Disturbance of cardiovascular structure and function in obesity and metabolic syndrome : implications for diagnosis, prevention and treatment of cardiovascular disease

Wong, Chiew Ying (2007). Disturbance of cardiovascular structure and function in obesity and metabolic syndrome : implications for diagnosis, prevention and treatment of cardiovascular disease PhD Thesis, School of Medicine, University of Queensland.

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Author Wong, Chiew Ying
Thesis Title Disturbance of cardiovascular structure and function in obesity and metabolic syndrome : implications for diagnosis, prevention and treatment of cardiovascular disease
School, Centre or Institute School of Medicine
Institution University of Queensland
Publication date 2007
Thesis type PhD Thesis
Supervisor Thomas Marwick
Total pages 282
Language eng
Subjects 11 Medical and Health Sciences
Abstract/Summary Obesity is a worldwide phenomenon of epidemic proportions. It has been estimated that there are more than 300 million obese humans worldwide and greater than 2 million adult Australians who are clinically obese. Epidemiology studies have linked obesity to heart failure. Overweight and obesity are potent predictors of subsequent clinical heart failure in Framingham Heart Study. Previous studies reported abnormal left ventricular (LV) diastolic function without consistent association with systolic dysfunction. There is limited information on the right ventricular changes. There are various limitations in the previous studies. Some of the earlier findings may reflect the role of co-morbidities that contribute to LV dysfunction (e.g. hypertension, diabetes, coronary artery disease and obstructive sleep apnoea). Furthermore, most of the previous studies used conventional echo techniques based on Doppler flow and blood pool information which were less sensitive than current measures and more load-dependent (e.g. mitral inflow velocities, IVRT and EF). Comprehensive echo- Doppler assessment is absent from most studies. Using conventional echocardiographic techniques, clinical heart disease is only detected when gross structural changes or (less reliably) when poorly defined changes in LV filling have occurred, and patients are already at increased cardiovascular risk. Overall, early stages of obese heart disease are not well characterized, largely due to associated comorbidities related to obesity such as coronary artery disease, sleep apnoea and hypertension. The pathophysiology of obesity cardiomyopathy likely involves structural but subclinical changes. The overall hypothesis of the studies undertaken in this thesis was that sensitive new echocardiographic techniques can make a major contribution to the understanding of myocardial dysfunction at an early stage in the development of obese heart disease. Further, this thesis hypothesizes that these new technologies will facilitate the evaluation of novel diagnostic strategies, and allows selection of at risk populations for intervention and quantification of the response to treatments in patients with obese heart disease or early myocardial changes. The thesis initially reviews the clinical aspects and pathophysiology of obese heart disease, emphasizing the independent role of excess weight, which may be a target for intervention. This is followed by a discussion of the current state of the art in echocardiographic assessment myocardial function, and potential new approaches which might allow more sensitive tissue characterization. The third chapter describes the metabolic testing, biochemical, vascular assessment and the other methodologies used in this thesis, with particular attention to the quantitative assessment of vascular function and structure. In chapter 4, new quantitative measures of LV long-axis systolic function (tissue Doppler, strain imaging and ultrasound backscatter), and conventional echocardiography, were assessed in 109 patients across a range of BMI with normal ejection fraction and free of cardiac symptoms, and compared with 33 matched controls. Obese and overweight patients had increased LV mass, reduced LV systolic tissue velocity, strain and backscatter parameters indicating systolic dysfunction, and reduced early diastolic myocardial velocity in a dose dependent manner across BMI groups. The severely obese subgroup has the most marked abnormalities in all parameters. These results indicate that excess weight is associated with diastolic dysfunction in particular, which may represent the earliest abnormality in obese heart disease. In addition, new quantitative echocardiographic techniques appear to be useful for evaluating subtle abnormalities of myocardial function in obese heart disease. In Chapter 5, we used these new techniques to assess the relationship of the number of features of the metabolic syndrome to early myocardial dysfunction and cardiorespiratory fitness in patients with metabolic syndrome. We studied 393 patients without cardiac symptoms, and screened to exclude significant coronary artery disease.. Myocardial systolic (myocardial systolic velocity, strain rate) and diastolic measures (myocardial early diastolic velocity) were highest in controls and became progressively lower in proportion to the number of metabolic syndrome components. The MS contributed to the reduced systolic and diastolic function in those with normal LV mass index. LV measures of strain rate and myocardial diastolic velocity (em) were independent predictors of exercise capacity. It was therefore concluded that reduced myocardial function is an independent predictor of exercise capacity in patients with metabolic syndrome and those who additionally have subclinical myocardial abnormalities and reduced cardiorespiratory fitness should be considered a potential target for primary intervention. Chapter 6, we evaluated LV torsion and rotational velocities by the novel method of speckle tracking echocardiography (STE). STE was proposed as a sensitive marker of LV function. We sought to evaluate the LV rotational motion and untwisting in obese subjects in comparison with tissue Doppler imaging (TDI). We demonstrated otherwise healthy obese subjects to have reduced global LV torsion as well as reduced regional rotation at the base and diastolic rotational velocities at both the base and the apex. Reduced LV torsion and rotational velocities were present even in those whose longitudinal function was preserved, indicating that the former abnormalities occur prior to any impaired systolic longitudinal function and the higher sensitivity of STE in detection of early myocardial disease. These results showed that the new ultrasound technologies enabled more objective assessment of left ventricular function. In Chapter 6, we therefore sought whether similar information could be obtained from myocardial velocities and strain indices of the right ventricle in obese subjects. We also sought to identify the determinants of RV dysfunction in overweight and obese subjects. Quantitative echocardiographic techniques similar to those used in earlier chapters were applied to 93 ambulatory overweight and obese subjects. RV tissue velocities and strain indices were reduced in obese patients irrespective of the presence and severity of sleep apnoea independent of age, gender, and blood pressure. These changes were shown to be associated with fasting insulin, adiponectin levels and reduced exercise capacity. In parallel with effects of obesity on the myocardium, obesity has effects on the vasculature. In order to understand the roles of the Metabolic Syndrome (MS) on the vasculature, in chapter 7, we examined whether MS clustering had similar additive impact on vascular structure and function beyond the atherosclerotic risk factors clustering. Components of MS synergistically impact vascular changes in patients with MS, although the clustering of atherosclerotic risk factors remains a better risk prediction for subclinical arterial changes. Next, we sought the relative prevalence of vascular and myocardial sequelae of obesity and MS. In chapter 8, we further examined the prevalence and associations of coronary artery disease (CAD), subclinical LV dysfunction (LVD), LV hypertrophy (LVH) and early vascular changes in 521 asymptomatic obese and diabetic populations in our community. The risk of CAD and vascular changes were disproportionably associated with DM as compared with MS. Both LV hypertrophy and LV dysfunction were prevalent in both diabetes and obesity. Finally, in chapter 9, the quantitative echo techniques which were validated as sensitive markers of myocardial dysfunction in chapter 4 were applied, together with vascular imaging, in an interventional study of the effect of weight reduction on early myocardial and vascular changes. Following lifestyle interventions of exercise with dieting, obese patients with successful weight reduction demonstrated increases in myocardial diastolic function, reduced myocardial tissue density and improved brachial arterial reactivity. This Increase in myocardial function was in turn related to improved exercise capacity. The results demonstrate that modest weight reduction through lifestyle intervention can modify myocardial function in metabolic heart disease and may provide a specific primary prevention strategy against risk of heart failure development.
Keyword Obesity -- Pathophysiology
Obesity -- Complications
Cardiovascular system -- Diseases -- Complications
Metabolic syndrome
Additional Notes Variant title: Cardiovascular disturbances in obesity & MS

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Created: Fri, 21 Nov 2008, 15:40:36 EST