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β3-Adrenergic receptor (β3AR) agonists have been shown to protect against ischemia–reperfusion injury (IRI). Since β3ARs are present both in cardiomyocytes and in endothelial cells, the cellular compartment responsible for this protection has remained unknown. Using transgenic mice constitutively expressing the human β3AR (hβ3AR) in cardiomyocytes or in the endothelium on a genetic background of null endogenous β3AR expression, we show that only cardiomyocyte expression protects against IRI (45 min ischemia followed by reperfusion over 24 h). Infarct size was also limited after ischemia–reperfusion in mice with cardiomyocyte hβ3AR overexpression on top of endogenous β3AR expression. hβ3AR overexpression in these mice reduced IRI-induced cardiac fibrosis and improved long-term left ventricular systolic function. Cardiomyocyte-specific β3AR overexpression resulted in a baseline remodeling of the mitochondrial network, characterized by upregulated mitochondrial biogenesis and a downregulation of mitochondrial quality control (mitophagy), resulting in elevated numbers of small mitochondria with a depressed capacity for the generation of reactive oxygen species but improved capacity for ATP generation. These processes precondition cardiomyocyte mitochondria to be more resistant to IRI. Upon reperfusion, hearts with hβ3AR overexpression display a restoration in the mitochondrial quality control and a rapid activation of antioxidant responses. Strong protection against IRI was also observed in mice infected with an adeno-associated virus (AAV) encoding hβ3AR under a cardiomyocyte-specific promoter. These results confirm the translational potential of increased cardiomyocyte β3AR expression, achieved either naturally through exercise or artificially through gene therapy approaches, to precondition the cardiomyocyte mitochondrial network to withstand future insults. [ABSTRACT FROM AUTHOR]

Aims Evidence on the association between subclinical atherosclerosis (SA) and cardiovascular (CV) events in low-risk populations is scant. To study the association between SA burden and an ischaemic scar (IS), identified by cardiac magnetic resonance (CMR), as a surrogate of CV endpoint, in a low-risk population. Methods and results A cohort of 712 asymptomatic middle-aged individuals from the Progression of Early SA (PESA-CNIC-Santander) study (median age 51 years, 84% male, median SCORE2 3.37) were evaluated on enrolment and at 3-year follow-up with 2D/3D vascular ultrasound (VUS) and coronary artery calcification scoring (CACS). A cardiac magnetic study (CMR) was subsequently performed and IS defined as the presence of subendocardial or transmural late gadolinium enhancement (LGE). On CMR, 132 (19.1%) participants had positive LGE, and IS was identified in 20 (2.9%) participants. Individuals with IS had significantly higher SCORE2 at baseline and higher CACS and peripheral SA burden (number of plaques by 2DVUS and plaque volume by 3DVUS) at both SA evaluations. High CACS and peripheral SA (number of plaques) burden were independently associated with the presence of IS, after adjusting for SCORE2 [OR for 3rd tertile, 8.31; 95% confidence interval (CI) 2.85–24.2; P < 0.001; and 2.77; 95% CI, 1.02–7.51; P = 0.045, respectively] and provided significant incremental diagnostic value over SCORE2. Conclusion In a low-risk middle-aged population, SA burden (CAC and peripheral plaques) was independently associated with a higher prevalence of IS identified by CMR. These findings reinforce the value of SA evaluation to early implement preventive measures. Clinical Trial Registration Progression of Early Subclinical Atherosclerosis (PESA) Study Identifier: NCT01410318. [ABSTRACT FROM AUTHOR]

Right ventricular (RV) failure remains the strongest determinant of survival in pulmonary hypertension (PH). We aimed to identify relevant mechanisms, beyond pressure overload, associated with maladaptive RV hypertrophy in PH. To separate the effect of pressure overload from other potential mechanisms, we developed in pigs two experimental models of PH (M1, by pulmonary vein banding and M2, by aorto-pulmonary shunting) and compared them with a model of pure pressure overload (M3, pulmonary artery banding) and a sham-operated group. Animals were assessed at 1 and 8 months by right heart catheterization, cardiac magnetic resonance and blood sampling, and myocardial tissue was analyzed. Plasma unbiased proteomic and metabolomic data were compared among groups and integrated by an interaction network analysis. A total of 33 pigs completed follow-up (M1, n = 8; M2, n = 6; M3, n = 10; and M0, n = 9). M1 and M2 animals developed PH and reduced RV systolic function, whereas animals in M3 showed increased RV systolic pressure but maintained normal function. Significant plasma arginine and histidine deficiency and complement system activation were observed in both PH models (M1&M2), with additional alterations to taurine and purine pathways in M2. Changes in lipid metabolism were very remarkable, particularly the elevation of free fatty acids in M2. In the integrative analysis, arginine–histidine–purines deficiency, complement activation, and fatty acid accumulation were significantly associated with maladaptive RV hypertrophy. Our study integrating imaging and omics in large-animal experimental models demonstrates that, beyond pressure overload, metabolic alterations play a relevant role in RV dysfunction in PH. [ABSTRACT FROM AUTHOR]

Aims Epigenetic age is emerging as a personalized and accurate predictor of biological age. The aim of this article is to assess the association of subclinical atherosclerosis with accelerated epigenetic age and to investigate the underlying mechanisms mediating this association. Methods and results Whole blood methylomics, transcriptomics, and plasma proteomics were obtained for 391 participants of the Progression of Early Subclinical Atherosclerosis study. Epigenetic age was calculated from methylomics data for each participant. Its divergence from chronological age is termed epigenetic age acceleration. Subclinical atherosclerosis burden was estimated by multi-territory 2D/3D vascular ultrasound and by coronary artery calcification. In healthy individuals, the presence, extension, and progression of subclinical atherosclerosis were associated with a significant acceleration of the Grim epigenetic age, a predictor of health and lifespan, regardless of traditional cardiovascular risk factors. Individuals with an accelerated Grim epigenetic age were characterized by an increased systemic inflammation and associated with a score of low-grade, chronic inflammation. Mediation analysis using transcriptomics and proteomics data revealed key pro-inflammatory pathways (IL6 , Inflammasome , and IL10) and genes (IL1B, OSM, TLR5 , and CD14) mediating the association between subclinical atherosclerosis and epigenetic age acceleration. Conclusion The presence, extension, and progression of subclinical atherosclerosis in middle-aged asymptomatic individuals are associated with an acceleration in the Grim epigenetic age. Mediation analysis using transcriptomics and proteomics data suggests a key role of systemic inflammation in this association, reinforcing the relevance of interventions on inflammation to prevent cardiovascular disease. [ABSTRACT FROM AUTHOR]

Clonal hematopoiesis of indeterminate potential (CHIP), defined as the presence of somatic mutations in cancer-related genes in blood cells in the absence of hematological cancer, has recently emerged as an important risk factor for several age-related conditions, especially cardiovascular disease. CHIP is strongly associated with normal aging, but its role in premature aging syndromes is unknown. Hutchinson-Gilford progeria syndrome (HGPS) is an ultra-rare genetic condition driven by the accumulation of a truncated form of the lamin A protein called progerin. HGPS patients exhibit several features of accelerated aging and typically die from cardiovascular complications in their early teens. Previous studies have shown normal hematological parameters in HGPS patients, except for elevated platelets, and low levels of lamin A expression in hematopoietic cells relative to other cell types in solid tissues, but the prevalence of CHIP in HGPS remains unexplored. To investigate the potential role of CHIP in HGPS, we performed high-sensitivity targeted sequencing of CHIP-related genes in blood DNA samples from a cohort of 47 HGPS patients. As a control, the same sequencing strategy was applied to blood DNA samples from middle-aged and elderly individuals, expected to exhibit a biological age and cardiovascular risk profile similar to HGPS patients. We found that CHIP is not prevalent in HGPS patients, in marked contrast to our observations in individuals who age normally. Thus, our study unveils a major difference between HGPS and normal aging and provides conclusive evidence that CHIP is not frequent in HGPS and, therefore, is unlikely to contribute to the pathophysiology of this accelerated aging syndrome. [ABSTRACT FROM AUTHOR]

Background and Purpose: Reperfusion therapy is the standard of care for ischaemic stroke; however, there is a need to identify new therapeutic targets able to ameliorate cerebral damage. Neutrophil β1 adrenoceptors (β1AR) have been linked to neutrophil migration during exacerbated inflammation. Given the central role of neutrophils in cerebral damage during stroke, we hypothesize that β1AR blockade will improve stroke outcomes. Experimental Approach: Rats were subjected to middle cerebral artery occlusion–reperfusion to evaluate the effect on stroke of the selective β1AR blocker metoprolol (12.5 mg·kg−1) when injected i.v. 10 min before reperfusion. Key Results: Magnetic resonance imaging and histopathology analysis showed that pre‐reperfusion i.v. metoprolol reduced infarct size. This effect was accompanied by reduced cytotoxic oedema at 24 h and vasogenic oedema at 7 days. Metoprolol‐treated rats showed reduced brain neutrophil infiltration and those which infiltrated displayed a high proportion of anti‐inflammatory phenotype (N2, YM1+). Additional inflammatory models demonstrated that metoprolol specifically blocked neutrophil migration via β1AR and excluded a significant effect on the glia compartment. Consistently, metoprolol did not protect the brain in neutrophil‐depleted rats upon stroke. In patients suffering an ischaemic stroke, β1AR blockade by metoprolol reduced circulating neutrophil–platelet co‐aggregates. Conclusions and Implications: Our findings describe that β1AR blockade ameliorates cerebral damage by targeting neutrophils, identifying a novel therapeutic target to improve outcomes in patients with stroke. This therapeutic strategy is in the earliest stages of the translational pathway and should be further explored. [ABSTRACT FROM AUTHOR]

Aims Clinical guidelines recommend early intravenous β-blockers during ongoing myocardial infarction; however, it is unknown whether all β-blockers exert a similar cardioprotective effect. We experimentally compared three clinically approved intravenous β-blockers. Methods and results Mice undergoing 45 min/24 h ischaemia–reperfusion (I/R) received vehicle, metoprolol, atenolol, or propranolol at min 35. The effect on neutrophil infiltration was tested in three models of exacerbated inflammation. Neutrophil migration was evaluated in vitro and in vivo by intravital microscopy. The effect of β-blockers on the conformation of the β1 adrenergic receptor was studied in silico. Of the tested β-blockers, only metoprolol ameliorated I/R injury [infarct size (IS) = 18.0% ± 0.03% for metoprolol vs. 35.9% ± 0.03% for vehicle; P  < 0.01]. Atenolol and propranolol had no effect on IS. In the three exacerbated inflammation models, neutrophil infiltration was significantly attenuated only in the presence of metoprolol (60%, 50%, and 70% reductions vs. vehicle in myocardial I/R injury, thioglycolate-induced peritonitis, and lipopolysaccharide-induced acute lung injury, respectively). Migration studies confirmed the particular ability of metoprolol to disrupt neutrophil dynamics. In silico analysis indicated different intracellular β1 adrenergic receptor conformational changes when bound to metoprolol than to the other two β-blockers. Conclusions Metoprolol exerts a disruptive action on neutrophil dynamics during exacerbated inflammation, resulting in an infarct-limiting effect not observed with atenolol or propranolol. The differential effect of β-blockers may be related to distinct conformational changes in the β1 adrenergic receptor upon metoprolol binding. If these data are confirmed in a clinical trial, metoprolol should become the intravenous β-blocker of choice for patients with ongoing infarction. Open in new tab Download slide Open in new tab Download slide [ABSTRACT FROM AUTHOR]

Objectives: To propose and validate a novel imaging sequence that uses a single breath-hold whole-heart 3D T1 saturation recovery compressed SENSE rapid acquisition (SACORA) at 3T. Methods: The proposed sequence combines flexible saturation time sampling, compressed SENSE, and sharing of saturation pulses between two readouts acquired at different RR intervals. The sequence was compared with a 3D saturation recovery single-shot acquisition (SASHA) implementation with phantom and in vivo experiments (pre and post contrast; 7 pigs) and was validated against the reference inversion recovery spin echo (IR-SE) sequence in phantom experiments. Results: Phantom experiments showed that the T1 maps acquired by 3D SACORA and 3D SASHA agree well with IR-SE. In vivo experiments showed that the pre-contrast and post-contrast T1 maps acquired by 3D SACORA are comparable to the corresponding 3D SASHA maps, despite the shorter acquisition time (15s vs. 188s, for a heart rate of 60 bpm). Mean septal pre-contrast T1 was 1453 ± 44 ms with 3D SACORA and 1460 ± 60 ms with 3D SASHA. Mean septal post-contrast T1 was 824 ± 66 ms and 824 ± 60 ms. Conclusion: 3D SACORA acquires 3D T1 maps in 15 heart beats (heart rate, 60 bpm) at 3T. In addition to its short acquisition time, the sequence achieves good T1 estimation precision and accuracy. [ABSTRACT FROM AUTHOR]

Calcific aortic valve disease (CAVD) is a significant cause of illness and death worldwide. Identification of early predictive markers could help optimize patient management. RNA-sequencing was carried out on human fetal aortic valves at gestational weeks 9, 13, and 22 and on a case-control study with adult noncalcified and calcified bicuspid and tricuspid aortic valves. In dimension reduction and clustering analyses, diseased valves tended to cluster with fetal valves at week 9 rather than normal adult valves, suggesting that part of the disease program might be due to reiterated developmental processes. The analysis of groups of coregulated genes revealed predominant immune-metabolic signatures, including innate and adaptive immune responses involving lymphocyte T-cell metabolic adaptation. Cytokine and chemokine signaling, cell migration, and proliferation were all increased in CAVD, whereas oxidative phosphorylation and protein translation were decreased. Discrete immune-metabolic gene signatures were present at fetal stages and increased in adult controls, suggesting that these processes intensify throughout life and heighten in disease. Cellular stress response and neurodegeneration gene signatures were aberrantly expressed in CAVD, pointing to a mechanistic link between chronic inflammation and biological aging. Comparison of the valve RNA-sequencing data set with a case-control study of whole blood transcriptomes from asymptomatic individuals with early aortic valve calcification identified a highly predictive gene signature of CAVD and of moderate aortic valve calcification in overtly healthy individuals. These data deepen and broaden our understanding of the molecular basis of CAVD and identify a peripheral blood gene signature for the early detection of aortic valve calcification. [ABSTRACT FROM AUTHOR]

Nonrevascularizable coronary artery disease is a frequent cause of hibernating myocardium leading to heart failure (HF). Currently, there is a paucity of therapeutic options for patients with this condition. There is a lack of animal models resembling clinical features of hibernating myocardium. Here we present a large animal model of hibernating myocardium characterized by serial multimodality imaging. Yucatan minipigs underwent a surgical casein ameroid implant around the proximal left anterior descending coronary artery (LAD), resulting in a progressive obstruction of the vessel. Pigs underwent serial multimodality imaging including invasive coronary angiography, cardiac magnetic resonance (CMR), and hybrid 18F-Fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT). A total of 43 pigs were operated on and were followed for 120 ± 37 days with monthly multimodality imaging. 24 pigs (56%) died during the follow-up. Severe LAD luminal stenosis was documented in all survivors. In the group of 19 long-term survivors, 17 (90%) developed left ventricular systolic dysfunction [median LVEF of 35% (IQR 32.5–40.5%)]. In 17/17, at-risk territory was viable on CMR and 14 showed an increased glucose uptake in the at-risk myocardium on 18FDG-PET/CT. The present pig model resembles most of the human hibernated myocardium characteristics and associated heart failure (systolic dysfunction, viable myocardium, and metabolic switch to glucose). This human-like model might be used to test novel interventions for nonrevascularizable coronary artery disease and ischemia heart failure as a previous stage to clinical trials. [ABSTRACT FROM AUTHOR]

This article discusses the association between subclinical atherosclerosis (SA) and epigenetic age acceleration (EAA) mediated by inflammation. The study identifies pathways and genes that suggest a pro-inflammatory phenotype, which may contribute to the long-term pathogenic consequences of SA. The authors suggest that further studies using single-cell RNA-seq are needed to identify specific immune cell subpopulations responsible for this association and to translate these findings into new therapeutic targets. The article also mentions the role of senescence and cellular senescence-associated secretory phenotype (SASP) in the pathogenic effect of SA. The authors agree with the notion that there are intrinsic immune characteristics of each individual that may modulate the response to traditional coronary risk factors, but more molecular information at the single-cell level is needed to examine this possibility conclusively. [Extracted from the article]

Aims: Myocardial infarction (MI) alters cardiac fibre organization with unknown consequences on ventricular arrhythmia. We used diffusion tensor imaging (DTI) of three-dimensional (3D) cardiac fibres and scar reconstructions to identify the main parameters associated with ventricular arrhythmia inducibility and ventricular tachycardia (VT) features after MI.Methods and Results: Twelve pigs with established MI and three controls underwent invasive electrophysiological characterization of ventricular arrhythmia inducibility and VT features. Animal-specific 3D scar and myocardial fibre distribution were obtained from ex vivo high-resolution contrast-enhanced T1 mapping and DTI sequences. Diffusion tensor imaging-derived parameters significantly different between healthy and scarring myocardium, scar volumes, and left ventricular ejection fraction (LVEF) were included for arrhythmia risk stratification and correlation analyses with VT features. Ventricular fibrillation (VF) was the only inducible arrhythmia in 4 out of 12 infarcted pigs and all controls. Ventricular tachycardia was also inducible in the remaining eight pigs during programmed ventricular stimulation. A DTI-based 3D fibre disorganization index (FDI) showed higher disorganization within dense scar regions of VF-only inducible pigs compared with VT inducible animals (FDI: 0.36; 0.36-0.37 vs. 0.32; 0.26-0.33, respectively, P = 0.0485). Ventricular fibrillation induction required lower programmed stimulation aggressiveness in VF-only inducible pigs than VT inducible and control animals. Neither LVEF nor scar volumes differentiated between VF and VT inducible animals. Re-entrant VT circuits were localized within areas of highly disorganized fibres. Moreover, the FDI within heterogeneous scar regions was associated with the median VT cycle length per animal (R2 = 0.5320).Conclusion: The amount of scar-related cardiac fibre disorganization in DTI sequences is a promising approach for ventricular arrhythmia stratification after MI. [ABSTRACT FROM AUTHOR]

Reperfusion, despite being required for myocardial salvage, is associated with additional injury. We hypothesize that infarct size (IS) will be reduced by a period of bloodless reperfusion with hemoglobin-based oxygen carriers (HBOC) before blood-flow restoration. In the pig model, we first characterized the impact of intracoronary perfusion with a fixed volume (600 ml) of a pre-oxygenated acellular HBOC, HBOC-201, on the healthy myocardium. HBOC-201 was administered through the lumen of the angioplasty balloon (i.e., distal to the occlusion site) immediately after onset of coronary occlusion at 1, 0.7, 0.4, or 0.2 ml/kg/min for 12, 17, 30, and 60 min, respectively, followed by blood-flow restoration. Outcome measures were systemic hemodynamics and LV performance assessed by the state-of-the-art cardiac magnetic resonance (CMR) imaging. The best performing HBOC-201 perfusion strategies were then tested for their impact on LV performance during myocardial infarction, in pigs subjected to 45 min mid-left anterior descending (LAD) coronary occlusion. At the end of the ischemia duration, pigs were randomized to regular reperfusion (blood-only reperfusion) vs. bloodless reperfusion (perfusion with pre-oxygenated HBOC-201 distal to the occlusion site), followed by blood-flow restoration. Hemodynamics and CMR-measured LV performance were assessed at 7- and 45-day follow-up. In modifications of the HBOC-201 procedure, glucose and insulin were included to support cardiac metabolism. A total of 66 pigs were included in this study. Twenty healthy pigs (5 per infusion protocol) were used in the study of healthy myocardium. Intracoronary administration of HBOC-201 (600 ml) at varying rates, including a flow of 0.4 ml/kg/min (corresponding to a maximum perfusion time of 30 min), did not damage the healthy myocardium. Slower perfusion (longer infusion time) was associated with permanent LV dysfunction and myocardial necrosis. A total of 46 pigs underwent MI induction. Compared with regular reperfusion, bloodless reperfusion with pre-oxygenated HBOC-201 alone increased IS. This effect was reversed by enrichment of pre-oxygenated HBOC-201 solution with glucose and insulin, resulting in no increase in IS or worsening of long-term ventricular function despite further delaying restoration of blood flow in the LAD. Bloodless reperfusion with a pre-oxygenated HBOC-201 solution supplemented with glucose and insulin is feasible and safe, but did not reduce infarct size. This strategy could be, however, used to deliver agents to the myocardium to treat or prevent ischemia/reperfusion injury before blood-flow restoration. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease (CVD) is a major cause of disability and premature death. Despite European guidelines advocating the use of medical therapies in CVD, many patients still do not achieve the guidelinerecommended treatment, which highlights the need for change and innovations in this field. This requirement has been widely recognised by the national ministries of health, several European cardiology societies, and the European Parliament, who support the initiation of strategies to improve and promote cardiovascular health. Discussion: One of the key risk factors to recurrent cardiovascular events is the lack of adherence to medication and this has been added to the agenda of the European Commission. With the intention to improve treatment adherence in CVD, polypills have been investigated and numerous studies demonstrate that they significantly improve medication adherence, which contributes to the improvement of health outcomes. In Europe, the first cardiovascular polypill, developed by a public-private partnership (CNIC-Ferrer), recently became available for general prescription as a therapy for CVD prevention. This polypill significantly improves adherence, preventing fatal and non-fatal cardiovascular events, and appears to be a cost-effective strategy to improve sustainability of the health care systems in CVD. Conclusions: Given the importance of urgent and simple solutions to restraining the pandemic nature of CVD, the polypill approach should therefore be considered by physicians and public health systems as an available and innovative option to improve cardiovascular health. [ABSTRACT FROM AUTHOR]

Beta-3 adrenergic receptor (b3AR) agonists have been shown to produce vasodilation and prevention of ventricular remodeling in different conditions. Given that these biological functions are critical in pulmonary hypertension (PH), we aimed to demonstrate a beneficial effect of b3AR agonists in PH. An experimental study in pigs (n = 34) with chronic PH created by pulmonary vein banding was designed to evaluate the acute hemodynamic effect and the long-term effect of b3AR agonists on hemodynamics, vascular remodeling and RV performance in chronic PH. Ex vivo human experiments were performed to explore the expression of b3AR mRNA and the vasodilator response of b3AR agonists in pulmonary arteries. Single intravenous administration of the b3AR agonist BRL37344 produced a significant acute reduction in PVR, and two-weeks treatment with two different b3AR selective agonists, intravenous BRL37344 or oral mirabegron, resulted in a significant reduction in PVR (median of -2.0 Wood units/m2 for BRL37344 vs. +1.5 for vehicle, p = 0.04; and -1.8 Wood units/m2 for mirabegron vs. +1.6 for vehicle, p = 0.002) associated with a significant improvement in magnetic resonance- measured RV performance. Histological markers of pulmonary vascular proliferation (p27 and Ki67) were significantly attenuated in b3AR agonists-treated pigs. b3AR was expressed in human pulmonary arteries and b3AR agonists produced vasodilatation. b3AR agonists produced a significant reduction in PVR and improved RV performance in experimental PH, emerging as a potential novel approach for treating patients with chronic PH. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the public health and economic benefits of adherence to a fixed-dose combination polypill for the secondary prevention of cardiovascular (CV) events in adults with a history of myocardial infarction (MI) in the UK. Design: Markov-model-based cost-effectiveness analysis, informed by systematic reviews, which identified efficacy, utilities and adherence data inputs. Setting: General practice in the UK. Participants: Patients with a mean age of 64.7 years, most of whom are men with a recent or non-recent diagnosis of MI and for whom secondary preventive medication is indicated and well tolerated. Intervention: Fixed-dose combination polypill (100 mg aspirin, 20 mg atorvastatin and 2.5, 5, or 10 mg ramipril) compared with multiple monotherapy. Primary and secondary outcome measures: CV events prevented per 1000 patients; cost per life-year gained; and cost per quality-adjusted life-year (QALY) gained. Results: The model estimates that for each 10% increase in adherence, an additional 6.7% fatal and non-fatal CV events can be prevented. In the base case, over 10 years, the polypill would improve adherence by ~20% and thereby prevent 47 of 323 (15%) fatal and non-fatal CV events per 1000 patients compared with multiple monotherapy, with an incremental cost-effectiveness ratio (ICER) of £8200 per QALY gained. Probabilistic sensitivity analyses for the base-case assumptions showed an 81.5% chance of the polypill being cost-effective at a willingness-to-pay threshold of £20 000 per QALY gained compared with multiple monotherapy. In scenario analyses that varied structural assumptions, ICERs ranged between cost saving and £21 430 per QALY gained. Conclusions: Assuming that some 450 000 adults are at risk of MI, a 10 percentage point uptake of the polypill could prevent 3260 CV events and 590 CV deaths over a decade.The polypill appears to be a cost- effective strategy to prevent fatal and non-fatal CV events in the UK. [ABSTRACT FROM AUTHOR]

Objective: To assess the agreement between self-reported and parent-reported dietary and physical activity habits in children; and to evaluate the socio-economic determinants of healthier habits (Mediterranean diet and physical activity) among children. Design: Cross-sectional analysis of children recruited to a cluster-randomized controlled trial (Program SI!). Information about children's and parents' dietary and physical activity habits was obtained through validated questionnaires (Program SI! questionnaires, Kidmed, Krece Plus and Predimed scores). Setting: Twenty-four schools in Madrid, Spain. Subjects: Children (n 2062) aged 3-5 years and their parents (n 1949). Results: There was positive agreement between parental- and self-reporting for three of the six children's habits examined. Parents' dietary and physical activity patterns were associated with those of their children. The main determinants of higher scores in children were higher parental age, the mother's scores, Spanish origin and higher awareness of human health (P<0·005). Children from parents with a low educational level had lower odds for scoring positively on items such as using olive oil (OR=0·23; 95 % CI 0·13, 0·41) and not skipping breakfast (OR=0·36; 95 % CI 0·23, 0·55), but higher odds for meeting the recommendations for consuming pulses (OR=1·71; 95 % CI 1·14, 2·55). Other habits being influenced by parental socio-economic status included the consumption of vegetables, fish, nuts, avoidance of fast food, and consumption of bakery products for breakfast. Conclusions: Children's habits may be influenced by their parents' health awareness and other socio-economic characteristics. These findings suggest that intervention strategies, even in very young children, should also target parents in order to achieve maximum success. [ABSTRACT FROM AUTHOR]

Imaging subclinical atherosclerosis holds the promise of individualized cardiovascular (CV) risk assessment. The large arsenal of noninvasive imaging techniques available today is playing an increasingly important role in the diagnosis and monitoring of subclinical atherosclerosis. However, there is a debate about the advisability of clinical screens for subclinical atherosclerosis and which modality is the most appropriate for monitoring risk and atherosclerosis progression. This article offers an overview of the traditional and emerging noninvasive imaging modalities used to detect early atherosclerosis, surveys population studies addressing the value of subclinical atherosclerosis detection, and also examines guideline recommendations for their clinical implementation. The clinical relevance of this manuscript lies in the potential of current imaging technology to improve CV risk prediction based on traditional risk factors and the present recommendations for subclinical atherosclerosis assessment. Noninvasive imaging will also help to identify individuals at high CV who would benefit from intensive prevention or therapeutic interventions. [ABSTRACT FROM AUTHOR]

Selective stimulation of β adrenergic-receptor (β3AR) has been shown to reduce infarct size in a mouse model of myocardial ischemia/reperfusion. However, its functional long-term effect and the cardioprotective mechanisms at the level of cardiomyocytes have not been elucidated, and the impact of β3AR stimulation has not been evaluated in a more translational large animal model. This study aimed at evaluating pre-perfusion administration of BRL37344 both in small and large animal models of myocardial ischemia/reperfusion. Pre-reperfusion administration of the β3AR agonist BRL37344 (5 μg/kg) reduced infarct size at 2-and 24-h reperfusion in wild-type mice. Long-term (12-weeks) left ventricular (LV) function assessed by echocardiography and cardiac magnetic resonance (CMR) was significantly improved in β3AR agonist-treated mice. Incubation with β3AR agonist (BRL37344, 7 μmol/L) significantly reduced cell death in isolated adult mouse cardiomyocytes during hypoxia/reoxygenation and decreased susceptibility to deleterious opening of the mitochondrial permeability transition pore (mPTP), via a mechanism dependent on the Akt-NO signaling pathway. Pre-reperfusion BRL37344 administration had no effect on infarct size in cyclophilin-D KO mice, further implicating mPTP in the mechanism of protection. Large-white pigs underwent percutaneous coronary ischemia/reperfusion and 3-T CMR at 7 and 45 days post-infarction. Pre-perfusion administration of BRL37344 (5 μg/kg) decreased infarct size and improved long-term LV contractile function. A single-dose administration of β3AR agonist before reperfusion decreased infarct size and resulted in a consistent and long-term improvement in cardiac function, both in small and large animal models of myocardial ischemia/reperfusion. This protection appears to be executed through inhibition of mPTP opening in cardiomyocytes. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) is prevalent and carries high morbidity and mortality, mostly due to right ventricular (RV) dysfunction. Postcapillary PH is the most frequent form but there are no large-animal models available. We developed and characterized a porcine model of postcapillary PH by non-restrictive banding of the confluent of both inferior pulmonary veins ( n = 10; sham controls n = 3). Right heart catheterization and magnetic resonance were performed before the procedure and monthly during 4 months. All banded animals developed PH. Compared to controls, banded animals presented higher mean pulmonary artery pressure [median (first to third quartile) 30 mmHg (25-37) vs. 20 mmHg (18-23); p = 0.018] and higher pulmonary vascular resistance [5.2 WU (3.8-7.1) vs. 2.3 WU (2.1-3.5); p = 0.028] after 2 months. Differences in indexed RV end-systolic volume [42 mL/m (36-53) vs. 24 mL/m (24-33); p = 0.028] and RV ejection fraction [59 % (54-63) vs. 66 % (64-68); p = 0.028] were also significant after 2 months. Differences remained significant throughout the study. Histopathology revealed increased lung weight and fibrosis but no increase in average water content. Also, remodeling on pulmonary arteries including increased medial and intimal thickness and fibrosis and RV myocardial disarray and fibrosis was demonstrated. Lung remodeling findings were similar in all pulmonary lobes. [ABSTRACT FROM AUTHOR]

Background: The onset of inadequate behaviors leading to the development of risk factors for chronic diseases is known to occur early in life. An effective program for health promotion should therefore focus on children and their environment, as the starting point for behavior development. The overarching objective of the Program SI! (Salud Integral - Comprehensive Health) is to intervene at the school level, to establish and develop life-lasting habits that will help preserving health during adulthood. The Program SI! comprises five consecutive subprograms according to the five stages of education in Spain, the first being in preschoolers. This study aims to evaluate the efficacy of Program SI! to establish and improve lifestyle behaviors in children (preschoolers aged 3-5 years), their parents, and teachers, and also improving the school environment. A secondary objective is to evaluate improvements in cardiovascular health-related markers (anthropometric parameters, blood pressure, and dietary and physical activity patterns) in these same children. Methods/design: 24 public schools from the city of Madrid (Spain) were allocated through stratified randomization to intervention or control. The intervention schools follow the Program SI!, which provides didactic units, emotions cards, healthy tips, and online resources. The intervention schools integrate the Program SI! into their scholar curriculum organized in four complete weeks during each academic year during the 3 years of preschool education. Control schools follow their normal curriculum. Primary outcomes are 1-year, and 3-year changes from baseline of scores for knowledge, attitudes, and habits (KAH) of children, their parents and teachers in regards to a healthy lifestyle. Secondary outcomes are 1-year, and 3-year changes from baseline in clinical and anthropometric parameters of children. Discussion: The Program SI! is a long-term health promotion program starting in 3 years old. It incorporates the traditional areas of intervention (diet and physical activity), introducing additional components such as knowledge of the human body and management of emotions to achieve a comprehensive intervention. The Program SI! is designed to be an effective, sustainable health promotion program for the adoption of healthy behaviors from early in life. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is the leading cause of death worldwide, affecting not only high-income but also low- and middle-income countries. Nearly 80 percent of all estimated cardiovascular disease-related deaths worldwide now occur in low- and middle-income countries, where nearly 30 percent of all deaths are attributable to cardiovascular disease. The health burden of cardiovascular disease and other chronic diseases is also accompanied by a significant deleterious economic impact at the level of both national economies and households. The global trends in the health and economic burden of cardiovascular disease provide a compelling argument in support of prioritizing urgent yet carefully planned efforts to prevent and control cardiovascular disease worldwide-and especially in low- and middle-income countries. After decades of escalating efforts to draw attention to the high burden of cardiovascular disease and other chronic diseases, this critically important issue is now emerging as a more central part of the global health and development agenda. The breadth of behavioral, biological, social, environmental, and systems-level factors that contribute to cardiovascular disease necessitates multisectoral approaches across the lifecourse that promote healthful lifestyles, reduce risk, and reduce cardiovascular-disease morbidity and mortality through the delivery of quality health care services. Given that the complex interactions among the determinants of cardiovascular disease vary in different contexts, real progress in control efforts will come through approaches that are driven by a country's disease burden and risk profile, capacities, resources, and priorities-approaches that are led by a country's key decision-makers and stakeholders, including governments, civil society, the private sector, and communities. Many countries are already establishing efforts to address chronic diseases. In addition to these locally driven efforts, success will require active engagement and sustained action from a wide array of stakeholders operating at global and regional levels. Mt Sinai J Med 79:632-640, 2012. © 2012 Mount Sinai School of Medicine [ABSTRACT FROM AUTHOR]

The article addresses the promotion of cardiovascular and cerebrovascular health. The factors that contribute to the global burden of cardiovascular disease (CVD) and related chronic diseases includes diet, blood pressure and anxiety. It discusses the crucial basis for developing policies and programs to address CVD and related chronic diseases.

Most organs in mammals, including the heart, show a certain level of plasticity and repair ability during gestation. This plasticity is, however, compromised for many organs in adulthood, resulting in the inability to repair organ injury, including heart damage produced by acute or chronic ischemic conditions. In contrast, lower vertebrates, such as fish or amphibians, retain a striking regenerative ability during their entire life, being able to repair heart injuries. There is a great interest in understanding both the mechanisms that allow heart plasticity during mammalian fetal life and those that permit adult cardiac regeneration in zebrafish. Here, we revise strategies for cardiomyocyte production during development and in response to injury and discuss differential regeneration ability of teleosts and mammals. Understanding these mechanisms may allow establishing alternative therapeutic approaches to cope with heart failure in humans. [ABSTRACT FROM AUTHOR]

Copyright of Archivos de Cardiología de México is the property of Publicidad Permanyer SLU and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The article presents abstracts on medical topics which include the risk factors of cardiovascular disease, the use of C-reactive protein in statin therapy, and the use of aspirin in preventing the primary cardiovascular events in people with diabetes.

Copyright of Actualidad Jurídica (1578-956X) is the property of Dykinson SL and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

(1) Background: Epidemiological studies have shown an inverse association between polyphenol intake and cardiovascular risk factors (CVRFs) in adults, but few have provided information about adolescents. The aim of this study was to evaluate the relationship between urinary total polyphenol excretion (TPE) and CVRFs in adolescents. (2) Methods: A cross-sectional study was performed in 1194 Spanish adolescents from the SI! (Salud Integral) program. TPE in urine samples was determined by the Folin–Ciocalteu method, after solid-phase extraction, and categorized into quartiles. The association between TPE and CVRFs was estimated using mixed-effect linear regression and a structural equation model (SEM). (3) Results: Linear regression showed negative associations among the highest quartile of TPE and body fat percentage (B = −1.75, p-value = <0.001), triglycerides (TG) (B = −17.68, p-value = <0.001), total cholesterol (TC) (B = −8.66, p-value = 0.002), and low-density lipoprotein (LDL)-cholesterol (LDL-C) (B = −4.09, p-value = 0.008) in boys, after adjusting for all confounder variables. Negative associations between TPE quartiles and systolic blood pressure (SBP), diastolic blood pressure (DBP), and TC were also found in girls. Moreover, a structural equation model revealed that TPE was directly associated with body composition and blood glucose and indirectly associated with blood pressure, TG, LDL-C, and high-density lipoprotein-cholesterol (HDL-C) in boys. (4) Conclusions: Higher concentrations of TPE were associated with a better profile of cardiovascular health, especially in boys, while in girls, the association was not as strong. [ABSTRACT FROM AUTHOR]

(1) Background: Epidemiological studies have shown an inverse association between polyphenol intake and cardiovascular risk factors (CVRFs) in adults, but few have provided information about adolescents. The aim of this study was to evaluate the relationship between urinary total polyphenol excretion (TPE) and CVRFs in adolescents. (2) Methods: A cross-sectional study was performed in 1194 Spanish adolescents from the SI! (Salud Integral) program. TPE in urine samples was determined by the Folin–Ciocalteu method, after solid-phase extraction, and categorized into quartiles. The association between TPE and CVRFs was estimated using mixed-effect linear regression and a structural equation model (SEM). (3) Results: Linear regression showed negative associations among the highest quartile of TPE and body fat percentage (B = −1.75, p-value = <0.001), triglycerides (TG) (B = −17.68, p-value = <0.001), total cholesterol (TC) (B = −8.66, p-value = 0.002), and low-density lipoprotein (LDL)-cholesterol (LDL-C) (B = −4.09, p-value = 0.008) in boys, after adjusting for all confounder variables. Negative associations between TPE quartiles and systolic blood pressure (SBP), diastolic blood pressure (DBP), and TC were also found in girls. Moreover, a structural equation model revealed that TPE was directly associated with body composition and blood glucose and indirectly associated with blood pressure, TG, LDL-C, and high-density lipoprotein-cholesterol (HDL-C) in boys. (4) Conclusions: Higher concentrations of TPE were associated with a better profile of cardiovascular health, especially in boys, while in girls, the association was not as strong. [ABSTRACT FROM AUTHOR]

A correction for the article "Dietary Patterns and Cardiovascular Risk Factors in Spanish Adolescents: A Cross-Sectional Analysis of the SI! Program for Health Promotion in Secondary Schools" is presented which is published in the previous 2019 issue of the periodical.

Previous studies on the association between dietary habits and cardiovascular risk factors (CVRF) in adolescents have generated conflicting results. The aim of this study was to describe dietary patterns (DP) in a large sample of Spanish adolescents and to assess their cross-sectional relationship with CVRF. In total, 1324 adolescents aged 12.5 ± 0.4 years (51.6% boys) from 24 secondary schools completed a self-reported food frequency questionnaire. DPs were derived by cluster analysis and principal component analysis (PCA). Anthropometric measurements, blood pressure, lipid profile, and glucose levels were assessed. Linear mixed models were applied to estimate the association between DPs and CVRF. Three DP-related clusters were obtained: Processed (29.2%); Traditional (39.1%); and Healthy (31.7%). Analogous patterns were obtained in the PCA. No overall differences in CVRF were observed between clusters except for z-BMI values, total cholesterol, and non-HDL cholesterol, with the Processed cluster showing the lowest mean values. However, differences were small. In conclusion, the overall association between DPs, as assessed by two different methods, and most analyzed CVRF was weak and not clinically relevant in a large sample of adolescents. Prospective analysis may help to disentangle the direction of these associations. [ABSTRACT FROM AUTHOR]

There is scarce evidence for pulmonary artery denervation (PADN) as a potential treatment for chronic postcapillary pulmonary hypertension (PH). We aimed to perform a proof-of-concept of PADN in a translational model of chronic PH. Nineteen pigs with chronic postcapillary PH (secondary to pulmonary vein banding) were randomized to surgical-PADN (using bipolar radiofrequency clamps) or sham procedure. Additionally, 6 healthy animals underwent percutaneous-PADN to compare the pulmonary artery (PA) lesion generated with both approaches. In the surgical-PADN arm, hemodynamic evaluation and cardiac magnetic resonance (CMR) were performed at baseline and at 2 and 3-month follow-up. Histological assessment was carried out at the completion of the protocol. Eighteen pigs (6 following surgical-PADN, 6 sham and 6 percutaneous-PADN) completed the protocol. A complete transmural PA lesion was demonstrated using surgical clamps, whereas only focal damage to adventitial fibers was observed after percutaneous-PADN. In the surgical-PADN arm, the hemodynamic profile did not significantly differ between groups neither at baseline [mean pulmonary artery pressure (mPAP) median values of 32.0 vs. 27.5 mmHg, P = 0.394 and indexed pulmonary vascular resistance (iPVR) 5.9 vs. 4.7 WU m2, P = 0.394 for PADN/sham groups, respectively] nor at any follow-up (mPAP of 35.0 vs. 35.0 mmHg, P = 0.236 and iPVR of 8.3 vs. 6.7 WU m2, P = 0.477 at third month in PADN/sham groups, respectively). Surgical-PADN was not associated with any benefit in RV anatomy or function on CMR/histology. In a large-animal model of chronic postcapillary PH, transmural PADN with surgical clamps was associated with a neutral pulmonary hemodynamic effect. [ABSTRACT FROM AUTHOR]