHA.124.035693
PMID
39344648
PMCID
PMC11681464
PubMedCentral® Posted Date
9-30-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Humans, Male, Female, Aged, Metagenomics, Middle Aged, Coronary Disease, United States, Aged, 80 and over, Risk Factors, Gram-Positive Bacterial Infections, Incidence, cardiovascular heart disease, Gemella morbillorum, MESA, metagenomics, Pseudomonas, Cardiovascular Disease
Abstract
BACKGROUND: Inflammation is a feature of coronary heart disease (CHD), but the role of proinflammatory microbial infection in CHD remains understudied.
METHODS AND RESULTS: CHD was defined in the MESA (Multi-Ethnic Study of Atherosclerosis) as myocardial infarction (251 participants), resuscitated arrest (2 participants), and CHD death (80 participants). We analyzed sequencing reads from 4421 MESA participants in the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program using the PathSeq workflow of the Genome Analysis Tool Kit and a 65-gigabase microbial reference. Paired reads aligning to 840 microbes were detected in >1% of participants. The association of the presence of microbe reads with incident CHD (follow-up, ~18 years) was examined. First, important variables were ascertained using a single regularized Cox proportional hazard model, examining change of risk as a function of presence of microbe with age, sex, education level, Life's Simple 7, and inflammation. For variables of importance, the hazard ratio (HR) was estimated in separate (unregularized) Cox proportional hazard models including the same covariates (significance threshold Bonferroni corrected
CONCLUSIONS: Metagenomics of whole-genome sequence reads opens a possible frontier for detection of pathogens for chronic diseases. The association of
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