Lipid trafficking in cardiovascular disease

The reduction of plasma apolipoprotein B (apoB)containing lipoproteins has long been pursued as the main modifiable risk factor for the development of cardiovascular disease (CVD). This has led to an intense search for strategies aiming at reducing plasma apoB-lipoproteins, culminating in reduction of overall CV risk. Despite 3 decades of progress, CVD remains the leading cause of morbidity and mortality worldwide and, as such, new therapeutic targets are still warranted. Clinical and preclinical research has moved forward from the original concept, under which some lipids must be accumulated and other removed to achieve the ideal condition in disease prevention, into the concept that mechanisms that orchestrate lipid movement between lipoproteins, cells and organelles is equally involved in CVD. As such, this review scrutinizes potentially atherogenic changes in lipid trafficking and assesses the molecular mechanisms behind it. New developments in risk assessment and new targets for the mitigation of residual CVD risk are also addressed

Lipid management in patients with chronic kidney disease.

An increased risk of cardiovascular disease, independent of conventional risk factors, is present even at minor levels of renal impairment and is highest in patients with end-stage renal disease (ESRD) requiring dialysis. Renal dysfunction changes the level, composition and quality of blood lipids in favour of a more atherogenic profile. Patients with advanced chronic kidney disease (CKD) or ESRD have a characteristic lipid pattern of hypertriglyceridaemia and low HDL cholesterol levels but normal LDL cholesterol levels. In the general population, a clear relationship exists between LDL cholesterol and major atherosclerotic events. However, in patients with ESRD, LDL cholesterol shows a negative association with these outcomes at below average LDL cholesterol levels and a flat or weakly positive association with mortality at higher LDL cholesterol levels. Overall, the available data suggest that lowering of LDL cholesterol is beneficial for prevention of major atherosclerotic events in patients with CKD and in kidney transplant recipients but is not beneficial in patients requiring dialysis. The 2013 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Lipid Management in CKD provides simple recommendations for the management of dyslipidaemia in patients with CKD and ESRD. However, emerging data and novel lipid-lowering therapies warrant some reappraisal of these recommendations