Previous Arterial Events Research Articles

Prevalence of heart failure with preserved ejection fraction in antiphospholipid antibodies syndrome. The multicenter ATHERO-APS study

Abstract Background The prevalence of heart failure with preserved ejection fraction (HFpEF) in patients with antiphospholipid syndrome (APS) is unknown. Methods Prospective multicenter cohort study including 125 patients: 91 primary APS (PAPS), 18 APS-SLE, and 16 carriers. HFpEF was diagnosed according to the 2019 European Society of Cardiology criteria: patients with ≥5 points among major and minor functional and morphological criteria including NT-ProBNP >220 pg/ml, left atrial (LA) enlargement, increased left ventricular filling pressure. Results Overall, 18 (14.4%) patients were diagnosed with HFpEF; this prevalence increased from 6.3% in carriers to 13.2% in PAPS and 27.8% in APS-SLE (Figure). Patients with HFpEF were older and with a higher prevalence of hypertension and previous arterial events. At logistic regression analysis, age, arterial hypertension, anticardiolipin antibodies IgG >40 GPL (odds ratio [OR] 3.43, 95% Confidence Interval [CI] 1.09–10.77, p=0.035), anti β-2-glycoprotein-I IgG >40 GPL (OR 5.28, 1.53–18.27, p=0.009), lupus anticoagulants DRVVT >1.25 (OR 5.20, 95% CI 1.10–24.68, p=0.038), (OR 3.56, 95% CI 1.11–11.47, p=0.033) and triple positivity (OR 3.56, 95% CI 1.11–11.47, p=0.033) were associated with HFpEF after adjustment for age and sex. Discussion HFpEF has a clinically relevant prevalence in patients with APS. The role of antiphospholipid antibodies in the pathogenesis and prognosis of HFpEF needs to be investigated. Funding Acknowledgement Type of funding sources: None.

Antiphospholipid Antibodies and Heart Failure with Preserved Ejection Fraction. The Multicenter ATHERO-APS Study.

Background. The prevalence of heart failure with preserved ejection fraction (HFpEF) in patients with antiphospholipid syndrome (APS) is unknown. Methods. A prospective multicenter cohort study including 125 patients was conducted: 91 primary APS (PAPS), 18 APS-SLE, and 16 carriers. HFpEF was diagnosed according to the 2019 European Society of Cardiology criteria: patients with ≥5 points among major and minor functional and morphological criteria including NT-ProBNP > 220 pg/mL, left atrial (LA) enlargement, increased left ventricular filling pressure. Results. Overall, 18 (14.4%) patients were diagnosed with HFpEF; this prevalence increased from 6.3% in carriers to 13.2% in PAPS and 27.8% in APS-SLE. Patients with HFpEF were older and with a higher prevalence of hypertension and previous arterial events. At logistic regression analysis, age, arterial hypertension, anticardiolipin antibodies IgG > 40 GPL (odds ratio (OR) 3.43, 95% confidence interval (CI) 1.09–10.77, p = 0.035), anti β-2-glycoprotein-I IgG > 40 GPL (OR 5.28, 1.53–18.27, p = 0.009), lupus anticoagulants DRVVT > 1.25 (OR 5.20, 95% CI 1.10–24.68, p = 0.038), and triple positivity (OR 3.56, 95% CI 1.11–11.47, p = 0.033) were associated with HFpEF after adjustment for age and sex. By multivariate analysis, hypertension (OR 19.49, 95% CI 2.21–171.94, p = 0.008), age (OR 1.07, 95% CI 1.00–1.14, p = 0.044), and aβ2GPI IgG > 40 GPL (OR 8.62, 95% CI 1.23–60.44, p = 0.030) were associated with HFpEF. Conclusion. HFpEF is detectable in a relevant proportion of APS patients. The role of aPL in the pathogenesis and prognosis of HFpEF needs further investigation.

Management of Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS), is an acquired autoimmune disorder characterised by thrombosis, pregnancy morbidity, and the presence of antiphospholipid antibodies (aPL). Although venous thromboembolism is the most common manifestation, thrombotic events in APS may also occur in virtually any vascular bed, with cerebral circulation being the arterial territory most commonly affected. As APS is a heterogeneous condition, its management should be tailored with a patient-centred approach based on individual risk assessment, which includes the aPL profile, concomitant auto-immune diseases, and traditional cardiovascular risk factors. Although literature data are conflicting regarding primary prophylaxis, there is some evidence indicating that antiplatelet agents may reduce the risk of a first thrombotic event in individuals with a high-risk profile. In patients with thrombotic APS, current evidence-based guidelines recommend lifelong vitamin K antagonists (VKAs), preferably warfarin. The optimal intensity of anticoagulation following arterial thrombosis remains controversial. Arterial thrombosis should be treated either with high-intensity warfarin at a target INR > 3.0, or low-dose aspirin (LDA) combined with moderate-intensity warfarin (INR 2.0–3.0). It is recommended to avoid direct oral anticoagulants (DOACs) in patients with high-risk APS, mainly those with triple-positive PL and previous arterial events. They would only be used exceptionally in selected patients with low-risk venous thromboembolism (VTE). In low-risk VTE patients currently treated with a DOAC due to warfarin intolerance or a previous unstable International Normalized Ratio on warfarin, the decision of continuing DOACs would be taken in carefully selected patients. In women with obstetric APS, the combination therapy with LDA plus heparin remains the conventional strategy.

Effectiveness and Safety of the Direct Oral Anticoagulants in Low-Risk Antiphospholipid Syndrome: A Case Series

Introduction: Thrombotic Antiphospholipid syndrome (TAPS) is an autoimmune condition where venous thromboembolism (VTE) and/or arterial thromboembolism (ATE) occurs in the presence of antiphospholipid antibodies (aPLs). TAPS is traditionally managed with long-term anticoagulation with vitamin K antagonists (VKA). Over the past decade, direct oral anticoagulants (DOACs) have been increasingly replacing VKAs as the oral anticoagulant of choice given their lower risk of bleeding, fixed dosing, and no requirement for routine monitoring. However, recent evidence has demonstrated inferiority of DOACs compared to VKAs in TAPS patients with high risk (triple positive) aPL profiles or previous arterial events. It remains unclear whether TAPS patients with low risk aPL profiles (single positive), and without previous ATE, can be treated effectively and safely with DOACs. Objectives: To assess the effectiveness and safety of DOACs at preventing recurrent VTE or ATE in TAPS patients with a low risk aPL profile, and without prior ATE. Methods: We conducted a retrospective review of all TAPS patients with a low risk aPL profile, without prior ATE, who were anticoagulated with a DOAC at two tertiary care hospitals in Toronto, Canada from January 2010 to July 2020. All patients with any positive aPL test results were first identified through the laboratory information system. This list was cross referenced with patients seen in specific thrombosis clinics and confirmed through individual electronic chart review. TAPS was defined as persistent (>12 weeks apart) lupus anticoagulant (LA) positivity, anti-cardiolipin titre (ACA) >40 GPL, or anti-2-glycoprotein 1 titre (a2GP1) >40 GPL, with a preceding thrombotic event. Patients were excluded if any of the aPLs were deemed to be simultaneously positive or if there was a history of previous ATE. a2GP1 was not systematically tested in all patients. Patient outcomes were assessed throughout the duration of anticoagulation with a DOAC. Recurrent VTE included deep vein thrombosis, pulmonary embolism, or VTE of atypical location, and required objective confirmation with appropriate diagnostic imaging. ATE included ischemic stroke, transient ischemic attack (TIA), myocardial infarction, or other systemic arterial embolism. Major bleeding (MB) and clinically relevant non major bleeding (CRNMB) were defined by International Society on Thrombosis and Hemostasis criteria. Results: 1195 patients were identified with at least one instance of single positive aPL who had been seen in one of the thrombosis clinics. Patients were excluded for the following reasons: 858 for non-persistent aPL positivity, 70 for simultaneous aPL positivity, 20 for a likely false positive LA due to DOAC therapy, 93 due to an absence of preceding VTE, 45 for history of previous ATE, and 59 due to no prior DOAC therapy. After exclusions, 50 patients were included in the analysis, encompassing 157.2 years of patient-follow up. The study population was comprised of 24 women and 26 men with a mean age of 49.6 (standard deviation (SD) 16.3)years at the start of DOAC therapy (Table 1). The mean duration of DOAC treatment was 37.7 (SD 23.8) months. Fifteen (30%) patients had prior diagnosis of systemic lupus erythematosus (SLE), while 4 (8%) had other systemic autoimmune disease diagnoses. Only 1 patient met criteria for obstetric APS, on the basis of 3 consecutive fetal losses before 10 weeks gestation. None of the patients had documented valvular disease or thrombocytopenia. All patients were treated initially with therapeutic dose rivaroxaban, although 6 (12%) patients were switched to therapeutic dose apixaban due to increased bruising or menorrhagia. Five patients on rivaroxaban and 3 patients on apixaban were switched to a reduced dose DOAC. No patient had recurrent VTE. One patient had a possible ATE as a TIA, presenting with an episode of loss of sight for 15 minutes while on reduced dose apixaban. None of the patients experienced MB. Two patients experienced CRNMB, both severe menorrhagia, one on therapeutic dose of rivaroxaban and the other patient on reduced dose of rivaroxaban. Conclusions: In our retrospective case series of 50 patients with TAPS, a low risk aPL profile and no previous ATE, DOACs were effective and safe in the secondary prevention of thrombotic events with no MB. Larger, prospective controlled studies are required to confirm these findings. Disclosures No relevant conflicts of interest to declare.

Vascular Ehlers-Danlos Syndrome: Long-Term Observational Study

BackgroundVascular Ehlers-Danlos syndrome (vEDS) is a rare genetic connective tissue disorder secondary to pathogenic variants within the COL3A1 gene, resulting in exceptional arterial and organ fragility and premature death. The only published clinical trial to date demonstrated the benefit of celiprolol on arterial morbimortality. ObjectivesThe authors herein describe the outcomes of a large cohort of vEDS patients followed ≤17 years in a single national referral center. MethodsAll patients with molecularly confirmed vEDS were included in a retrospective cohort study. After an initial work-up, patients were treated or recommended for treatment with celiprolol (≤400 mg/day) in addition to usual care and scheduled for yearly follow-up. vEDS-related events and deaths were collected and recorded for each patient. ResultsBetween 2000 and 2017, 144 patients (median age at diagnosis 34.5 years, 91 probands) were included in this study. After a median follow-up of 5.3 years, overall patient survival was high (71.6%; 95% confidence interval: 50% to 90%) and dependent on the type of COL3A1 variant, age at diagnosis, and medical treatment. At the end of the study period, almost all patients (90.3%) were treated with celiprolol alone or in combination. More than two-thirds of patients remained clinically silent, despite a large number (51%) with previous arterial events or arterial lesions at molecular diagnosis. Patients treated with celiprolol had a better survival than others (p = 0.0004). The observed reduction in mortality was dose-dependent: the best protection was observed at the dose of 400 mg/day versus <400 mg/day (p = 0.003). During the period surveyed, the authors observed a statistically significant difference in the ratio of hospitalizations for acute arterial events/hospitalizations for regular follow-up before and after 2011. ConclusionsIn this long-term survey, vEDS patients exhibited a low annual occurrence of arterial complications and a high survival rate, on which the overall medical care seems to have a positive influence.

The risk of ischaemic stroke in primary antiphospholipid syndrome patients: a prospective study.

The most common neurological manifestation of antiphospholipid syndrome (APS) is ischaemic stroke. Identifying patients with APS at high risk for developing any thrombotic event remains a major challenge. In this study, the aim was to identify predictive factors of ischaemic stroke in a cohort of primary APS (PAPS) patients who presented with new onset symptoms suggestive of acute stroke. This prospective multicentre study included 36 consecutive PAPS patients who presented with new onset symptoms suggestive of an acute stroke. Patients were prospectively followed up for 12 months. In 10 (28%) out of 36 PAPS patients [mean age 41 years (SD 13.4), 70% female], the suspicion of an acute stroke was confirmed by brain magnetic resonance imaging. Sixty per cent of these patients were <50 years old. Eight of the 10 patients had a history of previous venous thrombosis and were receiving vitamin K antagonist (VKA), with international normalized ratio target 2-3; one patient had a history of a previous arterial event receiving treatment with VKA target international normalized ratio 2-3 plus low dose aspirin; and one patient had a history of previous pregnancy morbidity receiving only low dose aspirin. Time in the therapeutic range for patients receiving VKA was 77.7% (SD 6.6%). Hypercholesterolaemia was significantly higher in patients with confirmed stroke compared to those without (P < 0.05). Similarly, a significantly higher rate of anti-β2 glycoprotein-I (β2GPI) antibodies (immunoglobulin G/immunoglobulin M; P < 0.05) and higher adjusted global APS score (aGAPSS) values were found in patients with a confirmed stroke [mean aGAPSS 8.9 (SD 4.7) vs. mean aGAPSS 6.4 (SD 2.5); P < 0.05]. Patients with PAPS, including young patients, have a high risk of recurrent thrombosis despite anticoagulation treatment. A careful risk assessment is mandatory to identify patients at risk for recurrence.

In Contemporary Patients with Polycythemia Vera, Rates of Thrombosis and Risk Factors Delineate a New Clinical Epidemiology

BackgroundCurrent risk stratification in Polycythemia Vera (PV), is designed to estimate the likelihood of thrombotic complications. In ECLAP large prospective study of 1638 PV cases diagnosed by Polycythemia Vera Study Group (PVSG) criteria, risk factors were age over 65 years and prior thrombotic events. After the JAK2V617F discovery, diagnosis has undergone substantial revision by the World Health Organization (WHO). Consequently, current risk factors determination should be described in patients diagnosed by the most recent recommendations and requires a large sample size with reliable and sufficiently long clinical course documentation. Accordingly, the current study includes 1545 patients with strictly WHO-defined PV diagnosed and followed-up in seven centers from Italy, Austria and the United States, belonging to the International Working Group for Myeloproliferative Neoplasm (MPN) Research and Treatment (IWG-MRT).Objective and design1) Describe the rate of thrombosis in this population;2) Report the sites and frequency of recurrences after a first arterial or venous event;3) Identify separately risk factors for arterial versus venous thrombosis and develop practically useful prognostic models.Results1. Presenting featuresThe characteristics of the cohort recruited reflected well the heterogeneity of epidemiologic and clinical features that are found in the routine clinical practice of PV. Arterial and venous thrombosis history before or at diagnosis was documented in 246 (16%) and 114 (7.4%) patients, respectively. The frequencies of arterial and venous thrombosis were lower than those recorded in the ECLAP4 (27% and 11% respectively) but comparable to those reported in the recent Cyto-PV2 (arterial 17%, venous 12%) studies. The discrepancy might be partly related to earlier diagnosis in the post-ECLAP JAK2mutation era.2. Thrombotic events after diagnosisMedian follow-up was 6.9 years and treatment included aspirin (84%) and cytoreductive agents (73%), in addition to phlebotomy. Post-diagnosis total major thrombosis rate was 2.62% pt/yr, lower than reported in the ECLAP trial (4.4% pt/yr) but comparable to the Cyto-PV study (2.7% pt/yr) where management of cardiovascular risk factors was more intensive than in ECLAP.Arterial or venous thrombosis occurred in 184 (12%, rate: 1.59 % pts/yr) and 137 (9%, rate: 1.05 % pts/yr) patients, respectively. In addition, prior arterial events were associated in 75% of cases with subsequent arterial events and in the remaining 25% with venous thrombosis including splanchnic vein events. Moreover, patients with prior venous events had recurrences in venous district in 61% of cases and in the arterial district in 39%.3. Risk factors for arterial versus venous thrombosis and prognostic modelsIn multivariable analysis, arterial thrombosis was predicted by previous arterial event (HR 1.7, 95% CI 1.2-2.4), and hypertension (HR 1.6, 95% CI 1.2-2.2) while predictors of venous events were previous venous thrombosis (HR 2.6, 95% CI 1.5-4.4), and age ≥ 65 years (HR 1.7, 95% CI 1.2-2.5). We used the above-mentioned risk factors in order to develop prognostic models allowing to identify patients at different probability to develop arterial or venous thrombosis. For arterial thrombosis, the absence of previous arterial thrombosis and hypertension defined lower-risk (rate 1.27 % pts/yr) while the presence of one or both identified higher-risk patients (rate 2.04 % pts/yr). Previous venous event and/or age ≥ 65 years identified patients at higher risk of venous (rate 1.62 % pts/yr) thrombosis and, if absent, patients at lower risk (rate 0.78 % pts/yr).ConclusionThe overall rate of thrombosis was half than in ECLAP and should be considered in future clinical trials. Of note, patients with a prior venous thrombosis had a more frequent subsequent recurrence in the venous district but a proportion of them (40%) had also arterial events; conversely, recurrences after previous arterial event were also registered in the leg and non-leg veins in 30 % of cases, indicating that in PV, venous and arterial thrombosis may share some common pathogenetic mechanisms. These findings may have practical implications and suggests antiplatelet therapy and anticoagulant therapy as the favorite choice to prevent arterial and venous thrombosis, respectively, but also suggests studies of antithrombotic drug combination. DisclosuresNo relevant conflicts of interest to declare.

Patients with longstanding primary antiphospholipid syndrome: retrospective analysis of organ damage and mortality.

To assess the prevalence of disease- and therapy-related complications and of the organ damage after a follow-up of 15 years or more in patients with primary antiphospholipid syndrome (PAPS). Medical records of patients prospectively followed in our centre for at least 15 years were retrospectively reviewed. Thirty-five Caucasian patients (33 female, two male) with diagnosis of PAPS followed from 1984 to 2013 with a mean age at onset of 32 years (SD 8.17) and a median follow-up of 20.5 years (range 15-30) were included. The occurrence of systemic autoimmune disease was observed in 14% of patients. Haemorrhagic, infective and neoplastic events were recorded in 34%, 6% and 9% respectively. Organ damage was present in 20% of patients at the end of the follow-up (17% neurological and 3% renal) and was significantly associated with the occurrence of thrombotic events (p: 0.027), particularly arterial (p<0.001). A 48-year-old patient died from sepsis. During long-term follow-up of PAPS systemic autoimmunity is not unexpected. Organ damage progresses in a significant proportion of patients especially if they have suffered previous arterial events. Our study clearly shows the possible evolution of the disease and of organ damage, suggesting that optimal therapy and optimal prophylaxis of each PAPS patient should be carefully identified and strictly applied.

AB0549 Patients with Long-Standing Primary Antiphospholipid Syndrome: Retrospective Analysis of Recurrences, Organ Damage and Mortality

BackgroundWhile acute manifestations related to APS are well known and their treatment is quite standardized, informations on the long-term outcome in affected patients are still very limited 1–3, even though...

Higher levels of plasma matrix metalloproteinase-2 are associated with a significantly increased risk of arterial thrombosis in patients with the antiphospholipid syndrome

Alterations in the structure of extracellular matrix (ECM) play akey role in atherothrombosis. Matrix metalloproteinases (MMPs), afamily of zinc-dependent proteases produced and released by endo-thelial and smooth muscle cells, monocytes and platelets, degradeECM. There is evidence that MMPs are involved in cardiovascular dis-ease [1,2], but also in inflammatory disorders of the respiratory, gas-trointestinal, osteoarticular and central nervous systems [3].Plasma levels of some MMPs, and in particular of MMP-2, havebeen established as biomarkers of cardiovascular risk [1,2], but theyhave also been found to be increased in connective tissue disorders,likerheumatoidarthritis,systemiclupuserythematosusandSjogren'ssyndrome [3].No data are available instead on plasma MMPs in the anti-phospholipid syndrome (APS), an autoimmune condition characterizedby the occurrence of thrombotic events or pregnancy complications as-sociated with antiphospholipid antibodies (aPL). Among thromboticmanifestations of APS, both arterial and venous thrombosis may occur.However, so far no features have been identi fied distinguishing APS pa-tients undergoing arterial thrombotic events versus those developingvenous thromboembolism (VTE).AimofthepresentstudywastoexplorewhetherplasmaMMP-2isincreased in APS patients and to test if this marker can identifypatients undergoing arterial versus venous thrombosis.77 patients with APS (both primary and secondary), definedaccording to the international consensus criteria [4], (48 females,mean age 47±8 years), and 69 age- and sex-matched healthy con-trols (40 females, mean age 45±7 years) without concomitant riskfactors for cardiovascular disease, enrolled in two previously pub-lishedstudies[5,6], wereincluded inthepresentstudy.OftheAPSpa-tients,30 (22primaryand 8 secondary)(39%)had ahistoryof arterialthrombosis (mean time from event: 3.7±3 years), 41 (53%) (29 pri-mary and 12 secondary) a history of VTE (mean time from event:5±3 years) and six (8%) had obstetric manifestations. A group of pa-tients with history of arterial thrombosis (n=30, 16 females, 7 MI,5 stroke, 18 PAD) but no APS was alsostudied to distinguishthe role ofMMP-2 as a marker of vascular disease per se from a specific increaselinked to APS. Informed consent was obtained from each patient andthe study protocol, conformed to the ethical guidelines of the Declara-tion of Helsinki, was approved by the Local Ethic Committees (deliber-ation number 433/03). The authors of this manuscript have certifiedthattheycomplywiththePrinciplesofEthicalPublishingintheInterna-tional Journal of Cardiology.Plasma, obtained by centrifugation of 3.8% citrated venous bloodat 3000 g for 20 min, was immediately frozen and stored at −80 °Cfor later assay of MMP-2 by zymography, as described [7]. Intra-and inter-assay coefficients of variation of MMP-2 measurementswere 2.3% and 3.9%, respectively (n=8). All measurements were car-ried out by investigators blinded as to the patients' characteristics.The association of MMP-2 levels with history of arterial or venousthrombosis was evaluated by binary logistic regression analysis.Odds ratio (OR) and 95% confidence intervals (CIs) were calculatedconsidering the thrombotic event (arterial vs venous) as dependentvariable. Independent variables were: MMP-2 levels and age as con-tinuous variables, and sex (male vs female), oral anticoagulation(yes/no) and triple positivity for aPL (LAC, ACA, anti-β2GPI) (yes/no), as dichotomous variables. A two-sidedp-valueb0.05 was consid-ered as statistically significant. All analyses were performed with thestatistical package SPSS for Windows.PlasmaMMP-2wassignificantly higher in APSpatientsthanin con-trol subjects (Fig. 1A). When further subdivided in relation to clinicalmanifestations, MMP-2 levels were significantly higher in patientswith a previous arterial event than in patients with a previous VTE orin healthy controls (Fig. 1B). APS patients with obstetric manifesta-tions had MMP-2 levels similar to those of patients with VTE(740.9±94.2 ng/ml). MMP-2 levels in patients without APS but withprevious arterial thrombosis were higher than controls (682.6±84.3

Ischemic vascular disease and antiphospholipid antibodies are associated with HLA-DRB1 *04/*13 alleles in systemic lupus erythematosus

BackgroundCardiovascular disease (CVD) is common in systemic lupus erythematosus (SLE) and SLE patients with antiphospholipid antibodies (anti-PL) are at particularly high risk. HLA-DRB1 genotypes are associated with SLE per se...

A STAT4 risk allele is associated with ischaemic cerebrovascular events and anti-phospholipid antibodies in systemic lupus erythematosus

ObjectiveTo investigate whether the risk allele for systemic lupus erythematosus (SLE) in the signal transducer and activator of transcription factor 4 (STAT4) gene, defined by the single nucleotide polymorphism (SNP)...

The impact of leukocytosis on survival, leukemic transformation, and thrombosis in polycythemia vera

7029 Background: A leukocyte count of &gt; 15 ×109/L has recently been associated with myocardial infarction in polycythemia vera (PV). In the current study, we examine the impact of such degree of leukocytosis on survival, leukemic transformation (LT), and thrombosis in a large cohort of PV patients from a single institution Methods: Data was abstracted from the medical records of a consecutive cohort of patients with PV defined by the World Health Organization criteria. Results: i. Patient characteristics The study cohort included 459 patients (median age, 60 years). Median follow-up was 64 months. ii. Survival In a multivariable analysis, advanced age, leukocyte count of = 15 × 109/L, and arterial thrombosis at diagnosis were significantly associated with inferior survival. A prognostic model based on age = 60 years and leukocyte count = 15 × 109/L separated low-risk, intermediate-risk, and high-risk patient groups with respective median survivals of 272, 162, and 108 months (p&lt;0.0001). iii. Leukemic transformation In a multivariable analysis, only leukocyte count was significantly associated with LT; median leukemia-free survival for patients with leukocyte count = 15 × 109/L was 273 months vs. not reached for those with lower leukocyte count (p&lt;0.0001). iv. Thrombosis at diagnosis In multivariable analysis, arterial thrombosis at diagnosis was significantly associated with previous history of arterial thrombosis, hypertension, and tobacco use; venous thrombosis at diagnosis was significantly associated with previous venous event and splenomegaly. v. Thrombosis during follow- up In multivariable analysis, arterial thrombosis during follow-up was significantly associated with previous arterial event, hypertension, and tobacco use; venous thrombosis during follow-up was significantly associated with previous venous event, diabetes mellitus, advanced age, and leukocyte count = 1,500 × 109/L. Conclusions: The current study for the first time identifies leukocytosis as a risk factor for inferior survival, LT risk, and venous thrombosis in PV. No significant financial relationships to disclose.

Subclinical atherosclerosis in systemic lupus erythematosus (SLE): the relative contribution of classic risk factors and the lupus phenotype

We aimed to examine the strength of association between traditional cardiovascular risk factors and carotid plaque development in systemic lupus erythematosus (SLE) patients and controls. We also aimed to determine which lupus-related factors are associated with carotid plaque and whether SLE sensitizes patients to the effects of traditional factors. We studied 200 women with SLE and 100 controls. Demographic and risk factor data were collected and SLE features, including autoantibody profiles and therapy were noted. All subjects had B- mode ultrasound of their carotid arteries examined for the presence and distribution of plaque. SLE patients <55 years old had more plaque (21% vs 3% P < 0.01) and more SLE patients had plaque in the internal carotid artery (11% vs 4%; P < 0.05). Traditional risk factor models performed less well in SLE compared with controls [area under Receiver Operator Characteristic curves (AUC ROC) = 0.76 vs 0.90; P < 0.01]. A multivariable model using SLE factors only, performed significantly better (AUC ROC = 0.87; P < 0.01). The final model in SLE included age and cigarette pack-years smoking as well as azathioprine exposure ever, antiphospholipid antibodies (APLA) and previous arterial events (AUC ROC = 0.88). SLE patients have a higher prevalence and different distribution of carotid plaque than controls. SLE factors perform significantly better than traditional risk factors in their association with atherosclerosis in SLE and these factors add to the influence of traditional risk factors rather than sensitizing lupus patients to traditional factors. The SLE phenotype helps identify patients at increased risk of atherosclerosis.

Prevalence and risk factors of carotid plaque in women with systemic lupus erythematosus.

To determine the prevalence of carotid atherosclerosis and associated risk factors in women with systemic lupus erythematosus (SLE). Carotid plaque and intima-media wall thickness (IMT) were measured by B-mode ultrasound in women with SLE. Risk factors associated with carotid plaque and IMT were determined at the time of the ultrasound scan and included traditional cardiovascular risk factors, SLE-specific variables, and inflammation markers. The 175 women with SLE were predominantly white (87%), with a mean age of 44.9 years (SD 11.5). Twenty-six women (15%) had a previous arterial event (10 coronary [myocardial infarction or angina], 11 cerebrovascular [stroke or transient ischemic attack], and 5 both). The mean +/- SD IMT was 0.71 +/- 0.14 mm, and 70 women (40%) had focal plaque. Variables significantly associated with focal plaque (P < 0.05) included age, duration of lupus, systolic, diastolic, and pulse pressure, body mass index, menopausal status, levels of total and low-density lipoprotein (LDL) cholesterol, fibrinogen and C-reactive protein levels, SLE-related disease damage according to the Systemic Lupus International Collaborating Clinics (SLICC) damage index (modified to exclude cardiovascular parameters), and disease activity as determined by the Systemic Lupus Activity Measure. Women with longer duration of prednisone use and a higher cumulative dose of prednisone as well as those with prior coronary events were more likely to have plaque. In logistic regression models, independent determinants of plaque (P < 0.05) were older age, higher systolic blood pressure, higher levels of LDL cholesterol, prolonged treatment with prednisone, and a previous coronary event. Older age, a previous coronary event, and elevated systolic blood pressure were independently associated with increased severity of plaque (P < 0.01). Older age, elevated pulse pressure, a previous coronary event, and a higher SLICC disease damage score were independently related to increased IMT (P < 0.05). B-mode ultrasound provides a useful noninvasive technique to assess atherosclerosis in women with SLE who are at high risk for cardiovascular disease. Potentially modifiable risk factors were found to be associated with the vascular disease detected using this method.