REN and obesity due to melanocortin 4 receptor deficiency: Mechanistically, LVH-inducing risk factors could be classified as three categories (19, 20): (a) pressure-related factors that mainly function by increasing the afterload of the heart, such as hypertension, arterial stiffness or vascular calcification; (b) volume-related factors that mainly function by increasing the preload of the heart, such as sodium and water retention, obesity, anemia and arteriovenous fistula; (c) load-independent factors that influences the metabolism, signal transduction or fibrosis of the heart, such as the activation of the renin-angiotensin-aldosterone system.