A Review on the Genetic, Environmental, and Lifestyle Aspects of the Early-Life Origins of Cardiovascular Disease
Introduction
Cardiovascular diseases are the leading cause of death worldwide, with a growing pattern notably in the low- and middle-income countries.1 Their related morbidities also impose huge economic burdens on various populations. Early identification of predisposing factors for cardiovascular diseases is essential for developing different levels of prevention. A major barrier to prevention, however, is that known environmental and genetic factors explain only part of the variability at risk for cardiovascular diseases. This partly reflects that the current research is mostly focusing on adulthood rather than primordial and primary prevention of cardiovascular diseases from early life, which is a critical, but poorly understood period in the pathogenesis of cardiovascular diseases.2
Atherosclerosis, the underlying pathology of cardiovascular diseases, originates in early life, even during the prenatal period. An adverse intrauterine environment and impaired fetal growth are well documented to contribute to the early development of atherosclerosis, with a long latency period between these and other exposures and adult cardiovascular diseases.3
Pediatric investigations on the environmental factors that may affect risk of cardiovascular diseases have examined a range of biomarkers. Vascular endothelial dysfunction commences in early life and is a central pathological status in the early development of atherosclerosis. The role of biomarkers of endothelial function in the development of cardiovascular diseases has thus been investigated. Consistent with this, early-life cardiovascular disease risk factors, particularly childhood obesity, are strongly associated with endothelial dysfunction and the development of atherosclerosis and cardiovascular diseases. More important, there is emerging evidence that childhood cardiovascular disease risk factors, such as hypertriglyceridemia, are independently predictive of adult cardiovascular diseases. There is also strong evidence that cardiovascular disease risk factors in childhood are associated with the cardiovascular disease precursor conditions or intermediate vascular end points in adulthood including diabetes, hypertension, and larger carotid intima-media thickness. Clustering of cardiovascular disease risk factors, which imparts an even greater risk than the sum of the individual risk factors in adults, also takes place in childhood. This clustering of cardiovascular disease risk factors not only tracks from childhood into adult life but also is associated with the antecedents of increased blood pressure and skin fold thickness in early infancy.2, 4
By the preschool years, low-birth-weight infants have early symptoms of impaired vascular health, including thicker carotid intima-media thickness and increased arterial stiffness. These infants also have higher concentrations of cardiovascular disease risk factors, such as adiposity, insulin resistance, and dyslipidemia as compared with those with normal birth weight.5, 6, 7, 8, 9, 10, 11, 12, 13
The relationship between compromised intrauterine nutrition and birth weight, however, is not simple, and other adiposity measures such as ponderal index (weight divided by length cubed) and abdominal circumference at birth may be better early-life predictors of adult cardiovascular disease risk than birth weight alone. Growth velocity in early postnatal life, particularly rapid “catch-up” growth during the first few months in low-birth-weight infants and weight gain in childhood, strongly affects endothelial function and subsequently the development of atherosclerosis and cardiovascular disease. It has been suggested that childhood weight gain diverts energy disproportionately to adipose tissue, particularly in the abdomen, thereby increasing metabolic load. Furthermore, animal studies have shown that nutritional “mismatch” may take place when intrauterine undernutrition is followed by the postnatal overnutrition, especially with energy-dense foods.14, 15, 16
Cardiovascular diseases have a complex multifactorial etiology. Given the increasing evidence regarding tracking of risk factors from childhood into adult life, the potential role of their genetic, prenatal, environmental, biological, and behavioral determinants should be underscored.
Section snippets
Fetal Origins of Cardiovascular Diseases
Early-life risk factors are now thought to be significant in the etiology of obesity, type 2 diabetes, atherosclerosis, and subsequent cardiovascular disease risk in adulthood, opening up the possibility that these common diseases could be prevented by achieving optimal fetal and infant development. In recent decades, a growing body of evidence proposed that early-life risk factors may affect the development of atherosclerosis and subsequent cardiovascular disease risk in adulthood.4, 17, 18, 19
Maternal Factors
Various maternal factors may increase the risk of cardiovascular diseases in their offspring. For instance, gestational diabetes, maternal smoking, pre-conceptual maternal obesity, and excess weight gain during pregnancy are suggested as early-life predictors of cardiovascular diseases in adulthood.
Genetic Predisposition
It is well documented that some individuals are more vulnerable to cardiovascular diseases and their risk factors. Such differences begin from early life. In recent years, different studies including genome-wide association studies and meta-analyses have identified common genetic variants that contribute to cardiovascular diseases and their risk factors, such as dyslipidemia.125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136 Likewise, the genetic predisposition to elevated blood
Socioeconomic Status in Early Life and Cardiovascular Disease Risk
Socioeconomic status is a well-documented determinant of health status at each period of life. Early-life socioeconomic status may program a pattern of biological and behavioral responses with long-term impacts on cardiovascular morbidity and mortality.219, 220, 221 The duration of time spent in a low socioeconomic status is also an important predictor of cardiovascular disease and related mortality, thus being in a low socioeconomic status from early life increases these risks.222, 223, 224
Growth Pattern
The growth pattern of young children may have long-term health effects, and different types of growth disorders may have adverse effects on cardiovascular diseases and their risk factors.
Dietary Habits
Dietary habits are established from early life. In addition to providing adequate nutrition for optimal growth and development, they are important for the promotion of healthy dietary habits and their impacts on tracking of cardiovascular risk factors from childhood to adulthood. The most important dietary issues that impact the development and the progress of cardiovascular disease are related to the calorie intake, the type of fat consumed, and the salt intake, as well as following the food
Environmental Factors
Although obese children and adolescents are more prone to cardiovascular diseases and their risk factors, a substantial number of normal-weight children and adolescents actually have at least some cardiometabolic risk factor.199, 201, 285 Environmental factors may be considered in this context. Moreover, in addition to genetic and lifestyle factors, prenatal exposures to environmental contaminants may have long-term effects on the growth pattern of children and development of cardiovascular
Conclusion
The role of various modifiable factors on the origins of cardiovascular disease emphasizes the importance of considering both high-risk and population-level approaches for primordial and primary prevention of cardiovascular disease. Establishment of healthy lifestyles, growth monitoring, and environmental protection activities should be considered in a life-course approach for health promotion and cardiovascular disease prevention from early life.
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