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Cardiovascular Disease: New Generation of Biomarkers and Future Therapeutic Concepts
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Cardiovascular Disease: New Generation of Biomarkers and Future Therapeutic Concepts

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Cardiology".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 60848

Special Issue Editors

Dr. David de Gonzalo-Calvo

E-Mail Website
Guest Editor
1. Institute of Biomedical Research of Barcelona (IIBB), Spanish National Research Council (CSIC), Barcelona, Spain
2. Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain
3. CIBERCV, Institute of Health Carlos III, Madrid, Spain
Interests: biomarker; cardiometabolic disease; cardiovascular disease; exercise; noncoding RNA; precision medicine
Dr. Christian Bär

E-Mail Website
Co-Guest Editor
1. Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany
2. REBIRTH Excellence Cluster, Hannover Medical School, Hannover, Germany
Interests: cardiovascular disease; cardiac regeneration; noncoding RNA therapy; telomere biology; aging

Special Issue Information

Dear Colleagues,

Despite the great advances in the management of cardiovascular disease, this condition persists as the most common noncommunicable disease and the leading cause of death worldwide. There is an urgent need to improve the clinical management of cardiovascular disease with regard to novel treatment concepts as well as the identification of new biomarkers. In this Special Issue, we will provide a comprehensive overview of the recent developments in cardiovascular disease, from novel tools to guide clinical decision-making, to promising next-generation therapeutic approaches.

We welcome the submission of original research and review articles on the following topics:

  1. Novel molecular mechanisms implicated in cardiovascular disease development;
  2. Recent advances in drug targets and therapeutic approaches;
  3. New biomarkers for diagnosis, prognosis and risk stratification;
  4. Prediction and monitorization of the therapeutic response;
  5. Drug repositioning;
  6. Alternative use of established clinical indicators;
  7. Advances in cardiovascular personalized medicine.

We encourage authors to include a section indicating the impact of the novel findings on the clinical management of the cardiovascular patient.

Dr. David de Gonzalo-Calvo
Dr. Christian Bär
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Biomarkers
  • Biomarker-guided therapy
  • Biomarker development and validation
  • Cardiac aging
  • Cardiac regeneration
  • Cardiovascular disease
  • Cardiovascular therapy
  • Diagnosis
  • Drug repositioning
  • Risk stratification

Published Papers (21 papers)

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Research

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11 pages, 8013 KiB  
Article
Pilot Study on the Role of Circulating miRNAs for the Improvement of the Predictive Ability of the 2MACE Score in Patients with Atrial Fibrillation
by José Miguel Rivera-Caravaca, Raúl Teruel-Montoya, Vanessa Roldán, Rosa Cifuentes-Riquelme, José Antonio Crespo-Matas, Ascensión María de los Reyes-García, Sonia Águila, María Piedad Fernández-Pérez, Laura Reguilón-Gallego, Laura Zapata-Martínez, Nuria García-Barberá, Vicente Vicente, Francisco Marín, Constantino Martínez and Rocío González-Conejero
J. Clin. Med. 2020, 9(11), 3645; https://doi.org/10.3390/jcm9113645 - 12 Nov 2020
Cited by 12 | Viewed by 1826
Abstract
Background. Atrial fibrillation (AF) increases the risk for stroke but also for non-stroke major adverse cardiovascular events (MACE). The 2MACE score was recently proposed to predict these events. Since the interest of microRNAs (miRNAs) in cardiovascular diseases is increasing, we aimed to [...] Read more.
Background. Atrial fibrillation (AF) increases the risk for stroke but also for non-stroke major adverse cardiovascular events (MACE). The 2MACE score was recently proposed to predict these events. Since the interest of microRNAs (miRNAs) in cardiovascular diseases is increasing, we aimed to investigate whether miRNA levels may improve the predictive performance of the 2MACE score. Methods. We included consecutive AF patients stable on vitamin K antagonist therapy. Blood samples were drawn at baseline and plasma expression of miRNAs was assessed. During a median of 7.6 (interquartile range (IQR) 5.4–8.0) years, the occurrence of any MACE (nonfatal myocardial infarction/cardiac revascularization and cardiovascular death) was recorded. Results. We conducted a miRNA expression analysis in plasma from 19 patients with and without cardiovascular events. The miRNAs selected (miR-22-3p, miR-107, and miR-146a-5p) were later measured in 166 patients (47% male, median age 77 (IQR 70–81) years) and all were associated with a higher risk of MACE. The addition of miR-107 and miR-146a-5p to the 2MACE score significantly increased the predictive performance (c-indexes: 0.759 vs. 0.694, p = 0.004), and the model with three miRNAs also improved the predictive performance compared to the original score (c-indexes: 0.762 vs. 0.694, p = 0.012). 2MACE models with the addition of miRNAs presented higher net benefit and potential clinical usefulness. Conclusions. Higher miR-22-3p andmiR-107 and lower miR-146a-5p levels were associated with a higher risk of MACE. The addition of these miRNAs to the 2MACE score significantly increased the predictive performance for MACE, which may aid to some extent in the decision-making process about risk stratification in AF. Full article
(This article belongs to the Special Issue Cardiovascular Disease: New Generation of Biomarkers and Future Therapeutic Concepts)
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13 pages, 967 KiB  
Article
The Effect of Anti-TNF Therapy on Cardiac Function in Rheumatoid Arthritis: An Observational Study
by Milad Baniaamam, M. Louis Handoko, Rabia Agca, Sjoerd C. Heslinga, Thelma C. Konings, Vokko P. van Halm and Mike T. Nurmohamed
J. Clin. Med. 2020, 9(10), 3145; https://doi.org/10.3390/jcm9103145 - 29 Sep 2020
Cited by 11 | Viewed by 2743
Abstract
Congestive heart failure (CHF) is the second most prevalent cause of death in rheumatoid arthritis (RA). The systemic inflammatory state in RA patients is deemed responsible for this finding. Anti-inflammatory treatment with anti-tumor necrosis factor (anti-TNF) therapy decreases CV risk and subsequently might [...] Read more.
Congestive heart failure (CHF) is the second most prevalent cause of death in rheumatoid arthritis (RA). The systemic inflammatory state in RA patients is deemed responsible for this finding. Anti-inflammatory treatment with anti-tumor necrosis factor (anti-TNF) therapy decreases CV risk and subsequently might improve the cardiac function by lowering the overall inflammatory state. This study investigated the effect of anti-TNF on the cardiac function in RA patients. Fifty one RA patients were included, of which thirty three completed follow-up. Included patients were >18 years, had moderate–high disease activity and no history of cardiac disease. Patients were assessed at baseline and after six months of anti-TNF treatment. Patients underwent conventional Speckle tracking and tissue Doppler echocardiography in combination with clinical and laboratory assessments at baseline and follow-up. The left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) showed no changes during follow-up, LVEF 63% (±9) to 62% (±8) p = 0.097 and GLS −20 (±4) to −20 (±3) p = 0.79, respectively. Furthermore, E/e’ nor E/A changed significantly between baseline and follow-up, respectively 8 (7–9) and 8 (7–9) p = 0.17 and 1.1 (±0.4) and 1.1 (±0.4) p = 0.94. Follow-up NT-proBNP decreased with 23%, from 89 ng/L (47–142) to 69 ng/L (42–155), p = 0.10. Regression analysis revealed no association between change in inflammatory variables and cardiac function. Echocardiography showed no effect of anti-TNF treatment on the cardiac function in RA patients with low prevalence of cardiac dysfunction. Moreover, NT-proBNP decreased, possibly indicating (subtle) improvement of the cardiac function. Full article
(This article belongs to the Special Issue Cardiovascular Disease: New Generation of Biomarkers and Future Therapeutic Concepts)
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13 pages, 1544 KiB  
Article
Sarcopenia Index as a Predictor of Clinical Outcomes in Older Patients with Coronary Artery Disease
by Hak Seung Lee, Kyung Woo Park, Jeehoon Kang, You-Jeong Ki, Mineok Chang, Jung-Kyu Han, Han-Mo Yang, Hyun-Jae Kang, Bon-Kwon Koo and Hyo-Soo Kim
J. Clin. Med. 2020, 9(10), 3121; https://doi.org/10.3390/jcm9103121 - 27 Sep 2020
Cited by 23 | Viewed by 3471
Abstract
To demonstrate the association of the serum creatinine/serum cystatin C ratio (sarcopenia index, SI) with clinical outcomes including cardiovascular and bleeding risk in older patients who underwent percutaneous coronary intervention (PCI), we analyzed a multicenter nation-wide pooled registry. A total of 1086 older [...] Read more.
To demonstrate the association of the serum creatinine/serum cystatin C ratio (sarcopenia index, SI) with clinical outcomes including cardiovascular and bleeding risk in older patients who underwent percutaneous coronary intervention (PCI), we analyzed a multicenter nation-wide pooled registry. A total of 1086 older patients (65 years or older) who underwent PCI with second-generation drug-eluting stents (DES) were enrolled. The total population was divided into quartiles according to the SI, stratified by sex. The primary clinical outcomes were major adverse cardiovascular events (MACE, all-cause death, myocardial infarction and target lesion revascularization) and thrombolysis in myocardial infarction major and minor bleeding during a 3-year follow-up period. In the total population, MACE occurred within 3 years in 154 (14.2%) patients. The lowest SI quartile group (Q1) had a significantly higher 3-year MACE rate (Q1 vs. Q2–4; 23.1% vs. 11.2%, p < 0.001), while bleeding event rates were similar between the groups (Q1 vs. Q2–4; 2.6% vs. 2.2%, p = 0.656). The Cox proportional hazard model showed that lower SI is an independent predictor for MACE events (HR 2.23, 95% CI 1.62–3.07, p < 0.001). The SI, a surrogate for the degree of muscle mass, is associated with cardiovascular and non-cardiovascular death, but not with bleeding in older patients who underwent PCI. Full article
(This article belongs to the Special Issue Cardiovascular Disease: New Generation of Biomarkers and Future Therapeutic Concepts)
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19 pages, 1634 KiB  
Article
GlycA Levels during the Earliest Stages of Rheumatoid Arthritis: Potential Use as a Biomarker of Subclinical Cardiovascular Disease
by Javier Rodríguez-Carrio, Mercedes Alperi-López, Patricia López, Ángel I. Pérez-Álvarez, Miriam Gil-Serret, Núria Amigó, Catalina Ulloa, Lorena Benavente, Francisco J. Ballina-García and Ana Suárez
J. Clin. Med. 2020, 9(8), 2472; https://doi.org/10.3390/jcm9082472 - 1 Aug 2020
Cited by 12 | Viewed by 2734
Abstract
This study aimed at evaluating the clinical relevance of glycoprotein profiles during the earliest phases of rheumatoid arthritis (RA) as biomarkers of cardiovascular (CV) risk and treatment response. Then, GlycA and GlycB serum levels were measured using 1H-nuclear magnetic resonance in 82 early [...] Read more.
This study aimed at evaluating the clinical relevance of glycoprotein profiles during the earliest phases of rheumatoid arthritis (RA) as biomarkers of cardiovascular (CV) risk and treatment response. Then, GlycA and GlycB serum levels were measured using 1H-nuclear magnetic resonance in 82 early RA patients, 14 clinically-suspect arthralgia (CSA), and 28 controls. Serum glycosyltransferase activity was assessed by a colorimetric assay. Subclinical CV disease was assessed by Doppler-ultrasound. We found that GlycA and GlycB serum levels were increased in RA (both p < 0.001), but not in CSA, independently of cardiometabolic risk factors. Increased serum glycosyltransferase activity paralleled GlycA (r = 0.405, p < 0.001) and GlycB levels (r = 0.327, p = 0.005) in RA. GlycA, but not GlycB, was associated with atherosclerosis occurrence (p = 0.012) and severity (p = 0.001). Adding GlycA to the mSCORE improved the identification of patients with atherosclerosis over mSCORE alone, increasing sensitivity (29.7 vs. 68.0%) and accuracy (55.8 vs. 76.6%) and allowing reclassification into more appropriate risk categories. GlycA-reclassification identified patients with impaired lipoprotein metabolism. Finally, baseline GlycA levels predicted poor clinical response upon anti-rheumatic treatment at 6 and 12 months in univariate and multivariate analysis. In sum, increased GlycA levels during the earliest stage of RA can be considered a powerful biomarker for CV risk stratification and treatment response. Full article
(This article belongs to the Special Issue Cardiovascular Disease: New Generation of Biomarkers and Future Therapeutic Concepts)
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15 pages, 1009 KiB  
Article
Changes in High-Density Lipoproteins Related to Outcomes in Patients with Acute Stroke
by Lourdes M. Varela, Elena Meseguer, Bertrand Lapergue, David Couret, Pierre Amarenco and Olivier Meilhac
J. Clin. Med. 2020, 9(7), 2269; https://doi.org/10.3390/jcm9072269 - 17 Jul 2020
Cited by 11 | Viewed by 1871
Abstract
Modifications in high-density lipoprotein (HDL) particle sizes and HDL-binding proteins have been reported in stroke patients. We evaluated whether the lipoprotein profile, HDL composition and functionality were altered in stroke patients according to their clinical outcome using the modified Rankin Score at 3 [...] Read more.
Modifications in high-density lipoprotein (HDL) particle sizes and HDL-binding proteins have been reported in stroke patients. We evaluated whether the lipoprotein profile, HDL composition and functionality were altered in stroke patients according to their clinical outcome using the modified Rankin Score at 3 months. Plasma samples were obtained from stroke patients treated with intravenous thrombolysis. Levels of cardiovascular and inflammatory markers in plasma were measured using the Human CVD Panel 1 (Milliplex® MAP). Lipoprotein subfractions from plasma were quantified by non-denaturing acrylamide gel electrophoresis, using the Lipoprint®-System (Quantimetrix®), and HDLs were isolated by ultracentrifugation. Relative amounts of paraoxonase-1 (PON1) and alpha-1 anti-trypsin (AAT) in the isolated HDLs were determined by Western blot. HDL anti-inflammatory function was evaluated in human blood–brain barrier endothelial cells stimulated with 100 ng/mL TNFα, and HDL antioxidant function was evaluated via their capacity to limit copper-induced low-density lipoprotein oxidation. Stroke patients with unfavorable outcomes had a lower proportion of small-sized HDLs and increased plasma levels of E-selectin (SELE) and the intercellular adhesion molecule 1 (ICAM1). HDLs from patients with unfavorable outcomes had lower levels of PON1 and displayed a blunted capacity to reduce the expression of SELE, interleukin 8 (IL8) and the monocyte chemoattractant protein-1 (MCP1) mRNA induced by TNFα in endothelial cells. These HDLs also had a reduced antioxidant capacity relative to HDLs from healthy donors. In conclusion, an increased ratio of large/small HDLs with impaired anti-inflammatory and antioxidant capacities was associated with unfavorable outcomes in stroke patients. Alteration of HDL functionality was mainly associated with a low amount of PON1 and high amount of AAT. Full article
(This article belongs to the Special Issue Cardiovascular Disease: New Generation of Biomarkers and Future Therapeutic Concepts)
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15 pages, 350 KiB  
Article
Estimated Population Prevalence of Heart Failure with Reduced Ejection Fraction in Spain, According to DAPA-HF Study Criteria
by Anna Camps-Vilaró, Juan F. Delgado-Jiménez, Núria Farré, Helena Tizón-Marcos, Jesús Álvarez-García, Juan Cinca, Irene R. Dégano and Jaume Marrugat
J. Clin. Med. 2020, 9(7), 2089; https://doi.org/10.3390/jcm9072089 - 3 Jul 2020
Cited by 7 | Viewed by 3408
Abstract
Heart failure (HF) is one of the main causes of morbidity, mortality, and high healthcare costs. Dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, reduced cardiovascular mortality and hospitalization for HF compared to placebo in patients with chronic HF, and reduced ejection fraction (EF) in [...] Read more.
Heart failure (HF) is one of the main causes of morbidity, mortality, and high healthcare costs. Dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, reduced cardiovascular mortality and hospitalization for HF compared to placebo in patients with chronic HF, and reduced ejection fraction (EF) in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) study. Our aim was to estimate the number of patients with DAPA-HF characteristics in Spain. Our literature review identified epidemiological studies whose objective was to quantify the prevalence of HF and its comorbidities in Spain. We estimated the prevalence of HF with reduced EF, of New York Heart Association (NYHA) functional class II–IV, and with a glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m². In this population, we analysed the prevalence of diabetes using data from the REDINSCOR (Spanish Network for Heart Failure) registry. Our estimations indicate there are 594,684 patients ≥45 years old with HF in Spain (2.6% of this population age group), of which 52.4%, 84.0%, and 93.9% have reduced EF, are NYHA II–IV, and have a GFR ≥ 30 mL/min/1.73 m², respectively. By our calculations, approximately 245,789 Spanish patients would meet the DAPA-HF patient profile, and therefore could benefit from the protective cardiovascular effects of dapagliflozin. Full article
(This article belongs to the Special Issue Cardiovascular Disease: New Generation of Biomarkers and Future Therapeutic Concepts)
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13 pages, 897 KiB  
Article
Identification of a miRNA Based-Signature Associated with Acute Coronary Syndrome: Evidence from the FLORINF Study
by Meyer Elbaz, Julien Faccini, Clémence Laperche, Elisa Grousset, Jérôme Roncalli, Jean-Bernard Ruidavets and Cécile Vindis
J. Clin. Med. 2020, 9(6), 1674; https://doi.org/10.3390/jcm9061674 - 1 Jun 2020
Cited by 7 | Viewed by 1989
Abstract
Background: The discovery of novel biomarkers that improve risk prediction models of acute coronary syndrome (ACS) is needed to better identify and stratify very high-risk patients. MicroRNAs (miRNAs) are essential non-coding modulators of gene expression. Circulating miRNAs recently emerged as important regulators and [...] Read more.
Background: The discovery of novel biomarkers that improve risk prediction models of acute coronary syndrome (ACS) is needed to better identify and stratify very high-risk patients. MicroRNAs (miRNAs) are essential non-coding modulators of gene expression. Circulating miRNAs recently emerged as important regulators and fine-tuners of physiological and pathological cardiovascular processes; therefore, specific miRNAs expression profiles may represent new risk biomarkers. The aims of the present study were: (i) to assess the changes in circulating miRNAs levels associated with ACS and (ii) to evaluate the incremental value of adding circulating miRNAs to a clinical predictive risk model. Methods and Results: The study population included ACS patients (n = 99) and control subjects (n = 103) at high to very high cardiovascular risk but without known coronary event. Based on a miRNA profiling in a matched derivation case (n = −6) control (n = 6) cohort, 21 miRNAs were selected for validation. Comparing ACS cases versus controls, seven miRNAs were significantly differentially expressed. Multivariate logistic regression analyses demonstrated that among the seven miRNAs tested, five were independently associated with the occurrence of ACS. A receiver operating characteristic curve analysis revealed that the addition of miR-122 + miR-150 + miR-195 + miR-16 to the clinical model provided the best performance with an increased area under the curve (AUC) from 0.882 to 0.924 (95% CI 0.885–0.933, p = 0.003). Conclusions: Our study identified a powerful signature of circulating miRNAs providing additive value to traditional risk markers for ACS. Full article
(This article belongs to the Special Issue Cardiovascular Disease: New Generation of Biomarkers and Future Therapeutic Concepts)
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12 pages, 821 KiB  
Article
Galectin-3 as the Prognostic Factor of Adverse Cardiovascular Events in Long-Term Follow up in Patients after Myocardial Infarction—A Pilot Study
by Przemysław Święcki, Robert Sawicki, Małgorzata Knapp, Karol Adam Kamiński, Katarzyna Ptaszyńska-Kopczyńska, Bożena Sobkowicz and Anna Lisowska
J. Clin. Med. 2020, 9(6), 1640; https://doi.org/10.3390/jcm9061640 - 29 May 2020
Cited by 6 | Viewed by 1826
Abstract
Galectin-3 (Gal-3) is a new independent risk factor in the development and severity of coronary artery disease (CAD). The aim of the study was to evaluate whether Gal-3 concentration has prognostic value and if it reflects the progression of atherosclerosis in carotid arteries [...] Read more.
Galectin-3 (Gal-3) is a new independent risk factor in the development and severity of coronary artery disease (CAD). The aim of the study was to evaluate whether Gal-3 concentration has prognostic value and if it reflects the progression of atherosclerosis in carotid arteries in patients with CAD after acute myocardial infarction (AMI). The analysis included 110 patients who were hospitalized due to AMI, treated with primary coronary intervention (PCI) and further attended a follow-up visit, and 100 healthy volunteers. The Gal-3 concentration and carotid ultrasound were evaluated at baseline and on a follow-up visit. We found that the Gal-3 concentration in the group with hyperlipidemia decreased during the observation (10.7 vs. 7.9 ng/mL, p = 0.00003). Patients rehospitalized during follow up had higher concentration of Gal-3 in the acute phase of myocardial infarction (MI) (10.7 vs. 7.2 ng/mL, p = 0.02; 10.1 vs. 8.0 ng/mL, p = 0.002, respectively). In the group of patients who had none of the following endpoints: subsequent MI, PCI, coronary artery bypass grafting (CABG) or stroke, there was a decrease in Gal-3 concentration at the follow-up visit. Parameters affecting the frequency of a composite endpoint occurrence are: the presence of atheromatous plaque in the carotid artery (p = 0.017), Gal-3 (p = 0.004) and haemoglobin (p = 0.03) concentration. In multivariate analysis, only Gal-3 concentration higher than 9.2 ng/mL at discharge was associated with a nine-fold increase of risk of composite endpoint occurrence (p = 0.0005, OR = 9.47, 95% CI 2.60–34.45). A significant decrease in Gal-3 concentration was observed in the group of patients after AMI without the endpoint occurrence during observation. Full article
(This article belongs to the Special Issue Cardiovascular Disease: New Generation of Biomarkers and Future Therapeutic Concepts)
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14 pages, 1814 KiB  
Article
Association of Circulating microRNAs with Coronary Artery Disease and Usefulness for Reclassification of Healthy Individuals: The REGICOR Study
by Irene R. Dégano, Anna Camps-Vilaró, Isaac Subirana, Nadia García-Mateo, Pilar Cidad, Dani Muñoz-Aguayo, Eulàlia Puigdecanet, Lara Nonell, Joan Vila, Felipe M. Crepaldi, David de Gonzalo-Calvo, Vicenta Llorente-Cortés, María Teresa Pérez-García, Roberto Elosua, Montserrat Fitó and Jaume Marrugat
J. Clin. Med. 2020, 9(5), 1402; https://doi.org/10.3390/jcm9051402 - 9 May 2020
Cited by 19 | Viewed by 3066
Abstract
Risk prediction tools cannot identify most individuals at high coronary artery disease (CAD) risk. Oxidized low-density lipoproteins (oxLDLs) and microRNAs are actively involved in atherosclerosis. Our aim was to examine the association of CAD and oxLDLs-induced microRNAs, and to assess the microRNAs predictive [...] Read more.
Risk prediction tools cannot identify most individuals at high coronary artery disease (CAD) risk. Oxidized low-density lipoproteins (oxLDLs) and microRNAs are actively involved in atherosclerosis. Our aim was to examine the association of CAD and oxLDLs-induced microRNAs, and to assess the microRNAs predictive capacity of future CAD events. Human endothelial and vascular smooth muscle cells were treated with oxidized/native low-density lipoproteins, and microRNA expression was analyzed. Differentially expressed and CAD-related miRNAs were examined in serum samples from (1) a case-control study with 476 myocardial infarction (MI) patients and 487 controls, and (2) a case-cohort study with 105 incident CAD cases and 455 randomly-selected cohort participants. MicroRNA expression was analyzed with custom OpenArray plates, log rank tests and Cox regression models. Twenty-one microRNAs, two previously undescribed (hsa-miR-193b-5p and hsa-miR-1229-5p), were up- or down-regulated upon cell treatment with oxLDLs. One of the 21, hsa-miR-122-5p, was also upregulated in MI cases (fold change = 4.85). Of the 28 CAD-related microRNAs tested, 11 were upregulated in MI cases-1 previously undescribed (hsa-miR-16-5p)-, and 1/11 was also associated with CAD incidence (adjusted hazard ratio = 0.55 (0.35–0.88)) and improved CAD risk reclassification, hsa-miR-143-3p. We identified 2 novel microRNAs modulated by oxLDLs in endothelial cells, 1 novel microRNA upregulated in AMI cases compared to controls, and one circulating microRNA that improved CAD risk classification. Full article
(This article belongs to the Special Issue Cardiovascular Disease: New Generation of Biomarkers and Future Therapeutic Concepts)
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18 pages, 1668 KiB  
Article
miR−21 and NT-proBNP Correlate with Echocardiographic Parameters of Atrial Dysfunction and Predict Atrial Fibrillation
by Jan-Thorben Sieweke, Tobias Jonathan Pfeffer, Saskia Biber, Shambhabi Chatterjee, Karin Weissenborn, Gerrit M. Grosse, Jan Hagemus, Anselm A. Derda, Dominik Berliner, Ralf Lichtinghagen, Denise Hilfiker-Kleiner, Johann Bauersachs, Christian Bär, Thomas Thum and Udo Bavendiek
J. Clin. Med. 2020, 9(4), 1118; https://doi.org/10.3390/jcm9041118 - 14 Apr 2020
Cited by 18 | Viewed by 3189
Abstract
This study aimed to investigate the association of circulating biomarkers with echocardiographic parameters of atrial remodelling and their potential for predicting atrial fibrillation (AF). In patients with and without AF (n = 21 and n = 60) the following serum biomarkers were [...] Read more.
This study aimed to investigate the association of circulating biomarkers with echocardiographic parameters of atrial remodelling and their potential for predicting atrial fibrillation (AF). In patients with and without AF (n = 21 and n = 60) the following serum biomarkers were determined: soluble ST2 (sST2), Galectin−3 (Gal-3), N-terminal pro-brain natriuretic peptide (NT-proBNP), microRNA (miR)−21, −29a, −133a, −146b and −328. Comprehensive transthoracic echocardiography was performed in all participants. Biomarkers were significantly altered in patients with AF. The echocardiographic parameter septal PA-TDI, indicating left atrial (LA) remodelling, correlated with concentrations of sST2 (r = 0.249, p = 0.048), miR−21 (r = −0.277, p = 0.012), miR−29a (r = −0.269, p = 0.015), miR−146b (r = −0.319, p = 0.004) and miR−328 (r = −0.296, p = 0.008). In particular, NT-proBNP showed a strong correlation with echocardiographic markers of LA remodelling and dysfunction (septal PA-TDI: r = 0.444, p < 0.001, LAVI/a’: r = 0.457, p = 0.001, SRa: r = 0.581, p < 0.001). Multivariate Cox regressions analysis highlighted miR−21 and NT-proBNP as predictive markers for AF (miR−21: hazard ratio (HR) 0.16; 95% confidence interval (CI) 0.04–0.7, p = 0.009; NT-proBNP: HR 1.002 95%CI 1.001–1.004, p = 0.006). Combination of NT-proBNP and miR−21 had the best accuracy to discriminate patients with AF from those without AF (area under the curve (AUC)= 0.843). Our findings indicate that miR−21 and NT-proBNP correlate with echocardiographic parameters of atrial remodeling and predict AF, in particular if combined. Full article
(This article belongs to the Special Issue Cardiovascular Disease: New Generation of Biomarkers and Future Therapeutic Concepts)
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12 pages, 584 KiB  
Article
Galectin-3 is Associated with Cardiovascular Events in Post-Acute Coronary Syndrome Patients with Type-2 Diabetes
by Ana Lorenzo-Almorós, Ana Pello, Álvaro Aceña, Juan Martínez-Milla, Óscar González-Lorenzo, Nieves Tarín, Carmen Cristóbal, Luis M Blanco-Colio, José Luis Martín-Ventura, Ana Huelmos, Carlos Gutiérrez-Landaluce, Marta López-Castillo, Andrea Kallmeyer, Ester Cánovas, Joaquín Alonso, Lorenzo López Bescós, Jesús Egido, Óscar Lorenzo and Jose Tuñón
J. Clin. Med. 2020, 9(4), 1105; https://doi.org/10.3390/jcm9041105 - 13 Apr 2020
Cited by 13 | Viewed by 2479
Abstract
Introduction: Type-2 diabetes mellitus (T2DM) is associated with early and severe atherosclerosis. However, few biomarkers can predict cardiovascular events in this population. Methods: We followed 964 patients with coronary artery disease (CAD), assessing plasma levels of galectin-3, monocyte chemoattractant protein-1 (MCP-1), and N-terminal [...] Read more.
Introduction: Type-2 diabetes mellitus (T2DM) is associated with early and severe atherosclerosis. However, few biomarkers can predict cardiovascular events in this population. Methods: We followed 964 patients with coronary artery disease (CAD), assessing plasma levels of galectin-3, monocyte chemoattractant protein-1 (MCP-1), and N-terminal fragment of brain natriuretic peptide (NT-proBNP) at baseline. The secondary outcomes were acute ischemia and heart failure or death. The primary outcome was the combination of the secondary outcomes. Results. Two hundred thirty-two patients had T2DM. Patients with T2DM showed higher MCP-1 (144 (113–195) vs. 133 (105–173) pg/mL, p = 0.006) and galectin-3 (8.3 (6.5–10.5) vs. 7.8 (5.9–9.8) ng/mL, p = 0.049) levels as compared to patients without diabetes. Median follow-up was 5.39 years (2.81–6.92). Galectin-3 levels were associated with increased risk of the primary outcome in T2DM patients (Hazard ratio (HR) 1.57 (1.07–2.30); p = 0.022), along with a history of cerebrovascular events. Treatment with clopidogrel was associated with lower risk. In contrast, NT-proBNP and MCP-1, but not galectin-3, were related to increased risk of the event in nondiabetic patients (HR 1.21 (1.04–1.42); p = 0.017 and HR 1.23 (1.05–1.44); p = 0.012, respectively), along with male sex and age. Galectin-3 was also the only biomarker associated with the development of acute ischemic events and heart failure or death in T2DM patients, while, in nondiabetics, MCP-1 and NT-proBNP, respectively, were related to these events. Conclusion: In CAD patients, galectin-3 plasma levels are associated with cardiovascular events in patients with T2DM, and MCP-1 and NT-proBNP in those without T2DM. Full article
(This article belongs to the Special Issue Cardiovascular Disease: New Generation of Biomarkers and Future Therapeutic Concepts)
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8 pages, 1009 KiB  
Article
Upstroke Time Per Cardiac Cycle as A Novel Parameter for Mortality Prediction in Patients with Acute Myocardial Infarction
by Po-Chao Hsu, Wen-Hsien Lee, Wei-Chung Tsai, Ying-Chih Chen, Nai-Yu Chi, Ching-Tang Chang, Chun-Yuan Chu, Tsung-Hsien Lin, Chee-Siong Lee, Wen-Ter Lai, Sheng-Hsiung Sheu and Ho-Ming Su
J. Clin. Med. 2020, 9(4), 904; https://doi.org/10.3390/jcm9040904 - 25 Mar 2020
Cited by 3 | Viewed by 2418
Abstract
Background: Acute myocardial infarction (AMI) is one of the leading causes of death in the world. How to simply predict mortality for AMI patients is important because the appropriate treatment should be done for the patients with higher risk. Recently, a novel parameter [...] Read more.
Background: Acute myocardial infarction (AMI) is one of the leading causes of death in the world. How to simply predict mortality for AMI patients is important because the appropriate treatment should be done for the patients with higher risk. Recently, a novel parameter of upstroke time per cardiac cycle (UTCC) in lower extremities was reported to be a good predictor of peripheral artery disease and mortality in elderly. However, there was no literature discussing the usefulness of UTCC for prediction of cardiovascular (CV) and overall mortality in AMI patients. Methods: 184 AMI patients admitted to the cardiac care unit were enrolled. Ankle-brachial index (ABI) and UTCC were measured by an ABI-form device in the same day of admission. Results: The median follow-up to mortality was 71 months. There were 36 CV and 124 overall mortality. Higher UTCC was associated with increased CV and overall mortality after multivariable analysis (P = 0.033 and P < 0.001, respectively). However, ABI was only associated with CV mortality and overall mortality in the univariable analysis but became insignificant after the multivariable analysis. In addition, after adding UTCC into a basic model including important clinical parameters, left ventricular ejection fraction, Charlson comorbidity index, and ABI, we found the basic model + UTCC had a better predictive value for overall mortality than the basic model itself (P < 0.001). Conclusions: Our study is the first one to evaluate the usefulness of UTCC in AMI patients for prediction of long-term mortality. Our study showed UTCC was an independent predictor of long-term CV and overall mortality and had an additive predictive value for overall mortality beyond conventional parameters. Therefore, screening AMI patients by UTCC might help physicians to identify the high-risk group with increased mortality. Full article
(This article belongs to the Special Issue Cardiovascular Disease: New Generation of Biomarkers and Future Therapeutic Concepts)
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23 pages, 3241 KiB  
Article
A Case-Control Study of Salivary Redox Homeostasis in Hypertensive Children. Can Salivary Uric Acid be a Marker of Hypertension?
by Mateusz Maciejczyk, Katarzyna Taranta-Janusz, Anna Wasilewska, Agnieszka Kossakowska and Anna Zalewska
J. Clin. Med. 2020, 9(3), 837; https://doi.org/10.3390/jcm9030837 - 19 Mar 2020
Cited by 38 | Viewed by 2877
Abstract
Oxidative stress plays a critical role in the pathogenesis of hypertension; however, there are no data on salivary redox homeostasis and salivary gland function in children with hypertension. A total of 53 children with hypertension and age- and sex-matched controls were classified for [...] Read more.
Oxidative stress plays a critical role in the pathogenesis of hypertension; however, there are no data on salivary redox homeostasis and salivary gland function in children with hypertension. A total of 53 children with hypertension and age- and sex-matched controls were classified for the study. The antioxidant barrier and oxidative/nitrosative stress were evaluated in non-stimulated (NWS) and stimulated (SWS) whole saliva, plasma, and erythrocytes, with Student’s t-test and Mann–Whitney U-test used for statistical analysis. We demonstrated that the activities of superoxide dismutase, catalase, and peroxidase were significantly higher in NWS, SWS, and erythrocytes of children with hypertension, similar to oxidative damage in proteins (advanced glycation end products) and lipids (malondialdehyde) as well as nitrosative stress markers (peroxynitrite and nitrotyrosine). The level of uric acid (UA) was significantly higher in NWS, SWS, and plasma of children with hypertension. UA concentration in SWS correlated positively with systolic and diastolic blood pressure and UA content in plasma. This parameter differentiates children with hypertension from healthy controls (AUC = 0.98) with a high degree of sensitivity (94%) and specificity (94%). Stimulated salivary flow was significantly lower in the hypertension group, similar to total protein content and salivary amylase activity. In summary, childhood hypertension is associated with hyposalivation as well as disturbances in antioxidant defense and enhanced oxidative/nitrosative damage both in the plasma/erythrocytes as well as saliva. Salivary UA may be a potential biomarker of hypertension in children. Full article
(This article belongs to the Special Issue Cardiovascular Disease: New Generation of Biomarkers and Future Therapeutic Concepts)
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12 pages, 1110 KiB  
Article
Modulation of SERCA in Patients with Persistent Atrial Fibrillation Treated by Epicardial Thoracoscopic Ablation: The CAMAF Study
by Celestino Sardu, Gaetano Santulli, Germano Guerra, Maria Consiglia Trotta, Matteo Santamaria, Cosimo Sacra, Nicola Testa, Valentino Ducceschi, Gianluca Gatta, Michele D' Amico, Ferdinando Carlo Sasso, Giuseppe Paolisso and Raffaele Marfella
J. Clin. Med. 2020, 9(2), 544; https://doi.org/10.3390/jcm9020544 - 17 Feb 2020
Cited by 24 | Viewed by 2587
Abstract
Objectives: To evaluate atrial fibrillation (AF) recurrence and Sarcoplasmic Endoplasmic Reticulum Calcium ATPase (SERCA) levels in patients treated by epicardial thoracoscopic ablation for persistent AF. Background: Reduced levels of SERCA have been reported in the peripheral blood cells of patients with AF. We [...] Read more.
Objectives: To evaluate atrial fibrillation (AF) recurrence and Sarcoplasmic Endoplasmic Reticulum Calcium ATPase (SERCA) levels in patients treated by epicardial thoracoscopic ablation for persistent AF. Background: Reduced levels of SERCA have been reported in the peripheral blood cells of patients with AF. We hypothesize that SERCA levels can predict the response to epicardial ablation. Methods: We designed a prospective, multicenter, observational study to recruit, from October 2014 to June 2016, patients with persistent AF receiving an epicardial thoracoscopic pulmonary vein isolation. Results: We enrolled 27 patients. Responders (n = 15) did not present AF recurrence after epicardial ablation at one-year follow-up; these patients displayed a marked remodeling of the left atrium, with a significant reduction of inflammatory cytokines, B type natriuretic peptide (BNP), and increased levels of SERCA compared to baseline and to nonresponders (p < 0.05). Furthermore, mean AF duration (Heart rate (HR) 1.235 (1.037–1.471), p < 0.05), Left atrium volume (LAV) (HR 1.755 (1.126–2.738), p < 0.05), BNP (HR 1.945 (1.895–1.999), p < 0.05), and SERCA (HR 1.763 (1.167–2.663), p < 0.05) were predictive of AF recurrence. Conclusions: Our data indicate for the first time that baseline values of SERCA in patients with persistent AF might be predictive of failure to epicardial ablative approach. Intriguingly, epicardial ablation was associated with increased levels of SERCA in responders. Therefore, SERCA might be an innovative therapeutic target to improve the response to epicardial ablative treatments. Full article
(This article belongs to the Special Issue Cardiovascular Disease: New Generation of Biomarkers and Future Therapeutic Concepts)
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12 pages, 270 KiB  
Article
Soluble ST2 is a Useful Biomarker for Grading Cerebral–Cardiac Syndrome in Patients after Acute Ischemic Stroke
by Pei-Hsun Sung, Hung Sheng Lin, Kuan-Hung Chen, John Y. Chiang, Sheung-Fat Ko, Pei-Lin Shao, Hsin-Ju Chiang, Chi-Hsiang Chu, Yi-Chen Li, Han-Tan Chai, Kun-Chen Lin and Hon-Kan Yip
J. Clin. Med. 2020, 9(2), 489; https://doi.org/10.3390/jcm9020489 - 11 Feb 2020
Cited by 5 | Viewed by 2579
Abstract
This study tested whether the soluble (s)ST2 is a superb biomarker predictive of moderate to severe cerebral–cardiac syndrome (CCS) (defined as coexisting National Institute of Health Stroke Scale (NIHSS) >8 and left-ventricular ejection fraction (LVEF) <60%) in patients after acute ischemic stroke (IS). [...] Read more.
This study tested whether the soluble (s)ST2 is a superb biomarker predictive of moderate to severe cerebral–cardiac syndrome (CCS) (defined as coexisting National Institute of Health Stroke Scale (NIHSS) >8 and left-ventricular ejection fraction (LVEF) <60%) in patients after acute ischemic stroke (IS). Between November 2015 and October 2017, a total of 99 IS patients were prospectively enrolled and categorized into three groups based on NIHSS, i.e., group 1 (NIHSS ≤ 8, n = 66), group 2 (NIHSS = 9-15, n = 14) and group 3 (NIHSS ≥ 16, n = 19), respectively. Blood samples were collected immediately after hospitalization, followed by transthoracic echocardiographic examination. The results showed that the flow cytometric analysis for assessment of inflammatory biomarkers of TLR2+/CD14+cells, TLR4+/CD14+cells, Ly6g+/CD14+cells, and MPO+/CD14+cells, and ELISA assessment for circulatory level of sST2 were significantly higher in groups 2/3 than in group 1 (all p < 0.01). However, these parameters did not show significant differences between groups 2 and 3 (all p > 0.05). The LVEF was significantly lower in group 3 than in group 1 (p < 0.001), but it displayed no difference between groups 1/2 or between groups 2/3. These inflammatory biomarkers ((TLR2+/CD14+cells// TLR4+/CD14+cells// MPO+/CD14+cells) and sST2)) were significantly positively correlated to NIHSS and strongly negatively correlated to LVEF (all p < 0.05). Multivariate analysis demonstrated that both MPO/CD14+cells >20% (p = 0.027) and sST2 ≥ 17,600 (p = 0.004) were significantly and independently predictive of moderate-severe CCS after acute IS. Receiver operating characteristic curve analysis demonstrated that sST2 was the most powerful predictor of CCS with a sensitivity of 0.929 and a specificity of 0.731 (p < 0.001). In conclusion, sST2 is a useful biomarker for prediction of CCS severity in patients after acute IS. Full article
(This article belongs to the Special Issue Cardiovascular Disease: New Generation of Biomarkers and Future Therapeutic Concepts)
17 pages, 1047 KiB  
Article
Does Chronic Kidney Disease Facilitate Malignant Myocardial Fibrosis in Heart Failure with Preserved Ejection Fraction of Hypertensive Origin?
by Rocio Eiros, Gregorio Romero-González, Juan Jose Gavira, Oscar Beloqui, Inmaculada Colina, Manuel Fortún Landecho, Begoña López, Arantxa González, Javier Díez and Susana Ravassa
J. Clin. Med. 2020, 9(2), 404; https://doi.org/10.3390/jcm9020404 - 3 Feb 2020
Cited by 15 | Viewed by 2740
Abstract
In hypertensive patients with heart failure (HF) a serum biomarker combination of high carboxy-terminal propeptide of procollagen type-I (PICP) and low carboxy-terminal telopeptide of collagen type-I to matrix metalloproteinase-1 (CITP:MMP-1) ratio identifies a histomolecular phenotype of malignant myocardial fibrosis (mMF) associated with severe [...] Read more.
In hypertensive patients with heart failure (HF) a serum biomarker combination of high carboxy-terminal propeptide of procollagen type-I (PICP) and low carboxy-terminal telopeptide of collagen type-I to matrix metalloproteinase-1 (CITP:MMP-1) ratio identifies a histomolecular phenotype of malignant myocardial fibrosis (mMF) associated with severe diastolic dysfunction (DD) and poor outcomes. As chronic kidney disease (CKD) facilitates MF and DD, we investigated the influence of CKD on the mMF biomarker combination in HF patients with preserved ejection fraction (HFpEF). Hypertensives (n = 365), 232 non-HF and 133 HFpEF, were studied, and 35% non-HF and 46% HFpEF patients had CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m2 or urine albumin-to-creatinine ratio ≥ 30 mg/g). Specific immunoassays were performed to determine biomarkers. Medians were used to establish the high PICP and low CITP:MMP-1 combination. A comparison with non-HF showed that the biomarker combination presence was increased in HFpEF patients, being associated with CKD in all patients. CKD influenced the association of the biomarker combination and HFpEF (p for interaction ≤ 0.019). The E:e’ ratio was associated with the biomarker combination in CKD patients. Among CKD patients with HFpEF, those with the biomarker combination exhibited higher (p = 0.016) E:e’ ratio than those without the pattern. These findings suggest that CKD facilitates the development of biomarker-assessed mMF and DD in hypertensive HFpEF patients. Full article
(This article belongs to the Special Issue Cardiovascular Disease: New Generation of Biomarkers and Future Therapeutic Concepts)
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11 pages, 1403 KiB  
Article
Circulating PCSK9 Level and Risk of Cardiovascular Events and Death in Hemodialysis Patients
by Hyeon Seok Hwang, Jin Sug Kim, Yang Gyun Kim, So-Young Lee, Shin Young Ahn, Hong Joo Lee, Dong-Young Lee, Sang Ho Lee, Ju Young Moon and Kyung Hwan Jeong
J. Clin. Med. 2020, 9(1), 244; https://doi.org/10.3390/jcm9010244 - 17 Jan 2020
Cited by 18 | Viewed by 2624
Abstract
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a promising new target for the prevention of cardiovascular (CV) events. However, the clinical significance of circulating PCSK9 is unclear in hemodialysis (HD) patients. A total of 353 HD patients were prospectively enrolled from June 2016 [...] Read more.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a promising new target for the prevention of cardiovascular (CV) events. However, the clinical significance of circulating PCSK9 is unclear in hemodialysis (HD) patients. A total of 353 HD patients were prospectively enrolled from June 2016 to August 2019 in a K-cohort. Plasma PCSK9 level was measured at the time of study enrollment. The primary endpoint was defined as a composite of CV event and death. Plasma PCSK9 level was positively correlated with total cholesterol level in patients with statin treatment. Multivariate linear regression analysis revealed that baseline serum glucose, albumin, total cholesterol, and statin treatment were independent determinants of circulating PCSK9 levels. Cumulative rates of composite and CV events were significantly higher in patients with tertile 3 PCSK9 (p = 0.017 and p = 0.010, respectively). In multivariate Cox-regression analysis, PCSK9 tertile 3 was associated with a 1.97-fold risk of composite events (95% CI, 1.13–3.45), and it was associated with a 2.31-fold risk of CV events (95% CI, 1.17–4.59). In conclusion, a higher circulating PCSK9 level was independently associated with incident CV events and death in HD patients. These results suggest the importance of future studies regarding the effect of PCSK9 inhibition. Full article
(This article belongs to the Special Issue Cardiovascular Disease: New Generation of Biomarkers and Future Therapeutic Concepts)
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12 pages, 506 KiB  
Article
IgG Anti-High Density Lipoprotein Antibodies Are Elevated in Abdominal Aortic Aneurysm and Associated with Lipid Profile and Clinical Features
by Javier Rodríguez-Carrio, Jes S. Lindholt, Marina Canyelles, Diego Martínez-López, Mireia Tondo, Luis M. Blanco-Colio, Jean-Baptiste Michel, Joan Carles Escolà-Gil, Ana Suárez and José Luis Martín-Ventura
J. Clin. Med. 2020, 9(1), 67; https://doi.org/10.3390/jcm9010067 - 26 Dec 2019
Cited by 12 | Viewed by 3215
Abstract
High-density lipoproteins cholesterol (HDLc) levels are decreased in abdominal aortic aneurysm (AAA), which is hallmarked by autoimmunity and lipid aortic deposits. To investigate whether IgG anti-HDL antibodies were present in AAA and their potential association with clinical features, IgG anti-HDL and total IgG [...] Read more.
High-density lipoproteins cholesterol (HDLc) levels are decreased in abdominal aortic aneurysm (AAA), which is hallmarked by autoimmunity and lipid aortic deposits. To investigate whether IgG anti-HDL antibodies were present in AAA and their potential association with clinical features, IgG anti-HDL and total IgG along with HDLc plasma levels were measured in 488 AAA patients and 184 controls from the Viborg Vascular (VIVA) study, and in tissue-conditioned media from AAA intraluminal thrombus and media layer samples compared to control aortas. Higher IgG anti-HDL levels were found in AAA compared to controls, even after correcting for total IgG, and after adjusting for potential confounders. IgG anti-HDL levels were correlated with aortic diameter in univariate and adjusted multivariate analyses. IgG anti-HDL antibodies were negatively associated with HDLc levels before and after correcting for potential confounders. Increased anti-HDL antibodies were identified in tissue-conditioned media from AAA samples compared to healthy aortas, with higher levels being observed in the media layer. In conclusion, increased IgG anti-HDL levels (both in plasma and in tissue) are linked to AAA, associated with aortic diameter and HDLc levels. These data suggest a potential immune response against HDL in AAA and support an emerging role of anti-HDL antibodies in AAA. Full article
(This article belongs to the Special Issue Cardiovascular Disease: New Generation of Biomarkers and Future Therapeutic Concepts)
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Review

Jump to: Research

20 pages, 281 KiB  
Review
Statin Treatment in Specific Patient Groups: Role for Improved Cardiovascular Risk Markers
by Alyssa M. B. White, Hillary R. Mishcon, John L. Redwanski and Ronald D. Hills, Jr.
J. Clin. Med. 2020, 9(11), 3748; https://doi.org/10.3390/jcm9113748 - 21 Nov 2020
Cited by 2 | Viewed by 4842
Abstract
Ample evidence supports the use of statin therapy for secondary prevention in patients with a history of atherosclerotic cardiovascular disease (ASCVD), but evidence is wanting in the case of primary prevention, low-risk individuals, and elderly adults 65+. Statins are effective in lowering low-density [...] Read more.
Ample evidence supports the use of statin therapy for secondary prevention in patients with a history of atherosclerotic cardiovascular disease (ASCVD), but evidence is wanting in the case of primary prevention, low-risk individuals, and elderly adults 65+. Statins are effective in lowering low-density lipoprotein (LDL), which has long been a target for treatment decisions. We discuss the weakening dependence between cholesterol levels and mortality as a function of age and highlight recent findings on lipoprotein subfractions and other superior markers of ASCVD risk. The efficacy of statins is compared for distinct subsets of patients based on age, diabetes, ASCVD, and coronary artery calcium (CAC) status. Most cardiovascular risk calculators heavily weight age and overestimate one’s absolute risk of ASCVD, particularly in very old adults. Improvements in risk assessment enable the identification of specific patient populations that benefit most from statin treatment. Derisking is particularly important for adults over 75, in whom treatment benefits are reduced and adverse musculoskeletal effects are amplified. The CAC score stratifies the benefit effect size obtainable with statins, and forms of coenzyme Q are discussed for improving patient outcomes. Robust risk estimator tools and personalized, evidence-based approaches are needed to optimally reduce cardiovascular events and mortality rates through administration of cholesterol-lowering medications. Full article
(This article belongs to the Special Issue Cardiovascular Disease: New Generation of Biomarkers and Future Therapeutic Concepts)
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9 pages, 928 KiB  
Review
Genetic Variants as Sudden-Death Risk Markers in Inherited Arrhythmogenic Syndromes: Personalized Genetic Interpretation
by Oscar Campuzano, Georgia Sarquella-Brugada, Elena Arbelo, Sergi Cesar, Paloma Jordà, Alexandra Pérez-Serra, Rocío Toro, Josep Brugada and Ramon Brugada
J. Clin. Med. 2020, 9(6), 1866; https://doi.org/10.3390/jcm9061866 - 15 Jun 2020
Cited by 5 | Viewed by 2245
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Cardiovascular Disease: New Generation of Biomarkers and Future Therapeutic Concepts)
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31 pages, 1276 KiB  
Review
Title: Human Serum/Plasma Glycoprotein Analysis by 1H-NMR, an Emerging Method of Inflammatory Assessment
by Rocío Fuertes-Martín, Xavier Correig, Joan-Carles Vallvé and Núria Amigó
J. Clin. Med. 2020, 9(2), 354; https://doi.org/10.3390/jcm9020354 - 27 Jan 2020
Cited by 52 | Viewed by 5283
Abstract
Several studies suggest that variations in the concentration of plasma glycoproteins can influence cellular changes in a large number of diseases. In recent years, proton nuclear magnetic resonance (1H-NMR) has played a major role as an analytical tool for serum and [...] Read more.
Several studies suggest that variations in the concentration of plasma glycoproteins can influence cellular changes in a large number of diseases. In recent years, proton nuclear magnetic resonance (1H-NMR) has played a major role as an analytical tool for serum and plasma samples. In recent years, there is an increasing interest in the characterization of glycoproteins through 1H-NMR in order to search for reliable and robust biomarkers of disease. The objective of this review was to examine the existing studies in the literature related to the study of glycoproteins from an analytical and clinical point of view. There are currently several techniques to characterize circulating glycoproteins in serum or plasma, but in this review, we focus on 1H-NMR due to its great robustness and recent interest in its translation to the clinical setting. In fact, there is already a marker in H-NMR representing the acetyl groups of the glycoproteins, GlycA, which has been increasingly studied in clinical studies. A broad search of the literature was performed showing a general consensus that GlycA is a robust marker of systemic inflammation. The results also suggested that GlycA better captures systemic inflammation even more than C-reactive protein (CRP), a widely used classical inflammatory marker. The applications reviewed here demonstrated that GlycA was potentially a key biomarker in a wide range of diseases such as cancer, metabolic diseases, cardiovascular risk, and chronic inflammatory diseases among others. The profiling of glycoproteins through 1H-NMR launches an encouraging new paradigm for its future incorporation in clinical diagnosis. Full article
(This article belongs to the Special Issue Cardiovascular Disease: New Generation of Biomarkers and Future Therapeutic Concepts)
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