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1. Baseline characteristics including blood and urine metal levels in the Trial to Assess Chelation Therapy 2 (TACT2).

Author

Navas-Acien, Ana, Santella, Regina M., Joubert, Bonnie R., Huang, Zhen, Lokhnygina, Yuliya, Ujueta, Francisco, Gurvich, Irina, LoIacono, Nancy J., Ravalli, Filippo, Ward, Cynthia D., Jarrett, Jeffery M., Salazar, Alfonsina De Leon, Boineau, Robin, Jones, Teresa L.Z., Mark, Daniel B., Newman, Jonathan D., Nathan, David M., Anstrom, Kevin J., and Lamas, Gervasio A.

Abstract

The reduction in cardiovascular disease (CVD) events with edetate disodium (EDTA) in the Trial to Assess Chelation Therapy (TACT) suggested that chelation of toxic metals might provide novel opportunities to reduce CVD in patients with diabetes. Lead and cadmium are vasculotoxic metals chelated by EDTA. We present baseline characteristics for participants in TACT2, a randomized, double-masked, placebo-controlled trial designed as a replication of the TACT trial limited to patients with diabetes. TACT2 enrolled 1,000 participants with diabetes and prior myocardial infarction, age 50 years or older between September 2016 and December 2020. Among 959 participants with at least one infusion, 933 had blood and/or urine metals measured at the Centers for Diseases Control and Prevention using the same methodology as in the National Health and Nutrition Examination Survey (NHANES). We compared metal levels in TACT2 to a contemporaneous subset of NHANES participants with CVD, diabetes and other inclusion criteria similar to TACT2's participants. At baseline, the median (interquartile range, IQR) age was 67 (60, 72) years, 27% were women, 78% reported white race, mean (SD) BMI was 32.7 (6.6) kg/m2, 4% reported type 1 diabetes, 46.8% were treated with insulin, 22.3% with GLP1-receptor agonists or SGLT-2 inhibitors, 90.2% with aspirin, warfarin or P2Y12 inhibitors, and 86.5% with statins. Blood lead was detectable in all participants; median (IQR) was 9.19 (6.30, 13.9) µg/L. Blood and urine cadmium were detectable in 97% and median (IQR) levels were 0.28 (0.18, 0.43) µg/L and 0.30 (0.18, 0.51) µg/g creatinine, respectively. Metal levels were largely similar to those in the contemporaneous NHANES subset. TACT2 participants were characterized by high use of medication to treat CVD and diabetes and similar baseline metal levels as in the general US population. TACT2 will determine whether chelation therapy reduces the occurrence of subsequent CVD events in this high-risk population. ClinicalTrials.gov. Identifier: NCT02733185. https://clinicaltrials.gov/study/NCT02733185 [ABSTRACT FROM AUTHOR]

Published
2024
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2. Factors Associated With Coronary Angiography Performed Within 6 Months of Randomization to the Conservative Strategy in the ISCHEMIA Trial.

Author

Pracoń, Radosław, Spertus, John A., Broderick, Samuel, Bangalore, Sripal, Rockhold, Frank W., Ruzyllo, Witold, Demchenko, Elena, Nageh, Thuraia, Grossman, Gabriel Blacher, Mavromatis, Kreton, Manjunath, Cholenahally N., Smanio, Paola E. P., Stone, Gregg W., John Mancini, G. B., Boden, William E., Newman, Jonathan D., Reynolds, Harmony R., Hochman, Judith S., and Maron, David J.

Abstract

BACKGROUND: ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) did not find an overall reduction in cardiovascular events with an initial invasive versus conservative management strategy in chronic coronary disease; however, there were conservative strategy participants who underwent invasive coronary angiography early postrandomization (within 6 months). Identifying factors associated with angiography in conservative strategy participants will inform clinical decision-making in patients with chronic coronary disease. METHODS: Factors independently associated with angiography performed within 6 months of randomization were identified using Fine and Gray proportional subdistribution hazard models, including demographics, region of randomization, medical history, risk factor control, symptoms, ischemia severity, coronary anatomy based on protocol-mandated coronary computed tomography angiography, and medication use. RESULTS: Among 2591 conservative strategy participants, angiography within 6 months of randomization occurred in 8.7% (4.7% for a suspected primary end point event, 1.6% for persistent symptoms, and 2.6% due to protocol nonadherence) and was associated with the following baseline characteristics: enrollment in Europe versus Asia (hazard ratio [HR], 1.81 [95% CI, 1.14–2.86]), daily and weekly versus no angina (HR, 5.97 [95% CI, 2.78–12.86] and 2.63 [95% CI, 1.51–4.58], respectively), poor to fair versus good to excellent health status (HR, 2.02 [95% CI, 1.23–3.32]) assessed with Seattle Angina Questionnaire, and new/more frequent angina prerandomization (HR, 1.80 [95% CI, 1.34–2.40]). Baseline lowdensity lipoprotein cholesterol <70 mg/dL was associated with a lower risk of angiography (HR, 0.65 [95% CI, 0.46–0.91) but not baseline ischemia severity nor the presence of multivessel or proximal left anterior descending artery stenosis >70% on coronary computed tomography angiography. CONCLUSIONS: Among ISCHEMIA participants randomized to the conservative strategy, angiography within 6 months of randomization was performed in <10% of patients. It was associated with frequent or increasing baseline angina and poor quality of life but not with objective markers of disease severity. Well-controlled baseline low-density lipoprotein cholesterol was associated with a reduced likelihood of angiography. These findings point to the importance of a comprehensive assessment of symptoms and a review of guideline-directed medical therapy goals when deciding the initial treatment strategy for chronic coronary disease. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Biomarkers and cardiovascular events in patients with stable coronary disease in the ISCHEMIA Trials.

Author

Newman, Jonathan D., Anthopolos, Rebecca, Ruggles, Kelly V., Cornwell, Macintosh, Reynolds, Harmony R., Bangalore, Sripal, Mavromatis, Kreton, Held, Claes, Wallentin, Lars, Kullo, Iftikar J., McManus, Bruce, Newby, L. Kristin K．, Rosenberg, Yves, Hochman, Judith S., Maron, David J., and Berger, Jeffrey S.

Abstract

Biomarkers may improve prediction of cardiovascular events for patients with stable coronary artery disease (CAD), but their importance in addition to clinical tests of inducible ischemia and CAD severity is unknown. To evaluate the prognostic value of multiple biomarkers in stable outpatients with obstructive CAD and moderate or severe inducible ischemia. The ISCHEMIA and ISCHEMIA CKD trials randomized 5,956 participants with CAD to invasive or conservative management from July 2012 to January 2018; 1,064 participated in the biorepository. Primary outcome was cardiovascular death, myocardial infarction (MI), or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. Secondary outcome was cardiovascular death or MI. Improvements in prediction were assessed by cause-specific hazard ratios (HR) and area under the receiver operating characteristics curve (AUC) for an interquartile increase in each biomarker, controlling for other biomarkers, in a base clinical model of risk factors, left ventricular ejection fraction (LVEF) and ischemia severity. Secondary analyses were performed among patients in whom core-lab confirmed severity of CAD was ascertained by computed cardiac tomographic angiography (CCTA). Baseline levels of interleukin-6 (IL-6), high sensitivity troponin T (hsTnT), growth differentiation factor 15 (GDF-15), N-terminal pro-B-type natriuretic peptide (NT-proBNP), lipoprotein a (Lp[a]), high sensitivity C-reactive protein (hsCRP), Cystatin C, soluble CD 40 ligand (sCD40L), myeloperoxidase (MPO), and matrix metalloproteinase 3 (MMP3). Among 757 biorepository participants, median (IQR) follow-up was 3 (2-5) years, age was 67 (61-72) years, and 144 (19%) were female; 508 had severity of CAD by CCTA available. In an adjusted multimarker model with hsTnT, GDF-15, NT-proBNP and sCD40L, the adjusted HR for the primary outcome per interquartile increase in each biomarker was 1.58 (95% CI 1.22, 2.205), 1.60 (95% CI 1.16, 2.20), 1.61 (95% 1.22, 2.14), and 1.46 (95% 1.12, 1.90), respectively. The adjusted multimarker model also improved prediction compared with the clinical model, increasing the AUC from 0.710 to 0.792 (P <.01) and 0.714 to 0.783 (P <.01) for the primary and secondary outcomes, respectively. Similar findings were observed after adjusting for core-lab confirmed atherosclerosis severity. Among ISCHEMIA biorepository participants, biomarkers of myocyte injury/distension, inflammation, and platelet activity improved cardiovascular event prediction in addition to risk factors, LVEF, and assessments of ischemia and atherosclerosis severity. These biomarkers may improve risk stratification for patients with stable CAD. [ABSTRACT FROM AUTHOR]

Published
2023
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4. Contemporary use of cardiovascular risk reduction strategies in type 2 diabetes. Insights from the diabetes collaborative registry.

Author

Arnold, Suzanne V., Gosch, Kensey, Kosiborod, Mikhail, Wong, Nathan D., Sperling, Laurence S., Newman, Jonathan D., Gamble, Cory L., Hamersky, Carol, Rajpura, Jigar, and Vaduganathan, Muthiah

Abstract

Cardiovascular disease remains the primary source of morbidity and mortality in type 2 diabetes (T2D). We characterized the change over time in the use of evidence-based therapies to reduce cardiovascular risk in US patients with T2D. Data from a longitudinal outpatient diabetes registry were used to calculate the prescription of SGLT2i or GLP-1RA over time and among those with high-risk comorbidities (atherosclerotic cardiovascular disease [ASCVD], heart failure [HF], chronic kidney disease [CKD]) and a diabetes cardiovascular composite score (DCCS; calculated as: #eligible medications prescribed/#eligible medications x 100 for SGLT2i, GLP-1RA, statin, antiplatelet/anticoagulant therapy, ACEi/ARB/ARNI). Scores ranged from 0% to 100% (higher=more optimal care). Among 1,001,542 outpatients from 391 US sites, 51.7% patients had ASVCD, 17.7% HF, and 23.0% CKD. The percentage of patients prescribed an SGLT2i or GLP-1RA increased over time (7.3% in 2013 to 28.8% in 2019), and 18.3% of patients with ASCVD, HF, or CKD were on at least one of these medications at last follow-up vs 25.5% of patients without any of these comorbidities. Mean DCCS was 54±36%; 54±25% in patients with ASCVD, HF, or CKD vs 52±50% in patients without any of these comorbidities (P <0.001 for both). In a hierarchical linear model, male sex, and a diagnosis of CKD were independently associated with higher DCCS whereas a diagnosis of HF or ASCVD was associated with a lower DCCS. In a large, contemporary cohort of patients with T2D, we found improvement in the use of SGLT2i and GLP-1RA but unexpectedly lower use in patients with ASCVD, heart failure, and CKD, highlighting a treatment-risk paradox. Further education is needed to shift the understanding of these medications as tools for glucose-lowering to cardiovascular risk reduction and to improve their implementation in clinical practice. [ABSTRACT FROM AUTHOR]

Published
2023
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5. Timing of Antihypertensive Drug Therapy: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Author

Maqsood, Muhammad Haisum, Messerli, Franz H., Skolnick, Adam H., Newman, Jonathan D., Berger, Jeffrey S., and Bangalore, Sripal

Abstract

Background: The timing of antihypertensive drugs administration is controversial. The aim was to compare the efficacy of dosing of antihypertensive drugs in the morning versus evening. Methods: A PubMed, EMBASE, and clinicaltrials.gov databases search for randomized clinical trials of antihypertensive therapies where patients were randomized to morning versus evening dosing. The outcomes were ambulatory blood pressure (BP) parameters (day-time, night-time, and 24/48-hour systolic blood pressure [SBP] and diastolic blood pressure [DBP]) and cardiovascular outcomes. Results: Of 72 randomized controlled trials included, evening dosing significantly reduced ambulatory BP parameters: 24/48-hour SBP (mean difference [MD]=1.41 mm Hg; [95% CI, 0.48–2.34]), DBP (MD=0.60 mm Hg [95% CI, 0.12–1.08]), night-time SBP (MD=4.09 mm Hg [95% CI, 3.01–5.16]), DBP (MD, 2.57 mm Hg [95% CI, 1.92–3.22]), with a smaller reduction in day-time SBP (MD=0.94 mm Hg [95% CI, 0.01–1.87]), and DBP (MD=0.87 mm Hg [95% CI, 0.10–1.63]), and numerically lower cardiovascular events compared with morning dosing. However, when controversial data by Hermida (23 trials, 25  734 patients) were omitted (P heterogeneity<0.05 for most outcomes), the above effect of evening dosing attenuated with no significant effect on 24/48-hour ambulatory blood pressure, day-time BP, and major adverse cardiac event and smaller reduction in night-time ambulatory SBP and DBP. Conclusions: Evening dosing of antihypertensive drugs significantly reduced ambulatory BP parameters and lowered cardiovascular events but the effect was mainly driven by trials by Hermida group. Unless the intention is to specifically lower night-time BP, antihypertensive drugs should be taken at a time of day that is convenient, optimizes adherence, and minimizes undesirable effects. [ABSTRACT FROM AUTHOR]

Published
2023
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7. Cause-Specific Mortality in Patients With Advanced Chronic Kidney Disease in the ISCHEMIA-CKD Trial.

Author

Sidhu, Mandeep S., Alexander, Karen P., Huang, Zhen, Mathew, Roy O., Newman, Jonathan D., O'Brien, Sean M., Pellikka, Patricia A., Lyubarova, Radmila, Bockeria, Olga, Briguori, Carlo, Kretov, Evgeny L., Mazurek, Tomasz, Orso, Francesco, Roik, Marek F., Sajeev, Chakkanalil, Shutov, Evgeny V., Rockhold, Frank W., Borrego, David, Balter, Stephen, and Stone, Gregg W.

Abstract

In ISCHEMIA-CKD, 777 patients with advanced chronic kidney disease and chronic coronary disease had similar all-cause mortality with either an initial invasive or conservative strategy (27.2% vs 27.8%, respectively). This prespecified secondary analysis from ISCHEMIA-CKD (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches–Chronic Kidney Disease) was conducted to determine whether an initial invasive strategy compared with a conservative strategy decreased the incidence of cardiovascular (CV) vs non-CV causes of death. Three-year cumulative incidences were calculated for the adjudicated cause of death. Overall and cause-specific death by treatment strategy were analyzed using Cox models adjusted for baseline covariates. The association between cause of death, risk factors, and treatment strategy were identified. A total of 192 of the 777 participants died during follow-up, including 94 (12.1%) of a CV cause, 59 (7.6%) of a non-CV cause, and 39 (5.0%) of an undetermined cause. The 3-year cumulative rates of CV death were similar between the invasive and conservative strategies (14.6% vs 12.6%, respectively; HR: 1.13, 95% CI: 0.75-1.70). Non-CV death rates were also similar between the invasive and conservative arms (8.4% and 8.2%, respectively; HR: 1.25; 95% CI: 0.75-2.09). Sudden cardiac death (46.8% of CV deaths) and infection (54.2% of non-CV deaths) were the most common cause-specific deaths and did not vary by treatment strategy. In ISCHEMIA-CKD, CV death was more common than non-CV or undetermined death during the 3-year follow-up. The randomized treatment assignment did not affect the cause-specific incidences of death in participants with advanced CKD and moderate or severe myocardial ischemia. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches–Chronic Kidney Disease [ISCHEMIA-CKD]; NCT01985360) [Display omitted] [ABSTRACT FROM AUTHOR]

Published
2023
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8. The trial to assess chelation therapy 2 (TACT2): Rationale and design.

Author

Lamas, Gervasio A., Anstrom, Kevin J., Navas-Acien, Ana, Boineau, Robin, Kim, Hwasoon, Rosenberg, Yves, Stylianou, Mario, Jones, Teresa L.Z., Joubert, Bonnie R., Santella, Regina M., Escolar, Esteban, Aude, Y. Wady, Fonseca, Vivian, Elliott, Thomas, Lewis, Eldrin F., Farkouh, Michael E., Nathan, David M., Mon, Ana C., Gosnell, Leigh, and Newman, Jonathan D.

Abstract

Background: Intravenous edetate disodium-based infusions reduced cardiovascular events in a prior clinical trial. The Trial to Assess Chelation Therapy 2 (TACT2) will replicate the initial study design.Methods: TACT2 is an NIH-sponsored, randomized, 2x2 factorial, double masked, placebo-controlled, multicenter clinical trial testing 40 weekly infusions of a multi-component edetate disodium (disodium ethylenediamine tetra-acetic acid, or Na2EDTA)-based chelation solution and twice daily oral, high-dose multivitamin and mineral supplements in patients with diabetes and a prior myocardial infarction (MI). TACT2 completed enrollment of 1000 subjects in December 2020, and infusions in December 2021. Subjects are followed for 2.5 to 5 years. The primary endpoint is time to first occurrence of all-cause mortality, MI, stroke, coronary revascularization, or hospitalization for unstable angina. The trial has >;85% power to detect a 30% relative reduction in the primary endpoint. TACT2 also includes a Trace Metals and Biorepository Core Lab, to test whether benefits of treatment, if present, are due to chelation of lead and cadmium from patients. Design features of TACT2 were chosen to replicate selected features of the first TACT, which demonstrated a significant reduction in cardiovascular outcomes in the EDTA chelation arm compared with placebo among patients with a prior MI, with the largest effect in patients with diabetes.Results: Results are expected in 2024.Conclusion: TACT2 may provide definitive evidence of the benefit of edetate disodiumbased chelation on cardiovascular outcomes, as well as the clinical importance of longitudinal changes in toxic metal levels of participants. [ABSTRACT FROM AUTHOR]

Published
2022
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9. Associations of a polygenic risk score with coronary artery disease phenotypes in the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial.

Author

Newman, Jonathan D., Douglas, Pamela S., Zhbannikov, Ilya, Ferencik, Maros, Foldyna, Borek, Hoffmann, Udo, Shah, Svati H., Ginsburg, Geoffrey S., Lu, Michael T., and Voora, Deepak

Abstract

A polygenic risk score (PGS) is associated with obstructive coronary artery disease (CAD) independent of traditional risk factors. Coronary computed tomography angiography (CTA) can characterize coronary plaques, including features of highrisk CAD. However, it is unknown if a PGS is associated with obstructive CAD and high-risk CAD phenotypes in patients with symptoms suggestive of CAD. [ABSTRACT FROM AUTHOR]

Published
2022
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10. Survival After Invasive or Conservative Management of Stable Coronary Disease

Author

Hochman, Judith S., Anthopolos, Rebecca, Reynolds, Harmony R., Bangalore, Sripal, Xu, Yifan, O’Brien, Sean M., Mavromichalis, Stavroula, Chang, Michelle, Contreras, Aira, Rosenberg, Yves, Kirby, Ruth, Bhargava, Balram, Senior, Roxy, Banfield, Ann, Goodman, Shaun G., Lopes, Renato D., Pracoń, Radosław, López-Sendón, José, Maggioni, Aldo Pietro, Newman, Jonathan D., Berger, Jeffrey S., Sidhu, Mandeep S., White, Harvey D., Troxel, Andrea B., Harrington, Robert A., Boden, William E., Stone, Gregg W., Mark, Daniel B., Spertus, John A., Maron, David J., Hochman, Judith S., Maron, David J., Reynolds, Harmony R., Bangalore, Sripal, Mavromichalis, Stavroula, Chang, Michelle, Contreras, Aira, Esquenazi-Karonika, Shari, Gilsenan, Margaret, Gwiszcz, Ewelina, Mathews, Patenne, Mohamed, Samaa, Naumova, Anna, Roberts, Arline, VanLoo, Kerrie, Anthopolos, Rebecca, Xu, Yifan, Troxel, Andrea B., Lu, Ying, Huang, Zhen, Broderick, Samuel, Guzmán, Luis, Selvanayagam, Joseph, Lopes, Renato D., Goodman, Shaun G., Steg, Gabriel, Juliard, Jean-Michel, Doerr, Rolf, Keltai, Matyas, Bhargava, Balram, Thomas, Boban, Sharir, Tali, Nikolsky, Eugenia, Maggioni, Aldo P., Kohsaka, Shun, Escobedo, Jorge, White, Harvey D., Pracoń, Radosław, Bockeria, Olga, López-Sendón, José, Held, Claes, Senior, Roxy, Banfield, Ann, Shaw, Leslee J., Phillips, Lawrence, Berman, Daniel, Kwong, Raymond Y., Picard, Michael H., Chaitman, Bernard R., Ali, Ziad, Min, James, Mancini, G.B. John, Leipsic, Jonathon, Guzmán, Luis, Hillis, Graham, Thambar, Suku, Joseph, Majo, Selvanayagam, Joseph, Beltrame, John, Lang, Irene, Schuchlenz, Herwig, Huber, Kurt, Goetschalckx, Kaatje, Hueb, Whady, Caramori, Paulo Ricardo, de Quadros, Alexandre, Smanio, Paola, Mesquita, Claudio, Lopes, Renato D., Vitola, João, Marin-Neto, José, da Silva, Expedito Ribeiro, Tumelero, Rogério, Andrade, Marianna, Alves, Alvaro Rabelo, Dall’Orto, Frederico, Polanczyk, Carisi, Figueiredo, Estevão, Howarth, Andrew, Gosselin, Gilbert, Cheema, Asim, Bainey, Kevin, Phaneuf, Denis, Diaz, Ariel, Garg, Pallav, Mehta, Shamir, Wong, Graham, Lam, Andy, Cha, James, Galiwango, Paul, Uxa, Amar, Chow, Benjamin (Ben), Hameed, Adnan, Udell, Jacob, Cheema, Asim, Hamid, Magdy, Hauguel-Moreau, Marie, Furber, Alain, Goube, Pascal, Steg, Philippe-Gabriel, Barone-Rochette, Gilles, Thuaire, Christophe, Slama, Michel, Doerr, Rolf, Nickenig, Georg, Bekeredjian, Raffi, Schulze, P. Christian, Merkely, Bela, Fontos, Geza, Vértes, András, Varga, Albert, Bhargava, Balram, Kumar, Ajit, Nair, Rajesh G., Grant, Purvez, Manjunath, Cholenahally, Moorthy, Nagaraja, Satheesh, Santhosh, Nath, Ranjit Kumar, Wander, Gurpreet, Christopher, Johann, Dwivedi, Sudhanshu, Oomman, Abraham, Mathur, Atul, Gadkari, Milind, Naik, Sudhir, Punnoose, Eapen, Kachru, Ranjan, Christopher, Johann, Kaul, Upendra, Sharir, Tali, Kerner, Arthur, Tarantini, Giuseppe, Perna, Gian Piero, Racca, Emanuela, Mortara, Andrea, Monti, Lorenzo, Briguori, Carlo, Leone, Gianpiero, Amati, Roberto, Salvatori, Mauro, Di Chiara, Antonio, Calabro, Paolo, Galvani, Marcello, Provasoli, Stefano, Fukuda, Keiichi, Kohsaka, Shun, Nakano, Shintaro, Laucevicius, Aleksandras, Kedev, Sasko, Khairuddin, Ahmad, Escobedo, Jorge, Riezebos, Robert, Timmer, Jorik, Heald, Spencer, Stewart, Ralph, Ramos, Walter Mogrovejo, Demkow, Marcin, Mazurek, Tomasz, Drozdz, Jarozlaw, Szwed, Hanna, Witkowski, Adam, Ferreira, Nuno, Pinto, Fausto, Ramos, Ruben, Popescu, Bogdan, Pop, Calin, Bockeria, Leo, Bockeria, Olga, Demchenko, Elena, Romanov, Alexander, Bershtein, Leonid, Jizeeri, Ahmed, Stankovic, Goran, Apostolovic, Svetlana, Adjic, Nada Cemerlic, Zdravkovic, Marija, Beleslin, Branko, Dekleva, Milica, Davidovic, Goran, Chua, Terrance, Foo, David, Poh, Kian Keong, Ntsekhe, Mpiko, Sionis, Alessandro, Marin, Francisco, Miró, Vicente, López-Sendón, José, Blancas, Montserrat Gracida, González-Juanatey, José, Fernández-Avilés, Francisco, Peteiro, Jesús, Luena, Jose Enrique Castillo, Held, Claes, Aspberg, Johannes, Rossi, Mariagrazia, Kuanprasert, Srun, Yamwong, Sukit, Johnston, Nicola, Donnelly, Patrick, Moriarty, Andrew, Senior, Roxy, Elghamaz, Ahmed, Gurunathan, Sothinathan, Karogiannis, Nikolaos, Shah, Benoy N., Trimlett, Richard H.J., Rubens, Michael B., Nicol, Edward D., Mittal, Tarun K., Hampson, Reinette, Gamma, Reto, De Belder, Mark, Nageh, Thuraia, Lindsay, Steven, Mavromatis, Kreton, Miller, Todd, Banerjee, Subhash, Reynolds, Harmony, Nour, Khaled, and Stone, Peter

Published
2023
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12. Causes of cardiovascular and noncardiovascular death in the ISCHEMIA trial.

Author

Sidhu, Mandeep S., Alexander, Karen P., Huang, Zhen, O'Brien, Sean M., Chaitman, Bernard R., Stone, Gregg W., Newman, Jonathan D., Boden, William E., Maggioni, Aldo P., Steg, Philippe Gabriel, Ferguson, Thomas B., Demkow, Marcin, Peteiro, Jesus, Wander, Gurpreet S., Phaneuf, Denis C., De Belder, Mark A., Doerr, Rolf, Alexanderson-Rosas, Erick, Polanczyk, Carisi A., and Henriksen, Peter A.

Abstract

Background: The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial demonstrated no overall difference in the composite primary endpoint and the secondary endpoints of cardiovascular (CV) death/myocardial infarction or all-cause mortality between an initial invasive or conservative strategy among participants with chronic coronary disease and moderate or severe myocardial ischemia. Detailed cause-specific death analyses have not been reported.Methods: We compared overall and cause-specific death rates by treatment group using Cox models with adjustment for pre-specified baseline covariates. Cause of death was adjudicated by an independent Clinical Events Committee as CV, non-CV, and undetermined. We evaluated the association of risk factors and treatment strategy with cause of death.Results: Four-year cumulative incidence rates for CV death were similar between invasive and conservative strategies (2.6% vs 3.0%; hazard ratio [HR] 0.98; 95% CI [0.70-1.38]), but non-CV death rates were higher in the invasive strategy (3.3% vs 2.1%; HR 1.45 [1.00-2.09]). Overall, 13% of deaths were attributed to undetermined causes (38/289). Fewer undetermined deaths (0.6% vs 1.3%; HR 0.48 [0.24-0.95]) and more malignancy deaths (2.0% vs 0.8%; HR 2.11 [1.23-3.60]) occurred in the invasive strategy than in the conservative strategy.Conclusions: In International Study of Comparative Health Effectiveness with Medical and Invasive Approaches, all-cause and CV death rates were similar between treatment strategies. The observation of fewer undetermined deaths and more malignancy deaths in the invasive strategy remains unexplained. These findings should be interpreted with caution in the context of prior studies and the overall trial results. [ABSTRACT FROM AUTHOR]

Published
2022
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14. Factors Associated With Coronary Angiography Performed Within 6 Months of Randomization to the Conservative Strategy in the ISCHEMIA Trial

Author

Pracoń, Radosław, Spertus, John A., Broderick, Samuel, Bangalore, Sripal, Rockhold, Frank W., Ruzyllo, Witold, Demchenko, Elena, Nageh, Thuraia, Grossman, Gabriel Blacher, Mavromatis, Kreton, Manjunath, Cholenahally N., Smanio, Paola E.P., Stone, Gregg W., Mancini, G.B. John, Boden, William E., Newman, Jonathan D., Reynolds, Harmony R., Hochman, Judith S., Maron, David J., Doan, John, Linefsky, Jason, Lee, Raven, Patel, Risha, Miller, Todd, Yang Cho, So, Milbrandt, Susan, Shelstad, Dawn, Banerjee, Subhash, Kamath, Preeti, Tejani, Ishita, Cobos, Stanley E., Quiles, Kirsten J., Dwyer, Raven R., Donnino, Robert M., Espinosa, Dalisa, Phillips, Lawrence M., Saric, Muhamed, Abdul-Nour, Khaled, Schley, Allison, Golden, Heather, Stone, Peter H., Osseni, Hermine, Wiyarand, Charlene, Douglass, Peter, Pomeroy, Hayley, Craft, Alexandra, Harvey, Bethany, Jang, James J., Anaya, Olivia, Yee, Gennie, Goold, Phoebe, Weitz, Steven, Giovannone, Steven, Pritchard, Lori, Arnold, Suzanne, Gans, Rosann, Henry O’Keefe, James, Jr, Kennedy, Paul, Shapiro, Michael D., Ganesan, Shobana, Schlichting, David, Naher, Aynun, El-Hajjar, Mohammad, Sidhu, Mandeep S., Fein, Steven A., Stewart, Wendy L., Torosoff, Mikhail T., Salmi, Kristin M., Lyubarova, Radmila, Mookherjee, Sulagna, Drzymalski, Krzysztof, McFalls, Edward O., Garcia, Santiago A., Bertog, Stefan C., Johnson, Debra K., Siddiqui, Rizwan A., Herrmann, Rebekah R., Ishani, Areef, Hansen, Ronnell A., Georges Khouri, Michel, Arges, Kristine, LeFevre, Melissa, Tomfohr, Jennifer, Goldberg, Jonathan L., Ann Byrne, Kimberly, Zappernick, Taissa, Goldweit, Richard, Canada, Sallie, Kakade, Meghana, Mieses, Patricia, Cobos, Stanley E., Dwyer, Raven R., Cohen, Ronny A., Espinosa, Dalisa, Mirrer, Brooks, Quiles, Kirsten J., Navarro, Victor, Rantinella, Magdalena, Rodriguez, Jessica, Mancilla, Olivia, Winchester, David E., Stinson, Susan, Kronenberg, Marvin, Weyand, Terry, Rogal, Philip, Crook, Sherron C., McFarren, Christopher, Heitner, John F., Ho, Jean, Khan, Saadat, Mohamed, Mahmoud, Dauber, Ira M., Soltau, Mary R., Rose, Delsa K., Wimmer, Rebecca J., Siegel, Kathy E., Derbyshire, Susan, Cannan, Charles, Dixon, Michelle, Leonard, Gerald, Sudarshan, Sriram, Heard, Ciarra, Gabriel, Viviana, Desire, Sukie, Mehta, Puja K., McDaniel, Michael, Rashid, Fauzia, Lerakis, Stamatios, Asier, Senait, Quyyumi, Arshed, Patel, Keyur, Wenger, Nanette K., Hedgepeth, Chester M., Gillis, Jennifer, Hurlburt, Heather, Manocchia, Megan, Rosen, Alan, Moore, Susan, Congdon, Elizabeth, Sahul, Zakir, Brandt, Gail, Marchelletta, Nora, Wippler, Kristina, Booth, David, Taul, Yvonne, Leung, Steve, Isaacs, Jennifer, Abdel-Latif, Ahmed, Bulkley, Viktoria, Reda, Hassan, Rodgers, Caroline, Ziada, Khaled, Setty, Sampoornima, Halverson, Kimberly E., Roraff, Christine, Thorsen, Jonean, Barua, Rajat S., Ojajuni, Amarachi, Olurinde, Oni, Surineni, Kamalakar, Hage, Fadi, Valaiyapathi, Badhma, Caldeira, Christiano, Davies, James E., Leesar, Massoud, Heo, Jaekyeong, Iskandrian, Amy, Al Solaiman, Firas, Singh, Satinder, Dajani, Khaled, Kartje, Carol M., El-Hajjar, Mohammad, Mesropian, Paul Der, Sacco, Joseph, Rawlins, Michele, McCandless, Brian, Thomson, Jennifer, Orgera, Marisa, Sidhu, Mandeep S., Colleen Rogge, Mary, Arif, Imran, Bunke, Julie, Kerr, Hanan, Unterbrink, Kendra, Fannon, Jacqueline, Burman, Cynthia, Trejo, Jorge F., Dubin, Marcia F., Fletcher, Gerald, Lane, Gary E., Neeson, Lynn M., Parikh, Pragnesh P., Pollak, Peter M., Shapiro, Brian P., Landolfo, Kevin, Gemignani, Anthony, Beaudry, Sarah, O’Rourke, Daniel, Meadows, Judith L., Tirado, Stephanie A., Halliday, Janet, Julian, Pamela, Call, Jason T., Stephanie, Lane, M., Stanford, Jennifer L., Hannan, Joseph, Bojar, Robert, Arsenault, Patricia, Kumar, Deepti, Sigel, Pamela, Mukai, John, Martin, Edward T., Brooks, Miriam, Vorobiof, Gabriel, Douangvila, Ladda, Gevorgyan, Rubine, Moorman, Alec, Ranjbaran, Fatima, Smith, Bryn, Ohmart, Carly, Kinlay, Scott, Hamburger, Robert J., Rocco, Thomas P., Ly, Samantha, Bhatt, Deepak L., Quinn, Margot C., Croce, Kevin, Temiyasathit, Sara, Quin, Jacquelyn A, Do, Jacquelyn, Anumpa, Jati, Tobin, Desiree, Zenati, Marco, Faxon, David P, Rayos, Glenn, Langdon, Jennifer, Werner Bayer, Marcia, Seedhom, Ashraf, O’Malley, Amanda, Sullenberger, Lance, Orvis, Erin, Kumkumian, Gregory, Murphy, Mandy, Greenberg, Ann, Iraola, Margaret, Sedlis, Steven P., Maranan, Leandro C., Donnino, Robert M., Lorin, Jeffrey, Tamis-Holland, Jacqueline E., Malinay, Ammy, Kornberg, Robert, Leber, Robert, Saba, Souheil, Edillo, Candice P., Lee, Michael W., Small, Delano R., Nona, Wassim, Alexander, Patrick B., Rehman, Iram, Badami, Umesh, Ostrander, Ann, Wasmiller, Stephanie, Marzo, Kevin, Drewes, Wendy, Patel, Dipti, Robbins, Inga H., Levite, Howard A., White, Jackie M, Shetty, Sanjay, Hallam, Alison, Patel, Mayuri, Hamroff, Glenn S., Spooner, Benjamin J, Hollenweger, Linda M, Little, Raymond W., Little, Holly, Zimbelman, Brandi D., Little, Tiffany, Lui, Charles Y., Eskelson, Nona A, Smith, Brigham R., Vezina, Daniel P., Khor, Lillian L., Abraham, Josephine D., Bull, David A., McKellar, Stephen H., Booth, David, Taul, Yvonne, Kotter, John, Rodgers, Caroline, Abdel-Latif, Ahmed, Isaacs, Jennifer, Bulkley, Viktoria, Hu, Bob, Kaneshiro, Renee, Labovitz, Arthur J., Berlowitz, Michael, Kirby, Bonnie J., Rogal, Philip, Tran, Nhi N., McFarren, Christopher, Jahrsdorfer, Catherine, Matar, Fadi, Caldeira, Christiano, Rodriguez, Fatima, Yunis, Reem, Schnittger, Ingela, Patro, Jhina, Fearon, William F., Deedwania, Prakash, Vega, Antonia, Reddy, Kiran, Sweeny, Joseph, Bloise-Adames, Hugo, Jimenez, Santa, Saint Vrestil, Nicole, Bhandari, Reyna, Spizzieri, Christopher, Schade, Danielle, Yost, Roxanne, Hochberg, Claudia P, Beardsley, Paula, Fine, Denise, Salerno, William D., Tancredi, Jana, Arakelian, Patricia, Mathus, Susan, O’Neill, Deborah, Wyman, Ray, Burkhardt, Joy, Hosino, Suellen, Lubyanaya, Oksana A., Salas, Jose D., Zarka, Amer, Aguirre, Maria, Shah, Anil V., Dhawan, Manu, Parra, Diana, Tran, Tri, Haldis, Thomas, Weick, Catherine, Fowler-Lehman, Katie, Spitzer, Natalie, Riedberger, Casey, Weick, Catherine, Kohn, Jeffrey A., Cobos, Stanley E., Dwyer, Raven R., Espinosa, Dalisa, Quiles, Kirsten J., Girotra, Saket, Drum, Carrie, Miller-Cox, Kimberly, Ollinger, Amy, Almousalli, Omar, Capasso-Gulve, Elizabeth, Melanie Loehr, Alaine, Mosley, Marlowe, Krishnam, Mayil S., Heydari, Shirin, Milliken, Jeffrey C., Lundeen, Andrea M., Patel, Pranav M., Karanjah, Edgar, Seto, Arnold H., Marfori, Wanda C., Harley, Kevin T., Hernandez-Rangel, Eduardo, Gibson, Michael A., Singh, Pam, Allen, Byron J., Coram, Rita, Marie Webb, Anne, Fridell, Ellie, Wilson, Heidi, Thomas, Sabu, Kim, Angela, Schwartz, Ronald G, Wilmot, Patrick, Chen, Wei, El Shahawy, Mahfouz, Stevens, Ramona, Stafford, James, Black, Loriane, Abernethy, William B., Hull, Amber B., Lim, Olivia J., Tucker, Helen C., Putnam, Natasha C., Hall, Linda L., Cauthren, Tia, Tucker, Trish, Zurick, Andrew, Horton, Hollie, Orga, Jan, Meyer, Thomas M., White, Joyce R., Morford, Ronald G., Baumann, Cynthia, Rutkin, Bruce, Seeratan, Vidya, Bokhari, Sabahat, Jimenez, Magnolia, Sokol, Seth I., Schultz, Cidney, Meisner, Jay, Russo, Jeanne, Hamzeh, Ihab, Misra, Arunima, Huda, Zohra, Wall Jr., Matthew, Boan, Araceli, Lenges De Rosen, Veronica, Alam, Mahboob, Turner, Michael C., Hinton, Christine R, Mulhearn, Thomas J., Good, Arnold P., Archer, Beth A., Dionne, Julia S., Allardyce, Cheryl A., Sikora, Lindsey N., Czerniak, Jennifer H., Mull, Jennifer A., Ferguson, Elizabeth, Laube, Frances, Shammas, Nicolas W., Shammas, Gail A, Christensen, Lori, Park, Holly, Chilton, Robert, Hecht, Joan, Nguyen, Patricia K., Vo, Davis, Hirsch, James, Jezior, Matthew, Bindeman, Jody, Salkind, Sara, Espinosa, Dalisa, Desimone, Lori-Ann, Gordon, Paul C., Felix-Stern, Lina, Crain, Thomas, Gomes, Jassira, Gordon, Catherine, Stenberg, Robert, Mann, Aimee, McCreary, Theresa, Pedalino, Ronald P., Cobos, Stanley E., Dwyer, Raven R., Espinosa, Dalisa, Quiles, Kirsten J., Wiesel, Joseph, Cobos, Stanley E., Dwyer, Raven R., Espinosa, Dalisa, Quiles, Kirsten J., Juang, George J., Gopaul, Candace, Hultberg, Karen, Huk, Tauqir, Hussain, Afshan, Al-Amoodi, Mohammed, Zambrano, Yesenia, Medina Rodriguez, Sarah, Milner, Trudie, Wohns, David, Mulder, Abbey, Van Oosterhout, Stacie, Lader, Ellis W., Meyer, Martha, Mumma, Michael, Clapp, Nancy L., Barrentine, Heather, Dharmarajan, Lekshmi, Jose, Jenne M., Cobos, Stanley E., Dwyer, Raven R., Espinosa, Dalisa, Quiles, Kirsten J., Manchery, Jenne, McGarvey Jr, Joseph F.X., McKinney, Vera, Schwarz, Linda, Downes, Thomas R., Kaczkowski, Scott M., Luckasen, Gary J., Jaskowiak, Adam J., Klitch, Joel, Cheong, Benjamin, Dees, Debra, Potluri, Srinivasa, Vasquez, Precilia, Mastouri, Ronald A., Breall, Jeffery A., Hannemann, Elise L., Revtyak, George E., Mae Foltz, Judy, Bazeley, Jonathan W., Li, Dayuan, DeRosa, Emily, Jorgenson, Beth, Riestenberg-Smith, Joyce, Giedd, Kenneth, Old, Wayne, Bariciano, Rebecca, Burt, Francis, Sokhon, Kozhaya, Waldron, Jessica, Mayon, Michelle, Gopal, Deepika, Valeti, Uma S., Ann Peichel, Gretchen, Kobashigawa, Jon, Starks, Brandy, Garcia, Lucilla, Thottam, Maria, Bhargava, Balram, Anand, Anjali, Chakanalil Govindan, Sajeev, Raj, Janitha, Gopalan Nair, Rajesh, Ravindran, Reshma, Rajalekshmi, VS, Nataraj, Nandita, Moorthy, Nagaraja, Nayak, Soundarya, Mylarappa, Mahevamma, Narayanappa, Suryaprakash, Pandit, Neeraj, Bajaj, Sheromani, Kumar Nath, Ranjit, Yadav, Vandana, Mishra, Girish, Dwivedi, S.K., Tewari, Roma, Narain, V.S., Mishra, Meenakshi, Chandra, Sharad, Patel, Shivali, Singh, Suman, Wander, Gurpreet S., Tandon, Rohit, Ralhan, Sarju, Kaur, Baljeet, Aslam, Naved, Gupta, Sonika, Goyal, Abhishek, Bhargava, Balram, Suvarna, Chandini, Karthikeyan, G., Ramakrishnan, S., Seth, Sandeep, Yadav, Rakesh, Singh, Sandeep, Roy, Ambuj, Parakh, Neeraj, Kumar Verma, Sunil, Narang, Rajiv, Mishra, Sundeep, Naik, Nitish, Sharma, Gautam, Kumar Choudhary, Shiv, Patel, Chetan, Gulati, Gurpreet, Sharma, Sanjeev, Bahl, V K, Mathew, Anoop, Mannekkattukudy Kurian, Binoy, Punnoose, Eapen, Avdhoot Gadkari, Milind, Rupesh Karwa, Sheetal, Gadage, Siddharth, Kolhe, Suvarna, Umesh Pillay, Tapan, Satheesh, Santhosh, Vindhya, R. J., Jain, Peeyush, Seth, Ashok, Singh Meharwal, Zile, Mathur, Atul, Verma, Atul, Kaul, Upendra, Bhatia, Mona, Sachdeva, Ankush, Indira Devi, Thounaojam, Jungla, Nungshi, Christopher, Johann, Manjula Rani, K., Menon, Rajeev, Sowjanya Reddy, M., Kumar, Nirmal, Preethi, K., Oomman, Abraham, sidh, Rinu R, Mao, Robert, Ramakrishnan, T., Solomon, Hilda, Francis, Rajesh, Naik, Sudhir, Vamshi, Priya P., Parveen Khan, Sajeeda, Christopher, Johann, Preethi, Kotiboinna, Kumar, Nirmal, Grant, Purvez, Hande, Shweta, Sonawane, Poonam, Kachru, Ranjan, Dubey, Abhishek, Rawat, Kavita, Kumar, Ajit, Ganapathi, Sanjay, K, Jayakumar, CP, Vineeth, Sivadasanpillai, Harikrishnan, Chacko, Manas, Sasidharan, Bijulal, Babu, Suresh, TR, Kapilamoorthy, Christopher, Johann, Reddy, Sowjanya, Polamuri, Praneeth, Rani, Manjula, Kaul, Upendra, Arambam, Priyadarshani, Singh, Bebek, Senior, Roxy, Fox, Keith AA, Young, Grace M., Carruthers, Kathryn, Senior, Roxy, Elghamaz, Ahmed, Gurunathan, Sothinathan, Karogiannis, Nikolaos, Young, Grace M., Shah, Benoy N, Kinsey, Christopher, Trimlett, Richard HJ, Kavalakkat, Raisa, Rubens, Michael B, Evans, Jo, Nicol, Edward D, Hassan, Ikraam, Mittal, Tarun K, Hampson, Reinette, Andreas Gamma, Reto, Williams, Sarah, Holland, Kim, Swan, Karen, de Belder, Mark A, Atkinson, Bev, Thambyrajah, Jeet, Kunhunny, Swapna, Davies, John R, Lindsay, Steven J., Atkinson, Craig, Kurian, John, Krannila, Carita, Jamil, Haqeel, Vinod, Manitha, Raheem, Osama, Hoye, Angela, Chaytor, Lisa, Cox, Leanne, Morrow, Julie, Rowe, Kay, Donnelly, Patrick, Kelly, Stephanie, Valecka, Bernardas, Regan, Susan, Turnbull, Dawn, Chauhan, Anoop, Fleming, Catherine, Ghosh, Arijit, Gratrix, Karen, Preston, Stephen, Barr, Craig, Cartwright, Anne, Alfakih, Khaled, Knighton, Abigail, Byrne, Jonathan, Martin, Katherine, Webb, Ian, Henriksen, Peter, Flint, Laura, Harrison, James, OKane, Peter, Lakeman, Nicki, Ljubez, Anja, de Silva, Ramesh, Conway, Dwayne S. G., Wright, Judith, Exley, Donna, Sirker, Alexander A, Andiapen, Mervyn, Richards, Amy J., Hoole, Stephen P, Wong, Lisa, Witherow, Fraser N., Munro, Melanie J., Johnston, Nicola, Harbinson, Mark, McEvoy, Michelle, Walsh, Simon, Brown, Caroline, Douglas, Hanna, Luckie, Matthew, Charles, Thabitha, Kolakaluri, Laurel, Phillips, Hannah, Sobolewska, Jolanta, Morby, Louise, Hallett, Karen, Corbett, Carolyn, Winstanley, Lynne, Jeetley, Paramjit, Smit, Angelique, Patel, Niket, Kotecha, Tushar, Travill, Christopher, Gent, Susan, Karimullah, Iqbal, Hussain, Nafisa, Al-Bustami, Mahmud, Braganza, Denise, Haines, Fiona, Taaffe, Joanne, Henderson, Robert, Burton, Jane, Pointon, Kate, Colton, Maria, Naik, Surendra, King, Rachel, Mathew, Thomas, Brown, Ammani, Docherty, Andrew, Berry, Colin, McCloy, Lisa, Collison, Damien, Robb, Kate, Roditi, Giles, Paterson, Craig, Crawford, Wenda, Kelly, Joanne, McGregor, Lorraine, Moriarty, Andrew J, Mackin, Anne, Glover, Jason D., Knight, Janet P, Pradhan, Jiwan, Mikhail, Ghada, Bose, Tuhina, Francis, Darrel P., Dzavik, Vladimir, Goodman, Shaun, Gosselin, Gilbert, Gosselin, Gilbert, Proietti, Anna, Brousseau, Myriam, Corfias, Magalie, Blaise, Patricia, Harvey, Luc, Diaz, Ariel, Rheault, Philippe, Barrero, Miguel, Gagné, Carl-Éric, Alarie, Patricia, Pépin-Dubois, Yanek, Arcand, Linda, Costa, Ricardo, Roy, Isabelle, Tung Sia, Ying, Montpetit, Estelle, Lemay, Catherine, Gisbert, Alejandro, Gervais, Pierre, Rheault, Alain, Drouin, Katia, Carl Phaneuf, Denis, Bergeron, Christine, Gosselin, Gilbert, Shelley, Christine, Masson, Christine, Garg, Pallav, Carr, Sandy, Bone, Catherine, Chow, Benjamin J.W., Moga, Ermina, Hessian, Renee C., Kourzenkova, Janetta, Beanlands, Rob S., Walter, Olga, Davies, Richard F., Bainey, Kevin R., Hogg, Norma, Welsh, Suzanne, Cheema, Asim N., Bagai, Akshay, Wald, Ron, Goodman, Shaun, Kushniriuk, Khrystyna, Joseph Graham, John, Hussain, Mohammed, Peterson, Mark, Bello, Olugbenga, Chow, Chi-Ming, Abramson, Beth, Nazir Cheema, Asim, Syed, Ishba, Hussain, Mohammed, Kushniriuk, Khrystyna, Cha, James, Otis, Judy, Otis, Rebecca, Howarth, Andrew G, Seib, Michelle M, Rivest, Sandra M, Sandonato, Rosa, Wong, Graham, Chow, Jackie, Starovoytov, Andrew, Uchida, Naomi, Meadows, Ngaire, Uxa, Amar, Asif, Nadia, Tavares, Suzana, Galiwango, Paul, Bozek, Bev, Kassam, Saleem, Shier, Maria, Mukherjee, Ashok, Larmand, Lori-Ann, Ricci, A. Joseph, Janmohamed, Amir, Hart, Brenda, Lam, Andy, Marucci, Jane, Tai, Sharon, Mehta, Shamir, Brons, Sonya, Beck, Chris, Wong, Glenda, Etherington, Krystal, Arumairajah, Thippeekaa, Udell, Jacob, Aprile, Maria, Karlsson, Sara, Webber, Susan, Généreux, Philippe, Mercure, Chantale, Hameed, Adnan, Aedy, Nancy, Daba, Ledjalem, Farquharson, Fran, Siddiqui, Anam, Carlos Carvalho, Antonio, Lopes, Renato D., Hueb, Whady, Emy Takiuti, Myrthes, Cury Rezende, Paulo, Eustáquio Ribeiro Silva, Expedito, Ciappina Hueb, Alexandre, Pizzol Caetano, Leonardo, Schaan de Quadros, Alexandre, Abdala Karam Kalil, Renato, Peixoto Deiro, Aline, Luiz da Costa Vieira, José, Manica Muller, Alice, Antonieta Pereira de Moraes, Maria, Píccaro de Oliveira, Pedro, Maria Ascoli, Bruna, Bridi, Leonardo, Zottis Poletti, Sílvia, Savaris, Simone, Vitola, João V, Cerci, Rodrigo J, Zier, Sandra S., Farias, Fabio R, Veiga Jr, Vilmar, Fernandes, Miguel M, Antonio Marin-Neto, José, Schmidt, André, de Oliveira Lima Filho, Moysés, Franca da Cunha, Diego, Mendes Oliveira, Ricardo, Reynaldo Abbud Chierice, João, Polanczyk, Carísi A., Rucatti, Guilherme G, Furtado, Mariana V., Igansi, Fernanda, Smidt, Luis F., Haeffner, Mauren P, Carlos Carvalho, Antonio, Almeida, Viviane, Pucci, Gustavo, Sanchez de Souza, Gabriela, Lyra, Flavio, Rabelo Alves Junior, Alvaro, Almeida, Mayana, dos Santos, Viviane, Dracoulakis, Marianna D. A., Oliveira, Natalia S, Lima, Rodolfo G. S. D, Figueiredo, Estevao, Edilena Paulino Azevedo, Bruna, Ricardo Caramori, Paulo, Bizzaro Santos, Marco, Germann, Amanda, Gomes, Vitor, Homem, Rosa, Magedanz, Ellen, Tumelero, Rogerio, Laimer, Rosane, Tognon, Alexandre, Dall’Orto, Frederico, Mesquita, Claudio T., Santos, Roberta P, Colafranseschi, Alexandre S., Oliveira Jr., Amarino C., Carvalho, Luiz A., Palazzo, Isabella C., Sousa, Andre S., Eustáquio Ribeiro da Silva, Expedito, Gabriel Melo de Barros e Silva, Pedro, Yumi Okada, Mariana, de Pádua Silva Baptista, Luciana, Paula Batista, Ana, Jamus Rodrigues, Marcelo, Nogueira Rabaça, Aline, Valério Coimbra de Resende, Marcos, Francisco Saraiva, Jose, Miranda Trama, Larissa, Silva, Talita, Thais de Souza Ormundo, Camila, Vicente, Carla, Costantini, Costantino, Pinheiro, Caroline, Komar, Daniele, Szwed, Hanna, Demkow, Marcin, Kepka, Cezary, Teresinska, Anna, Walesiak, Olga, Kryczka, Karolina, Malinowska, Katarzyna, Henzel, Jan, Solecki, Mateusz, Kaczmarska, Edyta, Mazurek, Tomasz, Maksym, Jakub, Wojtera, Karolina, Fojt, Anna, Szczerba, Ewa, Drozdz, Jaroslaw, Czarniak, Bartosz, Frach, Malgorzata, Szymczyk, Konrad, Niedzwiecka, Iwona, Sobczak, Sebastian, Ciurus, Tomasz, Jakubowski, Piotr, Misztal-Teodorczyk, Magdalena, Teodorczyk, Dawid, Swiderek, Marta, Fratczak, Aleksandra, Wojtala, Ewelina, Szkopiak, Marcin, Lebioda, Patrycja, Wlodarczyk, Michal, Plachcinska, Anna, Kusmierek, Jacek, Miller, Magdalena, Marciniak, Halina, Wojtczak-Soska, Karolina, Łuczak, Katarzyna, Tarchalski, Tomasz, Cichocka-Radwan, Anna, Szwed, Hanna, Karwowski, Jaroslaw, Anna Szulczyk, Grazyna, Witkowski, Adam, Kukuła, Krzysztof, Celińska-Spodar, Małgorzta, Zalewska, Joanna, Gajos, Grzegorz, Bury, Krzysztof, Pruszczyk, Piotr, Łabyk, Andrzej, Roik, Marek, Szramowska, Agnieszka, Zdończyk, Olga, Łoboz-Grudzień, Krystyna, Jaroch, Joanna, Sokalski, Leszek, Brzezińska, Barbara, Lesiak, Maciej, Łanocha, Magdalena, Reczuch, Krzysztof W., Kolodziej, Adam, Kalarus, Zbigniew, Swiatkowski, Andrzej, Szulik, Mariola, Musial, Wlodzimierz J., Marcinkiewicz-Siemion, Marta, Bockeria, Olga, Bockeria, Leo, Bockeria, Olga, Petrosyan, Karen, Kudzoeva, Zalina, Trifonova, Tatiana, Aripova, Nodira, Chernyavskiy, Alexander M., Naryshkin, Ivan A., Kretov, Evgeniy I., Kuleshova, Alena, Grazhdankin, Igor O., Malaev, Dastan, Bershtein, Leonid L., Sayganov, Sergey A., Subbotina, Irina, Kuzmina-Krutetskaya, Anastasia M., Gumerova, Victoria, Zbyshevskaya, Elizaveta V., Katamadze, Nana O., Nikolaeva, Olga B., Kozlov, Pavel S., Kozulin, Vikentiy Y., Lubinskaya, Ekaterina I., Luis Lopez-Sendon, Jose, Castro, Almudena, Lopez-Sendon, Jose, Fernández-Figares, Virginia, Castro, Almudena, Refoyo Salicio, Elena, Guzman, Gabriela, Galeote, Gabriel, Valbuena, Silvia, Peteiro, Jesús, Dolores Martínez-Ruíz, María, Pérez-Fernández, Ruth, Blanco-Calvo, Moisés, Cuenca-Castillo, José J, Alonso-Álvarez, Encarnación, Flores-Ríos, Xacobe, García-González, Paula, Prada-Delgado, Óscar, Barge-Caballero, Gonzalo, Ramon Gonzalez Juanatey, Jose, Seijas Amigo, Jose, Souto Bayarri, Miguel, Pubull Nuñez, Virginia, Ocaranza Sanchez, Raymundo, Cid Alvarez, Belen, Peña Gil, Carlos, Martinez Monzonis, Amparo, Sionis, Alessandro, Fernández Martínez, Ana, Vila Perales, Montserrat, Maria Padró, Josep, Serra Peñaranda, Antonio, García Picart, Joan, Ginel Iglesias, Antonino, Garcia-Moll Marimon, Xavier, Pons Lladó, Guillem, Carreras Costa, Francesc, Miro, Vicente, Igual, Begoña, Diez, Jose L, Calvillo, Pilar, Ortuño, F. Marin, Valdés Chávarri, M., Quintana Giner, M., Tello Montolliu, A., Romero Aniorte, A.I., Pinar Bermudez, E., Rivera Caravaca, JM., De La Morena, G., Gracida Blancas, Montserrat, Cañavate, Olga, Guerrero, Sonia, Riera, Silvia, Enrique Castillo Luena, Jose, Enrique Castillo Luena, Jose, Lasala, Maria, Fernandez-Aviles, Francisco, Lorenzo, Maria, Sobrino, Olga, Vazquez, Alexandra, Jiang, Lixin, Chen, Jiyan, Dong, Haojian, He, Peiyu, Xia, Chunli, Yang, Junqing, Zhong, Qi, Wu, Yongjian, Tian, Yanmeng, Li, Dongze, Ma, Yitong, Li, Xiaomei, Yang, Yining, Ma, Xiang, Yu, Zixiang, Zhao, Qian, Ji, Zheng, Li, Chunguang, Zhang, Lei, Zhao, Yu, Zhu, Bolin, Yang, Xinchun, Chen, Mulei, Chi, Hongjie, Wang, Yang, Zhang, Jing, Lin, Wenhua, Jing, Rui, Liu, Jingjing, Zeng, Hesong, Zhou, Qiang, Xu, Chang, Li, Zhuxi, Li, Junhua, Xiong, Luyang, Fu, Xin, Gao, Dan, Jiang, Dengke, Leng, Ran, Wang, Xutong, Yuan, Qianqian, Zhang, Lili, Yang, Bin, Bai, Ziliang, Li, Jianhua, Qi, Jie, Wang, Fei, Wang, Haitao, Yang, Bin, Yue, Zhou, Zhang, Zhulin, Wang, Songtao, Dong, Yumei, Mao, Jiajia, Zhang, Bin, Cheng, Gong, Li, Xiuhong, Yao, Xiaowei, Zhong, Nier, Zhou, Ning, Zhao, Yulan, Huang, Yaping, Zhou, Panpan, Fang, Xuehua, Su, Wei, Zeng, Qiutang, Kunwu, Yu, Peng, Yudong, Su, Xin, Su, Xi, Wang, Chen, Zhao, Yunhai, Li, Qingxian, Geng, Yaming, Wang, Yanfu, Nie, Shao-ping, Fan, Jing-yao, Feng, Si-ting, Wang, Xiao, Yan, Yan, Zhang, Hui-min, Yu, Qin, Chi, Lingping, Liu, Fang, Wang, Jian’an, Chen, Han, Jiang, Jun, Li, Huajun, Wang, Jian’an, Han, Yechen, Xu, Lihong, Zhang, Shuyang, Liu, Zhenyu, Liu, Zhenyu, Chen, Gang, Hu, Rongrong, Maggioni, Aldo P., Piero Perna, Gian, Pietrucci, Francesca, Marini, Marco, Gabrielli, Gabriele, Provasoli, Stefano, Di Donato, Anna, Verna, Edoardo, Monti, Lorenzo, Nardi, Barbara, Di Chiara, Antonio, Pezzetta, Francesca, Mortara, Andrea, Casali, Valentina, Galvani, Marcello, Attanasio, Chiara, Ottani, Filippo, Sicuro, Marco, Leone, Gianpiero, Pisano, Francesco, Bare, Cristina, Calabro, Paolo, Fimiani, Fabio, Formisano, Tiziana, Tarantini, Giuseppe, Barioli, Alberto, Cucchini, Umberto, Ramani, Federica, Luigi Andres, Anto, Racca, Emanuela, Rolfo, Fabrizio, Goletto, Cecilia, Briguori, Carlo, De Micco, Francesca, Amati, Roberto, Di Marco, Stefano, Vergoni, William, Tricoli, Martina, Russo, Aldo, Villella, Massimo, Fanelli, Raffaele, Douglas White, Harvey, Alsweiler, Caroline, Poh, Kian-Keong, Chai, Ping, Lau, Titus, Loh, Joshua P., Tay, Edgar L., Teoh, Kristine, Tan, Sik-Yin V, Teo, Lynette L., Sia, Winnie C, Ong, Ching-Ching, Leong, Audrey W, Wong, Raymond C., Loh, Poay-Huan, Kofidis, Theodoros, Xian Chan, Wan, Hui Chan, Koo, Foo, David, Hai Yan, Li, Loh Kwok Kong, Jason, Min Er, Ching, Haider Jafary, Fahim, Chua, Terrance, Ismail, Nasrul, Tun Kyaw, Min, Yip, Deborah, Doerr, Rolf, Doerr, Rolf, Stumpf, Juergen, Grahl, Dorit, Matschke, Klaus, Guenther, Franziska, Simonis, Gregor, Bonin, Kerstin, Kadalie, Clemens T., Sechtem, Udo, Wenzelburger, Ina, Ong, Peter, Gruensfelder, Susanne, Christian Schulze, P., Goebel, Bjoern, Lenk, Karsten, Nickenig, Georg, Sinning, Jan-Malte, Weber, Marcel, Werner, Nikos, Marthe Lang, Irene, Huber, Kurt, Schuchlenz, Herwig, Steinmaurer, Gudrun, Weikl, Stefan, Marthe Lang, Irene, Winter, Max-Paul, Andric, Tijana, Huber, Kurt, Tscharre, Maximilian, Jakl-Kotauschek, Gabriele, Wegmayr, Claudia, Jäger, Bernhard, Egger, Florian, Keltai, Matyas, Vertes, Andras, Sebo, Judit, Davidovits, Zoltan, Matics, Laszlone, Varga, Albert, Ágoston, Gergely, Fontos, Geza, Dekany, Gabor, Merkely, Bela, Bartykowszki, Andrea, Maurovich-Horvat, Pal, Kerecsen, Gabor, Jakal, Agnes, Hinic, Sasa, Djokic, Jelena, Zdravkovic, Marija, Mudrenovic, Vladan, Crnokrak, Bogdan, Beleslin, Branko D., Boskovic, Nikola N., Djordjevic-Dikic, Ana D., Petrovic, Marija T., Giga, Vojislav L., Dobric, Milan R., Stepanovic, Jelena J., Markovic, Zeljko Z., Mladenovic, Ana S., Cemerlic-Adjic, Nada, Velicki, Lazar, Kamenica, Sremska, Pupic, Ljiljana, Davidović, Goran, Simović, Stefan M., Vučić, Rada, Dekleva, Milica Nikola, Martinovic, Miroslav Stevo, Stevanovic, Gordana, Stankovic, Goran, Dobric, Milan, Apostolovic, Svetlana, Martinovic, Sonja Salinger, Stanojevic, Dragana, Escobedo, Jorge, Jesús-Pérez, Ramon de, Juarez, Benito, Baleón-Espinosa, Rubén, Campos-Santaolalla, Arturo S, Durán-Cortés, Elihú, Flores-Palacios, José M, García-Rincón, Andrés, Jiménez-Santos, Moisés, Peñafiel, Joaquín V, Ortega-Ramírez, José A, Valdespino-Estrada, Aquiles, Rosas, Erick Alexánderson, Canales Brassetti, María Fernanda, Vences Anaya, Diego Adrián, García, María Pérez, Carvajal Juarez, Isabel Estela, Rovalo, Magdalena Madero, Morales Rodríguez, Erick Donato, Selvanayagam, Joseph B., Rankin, Jamie, Murphy, Deirdre, Selvanayagam, Joseph B., Lee, Sau, Joseph, Majo X., Thomas, Prince, Thambar, Suku T., Chaplin, Melissa D, Boer, Stephanie C, Beltrame, John F., Stansborough, Jeanette K., Black, Marilyn, Hillis, Graham S., Bonner, Michelle M., Ireland, Kim F., Venn-Edmonds, Clare, Steg, Philippe-Gabriel, Abergel, Helene, Juliard, Jean-Michel, Thobois, Corine, Pasteur, C.H. Louis, Thuaire, Christophe, Tachot, Emilie, Dutoiu, Téodora, Laure, Christophe, Vassaliere, Christel, Steg, Philippe Gabriel, Abergel, Helene, Juliard, Jean-Michel, Fuentes, Axelle, Slama, Michel S., Eliahou, Ludivine, Cedex, Clamart, El Mahmoud, Rami, Dubourg, Olivier, Michaud, Pierre, Nicollet, Eric, Hadjih, Sarah, Cedex, Corbeil-Essonnes, Goube, Pascal, Brito, Patricia, Barone-Rochette, Gilles, Barone-Rochette, Gilles, Furber, Alain, Cornet, Charles, Bière, Loïc, Rautureau, Jeremy, Juceviciene, Agne, Kalibataite-Rutkauskiene, Irma, Keinaite, Laura, Laucevicius, Aleksandras, Laukyte, Monika, Celutkiene, Jelena, Mikolaitiene, Gelmina, Smigelskaite, Akvile, Tamasauskiene, Ilona, Urboniene, Agne, Kedhi, Elvin, Klinieken, Isala, Timmer, Jorik, Bouwhuis, Ilse, Hermanides, Rik, Nijmeijer, Lia, Kaplan, Eliza, Riezebos, Robert K., Samadi, Pouneh, Jeannette, Schoep, J. M., Dongen, Elise van, Elisabeth, Janzen, M., Niehe, Sander R., Suryapranata, Harry, Ahoud, Sandra, Vugt, Stijn van, Ramos, Ruben, Santa Marta, Hospital de, Cacela, Duarte, Santana, Ana, Fiarresga, Antonio, Sousa, Lidia, Marques, Hugo, Patricio, Lino, Selas, Mafalda, Bernanrdes, Luis, Silva, Filipa, Rio, Pedro, Freixo, Cláudia, Carvalho, Ramiro, Ferreira, Rui, Silva, Tiago, Rodrigues, Ines, Modas, Pedro, Portugal, Guilherme, Fragata, Jose, Pinto, Fausto J., Cabrita, Inês Zimbarra, Menezes, Miguel Nobre, Rocha, Andreia, Lopes, Guilhermina Cantinho, Figueiras, Francisca Patuleia, Almeida, Ana Gomes, Coelho, Andreia, CanVas Silva, Pedro, Capinha, Marta, Nobre, Angelo, Caetano, Maria Inês, Francisco, Ana Rita, Silva, Susana, Ferreira, Nuno, de Gaia, Vila Nova, Lopes, Ricardo L., Diaz, Rafael, Guzman, Luis, Tinnirello, Veronica, Figal, Julio César, Nicolás Mungo, Matías, Buenos Aires, Ciudad Autonoma de, Méndiz, Oscar, Cortés, Claudia, Favaloro, Roberto René, Alvarez, Carlos, Garcia, Marina, Blanca, Bahia, Courtis, Javier, Godoy, Valeria, Zeballos, Gabriela, Schiavi, Lilia, Actis, Maria Victoria, Rubio, Mariano, Scaro, Graciela, White, Harvey Douglas, Alsweiler, Caroline, Devlin, Gerard Patrick, Low, Liz, Fisher, Raewyn, Scales, Jayne, Abercrombie, Kirsty, Stewart, Ralph Alan Huston, Howell, Leah, White, Harvey Douglas, Patten, Cathrine, Benatar, Jocelyne, Kedev, Sasko, Mitevska, Irena Peovska, Kostovska, Elizabeta Srbinovska, Pejkov, Hristo, Held, Claes, Held, Claes, Eggers, Kai, Frostfelt, Gunnar, Björklund, Christina, Johnston, Nina, Andreasson, Maria, Olsowka, Maciej, Essermark, Marie, Åkerblom, Axel, Soveri, Inga, Aspberg, Johannes, Persson, Liselotte, Beyar, Rafael, Sharir, Tali, Nikolsky, Eugenia, Sharir, Tali, Harel, Or, Elian, Dan, Kerner, Arthur, Bentzvi, Margalit, Massalha, Samia, Helmer, Ludmila, Kohsaka, Shun, Fukuda, Keiichi, Ueda, Ikuko, Kohsaka, Shun, Fujita, Jun, Yasuda, Satoshi, Furukawa, Akemi, Hirase, Kanae, Nagai, Toshiyuki, Otsuka, Fumiyuki, Nishimura, Shigeyuki, Nakano, Shintaro, de Werf, Frans Van, Goetschalckx, Kaatje, Goetschalckx, Kaatje, Robesyn, Valerie, de Werf, Frans Van, Claes, Kathleen, White, Harvey Douglas, Alsweiler, Caroline, Hung, Chung-Lieh, Yang, Yi-Hsuan, Yun, Chun-Ho, Hou, Charles Jia-Yin, Kuo, Jen-Yuan, Yeh, Hung-I, Hung, Ta-Chuan, Li, Jiun-Yi, Chien, Chen-Yen, Tsai, Cheng-Ting, Liu, Chun-Chieh, Yu, Fa-Chang, Lin, Yueh-Hung, Lan, Wei-Ren, Yen, Chih-Hsuan, Tsai, Jui-Peng, Sung, Kuo-Tzu, Ntsekhe, Mpiko, Pandie, Shaheen, Philander (Nee Talliard), Constance, Viljoen, Charle A, Mtana, Noloyiso, De Andrade, Marianne, Maggioni, Aldo P., Moccetti, Tiziano, Anesini, Adriana, Rossi, M.Grazia, Maspoli, Simona, Mombelli, Manuela, Abdelhamid, Magdy, Talaat, Ahmed, Adel, Ahmed, Kamal, Ahmed, Mahrous, Hossam, Kaffas, Sameh El, Fishawy, Hussien El, Pop, Calin, Claudia, Matei, Popescu, Bogdan A., Ginghina, Carmen, Rosca, Monica, Deleanu, Dan, Beladan, Carmen C., Iliescu, Vlad A., Al-Mallah, Mouaz H., Zahrani, Sarah, Aljzeeri, Ahmed, Najm, Hani, Alghamdi, Ali, Mogrovejo Ramos, Walter Enrique, Monsalve Davila, Marco Antonio, White, Harvey Douglas, Alsweiler, Caroline, Kuanprasert, Srun, Mai, Chiang, Prommintikul, Arintaya, Nawarawong, Weerachai, Khwakhong, Supatchara, Woragidpoonpol, Surin, Chaiyasri, Anong, Tepsuwan, Thitipong, Mekara, Warangkana, Taksaudom, Noppon, Kulthawong, Supap, Rimsukcharoenchai, Chataroon, Amaritakomol, Anong, Euathrongchit, Juntima, Wannasopha, Yutthaphan, Yamwong, Sukit, Panpunuan, Pachara, Sritara, Piyamitr, Aramcharoen, Suthara, Meemuk, Krissada, White, Harvey Douglas, Alsweiler, Caroline, Khairuddin, Ahmad, Mokhtar, Noor Syamira, Hadi, Hafidz Abd, Basri, Nor Asiah, Yahaya, Shaiful Azmi, Yusnida, Irni, Hashim, Humayrah, Harrington, Robert, Williams, David, Alexander, Karen P., Berger, Jeffrey, Harrington, Robert, Mark, Daniel, O’Brien, Sean M., Rosenberg, Yves, Shaw, Leslee J., Ballantyne, Christie, Berman, Daniel, Beyar, Rafael, Bhargava, Balram, Buller, Chris, (Tony) Carvalho*, Antonio, Chaitman, Bernard R., Diaz, Rafael, Doerr, Rolf, Dzavik, Vladimir, Goodman, Shaun, Gosselin, Gilbert, Hachamovitch, Rory, Hamm, Christian, Held, Claes, Helm, Malte, Huber, Kurt, Jiang, Lixin, Keltai, Matyas, Kohsaka, Shun, Lang, Irene, Lopes, Renato, Lopez-Sendon, Jose, Maggioni, Aldo, Bairey Merz, C. Noel, Min, James, Peterson, Eric, Picard, Michael H., Selvanayagam, Joseph, Senior, Roxy, Sharir, Tali, Steg, Gabriel, Szwed, Hanna, de Werf, Frans Van, Weintraub, William, White, Harvey, Williams, David, Ballantyne, Christie, Calfas*, Karen, Chaitman, Bernard R., Champagne, Mary Ann, Davidson, Michael, Fleg, Jerome, McCullough, Peter A., Stone, Peter, Menasche, Philippe, Davidson*, Michael, Fremes, Stephen, Guyton, Robert, Mack, Michael, Mohr, Fred, Rao, Anupama, Sabik, Joe, Shapira, Oz, Taggart, David, Tatoulis, James, Williams, David, Blankenship, Jim, Brener, Sorin, Buller, Chris, Colombo, Antonio, Bruyne, Bernard de, Généreux, Philippe, Harrington, Robert, Kereiakes, Dean, Lefevre, Thierry, Moses, Jeffrey, Chaitman, Bernard R., Alexander, Karen P., Mahaffey, Ken, White, Harvey, Chaitman, Bernard R., Cruz-Flores, Salvador, Danchin, Nicholas, Feen, Eli, Garcia, Mario J., Hauptman, Paul, Laddu, Abhay A., Passamani, Eugene, Pina, Ileana L., Simoons, Maarten, Skali, Hicham, Thygesen, Kristian, Waters, David, Alexander, Karen P., Endsley, Patricia, Esposito, Gerard, Kanters, Jeffrey, Pownall, John, Stournaras, Dimitrios, Shaw, Leslee J., Berman, Daniel, Friedrich, Matthias, Hachamovitch, Rory, Kwong, Raymond, Min, James, Oliver, Dana, Picard, Michael H., Harrell, Frank, Blume, Jeffrey, Lee, Kerry, O’Brien, Sean M., Berger, Jeffrey, Held, Claes, Kullo, Iftikhar, McManus, Bruce, Newby, Kristin, Mark, Daniel, Cohen, David, Weintraub, William, Merz, C. Noel Bairey, Bugiardini, Raffaele, Celutkiene, Jelena, Escobedo, Jorge, Hoye, Angela, Lyubarova, Radmila, Mattina, Deirdre, Peteiro, Jesus, Alexander, Karen P., Berger, Jeffrey, Harrington, Robert, O’Brien, Sean M., Rosenberg, Yves, Mark, Daniel, Mark, Daniel, Shaw, Leslee J., Berman, Dan, Chaitman, Bernard R., Fleg, Jerome, Kwong, Raymond, Picard, Michael H., Senior, Roxy, Min, James, Leipsic, Jonathan, Ali, Ziad, Williams, David, Fleg, Jerome, Berger, Jeffrey, Chaitman, Bernard R., Alexander, Karen P., Alexander, Karen P., Fleg, Jerome, Mathew, Roy, O’Brien, Sean M., Sidhu, Mandeep, Friedman, Lawrence, Anderson, Jeffrey, Berg, Jessica, DeMets, David, Gibson, C. Michael, Lamas, Gervasio, Deming, Nicole, Himmelfarb, Jonathan, Ouyang, Pamela, Woodard, Pamela, Harrell, Frank, Nwosu, Samuel, Rosenberg, Yves, Fleg, Jerome, Kirby, Ruth, Jeffries, Neal, Berger, Jeffrey, Sidhu, Mandeep, Denaro*, Jean E., Mavromichalis, Stephanie, Chan, Kevin, Cobb, Gia, Contreras, Aira, Cukali, Diana, Ferket, Stephanie, Gabriel, Andre, Hansen, Antonietta, Roberts, Arline, Chang, Michelle, Islam, Sharder, Wayser, Graceanne, Yakubov, Solomon, Yee, Michelle, Callison, Caroline, Hogan, Isabelle, Qelaj, Albertina, Pirro, Charlotte, Loo, Kerrie Van, Wisniewski, Brianna, Gilsenan, Margaret, Lang, Bevin, Mohamed, Samaa, Esquenazi-Karonika, Shari, Mathews, Patenne, Naumova, Anna, Lyo, Jihyun, Setang, Vincent, Xavier, Mark, O’Brien, Sean M., Alexander, Karen P., Mark, Daniel B., Anstrom, Kevin, Baloch, Khaula, Blount, Janet, Cowper, Patricia, Davidson-Ray, Linda, Drew, Laura, Harding, Tina, Knight, J David, Liu, Diane Minshall, O’Neal, Betsy, Redick, Thomas, Jones, Philip, Nugent, Karen, Wang, Grace Jingyan, Shaw, Leslee J., Phillips, Lawrence, Goyal, Abhinav, Hetrick, Holly, Oliver, Dana, Berman, Daniel, Hayes, Sean W., Friedman, John D., Gerlach, R. James, Hyun, Mark, Miranda-Peats, Romalisa, Slomka, Piotr, Thomson, Louise, Kwong, Raymond Y., Friedrich, Matthias, Mongeon, Francois Pierre, Michael, Steven, Picard, Michael H., Hung, Judy, Scherrer-Crosbie, Marielle, Zeng, Xin, Chaitman, Bernard R., Eckstein, Jane, Guruge, Bandula, Streif, Mary, Ali, Ziad, Genereux, Philippe, Alfonso, Maria A., Corral, Maria P., Garcia, Javier J., Horst, Jennifer, Jankovic, Ivana, Konigstein, Maayan, Lustre, Mitchel B., Peralta, Yolayfi, Sanchez, Raquel, Min, James, Arsanjani, Reza, Budoff, Matthew, Elmore, Kimberly, Gomez, Millie, Hague, Cameron, Hindoyan, Niree, Leipsic, Jonathan, Nakanishi, Rine, Srichai-Parsia, M. Barbara, Yeoh, Eunice, Youn, Tricia, Maggioni, Aldo P., Bianchini, Francesca, Ceseri, Martina, Lorimer, Andrea, Magnoni, Marco, Orso, Francesco, Sarti, Laura, Tricoli, Martinia, Carvalho, Antonio, Lopes, Renato, Barbosa, Lilian Mazza, Duarte, Tauane Bello, Soares, Tamara Colaiácovo, Aveiro Morata, Julia de, Carvalho, Pedro, Carvalho Maffei, Natalia de, Egydio, Flávia, Kawakami, Anelise, Oliveira, Janaina, Piloto, Elissa Restelli, Pozzibon, Jaqueline, Goodman, Shaun, Camara, Diane, Mowafy, Neamat, Spindler, Caroline, Jiang, Lixin, Dai, Hao, Feng, Fang, Li, Jia, Li, Li, Liu, Jiamin, Xie, Qiulan, Zhang, Haibo, Zhang, Jianxin, Zhang, Lihua, Zhang, Liping, Zhang, Ning, Zhong, Hui, Diaz, Rafael, Escobar, Claudia, Martin, Maria Eugenia, Pascual, Andrea, Lopez-Sendon, José, Moraga, Paloma, Hernandez, Victoria, Castro, Almudena, Posada, Maria, Fernandez, Sara, Villanueva, José Luis Narro, Selgas, Rafael, Steg, Gabriel, Abergel, Helene, Juliard, Jean Michel, White, Harvey, Alsweiler, Caroline, de Werf, Frans Van, Claes, Kathleen, Goetschalckx, Kaatje, Luyten, Ann, Robesyn, Valerie, Selvanayagam, Joseph B., Murphy, Deirdre, Ahmed, Asker, Bhatt, Richa, Chadha, Nitika, Kumar, Vijay, Lubna, Sadath, Naik, Pushpa, Pandey, Shruti, Ramasamy, Karthik, Saleem, Mohammed, Sharma, Pratiksha, and Siddaram, Hemalata

Published
2024
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15. Outcomes in the ISCHEMIA Trial Based on Coronary Artery Disease and Ischemia Severity

Author

Reynolds, Harmony R., Shaw, Leslee J., Min, James K., Page, Courtney B., Berman, Daniel S., Chaitman, Bernard R., Picard, Michael H., Kwong, Raymond Y., O’Brien, Sean M., Huang, Zhen, Mark, Daniel B., Nath, Ranjit K., Dwivedi, Sudhanshu K., Smanio, Paola E.P., Stone, Peter H., Held, Claes, Keltai, Matyas, Bangalore, Sripal, Newman, Jonathan D., Spertus, John A., Stone, Gregg W., Maron, David J., and Hochman, Judith S.

Abstract

Supplemental Digital Content is available in the text.

Published
2021
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16. Effects of Home Particulate Air Filtration on Blood Pressure: A Systematic Review.

Author

Walzer, Dalia, Gordon, Terry, Thorpe, Lorna, Thurston, George, Xia, Yuhe, Zhong, Hua, Roberts, Timothy R., Hochman, Judith S., and Newman, Jonathan D.

Abstract

Air pollution is a major contributor to cardiovascular morbidity and mortality. Fine particulate matter <2.5 µm in diameter may be a modifiable risk factor for hypertension. The benefits of in-home air filtration on systolic blood pressure (BP) and diastolic BP are unclear. To examine the effects of in-home personal air cleaner use on fine particulate exposure and BP, we queried PubMed, Web of Science, Cochrane Central Register, Inspec, and EBSCO GreenFILE databases for relevant clinical trials. Included studies were limited to nonsmoking participants in smoke-free homes with active or sham filtration on indoor fine particulate concentrations and changes in systolic and diastolic BP. Of 330 articles identified, 10 trials enrolling 604 participants who met inclusion criteria were considered. Over a median 13.5 days, there was a significant reduction of mean systolic BP by ≈4 mm Hg (-3.94 mm Hg [95% CI, -7.00 to -0.89]; P=0.01) but a nonsignificant difference in mean diastolic BP (-0.95 mm Hg [95% CI, -2.81 to 0.91]; P=0.32). Subgroup analyses indicated no heterogeneity of effect by age, level of particulate exposure, or study duration. Given the variation in study design, additional study is warranted to confirm and better quantify the observed benefits in systolic BP found with personal air cleaner use. [ABSTRACT FROM AUTHOR]

Published
2020
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18. Myocardial infarction accelerates breast cancer via innate immune reprogramming

Author

Koelwyn, Graeme J., Newman, Alexandra A. C., Afonso, Milessa S., van Solingen, Coen, Corr, Emma M., Brown, Emily J., Albers, Kathleen B., Yamaguchi, Naoko, Narke, Deven, Schlegel, Martin, Sharma, Monika, Shanley, Lianne C., Barrett, Tessa J., Rahman, Karishma, Mezzano, Valeria, Fisher, Edward A., Park, David S., Newman, Jonathan D., Quail, Daniela F., Nelson, Erik R., Caan, Bette J., Jones, Lee W., and Moore, Kathryn J.

Abstract

Disruption of systemic homeostasis by either chronic or acute stressors, such as obesity1or surgery2, alters cancer pathogenesis. Patients with cancer, particularly those with breast cancer, can be at increased risk of cardiovascular disease due to treatment toxicity and changes in lifestyle behaviors3–5. While elevated risk and incidence of cardiovascular events in breast cancer is well established, whether such events impact cancer pathogenesis is not known. Here we show that myocardial infarction (MI) accelerates breast cancer outgrowth and cancer-specific mortality in mice and humans. In mouse models of breast cancer, MI epigenetically reprogrammed Ly6Chimonocytes in the bone marrow reservoir to an immunosuppressive phenotype that was maintained at the transcriptional level in monocytes in both the circulation and tumor. In parallel, MI increased circulating Ly6Chimonocyte levels and recruitment to tumors and depletion of these cells abrogated MI-induced tumor growth. Furthermore, patients with early-stage breast cancer who experienced cardiovascular events after cancer diagnosis had increased risk of recurrence and cancer-specific death. These preclinical and clinical results demonstrate that MI induces alterations in systemic homeostasis, triggering cross-disease communication that accelerates breast cancer.

Published
2020
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19. COVID-19 and the Heart and Vasculature

Author

Kadosh, Bernard S., Garshick, Michael S., Gaztanaga, Juan, Moore, Kathryn J., Newman, Jonathan D., Pillinger, Michael, Ramasamy, Ravichandran, Reynolds, Harmony R., Shah, Binita, Hochman, Judith, Fishman, Glenn I., and Katz, Stuart D.

Abstract

The coronavirus disease 2019 (COVID-19) pandemic presents an unprecedented challenge and opportunity for translational investigators to rapidly develop safe and effective therapeutic interventions. Greater risk of severe disease in COVID-19 patients with comorbid diabetes mellitus, obesity, and heart disease may be attributable to synergistic activation of vascular inflammation pathways associated with both COVID-19 and cardiometabolic disease. This mechanistic link provides a scientific framework for translational studies of drugs developed for treatment of cardiometabolic disease as novel therapeutic interventions to mitigate inflammation and improve outcomes in patients with COVID-19.

Published
2020
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20. Association of Sex With Severity of Coronary Artery Disease, Ischemia, and Symptom Burden in Patients With Moderate or Severe Ischemia: Secondary Analysis of the ISCHEMIA Randomized Clinical Trial

Author

Reynolds, Harmony R., Shaw, Leslee J., Min, James K., Spertus, John A., Chaitman, Bernard R., Berman, Daniel S., Picard, Michael H., Kwong, Raymond Y., Bairey-Merz, C. Noel, Cyr, Derek D., Lopes, Renato D., Lopez-Sendon, Jose Luis, Held, Claes, Szwed, Hanna, Senior, Roxy, Gosselin, Gilbert, Nair, Rajesh Gopalan, Elghamaz, Ahmed, Bockeria, Olga, Chen, Jiyan, Chernyavskiy, Alexander M., Bhargava, Balram, Newman, Jonathan D., Hinic, Sasa B., Jaroch, Joanna, Hoye, Angela, Berger, Jeffrey, Boden, William E., O’Brien, Sean M., Maron, David J., and Hochman, Judith S.

Abstract

IMPORTANCE: While many features of stable ischemic heart disease vary by sex, differences in ischemia, coronary anatomy, and symptoms by sex have not been investigated among patients with moderate or severe ischemia. The enrolled ISCHEMIA trial cohort that underwent coronary computed tomographic angiography (CCTA) was required to have obstructive coronary artery disease (CAD) for randomization. OBJECTIVE: To describe sex differences in stress testing, CCTA findings, and symptoms in ISCHEMIA trial participants. DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of the multicenter ISCHEMIA randomized clinical trial analyzed baseline characteristics of patients with stable ischemic heart disease. Individuals were enrolled from July 2012 to January 2018 based on local reading of moderate or severe ischemia on a stress test, after which blinded CCTA was performed in most. Core laboratories reviewed stress tests and CCTAs. Participants with no obstructive CAD or with left main CAD of 50% or greater were excluded. Those who met eligibility criteria including CCTA (if performed) were randomized to a routine invasive or a conservative management strategy (N = 5179). Angina was assessed using the Seattle Angina Questionnaire. Analysis began October 1, 2018. INTERVENTIONS: CCTA and angina assessment. MAIN OUTCOMES AND MEASURES: Sex differences in stress test, CCTA findings, and symptom severity. RESULTS: Of 8518 patients enrolled, 6256 (77%) were men. Women were more likely to have no obstructive CAD (&lt;50% stenosis in all vessels on CCTA) (352 of 1022 [34.4%] vs 378 of 3353 [11.3%]). Of individuals who were randomized, women had more angina at baseline than men (median [interquartile range] Seattle Angina Questionnaire Angina Frequency score: 80 [70-100] vs 90 [70-100]). Women had less severe ischemia on stress imaging (383 of 919 [41.7%] vs 1363 of 2972 [45.9%] with severe ischemia; 386 of 919 [42.0%] vs 1215 of 2972 [40.9%] with moderate ischemia; and 150 of 919 [16.3%] vs 394 of 2972 [13.3%] with mild or no ischemia). Ischemia was similar by sex on exercise tolerance testing. Women had less extensive CAD on CCTA (205 of 568 women [36%] vs 1142 of 2418 men [47%] with 3-vessel disease; 184 of 568 women [32%] vs 754 of 2418 men [31%] with 2-vessel disease; and 178 of 568 women [31%] vs 519 of 2418 men [22%] with 1-vessel disease). Female sex was independently associated with greater angina frequency (odds ratio, 1.41; 95% CI, 1.13-1.76). CONCLUSIONS AND RELEVANCE: Women in the ISCHEMIA trial had more frequent angina, independent of less extensive CAD, and less severe ischemia than men. These findings reflect inherent sex differences in the complex relationships between angina, atherosclerosis, and ischemia that may have implications for testing and treatment of patients with suspected stable ischemic heart disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01471522

Published
2020
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21. Clinical Management of Stable Coronary Artery Disease in Patients With Type 2 Diabetes Mellitus: A Scientific Statement From the American Heart Association

Author

Arnold, Suzanne V., Bhatt, Deepak L., Barsness, Gregory W., Beatty, Alexis L., Deedwania, Prakash C., Inzucchi, Silvio E., Kosiborod, Mikhail, Leiter, Lawrence A., Lipska, Kasia J., Newman, Jonathan D., and Welty, Francine K.

Abstract

Although cardiologists have long treated patients with coronary artery disease (CAD) and concomitant type 2 diabetes mellitus (T2DM), T2DM has traditionally been considered just a comorbidity that affected the development and progression of the disease. Over the past decade, a number of factors have shifted that have forced the cardiology community to reconsider the role of T2DM in CAD. First, in addition to being associated with increased cardiovascular risk, T2DM has the potential to affect a number of treatment choices for CAD. In this document, we discuss the role that T2DM has in the selection of testing for CAD, in medical management (both secondary prevention strategies and treatment of stable angina), and in the selection of revascularization strategy. Second, although glycemic control has been recommended as a part of comprehensive risk factor management in patients with CAD, there is mounting evidence that the mechanism by which glucose is managed can have a substantial impact on cardiovascular outcomes. In this document, we discuss the role of glycemic management (both in intensity of control and choice of medications) in cardiovascular outcomes. It is becoming clear that the cardiologist needs both to consider T2DM in cardiovascular treatment decisions and potentially to help guide the selection of glucose-lowering medications. Our statement provides a comprehensive summary of effective, patient-centered management of CAD in patients with T2DM, with emphasis on the emerging evidence. Given the increasing prevalence of T2DM and the accumulating evidence of the need to consider T2DM in treatment decisions, this knowledge will become ever more important to optimize our patients’ cardiovascular outcomes.

Published
2020
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22. Investigation of Motivational Interviewing and Prevention Consults to Achieve Cardiovascular Targets (IMPACT) trial.

Author

Gianos, Eugenia, Schoenthaler, Antoinette, Guo, Yu, Zhong, Judy, Weintraub, Howard, Schwartzbard, Arthur, Underberg, James, Schloss, Michael, Newman, Jonathan D., Heffron, Sean, Fisher, Edward A., and Berger, Jeffrey S.

Abstract

Background: Patients undergoing cardiovascular (CV) procedures often have suboptimal CV risk factor control and may benefit from strategies targeting healthy lifestyle behaviors and education. Implementation of prevention strategies may be particularly effective at this point of heightened motivation.Methods: A prospective, randomized, pilot study was conducted in 400 patients undergoing a nonurgent CV procedure (cardiac catheterization ± revascularization) to evaluate the impact of different prevention strategies. Patients were randomized in a 1:1:1 fashion to usual care (UC; group A, n = 134), in-hospital CV prevention consult (PC; group B, n = 130), or PC plus behavioral intervention program (telephone-based motivational interviewing and optional tailored text messages) (group C, n = 133). The primary end point was the Δ change in non-high-density lipoprotein cholesterol (non-HDL-C) from baseline to 6 month.Results: The mean age was 64.6 ± 10.8 years, 23.7% were female, and 31.5% were nonwhite. After 6 months, the absolute difference in non-HDL-C for all participants was -19.8 mg/dL (95% CI -24.1 to -15.6, P < .001). There were no between-group differences in the primary end point for the combined PC groups (B and C) versus UC, with a Δ adjusted between group difference of -5.5 mg/dL (95% CI -13.1 to 2.1, P = .16). Patients in the PC groups were more likely to be on high-intensity statins at 6 months (52.9% vs 38.1%, P = .01). After excluding participants with baseline non-HDL-C <100 mg/dL (initial exclusion criterion), Δ non-HDL-C and Δ low-density lipoprotein cholesterol were improved in the PC groups compared to UC (non-HDL-C -8.13 mg/dL [-16.00 to -0.27], P = .04; low-density lipoprotein cholesterol -7.87mg/dL [-15.10 to -0.64], P = .03).Conclusions: Although non-HDL-C reduction at 6 months following a nonurgent CV procedure was not significant in the overall cohort, an increased uptake in high-potency statins may translate into improved long-term health outcomes and cost reductions. [ABSTRACT FROM AUTHOR]

Published
2018
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23. Current and potential future distribution of the American dog tick (Dermacentor variabilis, Say) in North America.

Author

Minigan, Jordan N., Hager, Heather A., Peregrine, Andrew S., and Newman, Jonathan A.

Abstract

The American dog tick ( Dermacentor variabilis ) is medically and economically important in North America. This species is found across central and eastern North America from the Gulf Coast of Mexico through southern Canada. In parts of this region, D. variabilis is a vector for pathogens that cause diseases in humans and animals. Our aim was to determine whether climate change would affect the distribution of the climatically suitable area for D. variabilis in North America, to aid monitoring for potential future spread of tick-borne pathogens. We developed a species distribution model for D. variabilis to project where climate will likely be suitable for the tick in North America using a maximum entropy method, occurrence records from museum and laboratory archives, and 10 environmental variables relevant to climate requirements for the tick. We used four emissions scenarios from the Intergovernmental Panel on Climate Change's Fifth Assessment Report and 10 climate models from the Coupled Model Intercomparison Project (phase 5) to estimate potential future climate suitability and determine how the tick's distribution could change. Our consensus model projected that the area of suitable climate in North America could increase from present by approximately 50% by 2070. In areas beyond the current northern limit of D. variabilis , climate could become more suitable for the tick than at present, possibly resulting in a northward expansion in Canada, but the potential suitability of the southern range of D. variabilis could decrease, depending on the region and climate model. Due to the ability of D. variabilis to harbor and transmit pathogens, a change in the distribution of this species could also affect the risk of human and animal diseases throughout North America, particularly in the northern range of the tick. [ABSTRACT FROM AUTHOR]

Published
2018
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24. Dapagliflozin Effects on Biomarkers, Symptoms, and Functional Status in Patients With Heart Failure With Reduced Ejection Fraction

Author

Nassif, Michael E., Windsor, Sheryl L., Tang, Fengming, Khariton, Yevgeniy, Husain, Mansoor, Inzucchi, Silvio E., Mc-Guire, Darren K., Pitt, Bertram, Scirica, Benjamin M., Austin, Bethany, Drazner, Mark H., Fong, Michael W., Givertz, Michael M., Gordon, Robert A., Jermyn, Rita, Katz, Stuart D., Lamba, Sumant, Lanfear, David E., LaRue, Shane J., Lindenfeld, JoAnn, Malone, Michael, Margulies, Kenneth, Mentz, Robert J., Mutharasan, R. Kannan, Pursley, Michael, Umpierrez, Guillermo, Kosiborod, Mikhail, Malik, Ali O., Wenger, Nannette, Ogunniyi, Modele, Vellanki, Priyathama, Murphy, Brenda, Newman, Jonathan, Hartupee, Justin, Gupta, Charu, Goldsmith, Marcela, Baweja, Paramdeep, Montero, Manuel, Gottlieb, Stephen S., Costanzo, Maria Rosa, Hoang, Thanh, Warnock, Alicia, Allen, Larry, Tang, Wilson, Chen, Horng H., and Cox, John M.

Abstract

Supplemental Digital Content is available in the text.

Published
2019
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25. Potential Role of Metal Chelation to Prevent the Cardiovascular Complications of Diabetes.

Author

Calderon Moreno, Rossana, Navas-Acien, Ana, Escolar, Esteban, Nathan, David M, Newman, Jonathan, Schmedtje, John F, Diaz, Denisse, Lamas, Gervasio A, and Fonseca, Vivian

Abstract

For decades, there has been epidemiologic evidence linking chronic toxic metal exposure with cardiovascular disease, suggesting a therapeutic role for metal chelation. Given the lack of compelling scientific evidence, however, the indications for metal chelation were never clearly defined. To determine the safety and efficacy of chelation therapy, the National Institutes of Health funded the Trial to Assess Chelation Therapy (TACT). TACT was the first double-blind, randomized, controlled trial to demonstrate an improvement in cardiovascular outcomes with edetate disodium therapy in patients with prior myocardial infarction. The therapeutic benefit was striking among the prespecified subgroup of patients with diabetes.

Published
2019
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26. Diabetes mellitus is a coronary heart disease risk equivalent for peripheral vascular disease.

Author

Newman, Jonathan D., Rockman, Caron B., Kosiborod, Mikhail, Guo, Yu, Zhong, Hua, Weintraub, Howard S., Schwartzbard, Arthur Z., Adelman, Mark A., and Berger, Jeffrey S.

Abstract

Diabetes mellitus (diabetes) is associated with significantly increased risk of peripheral vascular disease. Diabetes is classified as a coronary heart disease (CHD) risk equivalent, but it is unknown whether diabetes is a CHD risk equivalent for peripheral vascular disease. The objective was to evaluate the odds of peripheral arterial disease (PAD) or carotid artery stenosis (CAS) among participants with diabetes, CHD, or both, compared with participants without diabetes or CHD, in a nationwide vascular screening database. We hypothesized that diabetes and CHD would confer similar odds of PAD and CAS.Methods: A cross-sectional analysis of all eligible Life Line Screening Inc participants age 30 to 90 years with ankle brachial indices for PAD (ankle brachial index <0.9 in either leg) and carotid artery duplex ultrasonographic imaging for CAS (internal CAS ≥50%) was performed (N=3,522,890).Results: Diabetes and CHD were present in 372,330 (10.7%) and 182,760 (5.8%) of participants, respectively; PAD and CAS were present in 155,000 (4.4%) and 130,347 (3.7%) of participants. After multivariable adjustment, PAD odds were 1.56 (95% CI 1.54-1.59) and 1.69 (95% CI 1.65-1.73) for participants with diabetes or CHD, respectively. Participants with both diabetes and CHD had 2.75-fold increased odds of PAD (95% CI 2.66-2.85). Findings were similar for CAS; compared with no diabetes or CHD, CAS odds increased for participants with diabetes alone (1.53, 95% CI 1.50-1.56), CHD alone (1.72, 95% CI 1.68-1.76), and both diabetes and CHD (2.57, 95% CI 2.49-2.66). Findings were consistent for women and men.Conclusion: In a large database of more than 3.5 million self-referred participants, diabetes was a CHD risk equivalent for PAD and CAS, and participants with comorbid diabetes and CHD had an especially robust association with PAD and CAS. Counseling regarding screening and prevention of peripheral vascular disease may be useful for patients with diabetes. [ABSTRACT FROM AUTHOR]

Published
2017
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27. Current and potential future distribution of the American dog tick (Dermacentor variabilis, Say) in North America

Author

Minigan, Jordan N., Hager, Heather A., Peregrine, Andrew S., and Newman, Jonathan A.

Abstract

The American dog tick (Dermacentor variabilis) is medically and economically important in North America. This species is found across central and eastern North America from the Gulf Coast of Mexico through southern Canada. In parts of this region, D. variabilisis a vector for pathogens that cause diseases in humans and animals. Our aim was to determine whether climate change would affect the distribution of the climatically suitable area for D. variabilisin North America, to aid monitoring for potential future spread of tick-borne pathogens. We developed a species distribution model for D. variabilisto project where climate will likely be suitable for the tick in North America using a maximum entropy method, occurrence records from museum and laboratory archives, and 10 environmental variables relevant to climate requirements for the tick. We used four emissions scenarios from the Intergovernmental Panel on Climate Change's Fifth Assessment Report and 10 climate models from the Coupled Model Intercomparison Project (phase 5) to estimate potential future climate suitability and determine how the tick's distribution could change. Our consensus model projected that the area of suitable climate in North America could increase from present by approximately 50% by 2070. In areas beyond the current northern limit of D. variabilis, climate could become more suitable for the tick than at present, possibly resulting in a northward expansion in Canada, but the potential suitability of the southern range of D. variabiliscould decrease, depending on the region and climate model. Due to the ability of D. variabilisto harbor and transmit pathogens, a change in the distribution of this species could also affect the risk of human and animal diseases throughout North America, particularly in the northern range of the tick.

Published
2018
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28. The effect of a vegan versus AHA DiEt in coronary artery disease (EVADE CAD) trial: Study design and rationale

Author

Shah, Binita, Ganguzza, Lisa, Slater, James, Newman, Jonathan D., Allen, Nicole, Fisher, Edward, Larigakis, John, Ujueta, Francisco, Gianos, Eugenia, Guo, Yu, and Woolf, Kathleen

Abstract

Multiple studies demonstrate the benefit of a vegan diet on cardiovascular risk factors when compared to no intervention or usual dietary patterns. The aim of this study is to evaluate the effect of a vegan diet versus the American Heart Association (AHA)-recommended diet on inflammatory and glucometabolic profiles in patients with angiographically defined coronary artery disease (CAD).

Published
2017
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29. Ciceronian Ethos and Clerical Masculinity in the Regensburg Rhetorical Letters

Author

Newman, Jonathan M.

Abstract

Abstract:The Regensburg Rhetorical Letters are fictional letters composed in the 1080s at the Regensburg cathedral school. They imitate Ciceronian texts to fashion a valorized masculine identity based in learning, eloquence, and public service for secular clerics in civil administration who were attacked for idleness and effeminacy by reformers like Peter Damian. Centering textual and rhetorical expertise, the Letters reveal the heterogeneity of clerical society and an early development of a professional rather than spiritual role for the clergy.Abstract:Les Lettres rhétoriques de Ratisbonne sont des lettres fictives composées dans les années 1080 à l’école cathédrale de Ratisbonne. Elles imitent les textes cicéroniens afin de créer une identité masculine valorisée qui s’appuie sur l’étude, l’éloquence et le service public pour les clercs séculiers actifs dans l’administration civile qui étaient attaqués pour leur oisiveté et leur caractère efféminé par des réformateurs comme Pierre Damien. Mettant de l’avant l’expertise textuelle et rhétorique, les Lettres révèlent l’hétérogénéité de la société cléricale et le développement précoce d’un rôle professionnel plutôt que spirituel pour le clergé.

Published
2017

31. Metal pollutants and cardiovascular disease: Mechanisms and consequences of exposure.

Author

Solenkova, Natalia V., Newman, Jonathan D., Berger, Jeffrey S., Thurston, George, Hochman, Judith S., and Lamas, Gervasio A.

Abstract

Introduction There is epidemiological evidence that metal contaminants may play a role in the development of atherosclerosis and its complications. Moreover, a recent clinical trial of a metal chelator had a surprisingly positive result in reducing cardiovascular events in a secondary prevention population, strengthening the link between metal exposure and cardiovascular disease (CVD). This is, therefore, an opportune moment to review evidence that exposure to metal pollutants, such as arsenic, lead, cadmium, and mercury, is a significant risk factor for CVD. Methods We reviewed the English-speaking medical literature to assess and present the epidemiological evidence that 4 metals having no role in the human body (xenobiotic), mercury, lead, cadmium, and arsenic, have epidemiologic and mechanistic links to atherosclerosis and CVD. Moreover, we briefly review how the results of the Trial to Assess Chelation Therapy (TACT) strengthen the link between atherosclerosis and xenobiotic metal contamination in humans. Conclusions There is strong evidence that xenobiotic metal contamination is linked to atherosclerotic disease and is a modifiable risk factor. [ABSTRACT FROM AUTHOR]

Published
2014
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32. Abstract 13334: Whole Blood Multi-Omic Characterization of the ISCHEMIA Cohort Reveals Vulnerable and Resilient Subtypes of Chronic Coronary Disease

Author

Cornwell, Macintosh G, Chen, Ze, Kullo, Iftikhar J, McManus, Bruce M, Newby, L Kristin K, Held, Claes, Bangalore, Sripal, Maron, David J, Hochman, Judith S, Reynolds, Harmony R, Berger, Jeffrey S, Newman, Jonathan D, and Ruggles, Kelly V

Abstract

Introduction:Chronic coronary disease (CCD) is a leading cause of death worldwide. Whole blood (WB) transcriptomic (RNA-seq) and methylation ‘omics’ data can discern molecular underpinnings of CCD and create molecular subtypes to aid risk prediction.Methods:Of 1,064 participants with moderate-severe ischemia (Age: 67.1±6.2, 19.4% Female, 17% non-White) from the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) biorepository, 646 participants had available WB RNA-seq and 737 had WB methylation data (Fig 1A). Unsupervised clustering and differential analyses identified omics-derived molecular subtypes. We identified co-regulated gene modules of each subtype, performed subtype-level enrichment of clinical variables, and performed Kaplan-Meier analyses for time to cardiovascular (CV) death or myocardial infarction (MI).Results:Multi-omic analysis revealed 4 RNA-seq-derived subtypes (RS) and 3 methylation-derived subtypes (MS). RNA-seq Subtype 1 (RS1) was enriched for molecular drivers indicative of an adaptive immune response, had clinical enrichment of female sex, statin use, and greater ischemia, and had decreased risk of CV death or MI (Fig 1B). RNA-seq Subtype 2 (RS2) was enriched for innate immune response pathway, and patients who were older and White, and was associated with increased risk of CV death or MI. Similarly, methylation subtypes also yielded a high-risk subtype (MS3) and a low-risk subtype (MS2) (Fig 1C). Integration of transcriptomic and methylomic subtypes led to further distinction of resilient and vulnerable subgroups.Conclusions:WB RNA-seq and methylation data identified molecularly-defined subtypes that informed the underlying disease pathology of CCD patients in ISCHEMIA. These subgroups were differentially enriched for clinical characteristics and event outcomes, demonstrating the potential use for blood-based omics tests to aid in the prognosis of CCD.

Published
2022
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33. Abstract 13582: Biomarkers of Adverse Cardiovascular Events in Chronic Coronary Disease: Data From the ISCHEMIA Trial

Author

Newman, Jonathan D, Ruggles, Kelly V, Cornwell, Macintosh, Anthopolos, Rebecca, Held, Claes, Kullo, Iftikhar J, Newby, L Kristin K, McManus, Bruce M, Bangalore, Sripal, Reynolds, Harmony R, Hochman, Judith S, Maron, David J, and Berger, Jeffrey S

Abstract

Introduction:Circulating biomarkers may improve prediction of cardiovascular (CV) events in chronic coronary disease (CCD). The incremental value of biomarkers in CCD after adjustment for clinical factors, inducible ischemia and coronary artery disease (CAD) severity is uncertain.Methods:756 ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) participants with site-determined moderate-severe ischemia and 9 assayed biomarkers (Figure) were included. Among participants with interpretable stress tests for ischemia and CAD by computed coronary tomography angiography (CCTA) (N=507), associations of biomarkers with the primary (CV death, myocardial infarction (MI), or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest) or secondary endpoints (CV death or MI) were evaluated using sequentially adjusted multivariable Cox proportional hazards models (Model 1=unadjusted, Model 2=clinical features, Model 3=Model 2 + multivessel CAD by CCTA, and Model 4=Model 3 + severe ischemia).Results:Median (IQR) participant age was 64 (57-70) years, 19% were female, 81% white, and 5% Hispanic. Hypertension (85%), diabetes (46%) and obesity (45%) were common, 28% had an estimated glomerular filtration rate <60 ml/min/1.73m2. Severe ischemia was present in 44%, and 39% had multivessel CAD (≥70% stenosis) by CCTA. Over 3.5 (2.4-4.7) years of follow-up there were 146 (19%) primary and 128 (17%) secondary endpoints. Soluble CD40L, GDF-15, NT-proBNP, hsTnT were associated with the primary and secondary endpoints in univariable and multivariable (adjusting for clinical features, multivessel CAD and severe ischemia) models.Conclusion:Biomarkers of inflammation (GDF-15), thrombosis (sCD40L), myocardial stretch (NT-proBNP) and injury (hs-troponin) were associated with CV endpoints in the ISCHEMIA trial independent of clinical features, multivessel CAD and severe ischemia.

Published
2022
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34. Is it Possible to Care for Ecosystems? Policy Paralysis and Ecosystem Management

Author

Garcia, Robert K. and Newman, Jonathan A.

Abstract

AbstractConservationists have two (non-mutually exclusive) types of arguments for why we should conserve ecosystems: instrumental and intrinsic value arguments. Instrumental arguments contend that we ought to conserve ecosystems because of the benefits that humans, or other morally relevant individuals, derive from ecosystems. Conservationists are often loath to rely too heavily on the instrumental argument because it could potentially force them to admit that some ecosystems are not at all useful to humans, or that if they are, they are not more useful than alternative configurations of those ecosystems. Consequently, conservationists often resort to an intrinsic value argument, contending that ecosystems are objectively valuable as ends in themselves, rather than merely as means to an end. If ecosystems have intrinsic value, then they have moral standing, which means that we must consider their needs and interests in any decisions we make about them. This paper concerns the significance of this move for individual and collective action on behalf of ecosystems. We show that even if there were ecosystems that had moral standing, we would lack adequate practical reasons to act on their behalf.

Published
2016
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35. Association between fine particulate matter exposure and subclinical atherosclerosis: A meta-analysis

Author

Akintoye, Emmanuel, Shi, Liuhua, Obaitan, Itegbemie, Olusunmade, Mayowa, Wang, Yan, Newman, Jonathan D, and Dodson, John A

Abstract

Background Epidemiological studies in humans that have evaluated the association between fine particulate matter (PM2.5) and atherosclerosis have yielded mixed results.Design In order to further investigate this relationship, we conducted a comprehensive search for studies published through May 2014 and performed a meta-analysis of all available observational studies that investigated the association between PM2.5and three noninvasive measures of clinical and subclinical atherosclerosis: carotid intima media thickness, arterial calcification, and ankle-brachial index.Methods and results Five reviewers selected studies based on predefined inclusion criteria. Pooled mean change estimates and 95% confidence intervals were calculated using random-effects models. Assessment of between-study heterogeneity was performed where the number of studies was adequate. Our pooled sample included 11,947 subjects for carotid intima media thickness estimates, 10,750 for arterial calcification estimates, and 6497 for ankle-brachial index estimates. Per 10 µg/m3increase in PM2.5exposure, carotid intima media thickness increased by 22.52 µm but this did not reach statistical significance (p= 0.06). We did not find similar associations for arterial calcification (p= 0.44) or ankle-brachial index (p= 0.85).Conclusion Our meta-analysis supports a relationship between PM2.5and subclinical atherosclerosis measured by carotid intima media thickness. We did not find a similar relationship between PM2.5and arterial calcification or ankle-brachial index, although the number of studies was small.

Published
2016
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37. Prognosis of Patients With Non-ST-Segment-Elevation Myocardial Infarction and Nonobstructive Coronary Artery Disease.

Author

Planer, David, Mehran, Roxana, Ohman, E. Magnus, White, Harvey D., Newman, Jonathan D., Xu, Ke, and Stone, Gregg W.

Abstract

Troponin elevation is a risk factor for mortality in patients with non-ST-segment-elevation acute coronary syndromes. However, the prognosis of patients with troponin elevation and nonobstructive coronary artery disease (CAD) is unknown. Our objective was therefore to evaluate the impact of nonobstructive CAD in patients with non-ST-segment-elevation acute coronary syndromes and troponin elevation enrolled in the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial.In the ACUITY trial, 3-vessel quantitative coronary angiography was performed in a formal substudy of 6921 patients presenting with non-ST-segment-elevation acute coronary syndromes. Patients with elevated admission troponin levels were stratified by the presence or absence of obstructive CAD (any lesion with quantitative diameter stenosis >50%). Propensity score matching was performed to adjust for baseline characteristics. Of 2442 patients with elevated troponin, 197 (8.8%) had nonobstructive CAD. Maximum diameter stenosis was 87.4 (73.2, 100.0) versus 22.6 (19.2, 25.7; P<0.0001) in patients with versus without obstructive CAD, respectively. Propensity matching yielded 117 patients with nonobstructive CAD and 331 patients with obstructive CAD, with no significant baseline differences between groups. In the matched cohort, overall 1-year mortality was significantly higher in patients with nonobstructive CAD (5.2% versus 1.6%; hazard ratio [95% confidence interval]=3.44 [1.05, 11.28]; P=0.04), driven by greater noncardiac mortality. Conversely, recurrent myocardial infarction and unplanned revascularization rates were significantly higher in patients with obstructive CAD.Patients with non-ST-segment-elevation acute coronary syndromes and elevated troponin levels but without obstructive CAD, while having low rates of subsequent myocardial infarction and unplanned revascularization, are still at considerable risk for 1-year mortality from noncardiac causes.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00093158. [ABSTRACT FROM AUTHOR]

Published
2014
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38. Effect of change in systolic blood pressure between clinic visits on estimated 10-year cardiovascular disease risk.

Author

Ye, Siqin, Wang, Y. Claire, Shimbo, Daichi, Newman, Jonathan D., Levitan, Emily B., and Muntner, Paul

Abstract

Abstract: Systolic blood pressure (SBP) often varies between clinic visits within individuals, which can affect estimation of cardiovascular disease (CVD) risk. We analyzed data from participants with two clinic visits separated by a median of 17 days in the Third National Health and Nutrition Examination Survey (n = 808). Ten-year CVD risk was calculated with SBP obtained at each visit using the Pooled Cohort Equations. The mean age of participants was 46.1 years, and 47.3% were male. The median SBP difference between the two visits was −1 mm Hg (1st to 99th percentiles: −23 to 32 mm Hg). The median estimated 10-year CVD risk was 2.5% and 2.4% at the first and second visit, respectively (1st to 99th percentiles −5.2% to +7.1%). Meaningful risk reclassification (ie, across the guideline recommended 7.5% threshold for statin initiation) occurred in 12 (11.3%) of 106 participants whose estimated CVD risk was between 5% and 10%, but only in two (0.3%) of 702 participants who had a 10-year estimated CVD risk of <5% or >10%. SBP variability can affect CVD risk estimation, and can influence statin eligibility for individuals with an estimated 10-year CVD risk between 5% and 10%. [Copyright &y& Elsevier]

Published
2014
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40. Association between annual visit-to-visit blood pressure variability and stroke in postmenopausal women: data from the Women's Health Initiative.

Author

Shimbo D, Newman JD, Aragaki AK, LaMonte MJ, Bavry AA, Allison M, Manson JE, Wassertheil-Smoller S, Shimbo, Daichi, Newman, Jonathan D, Aragaki, Aaron K, LaMonte, Michael J, Bavry, Anthony A, Allison, Matthew, Manson, JoAnn E, and Wassertheil-Smoller, Sylvia

Abstract

Accumulating evidence suggests that increased visit-to-visit variability (VVV) of blood pressure is associated with stroke. No study has examined the association between VVV of blood pressure and stroke in postmenopausal women, and scarce data exist as to whether this relation is independent of the temporal trend of blood pressure. We examined the association of VVV of blood pressure with stroke in 58,228 postmenopausal women enrolled in the Women's Health Initiative. Duplicate blood pressure readings, which were averaged, were taken at baseline and at each annual visit. VVV was defined as the SD for the participant's mean systolic blood pressure (SBP) across visits (SD) and about the participant's regression line with SBP regressed across visits (SDreg). Over a median follow-up of 5.4 years, 997 strokes occurred. In an adjusted model including mean SBP over time, the hazard ratios (95% CI) of stroke for higher quartiles of SD of SBP compared with the lowest quartile (referent) were 1.39 (1.03-1.89) for quartile 2, 1.52 (1.13-2.03) for quartile 3, and 1.72 (1.28-2.32) for quartile 4 (P trend <0.001). The relation was similar for SDreg of SBP quartiles in a model that additionally adjusted for the temporal trend in SBP (P trend <0.001). The associations did not differ by stroke type (ischemic versus hemorrhagic). There was a significant interaction between mean SBP and SDreg on stroke with the strongest association seen below 120 mmHg. In postmenopausal women, greater VVV of SBP was associated with increased risk of stroke, particularly in the lowest range of mean SBP. [ABSTRACT FROM AUTHOR]

Published
2012
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41. Association Between Annual Visit-to-Visit Blood Pressure Variability and Stroke in Postmenopausal Women.

Author

Shimbo, Daichi, Newman, Jonathan D., Aragaki, Aaron K., LaMonte, Michael J., Bavry, Anthony A., Allison, Matthew, Manson, JoAnn E., and Wassertheil-Smoller, Sylvia

Abstract

This article describes a study which examined the association between visit-to-visit variability (VVV) of blood pressure and stroke in postmenopausal women. The study population included 58,228 postmenopausal women enrolled in the Women's Health Initiative. Researchers measured blood pressure and heart rate at baseline and each annual study visit. They learned that the association did not differ by stroke type.

Published
2012
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42. Prevalence and persistence of foreign DNA beneath fingernails.

Author

Matte, Melinda, Williams, Linda, Frappier, Roger, and Newman, Jonathan

Subjects
FINGERNAILS, DNA analysis, DNA fingerprinting, FORENSIC sciences, DNA data banks, FORENSIC genetics
Abstract

Abstract: Fingernail scrapings and clippings are routinely examined for the presence of foreign DNA profiles in forensic casework where the case history suggests their evidentiary relevance. In order to better understand the significance of these findings, casework results from the Centre of Forensic Sciences (CFS) were analyzed and several controlled studies were conducted. In an analysis of casework data (n =265), 33% of fingernail samples contained a foreign source of DNA, 63% of which were detected at 5 or more STR loci. In a sampling of fingernails from the general population (n =178), 19% contained a foreign source of DNA, 35% of which were detected at 5 or more STR loci. In a study involving deliberate scratching of another individual (n =30), 33% of individuals had a foreign DNA profile beneath their fingernails from which the person they scratched could not be excluded as the source; however when sampling occurred ∼6h after the scratching event, only 7% retained the foreign DNA. This research suggests the incidence of foreign DNA profiles beneath fingernails in the general population is low but, when present, the majority is of limited significance and tends not to persist for an extensive period of time. These data are provided to assist the forensic analyst when providing his or her opinion as to the relevance of foreign DNA present under fingernails. [Copyright &y& Elsevier]

Published
2012
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43. Abstract 227: Statins Decrease Endothelial Cell Inflammation On Top Of Maximal Cholesterol Reduction: Findings From The American Heart Association Strategically Focused Cardiometabolic Health And Type 2 Diabetes Mellitus Research Network

Author

Jindal, Manila, Garshick, Michael S, Schlamp, Florencia, Barrett, Tessa, Giannarelli, Chiara, Newman, Jonathan, Fadzan, Maja, Heguy, Adriana, Fisher, Edward A, Goldberg, Ira J, and Berger, Jeffrey S

Abstract

Background:Dyslipidemia induces a proinflammatory endothelium and vascular dysfunction. Lipid lowering therapy (LLT) consistently reduces cardiovascular (CV) events. Clinical studies suggest that statin-based LLT has pleiotropic anti-inflammatory effects beyond cholesterol reduction. However, the impact of statins or ezetimibe on top of potent cholesterol reduction is unknown. Thus, on a background of PCSK9 inhibition (with evolocumab), we analyzed the effect of LLT with atorvastatin or ezetimibe on the endothelium using a novel direct brachial vein (BV) endothelial cell (EC) harvesting technique.Methods:CHORD (CHOlesterol lowering and Residual Risk in Diabetes) is an ongoing, prospective study designed to evaluate the effect of maximal LLT on CV risk. Subjects with LDL-C >100mg/dl were treated with evolocumab (140mg/2 weeks) and either atorvastatin (80mg/day) or ezetimibe (10mg/day) for 30 days. In a subset of participants, EC harvesting was performed by inserting a J-wire into the BV, and ECs were isolated and analyzed using next generation RNA sequencing.Results:Among 20 participants (11 atorvastatin, 9 ezetimibe) undergoing EC RNASeq, median LDL-C (130 mg/dl, IQR [110, 147]) decreased by 75% [67, 81] on background PCSK9 inhibition with no significant difference in 30-day LDL-C between atorvastatin (27 mg/dl [20, 32]) and ezetimibe (41 mg/dl [26, 53]) groups (p=0.07). Following cholesterol reduction, 850 genes were upregulated and 2468 were downregulated (p<0.05) with downregulation of eNOS, Endothelin-1, and Senescence pathways by canonical pathway analysis. When stratified by LLT, patients receiving atorvastatin had a significant decrease in inflammation and senescence pathways compared to patients receiving ezetimibe (Figure).Conclusions:Robust lipid lowering with PCSK9 inhibition plus statins, as opposed to ezetimibe has anti-inflammatory effects and suggests a preferred strategy to improve the endothelium and reduce CV risk.

Published
2022
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44. Abstract 134: Atorvastatin As Opposed To Ezetimibe Reduces Biomarkers Of Thrombosis In The Setting Of Aggressive Lipid Lowering Therapy: Findings From The American Heart Association Strategically Focused Cardiometabolic Health And Type 2 Diabetes Mellitus Research Network

Author

Garshick, Michael, Jindal, Manila, Myndzar, Khrystyna, Barrett, Tessa, Newman, Jonathan, Fadzn, Maja, Xia, Yuhe, Giannarelli, Chiara, Fisher, Edward, Goldberg, Ira J, and Berger, Jeffrey S

Abstract

Introduction:CHORD (CHOlesterol lowering and Residual Risk in Diabetes) is an ongoing, prospective, multicenter study designed to evaluate the effect of maximal cholesterol-lowering on cardiovascular (CV) risk. Aggressive lipid-lowering with HMG CoA-reductase inhibitors (e.g. statins), ezetimibe, and PCSK9 inhibitors (such as evolocumab) reduce atherothrombotic events. Statins reduce cholesterol dramatically and are also felt to have pleiotropic, anti-inflammatory properties. We compared the impact of statins and ezetimibe on thrombotic biomarkers after maximal lipid lowering with PCSK9 inhibition.Methods:CHORD enrolled subjects (n=57, mean age 52 ± 15 years, 44% male, 58% diabetes) with LDL-cholesterol >100mg/dl and treated with evolocumab (140mg every 2 weeks) plus either atorvastatin (80mg/day, n=27), or ezetimibe (10mg/day, n=30) for 30-days. High-sensitivity C-reactive protein (hs-CRP) and biomarkers of thrombosis (LEGENDplex Human Thrombosis Panel) were measured at baseline and follow-up.Results:Significant LDL-C reductions were observed in both the evolocumab + atorvastatin (130 mg/dl [123 - 145] to 31 mg/dl [27 - 39], p<0.001) and evolocumab + ezetimibe (127 mg/dl [106 - 138] to 38 mg/dl [27 - 56], p<0.001) groups. Hs-CRP was reduced after evolocumab + atorvastatin (18% reduction, p<0.01), but not evolocumab + ezetimibe. When compared to evolocumab + ezetimibe, greater reductions in P-selectin, D-Dimer, Factor IX, and a trend towards reduction in sCD40L, and PAI-1 were noted after evolocumab + atorvastatin (Figure 1).Conclusion:Despite similar levels of LDL-C reduction, statins plus evolocumab cause greater reductions in biomarkers of thrombosis and inflammation than ezetimibe and evolocumab. These data suggest that statins provide benefits over and above LDL-C reduction.

Published
2022
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45. The effect of hormone therapy on mean blood pressure and visit-to-visit blood pressure variability in postmenopausal women

Author

Shimbo, Daichi, Wang, Lu, Lamonte, Michael J., Allison, Matthew, Wellenius, Gregory A., Bavry, Anthony A., Martin, Lisa W., Aragaki, Aaron, Newman, Jonathan D., Swica, Yael, Rossouw, Jacques E., Manson, JoAnn E., and Wassertheil-Smoller, Sylvia

Abstract

Mean and visit-to-visit variability (VVV) of blood pressure (BP) are associated with an increased cardiovascular disease risk. We examined the effect of hormone therapy on mean and VVV of BP in postmenopausal women from the Women's Health Initiative (WHI) randomized controlled trials.

Published
2014
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47. Psychosocial care for persons affected by emergencies and major incidents: a Delphi study to determine the needs of professional first responders for education, training and support

Author

Drury, John, Kemp, Verity, Newman, Jonathan, Novelli, David, Doyle, Christopher, Walter, Darren, and Williams, Richard

Abstract

BackgroundThe role of ambulance clinicians in providing psychosocial care in major incidents and emergencies is recognised in recent Department of Health guidance. The study described in this paper identified NHS professional first responders’ needs for education about survivors’ psychosocial responses, training in psychosocial skills, and continuing support.MethodAmbulance staff participated in an online Delphi questionnaire, comprising 74 items (Round 1) on 7-point Likert scales. Second-round and third-round participants each received feedback based on the previous round, and responded to modified versions of the original items and to new items for clarification.ResultsOne hundred and two participants took part in Round 1; 47 statements (64%) achieved consensus. In Round 2, 72 people from Round 1 participated; 15 out of 39 statements (38%) achieved consensus. In Round 3, 49 people from Round 2 participated; 15 out of 27 statements (59%) achieved consensus. Overall, there was consensus in the following areas: ‘psychosocial needs of patients’ (consensus in 34/37 items); ‘possible sources of stress in your work’ (8/9); ‘impacts of distress in your work’ (7/10); ‘meeting your own emotional needs’ (4/5); ‘support within your organisation’ (2/5); ‘needs for training in psychosocial skills for patients’ (15/15); ‘my needs for psychosocial training and support’ (5/6).ConclusionsAmbulance clinicians recognise their own education needs and the importance of their being offered psychosocial training and support. The authors recommend that, in order to meet patients’ psychosocial needs effectively, ambulance clinicians are provided with education and training in a number of skills and their own psychosocial support should be enhanced.

Published
2013
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48. Centralized, Stepped, Patient Preference–Based Treatment for Patients With Post–Acute Coronary Syndrome Depression: CODIACS Vanguard Randomized Controlled Trial

Author

Davidson, Karina W., Bigger, J. Thomas, Burg, Matthew M., Carney, Robert M., Chaplin, William F., Czajkowski, Susan, Dornelas, Ellen, Duer-Hefele, Joan, Frasure-Smith, Nancy, Freedland, Kenneth E., Haas, Donald C., Jaffe, Allan S., Ladapo, Joseph A., Lespérance, Francois, Medina, Vivian, Newman, Jonathan D., Osorio, Gabrielle A., Parsons, Faith, Schwartz, Joseph E., Shaffer, Jonathan A., Shapiro, Peter A., Sheps, David S., Vaccarino, Viola, Whang, William, and Ye, Siqin

Abstract

IMPORTANCE Controversy remains about whether depression can be successfully managed after acute coronary syndrome (ACS) and the costs and benefits of doing so. OBJECTIVE To determine the effects of providing post-ACS depression care on depressive symptoms and health care costs. DESIGN Multicenter randomized controlled trial. SETTING Patients were recruited from 2 private and 5 academic ambulatory centers across the United States. PARTICIPANTS A total of 150 patients with elevated depressive symptoms (Beck Depression Inventory [BDI] score ≥10) 2 to 6 months after an ACS, recruited between March 18, 2010, and January 9, 2012. INTERVENTIONS Patients were randomized to 6 months of centralized depression care (patient preference for problem-solving treatment given via telephone or the Internet, pharmacotherapy, both, or neither), stepped every 6 to 8 weeks (active treatment group; n = 73), or to locally determined depression care after physician notification about the patient's depressive symptoms (usual care group; n = 77). MAIN OUTCOME MEASURES Change in depressive symptoms during 6 months and total health care costs. RESULTS Depressive symptoms decreased significantly more in the active treatment group than in the usual care group (differential change between groups, −3.5 BDI points; 95% CI, −6.1 to −0.7; P = .01). Although mental health care estimated costs were higher for active treatment than for usual care, overall health care estimated costs were not significantly different (difference adjusting for confounding, −$325; 95% CI, −$2639 to $1989; P = .78). CONCLUSIONS For patients with post-ACS depression, active treatment had a substantial beneficial effect on depressive symptoms. This kind of depression care is feasible, effective, and may be cost-neutral within 6 months; therefore, it should be tested in a large phase 3 pragmatic trial. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01032018

Published
2013
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50. Abstract 9856: Associations of a Polygenic Risk Score (PGS) with High Risk Coronary Artery Disease (CAD) in PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain)

Author

Newman, Jonathan D, Douglas, Pamela S, Zhbannikov, Ilya, Ferencik, Maros, Foldyna, Borek, Hoffmann, Udo, Shah, Svati H, Ginsburg, Geoffrey S, Lu, Michael T, and Voora, Deepak

Abstract

Introduction:PGSs summarize the polygenic risk for CAD and may have clinical utility. We tested whether a previously validated PGS for CAD is associated with coronary CT angiography (CTA) findings predictive of future cardiovascular events in the PROMISE trial, which randomized individuals with stable outpatient chest pain to standard of care vs. CTA.Methods:This nested case-control study compared genotyped PROMISE participants with no CAD (0% stenosis), obstructive CAD (oCAD, ≥50% stenosis) or high-risk CAD defined as either oCAD ≥70% stenosis, CAC >400, Leaman Score > 5 (measure of stenosis and plaque burden), or any high-risk plaque feature (positive remodeling, low attenuation, napkin ring sign) on CTA. The Illumina Global Screening Array with imputation from the 1000 Genomes reference panel was used with LDpred to calculate ancestry-adjusted PGS. We calculated adjusted odds ratios (aORs) of oCAD and high-risk CAD for PGS quintiles 2-5 with quintile 1 as the referent using logistic regression and age, sex, and European Society of Cardiology pre-test probability (PTP) for obstructive CAD as covariates.Results:Among the 518 participants, 414=no CAD, 86=oCAD, and 103=high risk CAD (overlap of oCAD and high-risk CAD=85), the median age (±S.D.) was 58 (±7) years, 58% were female, and 13% were of non-white race or Hispanic ethnicity. Baseline characteristics, family history of premature CAD, PTP risk score and medications were similar across PGRS quintiles (all P>0.2). After multivariate adjustment, PGRS quintile 5 was associated with significantly increased odds of oCAD ≥50% (aOR 6.09) and high-risk CAD (aOR 6.13) as compared with quintile 1.Conclusions:In a population of stable symptomatic outpatients, higher PGS was associated with oCAD and high-risk CAD on CTA, even after adjustment for age, sex and pretest probability of CAD. The PGS may be useful for risk stratification of outpatients with suspected CAD.

Published
2021
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