Implantation of a double allogeneic human engineered tissue graft on damaged heart: insights from the PERISCOPE phase I clinical trial.

BACKGROUND: In preclinical studies, the use of double allogeneic grafts has shown promising results in promoting tissue revascularization, reducing infarct size, preventing adverse remodelling and fibrosis, and ultimately enhancing cardiac function. Building upon these findings, the safety of PeriCord, an engineered tissue graft consisting of a decellularised pericardial matrix and umbilical cord Wharton's jelly mesenchymal stromal cells, was evaluated in the PERISCOPE Phase I clinical trial (NCT03798353), marking its first application in human subjects. METHODS: This was a double-blind, single-centre trial that enrolled patients with non-acute myocardial infarction eligible for surgical revascularization. Seven patients were implanted with PeriCord while five served as controls. FINDINGS: Patients who received PeriCord showed no adverse effects during post-operative phase and one-year follow-up. No significant changes in secondary outcomes, such as quality of life or cardiac function, were found in patients who received PeriCord. However, PeriCord did modulate the kinetics of circulating monocytes involved in post-infarction myocardial repair towards non-classical inflammation-resolving macrophages, as well as levels of monocyte chemoattractants and the prognostic marker Meteorin-like in plasma following treatment. INTERPRETATION: In summary, the PeriCord graft has exhibited a safe profile and notable immunomodulatory properties. Nevertheless, further research is required to fully unlock its potential as a platform for managing inflammatory-related pathologies. FUNDING: This work was supported in part by grants from MICINN (SAF2017-84324-C2-1-R); Instituto de Salud Carlos III (ICI19/00039 and Red RICORS-TERAV RD21/0017/0022, and CIBER Cardiovascular CB16/11/00403) as a part of the Plan Nacional de I + D + I, and co-funded by ISCIII-Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER) and AGAUR (2021-SGR-01437).

Clinical and prognostic implications of left ventricular dilatation in heart failure.

AIMS: To assess the agreement between left ventricular end-diastolic diameter index (LVEDDi) and volume index (LVEDVi) to define LV dilatation and to investigate the respective prognostic implications in patients with heart failure (HF). METHODS AND RESULTS: Patients with HF symptoms and LV ejection fraction (LVEF) < 50% undergoing cardiac magnetic resonance (CMR) were evaluated retrospectively. LV dilatation was defined as LVEDDi or LVEDVi above the upper normal limit according to published reference values. Patients were followed-up for the combined endpoint of cardiovascular death or HF hospitalization during 5 years. A total of 564 patients (median age 64 years; 79% men) were included. LVEDDi had a modest correlation with LVEDVi (r = 0.682, p < 0.001). LV dilatation was noted in 84% of patients using LVEDVi-based definition and in 73% using LVEDDi-based definition, whereas 20% of patients displayed discordant definitions of LV dilatation. During a median follow-up of 2.8 years, patients with both dilated LVEDDi and LVEDVi had the highest cumulative event rate (HR 3.00, 95% CI 1.15-7.81, p = 0.024). Both LVEDDi and LVEDVi were independently associated with the primary outcome (hazard ratio 3.29, 95%, p < 0.001 and 2.8, p = 0.009; respectively). CONCLUSIONS: The majority of patients with HF and LVEF < 50% present both increased LVEDDi and LVEDVi whereas 20% show discordant linear and volumetric definitions of LV dilatation. Patients with increased LVEDDi and LVEDVi have the worst clinical outcomes suggesting that the assessment of these two metrics is needed for better risk stratification.

Assessment of the Severity of Aortic Regurgitation by Noninvasive Imaging : Non-invasive MMI for AR.

PURPOSE OF THE REVIEW: The role of multimodality imaging in the evaluation of patients with aortic regurgitation is summarized in this review. RECENT FINDINGS: The etiology (mechanism) of the aortic regurgitation and the severity of aortic regurgitation and hemodynamic consequences are key in the decision making of patients with severe aortic regurgitation. While echocardiography remains as the leading technique to assess all these parameters, other imaging techniques have become essential for the accurate assessment of aortic regurgitation severity and the timing of aortic intervention. The anatomic suitability of transcatheter aortic valve implantation in inoperable patients with severe aortic regurgitation is usually assessed with computed tomography. Aortic regurgitation is a prevalent disease with various pathophysiological mechanisms that need a personalized treatment. The evaluation of the mechanism and severity of aortic regurgitation can be initially performed with echocardiography. Three-dimensional techniques, including echocardiography, have become very relevant for accurate assessment of the regurgitation severity and its hemodynamic consequences. Assessment of myocardial tissue characteristics with cardiac magnetic resonance is key in the risk stratification of patients and in the timing of aortic intervention. Computed tomography is important in the assessment of aortic dimensions and selection of patients for transcatheter aortic valve implantation.

Timing of cardiac magnetic resonance and diagnostic yield in patients with myocardial infarction with nonobstructive coronary arteries.

INTRODUCTION AND OBJECTIVES: The present study sought to establish the diagnostic yield of cardiovascular magnetic resonance (CMR) in a large cohort of patients admitted with myocardial infarction (MI) with nonobstructive coronary artery disease (MINOCA) based on the timing of referral to CMR. METHODS: Consecutive patients referred to CMR from January 2009 to February 2022 with a working diagnosis of MINOCA were retrospectively evaluated. Cine, T2-weighted, early, and late gadolinium-enhanced images were acquired and analyzed. The frequency of the underlying diagnosis and the association between timing of CMR and relative frequency of each diagnosis were assessed. RESULTS: We included 207 patients (median age 50 years, 60% men). Final diagnosis after CMR was achieved in 91% of the patients (myocarditis in 45%, MI in 20%, tako-tsubo cardiomyopathy in 19%, and other cardiomyopathies in 7%). The performance of CMR within 7 days of admission with MINOCA (median, 5 days; 117 patients) allowed a higher diagnostic yield compared with CMR performed later (median, 10 days; 88 patients) (96% vs 86%, P=.02). Although myocarditis was the most frequent diagnosis in both groups according to time to CMR, its frequency was higher among patients with a CMR performed within the first 7 days (53% vs 35%, P=.02). The frequency of other underlying diagnoses was not influenced by CMR timing. CONCLUSIONS: CMR led to an underlying diagnosis of MINOCA in 91% of patients and its diagnostic yield increased to 96% when CMR was performed within 7 days of admission. The most frequent diagnosis was myocarditis..

Determinants of the onset and prognosis of the post-COVID-19 condition: a 2-year prospective observational cohort study.

Background: At least 5-10% of subjects surviving COVID-19 develop the post-COVID-19 condition (PCC) or "Long COVID". The clinical presentation of PCC is heterogeneous, its pathogenesis is being deciphered, and objective, validated biomarkers are lacking. It is unknown if PCC is a single entity or a heterogeneous syndrome with overlapping pathophysiological basis. The large US RECOVER study identified four clusters of subjects with PCC according to their presenting symptoms. However, the long-term clinical implications of PCC remain unknown. Methods: We conducted a 2-year prospective cohort study of subjects surviving COVID-19, including individuals fulfilling the WHO PCC definition and subjects with full clinical recovery. We systematically collected post-COVID-19 symptoms using prespecified questionnaires and performed additional diagnostic imaging tests when needed. Factors associated with PCC were identified and modelled using logistic regression. Unsupervised clustering analysis was used to group subjects with PCC according to their presenting symptoms. Factors associated with PCC recovery were modelled using a direct acyclic graph approach. Findings: The study included 548 individuals, 341 with PCC, followed for a median of 23 months (IQR 16.5-23.5), and 207 subjects fully recovered. In the model with the best fit, subjects who were male and had tertiary studies were less likely to develop PCC, whereas a history of headache, or presence of tachycardia, fatigue, neurocognitive and neurosensitive complaints and dyspnea at COVID-19 diagnosis predicted the development of PCC. The cluster analysis revealed the presence of three symptom clusters with an additive number of symptoms. Only 26 subjects (7.6%) recovered from PCC during follow-up; almost all of them (n = 24) belonged to the less symptomatic cluster A, dominated mainly by fatigue. Recovery from PCC was more likely in subjects who were male, required ICU admission, or had cardiovascular comorbidities, hyporexia and/or smell/taste alterations during acute COVID-19. Subjects presenting with muscle pain, impaired attention, dyspnea, or tachycardia, conversely, were less likely to recover from PCC. Interpretation: Preexisting medical and socioeconomic factors, as well as acute COVID-19 symptoms, are associated with the development of and recovery from the PCC. Recovery is extremely rare during the first 2 years, posing a major challenge to healthcare systems. Funding: Fundació Lluita contra les Infeccions.

Left-to-right ventricular volume ratio and outcome in heart failure with preserved ejection fraction.

BACKGROUND: Age-specific and gender-specific reference values for left ventricular (LV) and right ventricle volumes are available. The prognostic implications of the ratio between these volumes in heart failure and preserved ejection fraction (HFpEF) have never been evaluated. METHODS: We examined all HFpEF outpatients undergoing a cardiac magnetic resonance from 2011 to 2021. The left-to-right ventricular volume ratio (LRVR) was defined as the ratio between the LV and right ventricle end-diastolic volume indexes (LVEDVi/RVEDVi). RESULTS: Among 159 patients [median age 58 years (interquartile range 49-69), 64% men, LV ejection fraction 60% (54-70%)] the median LRVR was 1.21 (1.07-1.40). Over 3.5 years (1.5-5.0), 23 patients (15%) experienced all-cause death or heart failure hospitalization, and 22 (14%) cardiovascular death or heart failure hospitalization. The risk of all-cause death or heart failure hospitalization increased with an LRVR less than 1.0 or at least 1.4. An LRVR less than 1.0 was associated with a higher risk of all-cause death or heart failure hospitalization [hazard ratio 5.95, 95% confidence interval (CI) 1.67-21.28; P = 0.006] and cardiovascular death or heart failure hospitalization (hazard ratio 5.68, 95% CI 1.58-20.35; P = 0.008) as compared with LRVR 1.0-1.3. Furthermore, an LRVR at least 1.4 was associated with a higher risk of all-cause death or heart failure hospitalization (hazard ratio 4.10, 95% CI 1.58-10.61; P = 0.004) and cardiovascular death or heart failure hospitalization (hazard ratio 3.71, 95% CI 1.41-9.79; P = 0.008) as compared with LRVR 1.0-1.3. These results were confirmed in patients without dilation of either ventricle. CONCLUSION: LRVR values less than 1.0 or at least 1.4 are associated with worse outcomes in HFpEF. LRVR may become a valuable tool for risk prediction in HFpEF.

Impact of dapagliflozin on cardiac remodelling in patients with chronic heart failure: The DAPA-MODA study.

AIMS: Dapagliflozin improves the prognosis of patients with heart failure (HF), regardless of left ventricular ejection fraction (LVEF). However, its effect on cardiac remodelling parameters, specifically left atrial (LA) remodelling, is not well established. METHODS AND RESULTS: The DAPA-MODA trial (NCT04707352) is a multicentre, single-arm, open-label, prospective and interventional study that aimed to evaluate the effect of dapagliflozin on cardiac remodelling parameters over 6 months. Patients with stable chronic HF receiving optimized guideline-directed therapy, except for any sodium-glucose cotransporter 2 inhibitor, were included. Echocardiography was performed at baseline, 30 and 180 days, and analysed by a central core-lab in a blinded manner to both patient and time. The primary endpoint was the change in maximal LA volume index (LAVI). A total of 162 patients (64.2% men, 70.5 ± 10.6 years, 52% LVEF >40%) were included in the study. At baseline, LA dilatation was observed (LAVI 48.1 ± 22.6 ml/m2 ) and LA parameters were similar between LVEF-based phenotypes (≤40% vs. >40%). LAVI showed a significant reduction at 180 days (-6.6% [95% confidence interval -11.1, -1.8], p = 0.008), primarily due to a decrease in reservoir volume (-13.8% [95% confidence interval -22.5, -4], p = 0.007). Left ventricular geometry improved with significant reductions in left ventricular mass index (-13.9% [95% confidence interval -18.7, -8.7], p < 0.001), end-diastolic volume (-8.0% [95% confidence interval -11.6, -4.2], p < 0.001) and end-systolic volume (-11.9% [95% confidence interval -16.7, -6.8], p < 0.001) at 180 days. N-terminal pro-B-type natriuretic peptide (NT-proBNP) showed a significant reduction at 180 days (-18.2% [95% confidence interval -27.1, -8.2], p < 0.001), without changes in filling Doppler measures. CONCLUSION: Dapagliflozin administration in stable out-setting patients with chronic HF and optimized therapy results in global reverse remodelling of cardiac structure, including reductions in LA volumes and improvement in left ventricular geometry and NT-proBNP concentrations.

Biophysical Tissue Characterization of Ventricular Tachycardia Substrate With Local Impedance Mapping to Predict Critical Sites.

BACKGROUND: New tools are needed to improve ventricular tachycardia (VT) substrate characterization and optimize outcomes. LI provides biophysical tissue characterization. OBJECTIVES: The purpose of this study was to test local impedance (LI)-based mapping to predict critical ventricular tachycardia components after myocardial infarction (MI). METHODS: One month after a nonreperfused anterior MI, endo-epicardial high-density electroanatomic mapping and endocardial LI mapping were performed in 23 Landrace Large X White pigs. LI thresholds were set using the blood pool value to define a 10 Ω range: low (blood pool +9Ω). RESULTS: Low LI was detected in low-voltage areas in 100% of cases, but intermediate LI was found in both core (87%) and border zone (12.5%) voltage areas. A total of 17 VTs were induced (VT isthmus identified in 9 animals). VT inducibility was associated with the size of intermediate LI area (OR: 1.19 [95% CI: 1.0-1.4]; P = 0.039) and the presence of specific LI patterns: LI corridor (OR: 15.0 [95% CI: 1.3-169.9]; P = 0.029); LI gradient (OR: 30.0 [95% CI: 2.1-421.1]; P = 0.012), high LI heterogeneity (OR: 21.7 [95% CI: 1.8-260.6]; P = 0.015), and presence of ≥2 low LI regions (OR: 11.3 [95% CI: 1.0-130.2]; P = 0.053). Potential VT isthmuses were in areas of intermediate LI and colocalized to LI patterns associated with VT inducibility in all cases (LI corridors or LI gradient). Low LI regions did not actively participate in the VT circuit (0%). CONCLUSIONS: LI mapping is feasible and may add useful characterization of the VT substrate. Specific LI patterns (ie, corridors, gradients) were associated with VT inducibility and colocalized with the VT isthmus, thus representing a potential new target for ablation in substrate-based procedures.

Imagen multimodal en la estenosis aórtica: nuevas fronteras diagnósticas y terapéuticas / Multimodality imaging in aortic stenosis: new diagnostic and therapeutic frontiers

El desarrollo del implante percutáneo de válvula aórtica ha revolucionado el tratamiento de la estenosis de válvula aórtica calcificada. Los pacientes ancianos a los que se consideraba inoperables ahora cuentan con un tratamiento eficaz y seguro que proporciona una mejor supervivencia. Además, las guías de práctica actuales tienden a recomendar una intervención más temprana para evitar las consecuencias irreversibles de la sobrecarga de presión de larga duración causada por la válvula aórtica estenótica. El momento adecuado para la intervención depende en gran medida de las técnicas de imagen que informan de la gravedad de la estenosis aórtica, pero también de las consecuencias hemodinámicas y el remodelado cardiaco. Si bien la fracción de eyección del ventrículo izquierdo sigue siendo uno de los principales parámetros funcionales para la estratificación del riesgo de los pacientes con estenosis aórtica grave, los avances en las técnicas de imagen han proporcionado nuevos parámetros estructurales y funcionales que permiten identificar a los pacientes que se beneficiarán de la intervención antes de que aparezcan síntomas o daño cardiaco irreversible. Además, el desarrollo de tratamientos médicos que pueden detener de manera efectiva la progresión de la estenosis aórtica depende en gran medida de la información que las técnicas de imagen aportan, y la caracterización de la actividad metabólica de la estenosis aórtica calcificada con técnicas de medicina nuclear o tomografía computarizada ha permitido monitorizar los efectos de esos tratamientos. El presente artículo de revisión brinda una visión actualizada de los avances en técnicas de imagen que caracterizan la fisiopatología y han cambiado el paradigma del tratamiento de la estenosis aórtica.(AU)

The advent of transcatheter aortic valve implantation has revolutionized the treatment of calcific aortic valve stenosis. Elderly patients who were previously considered inoperable have currently an efficacious and safe therapy that provides better survival. In addition, current practice guidelines tend to recommend earlier intervention to avoid the irreversible consequences of long-lasting pressure overload caused by the stenotic aortic valve. Appropriate timing of the intervention relies significantly on imaging techniques that provide information on the severity of the aortic stenosis as well as on the hemodynamic consequences and cardiac remodeling. While left ventricular ejection fraction remains one of the main functional parameters for risk stratification in patients with severe aortic stenosis, advances in imaging techniques have provided new structural and functional parameters that allow the identification of patients who will benefit from intervention before the occurrence of symptoms or irreversible cardiac damage. Furthermore, ongoing research aiming to identify the medical therapies that can effectively halt the progression of aortic stenosis relies heavily on imaging endpoints, and new imaging techniques that characterize the metabolic activity of calcific aortic stenosis have been proposed to monitor the effects of these therapies. The present review provides an up-to-date overview of the imaging advances that characterizes the pathophysiology and that have changed the management paradigm of aortic stenosis.(AU)

Multimodality imaging in aortic stenosis: new diagnostic and therapeutic frontiers.

The advent of transcatheter aortic valve implantation has revolutionized the treatment of calcific aortic valve stenosis. Elderly patients who were previously considered inoperable have currently an efficacious and safe therapy that provides better survival. In addition, current practice guidelines tend to recommend earlier intervention to avoid the irreversible consequences of long-lasting pressure overload caused by the stenotic aortic valve. Appropriate timing of the intervention relies significantly on imaging techniques that provide information on the severity of the aortic stenosis as well as on the hemodynamic consequences and cardiac remodeling. While left ventricular ejection fraction remains one of the main functional parameters for risk stratification in patients with severe aortic stenosis, advances in imaging techniques have provided new structural and functional parameters that allow the identification of patients who will benefit from intervention before the occurrence of symptoms or irreversible cardiac damage. Furthermore, ongoing research aiming to identify the medical therapies that can effectively halt the progression of aortic stenosis relies heavily on imaging endpoints, and new imaging techniques that characterize the metabolic activity of calcific aortic stenosis have been proposed to monitor the effects of these therapies. The present review provides an up-to-date overview of the imaging advances that characterizes the pathophysiology and that have changed the management paradigm of aortic stenosis.

Electrophysiological effects of adipose graft transposition procedure (AGTP) on the post-myocardial infarction scar: A multimodal characterization of arrhythmogenic substrate.

Objective: To assess the arrhythmic safety profile of the adipose graft transposition procedure (AGTP) and its electrophysiological effects on post-myocardial infarction (MI) scar. Background: Myocardial repair is a promising treatment for patients with MI. The AGTP is a cardiac reparative therapy that reduces infarct size and improves cardiac function. The impact of AGTP on arrhythmogenesis has not been addressed. Methods: MI was induced in 20 swine. Contrast-enhanced magnetic resonance (ce-MRI), electrophysiological study (EPS), and left-ventricular endocardial high-density mapping were performed 15 days post-MI. Animals were randomized 1:1 to AGTP or sham-surgery group and monitored with ECG-Holter. Repeat EPS, endocardial mapping, and ce-MRI were performed 30 days post-intervention. Myocardial SERCA2, Connexin-43 (Cx43), Ryanodine receptor-2 (RyR2), and cardiac troponin-I (cTnI) gene and protein expression were evaluated. Results: The AGTP group showed a significant reduction of the total infarct scar, border zone and dense scar mass by ce-MRI (p = 0.04), and a decreased total scar and border zone area in bipolar voltage mapping (p < 0.001). AGTP treatment significantly reduced the area of very-slow conduction velocity (<0.2 m/s) (p = 0.002), the number of deceleration zones (p = 0.029), and the area of fractionated electrograms (p = 0.005). No differences were detected in number of induced or spontaneous ventricular arrhythmias at EPS and Holter-monitoring. SERCA2, Cx43, and RyR2 gene expression were decreased in the infarct core of AGTP-treated animals (p = 0.021, p = 0.018, p = 0.051, respectively). Conclusion: AGTP is a safe reparative therapy in terms of arrhythmic risk and provides additional protective effect against adverse electrophysiological remodeling in ischemic heart disease.

GlycA and GlycB as Inflammatory Markers in Chronic Heart Failure.

The role of inflammation in heart failure (HF) has been extensively described, but it is uncertain whether inflammation exerts a different prognostic influence according to etiology. We aimed to examine the inflammatory state in chronic HF by measuring N-acetylglucosamine/galactosamine (GlycA) and sialic acid (GlycB), evolving proton nuclear magnetic resonance biomarkers of systemic inflammation, and explore their prognostic value in patients with chronic HF. The primary end point was a composite of all-cause death and HF readmission. A total of 429 patients were included. GlycB correlated with interleukin-1 receptor-like 1 in the whole cohort (r2 = 0.14, p = 0.011) and the subgroup of nonischemic etiology (r2 = 0.31, p <0.001). No association was found with New York Heart Association functional class or left ventricular ejection fraction. In patients with nonischemic HF (52.2%, n = 224), GlycA and GlycB exhibited significant association with the composite end point (hazard ratio [HR] 1.19, 95% confidence interval [CI] 1.06 to 1.33, p = 0.004 and HR 2.13, 95% CI 1.43 to 3.13, p <0.001; respectively) and GlycB with HF readmission after multivariable adjustment (HR 2.25, 95% CI 1.54 to 3.30, p <0.001). GlycB levels were also associated with a greater risk of HF-related recurrent admissions (adjusted incidence rate ratio 1.33, 95% CI = 1.07 to 1.65, p = 0.009). None of the markers were associated with the clinical end points in patients with ischemic HF. In conclusion, GlycA and GlycB represent an evolving approach to inflammation status with prognostic value in long-term outcomes in patients with nonischemic HF.

Acellular cardiac scaffolds enriched with MSC-derived extracellular vesicles limit ventricular remodelling and exert local and systemic immunomodulation in a myocardial infarction porcine model.

Rationale: Extracellular vesicles (EVs) from mesenchymal stromal cell (MSC) are a potential therapy for cardiac healing after myocardial infarction (MI). Nevertheless, neither their efficient administration nor therapeutic mechanisms are fully elucidated. Here, we evaluate the preclinical efficacy of a tissue engineering approach to locally deliver porcine cardiac adipose tissue MSC-EV (cATMSC-EV) in an acute MI pig model. Methods: After MI by permanent ligation of the coronary artery, pigs (n = 24) were randomized to Untreated or treated groups with a decellularised pericardial scaffold filled with peptide hydrogel and cATMSC-EV purified by size exclusion chromatography (EV-Treated group) or buffer (Control group), placed over the post-infarcted myocardium. Results: After 30 days, cardiac MRI showed an improved cardiac function in EV-Treated animals, with significantly higher right ventricle ejection fraction (+20.8% in EV-Treated; p = 0.026), and less ventricle dilatation, indicating less myocardial remodelling. Scar size was reduced, with less fibrosis in the distal myocardium (-42.6% Col I in EV-Treated vs Untreated; p = 0.03), a 2-fold increase in vascular density (EV-Treated; p = 0.019) and less CCL2 transcription in the infarct core. EV-treated animals had less macrophage infiltration in the infarct core (-31.7% of CD163+ cells/field in EV-Treated; p = 0.026), but 5.8 times more expressing anti-inflammatory CD73 (p = 0.015). Systemically, locally delivered cATMSC-EV also triggered a systemic effect, doubling the circulating IL-1ra (p = 0.01), and reducing the PBMC rush 2d post-MI, the TNFα and GM-CSF levels at 30d post-MI, and modulating the CD73+ and CCR2+ monocyte populations, related to immunomodulation and fibrosis modulation. Conclusions: These results highlight the potential of cATMSC-EV in modulating hallmarks of ischemic injury for cardiac repair after MI.

Perfil lipoproteico avanzado en individuos con metabolismo glucémico normal y alterado / Advanced lipoprotein profile in individuals with normal and impaired glucose metabolism

Introducción y objetivos: Varios tipos de lipoproteínas, aparte de las lipoproteínas de baja densidad (LDL), tienen relación causal con la enfermedad cardiovascular. Se analizó el perfil lipoproteico avanzado de individuos con metabolismo glucémico normal y alterado provenientes de una región mediterránea.Métodos: Estudio transversal en 929 participantes (463 normoglucémicos, 250 prediabéticos y 216 con diabetes tipo 2) sin insuficiencia renal, enfermedad cardiovascular ni tratamiento hipolipemiante. Se analizaron los perfiles lipoproteicos convencional y avanzado (resonancia magnética [RM] espectroscópica).Resultados: En comparación con los varones, las mujeres normoglucémicas mostraron menores concentraciones de triglicéridos y cLDL, menos partículas (P) de LDL y todas sus subclases y menos contenido en colesterol y triglicéridos, mayor concentración de P de lipoproteínas de alta densidad (HDL) y de todas sus variables relacionadas (p ≤ 0,05 para todas las comparaciones). En comparación con los normoglucémicos, los diabéticos mostraron una mayor concentración de P-VLDL grandes y pequeñas (p <0,05), además de una menor concentración de P-HDL totales y medianas (p <0,05). Se halló relación directa del perímetro de la cintura y el fatty liver index con un perfil proaterogénico.Conclusiones: Las mujeres mostraron un mejor perfil lipoproteico avanzado que los varones. Se halló relación directa de los índices de adiposidad relacionados con resistencia insulínica con un perfil lipídico proaterogénico. La RM mostró alteraciones en partículas lipoproteicas distintas de las LDL en los diabéticos, a menudo asociadas con mayor riesgo cardiovascular. Nuestros hallazgos confirman la utilidad del análisis lipoproteico avanzado mediante RM espectroscópica para descubrir nuevas dianas terapéuticas con que prevenir eventos cardiovasculares en los individuos en riesgo (AU)

Introduction and objectives: Several types of lipoproteins beyond low-density lipoproteins (LDL) are causally related to cardiovascular disease. We aimed to analyze an advanced lipoprotein profile in individuals with normal and impaired glucose metabolism from different cohorts of a Mediterranean region.Methods: Cross-sectional study in 929 participants (463 normoglycemia, 250 prediabetes, and 216 type 2 diabetes mellitus) with normal renal function, free from cardiovascular disease, and without lipid-lowering treatment. Conventional and advanced (nuclear magnetic resonance [NMR] spectroscopy) lipoprotein profiles were analyzed.Results: Compared with men, normoglycemic women showed lower serum triglyceride and LDL cholesterol concentrations, lower total LDL particles (P) as well as their subclasses and their cholesterol and triglyceride content, higher high-density lipoproteins (HDL)-P and all HDL-related variables (P≤ .05 for all comparisons). Compared with normoglycemic participants, diabetic participants showed higher large and small very LDL-P concentrations (P <.05) and lower total HDL-P and medium HDL-P concentrations (P <.05). Waist circumference and Fatty Liver Index were positively associated with a proatherogenic profile.Conclusions: Women had a better advanced lipoprotein profile than did men. Adiposity indexes related to insulin-resistance were positively associated with a proatherogenic lipid profile. NMR revealed altered lipoprotein particles other than LDL in participants with diabetes, frequently associated with an increased cardiovascular risk. Our findings support the usefulness of extended lipoprotein analysis by NMR spectroscopy to uncover new therapeutic targets to prevent cardiovascular events in at-risk participants (AU)