Sphingolipid Profiling: A Promising Tool for Stratifying the Metabolic Syndrome-Associated Risk

Metabolic syndrome (MetS) is a multicomponent risk condition that reflects the clustering of individual cardiometabolic risk factors related to abdominal obesity and insulin resistance. MetS increases the risk for cardiovascular diseases (CVD) and type 2 diabetes mellitus (T2DM). However, there still is not total clinical consensus about the definition of MetS, and its pathophysiology seems to be heterogeneous. Moreover, it remains unclear whether MetS is a single syndrome or a set of diverse clinical conditions conferring different metabolic and cardiovascular risks. Indeed, traditional biomarkers alone do not explain well such heterogeneity or the risk of associated diseases. There is thus a need to identify additional biomarkers that may contribute to a better understanding of MetS, along with more accurate prognosis of its various chronic disease risks. To fulfill this need, omics technologies may offer new insights into associations between sphingolipids and cardiometabolic diseases. Particularly, ceramides –the most widely studied sphingolipid class– have been shown to play a causative role in both T2DM and CVD. However, the involvement of simple glycosphingolipids remains controversial. This review focuses on the current understanding of MetS heterogeneity and discuss recent findings to address how sphingolipid profiling can be applied to better characterize MetS-associated risks.

Cardiovascular Diseases and Non-Alcoholic Fatty Liver Disease: Relationship and Pathogenetic Aspects of Pharmacotherapy

The association of non-alcoholic fatty liver disease (NAFLD) and cardiovascular risk is currently one of the actively studied areas. The incidence of non-alcoholic fatty liver disease continues to grow worldwide. In the structure of mortality rate of patients with non-alcoholic fatty liver disease, the first place is occupied by cardiovascular events: stroke and myocardial infarction. Studies have shown that the presence of severe liver fibrosis (F3-4) in NAFLD not only increases the risk of cardiovascular diseases (CVD), but also increases the risk of overall mortality by 69% due to mortality from cardiovascular causes. The degree of increased risk is associated with the degree of activity of non-alcoholic steatohepatitis (NASH). Despite the large number of works on this topic, we do not have a clear opinion on the impact on cardiovascular risk, interaction and the contribution of various factors, as well as algorithms for managing patients with non-alcoholic fatty liver disease to reduce the risk of cardiovascular diseases. This article describes the pathogenetic factors of formation of cardiovascular risks in patients with non-alcoholic fatty liver disease, proposed the idea of stratification of cardiovascular risks in these patients, taking into account changes in the structure of the liver (fibrosis) and function (clinical and biochemical activity) and also it describes the main directions of drug therapy, taking into account the common pathogenetic mechanisms for non-alcoholic fatty liver disease and cardiovascular diseases. The role of obesity, local fat depots, adipokines, and endothelial dysfunction as the leading pathogenetic factors of increased cardiovascular risk in patients with NAFLD is discussed. Among pathogenetically justified drugs in conditions of poly and comorbidity, hypolipidemic (statins, fibrates), angiotensin II receptor antagonists, beta-blockers, etc. can be considered. According to numerous studies, it becomes obvious that the assessment of cardiovascular risks in patients with NAFLD will probably allow prescribing cardiological drugs, selecting individualized therapy regimens, taking into account the form of NAFLD, and on the other hand, building curation taking into account the identified cardiovascular risks.

Diabetes, hypertension, and cardiovascular disease development

Background We aimed to compare cardiovascular risks among participants with T2DM with and without subsequent HTN and participants with HTN with and without subsequent T2DM. Methods From January 1, 2000, to December 31, 2018, we identified 16,236 matched pairs of T2DM participants with and without HTN (T2DM cohorts), 53,509 pairs of HTN participants with and without T2DM (HTN cohorts), and 21,158 pairs of comorbid HTN and T2DM participants with T2DM history or HTN history (comorbid cohorts) from Taiwan’s National Health Insurance Research Database. Cox proportional-hazard models were used to calculate the risk of cardiovascular disease. Results The mean follow-up time of this study was 6.75 years. Mean incident rates of coronary artery disease for T2DM cohorts, HTN cohorts, and comorbid cohorts were 16.80, 23.18, and 31.53 per 1000 person-years, respectively. The adjusted hazard ratios (HRs) (95% confidence intervals [95% CIs]) for incident coronary artery disease, stroke, and heart failure in T2DM participants with versus without HTN were 2.22 (2.07–2.37), 1.19 (1.16–1.23), and 0.92 (0.82–1.02), respectively; the adjusted HRs for HTN participants with versus without T2DM were 1.69 (1.55–1.84), 1.25 (1.21–1.30), and 0.98 (0.93–1.05), respectively; the adjusted HRs for comorbid T2DM and HTN participants with previous T2DM versus previous HTN were 2.78 (2.37–3.27), 1.20 (1.13–1.28), and 0.95 (0.88–1.03), respectively. Conclusions This nationwide cohort study demonstrated that both T2DM with subsequent HTN and HTN with subsequent diabetes were associated with higher cardiovascular disease risks.

Dietary Fibers and Nutraceuticals in Prevention of Hypertension

Hypertension is the major cause of mortality amongst many cardiovascular risk factors causing 7.5 million deaths annually. Macronutrient and micronutrient deficiencies are very common in general population and have broad-ranging physiological effects in-vivo which lessen inflammatory cascades and vascular reactivity. A recent trend is to perform nutritional epidemiological studies linking overall diet pattern to the lifestyle, examining the link between food and nutrients of diet to risk of chronic diseases. This chapter would deal with pharmacological and pathological basis of hypertension, utilization of dietary fibers, functional foods, nutraceuticals for hypertensive populations as well as to those with increased cardiovascular risks.

Environmental tobacco smoke and carotid intima–media thickness in healthy children and adolescents: a systematic review

Thicker carotid intima–media thickness (CIMT) has been a valid predictor for atherosclerosis development. A significant association between environmental tobacco smoke (ETS) and thickening of CIMT has been demonstrated in adults, whereas such association has scarcely been reviewed in paediatric population. The dominate electronic databases, including MEDLINE (Ovid), PubMed, Embase, CINAHL, Web of Science, Scopus, were searched from inception. Reference lists of retrieved articles were further scanned as to avoid any missing literatures. Newcastle-Ottawa scale was used to assess the quality of the included studies. Qualitative synthesis analyses were performed on the selected studies. 331 articles were retrieved, and 4 were finally selected. All four studies investigated the association between postnatal ETS and CIMT in children, and three of them reported a statistically significant positive association. Three studies investigated the association between prenatal maternal ETS and CIMT, and one of the three found a positive association. Two studies explored the association between postnatal maternal ETS and CIMT, one reported a positive association. Two studies used serum cotinine measurement to quantify ETS and demonstrated potential dose-response relationship with CIMT. ETS exposure may play an independent role in the development of cardiovascular risks in healthy children and adolescents. In the consideration of the great burden of respiratory and cardiovascular diseases, there is an urgent need of effective surveillance for paediatric population’s ETS exposure to reduce smoke exposure.

Cardiovascular risk in primary care: comparison between Framingham Score and waist circumference

Objectives: To estimate and compare the cardiovascular risk using the Framingham risk score (FRS) and waist circumference (WC) in primary care individuals and, secondarily, determine the main factors associated with these scores. Methods: Cross-sectional study involving individuals of both sexes attended in a primary health unit and aging between 30 and 74 years. The cardiovascular risks (FRS and WC) were stratified as low, intermediate, and high. The weighted Kappa coefficient was used to assess agreements between scores. Results: Fifty-five individuals (52.8 ± 9.4 years, 70.9% women) were evaluated. Using the FRS, 40.0% of the sample presented a low risk, 45.5% intermediate risk, and 14.5% high risk of cardiovascular disease. Conversely, when analyzed using the WC score, the highest frequency (71%) was observed in the high-risk category. Also, no agreement (K= 0.36; p= 0.55) was found between scores. FRS was associated with hypertension (p<0.01), diabetes (p=0.01), and stress in women (p=0.01), while the WC score was associated with hypertension (p=0.02), obesity (p<0.01), and high-density lipoprotein cholesterol HDL-c (p=0.03). Conclusions: Primary care individuals presented intermediate cardiovascular risk in the FRS and high risk in the WC, with no agreement between scores. Hypertension, diabetes, stress, obesity, and HDL-c represented the factors that were most associated with these scores.

Leptin and adiponectin in patients with chronic kidney disease and secondary hyperparathyroidism

Background. The results of studies evaluating the levels of adiponectin, leptin and their ratios in chronic kidney disease (CKD) are conflicting. It is assumed that hyperleptinemia and changes in adiponectin clearance are consequences of a decrease in the glomerular filtration rate, they exacerbate renal impairment and may affect the prognosis of survival due to cardiovascular events. It is known that secondary hyperaparathyroidism is the most frequent complication of CKD, which not only affects calcium-phosphorus metabolism and bone tissue, but also contributes to the development of pathological processes involving other hormonal and metabolic markers. Of greatest interest is the assessment of adipocytokine levels in the development of secondary hyperparathyroidism against the background of CKD as an independent factor of increasing cardiovascular risks. The purpose of the study was to assess adipocytokine levels (adiponectin, leptin) and their ratios in patients with different stages of chronic kidney disease and their relationship with manifestations of secondary hyperparathyroidism. Materials and methods. This cross-sectional study enrolled 160 people with CKD and 40 healthy individuals as a comparison group. Results. Leptin level reduction and an increase in the proportion of patients with hypoleptinemia with a decrease in the glomerular filtration rate were found, which may be an important factor determining nutritional status. Correlations were revealed between leptin level, body mass index (ρ = 0.411) and patients’ age (ρ = 0.189), as well as between leptin/adiponectin and adiponectin/leptin ratios (ρ = 0.395 and ρ = –0.395) and body mass index in patients with CKD persisting in subgroups by stage of renal failure. A relationship was found with sex for leptin and a decrease in its levels below normal values in both men and women. Conclusions. The proportion of patients with hyperadiponectinemia was significantly higher among those with end-stage CKD compared to patients with stages 1–2. There was no statistically significant relationship between adipocytokine and parathyroid hormone levels and the presence of secondary hyperparathyroidism in patients examined.

Methylenetetrahydrofolate (MTHFR), the One-Carbon Cycle, and Cardiovascular Risks

The 5-10-methylenetetrahydrofolate reductase (MTHFR) enzyme is vital for cellular homeostasis due to its key functions in the one-carbon cycle, which include methionine and folate metabolism and protein, DNA, and RNA synthesis. The enzyme is responsible for maintaining methionine and homocysteine (Hcy) balance to prevent cellular dysfunction. Polymorphisms in the MTHFR gene, especially C677T, have been associated with various diseases, including cardiovascular diseases (CVDs), cancer, inflammatory conditions, diabetes, and vascular disorders. The C677T MTHFR polymorphism is thought to be the most common cause of elevated Hcy levels, which is considered an independent risk factor for CVD. This polymorphism results in an amino acid change from alanine to valine, which prevents optimal functioning of the enzyme at temperatures above 37 °C. Many studies have been conducted to determine whether there is an association between the C677T polymorphism and increased risk for CVD. There is much evidence in favour of this association, while several studies have concluded that the polymorphism cannot be used to predict CVD development or progression. This review discusses current research regarding the C677T polymorphism and its relationship with CVD, inflammation, diabetes, and epigenetic regulation and compares the evidence provided for and against the association with CVD.

Cardiovascular risks in patients with psoriasis (literature review)

The article is of an overview nature and contains up-to-date information on comorbid cardiovascular pathology in psoriasis. Various studies have shown that psoriasis is associated with a higher prevalence of CVD risk factors, including hypertension, diabetes mellitus, dyslipidemia, obesity, and metabolic syndrome. The relationship between the severity of psoriasis and the risk of cardiovascular disease, as well as the prognostic risks with mortality rates, are discussed. Proposed common pathogenetic mechanisms include genetic factors, inflammatory pathways, adipokine secretion, insulin resistance, lipoprotein composition and function, angiogenesis, oxidative stress, and hypercoagulability.