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Bariatric surgery normalizes diabetes risk index by one month post-operation

Sinatra, Vincent J; Lin, BingXue; Parikh, Manish; Berger, Jeffrey S; Fisher, Edward A; Heffron, Sean P
AIM/OBJECTIVE:The Diabetes risk index (DRI) is a composite of NMR-measured lipoproteins and branched chain amino acids predictive of diabetes mellitus development. Bariatric surgery is indicated in patients with severe obesity, many of whom are at high-risk for developing diabetes. Substantial weight loss occurs following bariatric surgery and sustained weight loss likely contributes to reductions in the development of diabetes and cardiovascular disease. However, some evidence suggests that bariatric surgical procedures themselves may contribute to reducing risk of these conditions independent of weight loss. We aimed to investigate DRI and its association with reductions in body weight and adiposity over one year following bariatric surgery. METHODS:; n = 15). RESULTS:, but DRI decreased so that it no longer differed from that of normal BMI controls (1.9 [1, 17] vs control 12 [1, 20]; p = 0.35). Subjects continued to lose weight, whereas DRI remained similar, throughout follow-up with DRI 1.0 [1, 7] at 12 months. Changes in DRI did not correlate with changes in BMI, body weight or waist circumference at any time during follow-up. There was no difference in change in DRI between surgical procedures or pre-operative metabolic syndrome status. CONCLUSIONS:Our analysis of DRI scores supports the capacity of bariatric surgery to reduce risk of developing diabetes in severely obese individuals. Our findings suggest that bariatric surgical techniques may have inherent effects that improve cardiometabolic risk independent of reductions in body weight or adiposity.
PMID: 36350383
ISSN: 1432-5233
CID: 5357342

Survival After Invasive or Conservative Management of Stable Coronary Disease

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; Pracon, Radoslaw; 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
PMID: 36335918
ISSN: 1524-4539
CID: 5356892

Childhood environment early life stress, caregiver warmth, and associations with the cortisol diurnal curve in adulthood: The coronary artery risk development in young adults (CARDIA) study

Ortiz, Robin; Zhao, Songzhu; Kline, David M; Brock, Guy; Carroll, Judith E; Seeman, Teresa E; Jaffee, Sara R; Berger, Jeffrey S; Golden, Sherita H; Carnethon, Mercedes R; Joseph, Joshua J
BACKGROUND:Early life stress (ELS) is associated with increased morbidity and mortality across the lifecourse. Studies observing a relationship between ELS and stress physiology (cortisol), may help explain the connection to poor health outcomes, but have been limited by cortisol measures used. PURPOSE/OBJECTIVE:We examined the association between ELS measured by a Risky Family (RF) environment questionnaire, and adult diurnal cortisol profile inclusive of multiple cortisol measures. METHODS:RF and cortisol were collected from Coronary Artery Risk Development in Young Adults Study participants at follow-up (Year 15). Complete case (n = 672) data were included in multi-variable regression analyses with log transformed cortisol measures (outcomes) including wake-up cortisol, cortisol awakening response [CAR], AUC and five other cortisol diurnal curve measures. RESULTS:Participants were age 39.9 + /- 3.7 years and 51.6% Black. For every 1 unit increase in RF, there was a 1.4% greater wake-up cortisol and flatter CAR after adjustment for age, sex, income, and smoking (B=0.014, p = 0.023; B=-0.014, p = 0.028, respectively). Each unit increase in caregiver warmth/affection was associated with a 6.9% higher (steeper) CAR (B=0.069, p = 0.03). Results remained significant after adjusting for other covariates except social support in adulthood. An interaction between child abuse and caregiver warmth was nearly significant (p = 0.068), such that for those with exposure to the greatest caregiver warmth and lowest child abuse, CAR was steepest CONCLUSIONS: We demonstrate that ELS is associated with altered cortisol regulation in adulthood. However, further research is needed to assess how healthy relationships throughout the life course may modulate cortisol regulation in adulthood.
PMID: 36599226
ISSN: 1873-3360
CID: 5409982

Toward Personalized DAPT: Is There an Inter-Manufacturer Difference in Generic Clopidogrel Response?

Hall, Sylvie; Xia, Yuhe; Ahmed, Hamza; Iskhakov, Daniela; Feit, Frederick; Alviar, Carlos L; Berger, Jeffrey S; Keller, Norma; Bangalore, Sripal
OBJECTIVE:To compare rates of clopidogrel response among patients receiving medication produced by 2 different manufacturers after acute coronary syndrome (ACS) and/or percutaneous coronary intervention. METHODS:This quality-improvement project included 515 adult patients receiving clopidogrel for ACS or ischemic heart disease and referred for coronary angiography/ percutaneous coronary intervention. The project was divided into 2 phases: (1) retrospective collection of baseline data (April 2019-October 2020); and (2) two 12-week, prospective phases in which all clopidogrel in the hospital was restricted to a single manufacturer at a time (November 2020-May 2021). The primary outcome was clopidogrel response measured by platelet function testing, defined as adenosine diphosphate (ADP) response <40% on light transmission aggregometry. RESULTS:Of 515 total patients included in both phases (mean age, 64.5 ± 11.4 years; 351 men [68.2%]; 450 with ACS [87.4%]), 52% were found to be clopidogrel responders based on results of platelet function testing. Among 135 patients in the prospective phase, there was a significantly lower proportion of patients who were clopidogrel responders in the Manufacturer 1 group compared with the Manufacturer 2 group (34.8% vs 55.1%, respectively; P=.03). After adjustment for age, sex, body mass index, aspirin response, therapeutic hypothermia, left heart catheterization indication, clopidogrel loading dose, time between loading dose and lab measurement, and manufacturer, aspirin response (odds ratio 0.96; 95% confidence interval, 0.95-0.97; P<.001) and manufacturer (odds ratio, 2.45; 95% confidence interval, 1.18-5.22; P=.02) were associated with clopidogrel response. CONCLUSIONS:In a large public hospital, we observed that pharmacodynamic response to clopidogrel varied by drug manufacturer. Further investigation and/or regulation is needed to minimize inter-manufacturer variability.
PMCID:9761404
PMID: 36416902
ISSN: 1557-2501
CID: 5381662

Postinjury platelet aggregation and venous thromboembolism

Matthay, Zachary A; Hellmann, Zane J; Nunez-Garcia, Brenda; Fields, Alexander T; Cuschieri, Joseph; Neal, Matthew D; Berger, Jeffrey S; Luttrell-Williams, Elliot; Knudson, M Margaret; Cohen, Mitchell J; Callcut, Rachael A; Kornblith, Lucy Z
BACKGROUND:Posttraumatic venous thromboembolism (VTE) remains prevalent in severely injured patients despite chemoprophylaxis. Importantly, although platelets are central to thrombosis, they are not routinely targeted in prevention of posttraumatic VTE. Furthermore, platelets from injured patients show ex vivo evidence of increased activation yet impaired aggregation, consistent with functional exhaustion. However, the relationship of this platelet functional phenotype with development of posttraumatic VTE is unknown. We hypothesized that, following injury, impaired ex vivo platelet aggregation (PA) is associated with the development of posttraumatic VTE. METHODS:We performed a secondary analysis of 133 severely injured patients from a prospective observational study investigating coagulation and inflammation (2011-2019). Platelet aggregation in response to stimulation with adenosine diphosphate (ADP), collagen, and thrombin was measured at presentation (preresuscitation) and 24 hours (postresuscitation). Viscoelastic clot strength and lysis were measured in parallel by thromboelastography. Multivariable regression examined relationships between PA at presentation, 24 hours, and the change (δ) in PA between presentation and 24 hours with development of VTE. RESULTS:The 133 patients were severely injured (median Injury Severity Score, 25), and 14% developed VTE (all >48 hours after admission). At presentation, platelet count and PA were not significantly different between those with and without incident VTE. However, at 24 hours, those who subsequently developed VTE had significantly lower platelet counts (126 × 10 9 /L vs. 164 × 10 9 /L, p = 0.01) and lower PA in response to ADP ( p < 0.05), collagen ( p < 0.05), and thrombin ( p = 0.06). Importantly, the magnitude of decrease in PA (δ) from presentation to 24 hours was independently associated with development of VTE (adjusted odds ratios per 10 aggregation unit decrease: δ-ADP, 1.31 [ p = 0.03]; δ-collagen, 1.36 [ p = 0.01]; δ-thrombin, 1.41 [ p < 0.01]). CONCLUSION:Severely injured patients with decreasing ex vivo measures of PA despite resuscitation have an increased risk of developing VTE. This may have implications for predicting development of VTE and for studying platelet targeted chemoprophylaxis regimens. LEVEL OF EVIDENCE:Prognostic/Epidemiological; Level III.
PMCID:9585095
PMID: 35444156
ISSN: 2163-0763
CID: 5357812

Antiplatelet Effects of Clopidogrel Vs Aspirin in Virologically Controlled HIV: A Randomized Controlled Trial

Marcantoni, Emanuela; Garshick, Michael S.; Schwartz, Tamar; Ratnapala, Nicole; Cambria, Matthew; Dann, Rebecca; O'Brien, Meagan; Heguy, Adriana; Berger, Jeffrey S.
Patients with HIV exhibit platelet activation and increased risk of cardiovascular disease, the prevention of which is not fully known. Fifty-five HIV-positive patients were randomized to clopidogrel, aspirin, or no-treatment for 14 days, and the platelet phenotype and ability to induce endothelial inflammation assessed. Clopidogrel as opposed to aspirin and no-treatment reduced platelet activation (P-selectin and PAC-1 expression). Compared with baseline, platelet-induced proinflammatory transcript expression of cultured endothelial cells were reduced in those assigned to clopidogrel, with no change in the aspirin and no-treatment arms. In HIV, clinical trials of clopidogrel to prevent cardiovascular disease are warranted. (Antiplatelet Therapy in HIV; NCT02559414)
SCOPUS:85141772782
ISSN: 2452-302x
CID: 5370232

Sex differences in the prognostic value of troponin and D-dimer in COVID-19 illness

Mukhopadhyay, Amrita; Talmor, Nina; Xia, Yuhe; Berger, Jeffrey S; Iturrate, Eduardo; Adhikari, Samrachana; Pulgarin, Claudia; Quinones-Camacho, Adriana; Yuriditsky, Eugene; Horowitz, James; Jung, Albert S; Massera, Daniele; Keller, Norma M; Fishman, Glenn I; Horwitz, Leora; Troxel, Andrea B; Hochman, Judith S; Reynolds, Harmony R
BACKGROUND:Male sex, elevated troponin levels, and elevated D-dimer levels are associated with more complicated COVID-19 illness and greater mortality; however, while there are known sex differences in the prognostic value of troponin and D-dimer in other disease states, it is unknown whether they exist in the setting of COVID-19. OBJECTIVE:We assessed whether sex modified the relationship between troponin, D-dimer, and severe COVID-19 illness (defined as mechanical ventilation, ICU admission or transfer, discharge to hospice, or death). METHODS:We conducted a retrospective cohort study of patients hospitalized with COVID-19 at a large, academic health system. We used multivariable regression to assess associations between sex, troponin, D-dimer, and severe COVID-19 illness, adjusting for demographic, clinical, and laboratory covariates. To test whether sex modified the relationship between severe COVID-19 illness and troponin or D-dimer, models with interaction terms were utilized. RESULTS:Among 4,574 patients hospitalized with COVID-19, male sex was associated with higher levels of troponin and greater odds of severe COVID-19 illness, but lower levels of initial D-dimer when compared with female sex. While sex did not modify the relationship between troponin level and severe COVID-19 illness, peak D-dimer level was more strongly associated with severe COVID-19 illness in male patients compared to female patients (males: OR=2.91, 95%CI=2.63-2.34, p<0.001; females: OR=2.31, 95%CI=2.04-2.63, p<0.001; p-interaction=0.005). CONCLUSION/CONCLUSIONS:Sex did not modify the association between troponin level and severe COVID-19 illness, but did modify the association between peak D-dimer and severe COVID-19 illness, suggesting greater prognostic value for D-dimer in males with COVID-19.
PMCID:9597518
PMID: 36334466
ISSN: 1527-3288
CID: 5358922

Platelet LGALS3BP Induces Myeloid Inflammation In Systemic Lupus Erythematosus

El Bannoudi, Hanane; Cornwell, MacIntosh; Luttrell-Williams, Elliot; Engel, Alexis; Rolling, Christina; Barrett, Tessa J; Izmirly, Peter; Belmont, H Michael; Ruggles, Kelly; Clancy, Robert; Buyon, Jill; Berger, Jeffrey S
OBJECTIVE:Platelets are mediators of inflammation with immune effector cell properties, and have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). This study investigated the role of platelet associated lectin galactoside-binding soluble 3 binding protein (LGALS3BP) as a mediator of inflammation in SLE, and a potential biomarker associated with clinical phenotypes. METHODS:We performed RNA sequencing on platelets of patients with SLE (n=54) and age, sex, and race-matched controls (n=18) and measured LGALS3BP in platelet releasate and in circulating serum. We investigated the association between levels of LGALS3BP with the prevalence, disease severity, and clinical phenotpyes of SLE, and studied platelet-mediated effects on myeloid inflammation. RESULTS:). Platelet-released LGALS3BP was highly correlated with circulating LGALS3BP (R = 0.69, p < 0.0001). Circulating LGALS3BP correlated with the SLE disease activity index (R = 0.32, p = 0.0006). Specifically, circulating LGALS3BP was higher in SLE patients with lupus nephritis than those with inactive disease (4.0 μg/mL vs 2.3 μg/mL, P < 0.001). IFN-α induced LGALS3BP transcription and translation in a megakaryoblastic cell line (MEG-01) cells in a dose-dependent manner. Recombinant LGALS3BP and platelet releasates from SLE patients enhanced pro-inflammatory cytokine production by macrophages. CONCLUSIONS:These data support that platelets act as potent effector cells contributing to the pathogenesis of SLE by secreting proinflammatory LGALS3BP, which also represents a novel biomarker of SLE clinical activity.
PMID: 36245285
ISSN: 2326-5205
CID: 5360062

Effectiveness, safety, and healthcare costs associated with rivaroxaban versus warfarin among venous thromboembolism patients with obesity: a real-world study in the United States

Berger, Jeffrey S; Laliberté, François; Kharat, Akshay; Lejeune, Dominique; Moore, Kenneth Todd; Jung, Young; Lefebvre, Patrick; Ashton, Veronica
Prior observational studies suggest rivaroxaban is safe and effective among patients with morbid obesity who suffered a venous thromboembolism (VTE) event, but existing data are more limited in the broader population of VTE patients with obesity. This study assessed VTE recurrence, major bleeding, healthcare resource utilization, and healthcare costs among VTE patients with obesity who received rivaroxaban versus warfarin. VTE patients with obesity who initiated rivaroxaban or warfarin after a first VTE (index date) were identified from the IQVIA PharMetrics® Plus database (01/02/2011-09/30/2019). The follow-up period spanned from the index date until health plan disenrollment, end of data availability, cancer diagnosis/treatment, end of the 12 month post-index period, or (for the analysis of major bleeding) anticoagulant discontinuation or switch. Patient characteristics were balanced using inverse probability of treatment weighting. The weighted rivaroxaban (N = 8666) and warfarin cohorts (N = 5946) were well balanced (mean age = 51 years, females = 52%). Over a 9.6 months mean observation period, rivaroxaban users had a significantly lower risk of VTE recurrence [7.0% vs. 8.2%, HR(95% CI) = 0.85(0.75;0.97)] and a similar risk of major bleeding [4.1% vs. 3.6%, HR(95% CI) = 1.11(0.89;1.37)] relative to warfarin users at 12 months. Relative to warfarin users, rivaroxaban users had significantly fewer all-cause outpatient visits [RR(95% CI) = 0.71(0.70;0.74)]. The higher pharmacy costs incurred by rivaroxaban recipients (cost difference = $1252) were offset by lower medical costs (cost difference = - $2515, all p < 0.05) compared with warfarin recipients. Our findings suggest that rivaroxaban is safe and effective versus warfarin, and associated with lower medical costs among VTE patients with obesity.
PMID: 35562510
ISSN: 1573-742x
CID: 5249102

Aspirin for the Primary Prevention of Cardiovascular Disease: Time for a Platelet-Guided Approach

Cofer, Lucas B; Barrett, Tessa J; Berger, Jeffrey S
Aspirin protects against atherothrombosis while increasing the risk of major bleeding. Although it is widely used to prevent cardiovascular disease (CVD), its benefit does not outweigh its risk for primary CVD prevention in large population settings. The recent United States Preventive Services Task Force guidelines on aspirin use to prevent CVD reflect this clinical tradeoff as well as the persistent struggle to define a population that would benefit from prophylactic aspirin therapy. Past clinical trials of primary CVD prevention with aspirin have not included consideration of a biomarker relevant to aspirin's mechanism of action, platelet inhibition. This approach is at odds with the paradigm used in other key areas of pharmacological CVD prevention, including antihypertensive and statin therapy, which combine cardiovascular risk assessment with the measurement of mechanistic biomarkers (eg, blood pressure and LDL [low-density lipoprotein]-cholesterol). Reliable methods for quantifying platelet activity, including light transmission aggregometry and platelet transcriptomics, exist and should be considered to identify individuals at elevated cardiovascular risk due to a hyperreactive platelet phenotype. Therefore, we propose a new, platelet-guided approach to the study of prophylactic aspirin therapy. We think that this new approach will reveal a population with hyperreactive platelets who will benefit most from primary CVD prevention with aspirin and usher in a new era of precision-guided antiplatelet therapy.
PMCID:9484763
PMID: 36047408
ISSN: 1524-4636
CID: 5335002