Lipoprotein-associated phospholipase A2 as cardiovascular risk factor and therapeutic target in nephropatic patients

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a serine lipase associated with Low-Density Lipoproteins, that increases the oxidative stress in atherosclerotic lesions and makes the plaque instable. Lp-PLA2 is recognized as a risk factor for cardiovascular and peripheral artery disease in general population, in cardiac and dysmetabolic patients, but no data are available for subjects with renal failure. The aim of the present PhD thesis was to investigate the role of Lp-PLA2 among patients with advanced renal failure. Chapter 1. In 102 hemodialyzed patients, it has been demonstrated that Lp-PLA2, activity is increased and associated with a more inflammatory phenotype. Chapter 2. In the first clinical observational study, it was demonstrated for the first time that Lp PLA2 is an independent risk factor for cardiovascular morbidity and mortality in 102 hemodialyzed subjects, followed for 3 years. Chapter 3. In the second clinical observational study, LP-PLA2 was recognized, for the first time, as independently associated with peripheral artery disease, in 102 dialyzed subjects followed for 5 years. Chapter 4. Here, it is reported a personal experience, demonstrating that lipoprotein apheresis -PLA, and improves lower limb ulcers, just confirming its role as additional therapy. Chapter 5. It was demonstrated that: first, the Mediterranean diet is associated with lower levels of LP-PLA2 in 41 subjects with advanced renal failure. Second, the low protein diet is effective in decreasing Lp-PLA2, in 28 subjects with advanced renal failure. In conclusion with this PhD project it was demonstrated that, also among renal patients, Lp-PLA2 could be considered a risk factor for acute cardiovascular morbidity and mortality and peripheral artery disease. Lp-PLA2 could also represent a useful target for non-pharmacological approaches (lipoprotein-apheresis) and nutritional therapy.