P6414DNA hydroxymethylation combined with carotid plaques as a novel biomarker for coronary atherosclerosis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
D Zhang ◽  
D A N Jiang ◽  
P I N G Ge
Keyword(s):  
Risk Factors ◽  
Dna Methylation ◽  
Carotid Plaque ◽  
Coronary Atherosclerosis ◽  
Univariate Analysis ◽  
Diagnostic Value ◽  
Gensini Score ◽  
Carotid Plaques ◽  
History Of ◽  
Hs Crp

Abstract Background Accumulating evidence has shown the association between DNA methylation and hydroxymethylation and the development of atherosclerosis. However, little is known about the diagnostic value of DNA methylation and hydroxymethylation for coronary atherosclerosis. Carotid plaque has a significant correlation with coronary atherosclerosis, which is a common marker for coronary atherosclerosis. Purpose The major aim of the present study is to determine whether DNA methylation and hydroxymethylation combined with carotid plaques can be useful to the diagnosis of coronary atherosclerosis. Methods 113 patients undergoing carotid ultrasound were enrolled into the study and measured the levels of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC). Crouse score and Gensini score were used to evaluate the severity of carotid and coronary atherosclerosis, respectively. Results With the increasing of severity of carotid plaque and Crouse score, a stepwise upward trend was observed in 5-mC and 5-hmC levels, which were significantly correlated with the risk factors such as FPG and HbA1c levels, Crouse score and Gensini score. Crouse score and 5-hmC, not 5-mC, were the risk factors for coronary atherosclerosis after adjustment for the risk factors. Receiver operating characteristic (ROC) analysis for comparing their diagnostic value for coronary atherosclerosis indicated that 5-hmC combined with Crouse score was the diagnostic biomarker for coronary atherosclerosis, with the highest areas under the curve (AUC), valuable sensitivity and specificity. Logistic regression analysis Variables Univariate analysis Multivariate analysis OR (95% CI) P OR (95% CI) P History of DM 3.680 (1.645–8.235) 0.002 4.487 (0.227–88.680) 0.324 FPG (mmol/L) 1.782 (1.219–2.605) 0.003 0.972 (0.307–3.071) 0.961 HbA1c (%) 1.785 (1.191–2.674) 0.005 2.861 (0.717–11.422) 0.137 TC (mmol/L) 1.171 (0.913–1.502) 0.214 LDL-c (mmol/L) 1.383 (0.939–2.036) 0.100 hs-CRP (mg/L) 1.099 (1.020–1.184) 0.014 1.268 (1.013–1.588) 0.038 Crouse score 1.795 (1.445–2.230) <0.001 1.863 (1.053–3.297) 0.033 5-mC (%) 3.221 (1.851–5.604) <0.001 0.983 (0.386–2.505) 0.972 5-hmC (%) per 0.01% 1.484 (1.265–1.741) <0.001 1.767 (1.250–2.499) 0.001 Conclusions These findings suggest 5-hmC level combined with Crouse score may provide the meaningful information for coronary atherosclerosis diagnosis. Acknowledgement/Funding National Natural Science Foundation of China (No.81570212, No.31800976)

scholarly journals Prediction of subclinical coronary atherosclerosis in patients with high and very high cardiovascular risk

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
N Pogosova ◽  
NP Kachanova ◽  
YM Yufereva ◽  
OY Sokolova ◽  
IE Koltunov ◽  
...  
Keyword(s):  
Family History ◽  
Ct Angiography ◽  
Coronary Atherosclerosis ◽  
Subclinical Atherosclerosis ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Diagnostic Model ◽  
History Of ◽  
Hs Crp ◽  
Very High

Abstract Funding Acknowledgements Type of funding sources: None. Background Coronary atherosclerosis has a long subclinical period. It’s early detection may offer a possibility of timely initiation of preventive interventions Purpose To develop a diagnostic rule for detection of patients (pts) with high probability of subclinical atherosclerosis among those with high or very high cardiovascular (CV) risk. Methods This cross-sectional study enrolled 52 pts (32 men [62%]), aged 40 to 65 years [mean age 54.6 ± 8.0]) with high or very high CV risk (5-9 and ≥10% by The Systematic Coronary Risk Estimation Scale [SCORE], respectively). All participants underwent cardiac computed tomography (CT) angiography and calcium scoring. Traditional risk factors (RFs) (family history of premature CVD, smoking, overweight/obesity and abdominal obesity, hypertension, type 2 diabetes mellitus, lipids parameters (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides) and lipids-related markers (apolipoprotein A1, apolipoprotein B, ApoB/ApoA1 ratio), biomarkers of inflammation (high-sensitivity C-reactive protein [hs CRP], fibrinogen), indicator carbohydrate metabolism (glucose),  ankle-brachial index,  stress-test, carotid plaques according to ultrasound were evaluated in all pts. Psychological RFs were evaluated using Hospital Anxiety and Depression Scale and DS-14 for type D personality. Results All pts were divided into 2 groups according to the CT angiography results: pts in the main group (n = 21) had any non-obstructive lesions or calcium score &gt;0, pts in the control group (n = 31) had intact coronary arteries. The groups did not differ in age or gender. 26 multiple linear logistic models for any subclinical atherosclerosis were developed based on obtained diagnostic features. Taking into account R-square = 0.344 (p = 0.0008), the best fitting model was follows:  subclinical coronary atherosclerosis= -1.576 + 0.234 x SCORE ≥5%  + 0.541 x hs CRP &gt;2 g/l + 0.015 x heart rate  (bpm) + 0.311 family history of premature CVD.  The developed algorithm had sensitivity of 63% and  specificity of 80%. Conclusions The created diagnostic model diagnostic model suggests the presence of subclinical coronary atherosclerosis in patients with high / very high CV risk with a high degree of probability. This easy-to-use method can be used in routine clinical practice to improve risk stratification and management choices in high-risk pts.

scholarly journals Patients with SLE have higher risk of cardiovascular events and mortality in comparison with controls with the same levels of traditional risk factors and intima-media measures, which is related to accumulated disease damage and antiphospholipid syndrome: a case–control study over 10 years

2021 ◽  
Vol 8 (1) ◽  
pp. e000454
Author(s):  
Sofia Ajeganova ◽  
Ingiäld Hafström ◽  
Johan Frostegård
Keyword(s):  
Risk Factors ◽  
Antiphospholipid Syndrome ◽  
Carotid Plaque ◽  
Adverse Outcome ◽  
Density Lipoprotein ◽  
Index Score ◽  
Baseline Body Mass Index ◽  
Systemic Lupus ◽  
Increased Risk ◽  
History Of

ObjectiveSLE is a strong risk factor for premature cardiovascular (CV) disease and mortality. We investigated which factors could explain poor prognosis in SLE compared with controls.MethodsPatients with SLE and population controls without history of clinical CV events who performed carotid ultrasound examination were recruited for this study. The outcome was incident CV event and death. Event-free survival rates were compared using Kaplan-Meier curves. Relative HR (95% CI) was used to estimate risk of outcome.ResultsPatients (n=99, 87% female), aged 47 (13) years and with a disease duration of 12 (9) years, had mild disease at inclusion, Systemic Lupus Erythematosus Diseases Activity Index score of 3 (1–6) and Systemic Lupus International Collaborating Clinics (SLICC) Damage Index score of 0 (0–1). The controls (n=109, 91% female) were 49 (12) years old. Baseline carotid intima-media thickness (cIMT) did not differ between the groups, but plaques were more prevalent in patients (p=0.068). During 10.1 (9.8-10.2) years, 12 patients and 4 controls reached the outcome (p=0.022). Compared with the controls, the risk of the adverse outcome in patients increased threefold to fourfold taking into account age, gender, history of smoking and diabetes, family history of CV, baseline body mass index, waist circumference, C reactive protein, total cholesterol, high-density lipoprotein, low-density lipoprotein, dyslipidaemia, cIMT and presence of carotid plaque. In patients, higher SLICC score and SLE-antiphospholipid syndrome (SLE-APS) were associated with increased risk of the adverse outcome, with respective HRs of 1.66 (95% CI 1.20 to 2.28) and 9.08 (95% CI 2.71 to 30.5), as was cIMT with an HR of 1.006 (95% CI 1.002 to 1.01). The combination of SLICC and SLE-APS with cIMT significantly improved prediction of the adverse outcome (p<0.001).ConclusionIn patients with mild SLE of more than 10 years duration, there is a threefold to fourfold increased risk of CV events and death compared with persons who do not have SLE with similar pattern of traditional CV risk factors, cIMT and presence of carotid plaque. SLICC, SLE-APS and subclinical atherosclerosis may indicate a group at risk of worse outcome in SLE.

scholarly journals Semiquantified Noncalcified Coronary Plaque in Systemic Lupus Erythematosus

2012 ◽  
Vol 39 (12) ◽  
pp. 2286-2293 ◽  
Author(s):  
ADNAN N. KIANI ◽  
JENS VOGEL-CLAUSSEN ◽  
ARMIN ARBAB-ZADEH ◽  
LAURENCE S. MAGDER ◽  
JOAO LIMA ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Lupus Erythematosus ◽  
Univariate Analysis ◽  
Coronary Plaque ◽  
Systemic Lupus ◽  
History Of ◽  
Noncalcified Plaque

Objective.A major cause of morbidity and mortality in systemic lupus erythematosus (SLE) is accelerated coronary atherosclerosis. New technology (computed tomographic angiography) can measure noncalcified coronary plaque (NCP), which is more prone to rupture. We report on a study of semiquantified NCP in SLE.Methods.Patients with SLE (n = 147) with no history of cardiovascular disease underwent 64-slice coronary multidetector computed tomography (MDCT). The MDCT scans were evaluated quantitatively by a radiologist, using dedicated software.Results.The group of 147 patients with SLE was 86% female, 70% white, 29% African American, and 3% other ethnicity. The mean age was 51 years. In our univariate analysis, the major traditional cardiovascular risk factors associated with noncalcified plaque were age (p = 0.007), obesity (p = 0.03; measured as body mass index), homocysteine (p = 0.05), and hypertension (p = 0.04). Anticardiolipin (p = 0.026; but not lupus anticoagulant) and anti-dsDNA (p = 0.03) were associated with higher noncalcified plaque. Prednisone and hydroxychloroquine therapy had no effect, but methotrexate (MTX) use was associated with higher noncalcified plaque (p = 0.0001). In the best multivariate model, age, current MTX use, and history of anti-dsDNA remained significant.Conclusion.Our results suggest that serologic SLE (anti-dsDNA) and traditional cardiovascular risk factors contribute to semiquantified noncalcified plaque in SLE. The association with MTX is not understood, but should be replicated in larger studies and in multiple centers.

scholarly journals Risk Factors for Community Acquired Extended-Spectrum Β-lactamase (ESBL) Producing Enterobacteriaceae Urinary Tract Infections (UTIs)

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S345-S345
Author(s):  
Dheeraj Goyal ◽  
Kristin Dascomb ◽  
Peter S Jones ◽  
Bert K Lopansri
Keyword(s):  
Risk Factors ◽  
Urinary Tract ◽  
Urinary Catheter ◽  
Univariate Analysis ◽  
Prior History ◽  
Factors Associated ◽  
Extended Spectrum ◽  
History Of ◽  
Enterobacteriaceae Infections ◽  
Tract Infections

Abstract Background Community-acquired extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae infections pose unique treatment challenges. Identifying risk factors associated with ESBL Enterobacteriaceae infections outside of prior colonization is important for empiric management in an era of antimicrobial stewardship. Methods We randomly selected 251 adult inpatients admitted to an Intermountain healthcare facility in Utah with an ESBL Enterobacteriaceae urinary tract infection (UTI) between January 1, 2001 and January 1, 2016. 1:1 matched controls had UTI at admission with Enterobacteriaceae but did not produce ESBL. UTI at admission was defined as urine culture positive for &gt; 100,000 colony forming units per milliliter (cfu/mL) of Enterobacteriaceae and positive symptoms within 7 days prior or 2 days after admission. Repeated UTI was defined as more than 3 episodes of UTI within 12 months preceding index hospitalization. Cases with prior history of ESBL Enterobacteriaceae UTIs or another hospitalization three months preceding the index admission were excluded. Univariate and multiple logistic regression techniques were used to identify the risk factors associated with first episode of ESBL Enterobacteriaceae UTI at the time of hospitalization. Results In univariate analysis, history of repeated UTIs, neurogenic bladder, presence of a urinary catheter at time of admission, and prior exposure to outpatient antibiotics within past one month were found to be significantly associated with ESBL Enterobacteriaceae UTIs. When controlling for age differences, severity of illness and co-morbid conditions, history of repeated UTIs (adjusted odds ratio (AOR) 6.76, 95% confidence interval (CI) 3.60–13.41), presence of a urinary catheter at admission (AOR 2.75, 95% CI 1.25 – 6.24) and prior antibiotic exposure (AOR: 8.50, 95% CI: 3.09 – 30.13) remained significantly associated with development of new ESBL Enterobacteriaceae UTIs. Conclusion Patients in the community with urinary catheters, history of recurrent UTIs, or recent antimicrobial use can develop de novo ESBL Enterobacteriaceae UTIs. Disclosures All authors: No reported disclosures.

Skin cholesterol: test performance, evaluation of potential determinants and correlation analysis with cardiovascular risk factors and circulating markers of inflammation

VASA ◽  
2006 ◽  
Vol 35 (3) ◽  
pp. 167-173 ◽  
Author(s):  
Reiter ◽  
Wirth ◽  
Pourazim ◽  
Exner ◽  
Baghestanian ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Body Fat ◽  
Test Performance ◽  
Cardiovascular Events ◽  
Serum Lipids ◽  
Markers Of Inflammation ◽  
History Of ◽  
Hs Crp

Background: Skin cholesterol (SkC) has been suggested to be an additional risk predictor, so we evaluated the test performance, potential determinants of this marker as well as a potential correlation of SkC with markers of inflammation and the history of cardiovascular events. Patients and methods: SkC, determined by the non-invasive PREVU POC Skin Sterol test, as well as serum lipids, the body fat status, high-sensitive CRP (hs-CRP) and serum amyloid A (SAA) were evaluated in consecutive patients with and without documented atherosclerotic disease. Results: SkC was assessed in 201 patients. The within-day precision (CV) was 3.8%, the day-to-day CV of the right hand was 8.6% and 4.3% for the left hand, respectively. Neither univariate analysis nor multiple regressions identified a significant influence of age, sex, serum lipids, body fat status, smoking or diabetes mellitus on SkC, corresponding results were observed in a further analysis including 174 of these patients concerning hs-CRP and SAA (all p > 0.05). T-test analyses detected no significant differences between patients with and without a history of coronary, peripheral vascular and cerebrovascular events (all p > 0.05). Conclusions: The PREVU POC Skin Sterol test for the assessment of SkC proved an acceptable test performance. SkC is independent from serum lipids, traditional cardiovascular risk factors, two sensitive markers of systemic inflammation as well as the history of cardiovascular events indicating that the perception of this parameter as an established marker of vascular disease is premature.

Comparison of Hirschsprung Disease Characteristics between Those with a History of Postoperative Enterocolitis and Those without: Results from the Pediatric Colorectal and Pelvic Learning Consortium

2020 ◽  
Author(s):  
Mark A. Taylor ◽  
Brian T. Bucher ◽  
Ron W. Reeder ◽  
Jeffrey R. Avansino ◽  
Megan Durham ◽  
...  
Keyword(s):  
Risk Factors ◽  
Transition Zone ◽  
Private Insurance ◽  
Univariate Analysis ◽  
Hirschsprung Disease ◽  
Clinical Information ◽  
Retrospective Case ◽  
Disease Characteristics ◽  
History Of ◽  
Pull Through

Abstract Introduction The current understanding of Hirschsprung-associated enterocolitis (HAEC) is based mainly on single-center, retrospective studies. The aims of this study are to determine risk factors for postoperative HAEC using the Pediatric Colorectal and Pelvic Learning Consortium (PCPLC) database. Materials and Methods We performed a multicenter, retrospective, case–control study of children with Hirschsprung disease (HD) who had undergone a pull-through procedure and were evaluated at a PCPLC member site between February 2017 and March 2020. The cohort with a history of postoperative HAEC was compared with that without postoperative episodes of HAEC to determine relevant associations with postoperative HAEC. Results One-hundred forty of 299 (46.8%) patients enrolled had a history of postoperative HAEC. Patients with a rectosigmoid transition zone had a lower association with postoperative HAEC as compared with those with a more proximal transition zone (odds ratio [OR]: 0.46, 95% confidence interval [CI]: 0.26, 0.84, p < 0.01). Private insurance was protective against postoperative HAEC on univariate analysis (OR: 0.62, 95% CI: 0.38, 0.99, p = 0.047), but not on multivariate analysis (OR: 0.62, 95% CI: 0.37, 1.04, p = 0.07). Preoperative HAEC was not associated with the development of postoperative HAEC. Conclusion Patients with a rectosigmoid transition zone have less postoperative HAEC compared with patients with a more proximal transition zone. Multi-institutional collection of clinical information in patients with HD may allow for the identification of additional risk factors for HAEC and afford the opportunity to improve care.

scholarly journals Risk factors for a first thrombotic event in antiphospholipid antibody carriers: a prospective multicentre follow-up study

2011 ◽  
Vol 70 (6) ◽  
pp. 1083-1086 ◽  
Author(s):  
Amelia Ruffatti ◽  
Teresa Del Ross ◽  
Manuela Ciprian ◽  
Maria T Bertero ◽  
Sciascia Salvatore ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Univariate Analysis ◽  
Thrombotic Event ◽  
Multivariate Logistic Regression Analysis ◽  
Antiphospholipid Antibody ◽  
History Of ◽  
Ischaemic Attack ◽  
Independent Risk Factors

ObjectivesTo assess risk factors for a first thrombotic event in confirmed antiphospholipid (aPL) antibody carriers and to evaluate the efficacy of prophylactic treatments.MethodsInclusion criteria were age 18–65 years, no history of thrombosis and two consecutive positive aPL results. Demographic, laboratory and clinical parameters were collected at enrolment, once a year during the follow-up and at the time of the thrombotic event, whenever that occurred.Results258 subjects were prospectively observed between October 2004 and October 2008. The mean±SD follow-up was 35.0±11.9 months (range 1–48). A first thrombotic event (9 venous, 4 arterial and 1 transient ischaemic attack) occurred in 14 subjects (5.4%, annual incidence rate 1.86%). Hypertension and lupus anticoagulant (LA) were significantly predictive of thrombosis (both at p<0.05) and thromboprophylaxis was significantly protective during high-risk periods (p<0.05) according to univariate analysis. Hypertension and LA were identified by multivariate logistic regression analysis as independent risk factors for thrombosis (HR 3.8, 95% CI 1.3 to 11.1, p<0.05, and HR 3.9, 95% CI 1.1 to 14, p<0.05, respectively).ConclusionsHypertension and LA are independent risk factors for thrombosis in aPL carriers. Thromboprophylaxis in these subjects should probably be limited to high-risk situations.

scholarly journals Association of Testosterone, Insulin-Like Growth Factor-I, and C-Reactive Protein with Metabolic Syndrome in Chinese Middle-Aged Men with a Family History of Type 2 Diabetes

2005 ◽  
Vol 90 (12) ◽  
pp. 6418-6423 ◽  
Author(s):  
Peter C. Y. Tong ◽  
Chung-Shun Ho ◽  
Vincent T. F. Yeung ◽  
Maggie C. Y. Ng ◽  
Wing-Yee So ◽  
...  
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Family History ◽  
Total Testosterone ◽  
C Reactive Protein ◽  
Middle Aged ◽  
Reactive Protein ◽  
Igf I ◽  
History Of ◽  
Hs Crp

Context: Age-related declines in testosterone and IGF-I are associated with deposition of visceral fat, a component of the metabolic syndrome (MES). Objective: Testosterone and IGF-I may interact with familial disposition to diabetes mellitus to increase the association with MES. Design: We conducted a cross-sectional cohort study. Setting: The study was conducted in a university teaching hospital. Subjects: Study subjects included 179 middle-aged men with a family history of diabetes (FH) (aged 39.1 ± 8.1 yr) and 128 men without FH (aged 43.8 ± 8.5 yr). Main Outcome Measures: Clinical characteristics, frequency of MES using the World Health Organization criteria with Asian definitions of obesity (body mass index ≥ 25 kg/m2), and serum levels of total testosterone, IGF-I, and high-sensitive C-reactive protein (hs-CRP) were measured. Results: Men with FH had higher frequency of MES than those without FH [39.1 vs. 23.4% (P = 0.004)]. On multivariate analysis, smoking (former and current smokers), low total testosterone, and IGF-I but elevated hs-CRP levels explained 35% of the MES variance in men with FH. The frequency of MES increased with declining tertiles of total testosterone and IGF-I but increasing tertiles of hs-CRP. After adjustment for age and smoking history, subjects with all three risk factors had a 13-fold increase in risk association with MES compared with those without hormonal and inflammatory risk factors. These risk associations were not found in men without FH in whom only smoking (ex and current) and low total testosterone level were independent predictors for MES, which explained 14% of the variance. Conclusions: Clustering of FH, hormonal abnormalities, and high hs-CRP is associated with MES in Chinese middle-aged men.

scholarly journals Incidence and Risk Factors of Diabetic Foot Ulcer: A Population-Based Diabetic Foot Cohort (ADFC Study)—Two-Year Follow-Up Study

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Leila Yazdanpanah ◽  
Hajieh Shahbazian ◽  
Iraj Nazari ◽  
Hamid Reza Arti ◽  
Fatemeh Ahmadi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Diabetic Foot ◽  
Univariate Analysis ◽  
Previous History ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
Population Based ◽  
University Hospital ◽  
Foot Deformity ◽  
History Of

Aim/Introduction. This study was carried out to assess the incidence and risk factors of diabetic foot ulcer (DFU). Materials and Methods. In this prospective cohort study in a university hospital, all the participants were examined and followed up for new DFU as final outcome for two years. To analyze the data, the variables were first evaluated with a univariate analysis. Then variables with P value < 0.2 were tested with a multivariate analysis, using backward-elimination multiple logistic regression. Results. Among 605 patients, 39 cases had DFU, so we followed up the remaining 566 patients without any present or history of DFU. A two-year cumulative incidence of diabetic foot ulcer was 5.62% (95% CI 3.89–8.02). After analysis, previous history of DFU or amputation [OR = 9.65, 95% CI (2.13–43.78), P value = 0.003], insulin usage [OR = 5.78, 95% CI (2.37–14.07), P value < 0.01], gender [OR = 3.23, 95% CI (1.33–7.83), P value = 0.01], distal neuropathy [OR = 3.37, 95% CI (1.40–8.09), P value = 0.007], and foot deformity [OR = 3.02, 95% CI (1.10–8.29), P value = 0.032] had a statistically significant relationship with DFU incidence. Conclusion. Our data showed that the average annual DFU incidence is about 2.8%. Independent risk factors of DFU development were previous history of DFU or amputation, insulin consumption, gender, distal neuropathy, and foot deformity. These findings provide support for a multifactorial etiology for DFU.

Risk Factors for Thrombosis Among 1,545 Patients with Polycythemia Vera: An International Study.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2849-2849
Author(s):  
Guido Finazzi ◽  
Elisa Rumi ◽  
Alessandro M. Vannucchi ◽  
Maria Luigia Randi ◽  
Ilaria Nichele ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thrombosis ◽  
Board Of Directors ◽  
Arterial Thrombosis ◽  
Myeloproliferative Neoplasms ◽  
Univariate Analysis ◽  
Abnormal Karyotype ◽  
Advisory Committees ◽  
Free Survival ◽  
History Of

Abstract Abstract 2849 Background We have previously reported on the natural history of polycythemia vera (PV), focusing primarily on overall and leukemia-free survival (ASH Annual Meeting Abstracts. 2011;118(21):277-). In the current study, we present, on behalf of the International Working Group for Myeloproliferative neoplasms Resarch and Treatment (IWG-MRT), our analysis regarding risk factors for thrombosis. Methods Under the auspices of IWG-MRT, seven international centers of excellence for myeloproliferative neoplasms participated in the current study. The two principle investigators (AT and TB) reviewed all the cases and selected 1,545 patients who met the 2008 WHO criteria for PV, were age 18 years or older, diagnosed after 1970, and whose submitted data included diagnostically essential information. Results I: Presenting Features Median age was 61 years (range, 18–95; 51% females). Arterial and venous thrombosis history before or at diagnosis was documented in 246 (16%) patients and 114 (7.4%) patients, respectively. Major hemorrhage hemorrhage before or at diagnosis was documented in 17 (4.5%) patients. Other features at diagnosis included pruritus (36%), microvascular disturbances (28.5%), palpable splenomegaly (36%), abnormal karyotype (12%), leukoerythroblastosis (6%), increased LDH (50%), thrombocytosis (53%), extreme thrombocytosis (platelets >1 million mm3; 4%) leukocytosis (49%), JAK2 V617F (95%), other JAK2 mutations (3%), subnormal serum erythropoietin (Epo) level (81%), and endogenous erythroid colonies (EEC; 73%). History of hypertension (46%), hyperlipidemia (18.3%), diabetes (8.4%), and tobacco use (16%) was also obtained. Results II: Clinical Course To date, 347 (23%) deaths, 50 (3%) leukemic progressions, and 138 (9%) fibrotic transformations have been recorded. Overall, cytoreductive treatment was not used in 416 (27%) patients and the remaining were exposed to different agents based on physician discretion. Post-diagnosis arterial or venous thrombosis occurred in 184 (12%) and 137 (9%) patients, respectively. Results III: Risk Factors for thrombosis Arterial and venous thrombosis-free survival, from time of diagnosis, were separately analyzed using the occurrence of thrombosis as the endpoint (uncensored variable) and last follow-up or death before thrombosis as the censored variable. In univariate analysis, the following were significantly associated with post-diagnosis arterial thrombosis: advanced age, leukocyte count, presence of a leukoerythroblastic smear (LES), history of hypertension and history of arterial thrombosis before or at diagnosis; multivariable analysis using all these five parameters identified arterial thrombosis history (RR 2.5, 95% CI 1.6–4.0; p<0.0001), LES (RR 2.3, 95% CI 1.3–4.2; p=0.005) and history of hypertension (RR 1.6, 95% CI 1.1–2.4; p=0.02) as independent predictors of post-diagnosis arterial thrombosis. Only two parameters predicted post-diagnosis venous thrombosis, in univariate analysis, and both remained significant during multivariable analysis: abnormal karyotype (RR 3.1, 95% CI 1.7–5.4; p=0.0001) and history of venous thrombosis (RR 2.4, 95% CI 1.2–4.9). Of note, the type of JAK2 mutation or presence of either subnormal Epo or EEC did not influence either arterial or venous thrombosis. Results IV: Risk Stratification for arterial and venous thrombosis The figures below illustrated arterial or venous thrombosis-free survival of patients stratified by the absence of all risk factors or presence of one or ≥2 risk factors. For arterial thrombosis, the presence of ≥2 risk factors clearly delineated a high risk group (RR 3.1, 95% CI 1.9–5.0) whereas the presence of one (RR 2.4, 95% CI 1.4–4.2) or two risk factors (RR 10.1, 95% CI 3.6–28.2) for venous thrombosis delineated an intermediate and high risk group, respectively. Conclusions: History of arterial thrombosis and venous thrombosis are key risk factors, respectively, for recurrent arterial and venous thrombosis in PV. In addition, abnormal karyotype is a strong independent risk factor for venous thrombosis and the presence of leukoerythroblastosis and hypertension, for arterial thrombosis. This information allows for a simple and practical risk stratification and raises interesting pathogenetic implications that require further clarification. Disclosures: Vannucchi: Novartis: Membership on an entity's Board of Directors or advisory committees. Gisslinger:Novartis: Consultancy, Research Funding, Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau. Passamonti:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi-Aventis: Honoraria, Membership on an entity's Board of Directors or advisory committees.

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