Effect of An Interaction Between Age and Ferritin Level on Clinical Outcomes In Peripheral Arterial Disease (PAD)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4302-4302 ◽  
Author(s):  
Leo R. Zacharski ◽  
Bruce Chow ◽  
Galina Shamayeva ◽  
Philip Lavori
Keyword(s):  
Regression Model ◽  
Iron Reduction ◽  
Primary Outcome ◽  
Proportional Hazards ◽  
Ferritin Level ◽  
Cox Proportional Hazards ◽  
Entire Cohort ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression

Abstract Abstract 4302 Background: The hypothesis that increasing iron burden (assessed by the serum ferritin level) with age contributes to the pathogenesis of cardiovascular (CVD) and other diseases of aging was tested in a 24-hospital, 6-year prospective randomized single blinded clinical trial of iron reduction by calibrated phlebotomy (JAMA 2007;297:603-9; JNCI 2008;100:996-1002). The primary outcome was all cause mortality and the secondary outcome death plus non-fatal MI and stroke (total n = 1,277 patients with PAD). Mean follow-up ferritin levels were significantly reduced in iron reduction patients (p<0.001). Although iron reduction had no significant effect on CVD outcomes overall, an association was observed for the secondary endpoint by age quartile (p for interaction = 0.004). The Cox proportional hazards regression model showed improved primary (p=0.02) and secondary (p<0.001) endpoints in the youngest age quartile patients (age 43 to 61) randomized to iron reduction versus control. Age analyzed as a continuous variable in the Cox proportional hazards regression model and the log relative hazards plots revealed that age interacted nonlinearly with iron reduction in both the primary (p=0.04) and secondary (p<0.001) endpoints. HYPOTHESIS: Iron reduction has beneficial effects on overall CVD outcomes that can be masked by interactions between age and ferritin level. METHODS: Computer randomization to iron reduction (n = 636) versus control (n = 641) groups was stratified by age, ferritin level and other prognostic variables at entry. Data tracked prospectively (including data on compliance with intervention) were subjected to pre-planned, intent-to-treat analysis. RESULTS: Mean follow-up ferritin levels declined with increasing age at entry in control patients. Older age (p = 0.027) and higher ferritin levels (p<0.001) at entry predicted poorer compliance with phlebotomy in iron reduction patients. Separation of mean follow-up ferritin levels between groups diminished with increasing age at entry. Plots of mean follow-up ferritin levels versus the log relative hazard for the primary and secondary endpoints for iron reduction patients showed significantly improved outcomes with lower mean follow-up ferritin levels (p = 0.028 and 0.044 respectively). Improvement in the primary outcome with lower ferritin levels was also found upon analysis of the entire cohort (p = 0.037). Kaplan-Meier analysis of mean follow-up ferritin levels for the entire cohort comparing patients having ferritin levels above versus below the mean showed improved primary and secondary outcomes with lower ferritin levels (p = 0.003 and 0.067 respectively). CONCLUSIONS: Lower body iron burden predicted improved clinical outcomes in patients with cardiovascular disease regardless of age or randomization status. Two factors seemed to account for the lack of an effect of intervention in the overall cohort. First, serum ferritin levels decreased with increasing age in control patients, apparently because patients with higher iron stores were more likely to die earlier. Second, younger iron reduction patients were more likely to comply with the phlebotomy intervention. Consequently, iron reduction therapy had less of a potential effect in older compared to younger patients because mean follow-up ferritin levels between groups converged with increasing age. An implication for future studies, and possibly for practice, is that adequate iron reduction targeted to patients with higher ferritin levels is more likely to be effective. These findings suggest cost – effective strategies for improving outcomes in diseases of aging. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Replacement of potatoes with other vegetables and risk of myocardial infarction in the Danish Diet, Cancer and Health cohort

2021 ◽  
pp. 1-21
Author(s):  
Anne Mette L. Würtz ◽  
Mette D. Hansen ◽  
Anne Tjønneland ◽  
Eric B. Rimm ◽  
Erik B. Schmidt ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Similar Pattern ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Heterogeneous Group ◽  
Dietary Guidelines ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Root Vegetables

ABSTRACT Intake of vegetables is recommended for the prevention of myocardial infarction (MI). However, vegetables make up a heterogeneous group, and subgroups of vegetables may be differentially associated with MI. The aim of this study was to examine replacement of potatoes with other vegetables or subgroups of other vegetables and the risk of MI. Substitutions between subgroups of other vegetables and risk of MI were also investigated. We followed 29,142 women and 26,029 men aged 50-64 years in the Danish Diet, Cancer and Health cohort. Diet was assessed at baseline by using a detailed validated FFQ. Hazards ratios (HR) with 95% CI for the incidence of MI were calculated using Cox proportional hazards regression. During 13.6 years of follow-up, 656 female and 1,694 male cases were identified. Among women, the adjusted HR for MI was 1.02 (95% CI: 0.93, 1.13) per 500 g/week replacement of potatoes with other vegetables. For vegetable subgroups, the HR was 0.93 (95% CI: 0.77, 1.13) for replacement of potatoes with fruiting vegetables and 0.91 (95% CI: 0.77, 1.07) for replacement of potatoes with other root vegetables. A higher intake of cabbage replacing other vegetable subgroups was associated with a statistically non-significant higher risk of MI. A similar pattern of associations was found when intake was expressed in kcal/week. Among men, the pattern of associations was overall found to be similar to that for women. This study supports food-based dietary guidelines recommending to consume a variety of vegetables from all subgroups.

Development and Validation of a Prognostic Nomogram Model for Recurrence of Non-Muscle Invasive Bladder Cancer

2021 ◽  
Author(s):  
Sanhe Liu ◽  
Yongzhi Li ◽  
Diansheng Cui ◽  
Yuexia Jiao ◽  
Liqun Duan ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Risk Stratification ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Muscle Invasive Bladder Cancer ◽  
Clinicopathologic Characteristics ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Muscle Invasive

Abstract BackgroundDifferent recurrence probability of non-muscle invasive bladder cancer (NMIBC) requests different adjuvant treatments and follow-up strategies. However, there is no simple, intuitive, and generally accepted clinical recurrence predictive model available for NMIBC. This study aims to construct a predictive model for the recurrence of NMIBC based on demographics and clinicopathologic characteristics from two independent centers. MethodsDemographics and clinicopathologic characteristics of 511 patients with NMIBC were retrospectively collected. Recurrence free survival (RFS) was estimated using the Kaplan-Meier method and log-rank tests. Univariate Cox proportional hazards regression analysis was used to screen variables associated with RFS, and a multivariate Cox proportional hazards regression model with a stepwise procedure was used to identify those factors of significance. A final nomogram model was built using the multivariable Cox method. The performance of the nomogram model was evaluated with respect to its calibration, discrimination, and clinical usefulness. Internal validation was assessed with bootstrap resampling. X-tile software was used for risk stratification calculated by the nomogram model. ResultsIndependent prognostic factors including tumor stage, recurrence status, and European Association of Urology (EAU) risk stratification group were introduced to the nomogram model. The model showed acceptable calibration and discrimination (area under the receiver operating characteristic [ROC] curve was 0.85; the consistency index [C-index] was 0.79 [95% CI: 0.76 to 0.82]), which was superior to the EAU risk stratification group alone. The decision curve also proved well clinical usefulness. Moreover, all populations could be stratified into three distinct risk groups by the nomogram model. ConclusionsWe established and validated a novel nomogram model that can provide individual prediction of RFS for patients with NMIBC. This intuitively prognostic nomogram model may help clinicians in postoperative treatment and follow-up decision-making.

MODELLING THE DETERMINANTS OF UNDER-FIVE CHILD MORTALITY RATES USING COX PROPORTIONAL HAZARDS REGRESSION MODEL

2021 ◽  
Vol 4 (4) ◽  
pp. 401-408
Author(s):  
M. C. Musa ◽  
O. E. Asiribo ◽  
H. G. Dikko ◽  
M. Usman ◽  
S. S. Sani
Keyword(s):  
Regression Model ◽  
Child Mortality ◽  
Proportional Hazards ◽  
Mortality Rates ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Predictor Variables ◽  
Under Five ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression

An under-five childhood mortality rates in Nigeria is still high, despite efforts of government at all levels to combat the menace. This study examined some factors that significantly affect under-five child mortality. A sample of mothers with children under the age of five from Nigeria Demographic and Health Survey data (NDHS, 2013 & 2018) was used to assess the effect of some selected predictor variables (or covariates) on childhood survival. Cox proportional hazards model is essentially a regression model popularly used for investigating the association between the survival time and one or more predictor variables. The results from final fitted Cox proportional hazards regression model that the covariates, contraceptive used by the mother, state of residence, birth weight of child and type of toilet facility used by the h-ousehold were found to be significantly associated with under-five survival in the North Central Region of Nigeria. All the calculations are performed using the R software for statistical analysis.

scholarly journals Prognostic Significance of Serum Free Amino Acids in Head and Neck Cancers

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 428 ◽  
Author(s):  
Vit Vsiansky ◽  
Marketa Svobodova ◽  
Jaromir Gumulec ◽  
Natalia Cernei ◽  
Dagmar Sterbova ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Regression Model ◽  
Head And Neck ◽  
Cell Lines ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Transformed Cells ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression

Despite distinctive advances in the field of head and neck squamous cell cancer (HNSCC) biomarker discovery, the spectrum of clinically useful prognostic serum biomarkers is limited. As metabolic activities in highly proliferative transformed cells are fundamentally different from those in non-transformed cells, specific shifts in concentration of different metabolites may serve as diagnostic or prognostic markers. Blood amino acids have been identified as promising biomarkers in different cancers before, but little is known about this field in HNSCC. Blood amino acid profiles of 140 HNSCC patients were examined using high-performance liquid chromatography. Cox proportional hazards regression model was used to assess the prognostic value of amino acid concentrations in serum. Colony forming assay was used to identify the effect of amino acids that were significant in Cox proportional hazards regression models on colony forming ability of FaDu and Detroit 562 cell lines. In the multivariable Cox regression model for overall survival (OS), palliative treatment was associated with an unfavourable prognosis while high serum levels of methionine have had a positive prognostic impact. In the relapse-free survival (RFS) multivariable model, methionine was similarly identified as a positive prognostic factor, along with tumor localization in the oropharynx. Oral cavity localization and primary radio(chemo)therapy treatment strategy have been linked to poorer RFS. 1mM serine was shown to support the forming of colonies in both tested HNSCC cell lines. Effect of methionine was exactly the opposite.

Natriuretic Peptide Levels Correlate with Pulmonary Pressures and Prospective Mortality in SCD: Use of This Biomarker To Identify Prevalence and Mortality of Pulmonary Hypertension in the MSH Cohort.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1-1
Author(s):  
Roberto Machado ◽  
Martin Steinberg ◽  
Duane Bonds ◽  
Samir Ballas ◽  
William Blackwelder ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Cell Disease ◽  
Risk Of Death ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression

Abstract Pulmonary hypertension [PH-tricuspid regurgitant jet velocity (TRV) ≥2.5 m/s] is a common complication of sickle cell disease associated with high mortality. Identification of biomarkers of PH and mortality could facilitate screening and risk stratification in this population. Validated biomarkers would provide methods for retrospective evaluation of the prevalence and prognosis of PH in large historical cohorts of patients such as the Multicenter Study of Hydroxyurea in Sickle Cell Anemia(MSH). Because brain natriuretic peptide(BNP) is released from the ventricles during pressure strain, we hypothesized that BNP levels would correlate with the severity of PH and prospective risk of death in patients with SCD. BNP was measured in 45 African-American control subjects and 230 patients with SCD. Median (interquartile range) BNP(pg/ml) was higher in patients with PH than patients without PH or controls[+PH: 206(81–701),-PH: 47(26–104), C: 29, P&lt;0.001]. BNP levels directly correlated with age (R=0.32, P&lt;0.001), creatinine (R=0.22, P&lt;0.001), LDH(R=0.31, P&lt;0.001), TRV (R=0.5, P&lt;0.001), pulmonary vascular resistance (R=0.5, P=0.001); and inversely with hemoglobin(R=0.41, P&lt;0.001), cardiac output(R=0.47, P= 0.003) and 6-minute walk distance(R=0.51, P=0.001). The area under the ROC for BNP and the diagnosis of pulmonary hypertension was 0.84 (P&lt;0.001). A cutoff value of 160 pg/ml (corresponding to the 75th percentile for the population) had 58% sensitivity and 98% specificity for the diagnosis of PH. Cox proportional hazards regression identified BNP as an independent predictor of mortality(RR 2.17,95% CI 1.2–3.8, P =0.001) with clear mortality break point at the 75th percentile(160 pg/ml). To independently explore the prevalence and associated risk of PH in patients with sickle cell disease, a BNP value of 160 pg/ml was used as an indicator of PH. BNP levels were then measured in plasma samples collected in 121 patients who were enrolled in the MSH patient’s follow-up study that started in 1996. These patients had received hydroxyurea or placebo for two years, had moderately severe disease based on study entry criteria, and had 9-years of comprehensive follow-up. An abnormal BNP level ≥160 pg/ml was present in 30% of patients in the MSH cohort. BNP levels correlated directly with age(R=0.35, P&lt;0.001) and creatinine (R=0.24, P&lt;0.001), and inversely with hemoglobin(R=−0.54, P&lt;0.001). There was no correlation between BNP and rate of painful episodes or acute chest syndrome, use of hydroxyurea or leukocyte count. A high BNP level in the MSH cohort was associated with mortality by logistic regression(OR 3.04,95% CI 1.2–7.6, P = 0.018) and Cox proportional hazards regression analysis(RR 2.87, P=0.017). The relationship remained significant for continuous log- transformed BNP values and after adjustment for other covariates. These studies confirm that PH is common, mechanistically linked to hemolytic anemia and the major risk factor for death in SCD. Provocatively, the MSH analysis suggests that rates of pain episodes in this small sample of seriously ill patients were unrelated to risk of death: this risk was largely determined by a high BNP level, which is probably explained by undiagnosed hemolysis-associated PH.

γ-H2AX as a novel prognostic marker in patients with non-small lung cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e17553-e17553
Author(s):  
Dimitrios Matthaios ◽  
Panagiotis Hountis ◽  
Grigorios Trypsianis ◽  
Athanasios Zissimopoulos ◽  
Demosthenes Bouros ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Regression Analysis ◽  
Proportional Hazards ◽  
Prognostic Indicator ◽  
Cox Proportional Hazards ◽  
Independent Effect ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression

e17553 Background: Phosphorylation of the H2AX histone is an early indicator of DNA double-strand breaks and of the resulting DNA damage response. In the present study we assessed the expression of γ-Η2ΑΧ in a cohort of 96 patients with non-small cell lung carcinoma and evaluated its role as a prognostic indicator in resectable NCSLC patients. Methods: 96 parafin-embedded specimens of non-small lung cancer patients were examined. All patients underwent radical thoracic surgery of primary tumor (lobectomy or pneumonectomy) and regional lymph nodes dissection. γ-Η2ΑΧ expression was assessed by standard immunohistochemistry.Multivariate Cox proportional hazards regression analysis, using a backward selection approach, were performed to explore the independent effect of variables on survival. All tests were two tailed and statistical significance was considered for p values <0.05. Results: Follow-up was available for all patients; mean duration of follow-up was 27.50 ± 14.07 months (range 0.2-57 months, median 24 months). Sixty-three patients (65.2%) died during the follow-up period. The mean survival time was 32.2 ± 1.9 months (95% CI = 28.5 to 35.8 months; median 30.0 months); one, two and three-year survival rates were 86.5 ± 3.5%, 57.3 ± 5.1% and 37.1 ± 5.4% respectively. Low γ-H2AX expression was associated with a significant better survival as compared with those having high γ-H2AX expression (23.2 months for high γ-Η2ΑΧ expressin vs 35.3 months for low γ-H2AX expression, p=0.009; HR=1.95, 95% CI=1.15-3.30). Further investigation with multivariate Cox proportional hazards regression analysis revealed that high expression of γ-H2AX remained independent prognostic factors of worse overall survival (HR=2.15, 95% CI=1.22-3.79, p=0.026). Conclusions: Our study is the first study to demonstrate that overexpression of γ-Η2ΑΧ is an independent prognostic indicator of worse overall survival in patients with non-small lung cancer. Further studies are needed to confirm our results.

P6428The waist-to-body mass index ratio is a better predictor for cardiovascular outcome in patients with established atherosclerotic cardiovascular disease - No u-shaped phenomenon

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
C F Hsuan ◽  
F J Lin ◽  
W K Tseng ◽  
Y W Wu ◽  
W H Yin ◽  
...  
Keyword(s):  
Dose Response ◽  
Cardiovascular Events ◽  
Primary Outcome ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Atherosclerotic Cardiovascular Disease ◽  
Spline Regression ◽  
Anthropometric Parameters ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression

Abstract Background Many studies have observed an “obesity paradox” in patients with established atherosclerotic cardiovascular disease (ASCVD), in which the body mass index (BMI)-mortality curve is U-shaped. Purpose To search a better anthropometric parameter to predict the cardiovascular events in patients with ASCVD. Methods The study was conducted from the Taiwanese Secondary Prevention for patients with AtheRosCLErotic disease (T-SPARCLE) Registry. Adult patients with stable ASCVD were enrolled. The primary composite endpoint of this study is the time of the first major cardiovascular event, defined as cardiovascular death, nonfatal myocardial infarction or stroke, or cardiac arrest with resuscitation. Dose response association between primary outcome events and various traditional anthropometric parameters and a new parameter, the waist-to-BMI ratio, was examined using the Cox proportional hazards regression model. We used restricted cubic spline regression to investigate the potential nonlinear relationship between each anthropometric measure and primary outcome events. Results A total of 6921 patients with ASCVD were included in this analysis, and were followed up for a median of 2.5 years. Multivariable Cox proportional hazards regression showed a significant positive association between the waist-to-BMI ratio and the primary outcome events (adjusted hazard ratio 1.67, 95% CI 1.12–2.49, p=0.01). Other traditional anthropometric parameters, such as BMI, weight, waist and waist-hip ratio, did not showed significant associations (p=0.10, 0.31, 0.90, and 0.52, respectively). In the restricted cubic spline regression, the positive dose response association between the primary outcome and the waist-to-BMI ratio persisted across all the waist-to-BMI ratio, and was non-linear (the likelihood ratio test for nonlinearity was statistically significant, p<0.001) with a much steeper increase in the major cardiovascular event for the waist-to-BMI ratio >3.6 cm m2/kg. Dose response curve of waist/BMI ratio Conclusion This study found the waist-to-BMI ratio to be a better predictor for major adverse cardiovascular events in established ASCVD patients than other traditional anthropometric parameters.

Sign in / Sign up

Export Citation Format

Share Document