scholarly journals Inflammatory Biomarker Score Identifies Patients with Six-Fold Increased Risk of One-Year Mortality after Pancreatic Cancer

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4599
Author(s):  
Alisa D. Kjaergaard ◽  
Inna M. Chen ◽  
Astrid Z. Johansen ◽  
Børge G. Nordestgaard ◽  
Stig E. Bojesen ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
High Plasma ◽  
Carbohydrate Antigen ◽  
Ductal Adenocarcinoma ◽  
P Value ◽  
Inflammatory Biomarker ◽  
Reactive Protein ◽  
Hazard Ratios ◽  
Increased Risk ◽  
One Year

We examined whether elevated plasma C-reactive protein (CRP), carbohydrate antigen (CA) 19-9, interleukin-6 (IL-6) and YKL-40, individually or combined, can identify poor survivors among patients with pancreatic ductal adenocarcinoma (PDAC). We measured CRP, CA 19-9, IL-6 and YKL-40 in 993 patients at the time of PDAC diagnosis. The biomarker score was the sum of biomarker categories, coded 0, 1 and 2 for low, intermediate and high plasma concentrations, respectively. High vs. low levels of CRP, CA 19-9 and IL-6 were each independently associated with a two-fold increased risk of one-year mortality. CRP performed best in patients with advanced and CA 19-9 in patients with low cancer stages. YKL-40 was not associated with mortality and, therefore, was not included in the biomarker score. Compared to the biomarker score = 0, the multifactorially adjusted hazard ratios for one-year mortality were 1.56 (95% confidence interval: 0.99–2.44) for score = 1, 2.22 (1.41–3.49) for score = 2, 3.44 (2.20–5.38) for score = 3, 5.13 (3.21–8.17) for score = 4 and 6.32 (3.84–10.41) for score = 5–6 (p-value for trend = 3 × 10−31). This score performed better than any single biomarker or combination of biomarkers when examined in similarly sized or other categories. In conclusion, a combination score of elevated CRP, CA 19-9 and IL-6 identified patients with six-fold higher one-year mortality.

Women with high plasma levels of PBDE-47 are at increased risk of preterm birth

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Morgan R. Peltier ◽  
Michael J. Fassett ◽  
Yuko Arita ◽  
Vicki Y. Chiu ◽  
Jiaxiao M. Shi ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Los Angeles ◽  
Polybrominated Diphenyl Ethers ◽  
Flame Retardants ◽  
Plasma Concentrations ◽  
First Trimester ◽  
High Plasma ◽  
Thyroid Stimulating Hormone ◽  
Spontaneous Preterm Birth ◽  
Increased Risk

Abstract Objectives Nearly 100% of North American women have detectable levels of flame retardants such as polybrominated diphenyl ethers (PBDEs) in their plasma. These molecules have structural homology to thyroid hormones and may function as endocrine disruptors. Thyroid dysfunction has previously been associated with increased risk for preterm birth. Therefore, we conducted a multi-center, case-cohort study to evaluate if high plasma concentrations of a common PBDE congener in the first trimester increases the risk of preterm birth and its subtypes. Methods Pregnant women were recruited at the onset of initiation of prenatal care at Kaiser-Permanente Southern California (KPSC)-West Los Angeles and KPSC-San Diego medical centers. Plasma samples from women whose pregnancies ended preterm and random subset of those delivering at term were assayed for PBDE-47 and thyroid-stimulating hormone (TSH) by immunoassay. Quartile cutoffs were calculated for the patients at term and used to determine if women with exposures in the 4th quartile are at increased risk for preterm birth using logistic regression. Results We found that high concentrations of PBDE-47 in the first trimester significantly increased the odds of both indicated (adjusted odds ratio, adjOR=2.35, 95% confidence interval [CI]: 1.31, 4.21) and spontaneous (adjOR=1.76, 95% CI: 1.02, 3.03) preterm birth. Regardless of pregnancy outcome, TSH concentrations did not differ between women with high and low concentrations of PBDE-47. Conclusions These results suggest that high plasma concentrations of PBDE-47 in the first trimester, increases the risk of indicated and spontaneous preterm birth.

scholarly journals Influence of zinc deficiency on one year recurrence in children with nephrotic syndrome

2019 ◽  
Vol 8 (3) ◽  
pp. 243-246
Author(s):  
Fatemeh Ghafoorimehr ◽  
Mastaneh Moghtaderi ◽  
Behnaz Bazargani ◽  
Dariush Fahimi ◽  
Arash Abbasi
Keyword(s):  
Nephrotic Syndrome ◽  
Zinc Deficiency ◽  
Serum Zinc ◽  
Zinc Level ◽  
P Value ◽  
Chi Square ◽  
Mean Values ◽  
Increased Risk ◽  
Steroid Sensitive Nephrotic Syndrome ◽  
One Year

Introduction: Relapses in children with steroid sensitive nephrotic syndrome (SSNS) are common and sometimes triggered by various infections. Low zinc levels have been described in children with nephrotic states. It is supposed to that zinc deficiency might lead to dysregulation of immune system and an increased risk of infection. Objectives: This study sought to examine whether the plasma level of zinc in nephrotic patients is related to the number of relapses in these patients. Patients and Methods: Forty-three children aged 1-10 years were entered in this study. Baseline data including age, serum zinc level, number of relapses during one year was recorded. The t test and chi-square tests were used to compare the mean values and proportions respectively with significant P value (P < 0.05). Results: Forty-three children with storied sensitive nephrotic syndrome enrolled in this study. Twenty-three (53.5%) of them were male and 20 (46.5%) were female. Around 74.4 % of patients experienced relapses of nephrotic syndrome in one-year period. There was a significant relation between zinc deficiency and recurrence rate. Conclusion: Zinc deficiency is common in children suffering from nephrotic syndrome and is related to recurrence of relapses in these patients.

scholarly journals Increased Risk of Graves´ophthalmopathy in Patients With Increasing TRAb After Radioiodine Treatment and the Impact of CTLA4 on TRAb Titres

2021 ◽  
Author(s):  
Bushra Shahida ◽  
Kleoniki Tsoumani ◽  
Tereza Planck ◽  
Vijayachitra Modhukur ◽  
Pernilla Asp ◽  
...  
Keyword(s):  
Previous Treatment ◽  
University Hospital ◽  
P Value ◽  
Graves Ophthalmopathy ◽  
Increased Risk ◽  
Orbital Tissue ◽  
One Year ◽  
The Impact ◽  
The Relationship

Abstract Introduction. Treatment of Graves´ disease (GD) with radioiodine increases the risk of developing Graves´ ophthalmopathy (GO) but the link between thyroid and orbital tissue remains undefined.The aim was to investigate the relationship between GO and TRAb after treatment with radioiodine and to define the impact of risk genes.Methods. GD patients without ophthalmopathy or previous treatment with radioiodine were prospectively included at treatment with radioiodine for hyperthyroidism. A follow-up was performed one year later for registration of GO development. The study was performed at a University Hospital Clinic; referral center of all patients treated with radioiodine in the south of Sweden. The main outcome measures were development of TRAb, anti-TPO, anti-TG after three months and GO after 12 months and relationship to the genetic background (HLA, CTLA-4, CYR61).Results. Three months of radioiodine TRAb increased in two thirds of patients (p<0.0005) but not in the other third. Anti-TPO was associated with TRAb (R=0.362, p <0.0001) but not anti-TG. At follow-up one year later (n=204) 32 patients developed GO with a proportion of 70% in the group increasing in TRAb and 30 % in the group with unchanged or lower TRAb (p-value <0.0005). Patients with GO had higher levels of TRAb than patients without GO. CTLA-4 (rs231775 SNP) was significantly (p<0.005) associated with TRAb levels above the median three months after radioiodine.Conclusions. The increase in TRAb after treatment with radioiodine is associated with GO and a genetic variation in CTLA-4 is associated with higher levels of TRAb.

P4625On women with ST-elevation myocardial infarction: raised concentrations of pro-C-type natriuretic peptide predict increased one-year mortality

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
P Mark ◽  
M Frydland ◽  
O K Moeller-Helgested ◽  
L Holmvang ◽  
J E Moeller ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Mortality Rate ◽  
Natriuretic Peptide ◽  
Plasma Concentrations ◽  
St Elevation Myocardial Infarction ◽  
Risk Of Death ◽  
Increased Risk ◽  
All Cause Mortality ◽  
St Elevation ◽  
One Year

Abstract Introduction Endothelial C-type natriuretic peptide (CNP) contributes to the local regulation of vascular homeostasis including a vasodilatory function in the microcirculation when studied in animal models. Clinical investigations have shown that high concentrations of C-type natriuretic peptides in plasma are associated with adverse clinical outcome in subgroups of patients with cardiac disease. Purpose To determine the prognostic potential of pro-C-type natriuretic peptide (proCNP) measurement in plasma sampled on admission of patients with ST-elevation myocardial infarction (STEMI). Methods In 1760 patients (470 women, 1290 men) with confirmed STEMI, we measured proCNP concentration in plasma obtained on hospital admission before coronary angiography. We divided patients into groups of low, normal or raised proCNP concentrations based on lower and upper cut-off values of sex- and age-specific 95% reference intervals from a reference population (688 individuals). We estimated differences in baseline characteristics including medical history and determined the prognostic value of proCNP measurement by Kaplan-Meier plots including log-rank tests and Cox regression survival analyses (expressed as hazard ratio (HR) and 95% confidence interval). Results Raised proCNP concentrations in plasma were associated with a higher prevalence of hypertension (P<0.001), diabetes mellitus (P=0.009), and peripheral artery disease (P=0.023), and a higher one-year all-cause mortality rate compared with normal proCNP concentrations (Plog-rank = 0.009, HR: 1.6 (1.1–2.4)). However, when adjusted for sex, an interaction between sex and groups of normal vs. raised proCNP was found (P=0.030). In sex-stratified analyses only women with raised proCNP concentrations showed an increased one-year all-cause mortality rate (women: Plog-rank <0.001, HR: 2.6 (1.5–4.6), men: Plog-rank= 0.66, HR: 1.1 (0.6–1.9)). Furthermore, in women, stepwise increases of proCNP concentration in the upper range (proCNP concentration > median) were independently associated with increased risk of death within one year after adjusting for age, plasma concentrations of creatinine and proANP, and quartiles of plasma troponins (HR: 1.02 (1.00–1.05) per 1 pmol/L increase of proCNP, P=0.047). One-year all-cause mortality rates Conclusion In patients with STEMI, a raised concentration of proCNP from plasma sampled on admission was associated with a higher risk of death within one year. However, only women displayed this difference of mortality rate in sex-specific estimates. Moreover, stepwise increases of proCNP concentration in the upper range independently predicted a higher risk of one-year death in women following STEMI after adjusting for potential confounders.

scholarly journals Association Between Inflammatory Biomarker C-Reactive Protein and Radiotherapy-Induced Early Adverse Skin Reactions in a Multiracial/Ethnic Breast Cancer Population

2018 ◽  
Vol 36 (24) ◽  
pp. 2473-2482 ◽  
Author(s):  
Jennifer J. Hu ◽  
James J. Urbanic ◽  
L. Doug Case ◽  
Cristiane Takita ◽  
Jean L. Wright ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multivariable Analysis ◽  
High Sensitivity ◽  
Skin Toxicity ◽  
C Reactive Protein ◽  
Skin Reactions ◽  
Inflammatory Biomarker ◽  
Reactive Protein ◽  
Increased Risk ◽  
Nonobese Patients

Purpose This study examined an inflammatory biomarker, high-sensitivity C-reactive protein (hsCRP), in radiotherapy (RT)-induced early adverse skin reactions or toxicities in breast cancer. Patients and Methods Between 2011 and 2013, 1,000 patients with breast cancer who underwent RT were evaluated prospectively for skin toxicities through the National Cancer Institute–funded Wake Forest University Community Clinical Oncology Program Research Base. Pre- and post-RT plasma hsCRP levels and Oncology Nursing Society skin toxicity criteria (0 to 6) were used to assess RT-induced skin toxicities. Multivariable logistic regression analyses were applied to ascertain the associations between hsCRP and RT-induced skin toxicities after adjusting for potential confounders. Results The study comprised 623 white, 280 African American, 64 Asian/Pacific Islander, and 33 other race patients; 24% of the patients were Hispanic, and 47% were obese. Approximately 42% and 15% of patients developed RT-induced grade 3+ and 4+ skin toxicities, respectively. The hsCRP levels differed significantly by race and body mass index but not by ethnicity. In multivariable analysis, grade 4+ skin toxicity was significantly associated with obesity (odds ratio [OR], 2.17; 95% CI, 1.41 to 3.34], post-RT hsCRP ≥ 4.11 mg/L (OR, 1.61; 95% CI, 1.07 to 2.44), and both factors combined (OR, 3.65; 95% CI, 2.18 to 6.14). Above-median post-RT hsCRP (OR, 1.93; 95% CI, 1.03 to 3.63), and change in hsCRP (OR, 2.80; 95% CI, 1.42 to 5.54) were significantly associated with grade 4+ skin toxicity in nonobese patients. Conclusion This large prospective study is the first to our knowledge of hsCRP as an inflammatory biomarker in RT-induced skin toxicities in breast cancer. We demonstrate that nonobese patients with elevated RT-related change in hsCRP levels have a significantly increased risk of grade 4+ skin toxicity. The outcomes may help to predict RT responses and guide decision making.

P6476Surgery does not appear to improve survival in patients with endocarditis and substance use disorder

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Abdollah ◽  
S B Brogly ◽  
D Payne ◽  
K Lajkosz ◽  
N S Coverdale ◽  
...  
Keyword(s):  
Substance Use ◽  
Substance Use Disorder ◽  
Early Death ◽  
Population Based ◽  
Hospital Death ◽  
Term Survival ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Increased Risk ◽  
One Year

Abstract Background Cohort studies of surgery compared with medical treatment (MT) on endocarditis mortality are conflicting. We conducted a population-based study to estimate associations between treatment and mortality. Methods 1,381 patients with substance use disorder (SUD) and 5,053 without (NSUD) hospitalized for endocarditis were included. Treatment was modeled as a time-dependent variable: patients who underwent surgery after admission were classified as MT until surgery occurred and surgically treated thereafter. Patients without surgery were classified as MT. Adjusted hazard ratios (aHR) between treatment and death (in-hospital, 30 days, one, two, five years) by SUD status were estimated. Results Among SUD patients, there was a trend towards reduction in in-hospital death with surgery vs. MT (aHR 0.61 [95% CI: 0.35–1.04]), but no difference at 30 days (aHR 0.79 [95% CI: 0.42–1.48]). Mortality was higher in SUD patients who underwent surgery compared with MT at one (aHR 1.30 [95% CI: 0.95–1.76]), two (aHR 1.27 [95% CI: 0.97–1.65]), and five years (aHR 1.37 [95% CI: 1.09–1.72]). In NSUD patients, in-hospital mortality (aHR 0.93 [95% CI 0.76–1.16]) did not differ, but 30 day mortality (aHR 1.36 [95% CI 1.04–1.77]) was higher with surgery versus MT, and lower at one (aHR 0.87 [95% CI: 0.73–1.03]), two (aHR 0.75 [95% CI: 0.64–0.88]), and five years (aHR 0.70 [95% CI: 0.61–0.81]). Kaplan-Meier Survival Curves of Patients Interpretation Surgery compared with MT conferred no long-term survival benefit in SUD patients. In NSUD patients, surgery was associated with an initial increased risk of early death followed by a lower risk after one year. Acknowledgement/Funding Grant from Department of Surgery, Queen's University

Factors affecting 48-hour methotrexate levels following high-dose methotrexate (HDMTX) in lymphoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20033-e20033
Author(s):  
Darragh O'Donoghue ◽  
Huong Truong ◽  
Heidi Diann Finnes ◽  
Jennifer McDonald ◽  
Stephen M. Ansell ◽  
...  
Keyword(s):  
Prolonged Exposure ◽  
Plasma Concentrations ◽  
High Plasma ◽  
High Dose ◽  
Factors Affecting ◽  
Significant Toxicity ◽  
Increased Risk ◽  
Central Nervous System Penetration ◽  
Male Patients ◽  
Lymphoma Therapy

e20033 Background: HDMTX is an important component of lymphoma therapy due to its central nervous system penetration. Although HDMTX can be safely administered to most patients, it can cause significant toxicity with those who have prolonged exposure to high plasma concentrations of MTX due to delayed elimination. Therefore, serum MTX concentration monitoring is still a standard approach for identifying patients at high risk of developing MTX toxicity. A majority of MTX is excreted within the first 48 hours of infusion. Higher MTX plasma concentrations at 48 hrs increase the likelihood of delayed MTX elimination. This study will assess baseline characteristics associated with high 48-hour MTX levels (≥ 1µM) which has been associated with increased risk of complications. Methods: A retrospective review of the electronic medical record was conducted to identify lymphoma patients who received HDMTX from 1/1/2002 to 12/31/18. Baseline demographics including age, gender, comorbidities, body surface area, BMI, weight and baseline chronic kidney disease (CKD) were recorded. Demographics, HDMTX dosing per protocol (3.5g/m2 vs 8g/m2), HDMTX adjusted by renal function (CrCl < 100), and ratio of MTX dose to BSA (MTX/BSA) were compared to 48 hour MTX levels. Analysis was performed in JMP 15. Results: 2553 cycles were of HDMTX were identified. There was a significant association of increasing age, (p = 0.039), male patients (p < 0.001), 8g/m2 dosing (p < 0.001), higher MTX dose (p < 0.001), MTX/BSA (p < 0.001), GFR by CKD-EPI (p < 0.001) and lower number of comorbidities (p < 0.001) with 48-hour MTX levels ≥1. There was no significant association of 48-hour MTX levels ≥1 and GFR by Cockcroft-Gault (p = 0.73), baseline CKD (p = 0.78), and renal adjusted HDMTX (p = 0.52). Multivariate analysis revealed significance for MTX/BSA, gender, BSA, GFR by CKDEPI (p < 0.001), and age (P = 0.0002). Conclusions: Hematologists should be aware that age, gender, GFR by CKD-EPI, and ratio of MTX dose to BSA are associated with elevated 48-hour MTX levels ≥1.

Predictive value of germline ATM mutations in the CCTG PA.7 trial: Gemcitabine (GEM) and nab-paclitaxel (Nab-P) versus GEM, nab-P, durvalumab (D) and tremelimumab (T) as first-line therapy in metastatic pancreatic ductal adenocarcinoma (mPDAC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4135-4135
Author(s):  
Daniel John Renouf ◽  
Jonathan M. Loree ◽  
Jennifer J. Knox ◽  
Petr Kavan ◽  
Derek J. Jonker ◽  
...  
Keyword(s):  
Predictive Value ◽  
Checkpoint Inhibitors ◽  
High Plasma ◽  
Ductal Adenocarcinoma ◽  
P Value ◽  
Mutation Status ◽  
First Line Therapy ◽  
Randomized Phase Ii ◽  
Significant Difference ◽  
Pre Treatment

4135 Background: PA.7 evaluated whether combining PD-L1 and CTLA-4 inhibition with GEM and Nab-P increases efficacy. A previous analysis of the PA.7 data demonstrated high plasma based TMB (≥9 mut/Mb) was associated with improved OS in the Gem, Nab-P, D+T arm. DNA repair pathway aberrations beyond mismatch repair have been associated with potential immune sensitivity. We assessed the predictive value of germline ATM mutations in the PA.7 trial. Methods: This randomized phase II study (ClinicalTrials.gov NCT02879318) assessed the efficacy and safety of GEM, Nab-P, D, and T (arm A) vs. GEM and Nab-P (arm B) in patients (pts) with mPDAC (n = 180). The primary endpoint was overall survival (OS). Pre-treatment plasma was sequenced with the Predicine ATLAS next generation assay (600 gene, 2.4 Mb panel). 2-sided alpha set at 0.1. Results: 180 pts were randomized (119 to arm A and 61 to arm B) There was no significant difference in OS (9.8 months in arm A vs. 8.8 months in arm B, p-value 0.72) or PFS (5.5 months and 5.4 months respectively, HR 0.98, p-value 0.91). Plasma analysis was performed on 174/180 pts with available samples. 16/174 (9.2%) pts had germline ATM mutations, 12 in arm A and 4 in arm B. GEM, Nab-P, D+T was associated with improved OS in patients with ATM mutations (HR 0.10, 90% CI 0.03-0.37; median OS 13.9 months vs. 4.9 months) while no activity was seen in pts with ATM Wild Type (HR 0.99, 90% CI 0.73-1.33; median OS 9.79 months vs. 10.2 months); interaction p = 0.014. Germline ATM mutation status was independent of plasma TMB levels (Wilcoxon p = 0.76). Conclusions: Germline ATM mutation appeared predictive of benefit from the addition of dual immune checkpoint inhibitors (D and T) to Gem and Nab-P, with a significant interaction p-value. In addition to previous data from this trial regarding the predictive value of high plasma TMB (≥9 mut/Mb), this data further supports that there may be independent subgroups of PDAC, beyond MSI-H, that may benefit from immunotherapy, and trials evaluating immunotherapy in subgroups of PDAC with these profiles are warranted. Clinical trial information: NCT02879318.

scholarly journals Acute Cholecystitis with Significantly Elevated Levels of Serum Carbohydrate Antigen 19-9

2016 ◽  
Vol 10 (2) ◽  
pp. 410-416 ◽  
Author(s):  
Shuji Akimoto ◽  
Masataka Banshodani ◽  
Masahiro Nishihara ◽  
Junko Nambu ◽  
Yasuo Kawaguchi ◽  
...  
Keyword(s):  
Acute Cholecystitis ◽  
Antibiotic Treatment ◽  
Malignant Tumors ◽  
Standardized Uptake Value ◽  
High Elevation ◽  
Carbohydrate Antigen ◽  
Reactive Protein ◽  
Positron Emission ◽  
Serum Carbohydrate Antigen ◽  
One Year

Serum carbohydrate antigen 19-9 (CA 19-9), a marker of malignant tumors, is generally slightly elevated in benign conditions. We report a case of acute cholecystitis with a significantly elevated level of serum CA 19-9 based on positron emission tomography (PET)-computed tomography (CT) findings. A 65-year-old woman presented with abdominal pain and fever. A CT image revealed an enlarged gallbladder without tumor shadows. The C-reactive protein (CRP) level was elevated to 7.66 mg/dl. Moreover, the serum CA 19-9 level was significantly elevated to 19,392 U/ml. We started antibiotic treatment, because we suspected acute cholecystitis, but still, we could not ignore the possible presence of malignant tumors. After 11 days of antibiotic treatment, serum CRP and CA 19-9 levels decreased to 0.11 mg/dl and 1,049 U/ml, respectively. There was an accumulation of fluorine 18-labeled fluorodeoxyglucose (maximum standardized uptake value, 9.3) without tumor shadows in the liver, near the gallbladder, on the PET-CT examination. We considered the possibility that the inflammation had spread from the gallbladder to the liver, made a diagnosis of acute cholecystitis, and performed a cholecystectomy 33 days after treatment initiation. The serum CA 19-9 level decreased to 45 U/ml after the surgery. One year after the surgery, the patient was alive, and the serum CA 19-9 level was 34 U/ml. Acute cholecystitis with a significantly high elevation of the serum CA 19-9 level is rare. In such cases, it is important to confirm the change in the serum CA 19-9 level over time after antibiotic treatment and perform imaging studies to distinguish between inflammation and malignancy.

P946Abnormal ankle brachial indices are associated with ischemic stroke: evidence from a large cohort study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Bhatt ◽  
A S Tseng ◽  
M Girardo ◽  
C Firth ◽  
D Fortuin ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Peripheral Arterial Disease ◽  
Arterial Disease ◽  
P Value ◽  
Care Hospital ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Artery Disease ◽  
Peripheral Arterial

Abstract Background Peripheral arterial disease is a marker of aggressive atherosclerosis. The ankle brachial index (ABI) is a simple and non-invasive tool to diagnose peripheral arterial disease (PAD). Patients with PAD are at increased risk for ischemic strokes and other cardiovascular diseases. Purpose To evaluate the association of abnormal ABI and poorly compressible vessels with ischemic stroke in a large patient cohort. Methods We analyzed lower extremity vascular studies of all patients with ABI measurements at a tertiary care hospital between January 1996 and August 2018. PAD is defined as ABI<1.0, and poorly or non-compressible (PC/NC) arteries as ABI>1.4 while ABI between 1.0–1.4 is normal. Association of these ABIs with new ischemic stroke events post ABI measurement were analyzed after adjusting for high risk confounders such as atrial fibrillation. Hazard ratios (HR) were calculated using multivariable Cox proportional regression with 95% confidence intervals. Results In total, 38,016 unique patients (mean age 66.1±14.8 years, female 42.3%) were included. Abnormal ABI was found to be more prevalent among elderly male patients compared to patients with normal ABI. In contrast to non-PAD patients, both PAD and PC/NC patients as defined by ABI had a statistically significant risk of ischemic stroke, with PAD conferring the greatest risk compared to PC/NC vessels. The data is summarized in Table 1. Table 1 Unadjusted HR p-value Adjusted HR p-value PAD vs. No PAD 2.77 (2.62, 2.92) <0.001 2.10 (1.98, 2.22) <0.001 PC/NC vs. No PAD 2.11 (1.95, 2.28) <0.001 1.38 (1.26, 1.51) <0.001 PAD vs. PC/NC 1.37 (1.28, 1.46) <0.001 1.37 (1.28, 1.48) <0.001 Adjusted and unadjusted hazard ratios with p-values. HR adjusted for age, sex, atrial fibrillation, ischemic stroke, transient ischemic attack, chronic heart failure, diabetes mellitus, hyperlipidemia, hypertension, and coronary artery disease. PAD = Peripheral artery disease and PC/NC = poorly compressible/non-compressible. Conclusion This study adds to the growing body of evidence that PAD and poorly-compressible vessels are independently associated with an increased risk of ischemic stroke. Given the associated risk of cerebrovascular disease, clinicians should aggressively treat to minimize risk factors in those with abnormal ABIs.

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