For nearly seven decades, dyslipidemia has been widely recognized as one of the most important risk factors for the development and complications of atherosclerotic cardiovascular disease (ASCVD). Large epidemiological and clinical trials have provided robust evidence in support of the fact that the magnitude of low-density lipoprotein cholesterol (LDL-C) lowering, in front of all by statins, consistently predicts the reduction of ASCVD risk.

However, several questions related to more comprehensive, higher-quality management of elevated LDL-C levels remain to be answered. These include more consistent use of the highest possible doses of potent statins, easier prescription of combination therapies, faster and better identification of patients with dyslipidemia who would benefit from alternative treatment strategies, such as PCSK9 inhibition, as well as the issue of diagnosis and effective management of statin intolerance and its subjective equivalents. Additionally, the question of when to start and how aggressively to treat hypercholesterolemia in children, adolescents, and the elderly, as well as whether to treat with statins the ASCVD risk itself in very-high- and high-risk patients with “normal” (low) LDL-C levels.

Despite the unequivocal efficiency of statins, the issue of residual ASCVD risk related to dyslipidemia remains, even in patients with already low LDL-C, such as the challenge of the best possible management of patients with combined (mixed) hyperlipidemia, atherogenic dyslipidemia (lipid triad), or moderate hypertriglyceridemia. We face these challenges in most patients with metabolic syndrome and diabetes mellitus, increasing in prevalence.

Furthermore, the role of the increased levels and the potential clinical efficiency of much more effective lowering of lipoprotein (a) is an increasingly challenging topic. Although our armamentarium of available pharmacologic interventions is fortunately expanding, further well-designed studies are needed to assess the clinical effectiveness and long-term safety of any of these new pharmacological options.

The majority of up-to-date preventive cardiology guidelines encompass numerous, increasingly evidence-supported recommendations on the way to approach the difficulties of poor compliance and adherence to long-term lipid-lowering therapy. Further, different aspects of dyslipidemia diagnosis and therapy in the era of contemporary, so-called “4P” (predictive, preemptive, personalized, and participatory) medicine are worth discussing, primarily the perspectives of a more efficient use of individual genetic information for both diagnostic and therapeutic purposes. In general, a more personalized but comprehensive approach is required instead of a “one size fits for all” intervention.

In summary, with this Special Issue of Metabolites, it is our aim to critically review available evidence on some of the above listed challenges that need to be met. We would prefer to discuss the best possible choices on the update of existing and on the development of novel lipid diagnostic and more effective pharmacotherapeutics to scale back the burden of ASCVD.

Prof. Dr. Zlatko Fras
Dr. Borut Jug
Prof. Dr. Manfredi Rizzo
Dr. Peter E. Penson
Guest Editors

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