Kazuko Masuo Pages 184 - 199 ( 16 )
Obesity, hypertension and obesity-related hypertension are growing health problems. Several epidemiological studies have shown a high prevalence of cardiovascular complications and all cause of mortality in obesity and hypertension. Obesity and hypertension are important and independent risk factors for cardiovascular disease development. An integrated cardiovascular risk management approach involving aggressive blood pressure (BP) control should be adopted in patients at high cardiovascular risk (i.e. those with ischemic heart disease, end-organ damage, type 2 diabetes) and the use of well-tolerated antihypertensive agents with protective benefits beyond BP lowering. The identification and management of risk factors is an important part of the overall management of hypertensive patients. Given that obese patients are more predisposed to target organ damage development, stringent targets for blood pressure control have been set in clinical guidelines, including those of the Joint National Committee (JNC-7) , the World Health Organisation and the International Society of Hypertension (WHO/ISH) , the European Society of Hypertension (ESH)  and the Japanese Society of Hypertension (JSH-2009) . Pertinently, clinical trials and real-life evidence suggest that these targets are difficult to achieve. Hypertension in obesity is characterized by stimulation of the renin-angiotensin-aldosterone system (RAAS), elevated sympathetic activity, insulin resistance and selective leptin resistance. Importantly, these characteristics, even in isolation constitute risk factors for cardiovascular disease development and progression. It is therefore imperative that pharmacological treatments should be selected based on favourable effects on these factors. Furthermore, in choosing an antihypertensive agent, effectiveness needs to be accompanied by favourable metabolic, cardioprotective, and renal protective properties. Recent pharmacogenetic studies have shown that several polymorphisms may contribute to antihypertensive effectiveness. Weight loss is recommended as the first line of treatment for hypertension associated with obesity. Indeed, lifestyle modification including a low caloric diet, reducing sedentary behaviour and exercise form the foundation of all therapy. For the subjects who are more severe obesity or inability to undertake an exercise program, bariatric surgery are recommended. Anti-obesity drugs have been developed but unfortunately some were associated with significant side effects and were recently withdrawn from the markets in the United States, Europe and Australia. Leptin administration has a theoretical basis in obesity therapy and, while it has been examined in overweight and obese human subjects and in animal models, the anti-obesity effects of leptin administration are controversial. The combination of high blood pressure with obesity, for a variety of reasons, renders the hypertension difficult to control, with patients frequently requiring two or more types of medications to achieve blood pressure goals. Many large cohort studies have compared the efficacies of antihypertensive drug classes in hypertensive patients with the metabolic syndrome, however, there are few systemic reviews of antihypertensive drug treatments for patients with obesity. Moreover the mechanisms underlying both obesity and hypertension remain to be elucidated therby making it difficult to achieve blood pressure goals. In this review I aim to provide a synthesis of the current data examining both pharmacological and nonpharmacological antihypertensive treatments in those patients with obesity-related hypertension.
Hypertension, obesity, lifestyle modification, pharmacological treatments, insulin resistance, epidemiological studies, Calcium channel blockers, Angiotension II
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