Impact of excess adiposity on blood pressure and cardiovascular target organ damage

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dc.contributor.author Majane, Olebogeng Harold Isaia
dc.date.accessioned 2009-10-19T10:40:25Z
dc.date.available 2009-10-19T10:40:25Z
dc.date.issued 2009-10-19T10:40:25Z
dc.identifier.uri http://hdl.handle.net/10539/7371
dc.description Ph.D., Faculty of Health Sciences, University of the Witwatersrand, 2009 en_US
dc.description.abstract 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. en_US
dc.language.iso en en_US
dc.subject obesity en_US
dc.subject cardiovascular risks en_US
dc.title Impact of excess adiposity on blood pressure and cardiovascular target organ damage en_US
dc.type Thesis en_US


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