Publications by authors named "Jonathan D Newman"

Platelets are key mediators of atherothrombosis, yet, limited tools exist to identify individuals with a hyperreactive platelet phenotype. In this study, we investigate the association of platelet hyperreactivity and cardiovascular events, and introduce a tool, the Platelet Reactivity ExpreSsion Score (PRESS), which integrates platelet aggregation responses and RNA sequencing. Among patients with peripheral artery disease (PAD), those with a hyperreactive platelet response (>60% aggregation) to 0.

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  • - The study aimed to replicate a previous finding that EDTA-based chelation therapy reduces cardiovascular disease (CVD) events in individuals with diabetes and a history of myocardial infarction (MI).
  • - Conducted at 88 sites in the US and Canada, the trial involved 959 participants who were randomly assigned to receive either chelation therapy or a placebo, with a median follow-up of 48 months.
  • - Results showed no significant difference in CVD events between the chelation group (35.6% experienced a primary event) and the placebo group (35.7%), indicating that chelation may not provide the hoped-for benefits in this population.
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  • The study aimed to evaluate the effectiveness of coronary computed tomography angiography (CCTA) in assessing the risk of cardiovascular events through atherosclerotic plaque analysis in patients with ischemia.
  • Using quantitative computed tomography (AI-QCT), researchers analyzed plaque characteristics and examined their relationship to cardiovascular death or myocardial infarction over an average follow-up of 3.3 years.
  • Results showed that total plaque volume was the strongest predictor of adverse outcomes, and incorporating AI-QCT data improved predictive models beyond traditional risk factors.
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Cardiometabolic co-morbidities, diabetes (DM), hypertension (HTN), and obesity contribute to cardiovascular disease. Circulating biomarkers facilitate prognostication for patients with cardiovascular disease. We explored the relation between cardiometabolic co-morbidity burden in patients with chronic coronary disease and biomarkers of myocardial stretch, injury, inflammation, and platelet activity.

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The prevalence of diabetes is estimated to reach almost 630 million cases worldwide by the year 2045; of current and projected cases, over 90% are type 2 diabetes. Air pollution exposure has been implicated in the onset and progression of diabetes. Increased exposure to fine particulate matter air pollution (PM) is associated with increases in blood glucose and glycated hemoglobin (HbA1c) across the glycemic spectrum, including normoglycemia, prediabetes, and all forms of diabetes.

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Ubiquitous environmental exposures increase cardiovascular disease risk via diverse mechanisms. This review examines personal strategies to minimize this risk. With regard to fine particulate air pollution exposure, evidence exists to recommend the use of portable air cleaners and avoidance of outdoor activity during periods of poor air quality.

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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.

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Background: 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.

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Background: The ISCHEMIA trial found that patients with chronic coronary disease randomized to invasive strategy had better health status than those randomized to conservative strategy. It is unclear how best to translate these population-level results to individual patients.

Objectives: The authors sought to identify patient characteristics associated with health status from invasive and conservative strategies, and develop a prediction algorithm for shared decision-making.

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  • * In the ISCHEMIA trial, women had similar catheterization rates but significantly lower revascularization rates than men (73.4% vs. 81.2%, respectively).
  • * Despite these differences, there were no significant disparities in primary outcomes like cardiovascular death and myocardial infarction between women and men, indicating that both sexes responded similarly to treatment.
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  • - Researchers found that patients with COVID-19 have a heightened risk of heart complications for up to a year after infection, and this might be linked to the virus's impact on cardiovascular health.
  • - The study detected SARS-CoV-2 viral RNA in coronary artery lesions from deceased COVID-19 patients, indicating that the virus can directly infect these areas and influence inflammation.
  • - SARS-CoV-2 seems to target macrophages in atherosclerotic plaques, leading to increased inflammatory responses that may contribute to both immediate and long-term cardiovascular risks.
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Background: Identifying patients with the optimal risk:benefit for ticagrelor is challenging. The aim was to identify ticagrelor-responsive platelet transcripts as biomarkers of platelet function and cardiovascular risk.

Methods: Healthy volunteers (n=58, discovery; n=49, validation) were exposed to 4 weeks of ticagrelor with platelet RNA data, platelet function, and self-reported bleeding measured pre-/post-ticagrelor.

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  • - COVID-19 patients have an increased risk of heart-related issues, such as heart attacks and strokes, for up to a year after infection, possibly due to the body’s inflammatory response to the virus.
  • - Research shows that SARS-CoV-2 can be found in coronary artery plaque samples from severe COVID-19 patients, indicating the virus may directly infect these areas and cause local inflammation.
  • - The virus targets macrophages (a type of immune cell) within the plaque, especially in cholesterol-rich environments, leading to a strong inflammatory response that could potentially result in serious cardiovascular complications.
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Importance: 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.

Objectives: To evaluate the prognostic value of multiple biomarkers in stable outpatients with obstructive CAD and moderate or severe inducible ischemia.

Design And Setting: 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.

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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.

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  • Cardiovascular disease is a major health issue for people with type 2 diabetes (T2D), prompting an analysis of how often proven therapies are used to lower cardiovascular risk over time in the U.S.
  • Data from a large diabetes registry showed an increase in prescriptions for SGLT2 inhibitors and GLP-1 receptor agonists from 2013 to 2019, yet fewer patients with high-risk conditions (like heart failure or chronic kidney disease) were receiving these medications compared to those without these comorbidities.
  • The findings highlight a treatment-risk paradox, suggesting that while the use of certain medications has improved, there is still a gap in their use among those who would benefit the most, indicating a need for better education on
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Background: Whether initial invasive management in older vs younger adults with chronic coronary disease and moderate or severe ischemia improves health status or clinical outcomes is unknown.

Objectives: The goal of this study was to examine the impact of age on health status and clinical outcomes with invasive vs conservative management in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial.

Methods: One-year angina-specific health status was assessed with the 7-item Seattle Angina Questionnaire (SAQ) (score range 0-100; higher scores indicate better health status).

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Background: 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).

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Background: The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) compared an initial invasive versus an initial conservative management strategy for patients with chronic coronary disease and moderate or severe ischemia, with no major difference in most outcomes during a median of 3.2 years. Extended follow-up for mortality is ongoing.

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The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) found that there was no statistical difference in cardiovascular events with an initial invasive strategy as compared with an initial conservative strategy of guideline-directed medical therapy for patients with moderate to severe ischemia on noninvasive testing. In this study, we describe the reasons that potentially eligible patients who were screened for participation in the ISCHEMIA trial did not advance to enrollment, the step prior to randomization. Of those who preliminarily met clinical inclusion criteria on screening logs submitted during the enrollment period, over half did not participate due to physician or patient refusal, a potentially modifiable barrier.

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Background: The ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) trial randomized participants with chronic coronary disease (CCD) to guideline-directed medical therapy with or without angiography and revascularization. The study examined the association of nonadherence with health status outcomes.

Objectives: The study sought to compare 12-month health status outcomes of adherent and nonadherent participants with CCD with an a priori hypothesis that nonadherent patients would have better health status if randomized to invasive management.

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