👤 Salvatore Piro

Lipoprotein(a) (Lp(a)) is a proatherogenic particle that is considered an important cardiovascular risk modifier due to its association with atherosclerotic cardiovascular disease (ASCVD) as well as calcific aortic valve stenosis (CAVS). Data on the clinical burden associated with elevated lipoprotein(a) levels in patients at high and very high cardiovascular risk remain limited. We evaluated the prevalence of ASCVD and LDL-C target achievement in subjects with high and very high elevated Lp(a) levels referred to a lipid unit. In this retrospective study, 1755 subjects were evaluated; 265 with Lp(a) ≥240nmol/L were included. The population was divided into two groups: high Lp(a) (240-429nmol/L, n=216) and very high Lp(a) (≥430nmol/L, n=49). ASCVD prevalence was 58% in the very high group and 48% in the high group (p=0.23). Age and statin intensity were higher in the very high Lp(a) group. LDL-C target achievement was low in both groups: 20.0% and 25.4% of very high-risk patients reached <55mg/dL as well as 18.2% and 17.2% of high-risk patients reached <70mg/dL in very high and high Lp(a) groups, respectively. Subjects with elevated Lp(a) levels showed a high prevalence of ASCVD and low LDL-C target attainment despite high-intensity statin therapy. These findings support the need for Lp(a) screening and additional lipid-lowering strategies in high-risk patients. Show less

Familial hypercholesterolemia (FH) is characterized by elevated LDL-C and an increased risk of premature cardiovascular events. Inclisiran is a small interfering RNA that inhibits hepatic PCSK9 synthesis and promotes LDL-C clearance by enhancing LDLR expression on hepatocytes. This study aimed to evaluate the efficacy of six-months add-on inclisiran on lipid profile and PWV in FH; furthermore, we investigated the association between LDL-C reduction and PWV variation. This prospective observational study involved 78 genetically confirmed FH subjects with an LDL-C off-target despite high-intensity statins plus ezetimibe. All subjects obtained biochemical analysis and PWV evaluation at baseline and after six months add-on inclisiran. After six months add-on inclisiran, 41 % of subjects achieved LDL-C targets. Significant reductions of LDL-C (-41.5 %, p < 0.001), ApoB (-33.7 %, p < 0.01), Non-HDL-C (-35.9 %, p < 0.001), and Lp(a) (-18 %, p < 0.01) were observed, while PWV improved by 14.4 % (p < 0.001). In a secondary analysis, the Primary prevention group showed a higher prevalence of subjects on LDL-C target than the Secondary prevention group (59 % vs 23.1 %, p < 0.001). Both groups exhibited significant improvements of lipid profile and PWV (Δ - 14.1 %, p < 0.01 and Δ - 14.6 %, p < 0.001, respectively). Linear regression showed a significant association between ΔPWV and ΔLDL-C in the whole study population as well as in the Primary and Secondary prevention groups (p for all <0.001). Inclisiran significantly improved lipid profile and PWV in FH subjects. ΔPWV was significantly associated with ΔLDL-C. Show less

Familial hypercholesterolemia (FH) is characterized by lifelong elevated LDL-C levels and increased cardiovascular risk. PCSK9 inhibitors (PCSK9i) reduce LDL-C and Lp(a), however, the effect of dual lipid reduction on mechanical vascular function remains unclear. The aim of this study was to evaluate the efficacy of PCSK9i in reducing LDL-C and Lp(a) and to assess the relationship between the dual lipid reduction and the mechanical vascular profile improvement in FH subjects. This prospective observational study included 301 genetically confirmed FH subjects treated with PCSK9i added to high-intensity statins and ezetimibe. Biochemical and PWV measurements were performed at baseline and after six months. Subjects were stratified into four groups based on median values of ΔLDL-C and ΔLp(a). After six months of add-on PCSK9i, 44.9% of FH subjects achieved their LDL-C targets. Reductions were observed in LDL-C (− 49.8%, Dual lipid reduction with PCSK9i was associated with a pronounced mechanical vascular profile improvement in FH subjects; however, an intensive Lp(a) reduction may be needed to achieve a greater mechanical vascular benefit. Show less