Mechanisms and treatment of obesity-related hypertension: Part 2. Treatments

Abstract

Hypertension is a frequent comorbidity of obesity that significantly and independently increases the risk of cardiovascular and renal events. Obesity-related hypertension is a major challenge to the healthcare system because of the rapid increase in obesity prevalence world-wide. However, its treatment is still not specifically addressed by current guidelines. Weight loss (WL) per se reduces blood pressure (BP) and increases patient responsiveness to BP-lowering medications. Thus, a weight-centric approach is essential for the treatment of obesity-related hypertension.

Diet and physical activity are key components of lifestyle interventions for obesity-related hypertension, but, in real life, their efficacy is limited by poor long-term patient adherence and frequently require pharmacotherapy implementation to achieve target BP. In this context, first-generation anti-obesity drugs like orlistat, phentermine/topiramate and naltrexone/bupropion are poorly effective, whereas second-generation incretin agonists, including the GLP-1 receptor agonists liraglutide and semaglutide, and in particular the dual GLP-1/GIP co-agonist tirzepatide, substantially contribute to effective WL and BP control in obesity. SGLT2 inhibitors are weak body weight and BP-lowering medications, but clearly synergize the benefits of these medications. Bariatric surgery remains the gold standard treatment for severe ‘pathological’ obesity and related life-threatening complications. Renal denervation is a valuable rescue treatment for drug-resistant hypertension, commonly related to obesity.

Integrating a multifaceted weight-based approach with other strategies, like antihypertensive drugs and renal denervation, could specifically target the main neuro-hormonal and renal pathophysiological mechanisms of obesity-related hypertension, including sympathetic-nervous and renin-angiotensin-aldosterone systems overactivity, salt retention and volume expansion. This comprehensive strategy can provide a personalized algorithm for managing hypertension in obesity within the context of ‘precision medicine’ principles.