Publications by authors named "Christopher deFilippi"

Importance: In a mechanistic substudy of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) randomized clinical trial, pitavastatin reduced noncalcified plaque (NCP) volume, but specific protein and gene pathways contributing to changes in coronary plaque remain unknown.

Objective: To use targeted discovery proteomics and transcriptomics approaches to interrogate biological pathways beyond low-density lipoprotein cholesterol (LDL-C), relating statin outcomes to reduce NCP volume and promote plaque stabilization among people with HIV (PWH).

Design, Setting, And Participants: This was a post hoc analysis of the double-blind, placebo-controlled, REPRIEVE randomized clinical trial.

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Background: Proteomic phenotyping can provide insights into rejection pathophysiology, novel biomarkers, and therapeutic targets.

Methods: Within the prospective, multicenter Genomic Research Alliance for Transplantation study, 181 proteins were evaluated from blood drawn at the time of endomyocardial biopsy; protein fold change, logistic regression, and pathway analyses were conducted, with protein discovery adjusted for a 5% false discovery rate.

Results: Among 104 adult heart transplant patients (31% female sex, 53% Black race, median age 52 y), 74 had no rejection, 18 developed acute cellular rejection (ACR), and 12 developed antibody-mediated rejection (AMR).

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Cardiovascular disease (CVD), including atherosclerosis, valvular etiologies, or myocardial disorders, is typically asymptomatic for several years, representing an occult phase of illness. Readily available preventive treatments to reduce cholesterol and blood pressure, among other risk factors, have the potential to reduce and delay incident myocardial infarction (MI), heart failure, and cardiovascular (CV) deaths. Measurement of circulating levels of cardiac troponin T (cTnT) and troponin I (cTnI) released from cardiomyocytes, as a result of injury, has been the biochemical standard for the diagnosis of MI for more than 20 years.

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Background: We evaluated the Vitros® Immunodiagnostic Products N-terminal pro B-type natriuretic peptide (NT-proBNP) II assay for aiding in diagnosis of heart failure (HF) in patients with acute dyspnea.

Methods: Serum concentrations of NT-proBNP were measured in patient samples from 20 emergency departments across the United States. Study endpoints included sensitivity, specificity, likelihood ratios, and predictive values for diagnosis of acute HF according to age-stratified cutoffs (450, 900, and 1800 pg/mL), and a rule-out age-independent cutoff (300 pg/mL).

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Article Synopsis
  • * Conducted on 122 patients with moderate to severe aortic stenosis, the research identified specific circulating proteins that correlate with higher risks of heart failure, severe symptoms, and mortality.
  • * Key proteins linked to inflammation and immune responses were significantly associated with worse outcomes, particularly in patients showing reduced heart strain, suggesting new avenues for assessing patient risk beyond standard imaging methods.
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Background: Coronary plaque is common among people with HIV (PWH) with low-to-moderate traditional atherosclerotic cardiovascular disease (ASCVD) risk.

Objectives: The purpose of this study was to determine the association of high-sensitivity cardiac troponin T (hs-cTnT) levels with coronary plaque characteristics and evaluate if hs-cTnT improves identification of these features beyond traditional ASCVD risk factors among PWH.

Methods: Among PWH receiving stable antiretroviral therapy with low-to-moderate ASCVD risk and no known history of ASCVD, hs-cTnT levels and measures of plaque by coronary computed tomography angiography were assessed.

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  • The study focused on cardiovascular health among Chinese American immigrants in the MESA cohort, analyzing data from 746 participants over a median follow-up of 17.8 years.
  • Results indicated that longer residence in the U.S. is linked to a greater risk of cardiovascular disease death, while geographical differences showed varying survival probabilities between immigrants in Los Angeles and Chicago.
  • Key risk factors identified included elevated levels of certain biomarkers and cardiac imaging results, with no significant impact from the time of immigration on cardiovascular outcomes.
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Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome that may emerge from overlapping systemic processes associated with comorbidities. We assessed whether unique clusters of circulating proteins are associated with specific clinical characteristics and functional status at baseline and follow-up in a well-phenotyped cohort of patients with HFpEF.

Methods: We evaluated 368 proteins associated with cardiovascular disease and inflammation in prerandomization blood samples from 763 VITALITY-HFpEF (Vericiguat to Improve Physical Functioning in Daily Living Activities of Patients With HFpEF) participants who had a left ventricular ejection fraction ≥45% and a heart failure decompensation event within 6 months.

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Background: The COVID-19 pandemic disproportionately affected persons with underlying medical conditions. SARS-CoV-2 infection susceptibility and vaccine effectiveness in pediatric hematology-oncology patients were unknown.

Methods: From February to July 2022, anti-spike and anti-nucleocapsid Ig were assayed in 354 pediatric hematology-oncology subjects, including 53 oncology patients receiving chemotherapy (cancer), 150 patients with sickle cell disease (SCD), and 151 benign consult and long-term follow-up patients (controls).

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Importance: Identification of individuals at high risk for atherosclerotic cardiovascular disease within the population is important to inform primary prevention strategies.

Objective: To evaluate the prognostic value of routinely available cardiovascular biomarkers when added to established risk factors.

Design, Setting, And Participants: Individual-level analysis including data on cardiovascular biomarkers from 28 general population-based cohorts from 12 countries and 4 continents with assessments by participant age.

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  • The PARACOR-19 trial investigated whether the medication sacubitril/valsartan could improve heart health markers in patients who had recently recovered from COVID-19.
  • In this study involving 42 participants, the drug did not significantly affect the primary cardiac injury markers, high-sensitivity cardiac troponin T and soluble ST2, compared to a placebo.
  • However, exploratory results showed that sacubitril/valsartan led to notable reductions in other heart-related biomarkers, indicating it might help in reducing cardiac stress and improving collagen turnover.
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Introduction: Coronary artery calcium (CAC) scans contain useful information beyond the Agatston CAC score that is not currently reported. We recently reported that artificial intelligence (AI)-enabled cardiac chambers volumetry in CAC scans (AI-CAC™) predicted incident atrial fibrillation in the Multi-Ethnic Study of Atherosclerosis (MESA). In this study, we investigated the performance of AI-CAC cardiac chambers for prediction of incident heart failure (HF).

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Background: Coronary artery calcium (CAC) scans contain actionable information beyond CAC scores that is not currently reported.

Methods: We have applied artificial intelligence-enabled automated cardiac chambers volumetry to CAC scans (AI-CAC) to 5535 asymptomatic individuals (52.2% women, ages 45-84) that were previously obtained for CAC scoring in the baseline examination (2000-2002) of the Multi-Ethnic Study of Atherosclerosis (MESA).

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The professional landscape for clinical cardiologists and most physicians has changed dramatically in the last decade in the United States. By the end of 2020, 87% of cardiologists were integrated with a health system (employed or part of a professional services agreement). Physicians transitioning to a large employer are often dissatisfied with the lack of autonomy and the pressure from "one-size-fits-all" productivity targets.

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  • The study examined sex-related differences in outcomes for patients with cardiogenic shock (CS) using a standardized team-based approach (STBA), focusing on 520 patients over three years.
  • Women with acute myocardial infarction (AMI) showed greater baseline severity, while those with heart failure (HF) more frequently faced cardiac arrest and required more aggressive treatments compared to men.
  • Despite these findings, there were no significant differences in in-hospital mortality or major adverse events between sexes, suggesting the STBA may help reduce historical disparities in outcomes.
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Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that block immune checkpoints and therefore activate immune cells, allowing them to recognize and attack cancer cells. ICIs have revolutionized oncology practice, but their use has been complicated by immune-related adverse events (irAEs). Of cardiovascular (CV) irAEs, ICI-related myocarditis has received significant attention due to high mortality rates, ranging from 25% to 50%, despite its overall low incidence.

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Importance: Cardiovascular disease (CVD) is increased in people with HIV (PWH) and is characterized by premature noncalcified coronary plaque. In the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE), pitavastatin reduced major adverse cardiovascular events (MACE) by 35% over a median of 5.1 years.

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Background: Coronary artery calcium (CAC) scans contain actionable information beyond CAC scores that is not currently reported.

Methods: We have applied artificial intelligence-enabled automated cardiac chambers volumetry to CAC scans (AI-CAC), taking on average 21 seconds per CAC scan, to 5535 asymptomatic individuals (52.2% women, ages 45-84) that were previously obtained for CAC scoring in the baseline examination (2000-2002) of the Multi-Ethnic Study of Atherosclerosis (MESA).

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Background: Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to post-acute sequelae of SARS-CoV-2 (PASC) that can persist for weeks to years following initial viral infection. Clinical manifestations of PASC are heterogeneous and often involve multiple organs. While many hypotheses have been made on the mechanisms of PASC and its associated symptoms, the acute biological drivers of PASC are still unknown.

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Context: The relationship between thyroid dysfunction and measures of myocardial disease in older individuals remains to be defined.

Objective: To evaluate the impact of thyroid dysfunction on structure and function of the left heart chambers and blood markers of cardiac disease.

Methods: Cross-sectional analysis of the Cardiovascular Health Study, a community-based cohort of older individuals recruited from 4 urban areas in the United States.

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