A Critical Evaluation of the Fetal Origins Hypothesis and Its Implications for Developing Countries Historic and Early Life Origins of Hypertension in Africans 1 Terrence Forrester 2 Tropical Metabolism Research Unit, Tropical Medicine Research Institute, The University of the West Indies, Mona Campus, Kingston, Jamaica ABSTRACT Cardiovascular disease (CVD) causes 12.4 million deaths annually, most (9.6 million) occurring in developing countries. Hypertension, the most common CVD, arises within the context of obesity, but the underlying mechanisms remain obscure. Obesity and salt intake are two important risk factors for hypertension and are the focus of this paper. Traditional African populations show a low prevalence of hypertension, but hypertension is more common in migrant African populations in the West than in other ethnic groups. One explanation is genetic, but no causative gene has been confidently identified. Nongenetic susceptibilities such as fetal programming are an alternative explanation. Hypothetically, fetal programming induced by transient stimuli permanently alters fetal structure and function at the cellular, organ and whole-body levels. Birth weight is inversely related to blood pressure and hypertension risk, suggesting that susceptibility to hypertension risk factors such as obesity and salt sensitivity are themselves programmed. In support of this hypothesis, obesity (especially central obesity) is also inversely related to size at birth. Likewise, salt sensitivity might derive from undernutrition in utero, reducing the nephron number and resetting the pressure-natriuresis curve rightward. However, no robust human data or evidence of enhanced salt sensitivity among African-origin populations exist. In the United States, blacks have a greater prevalence of low birth weight than whites, suggesting that the higher prevalence of hypertension among blacks is related to fetal programming. Nevertheless, we need to be scrupulous in ascribing risk to the myriad other confounders of this relationship, including environmental and behavioral correlates of ethnicity, before concluding that excess risk of hypertension in Africans is programmed in utero. J. Nutr. 134: 211–216, 2004. KEY WORDS: ● hypertension ● fetal programming ● salt sensitivity ● Africans The development of chronic noncommunicable diseases (CNCD) 3 in epidemic proportions characterizes populations un- dergoing the nutrition and epidemiologic transitions (1–3). Car- diovascular disease (CVD) accounts for the lion’s share of prev- alent CNCD and causes 12.4 million deaths annually; the majority (9.6 million) of these deaths occur in developing coun- tries (4). Hypertension is the most common CVD. Its prevalence ranges from 0 to 40% across populations (5). It contributes 6% of all deaths, defining the disease as a major health problem globally. The prevalence of CVD is not homogeneous; it arises within the context of obesity and varies widely across popu- lations (6 –10). Obesity represents a sustained positive energy balance, and direct causal risk factors include energy-dense diets rich in oils, fats and simple sugars as well as reduction in physical activity. The mechanistic links between obesity and hypertension are still incompletely appreciated, although sev- eral hypotheses do exist; these include endothelial dysfunc- tion, insulin resistance and deranged renal body fluid control (11,12). The question therefore arises, that if the primary candidate in a hypothetical chain of causation of CVD is obesity, what are its root causes? In the broadest sense, obesity can be viewed as the price of social evolution. The development of agricul- ture 10,000 y ago created a surplus of food. The industrial revolution 300 y ago accelerated a process of dietary evolu- tion wherein dietary patterns shifted from predominantly plant based toward increasing incorporation of animal and processed foods. More recently, globalization has accelerated these di- etary and lifestyle shifts, particularly in the developing world, where the nutrition transition is taking place at a faster pace, putting these populations at greater risk of obesity and its comorbidities (1–3,13,14). Whereas wide population access to increased amounts of energy-dense foods drives the energy intake side of the energy budget equation, incorporation of 1 Presented at the Experimental Biology Meeting, April 11–15, 2003, San Diego, CA. The symposium was sponsored by the American Society for Nutri- tional Sciences and supported in part by the Society for International Nutrition Research and the International Life Sciences Institute. The proceedings are published as a supplement to The Journal of Nutrition. This supplement is the responsibility of the guest editors, to whom the editor of The Journal of Nutrition has delegated supervision of both technical conformity to the published regula- tions of The Journal of Nutrition and general oversight of the scientific merit of each article. The opinions expressed in this publication are those of the authors and are not attributable to the sponsors or the publisher, editor or editorial board of The Journal of Nutrition. Guest editors for the symposium publication are Linda S. Adair, Department of Nutrition, University of North Carolina, Chapel Hill, NC, and Andrew Prentice, MRC International Nutrition Group, London School of Hygiene and Tropical Medicine, London, U.K. 2 To whom correspondence should be addressed. E-mail: terrence.forrester@uwimona.edu.jm. 3 Abbreviations used: CNCD, chronic noncommunicable disease; CVD, car- diovascular disease; RAAS, renin angiotensin aldosterone system. 0022-3166/04 $8.00 © 2004 American Society for Nutritional Sciences. 211 by guest on December 9, 2015 jn.nutrition.org Downloaded from