Publications by authors named "Rocío Toro"

37 Publications

Predictive Factors of Pulmonary Embolism in Older Patients with SARS-CoV-2: The OCTA-COVID-19 Study.

J Clin Med 2021 Jul 5;10(13). Epub 2021 Jul 5.

School of Medicine, Alfonso X El Sabio University, Avda. de la Universidad, 1, Villanueva de la Callada, 28691 Madrid, Spain.

Background: The risk of pulmonary embolism (PE) has not been studied in older patients affected by COVID-19. We aimed to assess PE incidence and risk factors in a population of older patients infected with SARS-CoV-2.

Methods: An ambispective, observational cohort study. A total of 305 patients ≥ 75 years old had the SARS-CoV-2 infection from March to May 2020. The incidence rate of PE was estimated as the proportion of new cases within the whole sample. Youden's index was used to assess the cutoff point of D-dimer. To select factors associated with the risk of PE, time-to-event analyses were performed using cause-specific hazard models.

Results: In total, 305 patients with a median age of 87 years (62.3% female) were studied; 67.9% were referred from nursing homes and 90.4% received any type of anticoagulation. A total of 64.9% showed frailty and 44% presented with dementia. The PE incidence was 5.6%. The cutoff value of a D-dimer level over 2.59 mg/L showed a sensitivity of 82.4% and specificity of 73.8% in discriminating a PE diagnosis. In the multivariate analysis, the factors associated with PE were previous oncological events and D-dimer levels.

Conclusions: The PE incidence was 5.6%, and major risk factors for PE were oncological antecedents and increased plasma D-dimer levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10132998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268742PMC
July 2021

Personalized Genetic Diagnosis of Congenital Heart Defects in Newborns.

J Pers Med 2021 Jun 16;11(6). Epub 2021 Jun 16.

Biochemistry and Molecular Genetics Department, Hospital Clinic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08950 Barcelona, Spain.

Congenital heart disease is a group of pathologies characterized by structural malformations of the heart or great vessels. These alterations occur during the embryonic period and are the most frequently observed severe congenital malformations, the main cause of neonatal mortality due to malformation, and the second most frequent congenital malformations overall after malformations of the central nervous system. The severity of different types of congenital heart disease varies depending on the combination of associated anatomical defects. The causes of these malformations are usually considered multifactorial, but genetic variants play a key role. Currently, use of high-throughput genetic technologies allows identification of pathogenic aneuploidies, deletions/duplications of large segments, as well as rare single nucleotide variants. The high incidence of congenital heart disease as well as the associated complications makes it necessary to establish a diagnosis as early as possible to adopt the most appropriate measures in a personalized approach. In this review, we provide an exhaustive update of the genetic bases of the most frequent congenital heart diseases as well as other syndromes associated with congenital heart defects, and how genetic data can be translated to clinical practice in a personalized approach.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jpm11060562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235407PMC
June 2021

Plasma microrna expression profile for reduced ejection fraction in dilated cardiomyopathy.

Sci Rep 2021 Apr 6;11(1):7517. Epub 2021 Apr 6.

Biomedical Research and Innovation Institute of Cadiz (INiBICA), Research Unit, Puerta del Mar University Hospital, Av/Ana de Viya 21, 11009, Cadiz, Spain.

The left ventricular (LV) ejection fraction (EF) is key to prognosis in dilated cardiomyopathy (DCM). Circulating microRNAs have emerged as reliable biomarkers for heart diseases, included DCM. Clinicians need improved tools for greater clarification of DCM EF categorization, to identify high-risk patients. Thus, we investigated whether microRNA profiles can categorize DCM patients based on their EF. 179-differentially expressed circulating microRNAs were screened in two groups: (1) non-idiopathic DCM; (2) idiopathic DCM. Then, 26 microRNAs were identified and validated in the plasma of ischemic-DCM (n = 60), idiopathic-DCM (n = 55) and healthy individuals (n = 44). We identified fourteen microRNAs associated with echocardiographic variables that differentiated idiopathic DCM according to the EF degree. A predictive model of a three-microRNA (miR-130b-3p, miR-150-5p and miR-210-3p) combined with clinical variables (left bundle branch block, left ventricle end-systolic dimension, lower systolic blood pressure and smoking habit) was obtained for idiopathic DCM with a severely reduced-EF. The receiver operating characteristic curve analysis supported the discriminative potential of the diagnosis. Bioinformatics analysis revealed that miR-150-5p and miR-210-3p target genes might interact with each other with a high connectivity degree. In conclusion, our results revealed a three-microRNA signature combined with clinical variables that highly discriminate idiopathic DCM categorization. This is a potential novel prognostic biomarker with high clinical value.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-87086-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024336PMC
April 2021

Malignant Arrhythmogenic Role Associated with : A Comprehensive Interpretation Focused on a Personalized Approach.

J Pers Med 2021 Feb 15;11(2). Epub 2021 Feb 15.

Cardiovascular Genetics Center, University of Girona-IDIBGI, 17001 Girona, Spain.

The gene encodes the muscle-specific splicing factor RNA-binding motif 20, a regulator of heart-specific alternative splicing. Nearly 40 potentially deleterious variants in have been reported in the last ten years, being found to be associated with highly arrhythmogenic events in familial dilated cardiomyopathy. Frequently, malignant arrhythmias can be a primary manifestation of disease. The early recognition of arrhythmic genotypes is crucial in avoiding lethal episodes, as it may have an impact on the adoption of personalized preventive measures. Our study performs a comprehensive update of data concerning rare variants in that are associated with malignant arrhythmogenic phenotypes with a focus on personalized medicine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jpm11020130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918949PMC
February 2021

Rare Variants Associated with Arrhythmogenic Cardiomyopathy: Reclassification Five Years Later.

J Pers Med 2021 Feb 26;11(3). Epub 2021 Feb 26.

Cardiovascular Genetics Center, University of Girona-IdIBGi, Girona 17190, Spain.

Genetic interpretation of rare variants associated with arrhythmogenic cardiomyopathy (ACM) is essential due to their diagnostic implications. New data may relabel previous variant classifications, but how often reanalysis is necessary remains undefined. Five years ago, 39 rare ACM-related variants were identified in patients with features of cardiomyopathy. These variants were classified following the American College of Medical Genetics and Genomics' guidelines. In the present study, we reevaluated these rare variants including novel available data. All cases carried one rare variant classified as being of ambiguous significance (82.05%) or likely pathogenic (17.95%) in 2016. In our comprehensive reanalysis, the classification of 30.77% of these variants changed, mainly due to updated global frequencies. As in 2016, nowadays most variants were classified as having an uncertain role (64.1%), but the proportion of variants with an uncertain role was significantly decreased (17.95%). The percentage of rare variants classified as potentially deleterious increased from 17.95% to 23.07%. Moreover, 83.33% of reclassified variants gained certainty. We propose that periodic genetic reanalysis of all rare variants associated with arrhythmogenic cardiomyopathy should be undertaken at least once every five years. Defining the roles of rare variants may help clinicians obtain a definite diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jpm11030162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996798PMC
February 2021

Ischemic dilated cardiomyopathy pathophysiology through microRNA-16-5p.

Rev Esp Cardiol (Engl Ed) 2020 Oct 10. Epub 2020 Oct 10.

Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), Unidad de Investigación, Hospital Universitario de Puerta del Mar, Universidad de Cádiz, Cádiz, Spain; Departamento de Medicina, Facultad de Medicina, Universidad de Cádiz, Cádiz, Spain.

Introduction And Objectives: The expression levels of microRNA-16-5p (miR-16) are upregulated in ischemic cardiomyopathy and in animal models of ischemic dilated cardiomyopathy (iDCM), inducing myocardial apoptosis. We investigated the role of miR-16 in the adaptive cellular response associated with endoplasmic reticulum (ER) stress and autophagy in the apoptotic iDCM environment.

Methods: We quantified the miR-16 plasma levels of 168 participants-76 controls, 60 iDCM patients, and 32 familial DCM patients with the pathogenic variant of BAG3-by quantitative real-time polymerase chain reaction and correlated the levels with patient variables. The effects of intracellular miR-16 overexpression were analyzed in a human cardiac cell line. Apoptosis and cell viability were measured, as well as the levels of markers associated with ER stress, cardiac injury, and autophagy.

Results: Plasma miR-16 levels were upregulated in iDCM patients (P=.039). A multivariate logistic regression model determined the association of miR-16 with iDCM clinical variables (P <.001). In vitro, miR-16 overexpression increased apoptosis (P=.02) and reduced cell viability (P=.008). Furthermore, it induced proapoptotic components of ER stress, based on upregulation of the PERK/CHOP pathway. However, we observed augmentation of autophagic flux (P <.001) without lysosomal blockade by miR-16 as a possible cytoprotective mechanism.

Conclusions: MiR-16 is specifically associated with iDCM. In an ischemic setting, miR-16 activates ER stress and promotes inflammation followed by autophagy in human cardiac cells. Thus, autophagy may be an attempt to maintain cellular homeostasis in response to misfolded/aggregated proteins related to ER stress, prior to apoptosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rec.2020.08.012DOI Listing
October 2020

Genetic Variants as Sudden-Death Risk Markers in Inherited Arrhythmogenic Syndromes: Personalized Genetic Interpretation.

J Clin Med 2020 Jun 15;9(6). Epub 2020 Jun 15.

Cardiovascular Genetics Center, University of Girona-IDIBGI, 17190 Girona, Spain.

Inherited arrhythmogenic syndromes are the primary cause of unexpected lethal cardiac episodes in young people. It is possible that the first sign of the condition may be sudden death. Inherited arrhythmogenic syndromes are caused by genetic defects that may be analyzed using different technical approaches. A genetic alteration may be used as a marker of risk for families who carry the genetic alterations. Therefore, the early identification of the responsible genetic defect may help the adoption of preventive therapeutic measures focused on reducing the risk of lethal arrhythmias. Here, we describe the use of massive sequencing technologies and the interpretation of genetic analyses in inherited arrhythmogenic syndromes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm9061866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356862PMC
June 2020

Reanalysis and reclassification of rare genetic variants associated with inherited arrhythmogenic syndromes.

EBioMedicine 2020 Apr 5;54:102732. Epub 2020 Apr 5.

Cardiovascular Genetics Center, University of Girona-IDIBGI, C/ Dr Castany s/n, Parc Hospitalari Martí i Julià (M-2), 17190 Salt (Girona), Spain; Medical Science Department, School of Medicine, University of Girona, Girona, Spain; Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain; Cardiology Service, Hospital Josep Trueta, University of Girona, Girona, Spain. Electronic address:

Background: Accurate interpretation of rare genetic variants is a challenge for clinical translation. Updates in recommendations for rare variant classification require the reanalysis and reclassification. We aim to perform an exhaustive re-analysis of rare variants associated with inherited arrhythmogenic syndromes, which were classified ten years ago, to determine whether their classification aligns with current standards and research findings.

Methods: In 2010, the rare variants identified through genetic analysis were classified following recommendations available at that time. Nowadays, the same variants have been reclassified following current American College of Medical Genetics and Genomics recommendations.

Findings: Our cohort included 104 cases diagnosed with inherited arrhythmogenic syndromes and 17 post-mortem cases in which inherited arrhythmogenic syndromes was cause of death. 71.87% of variants change their classification. While 65.62% of variants were classified as likely pathogenic in 2010, after reanalysis, only 17.96% remain as likely pathogenic. In 2010, 18.75% of variants were classified as uncertain role but nowadays 60.15% of variants are classified of unknown significance.

Interpretation: Reclassification occurred in more than 70% of rare variants associated with inherited arrhythmogenic syndromes. Our results support the periodical reclassification and personalized clinical translation of rare variants to improve diagnosis and adjust treatment.

Funding: Obra Social "La Caixa Foundation" (ID 100010434, LCF/PR/GN16/50290001 and LCF/PR/GN19/50320002), Fondo Investigacion Sanitaria (FIS PI16/01203 and FIS, PI17/01690), Sociedad Española de Cardiología, and "Fundacio Privada Daniel Bravo Andreu".
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ebiom.2020.102732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136601PMC
April 2020

Sudden Cardiac Death and Copy Number Variants: What Do We Know after 10 Years of Genetic Analysis?

Forensic Sci Int Genet 2020 07 20;47:102281. Epub 2020 Mar 20.

Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona, Spain; Medical Science Department, School of Medicine, University of Girona, Spain; Centro de Investigación Biomédica en Red, Enfermedades Cardiovasculares (CIBERCV), Spain; Biochemistry and Molecular Genetics Department, Hospital Clinic, University of Barcelona-IDIBAPS, Spain. Electronic address:

Over the last ten years, analysis of copy number variants has increasingly been applied to the study of arrhythmogenic pathologies associated with sudden death, mainly due to significant advances in the field of massive genetic sequencing. Nevertheless, few published reports have focused on the prevalence of copy number variants associated with sudden cardiac death. As a result, the frequency of these genetic alterations in arrhythmogenic diseases as well as their genetic interpretation and clinical translation has not been established. This review summarizes the current available data concerning copy number variants in sudden cardiac death-related diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fsigen.2020.102281DOI Listing
July 2020

Peripheral microRNA panels to guide the diagnosis of familial cardiomyopathy.

Transl Res 2020 04 29;218:1-15. Epub 2020 Jan 29.

Biomedical Research and Innovation Institute of Cádiz (INiBICA) Research Unit, Puerta del Mar University Hospital University of Cádiz, Spain; Medicine Department, School of Medicine, University of Cádiz, Cádiz, Spain. Electronic address:

Etiology-based diagnosis of dilated cardiomyopathy (DCM) is challenging. We evaluated whether peripheral microRNAs (miRNAs) could be used to characterize the DCM etiology. We investigated the miRNA plasma profiles of 254 subjects that comprised 5 groups: Healthy subjects (n = 70), idiopathic DCM patients (n = 55), ischemic DCM patients (n = 60) and 2 groups of patients with pathogenic variants responsible for familial DCM in the LMNA (LMNA, n = 37) and BAG3 (BAG3, n = 32) genes. Diagnostic performance was assessed using receiver operating characteristic curves. In a screening study (n = 30), 179 miRNAs robustly detected in plasma samples were profiled in idiopathic DCM and carriers of pathogenic variants. After filtering, 26 miRNA candidates were selected for subsequent quantification in the whole study population. In the validation study, a 6-miRNA panel identified familial DCM with an AUC (95% confidence interval [CI]) of 87.8 (82.0-93.6). The 6-miRNA panel also distinguished between specific DCM etiologies with AUCs ranging from 85.9 to 89.9. Only 1 to 10 of the subjects in the first and second tertiles of the 6-miRNA panel were patients with familial DCM. Additionally, a 5-miRNA panel showed an AUC (95% CI) of 87.5 (80.4-94.6) for the identification of carriers with pathogenic variants who were phenotypically negative for DCM. The 5-miRNA panel discriminated between carriers and healthy controls with AUCs ranging from 83.2 to 90.8. Again, only 1 to 10 of the subjects in the lowest tertiles of the 5-miRNA panel were carriers of pathogenic variants. In conclusion, miRNA signatures could be used to rule out patients with pathogenic variants responsible for DCM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.trsl.2020.01.003DOI Listing
April 2020

Asymptomatic aortic stenosis in a geriatric population. The role of frailty and comorbidity in mortality.

Rev Esp Cardiol (Engl Ed) 2021 Feb 24;74(2):167-174. Epub 2019 Dec 24.

Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), Cádiz, Spain; Departamento de Medicina, Facultad de Medicina, Cádiz, Spain.

Introduction And Objectives: The prognosis of asymptomatic severe aortic stenosis (AS) has not been widely documented in elderly patients who are frequently frail and have comorbidities. We sought to analyze the factors that influence early mortality in geriatric patients with asymptomatic severe AS.

Methods: This ambispective cohort study included 104 patients aged 70 years or older with asymptomatic severe AS. Epidemiological, geriatric, clinical and echocardiographic variables were collected and compared between frail and nonfrail patients. During follow-up, the time from diagnosis to mortality and the causes of death were recorded.

Results: Overall, 59.6% of the patients were frail. During follow-up, 69.4% of the frail patients died, with a median time to mortality of 2.52 years (95%CI, 1.36-3.69). The overall 1-year survival rate in frail patients was 76%. On multivariate analysis, age (HR, 2.47; 95%CI, 1.00-6.12), a Charlson comorbidity index ≥ 5 (HR, 3.75; 95%CI, 1.47-9.52) and frailty (HR, 6.67; 95%CI, 1.43-9.52) were independently related to mortality. In total, 8.7% of the patients had a Charlson comorbidity index ≥ 5, and all these patients died during follow-up, with a median survival of 1.01 years (95%CI, 0.36-1.67). The area under the receiver operating characteristic curve of the Charlson index was 0.739 (95%CI, 0.646-0.832). In this population, values ≥ 5 showed high specificity (100%) but low sensitivity.

Conclusions: A high prevalence of frailty was present in geriatric patients with asymptomatic severe AS. Age, a Charlson index ≥ 5 and frailty were independent factors for mortality, conferring an unfavorable short-term prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rec.2019.11.006DOI Listing
February 2021

Emerging role of microRNAs in dilated cardiomyopathy: evidence regarding etiology.

Transl Res 2020 01 23;215:86-101. Epub 2019 Aug 23.

Research Unit, Biomedical Research and Innovation Institute of Cádiz (INiBICA), Puerta del Mar University Hospital, University of Cádiz, Cádiz, Spain; Department of Internal Medicine, Puerta del Mar Universitary Hospital, Cádiz, Spain; Department of Medicine, School of Medicine, University of Cádiz, Cádiz, Spain. Electronic address:

Dilated cardiomyopathy (DCM) is a heart muscle disease characterized by ventricular dilation and systolic dysfunction in the absence of abnormal loading conditions or coronary artery disease. This cardiac disorder is a major health problem due to its high prevalence, morbidity, and mortality. DCM is a complex disease with a common phenotype but heterogeneous pathological mechanisms. Early etiological diagnosis and prognosis stratification is crucial for the clinical management of the patient. Advances in imaging technology and genetic tests have provided useful tools for clinical practice. Nevertheless, the assessment of the disease remains challenging. Novel noninvasive indicators are still needed to assist in decision-making. microRNAs (miRNAs), a group of small noncoding RNAs, have been identified as key mediators of cell biology. They are found in a stable form in body fluids and their concentration is altered in response to stress. Previous research has suggested that the miRNA signature constitutes a novel source of noninvasive biomarkers for a wide array of cardiovascular diseases. Specifically, several studies have reported the potential role of miRNAs as clinical indicators among the etiologies of DCM. However, this field has not been reviewed in detail. Here, we summarize the evidence of intracellular and circulating miRNAs in DCM and their usefulness in the development of novel diagnostic, prognostic and therapeutic approaches, with a focus on DCM etiology. Although the findings are still preliminary, due to methodological and technical limitations and the lack of robust population-based studies, miRNAs constitute a promising tool to assist in the clinical management of DCM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.trsl.2019.08.007DOI Listing
January 2020

Differential expression of circulating miRNAs as a novel tool to assess BAG3-associated familial dilated cardiomyopathy.

Biosci Rep 2019 03 15;39(3). Epub 2019 Mar 15.

Univ Puerta del Mar, School of Medicine, Cadiz, Spain

A new familial dilated cardiomyopathy (FDCM) was found related to mutations in gene. MicroRNAs (miRNAs) represent new targets of FDCM, although no studies have assessed clinical association between Bcl2-associated athanogene 3 (BAG3)-related DCM and miRNAs. Here, we studied whether a clinical association between BAG3-related FDCM and circulating miRNAs may have diagnostic and prognostic value in a small cohort of familial related individuals carrying a BAG3 mutation (BAG3+) and/or diagnosed of dilated cardiomyopathy (DCM) (DCM+). The analysis of 1759 circulating miRNAs showed significant differences between BAG3+ and BAG3- individuals for miRNAs mir-3191-3p, 6769b-3p, 1249-ep, 154-5p, 6855-5p, and 182-5p, while comparisons between BAG3+/DCM+ versus BAG3+/DCM- were restricted to miRNAs mir-154-5p, 6885-5p, and 182-5p, showing significant correlation with systolic and diastolic blood pressure, A wave, left atrium length, and left atrium area. Additionally, when stratified by gender and age, miRNAs were statistically correlated with critical parameters, including left ventricle ejection fraction (LVEF) and ventricular diameter, in women and young men. Likewise, 56% of BAG3+/DCM+, significantly co-expressed mir-154-5p and mir-182-5p, and a slight 4% did not express such combination, suggesting that co-expression of mir-154-5p and mir-182-5p may potentially show diagnostic value. Further studies will require long-term follow-up, and validation in larger populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1042/BSR20180934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418398PMC
March 2019

Dilated Cardiomyopathy Due to BLC2-Associated Athanogene 3 (BAG3) Mutations.

J Am Coll Cardiol 2018 11;72(20):2471-2481

European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart (ERN GUARDHEART); APHP, Referral center for inherited cardiac diseases, ICAN, INSERM UMRS1166, Hôpital Pitié-Salpêtrière, Paris, France.

Background: The BAG3 (BLC2-associated athanogene 3) gene codes for an antiapoptotic protein located on the sarcomere Z-disc. Mutations in BAG3 are associated with dilated cardiomyopathy (DCM), but only a small number of cases have been reported to date, and the natural history of BAG3 cardiomyopathy is poorly understood.

Objectives: This study sought to describe the phenotype and prognosis of BAG3 mutations in a large multicenter DCM cohort.

Methods: The study cohort comprised 129 individuals with a BAG3 mutation (62% males, 35.1 ± 15.0 years of age) followed at 18 European centers. Localization of BAG3 in cardiac tissue was analyzed in patients with truncating BAG3 mutations using immunohistochemistry.

Results: At first evaluation, 57.4% of patients had DCM. After a median follow-up of 38 months (interquartile range: 7 to 95 months), 68.4% of patients had DCM and 26.1% who were initially phenotype-negative developed DCM. Disease penetrance in individuals >40 years of age was 80% at last evaluation, and there was a trend towards an earlier onset of DCM in men (age 34.6 ± 13.2 years vs. 40.7 ± 12.2 years; p = 0.053). The incidence of adverse cardiac events (death, left ventricular assist device, heart transplantation, and sustained ventricular arrhythmia) was 5.1% per year among individuals with DCM. Male sex, decreased left ventricular ejection fraction. and increased left ventricular end-diastolic diameter were associated with adverse cardiac events. Myocardial tissue from patients with a BAG3 mutation showed myofibril disarray and a relocation of BAG3 protein in the sarcomeric Z-disc.

Conclusions: DCM caused by mutations in BAG3 is characterized by high penetrance in carriers >40 years of age and a high risk of progressive heart failure. Male sex, decreased left ventricular ejection fraction, and enlarged left ventricular end-diastolic diameter are associated with adverse outcomes in patients with BAG3 mutations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacc.2018.08.2181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688826PMC
November 2018

Non-Invasive Detection of Extracellular Matrix Metalloproteinase Inducer EMMPRIN, a New Therapeutic Target against Atherosclerosis, Inhibited by Endothelial Nitric Oxide.

Int J Mol Sci 2018 Oct 19;19(10). Epub 2018 Oct 19.

Cardiology Department, University Francisco de Vitoria/Hospital Ramón y Cajal Research Unit (IRYCIS), CIBERCV, 28223 Madrid, Spain.

Lack of endothelial nitric oxide causes endothelial dysfunction and circulating monocyte infiltration, contributing to systemic atheroma plaque formation in arterial territories. Among the different inflammatory products, macrophage-derived foam cells and smooth muscle cells synthesize matrix metalloproteinases (MMPs), playing a pivotal role in early plaque formation and enlargement. We found increased levels of MMP-9 and MMP-13 in human endarterectomies with advanced atherosclerosis, together with significant amounts of extracellular matrix (ECM) metalloproteinase inducer EMMPRIN. To test whether the absence of NO may aggravate atherosclerosis through EMMPRIN activation, double NOS3/apoE knockout (KO) mice expressed high levels of EMMPRIN in carotid plaques, suggesting that targeting extracellular matrix degradation may represent a new mechanism by which endothelial NO prevents atherosclerosis. Based on our previous experience, by using gadolinium-enriched paramagnetic fluorescence micellar nanoparticles conjugated with AP9 (NAP9), an EMMPRIN-specific binding peptide, magnetic resonance sequences allowed non-invasive visualization of carotid EMMPRIN in NOS3/apoE over apoE control mice, in which atheroma plaques were significantly reduced. Taken together, these results point to EMMPRIN as a new therapeutic target of NO-mediated protection against atherosclerosis, and NAP9 as a non-invasive molecular tool to target atherosclerosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms19103248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214015PMC
October 2018

Plasma microRNAs as biomarkers for Lamin A/C-related dilated cardiomyopathy.

J Mol Med (Berl) 2018 08 14;96(8):845-856. Epub 2018 Jul 14.

CIBER Cardiovascular, Institute of Health Carlos III, Madrid, Spain.

Lamin A/C gene (LMNA)-related familial dilated cardiomyopathy (fDCM) is an aggressive heart disease that often leads to transplantation and sudden death. The aim of our study was to evaluate the circulating microRNA (miRNA) profiles of patients with LMNA pathogenic mutations. The study population (N = 75) included (i) patients with pathogenic LMNA mutations responsible for fDCM (LMNA), (ii) age- and sex-matched LMNA wild-type controls (LMNA control), and (iii) LMNA wild-type idiopathic DCM (iDCM) patients (LMNA iDCM). Detailed clinical information was obtained from each participant. A panel of 179 plasma miRNAs was evaluated using RT-qPCR. An initial screening study was performed in LMNA carriers and age-matched LMNA controls (N = 16). Forty-four miRNAs were specifically deregulated in LMNA carriers. Ten miRNA candidates were selected for subsequent validation after coexpression analyses and filtered for expression levels and statistical significance. Among the candidates, let-7a-5p, miR-142-3p, miR-145-5p and miR-454-3p levels were significantly increased in LMNA carriers compared to LMNA controls and iDCM patients (P < 0.050). These circulating miRNAs, and their combination, were also associated with the presence of pathogenic mutations in regression and ROC analyses. This signature also discriminates between LMNA healthy subjects and LMNA carriers who are phenotypically negative for DCM and between LMNA iDCM and LMNA-related DCM patients. Correlation and functional enrichment analyses supported their association with the pathophysiology of the disease. We demonstrated for the first time that a specific miRNA signature could serve as a novel non-invasive tool to assist in the diagnosis of patients with fDCM caused by LMNA pathogenic mutations. KEY MESSAGES: Let-7a-5p, miR-142-3p, miR-145-5p and miR-454-3p are differentially expressed in LMNA carriers. A composite score based on these miRNAs is a biomarker of mutations in the LMNA gene. This miRNA signature can be associated with the pathophysiology of familial DCM. The circulating miRNA profile can assist in the diagnosis of familial DCM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00109-018-1666-1DOI Listing
August 2018

Non-coding RNAs and exercise: pathophysiological role and clinical application in the cardiovascular system.

Clin Sci (Lond) 2018 05 20;132(9):925-942. Epub 2018 May 20.

Cardiovascular Research Unit, Luxembourg Institute of Health, Luxembourg, Luxembourg

There is overwhelming evidence that regular exercise training is protective against cardiovascular disease (CVD), the main cause of death worldwide. Despite the benefits of exercise, the intricacies of their underlying molecular mechanisms remain largely unknown. Non-coding RNAs (ncRNAs) have been recognized as a major regulatory network governing gene expression in several physiological processes and appeared as pivotal modulators in a myriad of cardiovascular processes under physiological and pathological conditions. However, little is known about ncRNA expression and role in response to exercise. Revealing the molecular components and mechanisms of the link between exercise and health outcomes will catalyse discoveries of new biomarkers and therapeutic targets. Here we review the current understanding of the ncRNA role in exercise-induced adaptations focused on the cardiovascular system and address their potential role in clinical applications for CVD. Finally, considerations and perspectives for future studies will be proposed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1042/CS20171463DOI Listing
May 2018

iNOS-Derived Nitric Oxide Induces Integrin-Linked Kinase Endocytic Lysosome-Mediated Degradation in the Vascular Endothelium.

Arterioscler Thromb Vasc Biol 2017 07 25;37(7):1272-1281. Epub 2017 May 25.

From the Biology Systems Department, Physiology, School of Medicine and Health Sciences, Universidad Alcalá (IRYCIS), Madrid, Spain (P.R., M.A., S.M., M.S.); Cardiology Department, University Francisco de Vitoria/Hospital Ramón y Cajal Research Unit (IRYCIS), Madrid, Spain (C.Z.); and Cardiology Department, School of Medicine, Cádiz University, Spain (R.T.).

Objective: ILK (integrin-linked kinase) plays a key role in controlling vasomotor tone and is decreased in atherosclerosis. The objective of this study is to test whether nitric oxide (NO) regulates ILK in vascular remodeling.

Approach And Results: We found a striking correlation between increased levels of inducible nitric oxide and decreased ILK levels in human atherosclerosis and in a mouse model of vascular remodeling (carotid artery ligation) comparing with iNOS (inducible NO synthase) knockout mice. iNOS induction produced the same result in mouse aortic endothelial cells, and these effects were mimicked by an NO donor in a time-dependent manner. We found that NO decreased ILK protein stability by promoting the dissociation of the complex ILK/Hsp90 (heat shock protein 90)/eNOS (endothelial NO synthase), leading to eNOS uncoupling. NO also destabilized ILK signaling platform and lead to decreased levels of paxillin and α-parvin. ILK phosphorylation of its downstream target GSK3-β (glycogen synthase kinase 3 beta) was decreased by NO. Mechanistically, NO increased ILK ubiquitination mediated by the E3 ubiquitin ligase CHIP (C terminus of HSC70-interacting protein), but ILK ubiquitination was not followed by proteasome degradation. Alternatively, NO drove ILK to degradation through the endocytic-lysosomal pathway. ILK colocalized with the lysosome marker LAMP-1 (lysosomal-associated membrane protein 1) in endothelial cells, and inhibition of lysosome activity with chloroquine reversed the effect of NO. Likewise, ILK colocalized with the early endosome marker EEA1 (early endosome antigen 1). ILK endocytosis proceeded via dynamin because a specific inhibitor of dynamin (Dyngo 4a) was able to reverse ILK endocytosis and its lysosome degradation.

Conclusions: Endocytosis regulates ILK signaling in vascular remodeling where there is an overload of inducible NO, and thus its inhibition may represent a novel target to fight atherosclerotic disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/ATVBAHA.117.309560DOI Listing
July 2017

Genetic basis of dilated cardiomyopathy.

Int J Cardiol 2016 Dec 21;224:461-472. Epub 2016 Sep 21.

Cardiovascular Genetics Center, IDIBGI, University of Girona, Girona, Spain; Medical Science Department, School of Medicine, University of Girona, Girona, Spain.

Dilated cardiomyopathy is a rare cardiac disease characterized by left ventricular dilatation and systolic dysfunction leading to heart failure and sudden cardiac death. Currently, despite several conditions have been reported as aetiologies of the disease, a large number of cases remain classified as idiopathic. Recent studies determine that nearly 60% of cases are inherited, therefore due to a genetic cause. Progressive technological advances in genetic analysis have identified over 60 genes associated with this entity, being TTN the main gene, so far. All these genes encode a wide variety of myocyte proteins, mainly sarcomeric and desmosomal, but physiopathologic pathways are not yet completely unraveled. We review the recent published data about genetics of familial dilated cardiomyopathy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijcard.2016.09.068DOI Listing
December 2016

Prognosis of patients with syncope seen in the emergency room department: an evaluation of four different risk scores recommended by the European Society of Cardiology guidelines.

Eur J Emerg Med 2017 Dec;24(6):428-434

aCardiology and Emergency Department, Virgen del Rocío University Hospital, University of Seville, Seville bDepartment of Medicine, University Cadiz, Cádiz, Spain.

Aim: To apply, analyze, and evaluate the four syncope risk scores recommended by the 2009 European guidelines and the different parameters that they use to predict death, syncope recurrence, and hospital readmission in the population seen in the emergency room department (ERD) for syncope.

Methods And Results: A total of 323 patients aged older than 14 years [mean age 59 (32-75) years] and seen in ERD for syncope over a 2-month period were included in the study; 50.7% were women. Patients were evaluated using the four risk scores and were followed up for at least 2 years. In all, 275 patients (85.2%) were discharged directly from ERD after evaluation. During 28±5 months of follow-up, 8% died, 18.3% presented a further syncopal episode, and 18.6% were readmitted to hospital. Only two of the four risk scores were useful in risk discrimination, but no statistically significant differences were detected between predicted risk and observed risk. Multivariate analysis indicated relationships between age and death, a history of cardiovascular disease and syncope recurrence, and between presyncopal palpitations and hospital readmission.

Conclusion: Although a large number of events occur after syncope, the risk scores recommended by guidelines overestimate risk, but there were no statistically significant differences between observed and predicted risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MEJ.0000000000000392DOI Listing
December 2017

Proteomic identification of putative biomarkers for early detection of sudden cardiac death in a family with a LMNA gene mutation causing dilated cardiomyopathy.

J Proteomics 2016 10 22;148:75-84. Epub 2016 Jul 22.

Medicine Department, School of Medicine, Universidad de Cádiz, Spain. Electronic address:

Unlabelled: Dilated cardiomyopathy (DCM) is a severe heart disease characterized by progressive ventricular dilation and impaired systolic function of the left ventricle. We recently identified a novel pathogenic mutation in the LMNA gene in a family affected by DCM showing sudden death background. We now aimed to identify potential biomarkers of disease status, as well as sudden death predictors, in members of this family. We analysed plasma samples from 14 family members carrying the mutation, four of which (with relevant clinical symptoms) were chosen for the proteomic analysis. Plasma samples from these four patients and from four sex- and age-matched healthy controls were processed for their enrichment in low- and medium-abundance proteins (ProteoMiner™) prior to proteomic analysis by 2D-DIGE and MS. 111 spots were found to be differentially regulated between mutation carriers and control groups, 83 of which were successfully identified by MS, corresponding to 41 different ORFs. Some proteins of interest were validated either by turbidimetry or western blot in family members and healthy controls. Actin, alpha-1-antytripsin, clusterin, vitamin-D binding protein and antithrombin-III showed increased levels in plasma from the diseased group. We suggest following these proteins as putative biomarkers for the evaluation of DCM status in LMNA mutation carriers.

Biological Significance: We developed a proteomic analysis of plasma samples from a family showing history of dilated cardiomyopathy caused by a LMNA mutation, which may lead to premature death or cardiac transplant. We identified a number of proteins augmented in mutation carriers that could be followed as potential biomarkers for dilated cardiomyopathy on these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jprot.2016.07.020DOI Listing
October 2016

Familial Dilated Cardiomyopathy Caused by a Novel Frameshift in the BAG3 Gene.

PLoS One 2016 8;11(7):e0158730. Epub 2016 Jul 8.

Cardiovascular Genetics Center, IDIBGI, University of Girona, Girona, Spain.

Background: Dilated cardiomyopathy, a major cause of chronic heart failure and cardiac transplantation, is characterized by left ventricular or biventricular heart dilatation. In nearly 50% of cases the pathology is inherited, and more than 60 genes have been reported as disease-causing. However, in 30% of familial cases the mutation remains unidentified even after comprehensive genetic analysis. This study clinically and genetically assessed a large Spanish family affected by dilated cardiomyopathy to search for novel variations.

Methods And Results: Our study included a total of 100 family members. Clinical assessment was performed in alive, and genetic analysis was also performed in alive and 1 deceased relative. Genetic screening included resequencing of 55 genes associated with sudden cardiac death, and Sanger sequencing of main disease-associated genes. Genetic analysis identified a frame-shift variation in BAG3 (p.H243Tfr*64) in 32 patients. Genotype-phenotype correlation identified substantial heterogeneity in disease expression. Of 32 genetic carriers (one deceased), 21 relatives were clinically affected, and 10 were asymptomatic. Seventeen of the symptomatic genetic carriers exhibited proto-diastolic septal knock by echocardiographic assessment.

Conclusions: We report p.H243Tfr*64_BAG3 as a novel pathogenic variation responsible for familial dilated cardiomyopathy. This variation correlates with a more severe phenotype of the disease, mainly in younger individuals. Genetic analysis in families, even asymptomatic individuals, enables early identification of individuals at risk and allows implementation of preventive measures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0158730PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4938129PMC
August 2017

Cardiometabolic Risk Related to the Association of hypertriglyceridemia-Low HDLc.

Curr Pharm Des 2016 ;22(3):365-71

Unit of Vascular Risk and Lipids, Department of Internal Medicine, General University Hospital Gregorio Marañon, School of Medicine of the Complutense University, 46 Dr Esquerdo, 28007 Madrid (Spain).

Aims: High levels of plasma triglycerides (TG) are a risk factor for cardiovascular diseases often associated with anomalies in other lipids or lipoproteins. However, results from randomized trials, suggesting that low high density lipoprotein cholesterol (HDLc) might not cause cardiovascular disease, as originally thought, have generated renewed interest in increased concentrations of TG. The objective has been to determine the prevalence and factors associated with hypertrigliceridemia (HTG) and with low HDLc.

Methods: Patients, included in the HTG Registry of the Spanish Association of Atherosclerosis, have been analyzed and anthropometric as well as metabolic data have been collected from them.

Results: 1349 patients have been evaluated. Low HDLc has been found in 60.86% (821). Factors significantly associated with low HDLc and HTG were the female sex, being overweight with an increase in the body mass index, using tobacco, diabetes mellitus, low-alcohol consumption and a low exercise rate. Among them, two types of association may be identified with anthropometric variables (especially in men) and metabolic variables (diabetes mellitus and metabolic syndrome). No significant differences have been found insofar as the prevalence of cardiovascular illness between both groups.

Conclusions: HTG - low HDLc association is very frequent and it is related to overweight-obesity and other metabolic disorders such as diabetes mellitus with or without metabolic syndrome. In addition, these findings underscore the intricate relationship between HDLc, TG, and glucose metabolism that need to be studied simultaneously. In this context, TG lowering treatment is suggested to be more strongly recommended to address the residual risk of atherosclerotic cardiovascular disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1381612822666151112150831DOI Listing
October 2016

A SHORT-TERM CIRCUIT RESISTANCE PROGRAMME REDUCED EPICARDIAL FAT IN OBESE AGED WOMEN.

Nutr Hosp 2015 Nov 1;32(5):2193-7. Epub 2015 Nov 1.

University of Cadiz, Spain..

Introduction: this study was conducted to ascertain the effects of resistance circuit training on epicardial adipose tissue (EAT) in obese aged women. A secondary objective was to assess muscle damage induced by supervised resistance training to confirm the intervention program was effective and safe.

Methods: in the present interventional study, a total of 48 obese aged women were recruited from the community. Twenty-four of them were randomly assigned to perform a 12-week resistance circuit training programme, 3-days per week. This training was circularly performed in 6 stations: arm curl, leg extension, seated row, leg curl, triceps extension and leg press. The Jamar handgrip electronic dynamometer was used to assess maximal handgrip strength of the dominant hand. Two experienced observers assessed EAT by transthoracic two-dimensional echocardiography. Lastly, serum samples were analysed using one-step sandwich assays for creatine kinase activity (CK) and myoglobin (MB) concentration.

Results: as was hypothesized, resistance training significantly reduced EAT thickness (8.4 ± 1.0 vs. 7.3 ± 1.3 mm; p = 0.014; d = 0.76) in the experimental group. Resistance training induced no significant changes in markers of muscle damage such as CK (181.6 ± 36.9 vs. 194.2 ± 37.8 U/l; p = 0.31) and MB (62.4 ± 7.1 vs. 67.3 ± 7.7 ng/ml; p = 0.26). No significant changes in any of the tested outcomes were found in the control group.

Conclusion: resistance training reduced EAT in aged obese women. A secondary finding was that the training program was effective and safe. While current results are promising, future studies are still required to consolidate this approach in clinical application.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3305/nh.2015.32.5.9696DOI Listing
November 2015

Statins for primary cardiovascular prevention in the elderly.

J Geriatr Cardiol 2015 Jul;12(4):431-8

Lipid and Vascular Risk Unit, Endocrinology department, Hospital del Mar. Spain.

The elderly population is increasing worldwide, with subjects > 65 years of age constituting the fastest-growing age group. Furthermore, the elderly face the greatest risk and burden of cardiovascular disease mortality and morbidity. Although elderly patients, particularly those older > 75, have not been well represented in randomized clinical trials evaluating lipid-lowering therapy, the available evidence supporting the use of statin therapy in primary prevention in older individuals is derived mainly from subgroup analyses and post-hoc data. On the other hand, elderly patients often have multiple co-morbidities that require a high number of concurrent medications; this may increase the risk for drug-drug interactions, thereby reducing the potential benefits of statin therapy. The aim of this review was to present the relevant literature regarding statin use in the elderly for their primary cardiovascular disease, with the associated risks and benefits of treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11909/j.issn.1671-5411.2015.04.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4554788PMC
July 2015

[METABOLIC SYNDROME IN PATIENTS WITH CLINICAL PHENOTYPE "HYPERTRIGLYCERIDEMIC WAIST"].

Nutr Hosp 2015 Sep 1;32(3):1145-52. Epub 2015 Sep 1.

Departamento de Medicina. Universidad de Cádiz, España..

Introduction: hypertriglyceridemic waist phenotype has been associated with metabolic syndrome.

Objetives: in the present work has been raised to study the relationship between hypertriglyceridemic waist phenotype and metabolic syndrome as well as other metabolic risk factors. And finally, assess whether it is associated with an increased cardiovascular risk.

Methods: this study was conducted recruiting patients in a national registry of hypertriglyceridemia of the Spanish Society of Artherosclerosis. The total number of patients included in the present study was 1 369. The criteria used to define the increased waist perimeter and metabolic syndrome were based on those established by the ATPIII or IDF, respectively.

Results: hypertriglyceridemic waist prevalence in patients with hypertriglyceridemia was near to 50% and 80% using ATPII and IDF anthropometric criteria, respectively. The prevalence of metabolic syndrome in these patients was close to 97% (ATPIII criteria) and 63% (IDF criteria). Also was significantly higher prevalence of hypertension and diabetes mellitus type 2. However, the association with cardiovascular disease does not depend on the existence of hypertriglyceridemic waist phenotype, but the existence (or not) of metabolic syndrome.

Conclusions: the CHTG can be used in clinical practice routine as a marker of metabolic alterations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3305/nh.2015.32.3.9138DOI Listing
September 2015

[Performance of entero-insular axis in an athletic population: diet and exercise influence].

Nutr Hosp 2015 May 1;31(5):2187-94. Epub 2015 May 1.

Departamento de Medicina, Facultad de Medicina, Cádiz..

Introduction: The relationship between physical exercise and appetite regulation can lead to improved competitive performance of athletes. Mediators of the entero-insular axis generate neurohumoral signals that influence on the appetite regulation and energy homeostasis.

Aim: Determine the influence of diet and prolonged exercise on intestinal peptide, ghrelin, resistin, leptin, and incretins (GLP-1 and GIP) in an athlete population.

Methods: It is a prospective intervention study, conducted from October 2012 to March 2013. 32 healthy semiprofessional rugby players, aged 13-39 years were included. Anthropometric measurements and blood samples were taken at time 0 and after six months of study. Athletes were randomized to a protein diet (PD) or Mediterranean diet (MD) and plasma levels of intestinal peptide, ghrelin, resistin, leptin, and incretins were calculated.

Results: In the PD group, GLP-1 and GIP plasmatic levels showed a significant decrease (p <0.03; p <0.01 respectively). GLP-1 and ghrelin plasmatic concentration demonstrated a significant decrease (p <0.03 respectively) in those who experienced gain of muscle mass (MM). Finally, the athletes related to the PD who showed increased total weight and muscle mass presented significantly decreased GLP-1 concentration (p <0.03 and p<0.002, respectively).

Conclusion: GLP-1 plasmatic concentration was decreased, with the PD suggesting to be more beneficial for the athletes in order to avoid hypoglycemia. Furthermore, muscle mass and total weight gain, linked to the PD, could enhance athletic performance in certain sport modalities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3305/nh.2015.31.5.8828DOI Listing
May 2015

Relationship between lipoprotein (a) and micro/macro complications in type 2 diabetes mellitus: a forgotten target.

J Geriatr Cardiol 2015 Mar;12(2):93-9

Department of Medicine, Cádiz University, School of Medicine, Cádiz 11002, C/ Dr Marañon S/N, Cádiz, Spain ; Department of Internal Medicine, University Hospital Puerta del Mar, Cádiz 11002, Ana de Viya S/N, Cádiz, Spain.

Objectives: Increased lipoprotein (a) serum concentrations seems to be a cardiovascular risk factor; this has not been confirmed in extracoronary atherosclerosis complications. We therefore wished to gain a deeper insight into relationship between the plasma concentrations of lipoprotein (a) and the micro- and macro-vascular complications of type 2 diabetes mellitus and to identify possible differences in this association.

Methods: This is a descriptive observational cross-sectional study. Two-hundred and seventeen elderly patients with type 2 diabetes mellitus were included from the internal medicine outclinic. Anthropometric data, analytical data (insulin reserve, basal and postprandial peptide C, glycosylated hemoglobin, renal parameters, lipid profile and clinical data as hypertension, obesity, micro- and macrovascular complications were collected.

Results: Patients were grouped according to the type 2 diabetes mellitus time of evolution. The mean plasma concentration of lipoprotein (a) was 22.2 ± 17.3 mg/dL (22.1 ± 15.9 mg/dL for males, and 22.1 ± 18.4 mg/dL for females). Patients with hypertension, coronary heart disease, cerebrovascular accident, microalbuminuria and proteinuria presented a statistically significant increased level of lipoprotein (a). Similarly, the patients with hyperlipoprotein (a) (≥ 30 mg/dL) presented significantly increased levels of urea and total cholesterol. In the multivariate regression model, the level of lipoprotein (a) is positively correlated with coronary heart disease and diabetic nephropathy (P < 0.01 and P < 0.005, respectively).

Conclusions: The elevation of plasma levels of lipoprotein (a) are associated with the development of coronary heart disease and diabe tic nephropathy. Therefore, we consider that the determination of lipoprotein (a) may be a prognostic marker of vascular complications in patients with type 2 diabetes mellitus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11909/j.issn.1671-5411.2015.02.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394322PMC
March 2015
-->