Atherogenic Lipoproteins Research Articles

Characterization of Polyvascular Disease in Heterozygous Familial Hypercholesterolemia: Its Association With Circulating Lipoprotein(a) Levels.

BackgroundHeterozygous familial hypercholesterolemia (HeFH) more likely exhibits extensive atherosclerotic disease at multiple vascular beds. Lipoprotein(a) (Lp(a)) is an atherogenic lipoprotein that elevates HeFH‐related atherosclerotic cardiovascular disease risks. Whether circulating Lp(a) level associates with polyvascular propagation of atherosclerosis in subjects with HeFH remains uncertain.Methods and ResultsThe current study analyzed 370 subjects with clinically diagnosed HeFH who received evaluation of systemic arteries. Polyvascular disease (polyVD) was defined as more than 2 coexisting atherosclerosis conditions including coronary artery disease, carotid stenosis, or peripheral artery disease. Clinical characteristics and lipid features were analyzed in subjects with HeFH and polyVD; 5.7% of patients with HeFH (21/370) had polyVD. They were more likely to have a clustering of risk factors, tendon (P<0.001) and skin xanthomas (P=0.004), and corneal arcus (P=0.026). Furthermore, an elevated Lp(a) level (P=0.006) and a greater frequency of Lp(a) level ≥50 mg/dL (P<0.001) were observed in subjects with HeFH and polyVD. On multivariable analysis adjusting risk factors and lipid‐lowering agents, Lp(a) ≥50 mg/dL (odds ratio [OR], 5.66 [95% CI, 1.68–19.0], P=0.005), age, and family history of premature coronary artery disease independently predicted polyVD in subjects with HeFH. Of note, the prevalence of polyVD rose to 33.3% in patients with HeFH and age >58 years old, family history of premature coronary artery disease, and Lp(a) ≥50 mg/dL (OR, 10.3 [95% CI, 3.12–33.4], P<0.001).ConclusionsAn increased level of circulating Lp(a) levels predicted concomitance of polyVD in patients with HeFH. The current findings suggest subjects with HeFH and Lp(a) ≥50 mg/dL as a high‐risk category who require meticulous screening of systemic vascular beds.

Abstract P3073: Altered Mitochondrial Mg 2+ Homeostasis In Liver Links Lipid Metabolism, Inflammation And Atherogenesis

Although evidences show the role of Mg 2+ in lipid metabolism and atherosclerosis, the molecular mechanism by which loss of Mg 2+ homeostasis promotes cardiovascular disease (CVD) is not known. Mg 2+ homeostasis is regulated by mitochondria and Mrs2 is the only known molecular machinery associated with mitochondrial Mg 2+ influx. To begin elucidating the importance of Mg 2+ homeostasis in lipid metabolism and CVD we made liver-specific Mrs2 KO mouse (Mrs2 Δhep ). Liver being the central hub of lipid metabolism, we asked whether loss of Mrs2 alters lipid metabolism and lipoprotein profile. Our results show increased accumulation of hepatic triacylglycerol (TG) and cholesterol in Mrs2 Δhep . Consistent with increased TG/cholesterol, plasma cholesterol and oxidized low density lipoprotein (ox-LDL) levels significantly differed between control and KO. Because ox-LDL contribute to atherosclerosis, we hypothesized altered hepatic lipid metabolism to induce inflammation, immune imbalance and accelerate lesions through modified atherogenic lipoprotein and cytokine profile. Quantification of plasma cytokines and chemokines were performed using the proteome profiler. Because T cells are critical drivers and modifiers of atherosclerosis, we quantified the lymphocyte and monocyte subsets by flow cytometry. Because T regulatory cells have anti-antherogenic roles, we studied the effect of ox-LDL on Tregs. Our results show increased and decreased levels of inflammatory and anti-inflammatory cytokines respectively in Mrs2 Δhep . In Mrs2 Δhep stimulation with ox-LDL showed an increased antigen specific proliferation of T-cells. We also observed increased and decreased population of Th17 and Tregs respectively. The decrease in Tregs population was attributed to increased apoptosis. In conclusion our observation suggests that high levels of ox-LDL in Mrs2 Δhep to induce inflammation and inflammatory cell expansion accompanied by apoptosis in Tregs. Our results conclude dysregulated Mg 2+ homeostasis to alter lipid metabolism and atherogenesis by inducing inflammation and compromised Tregs population. Our study will be the first of its kind to establish a triangular molecular link between Mg 2+ homeostasis, lipid metabolism, and atherogenesis.

Accelerated vascular ageing and retention of LDL in type 2 diabetes

Background and Aims : Patients with Type 2 Diabetes (T2D) are disproportionately affected by atherosclerosis compared with non-diabetics. We previously reported that the interstitial fluid-to serum ratio (IF:S) for atherogenic lipoproteins is reduced in T2D. Further measures related to pathophysiological functions of atherogenic lipoproteins in serum and IF may unveil novel insights in transvascular transport of cholesterol in atherosclerosis.

IGM autoantibodies against atherogenic lipoproteins and early manifestation of coronary heart disease

IGM autoantibodies against atherogenic lipoproteins and early manifestation of coronary heart disease

Statin therapy is not associated with insulin resistance in children and adolescents with familial hypercholesterolaemia

Background and Aims : Statins are first line therapy for lowering atherogenic low-density lipoprotein cholesterol (LDL-C) in patients with familial hypercholesterolaemia (FH). Statins were associated with an increased insulin resistance and the risk for type 2 diabetes. We aimed to assess the effect of statins on insulin resistance in children.

Effect of N-3 Polyunsaturated Fatty Acids on Lipid Composition in Familial Hypercholesterolemia: A Randomized Crossover Trial.

Individuals with familial hypercholesterolemia (FH) have an increased risk of cardiovascular disease. Treatment is mainly low-density lipoprotein cholesterol (LDL-C) reduction. How omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplements affect lipoproteins in FH subjects is unknown. We hypothesized that a high-dose n-3 PUFA supplement would reduce atherogenic lipoproteins and influence the high-density lipoprotein cholesterol (HDL-C) function. We performed a randomized, double-blinded crossover study with 34 genetically verified FH individuals (18–75 years, clinically stable, statin treatment > 12 months). Treatment was 4 g n-3 PUFAs (1840 mg eicosapentaenoic acid and 1520 mg docosahexaenoic acid daily) or four capsules of olive oil for three months in a crossover design with a washout period of three months. The defined outcomes were changes in triglycerides, lipoproteins, lipoprotein subfractions, apolipoproteins, and HDL-C function. After treatment with n-3 PUFAs, total cholesterol, LDL-C, and triglycerides were reduced compared to placebo (p ≤ 0.01 for all). Total HDL-C levels were unchanged, but the subfraction of large HDL-C was higher (p ≤ 0.0001) after n-3 PUFAs than after placebo, and intermediate HDL-C and small HDL-C were reduced after n-3 PUFAs compared to placebo (p = 0.02 and p ≤ 0.001, respectively). No changes were found in apolipoproteins and HDL-C function. N-3 PUFAs supplements reduced atherogenic lipoproteins in FH subjects, leaving HDL-C function unaffected.

The main side effects of statins in clinical practice

Statins have long occupied a central place in cardiovascular medicine, being an integral component of the prevention and treatment of atherosclerotic cardiovascular diseases (coronary heart disease and its main clinical forms, angina pectoris and myocardial infarction; transient ischemic attacks, ischemic strokes, etc.). By blocking a key enzyme of cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA-reductase), statins normalize the parameters of the lipid spectrum, primarily, the serum levels of atherogenic low-density lipoprotein cholesterol. However, in addition to the beneficial effects of statins, side effects are also characteristic, which are a significant problem in modern clinical practice due to the fact that they can cause dangerous disorders, forcing physicians to reduce dosages or completely cancel these drugs. Understanding the side effects and the mechanisms underlying their formation is important for improving the measures for the early detection, prevention and treatment of those disorders. This article discusses such side effects of statins as myotoxicity, hepatotoxicity, nephrotoxicity. The pathogenetic mechanisms underlying these toxic effects of statins are discussed. A particular attention is paid to the effect of statins on the oxidative stress, the mechanisms of oxidative damage to cellular macromolecules (lipids, proteins and DNA) and their potential role in the development of myotoxicity, hepatotoxicity and nephrotoxicity.

Management of Atherogenic Dyslipidemia in a Patient with LDL Discordance

<h3>Lead Author's Financial Disclosures</h3> Nothing to disclose. <h3>Study Funding</h3> None. <h3>Background/Synopsis</h3> We review a case of a 43-year-old male referred for optimal management of dyslipidemia and cardiovascular risk reduction. This is intended to highlight key features in diagnosis and management of atherogenic dyslipidemia in the setting of metabolic syndrome. <h3>Objective/Purpose</h3> To review a clinical scenario involving LDL discordance in a patient with atherogenic dyslipidemia and its impact on management. <h3>Methods</h3> Clinical management done at tertiary care lipid program. Advanced lipid testing including LDL particle number and size is ordered through Quest Diagnostics. <h3>Results</h3> A 43-year-old nonsmoker male with metabolic syndrome and recently diagnosed insulin dependent type 2 diabetes mellitus was referred to the lipid clinic for further evaluation. With subclinical atherosclerosis noted with calcium score of 6.6 at age 43 (50-75th percentile) and above-average carotid intimal medial thickness, he was treated with rosuvastatin 20 mg daily. Subsequently, he had a good response of ∼50% LDL reduction with LDL-c of 75 mg/dL. At this point, while most clinicians as well as guideline directed approach may suggest a sufficient management of his dyslipidemia, the advent of advanced lipid testing contrasts this dogma otherwise. LDL discordance noted based on higher-than-expected particle number strongly warrants further aggressive LDL lowering for optimal cardiovascular risk reduction in the setting of metabolic syndrome. <h3>Conclusions</h3> While calculated LDL cholesterol has been well established as a primary target of treatment to reduce cardiovascular risk, in patients with hypertriglyceridemia or metabolic syndrome, this may underestimate the true burden of atherogenic, cholesterol-carrying lipoproteins. Measurements of apoB or LDL particle number by NMR may more closely quantify the atherogenic lipoprotein load and thus prove to be better indices of cardiovascular disease risk than calculated LDL cholesterol or non-HDL cholesterol in such a population. In our clinical case, the patient may not be adequately treated based on a calculated LDL of 75 mg/dL on high intensity statin, however, an advanced lipid panel revealing LDL discordance suggests intensification and more aggressive LDL lowering for optimal cardiovascular risk reduction.

Apolipoprotein B, Residual Cardiovascular Risk After Acute Coronary Syndrome, and Effects of Alirocumab.

Background:Apolipoprotein B (apoB) provides an integrated measure of atherogenic risk. Whether apoB levels and apoB lowering hold incremental predictive information on residual risk after acute coronary syndrome beyond that provided by low-density lipoprotein cholesterol is uncertain.Methods:The ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) compared the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome and elevated atherogenic lipoproteins despite optimized statin therapy. Primary outcome was major adverse cardiovascular events (MACE; coronary heart disease death, nonfatal myocardial infarction, fatal/nonfatal ischemic stroke, hospitalization for unstable angina). Associations between baseline apoB or apoB at 4 months and MACE were assessed in adjusted Cox proportional hazards and propensity score–matched models.Results:Median follow-up was 2.8 years. In proportional hazards analysis in the placebo group, MACE incidence increased across increasing baseline apoB strata (3.2 [95% CI, 2.9–3.6], 4.0 [95% CI, 3.6–4.5], and 5.5 [95% CI, 5.0–6.1] events per 100 patient-years in strata <75, 75–<90, ≥90 mg/dL, respectively; Ptrend<0.0001) and after adjustment for low-density lipoprotein cholesterol (Ptrend=0.035). Higher baseline apoB stratum was associated with greater relative (Ptrend<0.0001) and absolute reduction in MACE with alirocumab versus placebo. In the alirocumab group, the incidence of MACE after month 4 decreased monotonically across decreasing achieved apoB strata (4.26 [95% CI, 3.78–4.79], 3.09 [95% CI, 2.69–3.54], and 2.41 [95% CI, 2.11–2.76] events per 100 patient-years in strata ≥50, >35–<50, and ≤35 mg/dL, respectively). Compared with propensity score–matched patients from the placebo group, treatment hazard ratios for alirocumab also decreased monotonically across achieved apoB strata. Achieved apoB was predictive of MACE after adjustment for achieved low-density lipoprotein cholesterol or non–high-density lipoprotein cholesterol but not vice versa.Conclusions:In patients with recent acute coronary syndrome and elevated atherogenic lipoproteins, MACE increased across baseline apoB strata. Alirocumab reduced MACE across all strata of baseline apoB, with larger absolute reductions in patients with higher baseline levels. Lower achieved apoB was associated with lower risk of MACE, even after accounting for achieved low-density lipoprotein cholesterol or non–high-density lipoprotein cholesterol, indicating that apoB provides incremental information. Achievement of apoB levels as low as ≤35 mg/dL may reduce lipoprotein-attributable residual risk after acute coronary syndrome.Registration:URL: https://www.clinicaltrials.gov; Unique identifier: NCT01663402.

Identification of different lipoprotein response types in people following a Mediterranean diet pattern with and without whole eggs

A Mediterranean (MED) diet decreases atherogenic lipoproteins and cardiovascular disease risk. We tested the hypothesis that daily consumption of whole eggs in a MED diet improves lipid metabolism compared with responses of both a control American diet and a MED diet without whole eggs. Thirty-nine overweight to obese participants were recruited into a randomized, crossover designed, controlled feeding trial evaluating 3 diets: a control, average American diet (AAD), a MED diet without whole eggs (MED-E), and a MED diet plus whole fresh eggs (1 whole egg/1000 kcal; MED+E). Treatments lasted 4 weeks followed by a >4-week washout period. Lipid concentrations, lipoprotein particle size, and number were determined at baseline and posttreatment. Intake of the AAD and MED-E decreased total cholesterol and low-density lipoprotein (LDL) concentrations (change from baseline, P < .05), without a treatment effect. Similarly, MED-E reduced (change from baseline, P < .05) triglyceride concentrations, without a treatment effect. Particle concentrations were reduced for intermediate-density lipoprotein (IDL; 26%, P < .05) and total LDL (8%, P < .05) by MED-E intake only. Very low-density lipoprotein size was reduced by MED-E intake (treatment effect, P = .04). Variability in responses, assessed by unsupervised machine learning, identified 3 main clusters of IDL- and LDL-type responses. Adoption of a MED diet meal plan without whole eggs improved lipid parameters associated with reduced cardiovascular disease risk. Significant treatment differences following inclusion of whole eggs were not observed. Individual differences in lipoprotein responses warrants further exploration.

Coronary heart disease and chronic kidney disease: the possibilities of PCSK9 inhibitors in the achievement of atherogenic lipoproteins target values

Objective: Possibilities evaluation of achieving the target values of atherogenic lipoproteins in patients with coronary heart disease (CHD) in combination with renal dysfunction during drug correction with PCSK9 inhibitors.Material and methods: The study included 76 men with CHD with very high cardiovascular risk divided into 2 groups: without chronic kidney disease (CKD) (n = 39) and with stage IIIA–IIIB CKD (n = 37). All patients did not reach the target values of lowdensity lipoprotein cholesterol (LDL cholesterol) after 8 weeks of the maximum dose of atorvastatin and ezetimibe, which was the motivation for the use of PCSK9‑alirocumab inhibitors, with control of the lipid profile and glomerular filtration rate for 6 months.Results: In the group of patients with CHD, 87.1% of patients (n = 34) reached the target values of LDL cholesterol, the level of LDL cholesterol decreased from 4.41 ± 0.19 mmol to 1.28 ± 0.14 mmol (p &lt; 0.001), in the group of patients with CHD + CKD stage IIIA–IIIB 56.7% of patients reached the target values (n = 21), the LDL cholesterol level decreased from 4.6 ± 0.2 mmol to 1.37 ± 0.09 mmol (p &lt; 0.001). There was no statistically significant change in the glomerular filtration rate during the study.Conclusion: The results of this study demonstrate the obvious effectiveness of PCSK9 inhibitors in achieving LDL cholesterol target values in patients with coronary heart disease with a very high cardiovascular risk. During the study, a decrease in the level of LDL cholesterol by more than 70% was noted. The absence of CKD in CHD patients increases the chance of achieving LDL cholesterol target values by 81% (OR 0.19).

Статины и окислительный стресс при сердечно-сосудистой патологии

Statins are a highly effective class of lipid-lowering drugs for the prevention of the risk of developing cardiovascular pathology. The main mechanism of action of statins is based on the inhibition of cholesterol formation, which leads to a decrease in serum levels of total cholesterol and atherogenic low-density lipoproteins. However, in addition to the main hypolipidemic effect, statins also have a significant effect on oxidative stress. This article discusses in detail the effect of statins on oxidative stress and its significance for cardiovascular pathology.

NLA scientific statement on statin intolerance: a new definition and key considerations for ASCVD risk reduction in the statin intolerant patient

Although statins are generally well tolerated, statin intolerance is reported in 5-30% of patients and contributes to reduced statin adherence and persistence, as well as higher risk for adverse cardiovascular outcomes. This Scientific Statement from the National Lipid Association was developed to provide an updated definition of statin intolerance and to inform clinicians and researchers about its identification and management. Statin intolerance is defined as one or more adverse effects associated with statin therapy which resolves or improves with dose reduction or discontinuation and can be classified as a complete inability to tolerate any dose of a statin or partial intolerance with inability to tolerate the dose necessary to achieve the patient-specific therapeutic objective. To classify a patient as having statin intolerance, a minimum of two statins should have been attempted, including at least one at the lowest approved daily dosage. This Statement acknowledges the importance of identifying modifiable risk factors for statin intolerance and recognizes the possibility of a “nocebo” effect (patient expectation of harm resulting in perceived side effects). To identify a tolerable statin regimen it is recommended that clinicians consider using several different strategies (e.g., different statin, dose, and/or dosing frequency). Non-statin therapy may be required for patients who cannot reach therapeutic objectives with lifestyle and maximal tolerated statin therapy. If so, therapies with outcomes data from randomized trials showing reduced cardiovascular events are favored. In high and very high risk patients who are statin intolerant, clinicians should consider initiating non-statin therapy while additional attempts are made to identify a tolerable statin in order to limit the time of exposure to elevated levels of atherogenic lipoproteins.

Proprotein convertase subtilisin/kexin type 9 inhibition after acute coronary syndrome or prior myocardial infarction.

Lowering low-density lipoprotein cholesterol (LDL-C) with statins or ezetimibe reduces major adverse cardiovascular events (MACE) in patients with coronary heart disease. Additional treatment with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors may lower LDL-C to levels not achievable with conventional lipid-lowering agents. This review summarizes findings from two large, placebo-controlled trials that evaluated the cardiovascular efficacy of monoclonal antibodies directed against PCSK9, added to background statin therapy, in patients with established atherosclerotic cardiovascular disease (ASCVD) or recent acute coronary syndrome (ACS) and persistent elevation of atherogenic lipoproteins despite statin treatment. The FOURIER trial with evolocumab and the ODYSSEY OUTCOMES trial with alirocumab demonstrated 15% overall reductions in MACE compared to placebo, associated with average achieved LDL-C levels as low as 30-40 mg/dl. Alirocumab treatment was associated with fewer deaths after ACS. Subgroups with large absolute treatment benefit included those with baseline LDL-C ≥100 mg/dl, diabetes, polyvascular or peripheral artery disease, prior coronary bypass surgery, statin intolerance, or elevated lipoprotein(a) levels. No safety concerns arose with use of PCSK9 monoclonal antibodies, even in patients who achieved LDL-C levels below 20 mg/dl. In selected patients with established ASCVD or recent ACS, PCSK9 inhibitors can play an important role in reducing the risk of MACE, and may also reduce the risk of death after ACS.

Chasing LDL cholesterol to the bottom — PCSK9 in perspective

Low-density lipoprotein (LDL) indubitably contributes causally to atherosclerosis, a leading challenge to health worldwide. Interventions that lower LDL cholesterol (LDL-C) have made remarkable inroads against this global scourge. Recent therapeutic advances have achieved ever lower levels of LDL-C. Improved cardiovascular outcomes continue to accrue from these interventions. In particular, the discovery of the role of proprotein convertase subtilisin/kexin type 9 (PCSK9) as the causal gene in autosomal-dominant hypercholesterolemia has led with remarkable speed to the development of novel agents to lower LDL-C concentrations beyond prior measures, and to alleviate further cardiovascular risk. We review how this story, and its position in the broader landscape of therapy to prevent atherosclerotic events, represents a notable victory of contemporary cardiovascular medicine and reflects successful partnerships between basic scientists, the pharmaceutical and biotechnology sectors, and clinical investigators. Continued cooperation in this manner promises to yield further progress in combating cardiovascular diseases beyond interventions on LDL-C. Libby and Tokgözoğlu discuss the management of atherogenic lipoproteins, notably low-density lipoprotein, with an emphasis on the role of strategies that target PCSK9.

Sex Differences in Lipid Metabolism: Implications for Systemic Lupus Erythematosus and Cardiovascular Disease Risk.

It is known that healthy women during childbearing years have a lower risk of cardiovascular disease (CVD) and coronary heart disease compared to age matched men. Various traditional risk factors have been shown to confer differential CVD susceptibilities by sex. Atherosclerosis is a major cause of CVD and mortality and sex differences in CVD risk could be due to reduced atherogenic low and very low-density lipoproteins (LDL and VLDL) and increased atheroprotective high density lipoproteins (HDLs) in women. In contrast, patients with systemic lupus erythematosus (SLE), a chronic inflammatory disease that predominately affects women, have an increased atherosclerotic and CVD risk. This increased CVD risk is largely associated with dyslipidaemia, the imbalance of atherogenic and atheroprotective lipoproteins, a conventional CVD risk factor. In many women with SLE, dyslipidaemia is characterised by elevated LDL and reduced HDL, eradicating the sex-specific CVD protection observed in healthy women compared to men. This review will explore this paradox, reporting what is known regarding sex differences in lipid metabolism and CVD risk in the healthy population and transgender individuals undergoing cross-sex hormone therapy, and provide evidence for how these differences may be compromised in an autoimmune inflammatory disease setting. This could lead to better understanding of mechanistic changes in lipid metabolism driving the increased CVD risk by sex and in autoimmunity and highlight potential therapeutic targets to help reduce this risk.

New insight into dyslipidemia-induced cellular senescence in atherosclerosis.

ABSTRACTAtherosclerosis, characterized by lipid‐rich plaques in the arterial wall, is an age‐related disorder and a leading cause of mortality worldwide. However, the specific mechanisms remain complex. Recently, emerging evidence has demonstrated that senescence of various types of cells, such as endothelial cells (ECs), vascular smooth muscle cells (VSMCs), macrophages, endothelial progenitor cells (EPCs), and adipose‐derived mesenchymal stem cells (AMSCs) contributes to atherosclerosis. Cellular senescence and atherosclerosis share various causative stimuli, in which dyslipidemia has attracted much attention. Dyslipidemia, mainly referred to elevated plasma levels of atherogenic lipids or lipoproteins, or functional impairment of anti‐atherogenic lipids or lipoproteins, plays a pivotal role both in cellular senescence and atherosclerosis. In this review, we summarize the current evidence for dyslipidemia‐induced cellular senescence during atherosclerosis, with a focus on low‐density lipoprotein (LDL) and its modifications, hydrolysate of triglyceride‐rich lipoproteins (TRLs), and high‐density lipoprotein (HDL), respectively. Furthermore, we describe the underlying mechanisms linking dyslipidemia‐induced cellular senescence and atherosclerosis. Finally, we discuss the senescence‐related therapeutic strategies for atherosclerosis, with special attention given to the anti‐atherosclerotic effects of promising geroprotectors as well as anti‐senescence effects of current lipid‐lowering drugs.

Interplay Between Dyslipidemia, Atherogenic Lipoproteins, and Residual Atherogenic Risk in Liver Transplant Recipients

Survival in liver transplant (LT) recipients is lower than matched controls,1Click or tap here to enter text. and cardiovascular disease (CVD) is the key contributor to this increased mortality.2 Given the central role of liver in lipoprotein metabolism, perturbation in normal physiological functions that occur with chronic liver disease (CLD), is associated with production of atherogenic lipoproteins such as small dense low-density lipoproteins (LDLs) (sdLDLs), which is associated with increased risk of atherosclerotic events in LT recipients and CLD.

Lipoprotein(a) concentration and the blood content of INFγ-producing T-helpers 17 (Th17/1) in males with premature coronary artery disease

Aim. To analyze the relationship of blood lipid profile parameters, including the level of lipoprotein(a) (Lp(a)), and the content of circulating CD4+ T-lymphocytes with premature coronary artery disease (CAD).Material and methods. This retrospective cross-sectional study included 76 men aged 40 to 79 years. Patients were divided into following groups: main group — patients with CAD (58 [54;64] years, n=56) onset before the age of 55; control group — patients (62 [57;66] years, n=20) without CAD and obstructive CAD and peripheral arterial disease. Statins were taken by 51 (91%) and 9 (45%) patients in the main and control groups, respectively. In serum and plasma samples, lipid spectrum parameters and Lp(a) concentration were determined. Cellular phenotyping was performed by direct immunofluorescence in a culture of mononuclear leukocytes isolated from blood. To determine cytokines, cells were in vitro activated with inhibitor of intracellular transport of secretory proteins. Cell fluorescence was determined using flow cytometry.Results. Patients of both groups were comparable in age, body mass index, prevalence of hypertension and diabetes. Blood Lp(a) concentrations were higher in the CAD group than in the control group (49 [10;102] mg/dL vs 12 [4,3;32] mg/ dL, p&lt;0,05). The content of INFγ-producing T-helpers 17 (Th17/1) was also higher in the CAD group (19 [15;24] vs 13 [11;22], % of Th17, p=0,05). Logistic regression revealed that elevated Lp(a) levels (≥30 mg/dL) and relative amounts of Th17/1 (&gt;14% of Th17) independently of each other, atherogenic lipoprotein cholesterol levels, classical risk factors, and statin use were associated with premature CAD in the general group of patients with odds ratio (OR) of 4,6 (95% confidence interval (CI), 1,1-20,2) and 10,9 (2,1-56,7), p&lt;0,05, respectively. The combination of Lp(a) &gt;30 mg/dl and Th17/1 over 14% significantly increased the risk of premature CAD (OR, 28,0, 95% CI, 4,31-181,75, p=0,0005).Conclusion. We have shown for the first time that an increased Lp(a) concentration with an increased Th17/1 content is associated with the premature CAD in men.

EVALUATION OF THE HEPATOTOXIC EFFECT OF LONG-TERM USE OF STATINS BASED ON THE RESULTS OF SHEAR WAVE ELASTOMETRY

Statins have been used in clinical practice for more than a quarter of a century. Over this period, their positions in various clinical guidelines have significantly strengthened. First, this group of drugs was used exclusively for the treatment of patients with a pronounced increase in the levels of atherogenic lipoproteins, but over time, the indications for their prescription have expanded considerably as well as the tactics of their use. The aim of our work is to determine the effect of statin therapy on hepatic tissue fibrosis in patients with steatohepatosis. We examined 87 patients (43 women and 44 men) with non-alcoholic steatohepatosis and liver fibrosis. The average age of the patient was 46.2 ± 4.6 years. The studies were carried out at the scientific and practical centre of the Department of Family Medicine and Therapy, Poltava State Medical University, and the Rheumatology Centre, Poltava Region Clinical Hospital. The severity of liver fibrosis was established based on 2D shear wave elastometry by transcutaneous shear wave approach in SWE mode using a convex transducer tuned to 3.5 MHz on an Ultima PA Expert ultrasound scanner (Radmir, Ukraine). The level of "stiffness" of the liver parenchyma by SWE was measured in kPa. The study included patients with liver fibrosis F2-F3 according to METAVIR. All patients received statin therapy during the study: 22 patients received rosuvastatin at a daily dose of 20 mg, 21 patients received atorvastatin at a daily dose of 20 mg, 22 patients received simvastatin at a daily dose of 20 mg, and 22 patients received lovastatin in a daily dose of 20 mg. In addition to a decrease in the level of low density lipoproteins, total cholesterol, triglycerides, systemic and long-term use of statins under the adequate treatment of steatohepatosis has led to a decrease in the severity of fibrotization of the hepatic parenchyma that is confirmed by both shear wave elastometry data and the scale data. At the same time, the difference between the indicators after the therapy in the groups of patients receiving rosuvastatin, simvastatin, atorvastatin and lovastatin showed no signs of reliability that may indicate a positive effect of inhibition of hydroxymethylglutaryl coenzyme A reductase on the progression of fibrotic changes. The use of statins in the integrated therapy of patients with steatohepatitis, in addition to normalizing the plasma lipid profile, can reduce the fibrotic changes in the liver parenchyma. It should be noted that there is no advantage to any of the medicines we investigated. Moreover, the statins used did not produce hepatotoxic effects.