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).