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Objective: Formerly preeclamptic women have an increased risk for cardiovascular and renal disease later in life. It is unknown which mechanisms contribute to this increased risk and whether this is induced by preeclampsia or by prepregnancy factors. We hypothesized that the increased risk for cardiovascular disease is partly due to an increased angiotensin II (ang II) responsiveness postpartum and that preeclampsia itself is involved in inducing this increased ang II responsiveness.Methods: In never-pregnant, formerly healthy pregnant rats and rats with former experimental preeclampsia [experimental preeclampsia model induced by low-dose endotoxin infusion on day 14 of pregnancy; endotoxin-infused pregnant rats (EP-rats)], ang II responsiveness was studied by measuring changes in blood pressure (BP) and proteinuria after chronic ang II infusion with osmotic minipumps (200ng/kg per min). In addition, we measured BP and responses to ang II (0.3, 1.0 and 3.0ng/kg per min) in 18 formerly early-onset preeclamptic, without comorbidities, and 18 formerly healthy pregnant women (controls).Results: In rats, a significantly higher systolic BP at termination was observed in formerly EP-rats vs. never-pregnant rats after ang II infusion (159.5 29.5 vs. 136.7 16.8; P = 0.049). In response to ang II, there was a significant increase in proteinuria in formerly EP-rats vs. healthy pregnant and never-pregnant rats (P < 0.01 for both). In humans, 1.0 ng/kg per min ang II showed a trend towards an increased mean arterial BP response in formerly preeclamptic women vs. controls (P = 0.057). Conclusion: Our data show an increased ang II responsiveness following (experimental) preeclampsia and support a role for preeclampsia itself in altered ang II responsiveness postpartum.

Women with a history of preeclampsia have an increased risk for cardiovascular diseases later in life. Persistent vascular alterations in the postpartum period might contribute to this increased risk. The current study assessed arterial stiffness under low sodium (LS) and high sodium (HS) conditions in a well-characterized group of formerly early-onset preeclamptic (fPE) women and formerly pregnant (fHP) women. Eighteen fHP and 18 fPE women were studied at an average of 5 yr after pregnancy on 1 wk of LS (50 mmol Na+/day) and 1 wk of HS (200 mmol Na+/day) intake. Arterial stiffness was measured by pulse-wave analysis (aortic augmentation index, AIx) and carotid-femoral pulse-wave velocity (PWV). Circulating markers of the renin-angiotensin aldosterone system (RAAS), extracellular volume (ECV), nitric oxide (NO), and hydrogen sulfide (H2S) were measured in an effort to identify potential mechanistic elements underlying adaptation of arterial stiffness. AIx was significantly lower in fHP women on LS compared with HS while no difference in AIx was apparent in fPE women. PWV remained unchanged upon different sodium loads in either group. Comparable sodium-dependent changes in RAAS, ECV, and NO/H2S were observed in fHP and fPE women. fPE women have an impaired ability to adapt their arterial stiffness in response to changes in sodium intake, independently of blood pressure, RAAS, ECV, and NO/H2S status. The pathways involved in impaired adaptation of arterial stiffness, and its possible contribution to the increased long-term risk for cardiovascular diseases in fPE women, remain to be investigated. Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/vascular-health-after-preeclampsia/ .

Background: Registry-based studies report an increased risk for end-stage kidney disease after hypertensive disorders of pregnancy (HDPs). It is unclear whether HDPs lead to an increased incidence of chronic kidney disease (CKD) and/or progression of kidney function decline. Study Design: Subanalysis of the Prevention of Renal and Vascular Endstage Disease (PREVEND) Study, a Dutch population-based cohort with follow-up of 5 visits approximately 3 years apart. Setting & Participants: Women without and with patient-reported HDPs (non-HDP, n = 1,805; HDP, n = 977) were identified. Mean age was 50 years at baseline and median follow-up was 11 years. Factor: An HDP. Outcomes: (1) The incidence of CKD using Cox regression and (2) the course of kidney function (estimated glomerular filtration rate [eGFR] and 24-hour albuminuria) over 5 visits using generalized estimating equation analysis adjusted for age, mean arterial pressure, and renin-angiotensin system (RAS) blockade. CKD was defined as eGFR < 60 mL/min/1.73 m2 and/or 24-hour albuminuria with albumin excretion > 30 mg, and end-stage kidney disease was defined as receiving dialysis or kidney transplantation. Results: During follow-up, none of the women developed end-stage renal disease and the incidence of CKD during follow-up was similar across HDP groups (HR, 1.04; 95% CI, 0.79-1.37; P = 0.8). Use of RAS blockade was higher after HDP at all visits. During a median of 11 years, we observed a decrease in eGFR in both groups, with a slightly steeper decline in the HDP group (98 ± 15 to 88 ± 16 vs 99 ± 17 to 91 ± 15 mL/min/1.73 m2; Pgroup < 0.01, Pgroup*visit < 0.05). The group effect remained significant after adjusting for mean arterial pressure, but disappeared after adjusting for RAS blockade. The 24-hour albuminuria did not differ between groups. Limitations: No obstetric records available. HDPs defined by patient report rather than health records. Conclusions: HDPs did not detectably increase the incidence of CKD. During follow-up, we observed no differences in albuminuria, but observed a marginally lower eGFR after HDP that was no longer statistically significant after adjusting for the use of RAS blockers. In this population, we were unable to identify a significant risk for kidney function decline after patient-reported HDP.

Formerly preeclamptic women have an increased risk for developing end-stage renal disease, which has been attributed to altered renal hemodynamics and abnormalities in the renin-angiotensin-aldosterone system. Whether this is due to preeclampsia itself or to comorbid conditions is unknown. Renal hemodynamics and responsiveness to ANG II during low Na+intake (7 days, 50 mmol Na+/24 h) and high Na+(HS) intake (7 days, 200 mmol Na+/24 h) were studied in 18 healthy normotensive formerly early-onset preeclamptic women (fPE women) and 18 healthy control subjects (fHP women), all selected for absence of comorbidity. At the end of each diet, renal hemodynamics and blood pressure were measured before and during graded ANG II infusion. Both HS intake and former preeclampsia increased filtration fraction (FF) without an interaction between the two. FF was highest during HS intake in fPE women [0.31 ± 0.12 vs. 0.29 ± 0.11 in fHP women, generalized estimating equation analysis (body mass index corrected), P = 0.03]. The renal response to ANG II infusion was not different between groups. In conclusion, fPE women have a higher FF compared with fHP women. As this was observed in the absence of comorbidity, preeclampsia itself might exert long-term effects on renal hemodynamics. However, we cannot exclude the presence of prepregnancy alterations in renal function, which, in itself, lead to an increased risk for preeclampsia. In experimental studies, an elevated FF has been shown to play a pathogenic role in the development of hypertension and renal damage. Future studies, however, should evaluate whether the subtle differences in renal hemodynamics after preeclampsia contribute to the increased long-term renal risk after preeclampsia.

Several studies reported sex differences in aldosterone. It is unknown whether these differences are associated with differences in volume regulation. Therefore we studied both aldosterone and extracellular volume in men and women on different sodium intakes. In healthy normotensive men ( n = 18) and premenopausal women ( n = 18) we investigated plasma aldosterone, blood pressure, and extracellular volume (125I-iothalamate), during both low (target intake 50 mmol Na+/day) and high sodium intake (target intake 200 mmol Na+/day) in a crossover setup. Furthermore, we studied the adrenal response to angiotensin II infusion (0.3, 1.0, and 3.0 ng·kg−1·min−1for 1 h) on both sodium intakes. Men had a significantly higher plasma aldosterone, extracellular volume, and systolic blood pressure than women during high sodium intake ( P < 0.05). During low sodium intake, extracellular volume and blood pressure were higher in men as well ( P < 0.05), whereas the difference in plasma aldosterone was no longer significant ( P = 0.252). The adrenal response to exogenous angiotensin II was significantly lower in men than in women on both sodium intakes. Constitutive sex differences in the regulation of aldosterone, characterized by a higher aldosterone and a lower adrenal response to exogenous angiotensin II infusion in men, are associated with a higher extracellular volume and blood pressure in men. These findings suggest that sex differences in the regulation of aldosterone contribute to differences in volume regulation between men and women.

Normal pregnancy requires adaptations of the maternal vasculature. During preeclampsia these adaptations are not well established, which may be related to maternal hypertension and proteinuria. The effects of preeclampsia on the maternal vasculature are not yet fully understood. We aimed to evaluate gene expression in aortas of pregnant rats with experimental preeclampsia using a genome wide microarray. Aortas were isolated from pregnant Wistar outbred rats with low-dose LPS-induced preeclampsia (ExpPE), healthy pregnant (Pr), non-pregnant and low-dose LPS-infused non-pregnant rats. Gene expression was measured by microarray and validated by real-time quantitative PCR. Gene Set Enrichment Analysis was performed to compare the groups. Functional analysis of the aorta was done by isotonic contraction measurements while stimulating aortic rings with potassium chloride. 526 genes were differentially expressed, and positive enrichment of “potassium channels”, “striated muscle contraction”, and “neuronal system” gene sets were found in ExpPE vs. Pr. The potassium chloride-induced contractile response of ExpPE aortic rings was significantly decreased compared to this response in Pr animals. Our data suggest that potassium channels, neuronal system and (striated) muscle contraction in the aorta may play a role in the pathophysiology of experimental preeclampsia. Whether these changes are also present in preeclamptic women needs further investigation.

Objectives: Non-invasive assessment of maternal hemodynamics in early pregnancy may be promising in evaluating maternal hemodynamic (mal)adaptation to pregnancy. We explored usage of applanation tonometry and Doppler ultrasound for assessment of cardiac output (CO), systemic vascular resistance (SVR) and arterial stiffness in early pregnancy.Methods: Pregnant healthy nulliparous women were studied during first trimester. Radial artery pressure waveform (augmentation index(AIx)), carotid-femoral pulse wave velocity (PWV) and cardiac output (CO) were measured by applanation tonometry (SphygmoCor), electrocardiogram and Doppler ultrasound (USCOM) and related to maternal demographic characteristics and literature concerning advanced pregnancy and non-pregnant subjects.Results: 116 women were studied during gestational age range of 7(+2)-14 weeks. Systolic and diastolic central blood pressure were correlated with systolic and diastolic brachial blood pressure respectively. Both measures of arterial stiffness (heart rate corrected AIx(AIx@75) and PWV) were correlated. AIx@75, PWV and SVR were correlated with central mean arterial pressure. CO was negatively correlated with AIx and associated with BMI. PWV was associated with age and BMI, whereas SVR was associated with age.Conclusions: Applanation tonometry and Doppler Ultrasound for assessment of maternal hemodynamics in early pregnancy revealed similar associations between different hemodynamic parameters and maternal characteristics as have previously been reported in advanced pregnancy and non-pregnant subjects. The SphygmoCor and the USCOM appear to be reliable methods for the assessment of maternal hemodynamics in early pregnancy. Obtaining a comprehensive hemodynamic profile using these modalities may offer insight in maternal (mal)adaptation to pregnancy. Future work needs to be done relating such measures to pregnancy outcome. (C) 2013 International Society for the Study of Hypertension in Pregnancy Published by Elsevier B.V. All rights reserved.

Objective: Since the cerebrovasculature likely plays a prominent role in the pathophysiology of eclampsia, we assessed the effects of low-dose endotoxin-induced experimental preeclampsia on the function and structure of rat posterior cerebral arteries (PCA) and mesenteric arteries (MA).Methods: Nonpregnant (NP) and pregnant (P) rats were infused with saline (NP-CTL, n = 9; P-CTL, n = 9) or low-dose endotoxin (NP-endotoxin, n = 9; P-endotoxin, n = 10). Myogenic activity, pressure of forced dilatation (FD) and structural properties were evaluated in PCA and MA.Results: PCA underwent FD between 125 and 150 mmHg in P-endotoxin (repeated measures ANOVA vs 75 mmHg; P Conclusion: Low-dose endotoxin-infusion during pregnancy, but not pregnancy alone, decreased the pressure of FD in PCA. This may predispose to cerebral autoregulatory breakthrough and edema formation during increased blood pressure as seen in eclampsia. (C) 2012 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Complicating up to 8% of pregnancies, preeclampsia is the most common glomerular disease worldwide and remains a leading cause of infant and maternal morbidity and mortality. Although the exact pathogenesis of this syndrome of hypertension and proteinuria is still incomplete, a consistent line of evidence has identified an imbalance of proangiogenic and anti-angiogenic proteins as a key factor in the development of preeclampsia. Furthermore, more attention has been recently addressed to the renin-angiotensin aldosterone system (RAAS), to provide understanding on the hypertension of preeclampsia. The imbalance of the RAAS and the imbalance between angiogenic and anti-angiogenic factors, which may be both common to preeclampsia and chronic kidney disease (CKD), might explain why a history of preeclampsia predisposes women to develop CKD. In this review, we briefly describe the characteristics of preeclampsia with a focus on the mechanisms of angiogenesis and the RAAS and its role in the pathogenesis of preeclampsia. Our main focus will be on the intriguing association between preeclampsia and the subsequent increased risk of developing CKD and on the potential mechanisms by which the risk of CKD is elevated in women with a history of preeclampsia.

Women with renal disease progress at a slower rate to end stage renal disease than men. As angiotensin II has both hemodynamic and direct renal effects, we hypothesized that the female protection may result from gender differences in responses to angiotensin II. Therefore, we studied gender differences in response to angiotensin II, during acute (human) and chronic (rats) angiotensin II administration. In young healthy men (n = 18) and women (n = 18) we studied the responses of renal hemodynamics ((125)I-iothalamate and (131)I-Hippuran) and blood pressure to graded angiotensin II infusion (0.3, 1.0, and 3.0 ng/kg/min for 1 h). Men had increased responses of diastolic blood pressure (P = 0.01), mean arterial pressure (P = 0.05), and a more pronounced decrease in effective renal plasma flow (P = 0.009) than women. We measured the changes in proteinuria and blood pressure in response to chronic administration (200 ng/kg/min for 3 weeks) of angiotensin II in rats. Male rats had an increased response of proteinuria compared with females (GEE analysis, P = 0.001). Male, but not female, angiotensin II-treated rats had increased numbers of renal interstitial macrophages compared to sham-treated rats (P < 0.001). In conclusion, gender differences are present in the response to acute and chronic infusion of angiotensin II. Difference in angiotensin II sensitivity could play a role in gender differences in progression of renal disease.

Some diseases associated with a temporary deterioration in kidney function and/or development of proteinuria show an apparently complete functional remission once the initiating trigger is removed. While it was earlier thought that a transient impairment of kidney function is harmless, accumulating evidence now suggests that these patients are more prone to developing renal failure later in life. We therefore sought to investigate to what extent renal functional changes, inflammation and collagen deposition are reversible after cessation of disease induction, potentially explaining residual sensitivity to damage. Using a rat model of Angiotensin II (Ang II)-induced hypertensive renal disease we show the development of severe hypertension (212 ± 10.43 vs. 146 ± 1.4 mmHg, p

Objective: We investigated endothelial dysfunction and the role of angiotensin (Ang)-II type I (AT1-R) and type II (AT2-R) receptor in the changes in the Ang-II sensitivity in experimental preeclampsia in the rat.Methods: Aortic rings were isolated from low dose lipopolysaccharide (LPS) infused pregnant rats (experimental preeclampsia; n=9), saline-infused pregnant rats (n=8), and saline (n=8) and LPS (n=8) infused non-pregnant rats. Endothelium-dependent acetylcholine--mediated relaxation was studied in phenylephrine-preconstricted aortic rings in the presence of vehicle, N-G-nitro-L-arginine methyl ester and/or indomethacin. To evaluate the role for AT1-R and AT2-R in Ang-II sensitivity, full concentration response curves were obtained for Ang-II in the presence of losartan or PD123319. mRNA expression of the AT1-R and AT2-R, eNOS and iNOS, COX1 and COX2 in aorta were evaluated using real-time RT-PCR.Results: The role of vasodilator prostaglandins in the aorta was increased and the role of endothelium-derived hyperpolarizing factor and response of the AT1-R and AT2-R to Ang-II was decreased in pregnant saline infused rats as compared with non-pregnant rats. These changes were not observed during preeclampsia.Conclusion: Pregnancy induced adaptations in endothelial function, which were not observed in the rat model for preeclampsia. This role of lack of pregnancy induced endothelial adaptation in the pathophysiology of experimental preeclampsia needs further investigation.

Atherosclerosis is accelerated in Wegener's granulomatosis (WG) patients. This study was aimed to assess which factors can predict progression of atherosclerosis in WG.23 WG patients (14 men; age 47+/-9 years, mean+/-SD) and 21 controls (12 men; age 47+/-10 years) were included. Intima-media thickness (IMT) was determined by ultrasound, as measure for atherosclerosis. After median follow-up of 72 months (interquartile range: 66-76), IMT was repeated. Traditional risk factors for cardiovascular disease were determined, as well as levels of C-reactive protein (CRP) and endothelial activation markers, including thrombomodulin, vascular cell adhesion molecule-1 (VCAM-1) and von Willebrand factor (vWf). Disease-related factors were recorded from time of diagnosis until end of follow-up.Maximum IMT at both evaluations was increased in patients. Patients had an increased prevalence of hypertension and increased levels of vWf and CRP. IMT progression was not different. IMT at follow-up was positively associated with age, blood pressure, CRP and VCAM-1, and negatively with HDL. During follow-up, disease activity was lower compared to the period from diagnosis until the first evaluation, and blood pressure and prevalence of dyslipidemia decreased in WG patients. Change in IMT was not correlated to any risk factor measured.Maximum IMT was increased in WG patients. Progression of IMT was not different between patients and controls, probably because disease activity was low and reduction of traditional risk factors was achieved during follow-up. We suggest that control of disease activity and treatment of traditional risk factors are important to prevent cardiovascular disease in WG.

Background: Peroxisome proliferator-activated receptor-γ (PPAR-γ), a nuclear receptor expressed in placental tissue plays a seminal role in pregnancy. We aimed to 1) investigate the effect of PPAR-γ antagonism during uncomplicated pregnancy in rats 2) investigate the role of PPAR-γ activation during complicated pregnancy using the reduced uterine perfusion pressure (RUPP) rat model of pre-eclampsia (PE). Methods: On gestational day (GD)11, a miniosmotic pump was inserted into the peritoneal cavity of pregnant rats and either vehicle or the PPAR-γ antagonist, T0070907 (1mg/kg/day), administered between GD11-15. In a separate study, either vehicle or the PPAR-γ agonist, rosiglitazone (5mg/kg/day), was administered (GD16-18) to normal pregnant or RUPP (produced via surgical reduction of uteroplacental perfusion on GD14) rats in either the absence or presence of the heme oxyenase 1 (HO-1) inhibitor, SnPP (50μmol/kg/day), via drinking water. Animals were chronically catheterized on GD18 for mean arterial blood pressure (MABP) measurement on GD19. In all groups, vascular function was assessed in response to the vasoconstrictor, U46619 (10–9–4×10–7M), and the vasodilators bradykinin (BK; 10–9–10–5M) and sodium nitroprusside (SNP; 10–9–10–5M). Results: Rats which received T0070907 had significantly elevated MABP (p

study is to assess cardiac function/remodelling at mid-gestation in normotensive women, some of whom subsequently developed PE. Methods: This was a prospective study on 351 women assessed at 20-23 weeks gestation. In particular, women at increased risk of developing PE (127 with high resistance uterine artery Doppler indices and 79 with PE in a previous pregnancy) were recruited. Women underwent blood pressure profiling, echocardiography, cardiac tissue Doppler and strain rate analysis. Results: PE subsequently developed in 53 women (22 preterm, 31 at term). Five (23%) of women who developed preterm PE exhibited evidence of global diastolic and/or systolic dysfunction as well as left ventricular remodelling at midgestation. These features were not evident in women who subsequently developed term PE or had a normal pregnancy outcome (p < 0.0001). Conclusions: This study demonstrates that impaired cardiac function and remodelling precede the onset of preterm PE by several weeks in a quarter of cases. The majority of women who develop preterm PE and all women who develop term PE have normal global cardiac function and geometry at mid-gestation. Women with mid-gestation abnormal cardiac findings may have preexisting myocardial dysfunction. These cardiac findings may be useful in screening for the onset of preterm PE and may persist in the postnatal period influencing the long-term cardiovascular outlook.

Background: Peroxisome proliferator-activated receptor-γ (PPAR-γ), a nuclear receptor expressed in placental tissue plays a seminal role in pregnancy. We aimed to 1) investigate the effect of PPAR-γ antagonism during uncomplicated pregnancy in rats 2) investigate the role of PPAR-γ activation during complicated pregnancy using the reduced uterine perfusion pressure (RUPP) rat model of pre-eclampsia (PE). Methods: On gestational day (GD)11, a miniosmotic pump was inserted into the peritoneal cavity of pregnant rats and either vehicle or the PPAR-γ antagonist, T0070907 (1mg/kg/day), administered between GD11-15. In a separate study, either vehicle or the PPAR-γ agonist, rosiglitazone (5mg/kg/day), was administered (GD16-18) to normal pregnant or RUPP (produced via surgical reduction of uteroplacental perfusion on GD14) rats in either the absence or presence of the heme oxyenase 1 (HO-1) inhibitor, SnPP (50μmol/kg/day), via drinking water. Animals were chronically catheterized on GD18 for mean arterial blood pressure (MABP) measurement on GD19. In all groups, vascular function was assessed in response to the vasoconstrictor, U46619 (10–9–4×10–7M), and the vasodilators bradykinin (BK; 10–9–10–5M) and sodium nitroprusside (SNP; 10–9–10–5M). Results: Rats which received T0070907 had significantly elevated MABP (p

Abstract 3663 Poster Board III-599 Introduction Thymus and Activation Related Chemokine (TARC) is produced in high amounts by Hodgkin and Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL). It attracts CCR4 positive Th2 and Treg cells, which are typically present in large numbers in the reactive infiltrate in cHL. TARC can be measured in the serum of cHL patients and is usually elevated in the presence of active disease, as compared to healthy controls. Higher levels are observed in advanced stage disease, compared to stage I disease. The goal of the current study was to correlate TARC serum levels to metabolic response to therapy as measured by FDG-PET scanning. Patients and methods Newly diagnosed cHL patients treated in our hospital were asked to participate. Serum samples were taken before the start of treatment, at the time of the mid treatment PET scan (after 2 cycles of ABVD for stage I and II, or mid BEACOPP or ABVD treatment for stage III and IV disease) and at the time of the PET scan after completion of chemotherapy. TARC serum levels were measured by ELISA and TARC immunohistochemistry was done on primary involved lymph node tissue. Results A total of 59 cHL patients, median age 40 (range 16-80) and 49% male participated. Eight patients had stage I, 26 stage II, 14 stage III and 10 stage IV disease. The known association of high pretreatment TARC levels with advanced stage was also significantly present in our data, supporting the hypothesis that serum TARC levels reflect tumor burden. Moreover, in stage I and II patients, bulky disease (27%) was associated with a significant higher TARC level, lending further support to this hypothesis. Compared to pretreatment values, TARC levels had decreased significantly at mid treatment and treatment completion to the range of healthy controls. Only in stage I there was no significant difference between pretreatment and mid or after treatment samples (see figure), probably due to the relatively large number of patients without elevated TARC before the start of therapy. In patients with a positive PET scan at mid treatment (26%), there was a trend for a higher TARC level (P=0.08) compared to PET negative patients. After completion of chemotherapy PET positivity (19%) was significantly associated with a higher TARC level. Three patients had a relapse and at that time TARC levels had clearly increased in comparison to the levels after treatment. Conclusions serum TARC levels are associated with tumor burden and metabolic response to therapy as measured by FDG-PET scan. Measurement of serum TARC levels is a potential tool to evaluate the response to therapy and to be used in follow up after completion of chemotherapy. Inclusion of more patients is necessary to further assess the clinical value of TARC serum levels and is ongoing. Disclosures: No relevant conflicts of interest to declare.

Abstract 748 Purpose: Thymus and Activation Regulated Chemokine (TARC) is highly expressed by the Hodgkin Reed Sternberg (HRS) tumor cells of classical Hodgkin lymphoma (cHL) in the vast majority of patients. This chemokine is released in the circulation and may serve as a cHL specific biomarker. We and others showed high serum levels of TARC before start of treatment and a significant decrease in serum TARC levels after treatment. The aim of the current study is to relate plasma TARC levels during treatment with response as observed by FDG-PET imaging in cHL patients. Patients and Methods: Sixty-three newly diagnosed cHL patients from the University Medical Center Groningen were included from 2005 until 2009. Patients were treated according to clinical trial (EORTC) or hospital protocols: 1st line treatment consisted of ABVD chemotherapy with or without involved node radiotherapy for stage I/II and ABVD or EscBEACOPP/BEACOPP chemotherapy for other stages. Plasma was collected before treatment and ideally also before start of every chemotherapy cycle, with at least a sample concurrent with mid-treatment FDG-PET evaluation and at completion of treatment. Plasma TARC levels were evaluated by ELISA. TARC expression in HRS cells was determined by immunohistochemistry (IHC) on tissue samples. Results: TARC staining was observed in the HRS cells in 95% of patients. Patients with negative TARC staining did not have elevated pre-treatment plasma TARC levels and were excluded from further analysis. Pre-treatment plasma TARC levels in stage II-IV disease were significantly higher compared to stage I disease (p < .001). Patients with bulky disease had significantly higher TARC values compared to patients without bulky disease (p = .04). Mid-treatment TARC was significantly elevated in 2 out of 54 patients with an available plasma sample (Figure 1). Mid-treatment FDG-PET was positive in 13/53 patients. Two patients had persistent mid-treatment FDG-PET activity in >2 nodes and these 2 patients were the only two patients with persistent high mid-treatment TARC. The other 11 mid-treatment FDG-PET positive patients only had residual FDG-PET positivity in 1 or 2 nodes and TARC was normalized in all 11 patients. Two of these 11 patients switched to EscBEACOPP dictated by the mid-treatment FDG-PET result since they were treated in the experimental arm of the EORTC H10 trial, while the 2 patients with >2 mid-treatment FDG-PET positive nodes and high TARC did not switch since they were treated in the standard arm of this trial. End-treatment TARC was significantly elevated in 2 out of 58 patients. 4/13 mid-treatment FDG-PET positive patients remained FDG-PET positive at end-treatment evaluation. The two patients with persistent activity in >2 nodes and high TARC at mid-treatment evaluation had progressive disease at end-treatment evaluation and TARC levels remained high. Of the 11 patients with mid-treatment FDG-PET positivity and low mid-treatment TARC, 9 became FDG-PET negative. Two patients (one of those who switched to EscBEACOPP) still had residual FDG-PET activity in the same spots at end-treatment evaluation while TARC remained low. The other patient proceeded to second line treatment but remained FDG-PET positive. However, both patients did not progress during 6 months follow-up without further treatment. Of note: after one cycle of first line chemotherapy we could already observe the same plasma TARC dynamics as observed at mid- and end-treatment evaluation (n=42, Figure 1). Conclusion: Mid-treatment plasma TARC levels outperformed mid-treatment FDG-PET imaging in predicting response to therapy in primary cHL patients. Moreover, TARC levels after one chemotherapy cycle could already predict final response to treatment. Evaluation of TARC dynamics before and during treatment in future clinical trials is needed to confirm the prognostic value of plasma TARC in cHL patients. Disclosures: No relevant conflicts of interest to declare.