Lipoprotein(a): An update on its role in human health and disease

Over the past few years, there has been an undiminished interest on lipoprotein(a) [Lp(a)]. High Lp(a) levels have been proposed as an independent causal risk factor for atherosclerotic cardiovascular disease (CVD). The main question that remains to be answered, however, is the potential clinical benefit of Lp(a) reduction. This will contribute to the enrichment of our knowledge on the exact pathophysiological role of this lipoprotein. This narrative review aims to summarize currently available data on the structure, metabolism, and pathogenicity of Lp(a).

Prevalence of Type 2 Diabetes and Cardiometabolic Risk Parameters in Evros

Introduction: The aim of this study was to estimate the prevalence of Type 2 Diabetes and related metabolic disorders in the Evros region. Material-Methods: A random sample of 541 people was studied using the Finnish Type 2 Diabetes Risk Score, and measurement of weight, height, waist and hip circumference, blood pressure, as well as Fasting Glucose and Postprandial Glucose with a reflectometer. The participants with a score of 15-20, score ≥20, FG ≥100 mg/dl and / or PG 140 mg/dl (n = 206) were subjected to a oral glucose tolerance test, according to WHO. Lipid profile, metabolic syndrome and cardiovascular risk were also assessed. Results: Prevalence of DM T2 in the study population was: 29.6%, and that of prediabetes was 10.9%. Obese (Body Mass Index ≥ 30 kg/m2) were: 52.5%, overweight (BMI 25-30kg/m2) were 33.2% and normal/low weight (BMI <25 kg/m2) were 14.1% of the population. Central obesity with a waist circumference of ≥ 102cm had 58,6% of men and ≥ 88cm 86,8% of women. Hypertension was 66.9% of the sample and 58.8% were on antihypertensive treatment. In 206 subjects, CHOL 200-239 mg/dl had 32.5% and CHOL≥ 240 mg/ dl 13.6%. 10.2% of women had HDL – CHOL <45 and <35:3,4 % of men. 5,9 % of subjects had LDL – CHOL≥ 160 mg/dl. 18% of subjects had TG: 200 – 499 mg/dl and TG ≥ 500 mg/dl:1.5%. High index Apo-B / Apo-A1 had 19.4% and Lp (a) 33% of individuals. 92.2% of these people had metabolic syndrome. Conclusions: The upward trend of DM T2 and cardiometabolic risk parameters raises the need for targeted prevention and treatment policies.

Ischemic stroke in patients with atrial fibrillation – do we need to treat with statins?

The relationship of dyslipidemia with atrial fibrillation (AF)-related stroke is not clear. The question whether patients with AF-related stroke should receive lipid lowering agents unanimously remains unanswered. Treatment with statins does not appear to be as protective as initially thought in terms of AF prevention; however, certain groups of patients may benefit from statin use. There is evidence that statins favorably affect stroke severity, in-hospital mortality, prognosis and survival of patients with AF-related stroke. Statin pretreatment is associated with better collateral circulation in patients with cardioembolic stroke. Importantly, AF frequently co-exists with several cardiovascular comorbidities, while patients with AF-related stoke may be prone to other cardiovascular events. The overall cardiovascular risk should be assessed in AF patients experiencing a stroke and treated in accordance with the proposed low density lipoprotein cholesterol (LDL-C) targets.

Genetics of severe hypercholesterolemia in the general population: Insights from the STANISLAS cohort

Background: Severe hypercholesterolemia (SH) is a common condition characterized by increased levels of total and low-density lipoprotein cholesterol (LDLc). Methods: The aim of this study is to screen for prevalence of hypercholesterolemia, perform heritability estimation of circulating lipoproteins and study the association between SH cases and surrogate cardiovascular disease markers among participants of STANISLAS cohort. Gene candidate analyses were utilized to investigate the association between lipid levels, SH and polymorphisms from the three commonly reported genes (APOB, LDLR and PCSK9). Results: Participants with SH (n=102; 6.9%) were older (58 vs. 51yr), had higher total cholesterol (290 vs. 209mg/dL), LDLc (206 vs. 136mg/dL) and triglycerides (114 vs. 88 mg/dL). Despite smoking less, they had carotid plaques more frequently (21.2 vs. 9.3%), higher cIMT (676 vs. 597µm), and had more frequent family history cardiovascular disease. The circulating lipid levels have an important heritability: LDLc 51.6%, HDLc 66.6%, total cholesterol 49.8%, and triglycerides 41.4%. The SNPs located in LDLR gene present the strongest association with LDLc levels: rs55997232, rs17242395, rs1010679, and rs11668477. Conclusion: In a healthy cohort, participants with SH had premature vascular damage. LDLc had an important component of heritability and SNPs linked to the LDLR gene presented a strong association with LDLc. These findings reinforce the need for an early identification and treatment of SH subjects, which is mostly polygenic.

Metabolically healthy obesity: Is it really benign?

Recently, a subgroup of patients with obesity but without cardiometabolic abnormalities has attracted considerable attention and has been characterized as metabolically healthy obese (MHO) patients. MHO is quite prevalent among patients with obesity. Even though these subjects have less pronounced metabolic abnormalities compared with patients with metabolically unhealthy obesity (MUO), they are at increased risk for progressing to MUO and for developing cardiovascular disease. Accordingly, diet, exercise and appropriate pharmacotherapy should be recommended to patients with MHO as strongly as in those with MUO.

Association of PCSK9 with human plasma Lipoproteins

Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) is a serine protease primarily expressed in the liver. The main function of circulating PCSK9 relates to its binding to the low-density lipoprotein receptor (LDL-R) in hepatocytes, increasing its endosomal and lysosomal degradation. This results in the inhibition of LDL-R recycling to the cell surface and therefore in the reduction of the hepatic LDL uptake, leading to the increase in plasma levels of LDL-cholesterol. Several studies have demonstrated that the plasma levels of PCSK9 are correlated with those of the ApoB-containing lipoproteins; LDL, Lp(a) and Triglyceride-Rich Lipoproteins (TRL). Furthermore, it has been shown that PCSK9 binds to the LDL and Lp(a) particles and significantly influences TRL metabolism. By contrast, controversial results exist concerning the association of PCSK9 with High Density Lipoprotein (HDL). In the present review we present existing data on the association of PCSK9 with human plasma lipoprotein particles and its possible pathophysiological role.

Pathogenetic mechanisms of statin dysglycemia and risk of new-onset diabetes

Statins are the cornerstone for primary and secondary prevention of cardiovascular disease as they have been proven to reduce cardiovascular morbidity and mortality. Statins act by inhibiting 3-hydroxy-3-methylglutaryl-CoA reductase, the rate limiting enzyme of cholesterol synthesis. Despite their important role in prevention of cardiovascular disease, there is evidence suggesting that they worsen glycaemia increasing the risk of type 2 diabetes by 10–12%, an effect that appears to differ by dose and type of statin used, with higher doses related to higher risk. Statins may cause hyperglycaemia through many pathways e.g., by increasing the intracellular concentration of calcium in the β-cell, leading to a decrease in insulin release and in addition may decrease the GLUT-4 transporter hindering the peripheral uptake of glucose. Diabetes is a major risk factor for cardiovascular disease, with statins offering remarkable protection, a property which should be stressed to the patient and perhaps even to healthcare personnel when hesitant to prescribe statins.

Mountain tea (Sideritis plants): A potential anti-atherogenic agent?

Atherosclerosis consists the leading cause of cardiovascular diseases. Over the last years, medicinal plants are considered as efficient agents in the prevention and adjuvant therapy of atherosclerosis. Mountain tea (Sideritis plants) is used as traditional remedy against common cold and gastrointestinal disorders. Its beneficial properties are attributed to its rich bioactive constituents. Polyphenols exhibit a broad range of pharmacological activities such as antioxidant, anti-inflammatory and anti-atherosclerotic effects. The present review summarizes and discusses the potential of mountain tea as an anti-atherogenic agent based on its bioactive chemical compounds and their reported pharmacological activities.

Do platelet mediators and coagulation factors affect the formation of neutrophil extracellular traps?

Aim: To investigate the effect of factor Xa (FXa), thrombin and platelets, under activation or resting conditions, on neutrophil extracellular traps (NETs) formation (NETosis). Materials and Methods: Neutrophils, isolated from apparently healthy volunteers, were challenged with 25-50 nM FXa, 0.2-8 U/mL thrombin, 5-100 μM adenosine diphosphate (ADP), 0.1-0.5 mM arachidonic acid (AA), 5-15 μg/mL collagen, 100 μM protease-activated receptor (PAR)-4 activating peptide, 10-100 μM PAR-2 activating peptide or 25-100 nM phorbol 12-myristate 13-acetate (PMA). Moreover, neutrophils were challenged with platelet-rich plasma (PRP), activated with ADP (at a concentration of either 20 μM, in an aggregometer, or of 50 μM, in situ). Neutrophils were incubated for 3.5 h at 37οC and 5% CO2 and an immunofluorescence protocol followed, in order to stain neutrophils and NETs for myeloperoxidase and DNA. Finally, NETs and neutrophils were microscopically visualized and the percentage of NET-releasing neutrophils of each of the above experimental conditions was evaluated. Results and Conclusion: Among the agonists studied, only PMA and AA, induced robust NETosis, at a threshold concentration of 25 nM and 0.25 mM, respectively. Furthermore, platelets pre-activated with ADP, but not resting platelets induce the formation of NETs, a phenomenon that is also observed when platelets were activated with ADP in situ, in the presence of neutrophils. The present results provide an additional mechanism through which platelets contribute to various pathophysiological conditions in which NETs are implicated, such as inflammation and thrombosis. The whole spectrum of platelet mediators that are implicated in NETosis needs to be further investigated.

Parental health status and children’s eating behaviors: An epidemiological study in 1728 Greek 10-12 years old students

Although the parental influence on children’s dietary habits has been widely studied, little is known about the effect of parental health status on children’s dietary behavior. Thus, the association between the parental burden of cardiometabolic disease and its impact on children’s eating habits and behaviors was examined. Material and Methods: 1,728 children aged 10-12 years old along with one of their parents were enrolled in a cross-sectional study conducted during 2014-2016. Among others, children’s dietary habits and parental medical history were recorded. Children’s adherence to the Mediterranean diet (MD) was evaluated through the KIDMED score while the parental health status was assessed through a cardiometabolic risk score calculated for this study. The working sample was 1,133 children with a recorded parental health status. Results: Most parents (92.1%) reported at most 2 cardiometabolic risk factors including overweight/obesity, diabetes mellitus, hypertension, and dyslipidemia. Ordinal logistic regression analyses showed a significant association between children’s eating habits and adherence to the MD with the parental burden of cardiovascular disease. Children showed 6% higher odds of higher adherence to the MD (OR: 1.06, 95% CI: 1.01-1.12) and 54% lower odds of not having breakfast at all (OR: 0.46, 95% CI: 0.27-0.80) for a one-unit increase in the cardiometabolic risk score. The stratified analysis revealed a significant association between KIDMED score and CVD risk score only among boys (OR: 1.09, 95% CI: 1.01-1.18). Conclusions: Parental health status is positively associated with children’s dietary behavior and adherence to the MD indicating an additional source of influence.