Atherosclerotic cardiovascular diseases (ASCVD) are a very important cause of premature death. The most important risk factor for ASCVD is lipid disorders. The incidence of lipid disorders and ASCVD is constantly increasing, which means that new methods of prevention and treatment of these diseases are still being searched for. In the management of patients with lipid disorders, the primary goal of therapy is to lower the serum LDL-C concentration. Despite the available effective lipid-lowering therapies, the risk of ASCVD is still increased in some patients. A high level of serum lipoprotein (a) (Lp(a)) is a risk factor for ASCVD independent of serum LDL-C concentration. About 20% of Europeans have elevated serum Lp(a) levels, requiring treatment to reduce serum Lp(a) concentrations in addition to LDL-C. Currently available lipid lowering drugs do not sufficiently reduce serum Lp(a) levels. Hence, drugs based on RNA technology, such as pelacarsen, olpasiran, SLN360 and LY3819469, are undergoing clinical trials. These drugs are very effective in lowering the serum Lp(a) concentration and have a satisfactory safety profile, which means that in the near future they will fill an important gap in the armamentarium of lipid-lowering drugs.

Lipoprotein(a) [Lp(a)] is made up of a low-density lipoprotein (LDL) particle and a specific apolipoprotein(a). The blood concentration of Lp(a) is approximately 90% genetically determined, and the main genetic factor determining Lp(a) levels is the size of the apo(a) isoform, which is determined by the number of KIV2 domain repeats. The size of the apo(a) isoform is inversely proportional to the blood concentration of Lp(a). Lp(a) is a strong and independent cardiovascular risk factor. Elevated Lp(a) levels ≥ 50 mg/dl (≥ 125 nmol/l) are estimated to occur in more than 1.5 billion people worldwide. However, determination of Lp(a) levels is performed far too rarely, including Poland, where, in fact, it is only since the 2021 guidelines of the Polish Lipid Association (PoLA) and five other scientific societies that Lp(a) measurements have begun to be performed. Determination of Lp(a) concentrations is not easy due to, among other things, the different sizes of the apo(a) isoforms; however, the currently available certified tests make it possible to distinguish between people with low and high cardiovascular risk with a high degree of precision. In 2022, the first guidelines for the management of patients with elevated lipoprotein(a) levels were published by the European Atherosclerosis Society (EAS) and the American Heart Association (AHA). The first Polish guidelines are the result of the work of experts from the two scientific societies and their aim is to provide clear, practical recommendations for the determination and management of elevated Lp(a) levels.

Familial hypercholesterolemia (FH) is an inherited disorder. The level of low-density lipoprotein cholesterol (LDL-C) in patients with homozygous FH can be twice as high as that in patients with heterozygous FH. The inhibition of ANGPTL3 shows an important therapeutic approach in reducing LDL-C and triglycerides (TG) levels and, thus, is a potentially effective strategy in the treatment of FH. Evinacumab is a monoclonal antibody inhibiting circulating ANGPTL3, available under the trade name Evkeeza^® for the treatment of homozygous FH. It was reported that evinacumab is effective and safe in patients with homozygous and heterozygous FH, as well as resistant hypercholesterolemia and hypertriglyceridemia. This paper summarizes existing knowledge on the role of ANGPTL3, 4, and 8 proteins in lipoprotein metabolism, the findings from clinical trials with evinacumab, a fully human ANGPTL3 mAb, and the place for this new agent in lipid-lowering therapy.

Elevated plasma Lp(a) levels, which occur in as many as 1.5 billion people worldwide, are an independent and causal risk factor for atherosclerotic cardiovascular disease and calcific aortic valve disease. Unlike low-density lipoprotein cholesterol, Lp(a) levels are approximately 90% genetically determined. Currently, no approved pharmacological therapies specifically target lowering Lp(a) concentrations. Several drugs, mainly RNA-based therapies, that specifically and potently lower Lp(a), are under investigation. Three of these new therapeutic agents are advancing through clinical development to evaluate whether reducing Lp(a) levels can decrease cardiovascular risk. The outcomes of these trials could potentially transform cardiovascular disease prevention strategies; however, once approved, the drugs will likely be used for secondary prevention and ongoing strategies for managing elevated Lp(a) in primary prevention will be important. Lipoprotein(a) research is a rapidly evolving field, but unanswered questions remain concerning the physiological function of Lp(a) and its true pathogenic mechanisms.

We included 510 consecutive patients from the departments of cardiology and endocrinology, as well as outpatient metabolic and lipid disorder clinics – as a part of the PMMHRI-Lp(a) Registry (NCT06610669), which design and details were presented elsewhere [7]. Medical history was retrospectively extracted from the electronic health records (EHRs). For the purposes of our study, we collected data regarding lipid profile with Lp(a), demographic data, comorbidities, and concomitant medication. We ranged Lp(a) levels based on the following categories: < 30 mg/dl (< 75 nmol/l), 30–50 mg/dl (75–125 nmol/l), > 50–180 mg/dl (> 125–450 nmol/l) and > 180 mg/dl (> 450 nmol/l). Statistical analysis was conducted utilizing Statistica v.13 software (TIBCO Software Inc., Palo Alto, CA, USA). Continuous variables were expressed as mean ± SD or median (25^th–75^th percentile), while categorical variables were presented as proportions. Group comparisons employed Student’s t-test for independent variables and the Mann-Whitney U test or χ² test with Yates’s correction, as applicable. A significance level of p < 0.05 was adopted for all calculations to denote statistical significance. Analysis of the relationship between dependent and independent variables was performed with the use of logistic regression with a backward stepwise method.

Hyperlipidemia is the most prevalent cardiovascular (CV) risk factors. We aimed to analyze the distribution of lipid parameters and clinical variables associated with elevated and non-elevated selected lipid factors in a cohort of all consecutive patients whose lipid profile was assessed at a multi-specialist clinical center. This cross-sectional study analyzed electronic medical records of consecutive patients treated between March and November 2024. Lipid parameters measured included: total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), apolipoprotein B (apoB), and lipoprotein (a) [Lp(a)]. Non-high-density lipoprotein cholesterol (non-HDL-C) was calculated as TC–HDL-C. We used multivariate analysis to identify factors associated with LDL-C, TG, and Lp(a) concentrations. A total of 10,597 patients were included in the analysis. The median lipid concentrations (mg/dL) were: TC 162 (IQR 132–198), LDL-C 94 (IQR 69–129), non-HDL-C 112 (IQR 88–146), apoB 78 (IQR 63–99), and Lp(a) 11 (IQR 5–29). Elevated LDL-C > 100 mg/dL was observed in 45.7% of patients, non-HDL-C > 130 mg/dL in 35.1%, and apoB > 100 mg/dL in 23.2%. A discordance between LDL-C and apoB concentrations was present in 23.7% of patients (p < 0.001), while LDL-C/non-HDL-C and apoB/non-HDL-C discordance rates were 13% and 12.6%, respectively (p < 0.001). Patients at very high CV risk had lower TC, LDL-C, non-HDL-C, and apoB concentrations compared to those with low-to-moderate and high CV risk (p < 0.001) and showed the highest median Lp(a) concentration of 13 mg/dL (IQR 5–31; p = 0.01). Goal achievements of LDL-C < 100 mg/dL, TG < 150 mg/dL, and Lp(a) < 30 mg/dL were associated with lipid-lowering treatment [OR 1.32 (95% CI 1.12–1.52)], atrial fibrillation [OR 1.31 (95% CI 1.11–1.54)], chronic coronary syndromes [OR 1.27 (95% CI 1.05–1.52)], smoking [OR 0.78 (95% CI 0.65–0.95)], BMI [OR 0.98 (95% CI 0.96–0.99)], and age [OR 1.006 (95% CI 1.002–1.009)]. The highest proportion of patients with results within the normal range was observed for apoB and the lowest for LDL-C. The highest discordance was observed between apoB/LDL-C, with similar discordance rates between LDL-C/non-HDL-C and apoB/non-HDL-C. Lipid profile control was associated with BMI, atrial fibrillation, age, chronic coronary syndrome, aortic stenosis, diabetes, male gender, lipid-lowering therapy, and smoking. These findings highlight the complexity of lipid management.