The Relevance of Biomarkers, Risk Factors and Gene– Environment Interactions in Disease: Scientific Developments and Therapeutic Approaches

PHILIP V. PEPLOW AND JAMES D. ADAMS JR

1.1 Introduction

An increasing prevalence of obesity, hypertension and cardiovascular disease, and diabetes has been reported for children and adults in many developed and developing countries. These conditions are interlinked and are associated with both immediate and long-term health effects.

Childhood obesity has more than doubled in children and tripled in adolescents in the past 30 years. In the United States of America the percentage of children aged 6–11 years who were obese increased from 7% in 1980 to nearly 18% in 2010. Likewise, the percentage of adolescents aged 12–19 years who were obese increased from 5% to 18% over the same time period. In 2010, more than one third of children and adolescents were overweight or obese. Overweightness and obesity are caused by caloric (energy) imbalance with too few calories expended for the amount of calories consumed, and are affected by various behavioral, genetic and environmental factors. Obese youth are more likely to have risk factors for cardiovascular disease such as high cholesterol or high blood pressure. Obese adolescents are more likely to have prediabetes, a condition in which blood glucose levels indicate a high risk of developing diabetes. Data from the National Health and Nutrition Examination Survey (NHANES) on the prevalence and control of hypertension in the USA between 1960 and 2008 have shown that the prevalence is higher in older individuals, non-Hispanic blacks, and women. It is unclear why non-Hispanic blacks are more likely to become hypertensive. Both genetic and environmental factors are probably important, one of which may be a greater likelihood of low birth weight, which appears to predict higher blood pressures in adulthood. NHANES data from 2007 to 2008 showed a 28 to 30% prevalence of hypertension in the 18 year and older population in the USA. This equates to approximately 65 million adult hypertensives in the USA, which is markedly higher than the estimated 43 million from the 1988–1991 NHANES survey. Thus, there has been a 50% increase in the number of adult hypertensives over a decade. With the increased prevalence of hypertension there has also been a marked increase in obesity and body mass index, and it has been estimated that one-half of the relative increased prevalence of hypertension may be due to an increased weight of the average individual. In surveys similar to the NHANES in Canada and Europe, the age- and sex-adjusted prevalence of hypertension ranged from 20 to 55%. Analysis of world-wide data suggested that 26% of the world adult population had hypertension in 2000. Rates of hypertension appear to be similar in developed and developing countries. Worldwide, hypertension is not adequately controlled, and control is worse in lower income countries.

There is increasing evidence that adult hypertension has its origins during childhood, as childhood blood pressure predicts adult blood pressure. Hypertension in childhood and adolescence may contribute to premature atherosclerosis and the early development of cardiovascular disease. Identifying children with hypertension and successfully treating their hypertension will have an important impact on long-term outcomes of cardiovascular disease. The definition of childhood hypertension is based on the normative distribution of blood pressure in healthy children. This contrasts with adult hypertension which is primarily defined by clinical outcomes (i.e. risk of cardiovascular disease and mortality) from large trials of antihypertensive therapy. This clinical definition cannot be applied to children because cardiovascular events other than left ventricular hypertrophy do not typically occur until adulthood. Body size is the most important determinant of blood pressure in children and adolescents.

In 2010, an estimated 19 million persons in the USA had diagnosed diabetes and another 7 million had undiagnosed diabetes. Since 1990, the prevalence of diagnosed diabetes in the USA has risen sharply among all age groups, both sexes, and all racial/ethnic groups for which data are available. The substantial increase in the prevalence of diagnosed diabetes is likely the result of improved survival of persons with diabetes and increasing diabetes incidence. Nationally representative data suggest that mortality among adults with diabetes in the USA declined substantially between 1997 and 2006, and at a faster rate than among adults without diabetes. This decline is paralleled by improvements in the health of persons with diabetes, including lower levels of risk factors for complications (e.g. hyperglycemia, uncontrolled blood pressure), decreased rates of complications associated with increased risk of death, and improvements in quality of care and medical treatments.

The main driver of the increase in diabetes prevalence is the increase in the incidence of diabetes in the USA since 1990. Increasing incidence could be the result of many factors, including changes in diagnostic criteria, enhanced detection of undiagnosed diabetes, demographic changes in the population (e.g....