Ph.D., Faculty of Health Sciences, University of the Witwatersrand, 2009 / Epidemiological trends suggest that obesity is becoming a major public health problem. Although obesity contributes toward cardiovascular risk by promoting the development of hypertension, dyslipidaemia and diabetes mellitus (conventional risk factors), there is increasing evidence to suggest that excess adiposity may increase risk through effects on cardiovascular target organs that are independent of conventional risk factors. These obesity-induced effects may be produced by mediating damage and dysfunction of large vessels and the heart, and by promoting the development of cardiac hypertrophy. However, the independent effect of excess adiposity on large vessels has not been confirmed in all studies. Moreover, whether the impact of excess adiposity on cardiac hypertrophy or cardiac damage and dysfunction is dependent on an interaction with blood pressure (BP) is uncertain. In the present thesis I addressed these questions. Before evaluating these questions I first identified the preferred clinical index of adiposity when predicting BP. In this regard, some, but not all studies support the notion that indexes of central adiposity (waist circumference or waist-to-hip ratio) are the preferred predictors of conventional BP over indexes of general (body mass index) or subcutaneous (skin-fold thickness) adiposity. Moreover, to my knowledge no study has been conducted in a large study sample to evaluate whether indexes of central adiposity are the preferred predictors of ambulatory BP, a measure of BP that is more closely associated with cardiovascular events than conventional BP. In the first study conducted in a relatively large, randomly selected population sample (n=300) with a high prevalence of excess adiposity (65%), I demonstrated that waist circumference is the only clinical index of adiposity that is associated with an increased conventional and ambulatory systolic and diastolic BP, independent of other indexes of adiposity. With regards to the effects of excess adiposity on large arteries, there is inconsistency in the reports demonstrating relations between indexes of adiposity and large artery dysfunction (arterial stiffness) independent of factors such as BP, heart rate and diabetes mellitus. As convincing independent relations between clinical indexes of adiposity and arterial stiffness have been noted in older, but not in younger populations, I hypothesized that age may determine whether excess adiposity promotes increases in arterial stiffness independent of confounders. Indeed, in 508 randomly selected persons from a population sample with a high prevalence of excess adiposity (~63% overweight or obese), I was able to show that age markedly influenced the independent relationship between indexes of central adiposity and an index of large artery stiffness in women but not in men after adjusting for confounders. The adjusted effect of indexes of central obesity on arterial stiffness was ~5-fold higher in older than in younger women. With respect to the impact of excess adiposity on cardiac growth, although severe obesity is associated with an enhanced impact of BP on left ventricular mass (LVM), there is uncertainty as to whether the same effects occur in milder forms of excess adiposity, data confounded by the high prevalence of participants receiving antihypertensive therapy in previous studies. In the present thesis I demonstrated in a randomly recruited population sample of 398 participants with a high prevalence of mild-to-moderate obesity and hypertension (~41%), but in whom antihypertensive use was limited (~17%), that adiposity is indeed associated with an enhanced impact of conventional and ambulatory BP or arterial stiffness on LVM index and wall thickness independent of additional conventional risk factors. With regards to the impact of obesity on cardiac function, although obesity is a risk factor for heart failure independent of other conventional cardiovascular risk factors, whether this effect occurs through changes in cardiac systolic chamber function is uncertain. In the present thesis I provide the first evidence to show in an animal model of genetic iv hypertension and dietary-induced obesity, that dietary-induced obesity promotes the progression from compensated cardiac hypertrophy to cardiac pump dysfunction without promoting hyperglycaemia. This effect was attributed to alterations in both intrinsic myocardial systolic dysfunction and cardiac dilatation, effects that were associated with excessive cardiomyocyte apoptosis and activation of enzymes that promote myocardial collagen degradation. Therefore in the present thesis I provide evidence to support the notion that waist circumference should hypertension and dietary-induced obesity, that dietary-induced obesity promotes the progression from compensated cardiac hypertrophy to cardiac pump dysfunction without promoting hyperglycaemia. This effect was attributed to alterations in both intrinsic myocardial systolic dysfunction and cardiac dilatation, effects that were associated with excessive cardiomyocyte apoptosis and activation of enzymes that promote myocardial collagen degradation. Therefore in the present thesis I provide evidence to support the notion that waist circumference should be measured when predicting BP changes, that excess adiposity does indeed decrease large vessel function independent of conventional risk factors, but that this effect is age-dependent, and that the deleterious effects of excess adiposity on cardiac hypertrophy and cardiac pump function are indeed dependent on an interaction with BP, but not other confounders.

Cette thèse tente d’apporter, en la sociologisant, des éléments de réponse à une question émanant du monde médical : pourquoi des individus atteints d’hypercholestérolémie et donc surexposés à des risques cardio-vasculaires ne mettent-ils pas en application les conseils diététiques formulés par leur médecin ? Trois phases d’enquête ont été menées : 1) des entretiens d’experts, dans le but d’identifier les controverses qui ont transformé l’hypercholestérolémie en un problème de santé publique majeur ; 2) des entretiens individuels et collectifs auprès de « mangeurs à risques », afin de saisir les principaux freins au suivi des règles hygiéno-diététiques prescrites et les formes de régulation sociale de la pathologie ; et 3) une enquête quantitative, avec passation de questionnaires auprès de 800 individus, ayant pour but la description socio-démographique de la population d’étude et la validation des résultats qualitatifs. Si les rapports à l’alimentation et à la santé apparaissent comme étant en partie surdéterminés par des variables sociales et culturelles, les résultats invitent surtout à resituer les individus dans leurs contextes interactionnels et familiaux. Les décisions alimentaires et les manières de faire face à cette pathologie chronique ne sont pas construites dans une perspective individuelle. Au final, l’articulation entre la sociologie de l’alimentation et les champs de la santé, du risque, de la famille et du genre a permis de renouveler la problématique de l’observance et d’ouvrir un vaste territoire de recherches sur les effets du « manger ensemble » et du « vivre ensemble ». En cela, la thèse entend contribuer à une sociologie de la décision alimentaire. / This thesis attends answering a question originated from the medical world, by framing it through a sociological perspective: why do some hypercholesterolaemic individuals not comply with their doctor’s dietetic advice although being overexposed to cardiovascular risks? Three surveys were conducted: 1) some experts’ interviews, so as to identify the controversies that have led hypercholesterolaemia to be considered as a major public health problem; some in-depth interviews and a focus group with “at risk eaters”, in order to grasp the main obstacles to the dietary compliance and the forms of social regulation for the pathology; and 3) a quantitative survey, carried out by questionnaires among 800 people and developed with the aim of collecting sociodemographic data on the population, and validating the qualitative results. Notwithstanding that the relations with food and health are partly over-determined by social and cultural variables, results underlined the need to situate individuals in their interactional and family environment. Neither eating choices nor the ways to cope with this chronic pathology are constructed within an individual perspective. Connecting the sociology of food with other works from the health, risk, family and gender domains eventually enabled revitalizing the compliance issue and initiating a vast field of researches on the effects of “eating together” and “living together”. This thesis therefore intends contributing to a sociology of eating choices.

Cardiovascular risk factors have expanded to include personality and other psychological characteristics. Negative affect (NA) has a longstanding history in cardiovascular health, but the path by which NA leads to cardiovascular disease (CVD) is yet to be defined. The following study examined the relationship of high NA and low extroversion (EX) with physiological cardiovascular markers in a sample of non-medical, professional adults. Our results indicated that individuals high in NA and low in EX displayed a significantly lower platelet count and a significantly higher mean platelet volume. Individuals high in NA displayed a significantly lower cholesterol risk ratio, while individuals high in EX displayed significantly higher platelet counts. Personality was not significantly related to blood pressure, high or low density lipoproteins. Understanding the relationships among psychological variables and physiological markers will help clinical researchers design interventions that reduce the likelihood of CVD.