Search

Objectives The aim of this study was to determine whether noncoronary measures from cardiac computed tomography (CT) may enhance the prognostic value of this imaging technology. Background When cardiac CT is performed for quantification of coronary artery calcium (CAC) score, information on other cardiac and thoracic structures is available. Methods Participants without known cardiovascular disease from the prospective population based Heinz Nixdorf Recall study underwent noncontrast cardiac CT for CAC score quantification. From CT, epicardial adipose tissue (EAT) volume, left ventricular and left atrial (LA) axial area index, ascending and descending aortic diameters, as well as aortic valve, mitral ring, and thoracic aortic calcification (TAC) were assessed. Incident cardiovascular events included myocardial infarction, stroke, and cardiovascular death. The prognostic value of CT-derived parameters was assessed by Cox regression analysis, receiver operating characteristics, and net reclassification improvement. Results From 3,630 subjects (59 ± 8 years of age, 46% male), 241 (6.6%) developed a cardiovascular event during 9.9 ± 2.6 years of follow-up. In multivariable Cox regression analysis including Framingham Risk Score, CAC (as log[CAC + 1]), and CT parameters, LA index (hazard ratio [HR]: 1.22 [95% confidence interval [CI]: 1.05 to 1.41] per SD; p = 0.010) and EAT volume (HR: 1.15 [95% CI: 1.01 to 1.30] per SD; p = 0.031) were significantly associated with incident events. In addition, presence of TAC showed an elevated event rate (HR: 1.33 [95% CI: 0.97 to 1.81]; p = 0.08), whereas all other CT-derived parameters showed no relevant association. The LA index, EAT volume, and presence of TAC together improved the prediction of events over Framingham Risk Score and CAC in receiver operating characteristics analysis (area under the curve: 0.749 to 0.764; p = 0.011), and let to a significant net reclassification improvement (HR: 38.0%; 95% CI: 25.1% to 50.8%). Conclusion Assessment of LA index, EAT volume, and TAC from non–contrast-enhanced cardiac CT improves the prediction of incident hard cardiovascular events above CAC and established risk factors, indicating that quantification of these noncoronary measures may improve the prognostic value of this imaging technology.

Purpose: Monosomy 3 (M3) in uveal melanoma (UM) obtained after enucleation is significantly associated with metastatic death. With improved biopsy techniques, samples from patients treated with eye-preserving methods have become available. As the choice of treatment depends on tumour size, patients treated with eye-preserving brachytherapy tend to have smaller tumours. It has to be determined if M3 is a valid marker for prognosis of these patients. Methods: Follow-up and clinical data were collected from a total of 451 UM patients: 291 patients were treated by brachytherapy. Tumour tissue was sampled by transretinal biopsy using the 23-gauge Essen biopsy forceps prior to therapy in 114 of them. Chromosome 3 status was determined by microsatellite analysis. Data were compared to those from 160 patients treated by enucleation. Results: Chromosome 3 status correlates significantly with disease-related survival in both patient groups. The proportion of tumours with M3 is lower in the brachytherapy group compared to patients treated with enucleation (25/77 32% and 102/144 71%, respectively). Conclusions: M3 is a valid marker for poor prognosis in uveal melanoma later treated by brachytherapy. The higher proportion of D3 tumours might explain, at least in part, the more favourable prognosis of patients treated by brachytherapy.

Background: Air pollution (AP) is an important environmental risk factor and atherosclerosis-based cardiovascular diseases are the leading cause of death in the westernized world. Epidemiological s...

Sleep characteristics are associated with incident cardiovascular diseases (CVD), but there is a lack of studies on the association between sleep characteristics and incidence/progression of coronary artery calcification (CAC).In the Heinz Nixdorf Recall Study, a population-based cohort study in Germany, CAC was assessed by electron-beam tomography at baseline and at 5-year follow-up. In an analysis set of 3043 subjects (age at baseline 45-74 years; 47% men), we fitted logistic and linear regression models to assess associations between self-rated sleep characteristics (nocturnal and total sleep duration; napping; various sleep disorders) and CAC incidence/CAC progression. Progression was measured as 5-year progression factor, as categories of absolute CAC change, and additionally characterized as rapid or slow compared to an extrapolation of baseline CAC values.We observed barely any association between sleep characteristics and CAC progression regardless of the chosen statistical approach; associations between sleep and CAC incidence were slightly larger, e.g., the geometric mean of the 5-year CAC progression factor was 6.8% (95% confidence interval: -9.5; 25.9) larger for ≤5 h, 2.9% (-7.3; 14.3) larger for 5.1-6.9 h and 7.1% (-2.4; 15.7) smaller for ≥7.5 h total sleep compared to 7-7.5 h total sleep. For subjects with any regular sleep disorder, the geometric mean of the 5-year CAC progression was 3.5% (-4.7; 11.2) smaller compared to subjects without any regular sleep disorder.In this German cohort study, sleep characteristics were barely associated with CAC progression.

Background Prognostication in heart failure with preserved ejection fraction (HFpEF) is challenging and novel biomarkers are urgently needed. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that plays a crucial role in cardiovascular and various inflammatory diseases. Whether MIF is involved in HFpEF is unknown. Methods and results Sixty-two patients with HFpEF were enrolled and followed up for 180 days. MIF plasma levels as well as natriuretic peptide (NP) levels were assessed. High MIF levels significantly predicted the combined end-point of all-cause death or hospitalization at 180 days in the univariate analysis (HR 2.41, 95% CI 1.12–5.19, p = 0.025) and after adjustment for relevant covariates in a Cox proportional hazard regression model (HR 2.35, 95% CI 1.05–5.27, p = 0.0374). Furthermore, MIF levels above the median were associated with higher pulmonary artery systolic pressure (PASP) as assessed by echocardiography (PASP 31 mmHg vs 48 mmHg in the low- and high-MIF group, respectively, p = 0.017). NPs significantly correlated with MIF in HFpEF patients (BNP p = 0.011; r = 0.32; NT-proBNP p = 0.027; r = 0.28). Conclusion MIF was associated with clinical outcomes and might be involved in the pathophysiology of pulmonary hypertension in patients with HFpEF. These first data on MIF in HFpEF should stimulate further research to elucidate the role of this cytokine in heart failure. Trial registration NCT03232671

Background Several studies have demonstrated the tremendous potential of using coronary artery calcium (CAC) in addition to traditional risk factors for coronary heart disease (CHD) risk prediction. However, to date, no risk score incorporating CAC has been developed. Objectives The goal of this study was to derive and validate a novel risk score to estimate 10-year CHD risk using CAC and traditional risk factors. Methods Algorithm development was conducted in the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective community-based cohort study of 6,814 participants age 45 to 84 years, who were free of clinical heart disease at baseline and followed for 10 years. MESA is sex balanced and included 39% non-Hispanic whites, 12% Chinese Americans, 28% African Americans, and 22% Hispanic Americans. External validation was conducted in the HNR (Heinz Nixdorf Recall Study) and the DHS (Dallas Heart Study). Results Inclusion of CAC in the MESA risk score offered significant improvements in risk prediction (C-statistic 0.80 vs. 0.75; p Conclusions An accurate estimate of 10-year CHD risk can be obtained using traditional risk factors and CAC. The MESA risk score, which is available online on the MESA web site for easy use, can be used to aid clinicians when communicating risk to patients and when determining risk-based treatment strategies.

Background Increased left ventricular (LV) size is associated with cardiovascular mortality and morbidity. Once non-contrast cardiac computed tomography (CT) is performed for other purposes, information of LV size is readily available. Purpose To determine the association of gated CT-derived LV size with cardiovascular risk factors and coronary artery calcification (CAC) and to describe age- and gender-specific normative values in a general population cohort. Material and Methods LV area was quantified from non-contrast-enhanced CT in axial, end-diastolic images at a mid-ventricular slice in participants of the population-based Heinz Nixdorf Recall Study, free of known cardiovascular disease. LV index (LVI) was calculated by the quotient of LV area and body surface area (BSA). Crude and adjusted regression analyses were used to determine the association of LVI with risk factors and CAC. Results Overall, 3926 subjects (age 59 ± 8 years, 53% women) were included in this analysis. From quantification in end-diastolic phase, men had larger LV index (2232 ± 296 mm2/m2 vs. 2088 ± 251 mm2/m2, both P 2/10 mmHg; women, 23.4 [18.1–28.6]), and antihypertensive medication (men, 45.2 [14.7–75.8] mm2; women: 46.5 [22.7–70.2], all P 2 ≤ 0.04). In multivariable regression, blood pressure, antihypertensive medication and cholesterol levels, remained associated with LVI ( P Conclusion Non-contrast cardiac CT derived LV index is associated with body size and hypertension. LVI is weakly linked with CAC-score. Further studies need to evaluate whether assessment of LV dimensions from cardiac CT helps identifying subjects with increased cardiovascular risk.

To investigate the relationship between LV size as determined by non-contrast enhanced cardiac CT with incident cardiovascular disease in the general population free of clinical cardiovascular disease.LV axial area was quantified from non-contrast CT in axial, end-diastolic images at a mid-ventricular slice in participants from the population-based Heinz Nixdorf recall study, free of cardiovascular disease (n=3926, 59±8years, 53%female). LV size index (LVI) was defined as the quotient of LV area and body surface area. Major CV events (coronary events, stroke, CV death) were assessed during follow-up. Association of LVI with events was assessed using Cox regression analysis in unadjusted and multivariable adjusted models.During 8.0±1.5years of follow-up, 219 subjects developed a major CV event. Those with events had larger LVI at baseline (2258±352 vs. 2149±276 mm2/m2, p0.0001). In univariate analysis, increase of LVI by 1 standard deviation was associated with 40% higher risk of events (HR(95%CI):1.41(1.26-1.59), p0.0001). Associations remained statistically significant after adjustment for CV risk factors (1.24(1.10-1.40), p=0.0007) and when further adjusting for CAC (1.21(1.07-1.37), p=0.003). There was a trend towards stronger association for subjects with low CAC-score (CAC100:1.41(1.16-1.71), p=0.0005, CAC≥100:1.24(1.06-1.44), p=0.006) in univariate analysis which persisted after multivariable adjustment (CAC100: 1.41(1.14-1.73), p=0.001, CAC≥100: 1.12(0.96-1.31), p=0.16).CT-derived LV size is associated with incident major CV events independent of traditional risk factors and CAC-score in a population-based cohort and may improve the prediction of hard events especially in subjects with low CAC-scores.

Objective The C825T polymorphism of the gene encoding the human G protein beta-3 subunit ( GNB3 ) is associated with hypertension and obesity. Moreover, genotypes of the GNB3 polymorphism have been associated with development of coronary artery disease, and the 825T allele is thought to influence the process of atherosclerosis. However, the potential of the C825T polymorphism to predict coronary events has been poorly explored in a longitudinal setting at the population level. Methods In 4159 Caucasian subjects from the Heinz Nixdorf Recall study cohort (age: 45–75 years, 48% male), genotypes of the GNB3 C825T polymorphism (rs5443) were determined and associated with fatal and non-fatal myocardial infarction (hard coronary events). Established cardiovascular risk factors were used to adjust for confounders. Results The median follow-up time was 9.9 years (1st/3rd quartiles 9.5/10.2). 148 subjects (3.6%) experienced a hard coronary event. The 10-year event-free survival rate was CC, 96.1%; CT 96.9%, TT, 93.7% ( p = 0.018). Multivariable analysis showed that the TT genotype is a significant risk factor for hard coronary events (hazard ratio (HR) = 1.9 (95% confidence interval (CI) 1.2–2.9); p = 0.008) after adjustment for age, sex, diabetes, systolic blood pressure, body mass index, high-density lipoprotein, and coronary artery calcification as determined by electron beam computed tomography at baseline. While prognosis in females was independent of GNB3 genotypes, analysis in males even elevated the HR for TT versus C-allele to 2.6 (95% CI 1.6–4.2; p Conclusion The GNB3 825 TT genotype is a significant and independent risk factor for hard coronary events independent of other established cardiovascular risk factors at a population level in males.

Statins are suggested to stabilize plaque by decreasing lipid-rich and necrotic plaque components and increasing plaque calcification [(1,2)][1]. However, to date the relationship between statin administration and progression of coronary artery calcification (CAC) is poorly understood, and existing

Background and aims As a modifiable lifestyle factor, diet is hypothesized to play an important role in the progression of atherosclerosis. The aim of this study was to explore associations of comprehensive dietary patterns derived by cluster analysis with degree and progression of coronary artery calcification (CAC) over five years of follow-up. Methods and results In the population-based Heinz Nixdorf Recall study, 3718 participants (45–75 years; 47.6% men) without coronary heart disease completed a food frequency questionnaire at baseline. Five distinct dietary patterns were identified using cluster analysis: “Health-conscious”, “Traditional German/Less alcohol”, “Mediterranean-like”, “Western” and “Animal fat/Alcohol” (used as reference). CAC was measured using electron-beam computed tomography at baseline and five years later. CAC after five years was predicted based on sex- and age-specific baseline percentiles. After comparing observed and predicted CAC Scores, CAC progression was classified as slow, expected, or rapid. Compared to “Animal fat/Alcohol” diet, a “Mediterranean-like” diet was associated with a relative risk (RR) for a rapid CAC progression in both sexes (men: 0.61; 95%-confidence interval [95%-CI]: 0.41; 0.90; women: 0.59; 95%-CI: 0.45; 0.78). Furthermore, reduced RRs were observed in women with a “Health-conscious” and a “Traditional German/Less alcohol” diet (0.63; 95%-CI: 0.47; 0.84, respectively 0.69; 95%-CI: 0.52; 0.90). No association was observed for a “Western” diet for both sexes. Similar results were revealed for degree of CAC. Conclusion The study results support the hypothesis that a “Mediterranean-like” diet is associated with a lower CAC-progression and lower degree of CAC in men and women.

Background Thoracic aortic calcification ( TAC ) and coronary artery calcification ( CAC ) are markers of subclinical atherosclerosis and are associated with incident major cardiovascular events. We investigated major determinants for incidence and progression of TAC and the association between TAC and CAC incidence and progression. Methods and Results In a population‐based cohort study, 3270 participants (aged 45–74 years, 53.1% women) received cardiac computed tomography at baseline and after a mean follow‐up of 5.1±0.3 years for quantification of calcification of the ascending (ATAC) and descending thoracic aorta (DTAC) and CAC. Multivariable relative risk regression analysis was used to investigate associations of cardiovascular risk factors with incident TAC , of baseline TAC with incident CAC, and of baseline CAC with incident TAC . Of 1243 participants with baseline TAC of 0, 517 (41.6%) revealed incident TAC after 5 years. Incidence of descending TAC was higher (34.5%) than ascending TAC (23.3%). Incident TAC after 5 years was associated with age (relative risk 1.26 [95% CI 1.21–1.33], per 5 years), blood pressure (relative risk 1.06 [95% CI 1.03–1.10], per 10 mm Hg), low‐density lipoprotein cholesterol (relative risk 1.08 [95% CI 1.04–1.12], per 20 mg/dL), and smoking (relative risk 1.28 [95% CI 1.07–1.53]). Among the 1185 participants without CAC at baseline, the risk of developing CAC was 28.3% when baseline TAC was present compared with 22.2% among those without baseline TAC (excess risk 6.1% [95% CI 1.2–11.0%]). The point estimate of excess risk for incident CAC was higher for ascending TAC (10.8% [95% CI 4.8–16.7%]) and low for descending TAC (1.8% [95% CI −3.2% to 6.7%]). Excess risk for developing ascending and descending TAC with present baseline CAC was 16.4% (95% CI 12.7–20.0%) and 15.6% (95% CI 10.8–20.4%), respectively. Conclusion TAC and CAC share similar major determinants for incident calcification. Participants with TAC , especially ascending TAC , are at elevated risk for development of CAC .

Donor livers marginally acceptable or acceptable according to extended criteria are more frequently transplanted due to the growing discrepancy between demand and availability of donor organs. One type of marginally acceptable graft is a steatotic donor liver, because it is more sensitive to ischemia-reperfusion injury. Thus, quantitative assessment of steatosis is crucial prior to liver transplantation. Extent of steatosis of 49 pre-reperfusion liver biopsies from patients who received orthotopic liver transplantation was assessed by three techniques: semi-quantitative histological evaluation, computerized histomorphometry, and NMR-based estimation of fat content. The findings were correlated to clinical data and to histological examination of corresponding post-reperfusion biopsies for quantification of ischemia-reperfusion injury. We found that values obtained through all three assessment methods were positively correlated. None of the values obtained by the three applied methods correlated with clinical outcome or extent of ischemia-reperfusion injury. Quantitative evaluation of steatosis by NMR yields results comparable to histological and morphometrical assessment. This technique is rapid (

Better prognostication of clinically localized prostate cancer (PCA) is urgently needed. Former studies using different study end-points provided controversial results regarding the prognostic value of serum chromogranin A (CGA) in clinically localized PCA. However, serum CGA was not tested for correlation with the most significant study end-point of long-term disease-specific survival (DSS). CGA and matrix metalloproteinase-7 (MMP7) levels were measured by the BRAHMS KRYPTOR in two independent patient groups with 127 serum and 110 plasma samples. CGA and MMP7 concentrations were correlated with clinicopathological and survival data. In addition, we tested the combinations of CGA with PSA and with a currently identified prognostic factor, MMP7, for their prognostic value. CGA concentrations were significantly elevated in advanced compared to clinically localized cases both in serum and plasma samples (45 vs. 23 ng/ml, p

BACKGROUND Left atrial appendage closure is a preventive treatment of atrial fibrillation-related thrombo-embolism. Patients with diabetes mellitus have increased risk for a negative outcome in percutaneous cardiac interventions. We assessed whether percutaneous left atrial appendage closure is safe and effective in patients with diabetes mellitus. METHODS We included 78 patients (mean age of 74.4 ± 8.3 years) with indication for left atrial appendage closure in an open-label observational single-centre study. RESULTS Patients with diabetes mellitus ( n = 31) were at higher thrombo-embolic and bleeding risk (CHA2DS2-VASc: 4.5 ± 0.9, HAS-BLED: 4.7 ± 0.7) compared to patients without diabetes mellitus ( n = 47, CHA2DS2-VASc: 3.5 ± 1.0, HAS-BLED: 4.1 ± 0.8; p < 0.001 for both). Pre- and periprocedural risk was elevated in patients with diabetes mellitus (Euro II-Score: 6.6 ± 3.7 vs 3.9 ± 1.9, p < 0.01; Society of Thoracic Surgeons (STS)-Score: 4.0 ± 2.5 vs 2.6 ± 1.2, p < 0.01). Procedural success was similar. Periprocedural major adverse cardiac and cerebrovascular events occurred in one patient from the control group (2.1%), whereas patients with diabetes mellitus had no events ( p = 0.672). Follow-up of 6 months revealed no bleeding complication in both groups. No stroke occurred in follow-up, and left atrial appendage flow velocity reduction (55.6 ± 38.6 vs 51.4 ± 19.1 cm/s, p = 0.474) and rate of postinterventional leakage in the left atrial appendage were comparable (0% vs 2.1%, p = 0.672). CONCLUSION Despite patients with diabetes mellitus are high-risk patients, the outcome of percutaneous left atrial appendage closure is similar to patients without diabetes mellitus.

Background Left atrial (LA) size is associated with cardiovascular mortality and morbidity. Once cardiac computed tomography (CT) is performed, information on LA size is readily available without additional contrast media or radiation exposure. Purpose To determine the association of CT-derived LA area and body surface area-adjusted (BSA) LA index with cardiovascular risk factors and describe age- and gender-specific normative values in a general population cohort. Material and Methods This study included 3945 participants (mean age, 59 ± 8 years; 53% women) from the community-based Heinz Nixdorf Recall Study. LA area in an axial image at the level of the mitral valve was quantified from non-contrast-enhanced electron-beam CT by manual delineations of the boundaries of the LA with exclusion of subjects with prevalent cardiovascular disease. Definition of normative values was performed in subjects without predictors of LA enlargement. Results LA quantification was feasible in all subjects. Men had larger LA size (1856 mm2 vs. 1677 mm2, P 2/m2 vs. 933 mm2/m2 for men and women, P 2 = 0.195, BSA: R2 = 0.216, both P 2/10 mmHg for systolic, 31.4 (25.4–37.4) mm2/5 mmHg for diastolic blood pressure, 214.6 (186.9–242.3) mm2 for antihypertensive medication, P 2 ≤ 0.026). Current smoking was associated with reduced LA size (–115.9 [–149.0 – –82.8] mm2, P Conclusion Non-contrast-enhanced cardiac CT enables LA quantification with body size, hypertension, and smoking status being predictors of LA size.

Objectives: This study sought to determine whether epicardial adipose tissue (EAT) volume predicts the progression of coronary artery calcification (CAC) score in the general population.Bac...

Bilirubin is a product of heme oxygenase and an antioxidant per se. In selected cohorts and patient studies, bilirubin was associated with decreased risk for cardiovascular events. We aimed to determine the association of serum bilirubin with coronary artery calcification (CAC) and incident cardiovascular disease in the unselected general population.Participants without prior coronary heart or liver disease were drawn from the population-based Heinz Nixdorf Recall study. CAC was measured from electron beam computed tomography and quantified using the Agatston method. Incident major cardiovascular events (coronary events, stroke, cardiovascular death) were assessed during follow-up. The association of bilirubin with CAC score and incident events was calculated using regression analysis.A total of 3,553 subjects (mean age 59.4 years, 44 % male) were included. Bilirubin was inversely correlated with CAC in men [estimated % change in (CAC + 1) per each gender-specific standard deviation of bilirubin [95 % confidence interval (CI): -6.1 (-11.6; -1.7) %, p = 0.032] but less so in women [-3.6 (-7.7; 0.2) %, p = 0.065], when adjusting for age only. With adjustment for traditional cardiovascular risk factors, the association was less pronounced [men: -2.5 (-7.5; 2.6) %, p = 0.35, women: -0.2 (-4.1; 3.5) %, p = 0.9]. Likewise, higher bilirubin by one standard deviation was associated with 19 % lower frequency of incident cardiovascular events in age- and gender-adjusted Cox regression analysis [hazard ratio (95 % CI): 0.81 (0.68; 0.96), p = 0.014]; this effect was slightly attenuated after adjustment for traditional cardiovascular risk factors [0.87 (0.73; 1.04), p = 0.13].Our data from a general population suggest that a potential protective role of bilirubin in the atherosclerosis process is largely secondary to a more beneficial risk factor profile.

Background: Computed tomography (CT) allows estimation of coronary artery calcium (CAC) progression. We evaluated several progression algorithms in our unselected, population-based cohort for risk prediction of coronary and cardiovascular events. Methods: In 3281 participants (45–74 years of age), free from cardiovascular disease until the second visit, risk factors, and CTs at baseline (b) and after a mean of 5.1 years (5y) were measured. Hard coronary and cardiovascular events, and total cardiovascular events including revascularization, as well, were recorded during a follow-up time of 7.8±2.2 years after the second CT. The added predictive value of 10 CAC progression algorithms on top of risk factors including baseline CAC was evaluated by using survival analysis, C-statistics, net reclassification improvement, and integrated discrimination index. A subgroup analysis of risk in CAC categories was performed. Results: We observed 85 (2.6%) hard coronary, 161 (4.9%) hard cardiovascular, and 241 (7.3%) total cardiovascular events. Absolute CAC progression was higher with versus without subsequent coronary events (median, 115 [Q1–Q3, 23–360] versus 8 [0–83], P 5y and 5-year risk factors. An excellent prognosis was found for 921 participants with double-zero CAC b =CAC 5y =0 (10-year coronary and hard/total cardiovascular risk: 1.4%, 2.0%, and 2.8%), which was for participants with incident CAC 1.8%, 3.8%, and 6.6%, respectively. When CAC b progressed from 1 to 399 to CAC 5y ≥400, coronary and total cardiovascular risk were nearly 2-fold in comparison with subjects who remained below CAC 5y =400. Participants with CAC b ≥400 had high rates of hard coronary and hard/total cardiovascular events (10-year risk: 12.0%, 13.5%, and 30.9%, respectively). Conclusions: CAC progression is associated with coronary and cardiovascular event rates, but adds only weakly to risk prediction. What counts is the most recent CAC value and risk factor assessment. Therefore, a repeat scan >5 years after the first scan may be of additional value, except when a double-zero CT scan is present or when the subjects are already at high risk.

BackgroundThe association between non-steroidal anti-inflammatory drugs (NSAIDs) and the incidence of valvular and arterial calcification is not well established despite known associations between these drugs and cardiovascular events.ObjectiveTo compare the association between the baseline use of aspirin with other NSAID class medications with the incidence and prevalence of aortic valve calcification (AVC) and coronary artery calcification (CAC).MethodsThe relationship of NSAID use to AVC and CAC detected by computed tomography was assessed in 6814 participants within the Multi-Ethnic Study of Atherosclerosis (MESA) using regression modeling. Results were adjusted for age, sex, ethnicity, study site, anti-hypertensive medication use, education, income, health insurance status, diabetes, smoking, exercise, body mass index, blood pressure, serum lipids, inflammatory markers, fasting glucose, statin medication use, and a simple diet score. Medication use was assessed by medication inventory at baseline which includes the use of non-prescription NSAIDs. MESA collects information on both incident and prevalent calcification. The 4814 participants of the Heinz Nixdorf Recall (HNR) Study, a German prospective cohort study with similar measures of calcification, were included in this analysis to enable replication.ResultsMean age of the MESA participants was 62 years (51% female). After adjustment for possible confounding factors, a possible association between aspirin use and incident AVC (Relative Risk(RR): 1.60; 95%Confidence Interval (CI): 1.19-2.15) did not replicate in the HNR cohort (RR: 1.06; 95%CI: 0.87-1.28). There was no significant association between aspirin use and incident CAC in the MESA cohort (RR 1.08; 95%CI: 0.91-1.29) or in the HNR cohort (RR 1.24; 95%CI: 0.87-1.77). Non-aspirin NSAID use was not associated with either AVC or CAC in either cohort. There were no associations between regular cardiac dose aspirin and incident calcification in either cohort.ConclusionBaseline NSAID use, as assessed by medication inventory, appears to have no protective effect regarding the onset of calcification in either coronary arteries or aortic valves.

Background Coronary atherosclerosis can be detected by computed tomography. The amount of coronary artery calcification (CAC) is related to cardiovascular risk factors, the strength of the gender specific relation between lipoprotein parameters and CAC has not extensively been studied. Especially, the role of routinely determined lipoproteins in contrast to less common and computed lipid parameters (e.g. ratios) remains to be clarified. Methods and results The study cohort ( n = 3956, 52% women, age 45–75 years) was randomly selected from three cities of a German metropolitan area. Lipoproteins–low-and high density lipoprotein (LDL-C/HDL-C), total cholesterol, apolipoprotein A-1 and B (apoA-1/apoB) as well as lipoprotein (a) (Lp(a)) were measured, while non-HDL-C was calculated. All participants received an electron-beam computed tomography (EBCT) for quantification of CAC. Adjusted for age and cardiovascular risk factors, CAC increased by a factor of 1.97 (1.51–2.57, 95% CI) and 1.94 (1.53–2.45, 95% CI) comparing the fourth to the first quartile of LDL-C for men and women, respectively. This association with LDL-C was also found after dichotomization of CAC at thresholds >0, ≥100 and ≥400. The best association of CAC was, however, found to be apoB and the second best was non HDL-C, in both men and women. For apoB, the model including all risk factors reached an explained variance for CAC of 20.2% in men and of 21.6% in women. When using LDL-C as a given parameter according to the current practice and advice, HDL-C in men and apoB in women provided an additional but small benefit. Conclusion ApoB showed the best association with CAC compared to all other tested lipoproteins. Neither the ratio LDL-C/HDL-C nor apoB/apoA-1, or Lp(a) revealed a closer association with CAC. While lipoproteins are related to CAC more closely in women than in men, their association with CAC is, however, not particularly strong. Our results may influence primary and secondary prevention advices in order to improve detection of subclinical atherosclerosis, for which lipoprotein parameters can only play a minor role.

Several biomarkers including B-type natriuretic peptide (BNP) have been suggested to improve prediction of coronary events and all-cause mortality. Moreover, coronary artery calcium (CAC) as marker of subclinical atherosclerosis is a strong predictor for cardiovascular mortality and morbidity. We aimed to evaluate the predictive ability of BNP and CAC for all-cause mortality and coronary events above traditional cardiovascular risk factors (TRF) in the general population.We followed 3782 participants of the population-based Heinz Nixdorf Recall cohort study without coronary artery disease at baseline for 7.3 ± 1.3 years. Associations of BNP and CAC with incident coronary events and all-cause mortality were assessed using Cox regression, Harrell's c, and time-dependent integrated discrimination improvement (IDI(t), increase in explained variance).Subjects with high BNP levels had increased frequency of coronary events and death (coronary events/mortality: 14.1/28.2% for BNP ≥100 pg/ml vs. 2.7/5.5% for BNP 100 pg/ml, respectively). Subjects with a BNP ≥100 pg/ml had increased incidence of hard endpoints sustaining adjustment for CAC and TRF (for coronary events: hazard ratio (HR) (95% confidence interval (CI)) 3.41(1.78-6.53); for all-cause mortality: HR 3.35(2.15-5.23)). Adding BNP to TRF and CAC increased measures of predictive ability: coronary events (Harrell's c, for coronary events, 0.775-0.784, p = 0.09; for all-cause mortality 0.733-0.740, p = 0.04; and IDI(t) (95% CI), for coronary events: 2.79% (0.33-5.65%) and for all-cause mortality 1.78% (0.73-3.10%).Elevated levels of BNP are associated with excess incident coronary events and all-cause mortality rates, with BNP and CAC significantly and complementary improving prediction of risk in the general population above TRF.

Bone is the most common site of metastasis in breast cancer. Detection relies on imaging technology which is costly and can only be performed to a certain degree. Bone markers are non-invasive, inexpensive and may potentially serve as predictive and prognostic surrogate endpoints in detecting bone metastases and response to bisphosphonates. This study analyzed the value of the serum bone turnover markers PINP and ICTP for bone metastases in metastatic breast cancer patients receiving zoledronic acid. The results were compared with the serum levels of CEA and CA 15-3, and analyzed with respect to the number of bone metastases as well as clinical response. Forty patients with confirmed bone metastases who received chemotherapy and/or hormonal therapy and zoledronic acid i.v. q4 weeks participated in the present study. blood (5 ml) was collected at the start of the study and q3 months for a period of one year for the analysis of PINP, ICTP, CEA and CA 15-3 using radioimmunoassays and ELISA, respectively. Imaging of bone metastases was performed at the same time points. In 29 out of 40 patients, more than 3 bone metastases were confirmed by imaging and 11 out of 40 patients presented with 3 or less. At the start of the study, the median value for ICTP was 6 µg/l and for PINP 58.7 µg/l. At the end of the study the median values were 4.5 µg/l for ICTP and 21 µg/l for PINP. When patients were stratified into responders and non-responders, a decrease in both PINP (P

Objectives This study sought to determine whether epicardial fat volume predicts coronary events in the general population. Background Epicardial adipose tissue (EAT) is suggested to promote plaque development in the coronary artery tree. Methods We quantified EAT volume in participants from the prospective population-based Heinz Nixdorf Recall cohort study free of cardiovascular disease. Incident coronary events were assessed during a follow-up period of 8.0 ± 1.5 years. Multivariable association of EAT with cardiovascular risk factors, coronary artery calcification (CAC), and coronary events was assessed using regression analysis. Results From the overall 4,093 participants (age 59.4 years, 47% male), 130 subjects developed a fatal or nonfatal coronary event. Incidence of coronary events increased by quartile of EAT (0.9% vs. 4.7% for 1st and 4th quartile, respectively, p Conclusions Epicardial fat is associated with fatal and nonfatal coronary events in the general population independent of traditional cardiovascular risk factors and complements information from cardiac computed tomography above the CAC score.

Thoracic aortic calcification (TAC) is associated with cardiovascular (CV) risk factors and prevalent coronary artery disease. We aimed to investigate whether TAC burden is associated with incident myocardial infarction (MI) and all-cause mortality in subjects without known coronary artery disease and to determine its predictive value for these endpoints.We used longitudinal data from the population-based prospective Heinz Nixdorf Recall Study. TAC and coronary artery calcification (CAC) scores were quantified from non-contrast enhanced electron beam computed tomography. Cox regression analysis was used to determine the association of TAC with incident MI or all-cause mortality, adjusting for CV risk factors and additionally for CAC-score in a separate step. Predictive value of TAC was assessed using Harrell's C index.Overall, 4040 participants without known coronary artery disease (59.4 years, 47% male) were included in this analysis. During a mean follow-up of 8.0 ± 1.5 years, we observed 136 coronary events and 304 deaths. In subjects with TAC0 vs TAC = 0, the incidence of nonfatal MI was 4.2% vs 2.0% (p 0.001), and all-cause mortality was 8.9% vs 5.2% (p 0.001). Risks for coronary events and for all-cause mortality increased significantly with increasing TAC-scores (p 0.001). After adjustment for CV risk factors, body mass index (BMI) and CV medication, a unit increase of TAC on a logarithmic scale (log(TAC + 1)) remained independently associated with coronary events (hazard ratio (HR) (95% confidence interval (CI)): 1.06 (1.00-1.14), p = 0.03) and all-cause mortality (HR 1.06 (1.01-1.12), p 0.01). After further adjustment for CAC-score (log(CAC + 1)), hazard ratios were attenuated for both endpoints (coronary events: 0.98 (0.91-1.05), p = 0.56, all-cause mortality: 1.03 (0.98-1.08), p = 0.33). When adding log(TAC + 1) to the model containing traditional risk factors and CAC, Harrell's C indices did not increase for coronary events (0.773-0.772, p = 0.66) or for all-cause mortality (0.741-0.743, p = 0.49).TAC is associated with incident coronary events and all-cause mortality independent of traditional CV risk factors in the general population. TAC fails to improve event prediction over CAC in both coronary events and all-cause mortality.

Early identification of patients at risk for thoracic aortic aneurysm (TAA) has the potential of improving prognosis. So far, however, "normal" aortic dimensions are not well defined, rendering identification of patients with enlarged aortas difficult. In the present study we aimed to (1) establish age- and gender-specific distribution of thoracic aortic diameters and (2) to determine the prevalence of asymptomatic TAA in a population-based European cohort.Diameters of ascending thoracic aorta (ATA) and descending thoracic aorta (DTA) were measured from electron beam computed tomography (EBCT) scans of 4129 participants aged 45 to 75 years from the Heinz Nixdorf Recall study. Age- and gender-specific percentiles were calculated for body-surface adjusted aortic diameters. Multivariable linear regression was used to evaluate the association between aortic diameters and cardiovascular risk factors including age, gender and body-surface area (BSA).Aortic diameters were generally greater in the ATA than in the DTA, and were greater in men than in women (ATA: 3.71 ± 0.4 cm vs. 3.45 ± 0.4 cm, p0.0001; DTA: 2.82 ± 0.3 cm vs. 2.54 ± 0.3 cm, p0.0001). Age, male gender, blood pressure and body-surface area were independently associated with aortic diameters in both ATA and DTA. Based on our measurements age- and gender-specific percentiles for indexed ATA and DTA diameters were computed. Aneurysms ≥ 5 cm were found in 12 (0.34%) out of the total of 4129 subjects.Since BSA was independently associated with increasing aortic diameters, correction of aortic diameters for BSA may be more helpful in order to reliably identify patients at risk for aneurysm formation. Based on the normal distribution of body-surface adjusted thoracic aortic diameters displayed in age- and gender-specific percentiles we suggest a cut-off point for aneurismal aortic diameter at the 95th percentile.

Objective To determine the role of hypertension for coronary artery calcification (CAC) progression. Methods The population-based Heinz Nixdorf Recall study recruited 4814 participants from a German urban population in 2000-2003. CAC was measured using electron-beam computed tomography at baseline and after 5 years. The present analyses refer to 3481 participants with repeat scan (coronary heart disease until 5 years excluded, age at baseline 45-74 years, and 53.1% women). Blood pressure (BP), Framingham risk factors, and antihypertensive medication were recorded at baseline. BP was staged according to Joint National Committee 7 guidelines. Participants under antihypertensive medication were classified as stage 2. CAC at 5 years was predicted from baseline using our dedicated, publicly available algorithm. CAC progression was accordingly classified as slow, expected, or rapid. Results Normotension was found in 20.5%, prehypertension in 27.2%, stage 1 hypertension in 15.8%, and stage 2 (ST2) in 36.5%. The frequency of rapid progression increases with BP stage (normotension: 16.7% to ST2: 21.1%, P = 0.004). Risk factor adjusted relative risk [RR (95% confidence interval), reference: normotension] of rapid progression was for prehypertension: 1.22 (0.98;1.51), stage 1: 1.29 (1.01;1.65), and ST2: 1.45 (1.17;1.79). Risk factor adjusted measures of CAC progression per 10 mmHg SBP were already elevated in women with BP below 140/90 mmHg: CAC onset, RR = 1.22 (1.07;1.40), rapid progression, RR = 1.17 (1.05;1.31), 5-year CAC progression, 6.7% (0.5;13.4). In men below 140/90 mmHg, only RR of rapid progression was considerably increased [RR = 1.11 (0.96;1.29)]. Conclusion CAC progression, a sign of ongoing target organ damage, is already accelerated in prehypertensive patients, a substantial proportion of our urban population.

Aims To compare the predictive value of coronary artery calcification (CAC), carotid intima-media thickness (CIMT) and ankle-brachial index (ABI) in a primary prevention cohort depending on risk factor profile to determine which of the three markers improves cardiovascular (CV) risk discrimination best in which risk group. Methods and Results We quantified CAC, CIMT, and ABI in 3108 subjects (mean age 59.2 ± 7.7, 47.1% male) without prevalent CV diseases from the population-based Heinz Nixdorf Recall study. Associations with incident major CV events (coronary event, stroke, CV death; n = 223) were assessed during a follow-up period of 10.3 ± 2.8 years with Cox proportional regressions in the total cohort and stratified by Framingham risk score (FRS) groups. Discrimination ability was evaluated with Harrell’s C. All three markers were associated with CV events (hazard ratio [95% confidence interval (CI)]: CAC: 1.31 (1.23–1.39) per 1-unit increase in log(CAC + 1) vs. CIMT: 1.27 (1.13–1.43) per 1 SD vs. ABI: 1.30 (1.14–1.49) per 1 SD, in FRS adjusted models). Considering reclassification, CAC lead to highest reclassification in the total cohort, while also for CIMT and ABI significant improvement in net-reclassification was observed [NRI (95% CI): CAC: 0.55 (0.42–0.69); CIMT: 0.32 (0.19–0.45); ABI: 0.19 (0.10–0.28)]. Conclusion Coronary artery calcification provides the best discrimination of risk compared with CIMT and ABI, particularly in the intermediate risk group, whereas CIMT may be an alternative measure for reassurance in the low risk group.

Sunitinib treatment leads to improvement in progression-free survival in patients with advanced pancreatic neuroendocrine tumours (pNETs). However, limited data exist regarding the effectiveness, safety and tolerability in clinical practice. We present the results of the first detailed pNET cohort analysis since sunitinib was approved. Patients with advanced, differentiated pNET treated with sunitinib were retrospectively analysed. All patients had progressive disease before start of sunitinib treatment. Twenty-one patients, with a median age of 64 years (range 28-78), were included in this study. Nineteen patients could be analysed for treatment effectiveness. Twelve (57%) patients exhibited either a partial response (1 patient) or stable disease (11 patients) according to the RECIST criteria. The median progression-free survival was 7.0 months (95% CI 3.0-12.0); the probability of being event-free at 6 months was 52.6% (95% CI 28.4-72.1). Potential influencing factors as Ki-67 index, age or duration of disease did not show significant correlations with the response to sunitinib therapy. Considering the differences in patients' characteristics, sunitinib in daily practice showed effectiveness parameters similar to the phase III trial.

Objectives The aim of this study was to assess the difference in indication for statin therapy by European Society of Cardiology (ESC) versus American Heart Association/American College of Cardiology (AHA/ACC) guidelines and to quantify the potential additional role of coronary artery calcification (CAC) score over updated guidelines in a primary prevention cohort. Background Recently, ESC and AHA/ACC updated the guidelines regarding statin therapy in primary prevention. Methods In 3,745 subjects (59 ± 8 years of age, 47% men) from the population based longitudinal Heinz Nixdorf Recall cohort study without cardiovascular disease or lipid-lowering therapy at baseline CAC score was assessed between 2000 and 2003. Subjects remained unaware of their initial CAC score. Statin indication was determined according to 2012 ESC and 2013 AHA/ACC guidelines based on subjects individual baseline characteristics. Results The frequency of statin recommendation was lower according to ESC compared to AHA/ACC guidelines (34% vs. 56%; p < 0.0001), whereas low CAC score (

High resting heart rate (RHR) predicts cardiovascular outcomes in patients with vascular disease and heart failure. We evaluated the prognostic value of RHR in a large contemporary population-based, prospective cohort of individuals without known coronary artery disease. Resting heart rate (RHR) was determined in 4091 individuals (mean age 59.2 ± 7.7; 53 % women) from the Heinz Nixdorf RECALL study, of whom, 3348 were free of heart rate lowering medication. During 10.5 years of follow-up (median), 159 (3.9 %) individuals developed a coronary event and 398 (9.7 %) died of any cause. Persons without any event (n = 3603) had similar heart rates as persons with coronary events (69.5 ± 11 versus 69.9 ± 11 bpm, p = 0.51) but lower heart rates than persons who died (72.3 ± 13 bpm, p

Purpose The aim of this study was to introduce population-based sex and age-stratified distributions of carotid intima media thickness (CIMT), to compare fixed cut-off and percentile values for subjects with and without known coronary heart disease (CHD) and to describe CIMT percentiles. Methods Between 2000 and 2003, a total of 4,814 subjects aged 45-75 years were recruited into the Heinz Nixdorf recall study (HNR). Ultrasound examination of extracranial arteries was performed and the CIMT was measured manually over a distance of 1 cm proximal to the bulb in the common carotid artery (CCA). Both sides were measured and the average of the right and left artery were calculated (mean CIMT). Results The CIMT was measured for 1,749 men and 1,802 women without prevalent CHD and 177 men and 50 women with prevalent CHD. Mean CIMT values were higher in men compared to women (men 0.71 ± 0.14 mm vs. women 0.65 ± 0.11 mm, p ≤ 0.0001) and in subjects with CHD compared to those without (men with and without CHD: 0.76 ± 0.14 mm and 0.70 ± 0.14 mm, p ≤ 0.0001, respectively; women with and without CHD: 0.73 ± 0.15 mm and 0.64 ± 0.11 mm, p ≤ 0.0001, respectively). In men the mean CIMT increased from 0.62 ± 0.10 mm in the youngest (45-49 years old) up to 0.79 ± 0.13 mm in the highest age group (≥ 70 years) (0.57 ± 0.08 mm up to 0.71 ± 0.12 mm in women, p ≤ 0.0001 for both). Conclusions Compared to international studies similar CIMT distributions were found in this study using both continuous and percentile distributions. However, lower CIMT values were observed in older participants, which can be explained by exclusion of carotid plaque formation in CIMT measurements.

Background and purpose Individual risk stratification requires reliable information on preexisting vascular disease. The intima-media thickness of the common carotid artery (CIMT) is a non-invasively accessible marker of atherosclerosis, which can be used for risk evaluation. Methods In a sample of 3669 initially stroke-free subjects aged 45–75 years belonging to the population-based Heinz Nixdorf Recall cohort, the predictive value of CIMT for incident stroke was evaluated over 85.3 ± 17.4 months in addition to established risk factors. Results In a multivariable Cox regression analysis with traditional cardiovascular risk factors including age, gender, systolic blood pressure, LDL and HDL, diabetes, body mass index, smoking and CIMT, CIMT was a moderate stroke predictor (hazard ratio = 1.20 per 0.1 mm, 95% confidence interval = 1.01–1.44; p = 0.043), additional to e.g. age (1.46 per 5 years, 1.21–1.75; p p = 0.008) and current smoking (1.93, 1.12–3.31; p = 0.014). CIMT was associated with stroke risk in subjects above but not below 65 years. CIMT predicted stroke events in men, but not women. CIMT discriminated stroke incidence specifically in subjects belonging to the highest Framingham risk score tercile. Conclusions CIMT is a moderate independent stroke predictor, which discriminates stroke incidence in subjects at high vascular risk.

Cardiac CT allows the detection and quantification of coronary artery calcification (CAC). Electron-beam CT (EBCT) has been widely replaced by high-end CT generations in the assessment of CAC. The aim of this study was to compare the CAC scores derived from an EBCT with those from a dual-source CT (DSCT).We retrospectively selected 92 patients (61 males; mean age, 60.7 ± 12 years) from our database, who underwent both EBCT and DSCT. CAC was assessed using the Agatston score by two independent readers (replicates: 1, 2; 3=mean of reading 1 and 2).EBCT scores were on average slightly higher than DSCT scores (281 ± 569 vs 241 ± 502; p0.05). In regression analysis R(2)-values vary from 0.956 (1) to 0.966 (3). We calculated a correction factor as EBCT=(DSCT+1)(1.026)-1. When stratifying into CAC categories (0, 1-99, 100-399, 400-999 and ≥1000), 79 (86%) were correctly classified. From those with positive CAC scores, 7 out of 61 cases (11%, κ=0.81) were classified in different categories. Using the corrected DSCT CAC score, linear regression analysis for the comparison to the EBCT results were r=0.971 (p0.001), with a mean difference of 6.4 ± 147.8. Five subjects (5.4%) were still classified in different categories (κ=0.84).CAC obtained from DSCT is highly correlated with the EBCT measures. Using the calculated correction factor, agreement only marginally improved the clinical interpretation of results. Overall, for clinical purposes, face value use of DSCT-derived values appears as useful as EBCT for CAC scoring.

Thoracic aortic calcification (TAC) and coronary artery calcium (CAC) have been proposed for risk assessment of coronary artery and cardiovascular disease events. The aim of this analysis is to assess the prevalence of TAC and to determine its relationship with cardiovascular risk factors and CAC in a general unselected population. TAC was measured from electron beam computed tomography scans and quantified by Agatston-Score in 4,025 participants aged 45-75 years (mean age 59.4 ± 7.8 years, 53% female) from the Heinz Nixdorf Recall Study. Multivariable generalized linear regression was used to evaluate relationships between TAC and cardiovascular risk factors and CAC. Overall 2,538/4,025 (63.1%) participants revealed TAC. Prevalence of TAC was greater in men than in women (65.2 vs. 61.7%, p = 0.009). TAC was most strongly associated with age, systolic blood pressure, smoking and high levels of LDL-cholesterol. Prevalence of CAC was significantly higher in participants with TAC than without (74.0 vs. 57.6%, p < 0.0001) demonstrating an increased risk of having CAC in the presence of TAC (prevalence ratio (PR) 1.29 [95% CI: 1.22-1.35], p < 0.0001, PR adjusted for risk factors 1.14 [1.09-1.20], p < 0.0001). In general population, TAC has high prevalence and largely shares cardiovascular risk factors with CAD while being independently associated with present CAC.

Background: Secondhand smoke (SHS) consists of fine particulate matter, carcinogens, and various toxins that affect large parts of the population. SHS increases the risk for acute cardiovascular events and may contribute to the development of atherosclerosis. Objectives: We investigated the association of SHS with coronary artery calcification (CAC). Methods: In this cross-sectional analysis, we used baseline data (2000–2003) from 1,766 never-smokers without clinically manifested coronary heart disease, 45–75 years of age, from the Heinz Nixdorf Recall Study, an ongoing, prospective, population-based cohort study in Germany. Self-reported frequent SHS at home, at work, and in other places was assessed by questionnaire. CAC scores were derived based on electron-beam computed tomography. We conducted multiple linear regression analysis using exposure to SHS as the explanatory variable and ln(CAC+1) as the response variable. We conducted logistic regression to estimate the odds ratio (OR) for presence of any CAC. Results: Frequent exposure to SHS was reported by 21.5% of participants. After adjustment for age, sex, and socioeconomic status, CAC + 1 was 21.1% [95% confidence interval (CI): –5.5%, 55.2%] higher in exposed than in unexposed participants. After adjusting for other cardiovascular risk factors, the association was attenuated (15.4%; 95% CI: –9.6%, 47.2%). SHS exposure was also associated with a CAC score > 0 (fully adjusted OR = 1.38; 95% CI: 1.03, 1.84). Conclusions: Self-reported frequent exposure to SHS was associated with subclinical coronary atherosclerosis in our cross-sectional study population. Considering the widespread exposure and the clinical relevance of coronary atherosclerosis, this result, if confirmed, is of public health importance.

BACKGROUND: Bone is the most common site of metastasis in breast cancer. The detection relies on imaging technology which is costly and can only be performed to a certain degree. Bone markers are noninvasive, inexpensive and potentially might serve as predictive and prognostive surrogate endpoints in detecting bone metastases and response to BPs. This study analyzes the value of the serum markers of type I collagen synthesis (PINP) and degradation (ICTP) as markers of bone metastases in mBC patients (pts) receiving ZOL. The results will be correlated with the levels of CEA and Ca 15-3 as well as the clinical response. MATERIALS AND METHODS: 38 mBC pts (mean age was 60 years: range, 35-86), with confirmed bone metastases who were received chemotherapy and/or hormonal therapy and ZOL iv q 4 wks were participating in our study. 5 ml blood were collected at the time of study start and q 3 months for one year for the analysis of PINP, ICTP, CEA and Ca 15-3 using radioimmunoassays and ECLIA System, respectively. Imaging of bone metastases was performed at the same time points. In this first analysis, data were correlated with the number of bone metastases at study start. RESULTS: At study baseline, PINP, ICTP, CEA and Ca 15-3 were analyzed in all pts. In 28/38 pts (73%) more than 3 bone metastases were confirmed by imaging and 10/38 pts (27%) presented with 3 or less bone metastases. The median value for ICTP was 6 µg/l (interquartile range 3.9-12.7) and for PINP 58.7 µg/l (43.5-164). Serum PINP and ICTP concentrations were significantly different when pts were stratified into > 3 bone metastases (median value ICTP 6.3 µg/l and PINP 75.3 µg/l) and 3 or less bone metastases (median value ICTP 4.1 µg/l and PINP 47 µg/l), respectively (P0.2). Statistical analysis for follow-up measurements will be available after having completed sampling for all 38 pts in 5 months. Up to now, 135 samples of all patients have been analyzed and there seems to be an association between the number of bone metastases, serum levels for PINP/ICTP and response to therapy. CONCLUSION: In contrast to serum tumor markers, the identification of PINP and ICTP permit to estimate the number of bone metastases and seems to be a useful tool for monitoring mBC pts undergoing BP therapy with ZOL for treatment of bone metastases. These results have to be confirmed in a larger prospective trial. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-09-33.

Objectives: Growth hormone (GH) secretory status and GH therapy influence cardiac muscle mass and function. Most patients with Prader-Willi syndrome (PWS) are GH-deficient (GHD), and are at risk to develop obesity-related cardiac problems. Few data exist on the development of cardiac dimensions under GH treatment in PWS. Study Design: In a retrospective study, cardiac dimensions measured echocardiographically in 26 children with PWS before and after 22.9 ± 11.0 months of GH therapy (0.035 mg/kg/day) were compared to those of 13 GHD children treated with GH (0.025–0.035 mg/kg/day) over 13.5 ± 4.2 months. Results: Low-normal left ventricular end-systolic [diastolic] diameter SDS increased in PWS patients (1.41, p < 0.0001 [1.23, p < 0.0001]) and in controls (0.61, p = 0.04 [0.78, p = 0.013]), becoming elevated above normal in 2/26 PWS patients. There was a trend for a higher GH effect on left ventricular end-systolic diameter in PWS (p = 0.071). Mean values of all echocardiographic dimensions remained in the normal range in both PWS patients and controls, before and under GH therapy. Conclusion: The response of cardiac dimensions to GH treatment is similar in PWS patients and GHD controls, with a trend towards more elevated left ventricular parameters in PWS. Therefore, regular echocardiographic assessment may be considered in PWS children with longer treatment duration.

Objectives The purpose of this study was to determine net reclassification improvement (NRI) and improved risk prediction based on coronary artery calcification (CAC) scoring in comparison with traditional risk factors. Background CAC as a sign of subclinical coronary atherosclerosis can noninvasively be detected by CT and has been suggested to predict coronary events. Methods In 4,129 subjects from the HNR (Heinz Nixdorf Recall) study (age 45 to 75 years, 53% female) without overt coronary artery disease at baseline, traditional risk factors and CAC scores were measured. Their risk was categorized into low, intermediate, and high according to the Framingham Risk Score (FRS) and National Cholesterol Education Panel Adult Treatment Panel (ATP) III guidelines, and the reclassification rate based on CAC results was calculated. Results After 5 years of follow-up, 93 coronary deaths and nonfatal myocardial infarctions occurred (cumulative risk 2.3%; 95% confidence interval: 1.8% to 2.8%). Reclassifying intermediate (defined as 10% to 20% and 6% to 20%) risk subjects with CAC Conclusions CAC scoring results in a high reclassification rate in the intermediate-risk cohort, demonstrating the benefit of imaging of subclinical coronary atherosclerosis. Our study supports its application, especially in carefully selected individuals with intermediate risk.

Data on cardiovascular risk in acromegaly are scanty and lack a clear correlation to epidemiological data.Our aim was an evaluation of cardiovascular risk factors in patients with active acromegaly, a calculation of the Framingham risk score (FRS) compared with age- and gender-matched controls of the general population, and an evaluation of the effect of IGF-I normalization.We conducted a retrospective, comparative study at a university referral center.A total of 133 patients with acromegaly (65 men, aged 45-74 yr) from the German Pegvisomant Observational Study were matched to 665 controls from the general population.Risk factors were measured at baseline and after 12 months of treatment with pegvisomant (n=62).Patients with acromegaly had increased prevalence of hypertension, mean systolic and diastolic blood pressure (BP), history of diabetes mellitus and glycosylated hemoglobin (all P0.001) and decreased high-density lipoprotein, low-density lipoprotein, and total cholesterol (all P0.001). FRS was significantly higher in patients with acromegaly compared with controls (P0.001). At 12 months, systolic BP (P=0.04) and glycosylated hemoglobin (P=0.02) as well as FRS (P=0.005) decreased significantly. IGF-I was normalized in 62% (41 of 62). In these patients, glucose and systolic and diastolic BP was significantly lower than in partially controlled patients.We found an increased prevalence of cardiovascular risk factors in acromegalic patients compared with controls. Control of acromegaly led to a significant decrease of FRS, implying a reduced risk for coronary heart disease. This was most significant in those patients who completely normalized their IGF-I levels.Disease control is important to reduce the likelihood for development of coronary heart disease.

Hyperthermic isolated limb perfusion with TNF-α and melphalan (HILP-TM) achieves high response rates in sarcomas. Melphalan resistance was previously reported to be associated with overexpression of metallothioneins (MTs). Objective of this study was to investigate the influence of MT expression on tumor responses in HILP-TM-treated soft tissue (STSs) and bone sarcomas (BS). In primary biopsies of 41 HILP-TM-treated sarcomas (37 STSs and 4 BS), MT expression was assessed by an immunoreactive score. The pathologic response to HILP-TM was quantified in the corresponding tumor resection specimens. We studied the association of MT-IRS between histological regression (responder >90%, or non-responder ≤90% regression), tumor proliferation, and other clinico-pathological parameters. MT expression was found in 70.7% (N = 29) of tumors (high 12.2%, moderate 19.5%, and low 39.0%). After HILP-TM, 20 cases (48.8%) were categorized as “responders” and 21 (51.2%) as “non-responders.” Six “responders” (14.6%) presented with complete regression. MT expression positively correlated with tumor proliferation but not with HILP-TM. HILP-TM showed a favorable response in a high rate of sarcomas. Although MT overexpression was observed in this cohort of sarcomas, the immunohistochemical MT status was not predictive of the tumor response after HILP-TM treatment.

One of the most important prognostic factors in advanced ovarian cancer is the macroscopic absence of residual tumor after primary surgery. The impact of surgical outcome on the survival of patients with International Federation of Gynecology and Obstetrics (FIGO) stage IV disease is less clear and is the subject of this study. Surgical and survival data were documented throughout the multicenter prospective randomized phase III trials of the AGO-OVAR (OVAR-3/-5/-7) and were used for this exploratory analysis. In these studies, 573 patients with FIGO stage IV disease were first operated, then randomized and homogenously treated with a combination therapy comprising the intravenous application of platinum and paclitaxel. The median progression-free survival and overall survival of patients with stage IV ovarian cancer were 12.6 and 26.1 months, respectively. Multivariable Cox regression analysis for overall survival revealed that residual tumor, mucinous histological type, multiple sites of metastases, and Eastern Cooperative Oncology Group performance status were statistically significant prognostic variables. Whereas patients with macroscopically complete resection had a statistically significant improved outcome, patients with residual disease of 0.1–1 cm and patients with residual tumor of >1 cm showed similar outcome. Macroscopically complete resection in FIGO stage IV disease, irrespective of the site of distant tumor spread, is an important prognostic factor and the only prognosticator amenable to improvement by therapy. Our results suggest possible advantages of a reasonable attempt at complete cytoreduction even in FIGO stage IV disease. In addition, tumor biology could be an important factor for achieving complete resection.

Exercise capacity and heart rate profile parameters obtained from exercise stress testing as well as the subclinical coronary atherosclerosis burden from cardiac CT have been suggested to improve cardiovascular (CV) risk stratification beyond traditional risk factors (RF) in persons at risk of CV events. To study the association of exercise stress-test variables with the coronary artery calcium (CAC) burden in relation to age, sex and traditional RF in subjects without known coronary artery disease from the general population. In 3,163 subjects, CV and RF were measured, a bicycle stress test was performed and the electron beam CT-based CAC-Agatston score was quantified. Exercise capacity, chronotropic response and an abnormal HR recovery were significantly and inversely related to CAC scores in men and women in univariate unadjusted analysis. This association was diminished after adjustment for age and sex and further after adjustment for traditional risk factors. In multivariate analysis, chronotropic response in men [estimate (95% CI): 0.94 (0.91–0.97), P = 0.0005] and an abnormal HR recovery (

Objectives Do prior percutaneous coronary interventions adversely affect the outcome of subsequent coronary artery bypass grafting? We investigated this effect on a multicenter basis. Methods Eight cardiac surgical centers provided outcome data of 37,140 consecutive patients who underwent isolated first-time coronary bypass grafting between January 2000 and December 2005. Twenty-two patient characteristics and outcome variables were retrieved. Three groups of patients were analysed for in-hospital mortality and in-hospital major adverse cardiac events: patients without a previous percutaneous coronary intervention, with 1 previous intervention, and with 2 or more previous percutaneous coronary interventions before bypass grafting. A total of 29,928 patients with complete information for prior percutaneous coronary intervention underwent final analysis. Unadjusted univariate and risk-adjusted multivariate logistic regression analysis as well as computed propensity score matching were performed, based on 14 major risk factors to correct for and minimize selection bias. Results A total of 10.3% of patients had 1 previous percutaneous coronary intervention, and 3.7% of patients had 2 or more previous interventions. Risk-adjusted multivariate logistic regression analysis revealed a significant association of 2 or more previous percutaneous coronary interventions with in-hospital mortality (odds ratio [OR], 2.0; confidence interval [CI], 1.4–3.0; P = .0005) and major adverse cardiac events (OR, 1.5; CI, 1.2–1.9; P = .0013). After propensity score matching, conditional logistic regression analysis confirmed the results of adjusted analysis. A history of 2 or more previous percutaneous coronary interventions was significantly associated with in-hospital mortality (OR, 1.9; CI, 1.3–2.7; P = .0016) and major adverse cardiac events (OR, 1.5; CI, 1.2–1.9; P = .0019). Conclusions Multicenter analysis confirms that a history of multiple previous percutaneous coronary interventions increases in-hospital mortality and the incidence of major adverse cardiac events after subsequent coronary artery bypass grafting. Critical discussion of the treatment strategy in these patients is warranted.

Purpose Preoperative chemotherapy is an accepted standard in the treatment of localized esophagogastric adenocarcinoma. Adding radiation therapy to preoperative chemotherapy appears promising, but its definitive value remains unknown. Patients and Methods Patients with locally advanced (uT3-4NXM0) adenocarcinoma of the lower esophagus or gastric cardia were randomly allocated to one of two treatment groups: induction chemotherapy (15 weeks) followed by surgery (arm A); or chemotherapy (12 weeks) followed by chemoradiotherapy (3 weeks) followed by surgery (arm B). Primary outcome was overall survival time. A total of 354 patients were needed to detect a 10% increase in 3-year survival from 25% to 35% by addition of radiation therapy. The study was prematurely closed due to low accrual. Results The median observation time was 46 months. A total of 126 patients were randomly assigned and 119 eligible patients were evaluated. The number of patients undergoing complete tumor resection was not different between treatment groups (69.5% v 71.5%). Patients in arm B had a significant higher probability of showing pathologic complete response (15.6% v 2.0%) or tumor-free lymph nodes (64.4% v 37.7%) at resection. Preoperative radiation therapy improved 3-year survival rate from 27.7% to 47.4% (log-rank P = .07, hazard ratio adjusted for randomization strata variables 0.67, 95% CI, 0.41 to 1.07). Postoperative mortality was nonsignificantly increased in the chemoradiotherapy group (10.2% v 3.8%; P = .26). Conclusion Although the study was closed early and statistical significance was not achieved, results point to a survival advantage for preoperative chemoradiotherapy compared with preoperative chemotherapy in adenocarcinomas of the esophagogastric junction.