Do Childhood Infections Cause Adult Cardiometabolic Disease?
Cardiovascular disease (CVD) and related metabolic conditions—together termed "cardiometabolic diseases"—account for much of the increasing global morbidity and mortality rates from noncommunicable disease. They account for more than twice the number of deaths from cancer and the disease burden is predicted to increase over the coming decades. Traditional cardiovascular risk factors (hypertension, diabetes mellitus, obesity, hypercholesterolemia, and smoking) do not account for all the attributable risk. Recent paradigm shifts in the understanding of these adult-onset conditions are that cardiometabolic diseases may have their origins very early in life and that risk parameters track from childhood into adulthood. Pathological changes, which may be partly reversible, accumulate silently for decades before causing disease in adulthood. Therefore, childhood remains a largely overlooked opportunity for prevention. The American Heart Association has stated that "cardiovascular disease is largely preventable"; however, effective primordial (ie, prevention of risk factors themselves) and primary prevention require an understanding of the very early determinants of risk.
Cardiometabolic diseases are multifactorial, chronic inflammatory conditions. Inflammatory responses begin in infancy, and these trajectories may persist into later life. On the one hand, these responses are protective; inflammation is a fundamental host response to infection, especially early in life during the maturation of the adaptive immune system. On the other, it seems that persistent inflammatory responses are ultimately maladaptive, with higher levels of inflammatory markers predicting clinical events and adverse outcomes; phase III trials specifically targeting inflammatory pathways are currently under way in adults with CVD.
There is thus considerable interest in the role of infection in the development of cardiometabolic risk and disease. This relationship was first suggested in the late 19th century, when rabbits infected with salmonella or streptococci after minor arterial injury developed more severe atherosclerosis. Here, we briefly review more recent human data on childhood infection and cardiometabolic diseases, including whether a single or multiple pathogens are implicated, the relationship of infection and inflammation with traditional risk factors, and the possible role of antibiotic exposures and the possible effects on the microbiome.
Introduction
Cardiovascular disease (CVD) and related metabolic conditions—together termed "cardiometabolic diseases"—account for much of the increasing global morbidity and mortality rates from noncommunicable disease. They account for more than twice the number of deaths from cancer and the disease burden is predicted to increase over the coming decades. Traditional cardiovascular risk factors (hypertension, diabetes mellitus, obesity, hypercholesterolemia, and smoking) do not account for all the attributable risk. Recent paradigm shifts in the understanding of these adult-onset conditions are that cardiometabolic diseases may have their origins very early in life and that risk parameters track from childhood into adulthood. Pathological changes, which may be partly reversible, accumulate silently for decades before causing disease in adulthood. Therefore, childhood remains a largely overlooked opportunity for prevention. The American Heart Association has stated that "cardiovascular disease is largely preventable"; however, effective primordial (ie, prevention of risk factors themselves) and primary prevention require an understanding of the very early determinants of risk.
Cardiometabolic diseases are multifactorial, chronic inflammatory conditions. Inflammatory responses begin in infancy, and these trajectories may persist into later life. On the one hand, these responses are protective; inflammation is a fundamental host response to infection, especially early in life during the maturation of the adaptive immune system. On the other, it seems that persistent inflammatory responses are ultimately maladaptive, with higher levels of inflammatory markers predicting clinical events and adverse outcomes; phase III trials specifically targeting inflammatory pathways are currently under way in adults with CVD.
There is thus considerable interest in the role of infection in the development of cardiometabolic risk and disease. This relationship was first suggested in the late 19th century, when rabbits infected with salmonella or streptococci after minor arterial injury developed more severe atherosclerosis. Here, we briefly review more recent human data on childhood infection and cardiometabolic diseases, including whether a single or multiple pathogens are implicated, the relationship of infection and inflammation with traditional risk factors, and the possible role of antibiotic exposures and the possible effects on the microbiome.