Neopterin, kynurenine metabolites, and indexes related to vitamin B6 are associated with post-stroke cognitive impairment: The Nor-COAST study.

BACKGROUND AND AIMS: We have previously shown that systemic inflammation was associated with post-stroke cognitive impairment (PSCI). Because neopterin, kynurenine pathway (KP) metabolites, and B6 vitamers are linked to inflammation, in our study we investigated whether those biomarkers were associated with PSCI. MATERIAL AND METHODS: The Norwegian Cognitive Impairment After Stroke study is a prospective multicenter cohort study of patients with acute stroke recruited from May 2015 through March 2017. Plasma samples of 422 participants (59 % male) with ischemic stroke from the index hospital stay and 3 months post-stroke were available for analyses of neopterin, KP metabolites, and B6 vitamers using liquid chromatography-tandem mass spectrometry. Mixed linear regression analyses adjusted for age, sex, and creatinine, were used to assess whether there were associations between those biomarkers and cognitive outcomes, measured by the Montreal Cognitive Assessment scale (MoCA) at 3-, 18-, and 36-month follow-up. RESULTS: Participants had a mean (SD) age of 72 (12) years, with a mean (SD) National Institutes of HealthStroke Scale score of 2.7 (3.6) at Day 1. Higher baseline values of quinolinic acid, PAr (i.e., an inflammatory marker based on vitamin B6 metabolites), and HKr (i.e., a marker of functional vitamin B6 status based on selected KP metabolites) were associated with lower MoCA score at 3, 18, and 36 months post-stroke (p < 0.01). Higher baseline concentrations of neopterin and 3-hydroxykynurenine were associated with lower MoCA scores at 18 and 36 months, and higher concentrations of xanthurenic acid were associated with higher MoCA score at 36 months (p < 0.01). At 3 months post-stroke, higher concentrations of neopterin and lower values of pyridoxal 5́-phosphate were associated with lower MoCA scores at 18- and 36-month follow-up, while lower concentrations of picolinic acid were associated with a lower MoCA score at 36 months (p < 0.01). CONCLUSION: Biomarkers and metabolites of systemic inflammation, including biomarkers of cellular immune activation, indexes of vitamin B6 homeostasis, and several neuroactive metabolites of the KP pathway, were associated with PSCI. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02650531.

Accelerometer-measured physical activity at 3 months as a predictor of symptoms of depression and anxiety 1 year after stroke: a multicentre prospective cohort study in central Norway.

OBJECTIVES: To study sedentary behaviour and physical activity at 3 months as predictors for symptoms of depression and anxiety at 1-year post-stroke. DESIGN: A prospective cohort study. PATIENTS: Patients with first-ever ischaemic stroke. METHODS: Mood was assessed 3- and 12-months post-stroke using the Hospital Anxiety and Depression Scale. Sedentary behaviour and physical activity were measured using accelerometry 3 months post-stroke. RESULTS: A total of 292 participants (116 (39.7%) females; mean age 71.7 (standard deviation 11.3) years) were included. At 12 months, 16.7% experienced depression and 19.5% anxiety, respectively. Adjusting for age and sex, regression analysis showed that comorbidity burden (ß 0.26; 95% confidence interval (95% CI) 0.02, 0.51; p = 0.038), stroke severity (ß 0.22; 95% CI 0.10, 0.35; p = 0.001), functional disability (ß 0.89, 95% CI 0.49, 1.30; p = 0.000), and global cognition (ß-0.15; 95% CI -0.25, -0.05; p = 0.004) predicted depression. Multi-adjusted analysis showed sedentary behaviour and physical activity did not significantly predict depression or anxiety (p > 0.05). CONCLUSION: Sedentary behaviour and physical activity did not significantly predict mood after stroke. Comorbidity burden, stroke severity, functional disability, and global cognition were identified as possible predictors of depression. More research is needed to determine the impact of physical activity on depression and anxiety symptoms.

Plasma Inflammatory Biomarkers Are Associated With Poststroke Cognitive Impairment: The Nor-COAST Study.

BACKGROUND: Inflammation is proposed to be involved in the pathogenesis of poststroke cognitive impairment. The aim of this study was to investigate associations between concentrations of systemic inflammatory biomarkers after ischemic stroke and poststroke cognitive impairment. METHODS: The Nor-COAST study (Norwegian Cognitive Impairment After Stroke) is a prospective observational multicenter cohort study, including patients hospitalized with acute stroke between 2015 and 2017. Inflammatory biomarkers, including the TCC (terminal C5b-9 complement complex) and 20 cytokines, were analyzed in plasma, collected at baseline, 3-, and 18 months poststroke, using ELISA and a multiplex assay. Global cognitive outcome was assessed with the Montreal Cognitive Assessment (MoCA) scale. We investigated the associations between plasma inflammatory biomarkers at baseline and MoCA score at 3-, 18-, and 36-month follow-ups; the associations between inflammatory biomarkers at 3 months and MoCA score at 18- and 36-month follow-ups; and the association between these biomarkers at 18 months and MoCA score at 36-month follow-up. We used mixed linear regression adjusted for age and sex. RESULTS: We included 455 survivors of ischemic stroke. Higher concentrations of 7 baseline biomarkers were significantly associated with lower MoCA score at 36 months; TCC, IL (interleukin)-6, and MIP (macrophage inflammatory protein)-1α were associated with MoCA at 3, 18, and 36 months (P<0.01). No biomarker at 3 months was significantly associated with MoCA score at either 18 or 36 months, whereas higher concentrations of 3 biomarkers at 18 months were associated with lower MoCA score at 36 months (P<0.01). TCC at baseline and IL-6 and MIP-1α measured both at baseline and 18 months were particularly strongly associated with MoCA (P<0.01). CONCLUSIONS: Higher concentrations of plasma inflammatory biomarkers were associated with lower MoCA scores up to 36 months poststroke. This was most pronounced for inflammatory biomarkers measured in the acute phase following stroke. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02650531.

Longitudinal Changes in Circulating Metabolites and Lipoproteins After Breast Cancer Treatment.

The multimodal treatment of breast cancer may induce long term effects on the metabolic profile and increase the risk of future cardiovascular disease. In this study, we characterized longitudinal changes in serum lipoprotein subfractions and metabolites after breast cancer treatment, aiming to determine the long-term effect of different treatment modalities. Further, we investigated the prognostic value of treatment-induced changes in breast cancer-specific and overall 10-year survival. In this study, serum samples from breast cancer patients (n = 250) were collected repeatedly before and after radiotherapy, and serum metabolites and lipoprotein subfractions were quantified by NMR spectroscopy. Longitudinal changes were assessed by univariate and multivariate data analysis methods applicable for repeated measures. Distinct changes were detectable in levels of lipoprotein subfractions and circulating metabolites during the first year, with similar changes despite large differences in treatment regimens. We detect increased free cholesterol and decreased esterified cholesterol levels of HDL subfractions, a switch towards larger LDL particles and higher total LDL-cholesterol, in addition to a switch in the glutamine-glutamate ratio. Non-survivors had different lipid profiles from survivors already at baseline. To conclude, our results show development towards an atherogenic lipid profile in breast cancer patients with different treatment regimens.

Risk Stratification in Patients with Ischemic Stroke and Residual Cardiovascular Risk with Current Secondary Prevention.

PURPOSE: Suboptimal secondary prevention in patients with stroke causes a remaining cardiovascular risk desirable to reduce. We have validated a prognostic model for secondary preventive settings and estimated future cardiovascular risk and theoretical benefit of reaching guideline recommended risk factor targets. PATIENTS AND METHODS: The SMART-REACH (Secondary Manifestations of Arterial Disease-Reduction of Atherothrombosis for Continued Health) model for 10-year and lifetime risk of cardiovascular events was applied to 465 patients in the Norwegian Cognitive Impairment After Stroke (Nor-COAST) study, a multicenter observational study with two-year follow-up by linkage to national registries for cardiovascular disease and mortality. The residual risk when reaching recommended targets for blood pressure, low-density lipoprotein cholesterol, smoking cessation and antithrombotics was estimated. RESULTS: In total, 11.2% had a new event. Calibration plots showed adequate agreement between estimated and observed 2-year prognosis (C-statistics 0.63, 95% confidence interval 0.55-0.71). Median estimated 10-year risk of recurrent cardiovascular events was 42% (Interquartile range (IQR) 32-54%) and could be reduced to 32% by optimal guideline-based therapy. The corresponding numbers for lifetime risk were 70% (IQR 63-76%) and 61%. We estimated an overall median gain of 1.4 (IQR 0.2-3.4) event-free life years if guideline targets were met. CONCLUSION: Secondary prevention was suboptimal and residual risk remains elevated even after optimization according to current guidelines. Considerable interindividual variation in risk exists, with a corresponding variation in benefit from intensification of treatment. The SMART-REACH model can be used to identify patients with the largest benefit from more intensive treatment and follow-up.

ABCD3-I and ABCD2 Scores in a TIA Population with Low Stroke Risk.

OBJECTIVES: We aimed to evaluate the ABCD3-I score and compare it with the ABCD2 score in short- (1 week) and long-term (3 months; 1 year) stroke risk prediction in our post-TIA stroke risk study, MIDNOR TIA. MATERIALS AND METHODS: We performed a prospective, multicenter study in Central Norway from 2012 to 2015, enrolling 577 patients with TIA. In a subset of patients with complete data for both scores (n = 305), we calculated the AUC statistics of the ABCD3-I score and compared this with the ABCD2 score. A telephone follow-up and registry data were used for assessing stroke occurrence. RESULTS: Within 1 week, 3 months, and 1 year, 1.0% (n = 3), 3.3% (n = 10), and 5.2% (n = 16) experienced a stroke, respectively. The AUCs for the ABCD3-I score were 0.72 (95% CI, 0.54 to 0.89) at 1 week, 0.66 (95% CI, 0.53 to 0.80) at 3 months, and 0.68 (0.95% CI, 0.56 to 0.79) at 1 year. The corresponding AUCs for the ABCD2 score were 0.55 (95% CI, 0.24 to 0.86), 0.55 (95% CI, 0.42 to 0.68), and 0.63 (95% CI, 0.50 to 0.76). CONCLUSIONS: The ABCD3-I score had limited value in a short-term prediction of subsequent stroke after TIA and did not reliably discriminate between low- and high-risk patients in a long-term follow-up. The ABCD2 score did not predict subsequent stroke accurately at any time point. Since there is a generally lower stroke risk after TIA during the last years, the benefit of these clinical risk scores and their role in TIA management seems limited. Clinical Trial Registration. This trial is registered with NCT02038725 (retrospectively registered, January 16, 2014).

Stroke risk after transient ischemic attack in a Norwegian prospective cohort.

BACKGROUND: Transient ischemic attack (TIA) is a risk factor of stroke. Modern treatment regimens and changing risk factors in the population justify new estimates of stroke risk after TIA, and evaluation of the recommended ABCD2 stroke risk score. METHODS: From October, 2012, to July, 2014, we performed a prospective, multicenter study in Central Norway, enrolling patients with a TIA within the previous 2 weeks. Our aim was to assess stroke risk at 1 week, 3 months and 1 year after TIA, and to determine the predictive value of the dichotomized ABCD2 score (0-3 vs 4-7) at each time point. We used data obtained by telephone follow-up and registry data from the Norwegian Stroke Register. RESULTS: Five hundred and seventy-seven patients with TIA were enrolled of which 85% were examined by a stroke specialist within 24 h after symptom onset. The cumulative incidence of stroke within 1 week, 3 months and 1 year of TIA was 0.9% (95% CI, 0.37-2.0), 3.3% (95% CI, 2.1-5.1) and 5.4% (95% CI, 3.9-7.6), respectively. The accuracy of the ABCD2 score provided by c-statistics at 7 days, 3 months and 1 year was 0.62 (95% CI, 0.39-0.85), 0.62 (95% CI, 0.51-0.74) and 0.64 (95% CI, 0.54-0.75), respectively. CONCLUSIONS: We found a lower stroke risk after TIA than reported in earlier studies. The ABCD2 score did not reliably discriminate between low and high risk patients, suggesting that it may be less useful in populations with a low risk of stroke after TIA. TRIAL REGISTRATION: Unique identifier: NCT02038725 (retrospectively registered, January 16, 2014).

Obstructive and restrictive pulmonary dysfunction in long-term lymphoma survivors after high-dose therapy with autologous stem cell transplantation.

BACKGROUND: Obstructive and restrictive dysfunction in long-term lymphoma survivors (LSs) after high-dose therapy with autologous stem-cell transplantation (HDT-ASCT) has not been addressed systematically previously. MATERIAL AND METHODS: LSs treated in Norway 1987-2008 with HDT-ASCT who performed spirometry, measurement of static lung volumes and echocardiography 2012-2014 at either Oslo or St. Olavs University Hospitals was eligible. Smoking data were recorded by questionnaire. Treatment data were collected from medical records or hospital databases. Factors associated with obstructive and restrictive impairments (dichotomous outcomes) were examined by Poisson regression. Linear regression with the margins post-estimation command was used to derive adjusted mean values of forced expiratory volume in 1 s (FEV1). We used the normative reference data recommended by the European Respiratory Society for calculating percent predicted values. RESULTS: A total of 226 LSs were studied, of whom 11.5 and 5.8% had obstructive and restrictive impairment, respectively. For women and men, mean FEV1 was 2.31 and 3.34 l corresponding to 11.4%- and 11.1%-points below that predicted from norms, respectively. In multivariable regression analyses, cumulative doxorubicin dose (400-775 mg/m2) and current smoking were associated with increased risk of obstructive impairment, and chest RT (>13-66 Gy) was associated with increased risk of restrictive impairment. Currently smoking LSs within the highest doxorubicin category (400-775 mg/m2), had the lowest adjusted mean FEV1. CONCLUSIONS: Despite intensive cancer treatment, our analysis showed modest reductions in obstructive parameters among long-term LSs after HDT-ASCT compared to normative reference data. To limit obstructive impairments in LSs after HDT-ASCT, we suggest that targeted smoking-cessation advice is directed towards patients who have received high cumulative doses of doxorubicin.

Valvular Dysfunction in Lymphoma Survivors Treated With Autologous Stem Cell Transplantation: A National Cross-Sectional Study.

OBJECTIVES: This study assessed the prevalence and associated risk factors for valvular dysfunction (VD) observed in adult lymphoma survivors (LS) after autologous hematopoietic stem cell transplantation (auto-HCT), and to determine whether anthracycline-containing chemotherapy (ACCT) alone in these patients is associated with VD. BACKGROUND: The prevalence of and risk factors for VD in LS after auto-HCT is unknown. Anthracyclines may induce heart failure, but any association with VD is not well-defined. METHODS: This national cross-sectional study included all adult LS receiving auto-HCT from 1987 to 2008 in Norway. VD was defined by echocardiography as either more than mild regurgitation or any stenosis. Observations in LS were compared with a healthy age- and gender-matched (1:1) control group. RESULTS: In total, 274 LS (69% of all eligible) participated. Mean age was 56 ± 12 years, mean follow-up time after lymphoma diagnosis was 13 ± 6 years, and 62% of participants were males. Mean cumulative anthracycline dosage was 316 ± 111 mg/m(2), and 35% had received radiation therapy involving the heart (cardiac-RT). VD was observed in 22.3% of the LS. Severe VD was rare (n = 9; 3.3% of all LS) and mainly aortic stenosis (n = 7). We observed VD in 16.7% of LS treated with ACCT alone (n = 177), corresponding with a 3-fold increased VD risk (odds ratio: 2.9; 95% confidence interval: 1.5 to 5.8; p = 0.002) compared with controls. Furthermore, the presence of aortic valve degeneration was increased in the LS after ACCT alone compared with controls (13.0% vs. 2.9%; p < 0.001). Female sex, age >50 years at lymphoma diagnosis, ≥3 lines of chemotherapy before auto-HCT, and cardiac-RT >30 Gy were identified as independent risk factors for VD in the LS. CONCLUSIONS: In LS, ACCT alone was significantly associated with VD and related to valvular degeneration. Overall, predominantly moderate VD was prevalent in LS, and longer observation time is needed to clarify the clinical significance of this finding.

Comparison of the validity of stroke diagnoses in a medical quality register and an administrative health register.

AIMS: Health registers are essential sources of data used in a wide range of stroke research, including epidemiological, clinical and healthcare studies. Regardless of the type of register, the data must be of high quality to be useful. In this study, we investigated and compared the correctness and completeness of the Norwegian Patient Register (an administrative health register) and the Norwegian Stroke Register (a medical quality register for acute stroke). METHODS: We reviewed the medical records for 5192 admissions to hospital in 2012 and defined cases of stroke in the two registers as true positive, false positive, true negative or false negative. We calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value with 95% confidence intervals assuming a normal approximation of the binomial distribution. RESULTS: The Norwegian Stroke Register was highly correct and relatively complete (sensitivity 88.1%, specificity 100% and PPV 98.6%). The Norwegian Patient Register was more complete, but less correct, when we included both the main and secondary diagnoses of stroke (sensitivity 96.8%, specificity 99.6% and PPV 79.7%); restricting the analyses to the main diagnoses of stroke resulted in less complete and more correct registrations (sensitivity 86.1%, specificity 99.9% and PPV 93.5%). CONCLUSIONS: The Norwegian Stroke Register and the Norwegian Patient Register are adequately complete and correct to serve as valuable sources of data for epidemiological, clinical and healthcare studies, as well as for administrative purposes.

Heart Failure and Asymptomatic Left Ventricular Systolic Dysfunction in Lymphoma Survivors Treated With Autologous Stem-Cell Transplantation: A National Cross-Sectional Study.

PURPOSE: We aimed to determine the prevalence of left ventricular systolic dysfunction (LVSD), including symptomatic (ie, heart failure [HF]) and asymptomatic LVSD in adult lymphoma survivors (LSs) after autologous hematopoietic stem-cell transplantation (auto-HCT) and to identify risk factors for LVSD in this population. PATIENTS AND METHODS: All LSs treated with auto-HCT as adults in Norway from 1987 to 2008 were eligible for this national cross-sectional study. Asymptomatic LVSD was defined as left ventricular ejection fraction less than 50% by echocardiography, and HF was defined according to current recommendations. The results in LSs were compared with those found in an age- and sex-matched (1:1) control group. RESULTS: We examined 274 LSs (69% of all eligible survivors); 62% were men, the mean (± standard deviation) age was 56 ± 12 years, and mean follow-up time from lymphoma diagnosis was 13 ± 6 years. The mean cumulative doxorubicin dose was 316 ± 111 mg/m(2), and 35% of LSs had received additional radiation therapy involving the heart. We found LVSD in 15.7% of the LSs, of whom 5.1% were asymptomatic. HF patients were symptomatically mildly affected, with 8.8% of all LSs classified as New York Heart Association class II, whereas more severe HF was rare (1.8%). Compared with controls, LSs had a substantially increased LVSD risk (odds ratio, 6.6; 95% CI, 2.5 to 17.6; P < .001). A doxorubicin dose ≥ 300 mg/m(2) and cardiac radiation therapy dose greater than 30 Gy were independent risk factors for LVSD. CONCLUSION: LVSD was frequent and HF more prevalent than previously reported in LSs after auto-HCT. Our results may help to identify LSs at increased LVSD risk and can serve as a basis for targeted surveillance strategies.

Exercise-induced vasodilation in healthy males: A marker of reduced endothelial function.

OBJECTIVES: Reduced arterial vasodilatatory capacity is a marker of coronary heart disease. The aim was to investigate if the difference between the vasodilatory response before and after exercise, as assessed by non-invasive methodology, is related to endothelial and inflammatory biomarkers. DESIGN: Post-ischemic hyperemia after 5 min of arterial occlusion was examined before and after a bicycle test with strain-gauge plethysmography (measuring peak reactive hyperemia in the forearm) and peripheral arterial tonometry (PAT hyperemia ratio: measuring pulse waves in the index finger relative to the contra-lateral index finger) in 30 healthy males. A low PAT hyperemia ratio or a low peak reactive hyperemia reflects endothelial dysfunction. Inflammatory and endothelial biomarkers were assessed. RESULTS: A low peak reactive hyperemia and a low PAT hyperemia ratio before the bicycle test was associated with a high percentage increase in peak reactive hyperemia after exercise (r = - 0.68, p < 0.001; r = - 0.35, p = 0.06, respectively). Asymmetric dimethylarginine and interleukin-10 were associated with the percentage increase in peak reactive hyperemia in multiple linear regression analyses (ß: 165 (confidence interval [CI], 34-296), p = 0.02; ß: 19 (CI, - 0.5-39), p = 0.06, respectively). CONCLUSIONS: The difference in the vasodilatory response before and after exercise, as assessed by non-invasive methodology, is related to endothelial and inflammatory biomarkers in healthy males.

Atherosclerotic lesions in lymphoma survivors treated with radiotherapy.

BACKGROUND AND PURPOSE: Radiotherapy causes premature atherosclerosis in Hodgkin's lymphoma survivors (HLSs). We determined whether atherosclerosis within the radiation field was predicted by traditional risk factors independent of radiation and compared the extent of atherosclerosis in HLSs treated with mantle field radiotherapy with non-irradiated patients. MATERIAL AND METHODS: Forty-three HLSs (median age 50 years, range 38-63) treated with mantle field radiotherapy were included. Cardiovascular risk factors were registered at first follow-up (FU-1) 5-13 years after treatment. A second follow-up (FU-2) occurred 18-27 years after treatment. At FU-2, in-field atherosclerosis was assessed by computed tomography with calculation of coronary artery calcium volume score (CACS) and pre-cranial artery atherosclerosis score (PAS). Peripheral endothelial dysfunction was assessed by ante-brachial strain-gauge plethysmography. CT angiography of pre-cranial vessels was also performed in 43 non-irradiated patients. RESULTS: Multiple linear regression analyses showed that cholesterol at FU-1 was a predictor of CACS (ß 308 (95% CI 213-403), p < 0.001), PAS (ß 3.67 (95% CI 2.29-5.04), p < 0.001) and peripheral endothelial dysfunction (ß 2.74 (95% CI 0.47-5.01), p = 0.02). There were more atherosclerotic lesions in HLSs (n = 141) than in non-irradiated patients (n = 73, p = 0.001). CONCLUSION: Irradiated arteries are characterized by widespread atherosclerotic lesions aggravated by elevated levels of cholesterol.

Left ventricular function assessed by two-dimensional speckle tracking echocardiography in long-term survivors of Hodgkin's lymphoma treated by mediastinal radiotherapy with or without anthracycline therapy.

Anthracycline therapy is well known for its adverse cardiac effects. However, few studies have been performed of the long-term follow-up of myocardial function in adult survivors of Hodgkin's lymphoma receiving anthracycline. Two-dimensional speckle tracking echocardiography is an accurate angle-independent modality for the quantification of left ventricular (LV) function. The aim of the present study was to investigate the long-term effect of anthracycline on LV systolic function. Echocardiography was performed in 47 survivors of Hodgkin's lymphoma 22 ± 2 years after successful mediastinal radiotherapy with (n = 27) or without (n = 20) anthracycline (doxorubicin) treatment and in 20 healthy controls. LV function was assessed by the LV ejection fraction and global longitudinal and circumferential strain. Both patient groups had received a similar dosage of radiation, and doxorubicin was given at a total dose of 309 ± 92 mg. The global longitudinal strain was reduced in patients receiving anthracycline with mediastinal radiotherapy compared to the other group receiving mediastinal radiotherapy alone or combined radiotherapy and regimens without anthracyclines (-16.1 ± 1.9% vs -17.5 ± 1.7%, respectively, p <0.05). Both patient groups had reduced strain compared to the healthy controls (-20.4 ± 1.7%, both p <0.001). The circumferential strain was also reduced in the treatment groups (-18.3 ± 3.2% and -17.8 ± 3.6% vs -22.5 ± 2.1%, both p <0.001). The LV ejection fraction did not differ between the patient groups (55 ± 8% vs 56 ± 6%, p = 1.0) but was reduced compared to that of the controls (62 ± 5%, both p <0.05). In conclusion, myocardial function was reduced in the survivors of Hodgkin's lymphoma 2 decades after successful treatment consisting of mediastinal radiotherapy with or without chemotherapy. Patients receiving anthracycline therapy had additional negative long-tem effects on LV systolic function.

Cardiovascular risk factors and morbidity in long-term survivors of testicular cancer: a 20-year follow-up study.

PURPOSE: To evaluate the prevalence of cardiovascular risk factors and long-term incidence of cardiovascular disease (CVD) in survivors of testicular cancer (TC). METHODS: Overall, 990 men treated for unilateral TC (1980 to 1994) were included in this national follow-up study (2007 to 2008). They were categorized into four treatment groups: surgery (n = 206), radiotherapy only (RT; n = 386), chemotherapy only (n = 364), and combined RT/chemotherapy (n = 34). Age-matched male controls from the general population (ie, NORMs) were included (n = 990). Survivors of TC who were diagnosed with CVD before or within 2 years after the TC diagnosis were excluded from analyses of CVD end points. RESULTS: Median observation time was 19 years (range, 13 to 28 years). All cytotoxic treatment groups had significantly increased prevalences of antihypertensive medication, and survivors in the RT and RT/chemotherapy groups had higher prevalences of diabetes (RT: odds ratio [OR], 2.3; 95% CI, 1.5 to 3.7; RT/chemotherapy: OR, 3.9; 95% CI, 1.4 to 10.9) compared with NORMs. Overall 74 survivors of TC (8.0%) experienced atherosclerotic disease during follow-up. Increased risks for atherosclerotic disease were observed in age-adjusted Cox regression analyses after any cytotoxic treatment when compared with surgery only (RT: hazard ratio [HR], 2.3; 95% CI, 1.04 to 5.3; chemotherapy: HR, 2.6; 95% CI, 1.1 to 5.9; RT/chemotherapy: HR, 4.8; 95% CI, 1.6 to 14.4). Treatment with cisplatin, bleomycin, and etoposide (BEP) alone had a 5.7-fold higher risk (95% CI, 1.9 to 17.1 fold) for coronary artery disease compared with surgery only and a 3.1-fold higher risk (95% CI, 1.2 to 7.7 fold) for myocardial infarction compared with NORMs. CONCLUSION: Treatment with infradiaphragmatic RT and/or cisplatin-based chemotherapy, particularly the BEP regimen, increases the long-term risk for CVD in survivors of TC.

Relation of coronary artery calcium score to premature coronary artery disease in survivors >15 years of Hodgkin's lymphoma.

Long-term survival in Hodgkin lymphoma (HL) survivors is complicated by an increased risk for coronary artery disease (CAD) due to radiation-induced endothelial damage. Our objective was to quantify total coronary artery calcium (CAC) in long-term HL survivors who had survived >or=15 years after treatment and relate it to the presence of verified CAD. Forty-seven HL survivors 50 +/- 7 years of age who had survived 22 +/- 3 years after mediastinal radiotherapy underwent CAC scoring (Agatston and volume scores) in a multidetector computed tomographic scanner. Total volume score was higher in 7 patients (15%) with verified CAD (median 439, range 8 to 2,057) compared to those without (median 68, 0 to 767, p = 0.022). Ten patients had CAC scores >200. Of these 10, 5 had undergone revascularization of coronary arteries. None of the 8 patients with a CAC score 0 had symptomatic CAD. In conclusion, postirradiation CAC can be quantified by CAC score and this may be a simple and suitable method to screen for CAD in long-term HL survivors. Patients with a CAC score >200 often have clinically significant CAD, and further investigation including angiography may be justified. Lower CAC scores, however, do not exclude CAD and further studies should be undertaken to define the best algorithm for follow-up of this patient group.