Nutritional interventions in childhood and cardiovascular disease risk

Disease of blood vessels (‘atherosclerosis’) that leads to heart attacks and strokes is the main cause of death and disability, the major consumer of health care resources and the most important health priority in Britain and indeed the Western World. Whilst heart attacks usually occur in adults, there is now strong evidence that the diet of babies and children has a major impact on the early processes that lead to blood vessel damage and, ultimately, heart disease later in life. During the past 25 years we have been conducting unique and ethical clinical trials where subjects have been randomly assigned to different early diets to test for the long-term consequences of early nutrition. Some of these trial populations have been followed into adulthood. These, together with our new trials, put us in a strong position to test the impact of early nutrition on later cardiovascular health. Our ultimate purpose is to underpin public health practices in this critical area. We plan to study accepted risk factors for heart disease (high blood pressure, high cholesterol, fatness and tendency to diabetes); and the first stages of atherosclerotic disease, using ultrasound techniques. We will also investigate the factors later in childhood (such as obesity) that can lead to atherosclerosis. The planned research will be conducted by Dr Atul Singhal and Professor Alan Lucas at the MRC Childhood Nutrition Centre, at the Institute of Child Health, London, in collaboration with a network of centres throughout Britain. Our work will help our understanding of the origins of atherosclerosis and will provide us with the knowledge to design early nutritional practices and interventions that could help reduce obesity, heart attacks and strokes in adults.
 

IMPORTANCE: atherosclerotic cardiovascular disease (CVD) is the main cause of death and disability, the major consumer of health care resources and the greatest public health priority in the West. Whilst clinical manifestations of CVD occur late in life, there is now strong evidence that the atherosclerotic process begins in children and that nutrition in infancy and childhood have a significant impact on its development. APPROACH: our proposed programme of translational research tests this concept experimentally using: (a) formal outcome trials that exploit our unique prospectively followed and new trial cohorts, randomised to different diets in infancy; and (b) mechanistic studies, imbedded within this framework. METHODS: the main proposed endpoints have been validated in children as measures of CVD risk and are at three levels, likely to have increasing clinical relevance: (i) classical cardiovascular risk factors that track into adulthood including blood pressure, adiposity, insulin resistance, and dyslipidaemia and (ii) functional vascular changes, notably flow-mediated endothelial dependent vasodilation, seen at the earliest stage in the atherosclerotic process and measured non-invasively using high-resolution vascular ultrasound; and (iii) structural changes associated with atherosclerosis, notably carotid arterial intima-media thickness and measures of vessel wall elasticity such as arterial distensibility and pulse wave velocity. STUDY PLAN: The work will focus on 1) the long-term impact, or ?programming? effects, of early nutrition on later CVD risk and the underlying mechanisms and 2) the role of obesity later in childhood, beyond the early programming windows, on the development of early atherosclerosis. Specifically, we will investigate the programming effects of early growth rate (notably our postnatal growth acceleration hypothesis), macronutrient intake and of specific dietary nutrients on long term vascular health and CVD risk. By exploiting a national intervention for childhood obesity, we will also investigate the impact of childhood adiposity (including visceral fat) and its treatment on CVD risk, early atherosclerosis and the underlying mechanisms. DESIGN: The proposed work is entirely experimental in design and powered to detect effects of nutritional interventions that are predicted to be an important basis for clinical, nutritional and public health practice. OBJECTIVE: the current programme, builds on our previous work showing large effect sizes for the impact of early nutrition on later risk markers for CVD in specific population subgroups; is now focused on the applicability to the general population; and will help develop evidence-based nutrition policies aimed at the primary prevention of cardiovascular disease.