Abstract WP219: Lipoprotein Subfractions Are Associated With Stroke Among 9,795 Patients in the Field Trial

Background: In the FIELD trial, a 5-year randomized double-blind placebo-controlled trial of fenofibrate vs. placebo in 9,795 adults with type 2 diabetes (T2D), the only standard lipid parameter correlating with microvascular (renal) events was triglycerides. Given the high prevalence of stroke among diabetic patients, we explored associations between lipoprotein subfractions and risk for stroke in the FIELD trial. Methods: We performed ultracentrifugation using the vertical auto profile (VAP, Atherotech) on plasma (baseline and after 6 weeks of fenofibrate). Analyses were performed using Cox proportional hazards and logistic regression for new on-study events. Results were adjusted for gender and fenofibrate or placebo allocation. Results: HDL related analytes (HDL-C, HDL3-C, apo A1, apoA2) correlated with reduced risk for all stroke. LDL and its subfractions and Lp(a)-C did not. VLDL and its subfractions, non-HDL-C, triglycerides, apo B, apo En, various ratios incorporating apo C3, and the ratios of apoB/A1 and apoB/apoA2 all correlated with increased risk for stroke. Conclusions: VAP identifies multiple lipoprotein subclasses, apoproteins, and VAP subclass/apoprotein ratios associated with stroke. Many of these measures improved with fenofibrate therapy.

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Abstract WP218: Increased Systolic Blood Pressure Variability Among Diabetic Patients is Associated With Higher Risk of Incident Stroke: A Secondary Analysis of ACCORDION

Stroke ◽

10.1161/str.51.suppl_1.wp218 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Adam H de Havenon ◽

Ka-Ho Wong ◽

Eva Mistry ◽

Mohammad Anadani ◽

Shadi Yaghi ◽

...

Keyword(s):

Blood Pressure ◽

Blood Pressure Variability ◽

Proportional Hazards ◽

Secondary Analysis ◽

Cox Proportional Hazards ◽

Diabetic Patients ◽

Adjusted Risk ◽

Cox Proportional Hazards Models ◽

Increased Risk

Background: Increased blood pressure variability (BPV) has been associated with stroke risk, but never specifically in patients with diabetes. Methods: This is a secondary analysis of the Action to Control Cardiovascular Risk in Diabetes Follow-On Study (ACCORDION), the long term follow-up extension of ACCORD. Visit-to-visit BPV was analyzed using all BP readings during the first 36 months. The primary outcome was incident ischemic or hemorrhagic stroke after 36 months. Differences in mean BPV was tested with Student’s t-test. We fit Cox proportional hazards models to estimate the adjusted risk of stroke across lowest vs. highest quintile of BPV and report hazard ratios along with 95% confidence intervals (CI). Results: Our analysis included 9,241 patients, with a mean (SD) age of 62.7 (6.6) years and 61.7% were male. Mean (SD) follow-up was 5.7 (2.4) years and number of BP readings per patient was 12.0 (4.3). Systolic, but not diastolic, BPV was higher in patients who developed stroke (Table 1). The highest quintile of SBP SD was associated with increased risk of incident stroke, independent of mean blood pressure or other potential confounders. (Table 2, Figure 1). There was no interaction between SBP SD and treatment arm assignment, although the interaction for glucose approached significance (Table 2). Conclusion: Higher systolic BPV was associated with incident stroke in a large cohort of diabetic patients. Future trials of stroke prevention may benefit from interventions targeting BPV reduction.

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Two-Year Change in Serum Total Cholesterol Is Associated With Incident Ischemic Stroke: Results From the Kailuan Study

Frontiers in Neurology ◽

10.3389/fneur.2021.710083 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yu Wang ◽

Anxin Wang ◽

Yingting Zuo ◽

Shouling Wu ◽

Xingquan Zhao

Keyword(s):

Ischemic Stroke ◽

Total Cholesterol ◽

Proportional Hazards ◽

Dynamic Change ◽

Cox Proportional Hazards ◽

Repeated Measurements ◽

Lipid Parameter ◽

Increased Risk ◽

The Relationship

Background and Purpose: Compared with one single measurement, dynamic change of lipid parameter calculated by repeated measurements has been recognized as a potential biometric to make stroke risk assessments. Total cholesterol (TC) is an important risk factor for stroke, but the relationship between TC change and incident stroke has not been investigated thoroughly. We thus aimed to explore the association between 2-year TC change and the risk of incident stroke, both ischemic and hemorrhagic, in the general population.Methods: From June 2006 to October 2007, a total of 70,999 participants with complete TC value at baseline (2006–2007) and the second examination (2008–2009) were included in our study. The change of TC was calculated as the 2-year follow-up TC subtracting baseline TC. Cox proportional hazards regression analysis was used to evaluate the association between the tertile of TC change and risk of incident stroke and stroke subtypes.Results: A total of 2,815 cases of stroke events were identified with a median follow-up period of 9.0 years. After adjusting for baseline TC and confounding factors, 2-year TC change was independently associated with increased risk of total stroke (HR 1.07, 95% CI 1.02–1.12) and ischemic stroke (HR 1.08, 95% CI 1.03–1.13) per SD (1.04 mmol/L) increase, while no significant association was obtained between TC change and intracerebral hemorrhage (p = 0.659).Conclusions: Increased 2-year TC change is associated with an elevated risk of incident total stroke and ischemic stroke, irrespective of the baseline TC value. Maintaining a sustained ideal level of TC is important for stroke prevention.

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Symptomatic Remission in Patients with Bipolar Mania: Results from a Double-Blind, Placebo-Controlled Trial of Risperidone Monotherapy

Progress in Neurotherapeutics and Neuropsychopharmacology ◽

10.1017/s1748232106000152 ◽

2007 ◽

Vol 2 (1) ◽

pp. 213-224

Author(s):

Srihari Gopal ◽

John L. Beyer ◽

David C. Steffens ◽

Michelle L. Kramer

Keyword(s):

Proportional Hazards ◽

Rating Scale ◽

Controlled Trial ◽

Significant Proportion ◽

Cox Proportional Hazards ◽

Sustained Remission ◽

Young Mania ◽

Double Blind ◽

First Onset ◽

Symptomatic Remission

ABSTRACTBackground: The purpose of this analysis was to compare symptomatic remission rates between risperidone and placebo in a completed randomized controlled trial. Design and Methods: Two hundred ninety (290) adult patients who met DSM-IV criteria for Bipolar I Disorder Manic or Mixed episode were randomized to flexible doses of risperidone or placebo for 3 weeks. An entry Young Mania Rating Scale (YMRS) score of > 20 was required at trial screening and baseline. Time to first onset of remission (as defined as a YMRS score of < 8) was assessed using Cox proportional hazards. Persence or absence of sustained remission was analyzed using logistic regression. Sustained remission was defined as maintaining a YMRS < 8 for the remainder of the trial or until censor. Results: After adjusting for presence of psychosis, baseline YMRS, gender, number of mood cycles in the previous year and treatment,the odds of sustained remission for subjects on risperidone was 5.6 (p < 0.0001). Similarly the adjusted hazard or remission for subjects on rsiperidone was 4.0 (p < 0.0001). Interpretaion: A statistically significant proportion of manic patients receiving risperidone monotherapy achieved symptomatic remission within 3 weeks as compared to placebo.

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Adjuvant lapatinib in women with early-stage HER2-positive breast cancer (HER2+ BC): Analysis of the hormone receptor-negative subgroup of the intent-to-treat (ITT) population of the TEACH trial.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.596 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 596-596

Author(s):

Ian Edward Smith ◽

Dianne M Finkelstein ◽

Joyce O'Shaughnessy ◽

Beverly Moy ◽

Bent Ejlertsen ◽

...

Keyword(s):

Hormone Receptor ◽

Proportional Hazards ◽

Early Stage ◽

Controlled Trial ◽

Disease Free Survival ◽

Cox Proportional Hazards ◽

Her2 Positive ◽

Double Blind ◽

Initial Recurrence

596 Background: TEACH is a randomized, double-blind, placebo (P)-controlled trial evaluating lapatinib (L) in reducing relapse risk in trastuzumab -naive patients (pts) previously treated with chemotherapy for HER2+ BC. The primary results (presented at SABCS 2011) showed a hazard ratio (HR) for disease-free survival (DFS) in L arm compared with P of 0.83 (95% confidence interval [CI] 0.70-1.00; stratified log-rank 2-sided P=.053). The predefined hormone receptor negative subgroup was analyzed, which in contrast to the hormone receptor positive subgroup of the ITT population (N=3147) had a significantly improved DFS. Methods: 3161 HER2+ BC pts (Stage I-IIIc) were randomized 1:1 to L daily or P for 1 year (yr). Primary endpoint was DFS in the ITT population. Central nervous system (CNS) recurrence rate was a secondary endpoint. A subgroup analysis by Cox Proportional Hazards Regression Models was performed for the hormone receptor negative pts from the ITT population. Results: 1288 pts (41%) comprised the hormone receptor negative subgroup of the ITT (L:639, and P:649). Median time from diagnosis to randomization was 2.4 (0.3-15) yrs, median follow-up was 4 yrs. Median age for this subgroup was 53 (24-87) yrs. With 85 events in L arm and 128 in P arm, the HR for DFS for hormone receptor negative pts was 0.68 (95%CI 0.52-0.89) favoring L. Most hormone receptor negative subgroups showed benefit for L: pts up to 1 yr from diagnosis (HR 0.64; 95%CI 0.41-0.99), node negative (HR 0.57; 95%CI 0.35-0.92), premenopausal (HR 0.59, 95%CI 0.37-0.94), and those who received prior anthracycline chemotherapy without taxanes (HR 0.63; 95%CI 0.43-0.92). Node positive patients had a trend to benefit from L (HR 0.74; 95%CI 0.53-1.03). CNS as one site of initial recurrence occurred in 1% in L (n=7) and P (n=8) arms. Conclusions: Lapatinib improved DFS in patients early or late in follow-up from diagnosis of HER2+, hormone receptor negative BC. Similar subset analyses are important in other large adjuvant anti-HER2 therapy trials. Results might provide a better understanding of the subtypes of HER2+ disease and help to further individualized therapy.

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Abstract 17580: Angina Pectoris in Diabetic Patients: Insights From the Duke Databank for Cardiovascular Disease

Circulation ◽

10.1161/circ.132.suppl_3.17580 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Robert J Mentz ◽

Adam Z Banks ◽

Samuel Broderick ◽

Adam D DeVore ◽

Karen Chiswell ◽

...

Keyword(s):

Angina Pectoris ◽

Proportional Hazards ◽

Medical Center ◽

Cox Proportional Hazards ◽

Diabetic Patients ◽

Increased Risk ◽

Patients With Diabetes ◽

Duke University ◽

Artery Disease

Background: Angina pectoris (AP) has different prognostic implications in various populations. Patients with diabetes mellitus (DM) may experience neuropathy such that AP may not be perceived in the setting of coronary artery disease (CAD). The association between the presence or absence of AP in DM patients with CAD is unknown. Methods: We analyzed DM patients with obstructive CAD who underwent coronary angiography at Duke University Medical Center from 2002 to 2011 and compared patients without AP to those with AP. DM and AP were defined based on physician-obtained past medical history at catheterization. Patients were categorized as no AP, atypical AP or typical AP within the 6 weeks prior. We assessed the association with subsequent cardiovascular (CV) death/CV hospitalization and all-cause mortality in patients with no or atypical AP relative to typical AP using multivariable Cox proportional hazards analysis. Results: In the Duke Databank, 5550 patients met criteria for inclusion and 1732 (31%) had no AP, 1075 (19%) had atypical AP and 2743 (50%) had typical AP. Those without AP more often had a prior MI and lower ejection fraction, but had similar HbA1c values compared to those with atypical AP or typical AP. Over a median follow-up of 5.4 years (IQR: 2.9-8.8), the lack of recent AP was associated with increased risk for outcomes (Table). Following adjustment, the lack of recent AP was independently associated with increased mortality compared to typical AP. Conclusions: In DM patients with CAD, the lack of AP was associated with increased mortality, but similar risk for CV events compared to patients with typical AP. Future studies are needed to assess whether these findings are related to increased severity of disease in those without AP or whether AP leads to differential management that improves survival.

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The Effect of Glycated Hemoglobin and Albumin-Corrected Glycated Serum Protein on Mortality in Diabetic Patients Receiving Continuous Peritoneal Dialysis

Peritoneal Dialysis International ◽

10.3747/pdi.2014.00011 ◽

2015 ◽

Vol 35 (5) ◽

pp. 566-575 ◽

Cited By ~ 3

Author(s):

Fenfen Peng ◽

Xi Xia ◽

Feng He ◽

Zhijian Li ◽

Fengxian Huang ◽

...

Keyword(s):

Peritoneal Dialysis ◽

Proportional Hazards ◽

Glycated Hemoglobin ◽

Cox Proportional Hazards ◽

Diabetic Patients ◽

Proportional Hazards Models ◽

Cox Proportional Hazards Models ◽

Increased Risk ◽

Continuous Peritoneal Dialysis

Objective To explore the effect of glycated hemoglobin (HbA1c) and albumin-corrected glycated serum proteins (Alb-GSP) on the mortality of diabetic patients receiving continuous peritoneal dialysis (PD). Methods In this single-center retrospective cohort study, incident diabetic PD patients from January 1, 2006, to December 31, 2010, were recruited, and followed up until December 31, 2011. The effect of HbA1c and Alb-GSP on mortality was evaluated by Cox proportional hazards models. Results A total of 200 patients (60% male, mean age 60.3 ± 10.6 years) with a mean follow-up of 29.0 months (range: 4.3 - 71.5 months) were recruited. Sixty-four patients died during the follow-up period, of whom 21 died of cardiovascular disease (CVD). Mean values for HbA1c, GSP and Alb-GSP were 6.7% (range: 4.1 - 12.5%), 202 μmol/L (range: 69 - 459 μmol/L), and 5.78 μmol/g (range: 2.16 - 14.98 μmol/g), respectively. The concentrations of GSP and Alb-GSP were closely correlated with HbA1c ( r = 0.41, p < 0.001 and r = 0.45, p < 0.001, respectively). In multivariate Cox proportional hazards models, patients with HbA1c ≥8% were associated with increased risk of all-cause mortality (hazard ratio [HR] = 2.29, 95% confidence interval [CI]: 1.06 - 4.96, p = 0.04), but no increased mortality in patients with 6.0% ≤ HbA1c ≤ 7.9%. Patients with Alb-GSP ≤ 4.50 μmol/g had increased all-cause and non-cardiovascular mortality (HR = 2.42, 95% CI: 1.13 - 5.19, p = 0.02; and HR = 2.98, 95% CI: 1.05 - 8.48, p = 0.04 respectively). Conclusions Increased HbA1c and decreased Alb-GSP may be associated with poorer survival in diabetic PD patients, with a non-significant trend observed for poorer survival with the highest level of Alb-GSP.

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Change of Treatment for Control of Chronic Graft-Versus-Host Disease (cGVHD) as a Time-Dependent Covariate for Nonrelapse Mortality and Survival.

Blood ◽

10.1182/blood.v110.11.833.833 ◽

2007 ◽

Vol 110 (11) ◽

pp. 833-833

Author(s):

Mary E.D. Flowers ◽

Barry Storer ◽

Paul Carpenter ◽

Afonso Vigorito ◽

Paulo Campregher ◽

...

Keyword(s):

Initial Treatment ◽

Hematopoietic Cell Transplantation ◽

Proportional Hazards ◽

Surrogate Marker ◽

Cox Proportional Hazards ◽

Time Dependent ◽

Prior History ◽

Double Blind ◽

Increased Risk ◽

New Treatment

Abstract Time to first exacerbation of cGVHD was reported recently as a prognostic risk factor for survival in a study of 96 patients (pts) by Kim et al. (doi:10.1038/sj.bmt.1705806). Pts with exacerbation of cGVHD experienced worse survival and higher nonrelapse mortality (NRM) compared to pts with no exacerbation. This association was particularly notable among pts with earlier onset of exacerbation. We conducted a retrospective study to validate these findings in 738 consecutive pts with cGVHD diagnosed after 5/1/01 without a prior history of recurrent or persistent malignancy after allogeneic hematopoietic cell transplantation. Pts had cGVHD according to NIH criteria, and the dataset did not include pts with persistent, recurrent or delayed onset of acute GVHD. Dates and the reasons for subsequent change of treatment after the initial treatment for cGVHD have been prospectively recorded since 05/01/01. Change of treatment is defined as addition of a new treatment for control of cGVHD, increased dose of corticosteroids to at least 1 mg/kg every other day for control of cGVHD, or addition of a topical immunosuppressive medication for treatment of a previously unaffected site. Change of treatment because of toxicity alone was not included, since the focus of the study was to use change of treatment as a surrogate marker for inadequate control of cGVHD. Fifty-six percent (397/738) of pts had a change of treatment for one or more of the following reasons: progressive signs or symptoms of cGVHD (n = 214), new site (n = 190), unimproved or persistent cGVHD (n = 118) or physician preference (n = 5). The median interval time to change of treatment was 3.8 months (range, 0.1–54), and 75% of the changes occurred within 9.1 months after the initial treatment. In time-dependent Cox proportional hazards regression models, change of treatment was associated with an increase in risk of NRM compared to pts without change of treatment [hazard ratio (HR), 2.14; 95% C.I, 1.5–3.1; p < 0.0001]. The HR for change of treatment within 4 months was 2.40 (95% C.I., 1.7–3.4), and the HR for a change of treatment beyond 4 months was 1.51 (95% C.I., 0.9–2.5). Thus, relative to a change of treatment within 4 months of cGVHD diagnosis, the increase in NRM associated with change in treatment after 4 months was somewhat attenuated (HR, 0.63; 95% C.I., 0.5–1.0; p = 0.05). Risk factors that were significant for changing treatment were skin involvement at diagnosis (HR, 1.31; 95% C.I, 1.0 – 1.7; p = 0.02), use of growth-factor mobilized blood cells for transplantation (HR, 1.41; 95% C.I, 1.0 – 1.9; p = 0.03), male recipient with female donor (HR, 1.26; 95% C.I, 1.0 – 1.6; p = 0.04), and HLA-mismatched recipient (HR, 1.32; 95% C.I, 1.0 – 1.7; p = 0.05). Changing treatment was strongly associated with decreased survival (HR, 3.82; 95% C.I. 2.8–5.2; p < 0.0001), but not with decreased risk of recurrent malignancy (HR = 0.80; 95% C.I., 0.5–1.3; p = 0.38). Our results show that a change of treatment is associated with increased risk of NRM, and that this increase may not be greatly affected by the time at which the change of treatment is made. The association of a change in treatment with increased NRM suggests that a first change of treatment at any time could be used as an indicator of unfavorable outcome in double-blind clinical trials of treatment for cGVHD.

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Factors that contribute to urban–rural gradients in risk of schizophrenia: Comparing Danish and Western Australian registers

Australian & New Zealand Journal of Psychiatry ◽

10.1177/00048674211009615 ◽

2021 ◽

pp. 000486742110096

Author(s):

Oleguer Plana-Ripoll ◽

Patsy Di Prinzio ◽

John J McGrath ◽

Preben B Mortensen ◽

Vera A Morgan

Keyword(s):

Confidence Interval ◽

Western Australia ◽

Urban Areas ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Indigenous Status ◽

Increased Risk ◽

The Relationship ◽

Western Australian

Introduction: An association between schizophrenia and urbanicity has long been observed, with studies in many countries, including several from Denmark, reporting that individuals born/raised in densely populated urban settings have an increased risk of developing schizophrenia compared to those born/raised in rural settings. However, these findings have not been replicated in all studies. In particular, a Western Australian study showed a gradient in the opposite direction which disappeared after adjustment for covariates. Given the different findings for Denmark and Western Australia, our aim was to investigate the relationship between schizophrenia and urbanicity in these two regions to determine which factors may be influencing the relationship. Methods: We used population-based cohorts of children born alive between 1980 and 2001 in Western Australia ( N = 428,784) and Denmark ( N = 1,357,874). Children were categorised according to the level of urbanicity of their mother’s residence at time of birth and followed-up through to 30 June 2015. Linkage to State-based registers provided information on schizophrenia diagnosis and a range of covariates. Rates of being diagnosed with schizophrenia for each category of urbanicity were estimated using Cox proportional hazards models adjusted for covariates. Results: During follow-up, 1618 (0.4%) children in Western Australia and 11,875 (0.9%) children in Denmark were diagnosed with schizophrenia. In Western Australia, those born in the most remote areas did not experience lower rates of schizophrenia than those born in the most urban areas (hazard ratio = 1.02 [95% confidence interval: 0.81, 1.29]), unlike their Danish counterparts (hazard ratio = 0.62 [95% confidence interval: 0.58, 0.66]). However, when the Western Australian cohort was restricted to children of non-Aboriginal Indigenous status, results were consistent with Danish findings (hazard ratio = 0.46 [95% confidence interval: 0.29, 0.72]). Discussion: Our study highlights the potential for disadvantaged subgroups to mask the contribution of urban-related risk factors to risk of schizophrenia and the importance of stratified analysis in such cases.

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The Relationship of Diabetes Mellitus to Efficacy of Immune Checkpoint Inhibitors in Patients with Advanced Non-Small Cell Lung Cancer

Oncology ◽

10.1159/000516671 ◽

2021 ◽

pp. 1-7

Author(s):

Oded Jacobi ◽

Yosef Landman ◽

Daniel Reinhorn ◽

Oded Icht ◽

Michal Sternschuss ◽

...

Keyword(s):

Diabetes Mellitus ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Proportional Hazards ◽

Checkpoint Inhibitors ◽

Negative Relationship ◽

Progression Free Survival ◽

Significant Negative Correlation ◽

Cox Proportional Hazards ◽

Diabetic Patients

Introduction: Immune checkpoint inhibitors (ICI) are the new standard therapy in patients with metastatic NSCLC (mNSCLC). Metformin, previously associated with improved chemotherapy efficacy in diabetic and nondiabetic cancer patients, was recently associated with increased ICI efficacy. In this study, we aimed to explore the correlations between diabetes mellitus (DM), metformin use, and benefit from ICI in mNSCLC patients. Methods: All mNSCLC patients treated with ICI in our center between February 2015 and April 2018 were identified. Demographic and clinical data were extracted retrospectively. Cox proportional hazards regression, t tests, and χ2 tests were employed to evaluate associations of progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and disease control rate (DCR), with DM status, metformin use, and HbA1c levels, as appropriate. Results: Of 249 mNSCLC patients treated with ICI, 57 (22.8%) had DM. Thirty-seven (64.9% of all diabetic patients) patients were treated with metformin. A significant negative correlation of DM with PFS and OS was demonstrated (HR 1.5 [1.01–2.06], p = 0.011, and HR 1.5 [1.08–2.08], p = 0.017, respectively). Metformin exposure had no significant correlation with PFS or OS in diabetic mNSCLC patients (HR 1.08 [0.61–1.93], p = 0.79, and HR 1.29 [0.69–2.39], p = 0.42, respectively). There were no differences between groups with respect to ORR and DCR. Conclusion: Our data show a potential negative relationship between DM and ICI efficacy in mNSCLC patients. In contrast to reports with chemotherapy, we found no positive relationship between metformin use and ICI therapy in diabetic patients with mNSCLC. Further studies are needed to evaluate the effect of metformin in nondiabetic mNSCLC patients.

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Elevated plasma growth and differentiation factor 15 predicts incident anemia in older adults aged 60 years and older

The Journals of Gerontology Series A ◽

10.1093/gerona/glaa324 ◽

2020 ◽

Author(s):

Yuko Yamaguchi ◽

Marta Zampino ◽

Toshiko Tanaka ◽

Stefania Bandinelli ◽

Yusuke Osawa ◽

...

Keyword(s):

Older Adults ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Differentiation Factor ◽

Hazards Model ◽

Increased Risk ◽

The Relationship

Abstract Background Anemia is common in older adults and associated with greater morbidity and mortality. The causes of anemia in older adults have not been completely characterized. Although elevated circulating growth and differentiation factor 15 (GDF-15) has been associated with anemia in older adults, it is not known whether elevated GDF-15 predicts the development of anemia. Methods We examined the relationship between plasma GDF-15 concentrations at baseline in 708 non-anemic adults, aged 60 years and older, with incident anemia during 15 years of follow-up among participants in the Invecchiare in Chianti (InCHIANTI) Study. Results During follow-up, 179 (25.3%) participants developed anemia. The proportion of participants who developed anemia from the lowest to highest quartile of plasma GDF-15 was 12.9%, 20.1%, 21.2%, and 45.8%, respectively. Adults in the highest quartile of plasma GDF-15 had an increased risk of developing anemia (Hazards Ratio 1.15, 95% Confidence Interval 1.09, 1.21, P<.0001) compared to those in the lower three quartiles in a multivariable Cox proportional hazards model adjusting for age, sex, serum iron, soluble transferrin receptor, ferritin, vitamin B12, congestive heart failure, diabetes mellitus, and cancer. Conclusions Circulating GDF-15 is an independent predictor for the development of anemia in older adults.

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