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Cardiovascular disease (CVD) is still a leading cause of morbidity and mortality, despite all the progress achieved as regards to both prevention and treatment. Having high levels of lipoprotein(a) [Lp(a)] is a risk factor for cardiovascular disease that operates independently. It can increase the risk of developing cardiovascular disease even when LDL cholesterol (LDL-C) levels are within the recommended range, which is referred to as residual cardiovascular risk. Lp(a) is an LDL-like particle present in human plasma, in which a large plasminogen-like glycoprotein, apolipoprotein(a) [Apo(a)], is covalently bound to Apo B100 via one disulfide bridge. Apo(a) contains one plasminogen-like kringle V structure, a variable number of plasminogen-like kringle IV structures (types 1–10), and one inactive protease region. There is a large inter-individual variation of plasma concentrations of Lp(a), mainly ascribable to genetic variants in the Lp(a) gene: in the general po-pulation, Lp(a) levels can range from <1 mg/dL to >1000 mg/dL. Concentrations also vary between different ethnicities. Lp(a) has been established as one of the risk factors that play an important role in the development of atherosclerotic plaque. Indeed, high concentrations of Lp(a) have been related to a greater risk of ischemic CVD, aortic valve stenosis, and heart failure. The threshold value has been set at 50 mg/dL, but the risk may increase already at levels above 30 mg/dL. Although there is a well-established and strong link between high Lp(a) levels and coronary as well as cerebrovascular disease, the evidence regarding incident peripheral arterial disease and carotid atherosclerosis is not as conclusive. Because lifestyle changes and standard lipid-lowering treatments, such as statins, niacin, and cholesteryl ester transfer protein inhibitors, are not highly effective in reducing Lp(a) levels, there is increased interest in developing new drugs that can address this issue. PCSK9 inhibitors seem to be capable of reducing Lp(a) levels by 25–30%. Mipomersen decreases Lp(a) levels by 25–40%, but its use is burdened with important side effects. At the current time, the most effective and tolerated treatment for patients with a high Lp(a) plasma level is apheresis, while antisense oligonucleotides, small interfering RNAs, and microRNAs, which reduce Lp(a) levels by targeting RNA molecules and regulating gene expression as well as protein production levels, are the most widely explored and promising perspectives. The aim of this review is to provide an update on the current state of the art with regard to Lp(a) pathophysiological mechanisms, focusing on the most effective strategies for lowering Lp(a), including new emerging alternative therapies. The purpose of this manuscript is to improve the management of hyperlipoproteinemia(a) in order to achieve better control of the residual cardiovascular risk, which remains unacceptably high. Full article

Hypertriglyceridemia (HTG) remains a risk-enhancing factor of atherosclerotic cardiovascular disease. We aimed to report real-world data on the management of patients with type V hyperlipoproteinemia (HLP5), an uncommon phenotype of dyslipidemia characterized by fasting chylomicronemia and severe HTG. Between July 2018 and May 2021, 90 patients with HTG, including 83 patients with type IV hyperlipoproteinemia (HLP4) and 7 patients with HLP5, were identified by plasma apolipoprotein B (apoB) and lipoprotein electrophoresis. Patients with HLP5 were younger, had higher total cholesterol (TC) (264.9 ± 26.7 mg/dL vs. 183.9 ± 26.1 mg/dL; p < 0.01) and higher triglyceride (TG) (1296.7 ± 380.5 mg/dL vs. 247.6 ± 96.1 mg/dL; p < 0.01), and had lower high-density lipoprotein cholesterol (HDL-C) (30.6 ± 4.8 mg/dL vs. 40.5 ± 8.7 mg/dL; p < 0.01) and lower low-density lipoprotein cholesterol (LDL-C) (62.9 ± 16.4 vs. 103.0 ± 21.1 mg/dL; p < 0.01) compared with patients with HLP4. Despite an aggressive use of statin and fenofibrate with greater reductions in TG (-65.9 ± 13.7% vs. -27.9 ± 30.5%; p < 0.01) following 6 months of treatment, patients with HLP5 had persistent HTG (440.1 ± 239.0 mg/dL vs. 173.9 ± 94.8 mg/dL; p < 0.01) and an increase in LDL-C (28.3 ± 57.2% vs. -19.5 ± 32.0%; p < 0.01) compared with patients with HLP4. Our findings highlight that the lack of novel TG-lowering medications and management guidelines remains an unmet medical need in patients with HLP5. Closely monitoring lipid profiles, full assessment of individual’s risk of cardiovascular disease, and emphasis on medication adherence are of clinical importance. Full article