Circulating microRNA-126 &122 in patients with coronary artery disease: Correlation with small dense LDL.

BACKGROUND: Coronary artery disease (CAD) and stroke are major causes of cardiovascular diseases related deaths. Conventional risk factors cannot explain the changes in atherosclerosis. New and useful diagnostic markers are required. MicroRNAs are small, noncoding RNA that regulate the gene expression implicated in the pathogenesis of various cardiovascular diseases. Endothelial dysfunction is involved in the early event of the atherosclerosis process. AIMS: The current study was designed to evaluate the vascular endothelium-enriched miRNAs would be altered in CAD patients. METHODS: Circulating miR-126 & 122 levels were measured in serum from 78 CAD patients and 60 non CDA patients by qRT-PCR analysis. RESULTS: MiR-122 was significantly down regulated in CAD patients (p = 0.001), however the level of miR-126 did not show any change (p = 0.507). Remarkably, the level of miR-126 was significantly decreased in patients with CAD and high small dense low density lipoprotein (sdLDL) level. The level of miR-126 was significantly increased when sdLDL was higher in patients with risk factors for CAD but did not have angiographically significant CAD. CONCLUSION: . In CAD patient's, miR-126 level was lowered compared to non CAD patients, however the difference was not significant (0.507). However we found a direct relationship between endothelium-enriched miR-126 and sdLDL in patients with or without CAD. Our finding suggests that miR-126 may have a potential role in sdLDL cholesterol metabolism. Mir-122 plays a role in cholesterol biosynthesis and deteriorates the cardiovascular system through the process of inflammation, apoptosis, oxidative stress and ECM deposition in a number of cardiovascular diseases.

Evolving concepts in the pathophysiology of atherosclerosis: from endothelial dysfunction to thrombus formation through multiple shades of inflammation.

Atherosclerosis is the anatomo-pathological substrate of most cardio, cerebro and vascular diseases such as acute and chronic coronary syndromes, stroke and peripheral artery diseases. The pathophysiology of atherosclerotic plaque and its complications are under continuous investigation. In the last 2 decades our understanding on the formation, progression and complication of the atherosclerotic lesion has greatly improved and the role of immunity and inflammation is now well documented and accepted. The conventional risk factors modulate endothelial function determining the switch to a proatherosclerotic phenotype. From this point, lipid accumulation with an imbalance from cholesterol influx and efflux, foam cells formation, T-cell activation, cytokines release and matrix-degrading enzymes production occur. Lesions with high inflammatory rate become vulnerable and prone to rupture. Once complicated, the intraplaque thrombogenic material, such as the tissue factor, is exposed to the flowing blood, thus inducing coagulation cascade activation, platelets aggregation and finally intravascular thrombus formation that leads to clinical manifestations of this disease. Nonconventional risk factors, such as gut microbiome, are emerging novel markers of atherosclerosis. Several data indicate that gut microbiota may play a causative role in formation, progression and complication of atherosclerotic lesions. The gut dysbiosis-related inflammation and gut microbiota-derived metabolites have been proposed as the main working hypothesis in contributing to disease formation and progression. The current evidence suggest that the conventional and nonconventional risk factors may modulate the degree of inflammation of the atherosclerotic lesion, thus influencing its final fate. Based on this hypothesis, targeting inflammation seems to be a promising approach to further improve our management of atherosclerotic-related diseases.

Heart rate variability modifications in response to different types of exercise training in athletes.

Spectral analysis of heart rate variability (HRV) is a long-standing technique to indirectly assess neural cardiac regulation. This article specifically addressed how spectral analysis of HRV could help to understand neural cardiovascular adaptations to long-term exercise training; and inform us on training status in athletes. We reviewed literature searching for articles investigating resting cardiovascular adaptations to long-term exercise training through spectral analysis of HRV in athletes, from amateur to world class categories, practicing different sport disciplines, and focusing, in particular, on a series of work performed over time in our laboratory, which may highlight how different types of exercise training differently affect neural cardiac regulation. Spectral analysis of HRV has been shown its capability of detecting different adaptational changes in cardiac autonomic nervous system (ANS) regulation attending physical training in athletes of different sport disciplines. Studies showed that spectral analysis of HRV provide results that are sport-dependent and differ at individual level. ANS adaptations to exercise training are presented and discussed. Reported studies indicate that spectral analysis of HRV is an effective tool to monitor and optimize the training process and to predict athletic achievements in competitions. Cardiac ANS adaptations are strongly dependant on the type of training being performed. The individual nature of cardiac ANS adaptations should be considered to properly interpret the observed findings.

Circulating microRNA-126 as an Independent Risk Predictor of Coronary Artery Disease: A Case-Control Study.

CONTEXT: Circulating microRNAs (miR) have revolutionized the field of molecular biology owing to their potential as a diagnostic as well as a prognostic biomarker of cardiovascular disease and dysfunctions. The present study aims to identify the circulating miR-126 and -122 as an independent risk predictors of coronary artery disease cases. METHODS AND MATERIAL: Blood samples were collected from coronary artery disease cases (n=100) and non-CAD cases (n=100). Serum RNA was isolated by Trizol method. MiR levels were measured by quantitative real-time polymerase chain reaction with the specific primer probe set. RESULTS: MiR-126 levels were significantly down-regulated in CAD cases compared to non-CAD cases (controls) (80.0% vs. 39.0%, χ2=14.95, p<0.001). The level of miR-122 was significantly up-regulated in CAD cases in comparison to its non-CAD variant (14.0% vs. 63.0%, χ2=21.23, p<0.001). Multivariate analysis found chest pain (OR=37.07, 95% CI=3.21-169.04, p=0.017) and miR-126 (OR=0.01, 95% CI=0.00-0.63, p=0.030) as independent risk predictors of CAD. CONCLUSION: The results of our study show the potential of circulating miR-126 as a novel non-invasive biomarker in the risk prediction of CAD. Further unraveling of the role of miR-122 and miR-126 in the pathogenesis and progression of CAD will add to our understanding of the disease process leading to a new diagnostic approach. HIGHLIGHTS: Mir-122 and -126 significantly differentiate non CAD cases from angiographically proven CAD casesChest pain and miR-126 might work as an independent risk predictor of coronary artery disease.

Cardiac troponins: are there any differences between T and I?

The most recent international guidelines recommend the measurement of cardiac troponin I (cTnI) and cardiac troponin T (cTnT) using high-sensitivity methods (hs-cTn) for the detection of myocardial injury and the differential diagnosis of acute coronary syndromes. Myocardial injury is a prerequisite for the diagnosis of acute myocardial infarction, but also a distinct entity. The 2018 Fourth Universal Definition of Myocardial Infarction states that myocardial injury is detected when at least one value above the 99th percentile upper reference limit is measured in a patient with high-sensitivity methods for cTnI or cTnT. Not infrequently, increased hs-cTnT levels are reported in patients with congenital or chronic neuromuscular diseases, while the hs-cTnI values are often in the normal range. Furthermore, some discrepancies between the results of laboratory tests for the two troponins are occasionally found in individuals apparently free of cardiac diseases, and also in patients with cardiac diseases. In this review article, authors discuss the biochemical, pathophysiological and analytical mechanisms which may cause discrepancies between hs-cTnI and hs-cTnT test results.

The different daily distribution of proteins does not influence the variations in body composition in a sample of subjects undergoing a low-calorie Mediterranean-type diet.

BACKGROUND: Controversy exists regarding whether the different daily balances of proteins between meals and snacks in a low-calorie diet may influence the effects on body composition (BC) results. Aim of this study is to evaluate BC changes made by a lifestyle intervention in a randomized homogeneous sample of two groups with equal daily caloric reduction but different protein distributions between meals. METHODS: Forty-seven men and women (mean age: 32±10 years; Body Mass Index: 28.4±2.4 kg/m2) consumed an energy-restricted diet (788 kcal/d below the requirement) for eight weeks in a free-living contest. Subjects consumed 90.1 g protein/d (1.10±0.16 g/kg/day) and were randomized in an EVEN (16.7% at breakfast, 32.8% at lunch, 31.3% at dinner, 19.2% at snacks; N.=23) or UNEVEN (15.4% at breakfast, 36.6% at lunch, 34.9% at dinner, 12.4% at snacks; N.=24) distribution pattern. The nutritional characteristics and caloric deficit of the two diets were similar. RESULTS: The total sample had an overall improvement in both BMI (-0.9±0.6) and fat mass (FM: -2.3±1.5), while lean body mass was preserved (LBM: 0.0±0.7). There were no significant differences between the two groups in variations in BC. CONCLUSIONS: In overweight and obese subjects undergoing a Mediterranean-type low-calorie diet, a different distribution of daily protein intake between meals and snacks does not result in significant differences in terms of FM loss and LBM maintenance. This is one of the first studies showing that nutritional dietary plans with different daily protein distribution show no particular differences in fat loss and lean mass maintenance.

Early evaluation of myocardial injury by means of high-sensitivity methods for cardiac troponins after strenuous and prolonged exercise.

All the latest international guidelines recommend that cardiac troponin (cTn) I and T should be considered the preferred biomarkers for diagnosis of acute myocardial infarction. However, only in the last 5 years, a progressive improvement in analytical performance of immunometric assays has allowed the measurement of circulating levels of cTnI and cTnT in the large part of apparently healthy adult subjects. The routine use of these high-sensitivity methods for cardiac troponin (hs-cTn) assay has in a short time demonstrated that cardiac troponin concentrations frequently increase after strenuous prolonged exercise in healthy athletes. This acute response of hs-cTn assay following exercise was at first considered to be physiological and without long-term adverse consequences. More recent studies have suggested that exercise-induced increases in hs-cTn values may not be always a physiological response to exercise, but, conversely, it should sometimes be considered as an early cardiovascular risk marker. The aim of this review is to provide an overview of acute and chronic effects of strenuous physical exercise on hs-cTn circulating levels and also to discuss the potential pathophysiological and clinical implications of biomarker responses.

Obesity, vitamin D status and physical activity: 1,25(OH)2D as a potential marker of vitamin D deficiency in obese subjects.

BACKGROUND: Obesity has been regarded to be protective against fracture in spite of its association with low levels of vitamin D. Vitamin D is the key regulator of bone metabolism and its deficiency contributes to higher level of parathyroid hormone (PTH), leading to the activation of bone turnover. METHODS: We studied 161 subjects of which 65 were young healthy subjects and 96 were elderly subjects. We measured creatinine, 25(OH)D, 1,25(OH)2D, PTH, albumin, and calcium plasma levels, we evaluated physical activity, and we calculated BMI. A sub-cohort of elderly subjects also underwent DXA scans. RESULTS: Overweight and obese subjects, as well as underweight ones, had lower levels of vitamin D but normal serum concentrations of 1,25(OH)2D and PTH was higher in underweight and obese subjects. Moreover, we found a nonlinear relationship between body mass index (BMI) and PTH with a significant U-shaped exponential regression. Regardless of BMI, 25(OH)D mean levels were higher in subjects who practice physical activity. CONCLUSIONS: These findings suggest that physical activity and BMI had a significant effect on the metabolism of bone and vitamin D, but the effect of BMI was different in underweight, normal weight or obese subjects. In obesity the real vitamin D deficiency could be estimate by serum 1,25(OH)2D concentrations whose lower levels contribute to the higher PTH production and consequently to bone loss and to a greater fracture risk.

Diet high in protein-rich foods with structured sport activity may be useless to lose fat mass and maintain fat-free mass.

BACKGROUND: The aim of this study was to demonstrate that a normal protein diet along with minimal sports activity can be enough to lose fat mass and maintain muscle mass. METHODS: All participants were prescribed a hypocaloric nutritionally balanced Mediterranean-style diet tailored to the individual for 8 weeks. Body composition and energy expenditure were measured. Sedentary patients (G1) were only recommended to perform minimal aerobic training, while sport subjects (G2) were prescribed structured physical activity and higher calorie and protein contents in the diet. RESULTS: There were no significant differences between the two groups for any of the measured parameters. CONCLUSIONS: The models of lifestyle changes that are currently circulating were for the most part ineffective. It does not appear to be necessary to increase the protein content of the diet above that recommended by guidelines in order to lose weight. Even prescribing specific physical activity is not necessary to maintain muscle mass.

Patient-specific three-dimensional aortic arch modeling for automatic measurements: clinical validation in aortic coarctation.

AIM: A validated algorithm for automatic aortic arch measurements in aortic coarctation (CoA) patients could standardize procedures for clinical planning. METHODS: The model-based assessment of the aortic arch anatomy consisted of three steps: first, machine-learning-based algorithms were trained on 212 three-dimensional magnetic resonance (MR) data to automatically allocate the aortic arch position in patients and segment the aortic arch; second, for each CoA patient (N = 33), the min/max aortic arch diameters were measured using the proposed software, manually and automatically, from noncontrast-enhanced three-dimensional steady-state free precession MRI sequence at five selected sites and compared ('internal comparison' referring to the same environment); third, moreover, the same min/max aortic arch diameters were compared, obtaining them independently, manually from common MR management software (MR Viewforum) and automatically from the model (external comparison). The measured sites were: aortic sinus, sino-tubular junction, mid-ascending aorta, transverse arch and thoracoabdominal aorta at the level of the diaphragm. RESULTS: Manual and software-assisted measurements showed a good agreement: the difference between diameter measurements was not statistically significant (at α = 0.05), with only one exception, for both internal and external comparison. A high coefficient of correlation was attained for both maximum and minimum diameters in each site (for internal comparison, R > 0.73 for every site, with P < 2 × 10). Notably, in tricuspid aortic valve patients external comparison showed no statistically significant difference at any measurement sites. CONCLUSION: The automatically derived aortic arch model, starting from three-dimensional MR images, could be a support to take the measurements in CoA patients and to quickly provide a patient-specific model of aortic arch anomalies.

The effects of a 50 km ultramarathon race on high sensitivity cardiac troponin I and NT-proBNP in highly trained athletes.

BACKGROUND: High sensitivity cardiac troponins I (hs-cTnI) and T (hs-cTnT) and natriuretic peptides (BNP and NT-proBNP) are universally recognized as cardiac reference biomarkers in patients with acute coronary syndromes and heart failure respectively. However, while on one hand the high sensitivity methods of cardiac biomarkers have provided answers to fundamental pathophysiological and clinical questions in patients with heart disease, less information is available on their assessment in paraphysiological conditions, such as high intensity exercise in healthy athletes. The aim of this study was to evaluate hs-cTnI and NT-proBNP in highly trained runners after a 50 km ultramarathon. METHODS: We have enrolled 20 highly trained male athletes who have run a 50 km ultramarathon. Blood samples were collected 2 hours before the start of the race (T0) and 20 minutes after the end of the race (T1). The blood concentrations of hs-cTnI and NT-proBNP measured before the race were within reference intervals in all runners. RESULTS: Hs-cTnI significantly increased after the end of the race (median: 19 ng/L [IQR: 12.5-25.75] versus 6 ng/L [IQR: 4.25-8.0]; P<0.001), in three cases over the upper reference limit (URL) of 34 ng/L. NT-proBNP also significantly increased (median: 78 ng/L [IQR: 68.25-87.75] versus 22 ng/L [IQR: 18.25-26.75]; P<0.001). Three other athletes reached concentration over the URL (125 ng/L). CONCLUSIONS: Our study showed a significant increase in hs-cTnI and NT-proBNP in highly trained athletes after a 50 km ultramarathon race, and 30% of runners had the values of cardiac biomarkers above URL. More studies with a larger number of athletes will be needed to better understand the effects of intense exercise on the heart of trained athletes.

The combined measurement of high-sensitivity cardiac troponins and natriuretic peptides: a useful tool for clinicians?

: An enormous amount of experimental and clinical evidence has clearly shown that the measurement of cardio-specific biomarkers is able to significantly and independently improve the diagnostic accuracy and risk stratification in cardiovascular diseases. Furthermore, many recent studies have reported that the measurement of cardio-specific biomarkers has a positive impact also on the management and outcome of patients with cardiovascular diseases. Considering the significant and independent information associated with cardio-specific biomarkers, several studies have recently reported that the combined dosage of natriuretic peptides and cardiac troponins may be convenient not only for the diagnosis, prognosis, and treatment of heart disease, but also for general screening of the population for individuals with high cardiovascular risk. Due to the higher cost of cardio-specific biomarkers compared with other laboratory tests, the clinical adequacy of the combined measurement of natriuretic peptides and cardiac troponins must be carefully evaluated. Consequently, an increase in the clinical use of a laboratory test should be based not only on the favorable pathophysiological characteristics of a biomarker, but also on the high performance of the methods used for biomarker dosing. The purpose of this review is to discuss the clinical relevance and the possible cost efficiency of the combined dosage of natriuretic peptides and cardiac troponins in some clinical conditions, in particular those most frequently observed in patients with critical illnesses admitted to the emergency room.

Effects of postprandial hydroxytyrosol and derivates on oxidation of LDL, cardiometabolic state and gene expression: a nutrigenomic approach for cardiovascular prevention.

BACKGROUND AND AIM: Cardiovascular diseases (CVDs) are the most frequent causes of death in the world. Inflammation and oxidative damage contribute significantly to the development of atherosclerosis and CVDs. European Food Safety Authority scientific opinion has acknowledged that hydroxytyrosol (3,4-dihydroxyphenylethanol) and derivatives, contained in extra virgin olive oil (EVOO), typically used in Mediterranean diet may play a crucial role in the reduction of the inflammatory pathway and in the prevention of CVDs. The aim of the study was to determine the effect in healthy volunteers of 25 g of phenols-rich EVOO (p-EVOO). METHODS: The clinical study was a randomized, controlled trial to determine the acute effect in the postprandial time of 25 g of p-EVOO. We evaluated nutritional status using anthropometric parameters, body composition, serum metabolites, oxidative stress biomarkers and gene expression of eight genes related to oxidative stress and human inflammasome pathways, lasting 2 h after p-EVOO administration. Twenty-two participants resulted as eligible for the study. RESULTS: A significant reduction of oxidized LDL, malondialdehyde, triglycerides and visceral adiposity index was highlighted (P < 0.05). Significant upregulation of catalase, superoxide dismutase 1 and upstream transcription factor 1 were observed (P < 0.05). CONCLUSION: The current study shows that intake of 25 g of p-EVOO has been able to be modulated, in the postprandial time, the antioxidant profile and the expression of inflammation and oxidative stress-related genes, as superoxide dismutase 1, upstream transcription factor 1 and catalase. We also observed a significant reduction of oxidized LDL, malondialdehyde, triglycerides and visceral adiposity index. We have demonstrated that a daily intake of phenols and antioxidants can reduce the inflammatory pathway and oxidative stress and therefore the risk of atherosclerosis and CVDs. More studies on a larger population are necessary before definitive conclusions can be drawn.Trial registration ClinicalTrials.gov NCT01890070.