With the introduction of ezetimibe and PCSK9 inhibitors and the growing evidence stemming from cardiovascular outcome trials on the possibility and the benefits of achieving very low levels of LDL-C with virtually no lower limit described [7, 9, 16, 17], the 2019 ESC/EAS guidelines for dyslipidemia management introduced an ambitious LDL-C target goal of < 55 mg/dL for very high-risk patients. This evidence concerns the gene PCSK9 and metabolic syndrome.