Cholesterol Lowering Therapy: Treat to Target or Reduce the Global Risk? The Unresolved Problem of Residual Risk

Background: Atherosclerotic Cardiovascular Disease (ASCVD) is the first cause of death in Western Countries. Several risk factors contribute to generate atherosclerosis and the preventive therapeutic approaches, in particular statin therapy, reduce the mortality. However, the residual risk in statin treated patients remains significant, despite reaching the low density lipoproteins cholesterol (LDL-C) goals. Methods: we reviewed the literature published in PUB-MED to discuss the role of residual dyslipidemia in particular high density lipoprotein cholesterol (HDL-C), triglycerides (TGs) and lipoprotein(a) [Lp(a)], genetic factors, suboptimal implementation of lifestyle therapy, mood disorders associated to low compliance to application of evidence-based therapies or related to ASCVD. Results: we summarized the current knowledge on the topic, evidencing its contradictory aspects. Conclusion: HDL-C is an important biomarker for predicting cardiovascular risk, but the classical HDL hypothesis is no longer correct and it is now being replaced by the HDL function hypothesis, thought more studies are needed to validate it. The connection between cardiovascular risk and levels of TGs is not so definite. APOE genotype and Lp(a) levels are two genetics factors associated to CV risk. Healthy lifestyle with particular dietetic factors, connected to psychological aspects, are very important for the optimal control of the global risk.