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.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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,
= 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.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Introduction: Patients with acute coronary syndrome (ACS) and atrial fibrillation (AF) treated with percutaneous coronary intervention (PCI) are at high risk of bleeding and thromboembolic events. ...Thus, optimal treatment strategies in this challenging subset have been controversial. Herein, we aim to investigate different triple antithrombotic treatment (TAT) strategies in patients with ACS and AF after PCI. Methods: This was a retrospective, single-center study based on all consecutive patients with the diagnosis of ACS and AF treated with vitamin K antagonists (VKA) or non-vitamin K antagonist oral anticoagulants (NOAC) plus dual antiplatelet therapy using a P2Y12 inhibitor (clopidogrel) and aspirin (for 1 to 3 months) and observed for 12 months for major adverse cardiac events (MACE) and major or clinically relevant non-major bleeding incidents. Results: MACE occurred in 26.6% of patients treated with the VKA and 30.9% with NOAC (p = 0.659). Bleeding occurred in 7.8% of patients treated with VKA and 7.4% with NOAC (ns). Conclusions: Among patients with ACS and AF who had undergone PCI, there was no significant difference in the risk of bleeding and ischemic events among those who received TAT with NOAC and VKA.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The aim of this study was a comparison of aortic valve calcium score (AVCS) between patients with hypercholesterolemia and genetic diagnosis of familial hypercholesterolemia with low-density ...lipoprotein receptor gene mutation (LDLR-M group), versus patients with hypercholesterolemia without LDLR gene mutation (LDLR-WT group). A total of 72 LDLR-M patients and 50 LDLR-WT patients were enrolled in the study and underwent CT as a part of an assessment of coronary calcium scoring. AVCS was determined and compared between the two patient groups. AVCS was significantly higher in the LDLR-M group in comparison to the LDLR-WT group (13.8 ± 37.9 vs. 0.94 ± 3.1, p = 0.03). The Yates' chi-squared test for independence revealed that LDLR mutation and AVCS were significantly dependable (Chi^2 = 6.106, p = 0.013). The LDLR mutation was a strong predictor of a high AVCS (OR 7.83, 95% CI 2.08-29.50, p = 0.002) on multivariate regression analysis. Among the traditional risk factors, age (odds ratio 1.12, 95% CI 1.05-1.18, p<0.001) and SBP (OR 1.04, 95% CI 1.00-1.07, p = 0.045) were also significant for high result of AVCS. An assessment of computed tomography calcium scores showed that LDLR-M patients have increased AVCS in comparison to those with LDLR-WT. In addition, LDLR mutation can be considered as an independent risk factor of having high AVSC even after adjustment for risk factors including cholesterol levels. This may result from the associated process connected with the regulatory role of LDLR in evolution of aortic valve calcifications.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cardiovascular (CV) events are the number one cause of lifetime disability and deaths worldwide. It is well known that traditional risk factors do not fully correlate with clinical outcomes; ...therefore, searching for other markers that would explain CV events’ occurrence seems essential. Of importance, one of the main factors at the origin of CV events is oxidative stress, causing inflammation and atherosclerotic plaque instability. Therefore, the present study was conducted to evaluate eight carefully selected genetic polymorphisms related to oxidative stress as risk modifiers for CV events. A cohort of 1020 patients with coronary atherosclerosis was analysed in a 7-year follow-up observational study. The following end points were assessed: CV death, myocardial infarction (MI) and a combined end point of CV death/MI/stroke. Our results show that single polymorphisms are not significant cardiovascular disease risk factors, but genetic risk score (GRS), defined as the accumulation of our eight studied polymorphisms, was significantly associated with the three. Specifically, low GRS was associated with a higher risk of CV death, MI and CV death/MI/stroke. In conclusion, when regarding CV events, GRS investigated here can become clinically meaningful and undoubtedly adds to the knowledge in stratifying the risk of CV events.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Being rich in polyunsaturated fatty acids, flaxseed (
L.) is thought to be able to decrease lipid levels and dampen inflammation. In this pilot study, we aimed to determine whether flaxseed ...supplementation could improve the profiles of lipids and inflammatory mediators in patients with severe hyperlipidemia resistant to conventional lipid-lowering pharmacotherapy and requiring lipoprotein apheresis. To this end, six patients received, blindly-in addition to their normal lipoprotein apheresis regimen-a 10-week dietary supplementation with flaxseed (28 g/d) administered in biscuits. This was followed by a 10-week washed out-period and a 10-week supplementation phase with whole wheat placebo. Blood samples were collected at the end of each phase, before the lipoprotein apheresis session. The primary endpoint was the lipid profile and the secondary endpoints were the concentrations of inflammatory mediators and tolerability. Flaxseed supplementation was well-tolerated and resulted in a consistent and significant decrease in total cholesterol and low-density lipoprotein (LDL) levels. The median (and range) percentage decrease was 11.5% (0-18.8) and 7.3% (4.4-26.6), for cholesterol (
= 0.015) and LDL-C (
= 0.003), respectively. On the other hand, there was no significant effect of flaxseed on lipoprotein(a) (Lp(a)), C-reactive protein (CRP), and interleukin 6 (IL-6) concentrations. These observations indicate that flaxseed can produce a cholesterol- and LDL-lowering effect in patients treated with lipoprotein apheresis. Thus, flaxseed supplementation may help to control cholesterol in this patient population. The flaxseed supplementation protocol applied may be of use for further adequately-powered studies to validate and extend our findings.
Background
Preeclampsia is a common and serious pregnancy-induced disease, with potential severe maternal and fetal complications. Recently, an increased lipoprotein (a) (Lpa) 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.
•Serum VLCFAs and VLC-MUFAs were eluted at 57% after lipoprotein apheresis (LA).•Serum VLCFAs and VLC-MUFAs remained low for 7 days after LA.•LA induces an acute increase in the serum levels of ...anti-inflammatory BCFAs.•Long-term regular biweekly LA decreased the serum levels of VLC-MUFAs and n3 PUFAs.
Lipoprotein apheresis (LA) is an extracorporeal treatment that transiently reduces lipoprotein (a) Lp(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.
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).
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 a 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.
After the LA procedure, a substantial change in serum FA composition along with low-density lipoprotein cholesterol (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 LA. After 1 year of regular LA, a substantial decrease in serum VLC-MUFAs and n3 polyunsaturated LA (PUFAs) were noted.
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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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.
Background: The Holter electrocardiogram (ECG) provides a long signal that represents the heart’s responses to both autonomic regulation and various phenomena, including heart tissue remodeling. Loss ...of information is a common result when using global statistical metrics. Method: Breaking the signal into short data segments (e.g., windows) provides access to transient heart rate characteristics. Symbolization of the ECG by patterns of accelerations and/or decelerations allows using entropic metrics in the assessment of heart rate complexity. Two types of analysis are proposed: (i) visualization of the pattern dynamics of the whole signal, and (ii) scanning the signal for pattern dynamics in a sliding window. The method was applied to a cohort of 42 heart transplant (HTX) recipients divided into the following groups: a left ventricle of normal geometry (NG), concentrically remodeled (CR), hypertrophic remodeled (H), and to the control group (CG) consisting of signals of 41 healthy coevals. The Kruskal–Wallis test was used to assess group differences. Statistical conclusions were verified via bootstrap methods. Results: The visualization of the group pattern dynamics showed severely limited autonomic regulations in HTX patients when compared to CG. The analysis (in segments) prove that the pattern dynamics of the NG group are different from the pattern dynamics observed in the CR and H groups. Conclusion: Dynamic pattern entropy estimators tested in moving windows recognized left ventricular remodeling in stable HTX patients.
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