Mechanisms mediated by environment and microbiome
Currently, environment is still the No. 1 element of health. It highly
associates with one’s cardiovascular health and CVD, and other mNCDs,
such as diabetes and cancer. First, socioeconomic environment or
vulnerabilities (50, 51), which includes ethnic differences, educational
attainment, employment, occupational class, income, and
personal relationships may affect individual health. For example, as a
proxy phenotype, there is an obvious link between educational attainment
and cognitive function (52-54). Second, natural (neighborhoods or built)
environment and air quality (55) are important factors of
cardiocerebrovascular health. “Water-Air-Radiation-Sound (WARS)”
pollutions (e.g., e-noise) (56-58) greatly increase the hazard of fCVD
(acute myocardial infarction, stroke).
Third, internal environment with a genetic or family history, new or
traditional modifiable risk factors (59), is a critical variable, such
as maternal adverse pregnancy outcomes (preterm birth, low birth weight)
(60, 61) as well as acute or chronic infection, e.g., COVID-19 (2),
abnormal blood pressure, diabetes, dyslipidemia, hyperuricemia, and
obesity. A recent study found that a genetic factor (ABO genotype) can
alter the composition of the gut microbiota (62), and this is a strong
evidence for internal environment associated with human health. Herein,
the gut microbiota4 may play a crucial role in the
development and progression of eCVD and fCVD. Sometimes positive
intracellular environmental stress in the cardiac cells can help the
heart repair (63). However, changes in the concentrations of
intracellular sodium, calcium, potassium, and ATP/ADP may link to
arrhythmias (64, 65). In addition, in a murine inflammation resolution
model of atherosclerotic plaque, reshaping of the gut microbiome has a
therapeutic effect (66).
Several known risk factors such as age, genetic variants, Y chromosome
(ChrY) structural aberrations and environmental stressors, link to
mosaic loss of ChrY (LOY) in human somatic cells (67), and as the most
commonly acquired mutation, it is associated with mNCDs including
cancer, Alzheimer’s disease, and fCVD. Maternal risk factors in
pregnancy (68) such as advanced age and a suboptimal in utero
environment (fetal growth restriction, preterm birth, and/or
preeclampsia) link to an increased risk of fCVD in adulthood for both
the mother and offspring. Sudden cardiac death in younger patients is
associated with isolated congenital coronary artery anomalies (69).
Acute coronary syndrome have distinct serum metabolome and gut microbial
profiling, which link to an increased risk of coronary artery disease
(CAD) (70).