509 results on '"A. Fuster"'
Search Results
2. Abstract 15798: Clonal Hematopoiesis of Indeterminate Potential is Associated With Pro-Inflammatory Markers in Patients With Established Coronary Artery Disease
- Author
-
SINNADURAI, SIAMALA, Vazquez, Enrique, Diez-Diez, Miriam, Quintas, Ana, Barrera Martinez, Jorge de la, Kondraciuk, Marcin, Sawicka-Smiarowska, Emilia, Chlabicz, Malgorzata, Sharma, Hari S., van der Spek, Peter, Sanchez-Cabo, Fatima, Fuster, Jose J, Dopazo, Ana, and Kaminski, Karol
- Published
- 2023
- Full Text
- View/download PDF
3. Abstract 12895: Classification of Patients According to the Cardiometabolic-Based Chronic Disease Model in a Preventive Cardiology Center
- Author
-
Hernandez Sevillano, Jose Joel, Babagoli, Masih, Mellacheruvu, Pranav, Chen, Yitong, Liu, Shelley, Johnson, Janet, Fuster, Valentin, and mechanick, Jeffrey
- Published
- 2023
- Full Text
- View/download PDF
4. Abstract 12563: Is Cardiometabolic Risk Reduction Sustainable in Routine Practice?
- Author
-
Hernandez Sevillano, Jose Joel, Babagoli, Masih, Mellacheruvu, Pranav, Chen, Yitong, Liu, Shelley, Johnson, Janet, Fuster, Valentin, and mechanick, Jeffrey
- Published
- 2023
- Full Text
- View/download PDF
5. Abstract 15407: Benefits of the Sglt2 Inhibitor Empagliflozin on Epicardial Adipose Tissue in Non-Diabetic Hfref
- Author
-
Santosgallego, Carlos G, Requena-Ibanez, Juan Antonio, Picatoste Botija, Maria Belen, Ishikawa, Kiyotake, Sanz, Javier, Fuster, Valentin, and Badimon, Juan J
- Published
- 2022
- Full Text
- View/download PDF
6. Abstract 13499: Unravelling the Pathophysiology of Right Ventricular Maladaptive Hypertrophy in Chronic Pulmonary Hypertension Through Imaging and Omics
- Author
-
Garcia-Lunar, Ines, Pereda, Daniel, Jorge, Inmaculada, Saiz Galindo, Jorge, Solanes, Nuria, Ascaso, Maria, Galan, Carlos, Rodr?guez Arias, Juan J, Jiménez, Francisco Rafael, Nuche Berenguer, Jorge, Dantas, Ana Paula V, Morán, María, Camafeita, Emilio, Rigol, Montserrat, Barbas, Coral, Vazquez, Jesus, Fuster, Valentin, Ibanez, Borja, and Garcia-Alvarez, Ana
- Published
- 2022
- Full Text
- View/download PDF
7. Abstract 13063: Clonal Hematopoiesis Associated With TET2 and DNMT3A Gene Driver Mutations Accelerates Aortic Valve Calcification in vitro and in vivo
- Author
-
Abplanalp, Wesley T, Schuhmacher, Bianca, Mas-Peiro, Silvia, Zuriaga, María A, Matesanz, Nuria, Fuster, Jose J, John, David, Muhly-Reinholz, Marion, Vasa-Nicotera, Mariuca, Merten, Maximilian, Hoffmann, Jedrzej, Zeiher, Andreas M, and Dimmeler, Stefanie
- Published
- 2022
- Full Text
- View/download PDF
8. Abstract 17275: The SGLT2 Inhibitor Empagliflozin Ameliorates Left Atrial Dilatation in Non-Diabetic Patients With Heart Failure With Reduced Ejection Fraction: A Secondary Analysis of the EMPATROPISM Trial
- Author
-
Santosgallego, Carlos G, Requena-Ibanez, Juan Antonio, Vargas, Ariana, Garcia-Ropero, Alvaro, Rodriguez-Cordero, Anderly, Pinney, Sean, MANCINI, Donna M, Lala, Anuradha, Contreras, Johanna P, Moreno, Pedro R, SANZ, Javier, Fuster, Valentin, and Badimon, Juan J
- Published
- 2020
- Full Text
- View/download PDF
9. Abstract 17157: The SGLT2 Inhibitor Empagliflozin Ameliorates Interstitial Myocardial Fibrosis and Aortic Stiffness in Non-Diabetic Patients With Heart Failure With Reduced Ejection Fraction: A Secondary Analysis of the EMPATROPISM Trial
- Author
-
Santosgallego, Carlos G, Requena-Ibanez, Juan Antonio, Vargas, Ariana P, Garcia-Ropero, Alvaro, Rodriguez-Cordero, Anderly, MANCINI, Donna M, Pinney, Sean, Lala, Anuradha, Contreras, Johanna P, Moreno, Pedro R, SANZ, Javier, Fuster, Valentin, and Badimon, Juan J
- Published
- 2020
- Full Text
- View/download PDF
10. Abstract 15096: Electrocardiographic QRS Amplitude Predicts Mortality in Hospitalized Patients With CoViD-19
- Author
-
Lampert, Joshua, Halperin, Jonathan, Giustino, Gennaro, Oates, Connor, Nelson, Kyle, Feinman, Jason, Pulaski, Matthew, Musikantow, Daniel, Turagam, Mohit, Miller, Michael, langan, marie-noelle, Koruth, jacob s, Dukkipati, Srinivas, Miller, Marc, Whang, William, Goldman, Martin, Fuster, Valentin, and Reddy, Vivek Y
- Published
- 2020
- Full Text
- View/download PDF
11. Oxidized Low-Density Lipoprotein Receptor in Lymphocytes Prevents Atherosclerosis and Predicts Subclinical Disease
- Author
-
Tsilingiri, Katerina, de la Fuente, Hortensia, Relaño, Marta, Sánchez-Díaz, Raquel, Rodríguez, Cristina, Crespo, Javier, Sánchez-Cabo, Fátima, Dopazo, Ana, Alonso-Lebrero, José L., Vara, Alicia, Vázquez, Jesús, Casasnovas, José M., Alfonso, Fernando, Ibáñez, Borja, Fuster, Valentín, Martínez-González, José, Martín, Pilar, and Sánchez-Madrid, Francisco
- Published
- 2019
- Full Text
- View/download PDF
12. Response by Fernández-Jiménez et al to Letters Regarding Article, “Dynamic Edematous Response of the Human Heart to Myocardial Infarction: Implications for Assessing Myocardial Area at Risk and Salvage”
- Author
-
Fernández-Jiménez, Rodrigo, Martin-García, Ana, Barreiro-Pérez, Manuel, Sánchez-González, Javier, Fuster, Valentin, Sánchez, Pedro L., and Ibanez, Borja
- Published
- 2018
- Full Text
- View/download PDF
13. Abstract 20214: Ethnic Disparities in Metabolic Syndrome Among Caregivers of Preschool Children in a Community-Based Trial
- Author
-
Latina, Jacqueline M, Fernandez-Jimenez, Rodrigo, Bansilal, Sameer, Vedanthan, Rajesh, Soto, Ana V, Jaslow, Risa, Santana, Maribel, Cortez, Briana, Schulman, Alexa, Fatterpekar, Monali, Hajjar, Roger, Kasarskis, Andrew, Fayad, Zahi A, and Fuster, Valentin
- Published
- 2017
14. Abstract 19046: The Role of the SYNTAX Score in Predicting Clinical Outcome in Diabetic Patients After Percutaneous Coronary Intervention and Coronary Artery Bypass Graft: A FREEDOM Trial Sub-analysis
- Author
-
Esper, Rodrigo B, Ribeiro, Expedito E, Hueb, Whady, Domanski, Michael, Hamza, Taye, Siami, Sandi, Farkouh, Michael E, and Fuster, Valentin
- Published
- 2017
15. Abstract 16764: A Human-Centered Design Approach to Develop a Microfinance and Group Medical Visit Model for Cardiovascular Risk Reduction in Western Kenya (BIGPIC Study)
- Author
-
Leung, Claudia, Naert, Mackenzie, Andama, Benjamin, Dong, Rae, Edelman, David, Horowitz, Carol, Kiptoo, Peninah, Manyara, Simon, Matelong, Winnie, Matini, Esther, Naanyu, Violet, Nyariki, Sarah, Pastakia, Sonak, Valente, Thomas, Fuster`, Valentin, Bloomfield, Gerald S, Kamano, Jemima, and Vedanthan, Rajesh
- Published
- 2017
16. Dynamic Edematous Response of the Human Heart to Myocardial Infarction: Implications for Assessing Myocardial Area at Risk and Salvage
- Author
-
Fernández-Jiménez, Rodrigo, Barreiro-Pérez, Manuel, Martin-García, Ana, Sánchez-González, Javier, Agüero, Jaume, Galán-Arriola, Carlos, García-Prieto, Jaime, Díaz-Pelaez, Elena, Vara, Pedro, Martinez, Irene, Zamarro, Ivan, Garde, Beatriz, Sanz, Javier, Fuster, Valentin, Sánchez, Pedro L., and Ibanez, Borja
- Published
- 2017
- Full Text
- View/download PDF
17. Abstract EP39: Examining Capabilities, Opportunity, And Motivation For Healthy Eating Behaviors In Latin American Restaurants: A Quantitative Application Of The COM-B Model To Inform Future Interventions
- Author
-
Melissa Fuster, Maria Santos, Terry T Huang, and Margaret A Handley
- Subjects
Physiology (medical) ,Cardiology and Cardiovascular Medicine - Abstract
Introduction: Latin American restaurants (LARs) are an increasingly important food source with the potential to positively influence diets to promote cardiovascular health. Yet, modifiable factors influencing food choices in LARs remain unclear. Determinants frameworks, such as the Capabilities, Opportunities, and Motivation for Behavior (COM-B Model) can help identify key drivers of dietary behaviors for informing intervention design. Objectives: (1) Apply the COM-B model to understand healthy eating behavior at LARs; (2) Examine differences in COM-B factors by ethnicity (Latin/Hispanic background), age, income, gender, and education. Methods: We developed a Likert scale to quantitatively assess the capabilities (physical and psychological), opportunities (social and physical), and motivation (reflective and automatic) factors associated with healthy eating in LARs. The scale was applied as part of an online survey with adults in the United States that reported eating food from LARs at least once a month (n=509). Bivariate analyses were used to examine the association between COM-B scores and demographic characteristics. Results: Within a possible range of 0-12, the mean COM-B total score was 7.35±1.97. Higher overall scores were significantly associated with being from a Latin background (p=0.04) and having a higher income (p=0.02). Within a possible range of 0-2 for COM-B area scores, the lowest score was found for Psychological Capability (0.95±0.97), where higher mean scores were found among men (p=0.03), older age (p=0.04), and those with higher education (p Conclusions: This work addresses a research gap to inform future interventions to improve community food environments through work with LARs. The application of the COM-B revealed areas for intervention, particularly the need to improve knowledge (Psychological Capability) and social opportunity, the areas with the lowest scores, to promote healthier eating behaviors at LARs. Future research can be used to promote innovative ways to change perceptions of Latin foods in LARs and awareness of existing healthy offerings, which at the same time may help motivate LARs owners in increasing healthy offerings.
- Published
- 2022
18. Abstract EP39: Examining Capabilities, Opportunity, And Motivation For Healthy Eating Behaviors In Latin American Restaurants: A Quantitative Application Of The COM-B Model To Inform Future Interventions
- Author
-
Fuster, Melissa, primary, Santos, Maria, additional, Huang, Terry T, additional, and Handley, Margaret A, additional
- Published
- 2022
- Full Text
- View/download PDF
19. Abstract 17275: The SGLT2 Inhibitor Empagliflozin Ameliorates Left Atrial Dilatation in Non-Diabetic Patients With Heart Failure With Reduced Ejection Fraction: A Secondary Analysis of the EMPATROPISM Trial
- Author
-
Sean Pinney, Johanna Contreras, Valentin Fuster, Carlos G. Santos-Gallego, Alvaro Garcia-Ropero, Anderly Rodriguez-Cordero, Pedro R. Moreno, Ariana P Vargas, Juan Antonio Requena-Ibanez, Anuradha Lala, Donna M. Mancini, Javier Sanz, and Juan J. Badimon
- Subjects
medicine.medical_specialty ,Ejection fraction ,business.industry ,medicine.disease ,Left atrial dilatation ,Physiology (medical) ,Diabetes mellitus ,Secondary analysis ,Heart failure ,Internal medicine ,medicine ,Empagliflozin ,Cardiology ,SGLT2 Inhibitor ,Cardiology and Cardiovascular Medicine ,business ,Non diabetic - Abstract
Background: SGLT2 inhibitors (SGLT2i) improve prognosis in HFrEF patients. We recently demonstrated in a porcine model of non-diabetic HFrEF that empagliflozin (EMPA) ameliorates adverse cardiac remodeling and improves LV systolic function. However, the effect of EMPA on left atrial (LA) dilatation has not yet been studied Hypothesis:: Empagliflozin ameliorates left atrial dilatation in non-diabetic HFrEF patients Methods: The EMPATROPISM clinical trial investigated the efficacy and safety of EMPA in non-diabetic HFrEF patients. 84 patients were randomized to EMPA 10mg daily for 6 months or placebo on top of optimal medical treatment, and were evaluated with cardiac magnetic resonance (CMR). LA Volumes were quantified by CMR using the Simpson method (the number of slices in the usual short axis SSFP cine sequence was increased to cover both LV and the whole of LA. The primary endpoint was change in LVEDV. Prespecified secondary endpoints were changes in maximal and minimal LA volumes (ΔMax LA Vol and ΔMin LA Vol) at the end of 6 months between both arms Results: 80 patients completed the follow up period. There were no differences at baseline in LVEDV (220±75 vs 209±68mL for EMPA vs placebo, p=0.5) or LVEF (36±8 vs 37±8%, p=0.7). There were no differences at baseline in both groups in either maximal or minimal LA volume (Table). In the primary endpoint, EMPA-treated patients showed decrease in LVEDV and increase in LVEF (ΔLVEDV -25±25 vs -1±25mL, p Conclusions: In HFrEF patients without diabetes, treatment with empagliflozin ameliorates left atrial dilatation. As LA volume is a surrogate for chronic filling pressures, this reduced LA volume suggest improved diastolic function with EMPA
- Published
- 2020
20. Abstract 17157: The SGLT2 Inhibitor Empagliflozin Ameliorates Interstitial Myocardial Fibrosis and Aortic Stiffness in Non-Diabetic Patients With Heart Failure With Reduced Ejection Fraction: A Secondary Analysis of the EMPATROPISM Trial
- Author
-
Pedro R. Moreno, Ariana P Vargas, Carlos G. Santos-Gallego, Javier Sanz, Donna M. Mancini, Juan J. Badimon, Sean Pinney, Valentin Fuster, Alvaro Garcia-Ropero, Anderly Rodriguez-Cordero, Johanna Contreras, Anuradha Lala, and Juan Antonio Requena-Ibanez
- Subjects
medicine.medical_specialty ,Ejection fraction ,business.industry ,medicine.disease ,Fibrosis ,Physiology (medical) ,Diabetes mellitus ,Heart failure ,Internal medicine ,Empagliflozin ,medicine ,Cardiology ,Aortic stiffness ,Myocardial fibrosis ,SGLT2 Inhibitor ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background: SGLT2 inhibitors (SGLT2i) improve prognosis in HFrEF patients. We recently demonstrated in a porcine model of non-diabetic HFrEF that empagliflozin (EMPA) ameliorates adverse cardiac remodeling and improves LV systolic function. However, the effect of EMPA on interstitial myocardial fibrosis (IMF) and aortic stiffness has not yet been studied Hypothesis: Empagliflozin ameliorates IMF and aortic stiffness in non-diabetic HFrEF patients Methods: The EMPATROPISM clinical trial (NCT 03485222) investigated the efficacy and safety of EMPA in non-diabetic HFrEF patients. 84 patients were randomized to EMPA 10mg daily for 6 months or placebo on top of optimal medical treatment, and were evaluated with cardiac magnetic resonance (CMR). IMF was assessed by CMR using extracellular volume (ECV) by T1 mapping. Aortic stiffness was quantified by pulse wave velocity (PWV) by CMR. The primary endpoint was change in LVEDV. Prespecified secondary endpoints were changes in ECV (ΔECV) and PWV (ΔPWV) at 6 months between both arms Results: 80 patients completed the follow up period. There were no differences at baseline in LVEDV (220±75 vs 209±68mL for EMPA vs placebo, p=0.5) or LVEF (36±8 vs 37±8%, p=0.7). There were no differences at baseline in both groups in either ECV or PWV (Table). In the primary endpoint, EMPA-treated patients showed decrease in LVEDV and increase in LVEF (ΔLVEDV -25±25 vs -1±25mL, p Conclusions: In HFrEF patients without diabetes, treatment with empagliflozin ameliorates IMF and aortic stiffness. This may explain the benefits of SGLT2i in HFrEF even in the absence of diabetes
- Published
- 2020
21. Abstract 15096: Electrocardiographic QRS Amplitude Predicts Mortality in Hospitalized Patients With CoViD-19
- Author
-
William Whang, Jonathan L. Halperin, Michael Miller, Valentin Fuster, Marc A. Miller, C. Oates, Marie-Noelle Langan, Mohit K. Turagam, Martin E. Goldman, Gennaro Giustino, Vivek Y. Reddy, Jacob S. Koruth, Matthew Pulaski, Joshua A. Lampert, Daniel Musikantow, Jason Feinman, Kyle Nelson, and Srinivas Dukkipati
- Subjects
medicine.medical_specialty ,Poor prognosis ,Coronavirus disease 2019 (COVID-19) ,medicine.diagnostic_test ,Hospitalized patients ,business.industry ,QRS complex ,Voltage amplitude ,Amplitude ,Physiology (medical) ,Internal medicine ,medicine ,Cardiology ,Cardiology and Cardiovascular Medicine ,business ,Electrocardiography - Abstract
Introduction: In a variety of cardiovascular diseases, low QRS voltage amplitude on the 12-lead ECG is associated with poor prognosis. We studied the relative frequency and importance of this phenomenon in hospitalized patients with SARS-coronavirus 2019 (CoViD-19) - a condition associated with myocardial injury in ~1/3 of patients. Methods: We performed a retrospective analysis of 800 consecutive patients with laboratory-confirmed CoViD-19 hospitalized from Mar 7 and Apr 12, 2020. Patients without a final disposition or telemetry data were excluded, resulting in 140 patients. On 12-lead ECG, low amplitude was defined as QRS amplitude Results: Among 140 patients, 33 (23.6%) met criteria for low QRS amplitude. Compared to patients without low amplitude, these patients had a higher risk of in-hospital mortality (72.7% vs 26.2%; p Conclusions: A reduction in electrocardiographic QRS amplitude in patients with CoViD-19 is the strongest clinical predictor of death, and may be useful for risk stratification during hospitalization. Further study is needed to elucidate the mechanisms underlying changes in QRS amplitude, and their relationship to disease severity.
- Published
- 2020
22. Abstract 17367: Infusion of the Ketone Body β-Hydroxybutyrate Improves Left Ventricular Systolic Function in an Animal Model of Heart Failure With Reduced Ejection Fraction
- Author
-
Carlos G SantosGallego, Juan Antonio Requena-Ibanez, Rodolfo San Antonio, Kiyotake Ishikawa, Belén Picatoste, Alvaro Garcia-Ropero, Javier Sanz, Roger Hajjar, Valentin Fuster, and Juan J Badimon
- Subjects
Physiology (medical) ,Cardiology and Cardiovascular Medicine - Abstract
Introduction: In vitro, ketone bodies (KB) are the most energetically efficient fuel for myocardium. Ex vivo, KB infusion in the perfusion medium of working rat hearts increases the heat of combustion (produced energy) by 31%. However, there is no report about the in vivo effects of KB on LV function. We hypothesized that KB infusion in HFREF would improve energy production and thus LV systolic function. Methods: HFREF was induced in 15 pigs by 2-hour balloon occlusion of LAD: proximal LAD (n=8, severe HREF) and mid LAD (n=7, moderate HFREF). At 2 months, LV systolic function was evaluated during saline infusion and during infusion of the KB β-hydroxybutyrate. Severe HFREF animals underwent cardiac MRI for baseline LVEF, feature tracking strains, and contractile reserve (ΔLVEF under dobutamine 5μg/kg/min). Moderate HFREF pigs underwent invasive hemodynamic assessment (dP/dt) and 3D-echocadiography (3D-LVEF and 3D-strains). Simultaneous sampling from coronary artery and coronary sinus was performed to measure myocardial fuel consumption. Results: Proximal and mid LAD occlusion resulted in severe and moderate LV systolic dysfunction, respectively. In the severe HFREF, ketone infusion improved baseline LVEF, feature-tracking strains (both longitudinal and circumferencial strain), and contractile reserve. In the moderate HFREF, ketone infusion improved 3D-LVEF, 3D-strains and dP/dt (Table). Ketone infusion switched myocardial metabolism from glucose to ketone consumption. Conclusions: Continuous infusion of the KB hydroxybutyrate improves LV systolic function independent of LV systolic dysfunction severity via a shift in myocardial fuel metabolism away from glucose oxidation (energy inefficient) toward a more energy-efficient fuel like KB. This effect can explain the mechanism of action of the benefits of SGLT2 inhibitors in heart failure, as empagliflozin-induced mild kyperketonemia may increase LV systolic function and thus improve patient outcomes.
- Published
- 2018
23. Household Fuel Use and Cardiovascular Disease Mortality
- Author
-
Christian C. Abnet, Sanford M. Dawsey, Farin Kamangar, Valentin Fuster, Reza Malekzadeh, Farhad Islami, Paolo Boffetta, Paul Brennan, Sumeet S. Mitter, Hooman Khademi, Rajesh Vedanthan, Akram Pourshams, and Paul D. Pharoah
- Subjects
Adult ,Male ,medicine.medical_specialty ,Air pollution ,030204 cardiovascular system & hematology ,010501 environmental sciences ,medicine.disease_cause ,01 natural sciences ,Article ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Physiology (medical) ,Environmental health ,Epidemiology ,medicine ,Humans ,Risk factor ,Stroke ,Disease burden ,Aged ,0105 earth and related environmental sciences ,Air Pollutants ,business.industry ,Disease mortality ,Environmental Exposure ,Environmental exposure ,Middle Aged ,medicine.disease ,Cardiovascular Diseases ,Female ,Cardiology and Cardiovascular Medicine ,business ,Fuel Oils ,Cohort study - Abstract
Background— Household air pollution is the third largest risk factor for global disease burden, but direct links with cardiovascular disease mortality are limited. This study aimed to evaluate the relationship between household fuel use and cardiovascular disease mortality. Methods and Results— The Golestan Cohort Study in northeastern Iran enrolled 50 045 individuals 40 to 75 years of age between 2004 and 2008 and collected data on lifetime household fuel use and other baseline exposures. Participants were followed up through 2012 with a 99% successful follow-up rate. Cox proportional hazards models were fitted to calculate hazard ratios for associations between pehen (local dung), wood, kerosene/diesel, or natural gas burning for cooking and heating and all-cause and cause-specific mortality, with adjustment for lifetime exposure to each of these fuels and potential confounders. A total of 3073 participants (6%) died during follow-up; 78% of these deaths were attributable to noncommunicable diseases, including cardiovascular, oncological, and respiratory illnesses. Adjusted 10-year hazard ratios from kerosene/diesel burning were 1.06 (95% confidence interval, 1.02–1.10) and 1.11 (95% confidence interval, 1.06–1.17) for all-cause and cardiovascular mortality, respectively. Subtype-specific analyses revealed a significant increase in ischemic heart disease (10-year hazard ratio, 1.14; 95% confidence interval, 1.06–1.21) and a trend toward cerebrovascular accident (10-year hazard ratio, 1.08; 95% confidence interval, 0.99–1.17) mortality. Stratification by sex revealed a potential signal for increased risk for all-cause and cardiovascular disease mortality among women compared with men, with similar risk for ischemic heart disease mortality. Conclusions— Household exposure to high-pollution fuels was associated with increased risk for all-cause and cardiovascular disease mortality. Replicating these results worldwide would support efforts to reduce such exposures.
- Published
- 2016
24. Response by Fernández-Jiménez et al to Letters Regarding Article, 'Dynamic Edematous Response of the Human Heart to Myocardial Infarction: Implications for Assessing Myocardial Area at Risk and Salvage'
- Author
-
Manuel Barreiro-Pérez, Rodrigo Fernández-Jiménez, Javier Sánchez-González, Borja Ibanez, Ana Martín-García, Pedro L. Sánchez, and Valentin Fuster
- Subjects
medicine.medical_specialty ,Myocardial Infarction ,Myocardial edema ,030204 cardiovascular system & hematology ,030218 nuclear medicine & medical imaging ,Clinical study ,Area at risk ,03 medical and health sciences ,0302 clinical medicine ,Physiology (medical) ,Internal medicine ,Edema ,medicine ,Humans ,In patient ,Myocardial infarction ,business.industry ,Myocardium ,Human heart ,Heart ,medicine.disease ,Cardiology ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,Cardiac magnetic resonance ,business - Abstract
We are grateful to Stiermaier et al, Sacha and Feusette, and Bulluck and Hausenloy for their interest and comments on our article,1 in which we showed that myocardial edema in the week after ST-segment–elevation myocardial infarction in humans is a bimodal phenomenon. We concur with Stiermaier et al on the implications of our findings, and the need to put these data into perspective. Indeed, in the discussion of our paper, we speculated on the potential explanations for divergent findings in the literature. It is important to note that our clinical study was specifically designed to validate the hypothesis generated in previous experimental studies,2,3 and thus the timing for each cardiac magnetic resonance (CMR) was exquisitely chosen. Thus, we first analyzed the dynamics of the initial wave of edema (online-only Data Supplement Figure I from Fernandez-Jimenez et al)1 to define the optimal timing for the first CMR scan in patients and not miss the initial wave of edema. The fact that this initial wave of edema peaks very early, and is significantly attenuated …
- Published
- 2018
25. Abstract 17367: Infusion of the Ketone Body β-Hydroxybutyrate Improves Left Ventricular Systolic Function in an Animal Model of Heart Failure With Reduced Ejection Fraction
- Author
-
SantosGallego, Carlos G, primary, Requena-Ibanez, Juan Antonio, additional, San Antonio, Rodolfo, additional, Ishikawa, Kiyotake, additional, Picatoste, Belén, additional, Garcia-Ropero, Alvaro, additional, Sanz, Javier, additional, Hajjar, Roger, additional, Fuster, Valentin, additional, and Badimon, Juan J, additional
- Published
- 2018
- Full Text
- View/download PDF
26. Abstract 16663: Child Health Promotion in Underserved Communities: Primary Results From the Cluster Randomized FAMILIA Trial
- Author
-
Fernandez-Jimenez, Rodrigo, primary, Jaslow, Risa, additional, Bansilal, Sameer, additional, Santana, Maribel, additional, Diaz-Munoz, Raquel, additional, Trabal, Giselle, additional, Latina, Jacqueline, additional, Soto, Ana V, additional, Vedanthan, Rajesh, additional, Giannarelli, Chiara, additional, Kovacic, Jason, additional, Bagiella, Emilia, additional, Kasarskis, Andrew, additional, Fayad, Zahi, additional, Hajjar, Roger J, additional, and Fuster, Valentin, additional
- Published
- 2018
- Full Text
- View/download PDF
27. Prevalence, Vascular Distribution, and Multiterritorial Extent of Subclinical Atherosclerosis in a Middle-Aged Cohort
- Author
-
Henrik Sillesen, Belén Oliva, Vicente Martinez de Vega, Jose M. Ordovas, Ginés Sanz, Jesús Molina, Luis Jesús Jiménez-Borreguero, Beatriz López-Melgar, Antonio Fernández-Ortiz, Javier Sánchez-González, Agustin Mocoroa, Stuart J. Pocock, José L. Peñalvo, Borja Ibanez, Martín Laclaustra, Juan C. Alonso-Farto, Gabriela Guzmán, Eliseo Guallar, Leticia Fernández-Friera, José M. Mendiguren, Fernando Civeira, Valentin Fuster, Laura García, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Banco Santander, Ministerio de Economía y Competitividad (España), Fundación ProCNIC, and Centro Nacional de Investigaciones Cardiovasculares Carlos III (España)
- Subjects
Carotid Artery Diseases ,Male ,Pathology ,population ,multidetector computed tomography ,Comorbidity ,Coronary Artery Disease ,Coronary Angiography ,Risk Factors ,Epidemiology ,Prevalence ,Aorta, Abdominal ,Prospective Studies ,Ultrasonography ,Subclinical infection ,education.field_of_study ,Age Factors ,Calcinosis ,risk assessment ,ultrasonography ,Middle Aged ,Plaque, Atherosclerotic ,Femoral Artery ,Cohort ,Disease Progression ,Female ,epidemiology ,Cardiology and Cardiovascular Medicine ,Adult ,medicine.medical_specialty ,Population ,Aortic Diseases ,Aortography ,Iliac Artery ,Physiology (medical) ,Internal medicine ,Multidetector Computed Tomography ,Multidetector computed tomography ,medicine ,Humans ,Distribution (pharmacology) ,Ankle Brachial Index ,education ,business.industry ,Atherosclerosis ,Spain ,Subclinical atherosclerosis ,Asymptomatic Diseases ,atherosclerosis ,business ,Follow-Up Studies - Abstract
Background— Data are limited on the presence, distribution, and extent of subclinical atherosclerosis in middle-aged populations. Methods and Results— The PESA (Progression of Early Subclinical Atherosclerosis) study prospectively enrolled 4184 asymptomatic participants 40 to 54 years of age (mean age, 45.8 years; 63% male) to evaluate the systemic extent of atherosclerosis in the carotid, abdominal aortic, and iliofemoral territories by 2-/3-dimensional ultrasound and coronary artery calcification by computed tomography. The extent of subclinical atherosclerosis, defined as presence of plaque or coronary artery calcification ≥1, was classified as focal (1 site affected), intermediate (2–3 sites), or generalized (4–6 sites) after exploration of each vascular site (right/left carotids, aorta, right/left iliofemorals, and coronary arteries). Subclinical atherosclerosis was present in 63% of participants (71% of men, 48% of women). Intermediate and generalized atherosclerosis was identified in 41%. Plaques were most common in the iliofemorals (44%), followed by the carotids (31%) and aorta (25%), whereas coronary artery calcification was present in 18%. Among participants with low Framingham Heart Study (FHS) 10-year risk, subclinical disease was detected in 58%, with intermediate or generalized disease in 36%. When longer-term risk was assessed (30-year FHS), 83% of participants at high risk had atherosclerosis, with 66% classified as intermediate or generalized. Conclusions— Subclinical atherosclerosis was highly prevalent in this middle-aged cohort, with nearly half of the participants classified as having intermediate or generalized disease. Most participants at high FHS risk had subclinical disease; however, extensive atherosclerosis was also present in a substantial number of low-risk individuals, suggesting added value of imaging for diagnosis and prevention. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01410318.
- Published
- 2015
28. Alternatively Spliced Tissue Factor Promotes Plaque Angiogenesis Through the Activation of Hypoxia-Inducible Factor-1α and Vascular Endothelial Growth Factor Signaling
- Author
-
Dongtak Jeong, Dong Kwon Yang, Jason C. Kovacic, Gerald A. Soff, Antoine Millon, Claudia Calcagno, Thomas Weber, Juan J. Badimon, Valentin Fuster, Zahi A. Fayad, Roger J. Hajjar, Chiara Giannarelli, David T. Rodriguez, Peter L. Faries, Matilde Alique, and Randolph Hutter
- Subjects
Male ,Vascular Endothelial Growth Factor A ,Pathology ,medicine.medical_specialty ,Angiogenesis ,Integrin ,Article ,Thromboplastin ,Neovascularization ,Mice ,chemistry.chemical_compound ,Tissue factor ,Apolipoproteins E ,Downregulation and upregulation ,Neointima ,Physiology (medical) ,medicine ,Animals ,Humans ,Protein kinase B ,Neovascularization, Pathologic ,biology ,Hypoxia-Inducible Factor 1, alpha Subunit ,Coronary Vessels ,Plaque, Atherosclerotic ,Up-Regulation ,Mice, Inbred C57BL ,Vascular endothelial growth factor ,Alternative Splicing ,Disease Models, Animal ,Carotid Arteries ,chemistry ,Hypoxia-inducible factors ,biology.protein ,Cancer research ,Endothelium, Vascular ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,Signal Transduction - Abstract
Background— Alternatively spliced tissue factor (asTF) is a novel isoform of full-length tissue factor, which exhibits angiogenic activity. Although asTF has been detected in human plaques, it is unknown whether its expression in atherosclerosis causes increased neovascularization and an advanced plaque phenotype. Methods and Results— Carotid (n=10) and coronary (n=8) specimens from patients with stable or unstable angina were classified as complicated or uncomplicated on the basis of plaque morphology. Analysis of asTF expression and cell type–specific expression revealed a strong expression and colocalization of asTF with macrophages and neovessels within complicated, but not uncomplicated, human plaques. Our results showed that the angiogenic activity of asTF is mediated via hypoxia-inducible factor-1α upregulation through integrins and activation of phosphatidylinositol-3-kinase/Akt and mitogen-activated protein kinase pathways. Hypoxia-inducible factor-1α upregulation by asTF also was associated with increased vascular endothelial growth factor expression in primary human endothelial cells, and vascular endothelial growth factor–Trap significantly reduced the angiogenic effect of asTF in vivo. Furthermore, asTF gene transfer significantly increased neointima formation and neovascularization after carotid wire injury in ApoE −/− mice. Conclusions— The results of this study provide strong evidence that asTF promotes neointima formation and angiogenesis in an experimental model of accelerated atherosclerosis. Here, we demonstrate that the angiogenic effect of asTF is mediated via the activation of the hypoxia-inducible factor-1/vascular endothelial growth factor signaling. This mechanism may be relevant to neovascularization and the progression and associated complications of human atherosclerosis as suggested by the increased expression of asTF in complicated versus uncomplicated human carotid and coronary plaques.
- Published
- 2014
29. Early Metoprolol Administration Before Coronary Reperfusion Results in Increased Myocardial Salvage
- Author
-
Javier Sanz, Juan J. Badimon, Gemma Vilahur, Mario J. Garcia, Borja Ibanez, Susanna Prat-Gonzalez, Valentin Fuster, Walter S. Speidl, Antonio Pinero, Giovanni Cimmino, Ibanez, Borja, Prat González, Susanna, Speidl, Walter S., Vilahur, Gemma, Pinero, Antonio, Cimmino, Giovanni, García, Mario J., Fuster, Valentin, Sanz, Javier, and Badimon, Juan J.
- Subjects
medicine.medical_specialty ,Physiology ,Swine ,medicine.medical_treatment ,Myocardial Infarction ,Myocardial Ischemia ,Ischemia ,Myocardial Reperfusion ,Antiarrhythmic agent ,Coronary reperfusion ,Imaging ,Necrosis ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Myocardial infarction ,Metoprolol ,medicine.diagnostic_test ,Animal ,business.industry ,Stroke Volume ,Magnetic resonance imaging ,Stroke volume ,Necrosi ,medicine.disease ,Magnetic Resonance Imaging ,Anesthesia ,Cardiology ,Cardiology and Cardiovascular Medicine ,Cardiac magnetic resonance ,business ,medicine.drug - Abstract
Background— β-Blockers improve clinical outcome when administered early after acute myocardial infarction. However, whether β-blockers actually reduce the myocardial infarction size is still in dispute. Cardiac magnetic resonance imaging can accurately depict the left ventricular (LV) ischemic myocardium at risk (T2-weighted hyperintense region) early after myocardial infarction, as well as the extent of necrosis (delayed gadolinium enhancement). The aim of this study was to determine whether early administration of metoprolol could increase myocardial salvage, measured as the difference between the extent of myocardium at risk and myocardial necrosis. Methods and Results— Twelve Yorkshire pigs underwent a 90-minute left anterior descending coronary occlusion, followed by reperfusion. They were randomized to metoprolol (7.5 mg during myocardial infarction) or placebo. Global and regional LV function, extent of myocardium at risk, and myocardial necrosis were quantified by cardiac magnetic resonance imaging studies performed 4 and 22 days after reperfusion in 10 survivors. Despite similar extent of myocardium at risk in metoprolol- and placebo-treated pigs (30.9% of LV versus 30.6%; P =NS), metoprolol resulted in 5-fold-larger salvaged myocardium (32.4% versus 6.2% of myocardium at risk; P =0.015). The LV ejection fraction significantly improved in metoprolol-treated pigs between days 4 and 22 (37.2% versus 43.0%; P =0.037), whereas it remained unchanged in pigs treated with placebo (35.1% versus 35.0%; P =NS). The extent of myocardial salvage was related directly to LV ejection fraction improvement ( P =0.031) and regional LV wall motion recovery ( P =0.039) at day 22. Conclusions— Early metoprolol administration during acute coronary occlusion increases myocardial salvage. The extent of myocardial salvage, measured as the difference between myocardium at risk and myocardial necrosis, was associated with regional and global LV motion improvement.
- Published
- 2007
30. Atrial Fibrillation Through the Years
- Author
-
Jason S. Chinitz, Valentin Fuster, Rajeev L. Narayan, and Prashant Vaishnava
- Subjects
Male ,Respiratory rate ,Electric Countershock ,Angiotensin-Converting Enzyme Inhibitors ,Jugular venous pressure ,Electrocardiography ,Heart Rate ,Physiology (medical) ,Atrial Fibrillation ,Heart rate ,Humans ,Medicine ,Myocardial infarction ,business.industry ,Anticoagulants ,Disease Management ,Atrial fibrillation ,Middle Aged ,medicine.disease ,Stroke ,Treatment Outcome ,Blood pressure ,Anesthesia ,Abdominal examination ,Heart failure ,Catheter Ablation ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Anti-Arrhythmia Agents - Abstract
Information about a real patient is presented in stages (boldface type) to an expert clinician (Dr Valentin Fuster), who responds to the information, sharing his reasoning with the reader (regular type). A discussion by the authors follows. A 61-year-old man presents with 2 weeks of exertional dyspnea. Pertinent medical history includes hypertension, nephrolithiasis, and internal hemorrhoids. He takes no medications and has no known drug allergies. His father died after a myocardial infarction at 57 years of age. He formerly smoked 1 pack of cigarettes daily for 15 years but ceased tobacco use 10 years before presentation. He ingests 2 glasses of alcohol weekly and denies illicit drug use. His caffeine intake is limited. He is an architect and is married, with healthy children. On physical examination, his temperature is 98.0°F, blood pressure is 130/85 mm Hg bilaterally, pulse is irregular at 130 beats per minute, and respiratory rate is 18 breaths per minute with an oxygen saturation of 97% while breathing room air. He is a slender white man in no distress. His jugular venous pressure is elevated at 14 cm H 2 O. There is no thyromegaly, and the carotid upstrokes are brisk, without bruits. Cardiovascular examination reveals a rapid and irregular heart rhythm with variation in the intensity of the first heart sound. The point of maximal impulse is not displaced. The remainder of the chest and abdominal examination is within normal limits. The extremities are warm and show mild pitting edema. Laboratory testing is significant for normal renal function and electrolytes, but a hemogram reveals a mild thrombocytopenia of 90 000 platelets/μL. ECG demonstrates atrial fibrillation (AF) with an average ventricular rate of 123 bpm ( Figure 1 ). Figure 1. The 12-lead ECG showing atrial fibrillation with a rapid ventricular rate. Dr Valentin Fuster : This is a …
- Published
- 2013
31. Polygenic Risk Score Identifies Subgroup With Higher Burden of Atherosclerosis and Greater Relative Benefit From Statin Therapy in the Primary Prevention Setting
- Author
-
Usman Baber, Daniel J. Rader, Ian Ford, Robin Young, Roxana Mehran, Nathan O. Stitziel, Dermot F. Reilly, Sekar Kathiresan, Pradeep Natarajan, Sandosh Padmanabhan, Naveed Sattar, Adam S. Butterworth, Valentin Fuster, Samantha Sartori, Butterworth, Adam [0000-0002-6915-9015], and Apollo - University of Cambridge Repository
- Subjects
0301 basic medicine ,Relative risk reduction ,Risk ,Adult ,Male ,medicine.medical_specialty ,Multifactorial Inheritance ,Adolescent ,polymorphism, genetic ,030204 cardiovascular system & hematology ,Article ,law.invention ,Cohort Studies ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Randomized controlled trial ,Cost of Illness ,law ,Risk Factors ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,Young adult ,Coronary atherosclerosis ,Subclinical infection ,Aged ,Aged, 80 and over ,business.industry ,Absolute risk reduction ,Middle Aged ,Atherosclerosis ,R1 ,3. Good health ,Surgery ,Clinical trial ,Primary Prevention ,030104 developmental biology ,vascular calcification ,Cardiovascular Diseases ,Female ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Cardiology and Cardiovascular Medicine ,business ,Cohort study - Abstract
Background: Relative risk reduction with statin therapy has been consistent across nearly all subgroups studied to date. However, in analyses of 2 randomized controlled primary prevention trials (ASCOT [Anglo-Scandinavian Cardiac Outcomes Trial–Lipid-Lowering Arm] and JUPITER [Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin]), statin therapy led to a greater relative risk reduction among a subgroup at high genetic risk. Here, we aimed to confirm this observation in a third primary prevention randomized controlled trial. In addition, we assessed whether those at high genetic risk had a greater burden of subclinical coronary atherosclerosis. Methods: We studied participants from a randomized controlled trial of primary prevention with statin therapy (WOSCOPS [West of Scotland Coronary Prevention Study]; n=4910) and 2 observational cohort studies (CARDIA [Coronary Artery Risk Development in Young Adults] and BioImage; n=1154 and 4392, respectively). For each participant, we calculated a polygenic risk score derived from up to 57 common DNA sequence variants previously associated with coronary heart disease. We compared the relative efficacy of statin therapy in those at high genetic risk (top quintile of polygenic risk score) versus all others (WOSCOPS), as well as the association between the polygenic risk score and coronary artery calcification (CARDIA) and carotid artery plaque burden (BioImage). Results: Among WOSCOPS trial participants at high genetic risk, statin therapy was associated with a relative risk reduction of 44% (95% confidence interval [CI], 22–60; P P =0.004) despite similar low-density lipoprotein cholesterol lowering. In a study-level meta-analysis across the WOSCOPS, ASCOT, and JUPITER primary prevention, relative risk reduction in those at high genetic risk was 46% versus 26% in all others ( P for heterogeneity=0.05). Across all 3 studies, the absolute risk reduction with statin therapy was 3.6% (95% CI, 2.0–5.1) among those in the high genetic risk group and 1.3% (95% CI, 0.6–1.9) in all others. Each 1-SD increase in the polygenic risk score was associated with 1.32-fold (95% CI, 1.04–1.68) greater likelihood of having coronary artery calcification and 9.7% higher (95% CI, 2.2–17.8) burden of carotid plaque. Conclusions: Those at high genetic risk have a greater burden of subclinical atherosclerosis and derive greater relative and absolute benefit from statin therapy to prevent a first coronary heart disease event. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifiers: NCT00738725 (BioImage) and NCT00005130 (CARDIA). WOSCOPS was carried out and completed before the requirement for clinical trial registration.
- Published
- 2016
32. Cholesterol Efflux and Atheroprotection
- Author
-
Xian-Cheng Jiang, Michael C. Phillips, W. Sean Davidson, Daniel J. Rader, Marc K. Hellerstein, George H. Rothblat, Zahi A. Fayad, Robert S. Rosenson, Alan T. Remaley, Alan R. Tall, Valentin Fuster, Laurent Yvan-Charvet, H. Bryan Brewer, and James A. Goldstein
- Subjects
Cholesterol 7 alpha-hydroxylase ,Article ,Diffusion ,chemistry.chemical_compound ,Physiology (medical) ,Cholesterylester transfer protein ,Animals ,Humans ,Phospholipid Transfer Proteins ,Scavenger receptor ,Liver X receptor ,ATP Binding Cassette Transporter, Subfamily G, Member 1 ,biology ,Cholesterol ,Macrophages ,Reverse cholesterol transport ,nutritional and metabolic diseases ,Biological Transport ,Scavenger Receptors, Class B ,Atherosclerosis ,Cholesterol Ester Transfer Proteins ,Biochemistry ,chemistry ,ABCA1 ,Models, Animal ,biology.protein ,ATP-Binding Cassette Transporters ,lipids (amino acids, peptides, and proteins) ,Lipoproteins, HDL ,Cardiology and Cardiovascular Medicine ,Lipoprotein - Abstract
High-density lipoprotein (HDL) has been proposed to have several antiatherosclerotic properties, including the ability to mediate macrophage cholesterol efflux, antioxidant capacity, antiinflammatory properties, nitric oxide–promoting activity, and ability to transport proteins with their own intrinsic biological activities.1 HDL particles are critical acceptors of cholesterol from lipid-laden macrophages and thereby participate in the maintenance of net cholesterol balance in the arterial wall and in the reduction of proinflammatory responses by arterial cholesterol-loaded macrophages. The pathways that regulate HDL-mediated macrophage cholesterol efflux and disposition of cholesterol involve cell membrane–bound transporters, plasma lipid acceptors, plasma proteins and enzymes, and hepatic cellular receptors (Figure 1). From the earliest proposed concept for HDL-mediated cholesterol efflux,2,3 the concentration of the cholesterol content in HDL particles has been considered a surrogate measurement for the efficiency of the “reverse cholesterol transport” (RCT) process; however, macrophage-derived cholesterol represents a minor component of the cholesterol transported by HDL particles.4–7 One important pathway for cholesterol-mediated efflux from macrophage foam cells involves interaction between the ATP-binding cassette transporter A1 (ABCA1) and cholesterol-deficient and phospholipid-depleted apolipoprotein (apo) A-I complexes (pre-β migrating HDL or very small HDL [HDL-VS]; Figure 2).1,8 Subsequently, the ATP-binding cassette transporter G1 (ABCG1) mediates macrophage cholesterol efflux through interactions (Figure 3) with spherical, cholesterol-containing α-HDL particles (small HDL [HDL-S], medium HDL [HDL-M], large HDL [HDL-L], and very large (HDL-VL).1 In contrast, the scavenger receptor class B type I (SR-BI) is a multifunctional receptor that mediates bidirectional lipid transport in the macrophage, which is dependent on the content of cholesterol in lipid-laden macrophages. A more established role for SR-BI in cholesterol trafficking involves selective uptake of cholesteryl esters from mature HDL by the liver. Recent studies suggest that polymorphisms in SR-BI contribute to the functional capacity of this cholesterol …
- Published
- 2012
33. Acute Coronary Events
- Author
-
Armin Arbab-Zadeh, Masataka Nakano, Valentin Fuster, and Renu Virmani
- Subjects
medicine.medical_specialty ,Acute coronary syndrome ,Myocardial Infarction ,Coronary Artery Disease ,Article ,Angina Pectoris ,Angina ,Coronary artery disease ,Coronary thrombosis ,Risk Factors ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,Myocardial infarction ,Acute Coronary Syndrome ,Coronary atherosclerosis ,Framingham Risk Score ,business.industry ,Coronary Thrombosis ,medicine.disease ,United States ,Coronary vasospasm ,Cardiology ,Morbidity ,Cardiology and Cardiovascular Medicine ,business - Abstract
In the United States alone, >400 000 Americans die annually of coronary artery disease, and >1 000 000 suffer acute coronary events, ie, myocardial infarction and sudden cardiac death.1 Considering the aging of our population and increasing incidence of diabetes mellitus and obesity, the morbidity from coronary artery disease and its associated costs will place an increasing, substantial burden on our society.2 Between 2010 and 2030, total direct medical costs spent in the United States for cardiovascular diseases are projected to triple from $273 billion to $818 billion.2 Although effective treatments are available and considerable efforts are ongoing to identify new strategies for the prevention of coronary events, predicting such events in an individual has been challenging.3 In hopes of improving our ability to determine the risk of coronary events, it is prudent to review our knowledge of factors that lead to acute coronary events. Coronary atherosclerosis is the underlying condition for coronary events with few exceptions. Events are rarely caused by coronary dissection, arteritis, myocardial bridging, thromboembolism, or coronary vasospasm without obvious coronary artery disease.4 In some of these instances, more sensitive tools for the detection of coronary artery disease revealed its presence after all.5 Coronary atherosclerosis is known to develop in childhood and adolescence, as evident from fatty streaks seen in pathology studies of individuals who died of trauma or other noncardiac causes.6 Depending on the constellation of genetic and environmental factors, coronary artery disease progresses throughout adulthood and is found in most middle-aged individuals in developed nations. Autopsy series in US communities among young adults (mean age, 36±14 years) who died of nonnatural causes revealed coronary atherosclerosis in >80% of the autopsy sample, with ≈8% having obstructive disease.7 Thus, most individuals ≥40 years of age in our society have …
- Published
- 2012
34. Abstract 19100: Transmural and Lateral Remodeling of the Post-infarction Scar Tissue: Serial Cardiac Magnetic Resonance Imaging Study From the Metocard-Cnic Trial
- Author
-
Marta Jimenez-Blanco, Rebeca Lorca, Jose Manuel García-Ruiz, Gonzalo Pizarro, Rodrigo Fernández-Jiménez, Ana García-Álvarez, Leticia Fernández-Friera, Valentin Fuster, and Borja Ibanez
- Subjects
Physiology (medical) ,Cardiology and Cardiovascular Medicine - Abstract
Background: The remodeling process that occurs following an acute myocardial infarction produces changes in the myocardial scar and the surrounding tissue. The spatial evolution of the scar has not been yet characterized using MRI. Purpose: To describe the spatial behavior of myocardial scar on its transmural and lateral dimensions following an acute myocardial infarction. Methods: A total of 220 patients with acutely reperfused anterior STEMI (METOCARD-CNIC trial population) were studied. All the patients underwent cardiac MRI at day 7 and 6 months after presentation. The spatial distribution of the scar was analyzed using short axis late gadolinium enhancement images. Endo and epicardial contours of each LV short axis slice was traced, and each one was divided by 100 cords for analysis (Figure 1A). The lateral extension was defined as the percentage of cords with enhancement in every slice, and the transmural extension as the percentage of enhancement within each cord, nested in the lateral extension (Figure 1B). All slices were weighed according to their relative mass. Data were compared by paired t test. Results: Six months after STEMI, myocardial scar was smaller in both dimensions (Figure 1C). Mean ± SEM lateral scar, as a percentage of cords affected, at 7 days and 6 months were, respectively, 27.9 ± 1.1 and 22.2 ± 1.0 (p < 0.001). Transmurality also decreased significantly, mean percentage at day 7 was 46.8 ± 1.5 and at 6 months 35.4 ± 1.4 (p < 0.001). All these changes were accompanied by an increase in LV end-diastolic volume (171.47 ± 2.5 and 190.61 ± 2.9 (p < 0.001)). Conclusions: The myocardial scar remodeling process following a STEMI includes a reduction in both its transmural and lateral extensions.
- Published
- 2015
35. Abstract 18987: Wavefront Progression of Necrosis During Myocardial Infarction Revisited: The Wave Expands From Endo to Epi as Well as From Center to Lateral Borders
- Author
-
Leticia Fernández-Friera, Ana García-Álvarez, Valentin Fuster, Marta Jimenez-Blanco, Rodrigo Fernández-Jiménez, Jose Manuel García-Ruiz, Rebeca Lorca, Gonzalo Pizarro, and Borja Ibanez
- Subjects
Wavefront ,education.field_of_study ,medicine.medical_specialty ,Pathology ,Necrosis ,Cord ,medicine.diagnostic_test ,business.industry ,Population ,Magnetic resonance imaging ,medicine.disease ,Coronary occlusion ,Physiology (medical) ,Internal medicine ,cardiovascular system ,medicine ,Cardiology ,cardiovascular diseases ,Myocardial infarction ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,education ,business ,Metoprolol ,medicine.drug - Abstract
Background and purpose: The widely accepted wavefront theory of myocardial necrosis during acute coronary occlusion describes its progression as a wavefront from endo towards epicardium. The lateral affection of the myocardium would be predetermined by the location of the coronary occlusion. At the time this phenomenon was firstly described, advanced imaging technology was not available. Current cardiac magnetic resonance (CMR) is able to accurately characterize the necrosis progression in vivo. Methods: A total of 220 patients with reperfused anterior STEMI (METOCARD-CNIC trial population) were studied. All the patients underwent cine, T2-weighted and late gadolinium enhancement CMR at day 5-7 after STEMI. Endo- and epicardial contours of each LV short axis slice was traced, and each one was divided by 100 cords for analysis. Infarct size was characterized in its 2 dimensions: lateral (defined as the percentage of cords with enhancement in every slice) and transmural extension (percentage of enhancement within each cord, nested in the lateral extension). All slices were weighed according to their relative mass. We compared these parameters between the cardioprotected metoprolol group and the control group. Results: A strong lineal correlation between transmural and lateral infarct extension was observed (r: 0.88, p Conclusions: The transmural and lateral extension of necrosis after myocardial infarction are directly correlated. A proven cardioprotective therapy prevented the necrosis progression in both dimensions. These findings cannot be explained by the classical wavefront theory, suggesting that the necrotic wavefront progresses also in the lateral direction.
- Published
- 2015
36. Abstract 15068: Expression of PW1 Identifies a New Candidate Cardiac Progenitor Population in the Adult Heart
- Author
-
Elisa Yaniz-Galende, Nathalie Mougenot, Jiqiu Chen, Sophie Nadaud, Giovanna Marazzi, Valentin Fuster, Roger Hajjar, David Sassoon, and Jean Sebastien Hulot
- Subjects
Physiology (medical) ,Cardiology and Cardiovascular Medicine - Abstract
Rationale: Adult myocardium contains a rare population of cardiac progenitor cells (CPCs), recruited in response to tissue injury, which are of central importance for the cardiac microenvironment after cardiac injury. However, their phenotype characterization and function in physiological and pathological has not yet been reported. Objective: Based on the identification of a cell population with very high expression of PW1 in different tissues, our goal was to determine the role that PW1+ cells play in the heart in a murine myocardial infarction model. Methods and Results: In this study we show that high expression of PW1 in cardiac cells (PW1+ cells), identified a rare population, located in the epicardium and interstitium in resting heart, increased in the injured and border area in response to myocardial infarction (MI). Using PW1-reporter mice, we defined three populations of CPCs that include fraction I (PW1-ckit+), II (PW1+ c-kit+) and III (PW1+ckit-) based on differential expression of PW1 and c-kit. We found that MI led to an increase of all the fractions especially fraction II. Furthermore, isolated PW1+ cells showed clonogenic capacity, measured as fibroblastic colony-forming units frequency, and differentiation capacity to give rise in vitro to several cardiac lineages. The phenotypic characterization of fractions I, II and III has also been studied by utilizing comparative gene expression profile as a screening tool. Taken together, these data identify a novel PW1+ cardiac progenitor population with the potential to undergo differentiation into multiple cardiac lineages, suggesting their involvement in cardiac repair in normal and pathological conditions. Conclusion: Based on the comparative phenotype analysis, we could demonstrate that the expression of PW1 identified a pure population of CPCs, augmented following MI, with clonogenic and multipotent capacity, which is likely to provide a novel target for therapeutic approaches aimed at improving cardiac repair.
- Published
- 2015
37. Abstract 18200: Intracoronary Delivery of Bioabsorbable Alginate Matrix (IK-5001) Ameliorates Adverse Post-infarction Left Ventricular Remodeling and Improves Left Ventricular Function in a Porcine Model of Reperfused Myocardial Infarction
- Author
-
Carlos G Santos-Gallego, Belén Picatoste, Ida U Njerve, Kiyotake Ishikawa, Jaime Aguero, Torsten Vahl, Nadjib Hammoudi, Javier Sanz, Jagat Narula, Roger J Hajjar, Martin D Meglasson, Valentin Fuster, and Juan J Badimon
- Subjects
Physiology (medical) ,Cardiology and Cardiovascular Medicine - Abstract
Background: Adverse cardiac remodeling after MI is associated with excessive degradation of the extracellular matrix (ECM). IK-5001 is a low viscosity injectable solution that provides the polysaccharide alginate. After intracoronary injection into the MI area it undergoes phase transition forming a hydrogel which can support the ECM. We hypothesized that administration of alginate post-MI would provide a temporary scaffold and attenuate adverse LV remodeling. Methods: Acute MI was induced in 16 pigs by balloon occlusion of the proximal LAD for 2 hours. Animals randomly received intracoronary alginate or saline 4 days post-MI. LV function and remodeling were evaluated with cardiac MRI, 3D-echo and pressure-volume loops at 1 and 2 months post-MI. Histology and Western blot analysis were performed after 2 months. Results: Both groups had similar LVEF and infarct size 4 days post-MI. Coronary angiography immediately after alginate injection showed no impairment in coronary flow. However, 2 months post-MI, alginate-treated pigs exhibited reduced LV remodeling compared with controls demonstrated by reduced LV end-systolic volume, LV mass and sphericity (Table). Alginate-treated pigs had less cardiomyocyte hypertrophy and decreased interstitial fibrosis. Consistent with this, chronic activation of Akt and ERK was reduced. Alginate pigs also showed lower plasma levels of BNP and aldosterone. Interestingly, after 2 months, alginate pigs showed better systolic LV function: higher LVEF, better contractile reserve with dobutamine, and higher dP/dt. Conclusions: Intracoronary administration of alginate ameliorates adverse post-MI LV remodeling at the anatomical, histological and molecular level, and mitigates neurohormonal activation in a porcine model of MI. Alginate also improves systolic LV function. Intracoronary injection of alginate represents an exciting novel treatment option to reduce post-MI remodeling that merits assessment in clinical studies.
- Published
- 2015
38. Abstract 18340: Alternatively Spliced Tissue Factor Promotes Atherosclerosis by Increasing Foam Cell Formation via LOX-1 and SR-A1 up-regulation
- Author
-
Daniel Alicea, Saboor Hekmaty, David T Rodriguez, Peter Bhandari, Dong Kwong Yang, Dongtak Jeong, Jason C Kovacic, Johan L Bjorkegren, Juan J Badimon, Thomas Weber, Roger J Hajjar, Valentin Fuster, and Chiara Giannarelli
- Subjects
Physiology (medical) ,lipids (amino acids, peptides, and proteins) ,Cardiology and Cardiovascular Medicine - Abstract
Introduction: Alternatively Spliced Tissue Factor (asTF) is an isoform of tissue factor that is expressed in human atherosclerotic plaques and promotes plaque progression in experimental atherosclerosis (Giannarelli C, Circulation 2014). Hypothesis: asTF is the isoform of tissue factor that most strongly promotes atherosclerosis by increasing foam cell formation. Methods: ApoE-/- mice (8 weeks old) were fed a Western-type diet starting 2 weeks before surgery. Immediately after transluminal wire injury of the left common carotid artery (LCCA), LCCA was incubated with lentivirus encoding asTF-GFP (asTF+;n=10), fl-TF-GFP (fl-TF+, n=10) or GFP (controls; n=5). Four weeks after, LCCA was removed and processed for the quantification of plaque size (H&E) and lipid accumulation (Oil-Red O). The effect of asTF on foam cell formation was tested in vitro by treating THP-1 derived macrophages with oxLDL (75μg/ml), with asTF (10nM) or vehicle. Total cholesterol (TC) and cholesterol esters (CE) were measured in lipid cell extracts. The mRNA levels of the oxLDL scavenger receptors LOX-1, SR-A1 and CD36 in macrophages and foam cells were assessed using qRT-PCR. Results: Plaque size and lipid accumulation were significantly greater in asTF+ vs. fl-TF+ and control mice (Fig.1, A-D). In vitro results showed that asTF promotes TC and CE accumulation in foam cells (Fig.1, E,F). Gene expression studies showed that asTF significantly increased the mRNA expression of scavenger receptors LOX-1, SR-A1 in both macrophages and foam cells (Fig.1, G-I). An increase in mRNA levels of CD36 (1.4-fold) was only detected in asTF-treated foam cells. Conclusions: In vivo results suggest that asTF promote plaque progression and lipid accumulation. In vitro studies imply that asTF promotes foam cell formation by increasing the expression of oxLDL scavenger receptors implicated in lipoprotein uptake by macrophages. These studies suggest a functional role for asTF in atherosclerotic plaque progression.
- Published
- 2015
39. Abstract 10383: Comparative Assessment of Medical Therapy, PCI, or CABG on Clinical Outcomes in Diabetic Patients With Stable CAD According to Coronary Angiography and Left Ventricular Function: Patient-level Meta-analysis of the BARI-2D, COURAGE, and FREEDOM Trials
- Author
-
G.B. John Mancini, Robert L. Frye, Flora S. Siami, Mandeep S. Sidhu, Michael E. Farkouh, Maria M. Brooks, Vera Bittner, Valentin Fuster, Pamela M. Hartigan, Helen Vlachos, Bernard R. Chaitman, and William E. Boden
- Subjects
medicine.medical_specialty ,Ejection fraction ,business.industry ,Proportional hazards model ,medicine.medical_treatment ,Hazard ratio ,Percutaneous coronary intervention ,medicine.disease ,Revascularization ,Coronary artery disease ,Physiology (medical) ,Internal medicine ,Conventional PCI ,Cardiology ,Medicine ,cardiovascular diseases ,Cardiology and Cardiovascular Medicine ,business ,Stroke - Abstract
Introduction: The benefits of optimal medical therapy (OMT) with or without percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery have been evaluated in patients with Type 2 Diabetes Mellitus (T2DM) and stable coronary artery disease (CAD) but analyses have not been stratified by detailed angiographic CAD burden or left ventricular ejection fraction (LVEF). Methods: A patient-level meta-analysis was undertaken among T2DM patients enrolled in COURAGE, BARI 2D and FREEDOM to assess the impact of randomization to OMT, PCI + OMT, or CABG + OMT on a composite end-point of Death/MI/Stroke and stratified by LVEF (≥ 50%, < 50%), 1, 2 or 3 vessel disease (VD) (% diameter stenosis ≥ 50%) and presence or absence of proximal left anterior descending (pLAD) disease. Hazard ratios (HR) for treatment groups were calculated from Cox regression models including all patients adjusting for trial and revascularization stratum in BARI 2D. Multivariable adjustment for risk factors was performed as a sensitivity analysis. Results: There were 5,034 patients included in the analysis (BARI 2D: n=2,368, COURAGE: n=766, FREEDOM: n=1,900) of whom 17% had LVEF < 50%, 29% had pLAD, and 77% had 2 or 3 VD. A total of 1,591 patients were randomized to OMT alone, 2,118 to PCI + OMT, and 1,325 to CABG + OMT. There were 1,116 events during a median 4.5 year follow-up. There was no significant effect on outcomes with OMT vs PCI + OMT irrespective of LVEF, presence/absence of pLAD and number of VD. By contrast, CABG + OMT significantly reduced the risk of Death/MI/Stroke in patients with 2 or 3 VD, irrespective of LVEF and presence/absence of pLAD (see Table). Results were similar with multivariable adjustment. Conclusions: In patients with T2DM and stable CAD, OMT alone appears to be as effective as PCI + OMT while CABG + OMT significantly reduces cardiovascular events in those with multivessel CAD, irrespective of LVEF or presence of pLAD.
- Published
- 2015
40. Abstract 16977: Estimating the Health Workforce Requirements for Hypertension Management in Rural Western Kenya
- Author
-
Danielle J Lee, Claire Kofler, Deborah Tulienge, Jemima H. Kamano, Sylvester Kimaiyo, Peninah Kiptoo, Hari Balasubramanian, Rajesh Vedanthan, and Valentin Fuster
- Subjects
Hypertension treatment ,business.industry ,Physiology (medical) ,Environmental health ,Workforce ,Medicine ,Hypertension management ,Disease ,Risk factor (computing) ,Cardiology and Cardiovascular Medicine ,business ,Health policy - Abstract
Background: Hypertension is a major risk factor for cardiovascular disease, and the leading risk factor for mortality in sub-Saharan Africa. Yet hypertension treatment and control rates are low. One strategy to address inadequate hypertension treatment in Kenya is task redistribution of care from physicians to nurses. However, the workforce requirements for comprehensive hypertension treatment are not well known. Objective: To develop a needs-based workforce estimation model in order to estimate the health workforce requirements for stable, long-term hypertension management in Kenya. Methods: A mixed-methods approach was used to assess a nurse-based hypertension program in western Kenya. We conducted 7 key informant interviews and 6 focus group discussions among program managers, nurses, community health workers, community leaders, and patients. Qualitative transcripts were analyzed using content analysis with deductive and inductive codes. We also conducted time-motion studies of 118 patient encounters over 7 clinical days in 7 rural health facilities. Finally, we conducted a two-round Delphi exercise, involving anonymous surveys of 8 experts in hypertension and chronic disease care. Results of the time-motion studies and Delphi exercise were summarized using descriptive statistics. The results were inputted into a needs-based health workforce estimation model using Microsoft Excel. Sensitivity analyses were performed, using alternate input values for disease complexity, follow-up interval, and nurse productivity. Results: For a total of 5000 patients, with 60%, 32%, and 8% requiring follow-up visits in 1, 2, and 3 months, respectively, we estimated that 3928 patient encounters are required per month. Our data yielded an estimated clinical capacity of each nurse full-time equivalent (FTE) at 81 patient encounters/month. Thus, 49 nurse FTEs would be required to treat 5000 hypertension patients. Conclusions: A simple needs-based workforce estimation model for hypertension management is able to provide workforce projections that are useful for program planning, human resource allocation, and policy formulation. This approach can serve as a benchmark for future studies to manage chronic diseases in low- and middle-income countries.
- Published
- 2015
41. Abstract 19765: Barriers to Implementation of a Health Promotion Program in Harlem, New York: The FAMILIA Study, an AHA Strategically Focused Research Network Study
- Author
-
Sameer Bansilal, Rajesh Vedanthan, Risa Jaslow, Martha Hadley, Amy Siskind, Carmina Marcial, Ana V Soto, Claire Kofler, Zahi A Fayad, and Valentin Fuster
- Subjects
Physiology (medical) ,Cardiology and Cardiovascular Medicine - Abstract
Objective: The Harlem area of New York City has among the highest obesity and diabetes prevalence rates in the city. Nearly half of the children in the Head Start program and about 94% of adults are overweight or obese. We sought to identify factors that may impact the implementation of an integrated family-based health promotion program for children aged 3-5 years and their caregivers in Harlem. Methods: We conducted a qualitative study consisting of 5 focus group discussions (FGD) at two Head Start preschool centers in Harlem, NY. The FGDs included the following participants: parents, teachers, directors, educational directors, nutritionists, cooks, health, mental health and social service professionals. Content analysis of the transcript and notes was performed to identify salient themes. Relationships between and among themes were formulated. Findings: Twenty-five individuals participated in the FGDs. Seven themes emerged as potential barriers to program implementation. Program implications and specific strategies to address them were generated (Table). Conclusions: Formative work prior to program implementation has revealed important, actionable issues that will be addressed during the intervention period. This type of approach may be useful for other health promotion programs in similar settings.
- Published
- 2015
42. Abstract 18673: JNK Inhibition Restores Endothelial Function in Type 2 Diabetes Mellitus
- Author
-
Rosa Breton-Romero, Bihua Feng, Monika Holbrook, Melissa G Farb, Jessica L Fetterman, Erika A Linder, Brittany D Berk, Nobuyuki Masaki, Robert M Weisbrod, Elica Inagaki, Noyan Gokce, Jose J Fuster, Kenneth Walsh, and Naomi M Hamburg
- Subjects
Physiology (medical) ,Cardiology and Cardiovascular Medicine - Abstract
Introduction: Diabetes mellitus type 2 is an increasingly public health problem and it is a major cause in the development of cardiovascular diseases. Endothelial dysfunction is a key mechanism that contributes to the pathogenesis of cardiovascular diseases and is a well-known feature of clinical diabetes. Prior studies have demonstrated an impaired nitric oxide bioavailability and a reduced endothelium-dependent vasodilation under diabetic conditions and in animal models, JNK activity has been widely described to be involved in systemic insulin resistance. Hypothesis: Our study aimed to evaluate the involvement of JNK in endothelial dysfunction, studying its potential role in altered eNOS activation and NO synthesis in diabetic patients. Methods: We measured endothelial function and JNK activity in freshly isolated endothelial cells from diabetic patients (n=38) and nondiabetic controls (n=40). Results: ECs from diabetic patients displayed impaired eNOS activation and reduced NO release after insulin and A23187 stimulation, consistent with the presence of endothelial dysfunction. JNK activation was higher in diabetic (**P=0.003), and was associated with lower flow-mediated dilation (r=-0.53, *P=0.02). In endothelial cells from diabetic patients, treatment with JNK chemical inhibitor (SP600125) restored eNOS activation and insulin response (***P Conclusions: In summary, our data suggest that JNK activation contributes to vascular insulin resistance and endothelial dysfunction in patients with type 2 diabetes and may represent a target in novel therapeutic opportunities.
- Published
- 2015
43. Abstract 17819: Implications of the Post-myocardial Infarction Bimodal Edematous Reaction for Quantifying Area at Risk, Infarct Size And Salvaged Myocardium by Cardiac Magnetic Resonance Imaging
- Author
-
Rodrigo Fernández-Jiménez, Carlos Galán-Arriola, Jaume Agüero, Javier Sánchez-González, Jaime García-Prieto, Gonzalo J López-Martin, Inés García-Lunar, Gonzalo Pizarro, Valentin Fuster, and Borja Ibanez
- Subjects
Physiology (medical) ,cardiovascular system ,cardiovascular diseases ,Cardiology and Cardiovascular Medicine - Abstract
Background: Contrary to the accepted view, it has been recently demonstrated that myocardial edema after ischemia/reperfusion (I/R) follows a bimodal pattern during the first week. Purpose: To study the implications of the bimodal edema phenomenon on the cardiac magnetic resonance (CMR)-measured area at risk (AAR), infarct size and salvaged myocardium. Methods: Closed-chest 40min I/R was performed in 20 pigs. True anatomical AAR was assessed by arterial enhanced multidetector computed tomography (CT) performed during coronary occlusion. CMR with CINE, T2-weighted short-tau inversion recovery and late gadolinium-enhanced (LGE) sequences were performed at every follow-up (120 min, 24 hours, day 4 and day 7 after reperfusion) for the quantification of left ventricular mass, edema (CMR-AAR), and necrosis (infarct size). Salvaged myocardium was calculated by correcting infarct size for CMR-AAR extent. Results: A sharp increase in left ventricular mass due to huge swelling of the ischemic tissue was detected in early reperfusion (Figure 1A and 1E) leading to overestimation of CMR-AAR as compared to true AAR by CT at this time-point (Figure 1B and 1E). Due to reabsorption of initial edema and presence of significant hemorrhage, CMR-AAR was barely detectable at 24 hours while due to the progression of the deferred wave of edema, CMR-AAR accurately delineated true AAR at day 4 and day 7 (Figure 1B and 1E). A progressive decrease in infarct size was shown in LGE sequences (Figure 1C and 1E). As a consequence, salvaged myocardium dynamically varied within the first week after I/R (Figure 1D). Conclusions: The bimodal edematous reaction after I/R greatly impacts on the non-invasive quantification of CMR-AAR, infarct size and salvaged myocardium by CMR. The most appropriate day to perform CMR after reperfused infarction seems to be around day 7 coinciding with the peak of the deferred wave of edema.
- Published
- 2015
44. Cellular Senescence, Vascular Disease, and Aging
- Author
-
Valentin Fuster, Jason C. Kovacic, Pedro Moreno, Elizabeth G. Nabel, and Vladimir Hachinski
- Subjects
Aging ,medicine.medical_specialty ,Systolic hypertension ,Population ,Disease ,Risk Factors ,Physiology (medical) ,Internal medicine ,Prevalence ,Humans ,Medicine ,Dementia ,Vascular Diseases ,education ,Pulse wave velocity ,Cellular Senescence ,Aged ,education.field_of_study ,business.industry ,Vascular disease ,medicine.disease ,Surgery ,Pulse pressure ,Cardiology ,Cardiology and Cardiovascular Medicine ,business ,Cell aging - Abstract
> You must remember this, > > A kiss is just a kiss, > > A sigh is just a sigh, > > The fundamental things apply, > > As time goes by. “As Time Goes By,” by Herman Hupfeld, Casablanca (1942)1 The increasing prevalence of older-age people in our society represents the culmination of centuries of medical, scientific, and social endeavors. At least in Western society, now relatively freed from pestilence, abject poverty, gross malnutrition, and polluted water and food sources, an increasing proportion of the population can expect to make it to old age. However, although US age-adjusted death rates from cardiovascular disease, coronary heart disease, and stroke continue to fall, a disproportionate number of people who reach old age (≈80% of people aged ≥80 years) suffer from these diseases.1a In this 2-part review, we consider important pathobiological changes that occur with aging in the cardiovascular system, exploring promising areas of recent scientific progress and novel insights that may be translatable into targeted clinical strategies to help to alleviate the excess morbidity and mortality imposed by cardiovascular disease in the elderly. In this second installment, we focus specifically on vascular disease states of the elderly, including systolic hypertension, vascular calcification, and dementia, and we review relevant basic and clinical discoveries that further elucidate these conditions. ### The Elderly Vascular Phenotype Aging is associated with various changes in the vascular system at differing structural and functional levels. At the macroscopic level, an increase in arterial lumen size and arterial wall thickening, mainly of the intima, are observed.2 In addition, increased vascular calcification and a generalized stiffening of the arterial tree lead to increased arterial wave reflectance, increased systolic blood pressure, decreased diastolic blood pressure, and a widened pulse pressure. An interesting aspect of vascular biology in which significant inroads have been made is our understanding of pulse wave velocity, which …
- Published
- 2011
45. 2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Updating the 2006 Guideline)
- Author
-
L Samuel, Wann, Anne B, Curtis, Craig T, January, Kenneth A, Ellenbogen, James E, Lowe, N A Mark, Estes, Richard L, Page, Michael D, Ezekowitz, David J, Slotwiner, Warren M, Jackman, William G, Stevenson, Cynthia M, Tracy, Valentin, Fuster, Lars E, Rydén, David S, Cannom, Jean-Yves, Le Heuzey, Harry J, Crijns, S Bertil, Olsson, Eric N, Prystowsky, Jonathan L, Halperin, Juan Luis, Tamargo, G Neal, Kay, Alice K, Jacobs, Jeffrey L, Anderson, Nancy, Albert, Judith S, Hochman, Christopher E, Buller, Frederick G, Kushner, Mark A, Creager, Erik Magnus, Ohman, Steven M, Ettinger, Robert A, Guyton, Lynn G, Tarkington, Clyde W, Yancy, Gayle R, Whitman, Cardiologie, and RS: CARIM School for Cardiovascular Diseases
- Subjects
medicine.medical_specialty ,Antithrombotic Agent ,Cardiology ,Rhythm control ,antiplatelet therapy ,Physiology (medical) ,catheter ablation ,Atrial Fibrillation ,medicine ,Humans ,rate control ,rhythm control ,anticoagulant therapy ,business.industry ,Task force ,Disease Management ,Rate control ,American Heart Association ,Guideline ,thromboembolism ,antithrombotic agents ,United States ,Surgery ,AHA Scientific Statements ,Anticoagulant therapy ,Family medicine ,Practice Guidelines as Topic ,Cardiology and Cardiovascular Medicine ,business - Abstract
Valentin Fuster, MD, PhD, FACC, FAHA, FESC, Co-Chair; Lars E. Ryden, MD, PhD, FACC, FESC, FAHA, Co-Chair; David S. Cannom, MD, FACC; Harry J. Crijns, MD, FACC, FESC; Anne B. Curtis, MD, FACC, FAHA; Kenneth A. Ellenbogen, MD, FACC, FHRS† Jonathan L. Halperin, MD, FACC, FAHA; G. Neal Kay, MD, FACC
- Published
- 2011
46. Targeted Molecular Probes for Imaging Atherosclerotic Lesions With Magnetic Resonance Using Antibodies That Recognize Oxidation-Specific Epitopes
- Author
-
Karen C. Briley-Saebo, Seung-Hyuk Choi, Juan Gilberto S. Aguinaldo, Zahi A. Fayad, Joseph L. Witztum, Willem J. M. Mulder, Sotirios Tsimikas, Peter X. Shaw, Esad Vucic, Valentin Fuster, and Medical Biochemistry
- Subjects
Biodistribution ,Pathology ,medicine.medical_specialty ,Apolipoprotein B ,Gadolinium ,Contrast Media ,chemistry.chemical_element ,Micelle ,Antibodies ,Article ,Epitope ,Epitopes ,Mice ,Apolipoproteins E ,Antibody Specificity ,Physiology (medical) ,medicine ,Animals ,Humans ,Tissue Distribution ,Aorta, Abdominal ,Micelles ,Phospholipids ,Mice, Knockout ,medicine.diagnostic_test ,biology ,business.industry ,Macrophages ,Magnetic resonance imaging ,Atherosclerosis ,Magnetic Resonance Imaging ,Molecular biology ,Lipoproteins, LDL ,Mice, Inbred C57BL ,Disease Models, Animal ,Cross-Linking Reagents ,chemistry ,Molecular Probes ,Thioglycolates ,biology.protein ,Feasibility Studies ,Antibody ,Cardiology and Cardiovascular Medicine ,business ,Oxidation-Reduction ,Lipoprotein - Abstract
Background— Oxidized low-density lipoprotein plays a key role in the initiation, progression, and destabilization of atherosclerotic plaques and is present in macrophages and the lipid pool. The aim of this study was to assess the feasibility of magnetic resonance imaging of atherosclerotic lesions in mice using micelles containing gadolinium and murine (MDA2 and E06) or human (IK17) antibodies that bind unique oxidation-specific epitopes. Methods and Results— MDA2 micelles, E06 micelles, IK17 micelles, nonspecific IgG micelles, and untargeted micelles (no antibody) were prepared and characterized with respect to pharmacokinetics and biodistribution in wild-type and atherosclerotic apolipoprotein E–deficient (apoE −/− ) mice. Magnetic resonance imaging was performed at 9.4 T over a 96-hour time interval after the administration of 0.075–mmol Gd/kg micelles. MDA2, E06, and IK17 micelles exhibited a longer plasma half-life than IgG or untargeted micelles in apoE −/− but not wild-type mice. In apoE −/− mice, MDA2 and IK17 micelles showed maximal arterial wall uptake at 72 hours and E06 micelles at 96 hours, manifested by 125% to 231% enhancement in magnetic resonance signal compared with adjacent muscle. Confocal microscopy revealed that MDA2, IK17, and E06 micelles accumulated within atherosclerotic lesions and specifically within macrophages. Intravenous injection of free MDA2 before imaging with MDA2 micelles resulted in significantly diminished magnetic resonance signal enhancement. IgG micelles and untargeted micelles showed minimal enhancement in apoE −/− mice. There was no significant signal enhancement with all micelles in wild-type mice. Conclusions— Magnetic resonance imaging with micelles containing gadolinium and oxidation-specific antibodies demonstrates specific targeting and excellent image quality of oxidation-rich atherosclerotic lesions.
- Published
- 2008
47. Polygenic Risk Score Identifies Subgroup With Higher Burden of Atherosclerosis and Greater Relative Benefit From Statin Therapy in the Primary Prevention Setting
- Author
-
Natarajan, Pradeep, primary, Young, Robin, additional, Stitziel, Nathan O., additional, Padmanabhan, Sandosh, additional, Baber, Usman, additional, Mehran, Roxana, additional, Sartori, Samantha, additional, Fuster, Valentin, additional, Reilly, Dermot F., additional, Butterworth, Adam, additional, Rader, Daniel J., additional, Ford, Ian, additional, Sattar, Naveed, additional, and Kathiresan, Sekar, additional
- Published
- 2017
- Full Text
- View/download PDF
48. ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation—Executive Summary
- Author
-
Veronica Dean, Anne B. Curtis, Jean-Yves Le Heuzey, Jean-Jacques Blanc, Andrzej Budaj, Silvia G. Priori, Harry J.G.M. Crijns, Barbara Riegel, Keith McGregor, A. John Camm, Eric N. Prystowsky, Ady Osterspey, Samuel Wann, S. Bertil Olsson, Jonathan L. Halperin, David S. Cannom, Lars Rydén, Kenneth Dickstein, João Morais, Catherine Despres, Jeffery L. Anderson, Alice K. Jacobs, John Lekakis, Sidney C. Smith, Rick A. Nishimura, Aha Task Force Members, Richard L. Page, G. Neal Kay, Valentin Fuster, Elliott M. Antman, José Luis Zamorano, Jaap W. Deckers, Cynthia D. Adams, Joseph P. Ornato, Kenneth A. Ellenbogen, Juan Tamargo, Marco Metra, James E. Lowe, and Sharon A. Hunt
- Subjects
medicine.medical_specialty ,Executive summary ,business.industry ,Physiology (medical) ,Heart rate ,ANTIARRHYTHMIA AGENTS ,medicine ,Atrial fibrillation ,Cardiology and Cardiovascular Medicine ,Intensive care medicine ,business ,medicine.disease - Published
- 2006
49. ACC/AHA 2006 Guideline Update on Perioperative Cardiovascular Evaluation for Noncardiac Surgery: Focused Update on Perioperative Beta-Blocker Therapy
- Author
-
Fleisher, Lee A., Beckman, Joshua A., Brown, Kenneth A., Calkins, Hugh, Chaikof, Elliott, Fleischmann, Kirsten E., Freeman, William K., Froehlich, James B., Kasper, Edward K., Kersten, Judy R., Riegel, Barbara, Robb, John F., Smith, Sidney C., Jacobs, Alice K., Adams, Cynthia D., Anderson, Jeffrey L., Antman, Elliott M., Faxon, David P., Fuster, Valentin, Halperin, Jonathan L., Hiratzka, Loren F., Hunt, Sharon A., Lytle, Bruce W., Nishimura, Rick, and Page, Richard L.
- Subjects
medicine.medical_specialty ,Adrenergic beta-Antagonists ,Diagnostic Techniques, Cardiovascular ,Perioperative Care ,Physiology (medical) ,Internal medicine ,Humans ,Medicine ,Randomized Controlled Trials as Topic ,Personal interest ,business.industry ,Beta blocker therapy ,Task force ,Conflict of interest ,American Heart Association ,Perioperative ,Guideline ,Combined Modality Therapy ,Cardiovascular Diseases ,Delayed-Action Preparations ,Surgical Procedures, Operative ,Practice Guidelines as Topic ,Sympatholytics ,Cardiology ,Cardiology and Cardiovascular Medicine ,business ,Noncardiac surgery - Abstract
The American College of Cardiology/American Heart Association (ACC/AHA) Task Force on Practice Guidelines makes every effort to avoid any actual, potential, or perceived conflict of interest that might arise as a result of an industry relationship or personal interest of the writing committee.
- Published
- 2006
50. Abstract 16942: Alternatively Spliced Tissue Factor promotes plaque progression, inflammation and angiogenesis in experimental atherosclerosis
- Author
-
Dongtak Jeong, Roger J. Hajjar, Valentin Fuster, Chiara Giannarelli, David T. Rodriguez, Daniel Alicea, Jason C. Kovacic, Dong Kwon Yang, Juan J. Badimon, Miriam Merad, Thomas Weber, and Aleksey Chudnovskiy
- Subjects
Gene isoform ,Experimental atherosclerosis ,business.industry ,Angiogenesis ,Plaque progression ,Inflammation ,Gene transfer ,medicine.disease_cause ,Vulnerable plaque ,Tissue factor ,Physiology (medical) ,Cancer research ,Medicine ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Abstract
Introduction: Alternatively Spliced Tissue Factor (asTF) is novel isoform of tissue factor with angiogenic activity mediated via HIF-1α signaling (Giannarelli, AHA 13). asTF is highly expressed in human complicated atherosclerotic plaques (Giannarelli, ACC 13); however, it is unknown whether asTF has a functional role in atherogenesis. Hypothesis: asTF promotes atherosclerotic plaque progression, inflammation and angiogenesis. Methods: ApoE-/- mice (8-weeks old; n=15) were fed a Western-type diet from 2 weeks before surgery continuing through the experiment. Immediately after transluminal wire injury of the left common carotid artery (LCCA), LCCA was incubated with lentivirus encoding asTF-GFP (asTF+ group; n=10) or GFP (asTF- control group; n=5). Four weeks after, blood and spleen were collected for flow cytometry analysis of neutrophils and monocytes. LCCA was removed and processed for H&E, Oil-Red O staining and immunostaining for macrophages (MOMA-2 and MAC-3), vascular smooth muscle cells (VSMC, α-actin), endothelial cells (CD31) and HIF-1α. Results: Neointimal thickness and plaque lipid accumulation were significantly greater in asTF+ vs asTF- mice (Fig 1, A-C). An increase in plaque macrophages, neovessels and HIF-1α was observed in asTF+ vs asTF- (Fig 1, D-F). Medial thickness and VSMC density were similar between groups. Increased circulating neutrophils and Ly6C high (classical/inflammatory) monocytes were observed in asTF+ vs asTF- mice (Fig 1, G,H). In contrast, circulating Ly6C low (patrolling) monocytes were significantly reduced (Fig 1, I). Similar findings were observed in the spleen (Fig 1, J-L). Conclusions: Our results demonstrate that asTF expressed within atherosclerotic lesions promotes plaque progression towards a more advanced phenotype and is associated with systemic proinflammatory status. These data makes asTF an attractive marker of plaque vulnerability and a potential therapeutic target for plaque stabilization.
- Published
- 2014
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.