The work of this group is focused on prevention of cardiometabolic disease in the young. More people die from such disease worldwide than from any other cause. The majority of these deaths are due to coronary heart disease (CHD) and stroke, potentially preventable conditions.
The United Kingdom, in common with most developed nations, has seen a significant reduction in the burden of cardiovascular disease (CVD) since the early 1980s. By the year 2000, for example, CHD mortality had fallen by 54%. Much of this change (~66%) was attributable to reduced rates of smoking, lower cholesterol due to better diets and statins, and reduced blood pressure, due in part to better treatment. Thus primary prevention strategies have had a major impact on CHD mortality, four-fold greater than that of secondary prevention. Nevertheless, CHD remains the single disease with the highest mortality in the UK. Economic modelling studies suggest that even prevention strategies with modest aims e.g. reducing mean cholesterol or blood pressure levels by 5% would have major health benefits and save the UK at least £100m annually. Thus, primary prevention strategies are medically effective and cost effective. However, primordial prevention has the potential for even greater benefits than can be achieved through existing primary prevention strategies alone.
Primordial prevention targets the earliest origins of CVD, with a focus on preventing the development of its risk factors, e.g. hypertension, hypercholesterolaemia or type II diabetes, rather than on their treatment. Unsustainable and escalating healthcare costs make better prevention an economic necessity. Our group aims to understand the abnormal metabolic and cardiovascular physiology in children that precedes the development of primary cardiometabolic risk factors and to establish strategies to normalise such physiology before irreversible organ damage and the development of disease occurs.
- Define the metabolic abnormalities associated with childhood obesity and sedentary behaviour that precede the development of primary cardiovascular risk factors such as hypertension, dyslipidaemia, and type II diabetes. Although some children demonstrate these risk factors, particularly in adolescence, most children do not. This contrasts with findings of established atheroma in a significant number of “healthy” children in the community. Therefore, the early development of cardiometabolic disease is largely opaque to current methods of risk determination. The group seeks to develop new risk markers, drawn from detailed physiological investigation initially, based on advanced metabolic and cardiovascular imaging (MRI & MRS) studies with the eventual aim of translation to more accessible risk markers once risk development in the young is better understood.
- Establish reversibility of the abnormal early cardiometabolic phenotype in the young. The benefits of current public health strategies, such as promotion of exercise or diet in the young are known but the mechanisms through which they act are not well understood and it remains unclear which individuals are most likely to benefit from which interventions. For example, most interventions target weight-loss, despite evidence that improved metabolic health may result from lifestyle changes that do not require weight-loss. A “one-size-fits-all” approach to public health interventions is currently promoted. However, targeted intervention in those at greatest risk could prove more cost-effective and reduce the burden of the most severe disease.
- Define economically viable targeted interventions in the young. Appropriately targeted interventions may be more cost-effective and more clinically effective than population-wide public health measures. We aim to identify high-risk groups and individualised interventional approaches to cardiometabolic risk in these groups, working with economic models to demonstrate cost-effectiveness and deliverability of new measures.
OxSOCRATES - Oxfordshire Sedentariness, Obesity & Cardiometabolic Risk in Adolescents – a Trial of Exercise in Schools
This study uses advanced imaging, blood tests and a meal-challenge to comprehensively characterise how early metabolic dysfunction (liver and muscle fat, insulin resistance, skeletal muscle energetics) affects cardiovascular health (arterial stiffness, myocardial energetics, gut vasoreactivity, diastolic function, blood pressure trajectory, left ventricular hypertrophy) in 210 adolescents (110 obese, 50 sedentary normal-weight, 50 high-activity). Reversibility of this phenotype will be tested in the obese by randomised controlled trial, comparing 8-week supervised exercise to a low-activity sham intervention. This study will provide the platform for developing practical, effective CVD prevention in children that is not simply focused on weight-loss.
Alexander Jones (PI),
Professor Helen Dawes, Brookes University
Professor Fredrik Karpe, OCDEM
Professor Stefan Neubauer, OCMR
Professor Oliver Rider, OCMR
Dr Ladislav Valkovic, OCMR
Comprehensive MRI assessment of the cardiovascular responses to food ingestion in Fontan physiology.
Hauser JA. et al, (2020), Am J Physiol Heart Circ Physiol, 319, H808 - H813
Maternal B12, Folate and Homocysteine Concentrations and Offspring Cortisol and Cardiovascular Responses to Stress.
Krishnaveni GV. et al, (2020), J Clin Endocrinol Metab, 105
Maternal B12, folate and homocysteine concentrations and offspring cortisol and cardiovascular responses to stress
Krishnaveni GV. et al, (2020), Journal of Clinical Endocrinology and Metabolism
Tissue Sodium Content and Arterial Hypertension in Obese Adolescents.
Roth S. et al, (2019), J Clin Med, 8