Associations of genetic and infectious risk factors with coronary heart disease

Abstract

Coronary heart disease (CHD) is one of the most pressing health problems of our time and a major cause of preventable death. CHD results from complex interactions between genetic and environmental factors. Using multiplex serological testing for persistent or frequently recurring infections and genome-wide analysis in a prospective population study, we delineate the respective and combined influences of genetic variation, infections, and low-grade inflammation on the risk of incident CHD. Study participants are enrolled in the CoLaus|PsyCoLaus study, a longitudinal, population-based cohort with baseline assessments from 2003 through 2008 and follow-up visits every 5 years. We analyzed a subgroup of 3459 individuals with available genome-wide genotyping data and immunoglobulin G levels for 22 persistent or frequently recurring pathogens. All reported CHD events were evaluated by a panel of specialists. We identified independent associations with incident CHD using univariable and multivariable stepwise Cox proportional hazards regression analyses. Of the 3459 study participants, 210 (6.07%) had at least one CHD event during the 12 years of follow-up. Multivariable stepwise Cox regression analysis, adjusted for known cardiovascular risk factors, socioeconomic status, and statin intake, revealed that high polygenic risk (hazard ratio [HR] 1.31, 95% CI 1.10–1.56, p=2.64 × 10−3) and infection with Fusobacterium nucleatum (HR 1.63, 95% CI 1.08–2.45, p=1.99 × 10−2) were independently associated with incident CHD. In a prospective, population-based cohort, high polygenic risk and infection with F. nucleatum have a small, yet independent impact on CHD risk.

Ectopic colonization by oral bacteria as an emerging theme in health and disease

“…As in the case of neurological diseases, there is still little evidence to support a role for ectopic colonization by oral bacteria in cardiovascular diseases. Very recently, Hodel et al ( 2023 ) pointed out a positive correlation between the detection of antibodies against the oral pathobiont F. nucleatum and a higher risk of suffering from coronary heart disease. A previous study demonstrated that F. nucleatum can migrate from the oral cavity to arterial plaques (Figuero et al 2011 ).…”

“…For years, the exact origin and nature of ectopically colonizing oral strains has been an open question in the field. Indeed, most of the studies assessing for ectopic colonization by oral bacteria are based on 16S rRNA gene amplicon sequencing data (Muhlebach et al 2018 , Dinakaran et al 2019 , Chen et al 2020 , 2021 , Yin et al 2021 , Hodel et al 2023 ), thus not allowing for strain-level inference and comparisons. In recent years, several studies have started to tackle this question by analyzing in parallel the microbiome in the saliva as well as from ectopically colonized sites.…”

“…However, in the last years, there has been accumulating evidence highlighting the central role of ectopic colonization by oral bacteria in distant places including the intestine, placenta, nasal tissue, lungs and upper airways, and aorta, contributing to many noncommunicable diseases including inflammatory bowel diseases (IBDs) (Atarashi et al 2017 , Dinakaran et al 2019 , Hu et al 2021 , Molinero et al 2022 , Rojas-Tapias et al 2022 , Rashidi et al 2023 ), undernutrition (Vonaesch et al 2018 , 2022 , Chen et al 2020 , Collard et al 2022 ), preterm birth (Van der Haar et al 2018 , Yin et al. 2021 ), neurological diseases (Nicholson and Landry 2022 ), liver diseases (Joossens 2021 ), lung diseases (Joossens 2021 ), heart diseases (Hodel et al 2023 ), or colonic cancer (Flemer et al 2018 , Rashidi et al 2023 ). There is thus an increased interest in understanding the molecular mechanisms that lead to the colonization and maintenance of oral bacteria at ectopic sites.…”