Human In Vitro Oxidized Low-Density Lipoprotein (oxLDL) Increases Urinary Albumin Excretion in Rats.

Hypercholesterolemia-associated oxidative stress increases the formation of oxidized low-density lipoprotein (oxLDL), which can affect endothelial cell function and potentially contribute to renal dysfunction, as reflected by changes in urinary protein excretion. This study aimed to investigate the impact of exogenous oxLDL on urinary excretion of albumin and nephrin. LDL was isolated from a patient with familial hypercholesterolemia (FH) undergoing lipoprotein apheresis (LA) and was oxidized in vitro with Cu (II) ions. Biochemical markers of LDL oxidation, such as TBARS, conjugated dienes, and free ε-amino groups, were measured. Wistar rats were treated with a single intraperitoneal injection of PBS, LDL, or oxLDL (4 mg of protein/kg b.w.). Urine was collected one day before and two days after the injection. We measured blood lipid profiles, urinary protein excretion (specifically albumin and nephrin), and markers of systemic oxidative stress (8-OHdG and 8-iso-PGF2α). The results showed that injection of oxLDL increased urinary albumin excretion by approximately 28% (310 ± 27 µg/24 h vs. 396 ± 26 µg/24 h, p = 0.0003) but had no effect on nephrin excretion. Neither PBS nor LDL had any effect on urinary albumin or nephrin excretion. Additionally, oxLDL did not affect systemic oxidative stress. In conclusion, hypercholesterolemia may adversely affect renal function through oxidatively modified LDL, which interferes with the renal handling of albumin and leads to the development of albuminuria.

Recommendations of the Experts of the Polish Cardiac Society (PCS) and the Polish Lipid Association (PoLA) on the diagnosis and management of elevated lipoprotein(a) levels.

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.

Lipoprotein apheresis affects the concentration of extracellular vesicles in patients with elevated lipoprotein (a).

Lipoprotein apheresis (LA) is a therapeutic option for hyperlipoproteinemia(a) (hyper-Lp(a)) and atherosclerotic cardiovascular disease (ASCVD). LA improves blood rheology, reduces oxidative stress parameters and improves endothelial function. The underlying molecular mechanisms of LA beneficial effects are unknown, but it has been suggested that LA exhibits multiple activities beyond simply removing lipoproteins. We hypothesized that LA removes not only lipoproteins, but also extracellular vesicles (EVs). To test this hypothesis, we performed a prospective study in 22 patients undergoing LA for hyper-Lp(a) and ASCVD. Different EVs subtypes were measured before and directly after LA, and after 7 days. We used calibrated flow cytometry to detect total particle concentration (diameter > ~ 100 nm), total lipoproteins concentration (diameter > 200 nm, RI > 1.51), total EV concentration (diameter > 200 nm, RI < 1.41), concentrations of EVs derived from erythrocytes (CD235a+; diameter > 200 nm, RI < 1.41), leukocytes (CD45+; diameter > 200 nm, RI < 1.41) and platelets (CD61+, PEVs; diameter > 200 nm, RI < 1.41). LA reduced the concentrations of all investigated EVs subtypes and lipoproteins. Lp(a) concentration was lowered by 64.5% [(58% - 71%); p < 0.001]. Plasma concentrations of EVs > 200 nm in diameter derived from platelets (CD61 +), leukocytes (CD45+) and erythrocytes (CD235a+) decreased after single LA procedure by 42.7% [(12.8-54.7); p = 0.005], 42.6% [(29.7-54.1); p = 0.030] and 26.7% [(1.0-62.7); p = 0.018], respectively, compared to baseline. All EV subtypes returned to the baseline concentrations in blood plasma after 7 days. To conclude, LA removes not only Lp(a), but also cell-derived EVs, which may contribute to LA beneficial effects.

Fatty acid analysis in serum of patients with elevated lipoprotein(a) and cardiovascular disease undergoing lipoprotein apheresis.

BACKGROUND: Lipoprotein apheresis (LA) is an extracorporeal treatment that transiently reduces lipoprotein (a) by 60% and leads to an 80-92% reduction in major adverse cardiovascular events. LA has a significant impact on lipid profile in serum of patients with atherosclerotic cardiovascular disease. OBJECTIVE: To investigate the effects of LA on the composition of serum fatty acids (FAs), focusing on those which could have an impact on cardiovascular disease (CVD). METHODS: This is a prospective study in the First Department of Cardiology of the Medical University of Gdansk, Poland. Serum samples were collected from 28 patients before LA, just after the procedure, and 7 days after LA. Additionally, in a smaller group of patients, the samples were collected after second tour of LA (2 weeks later), as well as after 1 year from the first procedure. The serum FA profile was analyzed using gas chromatography-mass spectrometry. RESULTS: After the LA procedure, a substantial change in serum FA composition along with LDL-C and Lp(a) decrease were observed 7 days after procedure, but these parameters returned to the values similar to those before procedure after 14 days. Very long-chain FAs (VLCFAs) and very long-chain monounsaturated FAs (VLC-MUFAs) were eluted at 57% and remained low even 7 days after LA (p=0.027 and p < 0.001, respectively). We also observed an increase in the percentage of total branched-chain FAs (BCFAs) (p=0.004) and anteiso BCFAs (p=0.012) after FA. After 1 year of regular LA, a substantial decrease in serum VLC-MUFAs and n3 polyunsaturated FA (PUFAs) were noted. CONCLUSIONS: Decreased VLCFAs and VLC-MUFAs involved in CVD development remained low even 7 days after LA. An acute increase in the levels of anti-inflammatory BCFAs was observed. In turn long-term regular administration of LA substantially decreased VLC-MUFA and n3 PUFA.

Case report: lipoprotein apheresis reduces the risk of cardiovascular events and prolongs pregnancy in a woman with severely elevated lipoprotein(a), cardiovascular disease, and a high risk of preeclampsia.

Background: Preeclampsia is a common and serious pregnancy-induced disease, with potential severe maternal and fetal complications. Recently, an increased lipoprotein (a) (Lp[a]) concentration, an important factor in cardiovascular diseases (CVDs) pathogenesis, has been identified as a sensitive and specific marker of preeclampsia severity. Although lipoprotein apheresis (LA) is currently used in patients with hyperlipoproteinemia(a) and CVD, real-life data on its efficacy among pregnant women with an increased risk of preeclampsia are limited. Case presentation: We present the case of a pregnant woman with severely elevated Lp(a), two previous episodes of the acute coronary syndrome and multivessel coronary disease treated with long-term LA before pregnancy, and a high risk of preeclampsia (as assessed using combined test screening). An increased pulsatility index and early diastolic notch were observed on Doppler interrogation at 18 weeks' gestation. Biweekly LA therapy was re-initiated at 21 weeks' gestation. The LA safely removed 70% of the serum Lp(a) concentration and reduced low-density lipoprotein-cholesterol (LDL-C) levels by 60%. We also observed an improvement in her urine protein/creatinine ratio, a reduction in the pulsatility index, and a notch on Doppler interrogation. The pregnancy lasted until week 36, when severe preeclampsia prompted an emergency cesarean delivery. Conclusion: Pregnancy in women with elevated Lp(a), CVD, and a high risk of preeclampsia can present challenges in clinical management. Our case report indicates the benefits of LA in preventing atherosclerotic CVD progression during pregnancy, its potential influence on uteroplacental circulation, and prolongation of pregnancy for the best possible intrauterine fetus development. LA may be considered as a treatment option during pregnancy in such conditions. In addition, in pregnant women with CVD, we suggest screening using a combined test and measurement of Lp(a) as a marker of preeclampsia severity.

Aortic Wall Thickness as a Surrogate for Subclinical Atherosclerosis in Familial and Nonfamilial Hypercholesterolemia: Quantitative 3D Magnetic Resonance Imaging Study and Interrelations with Computed Tomography Calcium Scores, and Carotid Ultrasonography.

We aimed to compare the extent of subclinical atherosclerosis in the ascending and descending aortas by measuring wall area and thickness using 3D cardiovascular magnetic resonance imaging (aAWAI and dAWAI) in patients with asymptomatic familial hypercholesterolemia (FH) and nonfamilial hypercholesterolemia (NFH). We also aimed to establish the interrelations of CMR parameters with other subclinical atherosclerosis measurements, such as calcium scores, obtained using computed tomography in coronary arteries (CCS) and ascending and descending aorta (TCSasc and TCSdsc), as well as the carotid intima-media thicknesses (cIMT) using ultrasonography. A total of 60 patients with FH (29 men and 31 women), with a mean age of 52.3 ± 9.6 years, were analyzed. A subclinical atherosclerosis assessment was also performed on a group consisting of 30 age- and gender-matched patients with NFH, with a mean age of 52.5 ± 7.9 years. We found the ascending and descending aortic wall areas and thicknesses in the FH group to be significantly increased than those of the NFH group. A multivariate logistic regression analysis showed that a positive FH mutation value was a strong predictor of high aAWAI and dAWAI independent of the LDL cholesterol level. Correlations across CMR atherosclerotic parameters, calcium scores, and cIMT in the FH and NFH groups, were significant but low. Most of the atherosclerosis tests with high results belonged to the FH group. We found that patients with documented heterozygous FH had a higher atherosclerosis burden in the aorta compared to patients with severe hypercholesterolemia without FH gene mutation. Atherosclerosis is not severe in asymptomatic patients with FH, but is more pronounced and also more diffuse than in patients with NFH. The etiology of hypercholesterolemia, and not just cholesterol levels, plays a significant role in determining the degree of subclinical atherosclerosis.

Lipoprotein(a) As a Potential Predictive Factor for Earlier Aortic Valve Replacement in Patients with Bicuspid Aortic Valve.

Bicuspid aortic valve (BAV) affects 0.5-2% of the general population and constitutes the major cause of severe aortic valve stenosis (AVS) in individuals ≤70 years. The aim of the present study was to evaluate the parameters that may provide information about the risk of AVS developing in BAV patients, with particular emphasis on lipoprotein(a) (Lp(a)), which is a well-recognized risk factor for stenosis in the general population. We also analyzed the impact of autotaxin (ATX) and interleukin-6 (IL-6) as parameters potentially related to the pathomechanism of Lp(a) action. We found that high Lp(a) levels (>50 mg/dL) occurred significantly more frequently in patients with AVS than in patients without AVS, both in the group below and above 45 years of age (p = 0.036 and p = 0.033, respectively). Elevated Lp(a) levels were also strictly associated with the need for aortic valve replacement (AVR) at a younger age (p = 0.016). However, the Lp(a) concentration did not differ significantly between patients with and without AVS. Similarly, we observed no differences in ATX between the analyzed patient groups, and both ATX activity and concentration correlated significantly with Lp(a) level (R = 0.465, p < 0.001 and R = 0.599, p < 0.001, respectively). We revealed a significantly higher concentration of IL-6 in young patients with AVS. However, this observation was not confirmed in the group of patients over 45 years of age. We also did not observe a significant correlation between IL-6 and Lp(a) or between CRP and Lp(a) in any of the analyzed groups of BAV patients. Our results demonstrate that a high level of Lp(a), greater than 50 mg/dL, may be a significant predictive factor for earlier AVR. Lp(a)-related parameters, such as ATX and IL-6, may be valuable in providing information about the additional cardiovascular risks associated with developing AVS.

Lipid Profile, Lp(a) Levels, and HDL Quality in Adolescents with Down Syndrome.

The improvement in the lifespan of individuals with Down syndrome (DS) has created interest in the context of the development of age-related diseases. Among them is atherosclerosis-based cardiovascular disease (CVD), which seems to be an especially urgent and important issue. The aim of the present study was to evaluate the lipid markers that may clarify cardiovascular risk profiles in individuals with DS. To this end, we analyzed lipid profile parameters, including lipoprotein(a) (Lp(a)) levels, protein composition, and the antioxidative properties of high-density lipoprotein (HDL), in 47 adolescents with DS and 47 individuals without DS. Compared with the control group (C), subjects with DS had significantly increased concentrations of low-density lipoprotein cholesterol (105 ± 31 vs. 90 ± 24 mg/dL, p = 0.014), non-high-density lipoprotein cholesterol (120 ± 32 vs. 103 ± 26 mg/dL, p = 0.006), and triglycerides (72 [55−97] vs. 60 [50−77] mg/dL, p = 0.048). We found that patients with DS were characterized by significantly higher Lp(a) levels (31.9 [21.5−54.3] vs. 5.2 (2.4−16.1) mg/dL, p < 0.001). In fact, 57% of individuals with DS had Lp(a) levels above 30 mg/dL, which was approximately four times higher than those in the control group (DS 57% vs. C 15%). Apart from decreased high-density lipoprotein cholesterol levels in the subjects with DS (53 ± 11 vs. 63 ± 12 mg/dL, p < 0.001), differences in parameters showing the quality of HDL particles were observed. The concentrations of the main proteins characterizing the HDL fraction, apolipoprotein A-I and apolipoprotein A-II, were significantly lower in the DS group (144 ± 21 vs. 181 ± 33 mg/dL, p < 0.001; 33 ± 6 vs. 39 ± 6 mg/dL, p < 0.001, respectively). No significant differences between the groups were observed for the concentration of paraoxonase-1 (DS 779 ± 171 vs. C 657 ± 340 ng/mL, p = 0.063), enzyme activities toward paraoxon (DS 219 [129−286] vs. C 168 [114−272] IU/L, p = 0.949), or phenyl acetate (DS 101 ± 20 vs. C 93 ± 21 kIU/L, p = 0.068). There were no differences in myeloperoxidase activity between the study groups (DS 327 [300−534] vs. C 426 [358−533] ng/mL, p = 0.272). Our results are the first to demonstrate an unfavorable lipid profile combined with higher Lp(a) levels and quality changes in HDL particles in individuals with DS. This sheds new light on cardiovascular risk and traditional healthcare planning for adolescents with DS.

Effect of Flaxseed (Linum usitatissimum L.) Supplementation on Vascular Endothelial Cell Morphology and Function in Patients with Dyslipidaemia-A Preliminary Observation.

CONTEXT: Flaxseed has a characteristic fatty acids composition and unique phytonutrient profile that may have health-promoting properties. OBJECTIVE: This study aimed to determine the effects of 10 weeks of supplementation with the flaxseed (28 g/day) on endothelial cells (EC) function, serum lipids and proinflammatory mediators in patients with mild and severe dyslipidaemia. MATERIALS AND METHODS: Eleven lean patients with severe dyslipidaemia treated with apheresis (group 1; 10 weeks treated in four phases: (i) ordinary diet, (ii) ordinary diet + flaxseed, (iii) ordinary diet (wash out), (iv) ordinary diet + placebo) and eleven obese patients with mild dyslipidaemia-not treated with apheresis (group 2; 10 weeks treated in two phases: (i) ordinary diet, (ii) low fat diet + flaxseed). Flaxseed was given blindly. Serum was collected at the end of each phase of the study. ECs were exposed in vitro to the medium supplemented with pooled serum taken from patients from both groups to detect their morphological changes using light and electron microscopy. ECs proliferation was also measured at the end of each study phase. RESULTS: Serum vascular endothelial growth factor was decreased after flaxseed supplementation but only in group 1. ECs proliferation was increased after flaxseed supplementation only in obese patients. ECs exposed to medium supplemented with obese patients' serum revealed the following cellular abnormalities: accumulation of lipid droplets, changes of rough endoplasmic reticulum and mitochondria, and flaxseed did not reverse observed changes. At the same time, flaxseed supplementation decreases total cholesterol in both tested groups, low-density lipoprotein cholesterol in group 1 and triglycerides in group 2. CONCLUSIONS: Our findings support the potential role of flaxseed in treating dyslipidaemia but indicate only a slight impact on endothelial cell function.

Cancer Therapy-Related Cardiovascular Complications in Clinical Practice: Current Perspectives.

Cardiovascular (CV) diseases and cancer are the leading causes of death in Europe and the United States. Both diseases have extensive overlap and share common risk factors, symptoms, and outcomes. As the number of patients with both cancer and CV diseases continues to rise, the field of cardio-oncology is gaining increased attention. A frequent problem during anti-cancer treatment is cardiotoxicity caused by the side-effects of chemo-, immuno-, targeted, and radiation therapies. This problem may manifest as acute coronary syndrome, myocarditis, arrhythmias, or heart failure. Modern cardio-oncology spans many different research areas. While some researchers focus on treating patients that have already developed cardiotoxicity, others aim to identify new methods for preventing cardiotoxicity before, during, and after anti-cancer therapy. Both groups share the common understanding that regular monitoring of cancer patients is the basis for optimal medical treatment. Optimal treatment can only be achieved through close cooperation between cardiologists and oncologists. This review summarizes the current views on cardio-oncology and discusses the cardiotoxicities associated with commonly used chemotherapeutics.

Non-HDL-C/TG ratio indicates significant underestimation of calculated low-density lipoprotein cholesterol (LDL-C) better than TG level: a study on the reliability of mathematical formulas used for LDL-C estimation.

OBJECTIVES: Low-density lipoprotein cholesterol (LDL-C) is the main laboratory parameter used for the management of cardiovascular disease. The aim of this study was to compare measured LDL-C with LDL-C as calculated by the Friedewald, Martin/Hopkins, Vujovic, and Sampson formulas with regard to triglyceride (TG), LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C)/TG ratio. METHODS: The 1,209 calculated LDL-C results were compared with LDL-C measured using ultracentrifugation-precipitation (first study) and direct (second study) methods. The Passing-Bablok regression was applied to compare the methods. The percentage difference between calculated and measured LDL-C (total error) and the number of results exceeding the total error goal of 12% were established. RESULTS: There was good correlation between the measurement and calculation methods (r 0.962-0.985). The median total error ranged from -2.7%/+1.4% (first/second study) for Vujovic formula to -6.7%/-4.3% for Friedewald formula. The numbers of underestimated results exceeding the total error goal of 12% were 67 (Vujovic), 134 (Martin/Hopkins), 157 (Samspon), and 239 (Friedewald). Less than 7% of those results were obtained for samples with TG >4.5 mmol/L. From 57% (Martin/Hopkins) to 81% (Vujovic) of underestimated results were obtained for samples with a non-HDL-C/TG ratio of <2.4. CONCLUSIONS: The Martin/Hopkins, Vujovic and Sampson formulas appear to be more accurate than the Friedewald formula. To minimize the number of significantly underestimated LDL-C results, we propose the implementation of risk categories according to non-HDL-C/TG ratio and suggest that for samples with a non-HDL-C/TG ratio of <1.2, the LDL-C level should not be calculated but measured independently from TG level.

Cardiovascular events in patients with familial hypercholesterolemia and hyperlipoproteinaemia (a): Indications for lipoprotein apheresis in Poland.

BACKGROUND: Lipoprotein apheresis (LA) is a safe method of reducing atherogenic lipoproteins and improving cardiovascular (CV) outcomes. We aimed to assess the reductions in low-density lipoprotein cholesterol (LDL-C) and lipoprotein (a) [Lp(a)] levels in patients undergoing regular LA therapy and to evaluate its influence on the incidence rate of adverse cardiac and vascular events (ACVE) and major adverse cardiac events (MACE). METHODS: A longitudinal study in Poland evaluated the prospective and retrospective observational data of 23 patients with hyperlipoproteinaemia (a) [hyper-Lp(a)] and familial hypercholesterolemia (FH), undergoing 1014 LA sessions between 2013 and 2020. Their pre- and post-apheresis LDL-C and Lp(a) levels were assessed to calculate the acute percent reductions. The time period used to evaluate annual rates of ACVE and MACE before and after initiation of LA was matched in each patient. RESULTS: The pre-apheresis LDL-C and Lp(a) concentrations were 155 (107-228) (mg/dL) (median and interquartile range) and 0.56 (0.14-1.37) (g/L), respectively. LA therapy resulted in a reduction of LDL-C to 50 (30-73.5) (mg/dL) and of Lp(a) to 0.13 (0.05-0.34) (g/L), representing a percent reduction of 70.0% and 72.7% for LDL-C and Lp(a), respectively. We found a significant reduction in the annual rate of ACVE (0.365[0.0-0.585] vs (0.0[0.0-0.265]; P = .047) and MACE (0.365[0.0-0.585] vs 0.0[0.0-0.265]; P = .031). CONCLUSIONS: The findings of our study indicate that LA treatment in patients with hyperlipoproteinaemia (a) and FH on maximally tolerated lipid lowering therapies leads to a substantial reduction in LDL-C and Lp(a) concentrations and lowers CV event rates in Polish patients.

The effect of Cistus incanus herbal tea supplementation on oxidative stress markers and lipid profile in healthy adults.

BACKGROUND: Oxidative stress and dyslipidemia play a critical role in the development of cardiovascular disease (CVD). Regular intake of polyphenol-rich diets is associated with a reduced risk of CVDs. METHODS: The present study was a pilot study with 24 healthy volunteers and was designed to determine if a 12-week administration of Cistus incanus herbal tea, containing phenolic acids and flavonoids, reduces cardiovascular risk factors including oxidative stress and dyslipidemia in healthy adults. Phenolic compounds profile and antibacterial activity of Cistus incanus infusion were also measured. RESULTS: Herbal infusion led to improvement in lipid profile by increase (D4%, p = 0.033) high-density lipoprotein cholesterol concentration and decrease triglyceride (D14%, p = 0.013) concentrations. In addition, the Cistus incanus diet was associated with decreased serum concentrations of malondialdehyde (D16%, p < 0.01) and advanced oxidation protein products (D18%, p < 0.001). CONCLUSIONS: Cistus incanus administration decreases cardiovascular risk factors including oxidative stress and dyslipidemia and this action supports the idea of using Cistus incanus tea on a daily basis as an effective dietary component for prevention of atherosclerotic CVD.

Carotid intima-media thickness (IMT) in patients with severe familial and non-familial hypercholesterolemia: The effect of measurement site on the IMT correlation with traditional cardiovascular risk factors and calcium scores.

BACKGROUND: The carotid intima-media thickness (IMT) measurement may be carried out proximally (pIMT) or distally (dIMT) in relation to the bulb of the common carotid artery which has significant implications on the results and correlation with risk factors. The aim of the study was to compare the pIMT and dIMT in patients with familial hypercholesterolemia confirmed by genetic testing (FH group) and patients with severe non-familial hypercholesterolemia, with negative results of genetic testing (NFH group) and to determine the correlation of results with traditional atherosclerotic risk factors and calcium scores. METHODS: A total of 86 FH and 50 NFH patients underwent pIMT and dIMT measurements of both carotid arteries as well as computed tomography (CT) with coronary and thoracic aorta calcium scoring. RESULTS: The meanpIMT of both right and left common carotid artery were significantly higher in patients with FH compared to the NFH group (meanpRIMT 0.721 ± 0.152 vs. 0.644 ± 0.156, p < 0.01, meanpLIMT 0.758 ± 0.173 vs. 0.670 ± 0.110, p < 0.01). Patient age, pre-treatment lowdensity lipoprotein (LDL) cholesterol levels (LDLmax) at baseline and systolic blood pressure were independent predictors of pIMT increases in both carotid arteries. Smoking history, age and LDLmax were independent predictors of dIMT increase. There was a significant correlation between the calcium scores of the ascending aorta, coronary artery and aortic valve and all IMT parameters. CONCLUSIONS: The IMT measured proximally better between patients with familial and non-familial hypercholesterolemia. The association between IMT and traditional cardiovascular risk factors varies between measurement sites. IMT values correlate CT calcium scores in all patients with hypercholesterolaemia regardless of genetic etiology.

Detection of Lipoprotein X (LpX): A challenge in patients with severe hypercholesterolaemia.

BACKGROUND: Lipoprotein X (LpX) is an abnormal lipoprotein fraction, which can be detected in patients with severe hypercholesterolaemia and cholestatic liver disease. LpX is composed largely of phospholipid and free cholesterol, with small amounts of triglyceride, cholesteryl ester and protein. There are no widely available methods for direct measurement of LpX in routine laboratory practice. We present the heterogeneity of clinical and laboratory manifestations of the presence of LpX, a phenomenon which hinders LpX detection. METHODS: The study was conducted on a 26-year-old female after liver transplantation (LTx) with severely elevated total cholesterol (TC) of 38 mmol/L and increased cholestatic liver enzymes. TC, free cholesterol (FC), cholesteryl esters (CE), triglycerides, phospholipids, HDL-C, LDL-C, and apolipoproteins AI and B were measured. TC/apoB and FC:CE ratios were calculated. Lipoprotein electrophoresis was performed using a commercially available kit and laboratory-prepared agarose gel. RESULTS: Commercially available electrophoresis failed to demonstrate the presence of LpX. Laboratory-prepared gel clearly revealed the presence of lipoproteins with γ mobility, characteristic of LpX. The TC/apoB ratio was elevated and the CE level was reduced, confirming the presence of LpX. Regular lipoprotein apheresis was applied as the method of choice in LpX disease and a bridge to reLTx due to chronic liver insufficiency. CONCLUSIONS: The detection of LpX is crucial as it may influence the method of treatment. As routinely available biochemical laboratory tests do not always indicate the presence of LpX, in severe hypercholesterolaemia with cholestasis, any discrepancy between electrophoresis and biochemical tests should raise suspicions of LpX disease.

Monitoring the Effects of Hypolipidemic Treatment in Children with Familial Hypercholesterolemia in Poland.

Familial hypercholesterolemia (FH) is the most common monogenic autosomal dominant disorder. FH results in an increased cardiovascular mortality rate. However, cardiovascular risk control factors enable the avoidance of approximately 80% of strokes and cardiovascular diseases. Therefore, early detection and implementation of lipid-lowering treatment is essential. In the present study, 57 pediatric patients aged 9.57 ± 3.26 years with FH were enrolled in the study. Researchers checked the lipid profile and performed the ultrasound imaging including intima-media thickness (IMT) measurement and echo (e)-tracking in the study group. Patients were treated with a low-cholesterol diet solely or along with pharmacological treatment with statins. Subsequently, patients were monitored for 12 months. The positive results of dietary treatment were observed in 40 patients. The efficacy of 12 months of nutritional therapy along with pharmacological treatment was reported in 27 patients. We observed a significant decrease in the carotid beta index stiffness and an insignificant decrease in the IMT in the group of patients treated with statins. The obtained data show that statin therapy in children with FH allow for the reduction of the degree of atherosclerotic vessel changes.

The Impact of Lipoprotein Apheresis on Oxidative Stress Biomarkers and High-Density Lipoprotein Subfractions.

Lipoprotein apheresis (LA) treatment results in a substantial reduction of low-density lipoprotein- (LDL-) cholesterol and lipoprotein(a) concentrations, which consequently decreases the rate of cardiovascular events. The additional benefit of LA may be associated with its impact on the composition and quality of high-density lipoprotein (HDL) particles, inflammation, and oxidative stress condition. To verify the effects of LA procedure, the current study is aimed at analyzing the effect of a single apheresis procedure with direct hemadsorption (DALI) and cascade filtration (MONET) on oxidative stress markers and HDL-related parameters. The study included eleven patients with familial hypercholesterolemia and hyperlipoproteinemia(a) treated with regular LA (DALI or MONET). We investigated the pre- and postapheresis concentration of the lipid-related oxidative stress markers 8-isoPGF2, oxLDL, TBARS, and PON-1. We also tracked potential changes in the main HDL apolipoproteins (ApoA-I, ApoA-II) and cholesterol contained in HDL subfractions. A single session of LA with DALI or MONET techniques resulted in a similar reduction of lipid-related oxidative stress markers. Concentrations of 8-isoPGF2 and TBARS were reduced by ~60% and ~30%, respectively. LA resulted in a 67% decrease in oxLDL levels along with a ~19% reduction in the oxLDL/ApoB ratio. Concentrations of HDL cholesterol, ApoA-I, ApoA-II, and PON-1 activity were also reduced by LA sessions, with more noticeable effects seen in the MONET technique. The quantitative proportions between HDL2 and HDL3 cholesterol did not change significantly by both methods. In conclusion, LA treatment with MONET or DALI system has a small nonselective effect on lowering HDL particles without any changes in the protein composition of these particles. Significant reduction in the level of oxidative stress parameters and less oxidation of LDL particles may provide an additional benefit of LA therapy.

Exertional heat stroke in an amateur runner - Challenges in diagnostics and the role of unhealthy competition.

Exertional heat stroke (EHS) is a potentially life-threatening condition with a variety of symptoms and abnormal laboratory findings. Nevertheless, data evaluating the course of making an EHS diagnosis in real-life practice, as well as the role of predisposing psychological components are limited. Thus, the aim of our study was to present a multi-faceted differentiation process and show the role of unhealthy competition in the development of EHS. We describe a case of a young amateur runner, admitted to the hospital due to loss of consciousness, further mental confusion, and increased body temperature above 40°C. Head scans excluded brain haemorrhage and stroke. Elevated troponin I levels suggested an acute coronary syndrome (ACS) or myocarditis. An increase of procalcitonin levels, signs of rhabdomyolysis and severe liver injury resulted in evaluation for infection and acute hepatic damage. Subsequently, the patient's negative results pointed us to a diagnosis of EHS. In-depth anamnesis revealed that the patient's excessive effort during the race was linked to the male-female competition. EHS can present diagnostic challenges, as it mimics various diseases, such as stroke, myocarditis, ACS, infection, or liver dysfunction. In addition, the role of psychological components, such as unhealthy competition, in the development of EHS should be considered.