Q1 HR Research Articles

Soluble endothelial cell-selective adhesion molecule and incident cardiovascular events in a multiethnic population

Cell adhesion molecules are key regulators of atherosclerotic plaque development, but circulating levels of soluble fragments, such as intercellular adhesion molecule (sICAM-1) and vascular cell adhesion molecule (sVCAM-1), have yielded conflicting associations with atherosclerotic cardiovascular disease (ASCVD). Endothelial cell-selective adhesion molecule (ESAM) is expressed exclusively in platelets and endothelial cells, and soluble ESAM (sESAM) levels have been associated with prevalent subclinical atherosclerosis. We therefore hypothesized that sESAM would be associated with incident ASCVD. sESAM, sICAM-1, and sVCAM-1 were measured in 2,442 participants without CVD in the Dallas Heart Study, a probability-based population sample aged 30-65 years enrolled between 2000 and 2002. ASCVD was defined as first myocardial infarction, stroke, coronary revascularization, or CV death. A total of 162 ASCVD events were analyzed over 10.4 years. Increasing sESAM was associated with ASCVD, independent of risk factors (HR Q4 vs Q1: 2.7, 95% CI 1.6-4.6). Serial adjustment for renal function, sICAM-1, VCAM-1, and prevalent coronary calcium did not attenuate these associations. Continuous ESAM demonstrated similar findings (HR 1.31, 95% CI 1.2-1.4). Addition of sESAM to traditional risk factors improved discrimination and reclassification (delta c-index: P = .009; integrated-discrimination-improvement index P = .001; net reclassification index = 0.42, 95% CI 0.15-0.68). Neither sICAM-1 nor sVCAM-1 was independently associated with ASCVD. sESAM but not sICAM-1 or sVCAM-1 levels are associated with incident ASCVD. Further studies are warranted to investigate the role of sESAM in ASCVD.

Association between hospital volume and overall survival of patients with metastatic non-small cell lung cancer.

9044 Background: Prior studies have shown superior surgical outcomes of stage I-III non-small cell lung cancer (NSCLC) in centers with higher patient volumes. However, there is a lack of such information in stage IV NSCLC. In this study, we aim to determine the association between the number of patients with stage IV NSCLC treated annually at a treatment facility (volume) and all-cause mortality (outcome). Methods: Using the National Cancer Database, we identified patients diagnosed with stage IV NSCLC between 2004 and 2013. We classified the facilities by quartiles (Q; mean patients with NSCLC treated per year): Q1: < 13.8; Q2: 13.8 to 23.6, Q3: 23.6 to 30.3, and Q4: > 30.3. We used sandwich variance estimators to account for clustering of patients within facilities and Cox regression to determine the volume-outcome relationship, adjusting for demographic (sex, age, race), socioeconomic (insurance type), receipt of chemotherapy, and comorbid (Charlson-Deyo score) factors and year of diagnosis. Results: There were 281,654 patients with stage IV NSCLC treated at 1,275 facilities. The median age at diagnosis was 66 years, and 55.7% were men. The median annual facility volume was 23.6 patients per year (range, 1.0 to 301.4). The distribution of patients according to facility volume was: Q1: 6.6%, Q2: 14.9%, Q3: 25.4%, and Q4: 53.1%. The unadjusted median overall survival by facility volume was: Q1: 4.4 months, Q2: 4.5 months, Q3: 4.7 months, and Q4: 5.3 months ( P< .001). Multivariable analysis showed that facility volume was independently associated with all-cause mortality. Compared with patients treated at Q4 facilities, patients treated at lower-quartile facilities had a small but significantly higher risk of death (Q3 hazard ratio [HR], 1.05 [95% CI, 1.03 to 1.07]; Q2 HR, 1.06 [95% CI, 1.03 to 1.09]; Q1 HR, 1.09 [95% CI, 1.06 to 1.13]). Conclusions: Patients who were treated for stage IV NSCLC at lower-volume facilities had a significantly higher risk of all-cause mortality compared with those who were treated at lower-volume facilities. [Table: see text]

Admission Low Magnesium Level Is Associated with In-Hospital Mortality in Acute Ischemic Stroke Patients

Background: Low magnesium levels are associated with an elevated risk of stroke. In this study, we investigated the association between magnesium levels on hospital admission and in-hospital mortality in acute ischemic stroke (AIS) patients. Methods: A total of 2,485 AIS patients, enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city, were included in this study. The patients were divided into 4 groups according to their level of admission magnesium: Q1 (<0.82 mmol/L), Q2 (0.82-0.89 mmol/L), Q3 (0.89-0.98 mmol/L), and Q4 (≥0.98 mmol/L). Cox proportional hazard model was used to estimate the effect of magnesium on all-cause in-hospital mortality in AIS patients. Results: During hospitalization, 92 patients (3.7%) died from all causes. The lowest serum magnesium level (Q1) was associated with a 2.66-fold increase in the risk of in-hospital mortality in comparison to Q4 (hazard ratio [HR] 2.66; 95% CI 1.55-4.56; p-trend < 0.001). After adjusting for age, sex, time from onset to hospital admission, baseline National Institutes of Health Stroke Scale score, and other potential covariates, HR for Q1 was 2.03 (95% CI 1.11-3.70; p-trend = 0.014). Sensitivity and subgroup analyses further confirmed a significant association between lower magnesium levels and a high risk of in-hospital mortality. Conclusions: Decreased serum magnesium levels at admission were independently associated with in-hospital mortality in AIS patients.

Abstract P038: Serum Calcium, 25-hydroxyvitamin D and Incidence of Abdominal Aortic Aneurysm: The Atherosclerosis Risk in Communities Study

Introduction: Serum concentrations of calcium and 25-hydroxyvitamin D [25(OH)D] may potentially contribute to the development of abdominal aortic aneurysms (AAA), likely predominately through established AAA risk factors such as hypertension and inflammation. To date, no prospective epidemiologic studies have examined the association between calcium and 25(OH)D and AAA risk. Hypothesis: We hypothesized that 20-year risk of AAA is higher among individuals with elevated serum calcium and among those with low serum of 25(OH)D. Methods: Serum calcium and 25(OH)D were measured in Atherosclerosis Risk in Communities (ARIC) study participants without prior AAA and who attended visit 2 (1990-92) (N=13,452). Serum calcium was corrected for serum albumin. AAA events were identified through 2011 via annual follow-up phone calls for hospitalized AAAs, and through Medicare for both hospitalized and outpatient AAAs. Multi-variable Cox proportional hazards models were used. Calcium was modeled as quartiles and 25(OH)D as &lt;10, 10-&lt;20, 20-&lt;30, ≥30 ng/ml. Additionally, sex-stratified analysis was conducted. Results: The participants were mean±SD age 57±6y, 44% men and 75% white. Mean serum concentrations were 9.2±0.4 mg/dl for calcium and 24.3±8.5 ng/ml for 25(OH)D. Over a median 19.7 years of follow-up, 484 AAA cases were identified. High serum calcium was associated with an increased incidence of AAA [HR Q4 v Q1=1.60 (95% CI: 1.24-2.08)] after adjustment for demographics and with additional adjustment for height, weight and smoking [1.39 (1.05-1.82)], but not after other CVD risk factors were controlled for [1.20 (0.91-1.58)]. In the fully adjusted model, a sex-interaction was present [p-value sex*calcium interaction=0.03], whereby the association was present in women [2.28 (1.20-4.34)] not men [1.05 (0.75-1.47)]. Those with 25(OH)D ≥30 ng/ml vs. &lt;10 ng/ml had a HR for AAA of 1.54 (1.03-2.29) after demographic adjustment, but the association was attenuated with further adjustment for height, weight and smoking [1.24 (0.82-1.88)]. No sex-25(OH)D interaction was detected. As such, stratified results are not presented. Conclusions: In this large prospective cohort, there was little evidence that markers of vitamin D metabolism are associated with risk of incident AAA. The positive association of calcium with AAA among women may warrant further investigation and replication in other populations.

Effect of extended postoperative recovery on long-term oncological outcomes.

765 Background: Curative cancer surgery remains the cornerstone of treatment of localized malignancies. Extended post operative recovery (eLOS) is associated with debility and immunosuppression. We hypothesized that eLOS is associated with worse long term oncological outcome. Methods: The NCDB participant user file from 2004-13 was utilized to identify patients with localized gastrointestinal malignancies undergoing curative cancer resections. Quartiles (Qx) of length of stay (LOS) were calculated based on histology and site specific indicators. Survival modeling was performed using cox-proportional hazards and conditional models were created. Alpha of 0.05 was set for statistical significance. Results: Of 1,616,215 patients in the cohort, 577,860 patients were included who met inclusion criteria. Majority of patients were ≥65 years (56%) with a predominance of colon cancer (70%). The median length of stay (LOS) varied from 5 days (partial hepatectomy) to 10 days (esophagectomy). After adjusting for age, gender, stage, and site of disease, increasing length of stay was significantly associated with worse oncological survival with a dose response effect (Q1 HR 1.0, Q2 1.12 (1.10-1.14) p&lt;0.001, Q3 1.42 (1.41-1.44) p&lt;0.001 and Q4 1.82(1.80-1.85), p&lt;0.001). Conditional overall survival for patients who survived 3, 6 and 12 months after surgery, was worse with eLOS (p&lt;0.001). Conclusions: Longer than expected length of stay after an index curative cancer operation leads to worse overall oncological outcomes. This effect persists even after excluding patients who suffer delayed post-operative mortality within 12 months after the operation. More research needs to be done to determine if this outcome is related to perioperative immunosuppression.

Dietary Inflammatory Index, Bone Mineral Density, and Risk of Fracture in Postmenopausal Women: Results From the Women's Health Initiative.

Previous studies suggest that bone loss and fracture risk are associated with higher inflammatory milieu, potentially modifiable by diet. The primary objective of this analysis was to evaluate the association of the dietary inflammatory index (DII), a measure of the inflammatory potential of diet, with risk of hip, lower-arm, and total fracture using longitudinal data from the Women's Health Initiative Observational Study and Clinical Trials. Secondarily, we evaluated changes in bone mineral density (BMD) and DII scores. DII scores were calculated from baseline food frequency questionnaires (FFQs) completed by 160,191 participants (mean age 63 years) without history of hip fracture at enrollment. Year 3 FFQs were used to calculate a DII change score. Fractures were reported at least annually; hip fractures were confirmed by medical records. Hazard ratios for fractures were computed using multivariable-adjusted Cox proportional hazard models, further stratified by age and race/ethnicity. Pairwise comparisons of changes in hip BMD, measured by dual-energy X-ray absorptiometry from baseline, year 3, and year 6 were analyzed by quartile (Q1 = least inflammatory diet) of baseline DII scores in a subgroup of women (n = 10,290). Mean DII score improved significantly over 3 years (p < 0.01), but change was not associated with fracture risk. Baseline DII score was only associated with hip fracture risk in younger white women (HR Q4,1.48; 95% CI, 1.09 to 2.01; p = 0.01). There were no significant associations among white women older than 63 years or other races/ethnicities. Women with the least inflammatory DII scores had less loss of hip BMD (p = 0.01) by year 6, despite lower baseline hip BMD, versus women with the most inflammatory DII scores. In conclusion, a less inflammatory dietary pattern was associated with less BMD loss in postmenopausal women. A more inflammatory diet was associated with increased hip fracture risk only in white women younger than 63 years. © 2016 American Society for Bone and Mineral Research.

Association Between Treatment Facility Volume and Mortality of Patients With Multiple Myeloma.

Purpose To determine the association between the number of patients with multiple myeloma (MM) treated annually at a treatment facility (volume) and all-cause mortality (outcome). Methods Using the National Cancer Database, we identified patients diagnosed with MM between 2003 and 2011. We classified the facilities by quartiles (Q; mean patients with MM treated per year): Q1: < 3.6; Q2: 3.6 to 6.1, Q3: 6.1 to 10.3, and Q4: > 10.3. We used random intercepts to account for clustering of patients within facilities and Cox regression to determine the volume-outcome relationship, adjusting for demographic (sex, age, race, ethnicity), socioeconomic (income, education, insurance type), geographic (area of residence, treatment facility location, travel distance), and comorbid (Charlson-Deyo score) factors and year of diagnosis. Results There were 94,722 patients with MM treated at 1,333 facilities. The median age at diagnosis was 67 years, and 54.7% were men. The median annual facility volume was 6.1 patients per year (range, 0.2 to 109.9). The distribution of patients according to facility volume was: Q1: 5.2%, Q2: 12.6%, Q3: 21.9%, and Q4: 60.3%. The unadjusted median overall survival by facility volume was: Q1: 26.9 months, Q2: 29.1 months, Q3: 31.9 months, and Q4: 49.1 months ( P < .001). Multivariable analysis showed that facility volume was independently associated with all-cause mortality. Compared with patients treated at Q4 facilities, patients treated at lower-quartile facilities had a higher risk of death (Q3 hazard ratio [HR], 1.12 [95% CI, 1.08 to 1.16]; Q2 HR, 1.17 [95% CI, 1.12 to 1.21]; Q1 HR, 1.22 [95% CI, 1.17 to 1.28]). Conclusion Patients who were treated for MM at higher-volume facilities had a lower risk of mortality compared with those who were treated at lower-volume facilities.

The Dietary Inflammatory Index Is Associated with Prostate Cancer Risk in French Middle-Aged Adults in a Prospective Study

Background: Chronic inflammation is one of the mechanisms involved in carcinogenesis. Diet is a major source of pro- and anti-inflammatory compounds. The Dietary Inflammatory Index (DII) was designed to estimate its overall inflammatory potential.Objective: Our objective was to investigate the associations between the DII and overall, breast, and prostate cancer risks.Methods: This prospective study included 6542 participants [3771 women and 2771 men with a mean ± SD age of 49.2 ± 6.4 y and a BMI (in kg/m2) of 24.0 ± 3.6 at baseline] from the Supplémentation en VItamines et Minéraux AntioXydants (SU.VI.MAX) cohort who completed at least six 24-h dietary records during the first 2 y of follow-up. The DII was based on 36 food variables. Higher scores corresponded to more proinflammatory diets. A total of 559 incident cancers were diagnosed (median follow-up, 12.6 y), including 158 female breast and 123 prostate cancers (the 2 main cancer sites in this cohort). Associations were characterized by multivariable Cox proportional hazards models. Stratified analyses were performed according to the median of usual daily alcohol intake.Results: Sex-specific quartiles of the DII were positively associated with prostate cancer risk [quartile (Q) 4 compared with Q1, HR: 2.08; 95% CI: 1.06, 4.09] but not with overall or breast cancer risks. There was an interaction between the DII and alcohol intake (grams per day) on overall cancer risk (P-interaction = 0.02): the DII was positively associated with overall cancer risk in low-to-moderate alcohol drinkers (Q4 compared with Q1 HR: 1.75; 95% CI: 1.15, 2.68; P-trend = 0.02), whereas no association was detected in higher consumers of alcohol (P-trend = 0.8). This interaction was also observed for breast cancer (P-interaction = 0.001).Conclusion: Consistent with mechanistic data, findings from this study indicated that proinflammatory diets are associated with increased prostate cancer risk and, in low-to-moderate alcohol drinkers, with increased overall and breast cancer risk. The SU.VI.MAX trial was registered at clinicaltrials.gov as NCT00272428.

Model for end-stage liver disease excluding international normalized ratio (MELD-XI) score predicts heart transplant outcomes: Evidence from the registry of the United Network for Organ Sharing

Hepato-renal function is a valuable predictor of success after left ventricular assist device therapy and heart transplantation. Hence, we analyzed the importance of the Model for End-stage Liver Disease excluding international normalized ratio (MELD-XI) score to outcomes after heart transplant. Adults undergoing heart transplant from the United Network for Organ Sharing (UNOS) database were identified (1994 to 2014). Individual MELD-XI scores were calculated; patients were stratified by MELD-XI quartiles (Q1 to Q4). Multivariate logistic regression and the Cox proportional hazard model were implemented to determine any association between MELD-XI scores, survival and other outcomes. From 39,711 patients undergoing OHT during the study period, MELD-XI score [median 10.7 (interquartile range 7.0 to 14.4)] was calculated for 36,005 patients (76% male and 75% white, 34% Status 1A). Higher MELD-XI scores had higher rates of pre-transplant extracorporeal membrane oxygenation, intra-aortic balloon pump, inotrope use and mechanical ventilation (p < 0.001 for all). Adjusted long-term mortality (median follow-up 8.1 years) was associated with MELD-XI score (hazard ratio [HR] 1.021 [1.016 to 1.026], p < 0.001). The highest MELD-XI quartile was associated with an HR 1.364 [1.255 to 1.482] risk of mortality compared with Q1. MELD-XI score was also associated with increased post-transplant infections (adjusted HR Q4 vs Q1: 1.364 [1.153 to 1.614], p < 0.001), stroke (adjusted HR Q4 vs Q1: 1.410 [1.074 to 1.852], p = 0.013), dialysis (adjusted HR Q4 vs Q1: 3.982 [3.386 to 4.683], p < 0.001), rejection (adjusted HR Q4 vs Q1: 1.519 [1.286 to 1.795], p = 0.003) and prolonged hospitalization (adjusted HR Q4 vs Q1: 1.635 [1.429 to 1.871], p < 0.001). Hepato-renal dysfunction, measured with MELD-XI score, predicts morbidity and mortality in patients undergoing orthotopic heart transplantation. Etiology of hepato-renal dysfunction should be sought and treated before heart transplantation.

Fish, n - 3 polyunsaturated fatty acids and n - 6 polyunsaturated fatty acids intake and breast cancer risk: The Japan Public Health Center-based prospective study.

Limited and inconsistent studies exist on the association between the intake of fish, n - 3 polyunsaturated fatty acids (PUFA) and n - 6 PUFA and breast cancer. Fish and n - 3 PUFA support various body functions and are thought to reduce the carcinogenesis risk while n - 6 PUFA may have a positive association with cancer risk. We examined the association between intake of fish, n - 3 PUFA [including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA) and alpha-linolenic acid (ALA)] and n - 6 PUFA and breast cancer with subanalyses on estrogen (ER) and progesterone receptor (PR) status. We investigated 38,234 Japanese women aged 45-74 years from the Japan Public Health Center-based prospective study (JPHC study), and during 14.1 years of follow-up time, 556 breast cancer cases were newly diagnosed. Breast cancer risk was not associated with the intake of total fish, n - 3 PUFA and n - 6 PUFA when analyzed in totality through multivariable Cox proportional hazards regression models with age as the time scale. Intake of total n - 6 was positively associated with the development of ER+PR+ tumors [multivariable-adjusted HR Q4 vs. Q1 = 2.94 (95% CI: 1.26-6.89; ptrend = 0.02)]. Intake of EPA was associated with a decreased breast cancer risk for ER+PR+ tumors [multivariable-adjusted HR Q2 vs. Q1 = 0.47 (95% CI: 0.25-0.89; ptrend =0.47)]. While the overall association between the intake of total fish, n - 3 PUFA and n - 6 PUFA and breast cancer risk is null, for ER+PR+ tumors, a positive association was seen between n - 6 intake and breast cancer, and a marginally significant inverse association was observed for EPA intake.

Subtypes of fruit and vegetables, variety in consumption and risk of colon and rectal cancer in the European Prospective Investigation into Cancer and Nutrition.

Previously, a lower risk of colorectal cancer was observed with fruit and vegetable consumption in the European Prospective Investigation into Cancer and Nutrition within a follow-up period of 9 years which was not fully supported by a recent meta-analysis. Therefore, we were interested in the relation with extended follow-up, also focusing on single subtypes and a variety of intake of fruit and vegetables. Fruit and vegetable consumption was assessed at baseline. After an average of 13 years of follow-up, 3,370 participants were diagnosed with colon or rectal cancer. Diet diversity scores were constructed to quantify variety in fruit and vegetable consumption. A lower risk of colon cancer was observed with higher self-reported consumption of fruit and vegetable combined (HR Q4 vs. Q1 0.87, 95% CI 0.75-1.01, p for trend 0.02), but no consistent association was observed for separate consumption of fruits and vegetables. No associations with risk of rectal cancer were observed. The few observed associations for some fruit and vegetable subtypes with colon cancer risk may have been due to chance. Variety in consumption of fruits and vegetables was not associated with a lower risk of colon or rectal cancer. Although a lower risk of colon cancer is suggested with high consumption of fruit and vegetables, this study does not support a clear inverse association between fruit and vegetable consumption and colon or rectal cancer beyond a follow-up of more than 10 years. Attenuation of the risk estimates from dietary changes over time cannot be excluded, but appears unlikely.

Abstract P320: Dietary Flavonoid Intake and Ischemic Stroke

Introduction: Diets rich in plant-based foods have been associated with lower stroke risk. Plant-based foods contain a variety of potentially cardioprotective compounds, including flavonoids. We assessed the hypothesis that total flavonoid and flavonoid subclass intakes are associated with incident ischemic stroke in a population-based cohort oversampled for non-Hispanic blacks and Stroke Belt residents. Methods: Between 2003 and 2007, REGARDS enrolled black and white Americans age ≥ 45 years. Participants were 20,413 men and women who completed a Block 98 food frequency questionnaire (FFQ) and without stroke at baseline. Total flavonoid and flavonoid subclass (anthocyanidin, flavan-3-ol, flavanone, flavonol, flavone, proanthocyanidin and isoflavone) intakes were estimated using the food consumption reported by the FFQ and the flavonoid contents of each food using USDA databases. Incident strokes were captured by participant report and adjudicated by experts. Quintiles of flavonoid intake were examined as predictors of incident stroke using Cox regression models using the first quintile as the referent. Tests for trend used the quintile medians. Results: Adjusting for age and caloric intake, there was a statistically significant inverse association between total flavonoid intake and ischemic stroke (Q5 v Q1: HR=0.68; 95% CI=0.51, 0.90; p-trend=0.04) however, this association weakened after additional adjustment for demographic, socioeconomic and health behavior factors as well as self-reported CHD at baseline (Q5 v Q1: HR=0.77; 95% CI=0.58, 1.03; p-trend=0.31). A similar pattern was seen for flavanones (age, energy adjusted HR=0.74; 95% CI= 0.57, 0.95; p-trend=0.02; fully adjusted HR= 0.82; 95%CI=0.65, 1.05; p-trend=0.06). Effect estimates for total flavonoids, flavanones, proanthocyanidins, and isoflavones, suggested a protective, though nonlinear association with risk reduction emerging at the second quintile, though these did not achieve statistical significance (total flavonoids, fully adjusted HR (95% CI): Q2= 0.80 (0.61, 1.04); Q3= 0.85 (0.65, 1.11); Q4=0.92 (0.70, 1.19); Q5= 0.77 (0.58, 1.03)). Total flavonoid and flavanone intake were significantly associated with IS in fully adjusted models in women (total: Q5 v Q1 HR=0.62; 95% CI= 0.41, 0.94; p-trend=0.15; flavanones HR=0.65; 95% CI=0.44, 0.95; p-trend=0.03) but not in men (total: Q5 v Q1 HR=0.95; 95% CI= 0.63, 1.42; flavanones HR=0.80; 95% CI=0.58, 1.09; p-interaction=0.67). There was no effect modification by race or region of residence. Conclusion: Total dietary flavonoids and flavanones are associated with a reduction in risk of incident ischemic stroke, particularly in women. The emergence of a protective effect at the second quintile for total flavonoids, flavanones, proanthocyanidins and isoflavones is consistent with previous studies of dietary flavonoid intake and CVD mortality.

Prediagnostic intake of dairy products and dietary calcium and colorectal cancer survival--results from the EPIC cohort study.

We investigated whether prediagnostic reported intake of dairy products and dietary calcium is associated with colorectal cancer survival. Data from 3,859 subjects with colorectal cancer (42.1% male; mean age at diagnosis, 64.2 ± 8.1 years) in the European Investigation into Cancer and Nutrition cohort were analyzed. Intake of dairy products and dietary calcium was assessed at baseline (1992-2000) using validated, country-specific dietary questionnaires. Multivariable Cox regression models were used to calculate HR and corresponding 95% confidence intervals (CI) for colorectal cancer-specific death (n = 1,028) and all-cause death (n = 1,525) for different quartiles of intake. The consumption of total dairy products was not statistically significantly associated with risk of colorectal cancer-specific death (adjusted HR Q4 vs. Q1, 1.17; 95% CI, 0.97-1.43) nor that of all-cause death (Q4 vs. Q1, 1.16; 95% CI, 0.98-1.36). Multivariable-adjusted HRs for colorectal cancer-specific death (Q4 vs. Q1) were 1.21 (95% CI, 0.99-1.48) for milk, 1.09 (95% CI, 0.88-1.34) for yoghurt, and 0.93 (95% CI, 0.76-1.14) for cheese. The intake of dietary calcium was not associated with the risk of colorectal cancer-specific death (adjusted HR Q4 vs. Q1, 1.01; 95% CI, 0.81-1.26) nor that of all-cause death (Q4 vs. Q1, 1.01; 95% CI, 0.84-1.21). The prediagnostic reported intake of dairy products and dietary calcium is not associated with disease-specific or all-cause risk of death in patients diagnosed with colorectal cancer. The impact of diet on cancer survival is largely unknown. This study shows that despite its inverse association with colorectal cancer risk, the prediagnostic intake of dairy and dietary calcium does not affect colorectal cancer survival.

Prognostic Value of Elevated Serum Ceruloplasmin Levels in Patients With Heart Failure

BackgroundCeruloplasmin (Cp) is a copper-binding acute-phase protein that is increased in inflammatory states and deficient in Wilson's disease. Recent studies demonstrate that increased levels of Cp are associated with increased risk of developing heart failure. Our objective was to test the hypothesis that serum Cp provides incremental and independent prediction of survival in stable patients with heart failure. Methods and ResultsWe measured serum Cp levels in 890 patients with stable heart failure undergoing elective cardiac evaluation that included coronary angiography. We examined the role of Cp levels in predicting survival over 5 years of follow-up. Mean Cp level was 26.6 ± 6.9 mg/dL and demonstrated relatively weak correlation with B-type natriuretic peptide (BNP; r = 0.187; P < .001). Increased Cp levels were associated with increased 5-year all-cause mortality (quartile [Q] 4 vs Q1 hazard ratio [HR] 1.9, 95% confidence interval [CI] 1.4–2.8; P < .001). When controlled for coronary disease traditional risk factors, creatinine clearance, dialysis, body mass index, medications, history of myocardial infarction, BNP, left ventricular ejection fraction (LVEF), heart rate, QRS duration, left bundle branch blockage, and implantable cardioverter-defibrillator placement, higher Cp remained an independent predictor of increased mortality (Q4 vs Q1 HR 1.7, 95% CI 1.1–2.6; P < .05). Model quality was improved with addition of Cp to the aforementioned covariables (net reclassification improvement of 9.3%; P < .001). ConclusionsCeruloplasmin is an independent predictor of all-cause mortality in patients with heart failure. Measurement of Cp may help to identify patients at heightened mortality risk.

Abstract P348: A Novel Antioxidant Score Independently Predicts CVD Mortality Better than Any Single Antioxidant: Longitudinal Data from the Third National Health and Nutrition Examination Survey (1988-94)

Despite the implication of oxidative stress in CVD development, neither blood levels of nor supplementation with any one individual antioxidant is consistently related to CVD incidence and death. Thus, the relationship between diet-derived antioxidants and CVD remains unclear. However, many analyses consider the predictive value of only a few antioxidant markers in isolation, which may not reflect overall antioxidant status. We developed an antioxidant score and tested the hypothesis that it would be a more robust predictor of CVD death than concentrations of single antioxidants in aging adults. Quintiles of 10 serum antioxidant concentrations (α-carotene, β-carotene, β-cryptoxanthin, lutein, lycopene, vitamins A, C, E, retinyl esters and selenium), collected at baseline from 7094 (weighted N = 58,875,272) adults aged 50+ years enrolled in the Third National Health and Nutrition Examination Survey (1988-1994) were used as predictors in a time-to-death analysis using Cox regression modeling. Forty-two percent (N=3695, weighted to 26189208) of the sample was deceased at 12-18 year follow-up, with 1362 deceased due to CVD. In models adjusted for known demographic, behavioral and biological risk factors, concentration quintiles of the individual antioxidants α-carotene, lycopene, selenium and retinyl ester were significantly associated with CVD death (ps for trend ranged from 0.015 to 0.042, HRs of quintile 1 vs 5 ranged from 1.34 to 1.52). A stepwise regression method was used to identify the best combination of candidate markers, and an antioxidant score was computed using only those 6 markers (vitamins C and E, lycopene, selenium, α and β-carotene). Quintiles of the antioxidant score were also significantly associated with risk of death (p for trend = 0.004, HR for Q1 vs. Q5 = 1.88) and in a more predictive manner than a score using all 10 antioxidants (p for trend = 0.016, HR for Q1 vs. Q5 = 1.69). After controlling for traditional risk factors, an antioxidant score including vitamins C and E, lycopene, selenium, α and β-carotene was more strongly associated with rates of CVD death than individual antioxidants in a large nationally representative sample of aging adults. An antioxidant score may more closely reflect oxidative status than measures of single dietary antioxidants, and therefore be more useful when assessing risk of CVD death.

High hip fracture risk in men with severe aortic calcification: MrOS study

A significant link between cardiovascular disease and osteoporosis is established in postmenopausal women, but data for men are scarce. We tested the hypothesis that greater severity of abdominal aortic calcification (AAC) was associated with an increased risk of nonspine fracture in 5994 men aged ≥ 65 years. AAC was assessed on 5400 baseline lateral thoracolumbar radiographs using a validated visual semiquantitative score. Total hip bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. Incident nonspine fractures were centrally adjudicated. After adjustment for age, body mass index (BMI), total hip BMD, fall history, prior fracture, smoking status, comorbidities, race, and clinical center, the risk of nonspine fracture (n=805) was increased among men with higher AAC (hazard ratio [HR] quartile 4 [Q4] [AAC score ≥ 9] versus quartile 1 [Q1] [0-1], 1.36; 96% confidence interval [CI], 1.10-1.68). This association was due to an increased risk of hip fracture (n=178) among men with higher AAC (HR Q4 versus Q1, 2.33; 95% CI, 1.41-3.87). By contrast, the association between AAC and the risk of nonspine, nonhip fracture was weaker and not significant (HR Q4 versus Q1, 1.22; 95% CI, 0.96-1.55). The findings regarding higher AAC and increased risk of fracture were not altered in additional analyses accounting for degree of trauma, estimated glomerular filtration rate, presence of lumbar vertebral fractures (which may bias AAC assessment), preexisting cardiovascular disease, ankle brachial index, or competing risk of death. Thus, in this large cohort of elderly men, greater AAC was independently associated with an increased risk of hip fracture, but not with other nonspine fractures. These findings suggest that AAC assessment may be a useful method for identification of older men at high risk of hip fracture.

Post-surgical highly sensitive C-reactive protein (hsCRP) and prognosis in early stage in breast cancer (BC).

550 Background: Obesity, commonly associated with inflammation, is associated with poor prognosis in BC. Previous research suggests CRP, an obesity-associated marker of systemic inflammation, may mediate the adverse prognostic effects of obesity and be associated with fatigue. We examined the association of hsCRP with obesity-related factors, fatigue and distant disease-free and overall survival (DDFS, OS) in an early BC cohort. Methods: 501 non-diabetic women with T1-3, N0-1, M0 BC diagnosed 1989-96 provided fasting blood (mean 7.7 ± 4.3 weeks after surgery, prior to systemic therapy, stored at -80°C) which was analyzed for hsCRP (Roche Elecsys immunochemistry). 359 women also completed the EORTC QLQ-C30 (mean 8 ± 3.9 weeks post-surgery). Women were followed prospectively to 2007. Data were analyzed using Spearman's rank correlation coefficients (r) and Cox models. Results: Mean age was 50.5 ± 9.7 years; 282/159/24/36 subjects had T1/T2/T3/TX cancers; 350 were N0; 306 had ER+ and 278 PgR+ cancers (HER2 was not performed); 76/208/142 cancers were grade 1/2/3; adjuvant treatment involved radiation (369 subjects), chemotherapy (196), tamoxifen (107). Median hsCRP was 0.9 mg/L (25th/75th percentiles: 0.4/2.4 mg/L). hsCRP was correlated (all p &lt; 0.0001) with age (r = 0.25), Body Mass Index (BMI, r = 0.6), insulin (r = 0.44), Homeostasis Model Assessment (r = 0.45) and leptin (r = 0.54), but not with EORTC fatigue (r = 0.02), T or N stage, grade or ER/PgR status (any + vs. both -). Median follow-up was 12 years. hsCRP was not associated with DDFS or OS in univariate analyses (Q4 vs. Q1 HR 1.03, 95% CI 0.69-1.52, p = 0.9 and HR 1.27, 95% CI 0.86-1.86, p = 0.24 respectively) or multivariate analyses adjusting for age, T, N, grade, ER/PgR status, treatment (HR 1.02, 95% CI 0.66-1.59, p = 0.93 and HR 1.17, 95% CI 0.76-1.81, p = 0.48 respectively). Conclusions: hsCRP (measured post-op, prior to systemic therapy) was associated with age, BMI and obesity associated physiologic factors; it was not associated with fatigue, DDFS or OS. Funded by The Breast Cancer Research Foundation (New York), The Canadian Cancer Society Research Institute (formerly The Canadian Breast Cancer Research Initiative).

Abstract P067: HDL Particles, Immune Activation, Inflammatory and Coagulation Markers in Relation to CVD and All-Cause Mortality Among Adults Aged 80+

HDL particles, particularly small HDL particles, may be more functional (e.g. anti-inflammatory) than large HDL particles which carry more cholesterol, but levels are little affected by recent HDL-raising therapies that substantially raised HDL-C without decreasing CHD. Furthermore, lower levels of total and small HDL particles predict CHD and CVD, but have not been evaluated among elderly adults, for whom lipids are generally not positively related to CVD. Therefore, we hypothesized that among adults aged 80+, incident CVD and all-cause CVD mortality would be related to lower levels of total and small HDL particles in addition to higher levels of coagulation, inflammation and immune response biomarkers. Participants (n=162) without dementia at baseline (2001-2002) were followed through 2011 for incident CVD and total mortality. Concentrations of HDL particles (HDL-P) were measured by NMR spectroscopy (LipoScience, Inc), D-dimer, IL-6, sCD-14, and sIL-2r were measured using ELISA (R&amp;D Systems), and soluble receptors sIL6r, and sTNFr1/r2 were measured by Multiplex Panel (Millipore) on stored baseline plasma. Among adults with mean age=83.5 years at baseline, both CVD and total mortality over 8 years follow-up (mean= 5.2 years) were associated with lower baseline levels of total and small HDL-P (but not HDL-C, large HDL-P or larger mean HDL particle size), and higher levels of IL-6, sTNFr1 and sTNFr2 (Table). Total mortality was also associated with higher levels of D-dimer and sIL2r. In Cox models adjusted for age, sex and lipid-lowering medication, lower small HDL-P remained inversely associated with total and CVD mortality, with HR (95%CI) for Q1 vs. Q4 = 3.35(1.30, 8.62) and 5.39 (1.15, 25.34) respectively, and higher IL-6 remained associated with CVD mortality HR(95% CI) for Q4 vs. Q1= 5.22 (1.10, 24.75). Among adults aged 80+, higher IL-6 and lower total and small HDL-P levels were associated with incident CVD and total mortality over 8 years, suggesting an important anti-inflammatory role for HDL particles in late life.

Dietary patterns and the risk of type 2 diabetes in overweight and obese individuals

Although overweight is an important determinant of diabetes risk, it remains unclear whether food choices can still influence the risk for type 2 diabetes in overweight persons. In this paper, we aim to clarify the role of dietary patterns in the development of type 2 diabetes in overweight and obese individuals. We studied 20,835 overweight and obese participants in the Dutch part of the European Investigation into Cancer and Nutrition (EPIC-NL) study. Dietary intake was measured using a validated food frequency questionnaire, and dietary patterns were generated using factor analysis. Incident type 2 diabetes was verified against medical records. Cox proportional hazards models were used to assess the association between the dietary patterns (factor scores categorized in quartiles) and incident type 2 diabetes. Scoring on Pattern 1, characterized by fish, wine, chicken, raw vegetables and fruit juices, was not associated with type 2 diabetes risk after confounder adjustment. A high score on Pattern 2, characterized by soft drinks, fries and snacks, was associated with higher risk of type 2 diabetes (HR Q4 vs. Q1 (95 % CI): 1.70 (1.31; 2.20), P(trend) ≤ 0.0001), particularly among less active individuals [less active: HR Q4 vs. Q1 (95 % CI): 2.14 (1.48; 3.09), P(trend) = 0.00004, more active: HR Q4 vs. Q1 (95 % CI): 1.35 (0.93; 1.97), P(trend) = 0.01; P(interaction) = 0.02]. A high score on a pattern high in soft drinks, fries and snacks and low in fruit and vegetables was associated with higher risk of type 2 diabetes in overweight and obese subjects especially among physically less active individuals.

Rest/Activity Rhythms and Cardiovascular Disease in Older Men

Prior studies have suggested an increased risk of cardiovascular disease (CVD)-related mortality in older adults with disturbed circadian rest/activity rhythms (RARs). The objective goal of this study was to examine the association between disrupted RARs and risk of CVD events in older men. A total of 2968 men aged 67 yrs and older wore wrist actigraphs for 115 ± 18 consecutive hours. RAR parameters were computed from wrist actigraphy data and expressed as quartiles (Q). CVD events consisted of a composite outcome of coronary heart disease (CHD), stroke, and peripheral vascular disease (PVD) events. Secondary analyses examined associations between RARs and individual components of the composite outcome (CHD, stroke, and PVD). There were 490 CVD events over an average of 4.0 ± 1.2 yrs. Overall, reduced amplitude (HR = 1.31, 95% confidence interval [CI] 1.01–1.71 for Q2 vs. Q4) and greater minimum (HR = 1.33, 95% CI 1.01–1.73 for Q4 vs. Q1) were associated with an increased risk of CVD events in multivariable-adjusted models. In secondary analyses, there was an independent association between reduced amplitude (HR = 1.36, 95% CI 1.00–1.86) and greater minimum activity counts (HR = 1.39, 95% CI 1.02–1.91) with increased risk of CHD events. Reduced F value (HR = 2.88, 95% CI 1.41–5.87 for Q1 vs. Q4 and HR = 2.71, 95% CI 1.34–5.48 for Q2 vs. Q4) and later occurring acrophase of the RAR (HR = 1.65, 95% CI 1.04–2.63 for Q4 vs. Q2–3) were associated with an increased risk of PVD events. Results were similar in men without a history of CVD events. The findings revealed that among older men, measures of decreased circadian activity rhythm robustness (reduced amplitude and greater minimum activity) were associated with an increased risk of CVD events, primarily through increased risk of CHD or stroke events, whereas measures of reduced circadian activity rhythmicity were not associated with risk of CVD events overall, but were associated with an increased risk of PVD events. These results should be confirmed in other populations. (Author correspondence: E-mail: ames0047@umn.edu)