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  • Ovid Technologies (Wolters Kluwer Health)  (47)
  • Berger, Jeffrey S  (47)
  • 1
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    Abstract 2220: The Relative Safety and Efficacy of Clopidogrel in Women and Men: Meta-Analysis of 79,613 Patients Enrolled in CREDO, CURE, CLARITY-TIMI 28, COMMIT, and CHARISMA
    Ovid Technologies (Wolters Kluwer Health) ; 2007
    In:  Circulation Vol. 116, No. suppl_16 ( 2007-10-16)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 116, No. suppl_16 ( 2007-10-16)
    Abstract: Background : Previous analyses have demonstrated sex-based differences in the efficacy of several anti-platelet medications. Little is known about the safety and efficacy of clopidogrel in women and men. Methods : We performed a meta-analysis of all blinded randomized clinical trials comparing clopidogrel and placebo (CREDO, CURE, CLARITY-TIMI 28, COMMIT, and CHARISMA). The relative safety and efficacy of clopidogrel at reducing cardiovascular events (death, MI or stroke) in women and men was estimated using random-effects modeling. Results : In all 79,613 patients, there was a reduction of cardiovascular events with clopidogrel vs placebo (9.7% vs 8.7%; OR 0.88 [0.84–0.93], P 〈 0.01). Among the 23,522 women enrolled, there were 1289/11757 (11.0%) cardiovascular events in the clopidogrel group vs. 1372/11766 (11.7%) in the placebo group (OR 0.93 [0.86–1.01] , P=0.09). Clopidogrel had its greatest effect in reducing the risk of MI (OR 0.82 [0.70–0.95], P=0.01) in women. No significant reduction was noted for stroke (OR 0.91 [0.67–1.24] , P=0.56) or death (OR 0.99 [0.90–1.08], P=0.78). Among the 56,091 men enrolled, there were 2166/28064 (7.7%) cardiovascular events in the clopidogrel group vs 2492/28027 (8.9%) in the placebo group (OR 0.85 [0.79–0.91] , P 〈 0.01). Clopidogrel significantly reduced the risk of MI (OR 0.84 [0.76–0.92], P 〈 0.01), stroke (OR 0.83 [0.71–0.96], P=0.01), and death (OR 0.91 [0.84–0.98] , P 〈 0.01). Clopidogrel increased the risk of major bleeding in both women (1.6% vs 1.1%, OR 1.43 [1.14–1.79]) and men (1.2% vs 1.0%, OR 1.21 [1.03–1.42] ). The safety and efficacy were similar in patients with an acute coronary syndrome and established cardiovascular disease. There was no evidence of statistical heterogeneity (as measured by the Q-test and I 2 ) in pooled analyses comparing women and men for the composite endpoint, its individual components, or bleeding. Conclusions : Clopidogrel reduces the risk of cardiovascular events in both women and men. While the directionality and proportionality of the reductions are roughly similar, the effect was driven by a reduction of MI in women. The reduction of MI, stroke and death by clopidogrel in men were all significant. Clopidogrel increased the risk of major bleeding by 43% in women and 21% in men.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.116.suppl_16.II_483
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2007
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  • 2
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    Abstract 14653: Genome-wide Association Study of Peripheral Artery Disease and Critical Limb Ischemia Identifies Novel Genetic Loci and Coagulation Pathways
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Circulation Vol. 142, No. Suppl_3 ( 2020-11-17)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 142, No. Suppl_3 ( 2020-11-17)
    Abstract: Introduction: The pathogenesis of peripheral artery disease (PAD) and critical limb ischemia (CLI) are poorly understood. Hypothesis: We hypothesize that genetic factors related to abnormalities in coagulation or fibrinolysis, in addition to atherosclerosis, could play an important role in PAD patients and PAD with CLI patients. Methods: A genome-wide association study (GWAS) was performed testing for associations between single-nucleotide variants (SNVs) and PAD case-control (3,190 cases and 463,495 controls) and subgroup analysis of PAD with CLI case-control (142 cases and 3,048 controls) in the UK Biobank cohort. To further validate the results, we selected SNVs with the most significant Cochrane-Armitage trend p values without evidence of strong linkage disequilibrium (r2 〉 0.8) for PAD with CLI case-control in the BioMe Biobank. We tested for association using BOLT-LMM with adjustment for age, sex, BMI, and the first ten principal components to control for population structure. The SNV association tests' significance level was set at P 〈 5x10–8 after Bonferroni correction. Results: 363 SNVs from 81 genetic loci reached the threshold for statistical significance based on a Bonferroni correction (p 〈 5x10–8). (Figure) We then performed a subgroup analysis between PAD patients and PAD with CLI patients in the UK Biobank. We identified 63 SNVs with 52 genetic loci independent for PAD with CLI in the UK Biobank. We further validated those 63 SNVs with 52 genetic loci in the BioMe Biobank. In the validation cohort, 2 genetic loci ( PLG and CDKN2B ) were independent for PAD with CLI. On pathway analyses, we identify several new loci that implicate thrombotic, inflammation, glycosaminoglycan synthesis, coagulation, and fibrinolytic pathways involved in PAD along with known atherosclerosis pathways (p 〈 0.05). Conclusions: We show that PLG gene related to coagulation pathways in PAD may play an important role in coagulation-related PAD pathogenesis.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.142.suppl_3.14653
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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  • 3
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    Abstract 16449: Sex Differences in Myocardial Injury and Outcomes of Covid-19 Infection
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Circulation Vol. 142, No. Suppl_3 ( 2020-11-17)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 142, No. Suppl_3 ( 2020-11-17)
    Abstract: Background: Myocardial injury is associated with higher mortality of COVID-19 and more complicated disease course. Little is known about sex differences in COVID-19-associated myocardial injury. We hypothesized that sex modifies the relationship between myocardial injury and severe COVID-19 infection. Methods: This is a cross-sectional study of all hospitalized patients with COVID-19 at a large health system in New York City between 3/2/20 - 5/12/20. We defined severe COVID-19 infection as ICU admission, mechanical ventilation, discharge to hospice, or death. Using multivariable logistic regression, we assessed whether sex modified the effect of peak troponin on the odds of severe COVID-19 infection, adjusting for demographics, co-morbidity, and laboratory values, and did the same for D-dimer. Results: Among 2,746 patients hospitalized with COVID-19, 650 (23.7%) required ICU admission, 648 (23.7%) required mechanical ventilation, and 680 (24.8%) died or were discharged to hospice. Peak troponin was higher in men than women (median 0.06, interquartile range [IQR] 0.01- 0.10 vs. 0.05 [IQR 0.01-0.10] , p=0.02). Men were more likely to be admitted to the ICU and to receive mechanical ventilation (Table). After adjustment for demographics, medical history and other laboratory values, peak troponin level was associated with higher odds of severe COVID-19 illness: OR 1.51 per ng/mL, 95% CI 1.27-1.88, p 〈 0.001. This association was modified by sex: the OR for severe COVID-19 per ng/mL peak troponin was 1.30 in women (95% CI 1.11-1.65) and 1.92 (95% CI 1.42-2.78) in men, p-interaction=0.047. There was no interaction between sex and D-dimer on severe COVID-19. Conclusions: Sex modifies the relationship between myocardial injury and severe COVID-19, with men having higher odds of severe COVID-19 infection associated with increasing peak troponin. Sex differences in myocardial injury may play a role in poorer outcome among men.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.142.suppl_3.16449
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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    FH Potsdam
  • 4
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    Abstract 368: Severe Obesity and Bariatric Surgery Alter the Platelet mRNA Profile
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 38, No. Suppl_1 ( 2018-05)
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 38, No. Suppl_1 ( 2018-05)
    Abstract: Mechanisms explaining the relationship between obesity and CVD are needed. Platelets are increasingly recognized as immune cells; the platelet transcriptome and sheddome can modulate the function of disparate cells and tissues. Despite growing recognition of the importance of the platelet transcriptome, low levels of RNA in platelets makes assessment difficult. Unbiased platelet RNA profiling specifically in obesity has not previously been performed. We performed a prospective study investigating the association between severe obesity and weight loss via bariatric surgery and platelet function and RNA profile in 25 pre-menopausal, non-diabetic women (31.9 ± 7.6 years; 43.0 ± 6.5 kg/m 2 ) who underwent sleeve gastrectomy. Ten women of similar age and racial background with normal BMI (22.8 ± 2.3kg/m 2 ) served as control subjects. Platelet function via light transmission aggregometry and surface expression via flow cytometry was assessed before and after surgery. RNAseq was performed on platelet RNA isolates of 8 obese women before and 5 after surgery and 5 control subjects. Platelet count, size, age (reticulated platelets) and aggregation measures did not differ between control and obese women. However, surface markers (eg P-selectin and CD40) of platelet activation were significantly higher in obesity. mRNA sequencing demonstrated 〉 600 RNA transcripts differentially abundant (P 〈 0.05 and base mean counts ≥5) in obesity. Notably, platelet S100A9 and AGER , established markers of CV risk, were 2 of the most highly upregulated transcripts in obesity. Pathway analyses identified eIF2 and mTOR signaling and protein translation broadly to be upregulated. At 6 months after surgery, subjects lost 26.1 ± 5.8% body weight, but only a small fraction of transcripts (46/630; which included AGER) exhibited significantly altered expression. Platelet activation (not aggregation) was increased and the platelet transcriptome was altered in obesity. Given platelets’ ability to act as immune cells and transfer their RNA cargo to other cells important in atherothrombosis, the altered platelet RNA profile in obesity may contribute to increased risk of CVD. More substantial degrees or duration of weight loss may be necessary to rectify the altered platelet RNA profile.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/atvb.38.suppl_1.368
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
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  • 5
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    Abstract 256: The Direct Characterization of Endothelial Inflammation in Patients with Psoriasis
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 38, No. Suppl_1 ( 2018-05)
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 38, No. Suppl_1 ( 2018-05)
    Abstract: Objective: Psoriasis, an inflammatory autoimmune disease, increases the risk of cardiovascular disease (CVD). Active psoriatic disease is linked to systemic vascular inflammation, yet how this contributes to CVD is unknown. Using in vivo and ex-vivo measures of the vascular endothelium our study investigates the vascular health of psoriasis patients to better understand the mechanism(s) that predispose psoriatics to CVD. Methods: Ten patients with active psoriasis (average age 46 years, 50% male (5 of 10), 6% [3.5% – 90%] body surface area involvement) were compared to age- and sex- matched controls. In vivo vascular endothelial function was assessed by brachial artery reactivity testing (BART, %) with high resolution ultrasonography. Venous endothelial cells were collected from the brachial vein using guidewires inserted through an angiocatheter and isolated with magnetic beads directed against CD146. Following collection, endothelial RNA was isolated, converted to cDNA and inflammatory gene profiling performed by RT-qPCR with Taqman probes and primers. Results: Transcriptomic profiling of venous endothelial cells revealed upregulation of genes associated with inflammatory cytokines and chemokines ( lymphotoxin beta [2.5 - fold], CCL3 [3.5 - fold], and IL-1 β [2.8 - fold], P 〈 0.05 for all) and genes related to intracellular adhesion and inflammation ( ICAM1 [2.3 – fold] and COX-2 [1.4 – fold], P 〈 0.05 for both) in psoriatics vs. controls. Unexpectedly, endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (higher levels indicate healthy endothelial NO production) were upregulated (2 - 3 fold) in psoriatics vs. controls (p = 0.24, p = 0.14 respectively). BART was also higher in psoriatics when compared to controls (7.1 ± 1% vs. 3.9 ± 2.7%, P = 0.03). Conclusion: This cross-sectional study is the first to directly examine the vascular endothelium of psoriatic patients. Compared to controls, active psoriatic disease was associated with upregulation of cytokines, chemokines and genes regulating intracellular adhesion as well as increased expression of eNOS, and increased BART. These findings suggest potential mechanisms to explain the increased prevalence of atherosclerosis and CVD risk seen in those with psoriasis.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/atvb.38.suppl_1.256
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
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  • 6
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    Abstract 514: Development and Validation of Risk Model for Predicting Prevalence of Peripheral Artery Disease in a Low to Intermediate Risk Population
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 36, No. suppl_1 ( 2016-05)
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 36, No. suppl_1 ( 2016-05)
    Abstract: Background: Peripheral artery disease (PAD) is associated with impaired quality of life and significant cardiovascular morbidity and mortality, yet remains under recognized and under diagnosed. Objectives: This study sought to develop and validate a risk model for the identification of individuals at risk for PAD that could be useful in the clinical setting. Methods: Twenty three variables assessed in ≈3.2 million self-referred participants without established cardiovascular disease from 2003 to 2008 who completed a medical and lifestyle questionnaire in the United States were evaluated by screening ankle brachial indices 〈 0.90 for PAD. Subjects were divided into a derivation cohort (1.57 million) and a validation cohort (1.57 million). Lasso variable selection was used in the derivation cohort to develop the best-fitting parsimonious prediction models. Discrimination and calibrations was evaluated using the C statistic and the Hosmer-Lemeshow calibration statistic. Results: The overall prevalence of PAD was 3.96%. Using lasso variable selection, 11 variables were included in complex best-fitting model: age, sex, race, marital status, BMI group, smoking status, hypertension, diabetes, family history of PAD, physical activity, and inter-arm systolic blood pressure difference. In the validation cohort, the C-statistics for this model was .746 and the calibration was excellent (P=0.38; no significant deviation between predicted and observed outcomes). The current risk score has improved discrimination and calibration compared with other existing risk scores for PAD. Conclusion: This robust PAD risk calculator derived from a diverse population across the US provides a good risk estimate of PAD and is anticipated to assist in identifying subjects at risk for PAD.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/atvb.36.suppl_1.514
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
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  • 7
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    Abstract 125: Association Between Abo Blood Group, Von Willebrand Factor and Factor VIII in Patients Undergoing Vascular Surgery
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 37, No. suppl_1 ( 2017-05)
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 37, No. suppl_1 ( 2017-05)
    Abstract: Background: ABO blood groups have been associated with functional effects on factor VIII (FVIII), von Willebrand factor (vWF) and incident atherothrombosis. This study sought to examine the association between ABO blood type, FVIII and vWF in patients undergoing vascular surgery. Method: This is a retrospective analysis of data from a cohort of 181 patients undergoing elective vascular surgery. ABO blood type, FVIII and vWF was measured before surgery. The primary end point was the occurrence of MACE (defined as myocardial necrosis, myocardial infarction, stroke or death) within 30-days after surgery. Multivariable logistic regression modeling was used to estimate odds of MACE. Results: The mean age was 71.6 ± 9.8 and 29% were female. Non-O blood type was present in 105 patients (70 A, 27 B, 8 AB) and type O in 76 patients. Non-O had higher FVIII (128.2 ± 44.7 vs 112.4 ± 42.4, P 〈 0.001) and vWF (176.0 ± 54.0 vs 133.2 ± 41.0, P 〈 0.001) than type O. Thirty day MACE occurred in 38 (21.0%) patients; 25% in non-O and 15.8% in type O (P=0.13). After adjustment for age, sex, race, prior coronary artery disease and heart failure, patients with non-O blood type (vs. O) had a higher incidence of 30-day MACE (odds ratio 2.1, 95% CI 0.9 to 5.1, P=0.08) although statistical significance was not reached. There was no significant association between FVIII and vWF and 30-day MACE. Conclusions: Non-O blood type was associated with higher levels of FVIII and vWF and a trend towards increased 30-day MACE in patients undergoing vascular surgery. Larger studies across of ABO blood groups and perioperative events in different types of surgeries are warranted.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/atvb.37.suppl_1.125
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
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  • 8
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    Abstract 15888: Platelet Activation is Associated With All-cause Mortality in Patients With Covid-19
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Circulation Vol. 142, No. Suppl_3 ( 2020-11-17)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 142, No. Suppl_3 ( 2020-11-17)
    Abstract: Background: COVID-19 is a global pandemic with patients at increased risk for all-cause mortality. Virus-platelet interactions are linked to viral pathogenesis and increased risk of adverse events. Aim: To investigate the relationship between in vivo platelet activity markers and all-cause mortality in hospitalized patients with COVID-19. Method: Plasma samples were collected from 100 hospitalized patients on the day of PCR-confirmed COVID-19 diagnosis. Thromboxane B 2 (TxB 2 ), P-selectin, and soluble CD40 ligand (sCD40L) were measured in plasma, and mean platelet volume (MPV) assessed. Subjects were followed until discharge or death. Results: Among 100 patients, the median age was 65 years (IQR: 55, 75), 39% were female, and 32 died or experienced a thrombotic event. The baseline platelet activation markers, P-selectin (p=0.02), sCD40L (p=0.03) and MPV (p=0.005) were higher in patients who died. After adjustment for age, sex, race/ethnicity, platelet count, antiplatelet therapy, and chronic obstructive pulmonary disease, TxB 2 (p=0.036), P-selectin (p=0.007), sCD40L (p=0.02) and MPV (p=0.01) were each independently associated with death after multivariable adjustment ( Table 1 ). Conclusions: Biomarkers of platelet activation are significantly associated with death or thrombosis in patients hospitalized with COVID-19. Our findings suggest multiple platelet activation mechanisms may contribute to adverse events. Further investigation into the mechanistic role of platelets in COVID-19 pathogenesis and the potential role of antiplatelet therapy is warranted. Table 1. Multivariable regression models of all-cause mortality. Odds ratios (OR) from logistic regression analysis per SD increase for biomarker levels adjusted for age, sex, race, antiplatelet therapy, platelet count, and chronic obstructive pulmonary disease (COPD).
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.142.suppl_3.15888
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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    FH Potsdam
  • 9
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    Abstract 13299: Myocardial Injury in Adults Hospitalized With Covid-19
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Circulation Vol. 142, No. Suppl_3 ( 2020-11-17)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 142, No. Suppl_3 ( 2020-11-17)
    Abstract: Background: Myocardial injury is frequently identified in patients with Coronavirus Disease 2019 (COVID-19). The incidence and outcome of myocardial injury at presentation and during the course of hospitalization for COVID-19 are uncertain. Methods: Consecutive adults (age ≥18) with COVID-19 admitted to a health care system with 4 large hospitals in New York between March 1st and April 16th, 2020 were identified. Initial and peak cardiac troponin (cTn) measurements were recorded. Myocardial injury was defined by cTn above the laboratory upper limit of normal. Thrombotic events, critical illness, and in-hospital mortality was determined. Results: Among 3,116 adults with COVID-19 and ≥1 cTn measurement, myocardial injury was present in 606 (19%) patients at hospital admission, with a median cTn of 0.10 ng/mL [range 0.04-91.8 ng/mL]. Patients with myocardial injury were older, more likely male, and more likely to have cardiovascular disease. Thrombotic events (38% vs. 10%, p 〈 0.001; adjusted odds ratio [aOR] 3.54, 95 CI 2.91-4.53), critical illness (58% vs. 32%, p 〈 0.001; aOR 1.55, 95% CI 1.22-1.90) and mortality (41% vs. 17%, p 〈 0.001; aOR 1.67, 95% CI 1.31-2.15), were more frequent in patients with versus without myocardial injury at presentation. Myocardial injury based on the peak cTn during hospitalization was detected in 956 (31%) patients and was also associated with thrombotic events (36% vs. 7%, p 〈 0.001; aOR 6.56, 95% CI 5.09-9.85), critical illness (67% vs. 24%, p 〈 0.001; aOR 6.05, 95% CI 5.05-7.87), and mortality (43% vs. 13%, p 〈 0.001; aOR 3.83, 95% CI 3.15-5.03) versus those without myocardial injury. Patients with the highest cTn had the greatest risk of adverse events (Figure). Conclusions: Myocardial injury was observed in 1 in ~5 patients with COVID-19 at hospital presentation, and 1 in ~3 based on the peak cTn. Initial and peak cTn measurements were markers of adverse outcomes. The optimal management of myocardial injury in COVID-19 requires further study.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.142.suppl_3.13299
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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    FH Potsdam
  • 10
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    Abstract 11420: Platelet Activity Mediates Increased Cardiovascular Risk in Patients with End-Stage Kidney Disease and Peripheral Artery Disease
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Circulation Vol. 144, No. Suppl_1 ( 2021-11-16)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 144, No. Suppl_1 ( 2021-11-16)
    Abstract: Background: End-stage kidney disease (ESKD) and peripheral artery disease (PAD) are frequently co-prevalent and each associated with increased cardiovascular (CV) risk. Platelets drive PAD pathogenesis and mediate atherothrombosis. Their function and influence on CV risk in ESKD remain unclear. We hypothesized that ESKD is associated with heightened platelet activity and incident cardiac and limb events in patients with PAD. Methods: The Platelet Activity and Cardiovascular Events study enrolled 289 patients with PAD undergoing lower extremity revascularization (LER). We measured platelet activity prior to LER via light transmission aggregometry in response to submaximal ADP, collagen, serotonin, epinephrine, and arachidonic acid. We followed patients for a median of 18 months for a primary endpoint of major adverse CV event (MACE; MI, stroke, death) and a secondary composite of major adverse CV or limb event (MACLE; MACE or acute limb ischemia). Results: Among enrolled subjects, 25 (9%) had ESKD. They were younger and more likely to have a history of coronary artery disease (CAD), heart failure, and critical limb ischemia (CLI) than those without ESKD (P 〈 0.05 for each). Aggregation in response to epinephrine 2.0 uM after 5 minutes and at maximum was greater in those with compared to without ESKD (61% vs. 48%; P=0.004 and 77% vs. 60%; P=0.001, respectively). After multivariable adjustment, patients with vs. without ESKD were at greater risk for CV events ( Figure ). Platelet aggregation in response to submaximal epinephrine stimulation had a 32% and 45% mediating effect on the excess risk for MACE and MACLE, respectively, associated with ESKD ( Figure ). Conclusions: In patients with PAD, ESKD was associated with increased platelet aggregation in response to submaximal epinephrine that partially mediated increased risk for incident cardiac and limb events. Platelet activity appears to be an important mechanism underlying CV risk in ESKD.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.144.suppl_1.11420
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
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