Pharmacological Treatments for Obesity-Related Hypertension

Abstract

Obesity, hypertension and obesity-related hypertension are growing health problems. Hypertension is an important risk factor for cardiovascular disease (CVD), particularly in patients with obesity, diabetes, and metabolic disease. Obese subjects are frequently associated with hypertension, diabetes mellitus, metabolic disease, and end-organ damage (i.e. end-stage renal damage). An integrated cardiovascular risk management approach is being adopted: aggressive blood pressure (BP) control is important in patients with high CVD risk, and well-tolerated antihypertensive agents with protective benefits beyond BP lowering are advantageous. The identification and management of these CVD risk factors is an important part of the overall management of hypertensive patients. Because patients in these special populations such as subjects with obesity or metabolic syndrome are more predisposed to target organ damage, stringent targets for blood pressure control have been set in clinical guidelines, however clinical trial and real-life evidence suggest that these targets are difficult to achieve.The first line of treatment of obesity and metabolic syndrome associated with obesity are weight loss with a lifestyle modification such as low caloric diet and exercise (see the previous chapter) or gastric band/gastric bypass surgery or bariatric surgery. Recently, anti-obesity drugs (Orlistat, Sibutramine) have been developed, but the precise effects on blood pressure and neurohormonal parameters have not been fully clarified. In addition, leptin administration (pegylated recombinant leptin; PEG-OB) as theoretical treatment for obesity has been examined in overweight or obese human and in animal models. Central leptin gene therapy was also examined in animal models. However, the anti-obesity effects of leptin administration were controversial.Recently, many clinical and epidemiological studies have shown that angiotensin II receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) are highly efficacious, persistent, well-tolerated antihypertensive agents, with additional benefits in obesity-related hypertension, cardiovascular pathogenesis, end-organ damage, and in metabolic syndrome. For example, the Irbesartan/HCTZ combination therapy Blood Pressure Reductions in Diverse Patient Populations (INCLUSIVE) trial has shown comparable antihypertensive efficacy and tolerability regardless of BMI or diabetes status. Another observation is emerging that Telmisartan, in addition to blocking the angiotensin II type 1 receptor, activates the peroxisome proliferator-activated receptor (PPAR)-gamma, a well-known target for treatment of the metabolic syndrome and diabetes. This clinical evidence perhaps argues against this, with the The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) showing no benefit for Telmisartan compared with Ramipril, in prevention of new diabetes development.Another antihypertensive drug class with favourable properties are the centrally acting Imidazolin, M...