Difference in cardiovascular disease incidence by sociodemographic factors in adolescent and young adult (AYA) cancer survivors.

6565 Background: AYA cancer survivors are at increased risk of developing cardiovascular disease (CVD) compared to AYAs without a history of cancer. In AYA cancer survivors, few population-based studies have focused on CVD risk and none have considered whether the occurrence of CVD differs by sociodemographic factors. Methods: Analyses focused on 64,918 patients aged 15-39 y at diagnosis for one of 14 first primary cancers during 1996-2010 and surviving > 2 years after diagnosis, with follow-up through 2013. Data were obtained from the California Cancer Registry and State hospital discharge data. CVD included coronary artery disease, heart failure, and stroke. We estimated the cumulative incidence of developing CVD, accounting for death as a competing risk, stratified by race/ethnicity, neighborhood socioeconomic status (SES) at diagnosis, health insurance status at diagnosis/initial treatment and cancer type. We examined the impact of CVD on mortality using multivariable Cox proportional hazards regression with CVD as a time-dependent covariate. Results: Overall, 2374 (3.7%) patients developed CVD, and 7690 (11.9%) died over the follow-up period. Survivors of acute myeloid leukemia (12.6%), acute lymphoid leukemia (11.1%), central nervous system cancer (9.0%) and non-Hodgkin lymphoma (6.0%) had the highest incidence of CVD at 10-years. Incidence was significantly higher among Blacks (6.7%) at 10-years than non-Hispanic Whites (3.0%), Hispanics (3.7%) and Asian/Pacific Islanders (3.7%) (p < 0.001). AYA survivors with public or no insurance (vs private) had a higher 10-year incidence of CVD (5.8% vs 2.9%; p < 0.001), as did survivors residing in low (vs high) SES neighborhoods (4.1% vs 2.7%; p < 0.001). These sociodemographic differences in CVD incidence were apparent across most cancer sites. The risk of death was increased by five-fold or higher among AYAs who developed CVD. Conclusions: AYA cancer survivors who were uninsured or publicly insured, of Black race/ethnicity, or who resided in lower SES neighborhoods are at increased risk for developing CVD and experiencing higher mortality. The proactive management of CVD risk factors in these subgroups may improve patient outcomes.

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Long-term risk of cardiovascular disease among colorectal cancer survivors in a population-based cohort study.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.7_suppl.113 ◽

2018 ◽

Vol 36 (7_suppl) ◽

pp. 113-113 ◽

Cited By ~ 2

Author(s):

David Baraghoshi ◽

Makenzie L. Hawkins ◽

Sarah Abdelaziz ◽

Jihye Park ◽

Yuan Wan ◽

...

Keyword(s):

Colorectal Cancer ◽

Cardiovascular Disease ◽

Cancer Survivors ◽

Cancer Diagnosis ◽

Cvd Risk ◽

Colorectal Cancer Survivors ◽

Increased Risk ◽

After Cancer

113 Background: In the United States, colorectal cancer is the fourth most common cancer and one of the leading causes of cancer death. Few studies have examined the relationship between colorectal cancer survivorship and long-term cardiovascular disease (CVD) risk. Methods: Individuals diagnosed with colorectal cancer were identified using the Utah Population Database. For a comparison group, up to 5 cancer-free individuals were matched by birth year, birth state, follow-up time and sex to each cancer case. For individuals with > 10 years of follow-up, we estimated CVD risk > 10 years after cancer diagnosis. Cox regression models were used to estimate hazard ratios (HR) and 95% Confidence Intervals. Results: Among 1,749 colorectal cancer survivors who had survived for at least 10 years, 1,001 (57.2%) were diagnosed with CVD > 10 years after cancer diagnosis. Compared to the general population, colorectal cancer survivors had an increased risk of CVD > 10 years after cancer diagnosis: HR = 2.84 (95% CI = 2.59, 3.11) for hypertension; HR = 2.66 (95% CI 2.37, 2.98) for diseases of the heart; HR = 3.91 (95% CI = 3.33, 4.58) for diseases of the arteries, arterioles and capillaries; HR = 2.58 (95% CI = 2.46, 2.99) for diseases of the veins and lymphatics; HR = 2.98 (95% CI = 2.36, 3.76) for cerebrovascular disease. Colorectal cancer survivors with ≥1 comorbidity had an increased risk of CVD > 10 years after cancer diagnosis compared to survivors with no comorbidities (HR = 1.7, 95% CI = 1.49, 1.95). Colorectal cancer survivors who were ≥65 years had an increased risk of CVD > 10 years after cancer diagnosis. Colorectal cancer survivors who were obese at the time of diagnosis had an increased risk of CVD > 10 years after cancer diagnosis when compared to survivors with normal BMIs (HR = 1.25; 95% CI = 1.06, 1.49). Conclusions: Compared to the general population, colorectal cancer survivors had an increased risk of CVD during the > 10 year follow-up period. Within colorectal cancer survivors, there was an increased risk of CVD for those that were older, had ≥1 comorbidity and were obese. The increased risk of CVD among survivors may be attributable to the lifestyle risk factors shared by colorectal cancer and CVD.

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Prevalence and Predictors of Delayed Cardiovascular Disease (CVD) Among Survivors of Adults with Hematologic Malignancies

Blood ◽

10.1182/blood.v124.21.857.857 ◽

2014 ◽

Vol 124 (21) ◽

pp. 857-857

Author(s):

Saro Armenian ◽

Lanfang Xu ◽

Can-Lan Sun ◽

Len Farol ◽

Smita Bhatia ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Cardiovascular Risk ◽

Cancer Survivors ◽

Cardiovascular Risk Factors ◽

Cancer Diagnosis ◽

Hematologic Malignancies ◽

Cvd Risk ◽

Increased Risk

Abstract Introduction: Advances in treatment strategies and supportive care have resulted in a growing number of long-term survivors of hematologic malignancies. In the general U.S. population, CVD (heart failure, stroke, myocardial infarction) is a leading cause of morbidity and mortality, and cardiovascular risk factors (CVRFs: diabetes, hypertension and dyslipidemia) are well-established modifiers of CVD risk. Childhood (Circulation 2013 22;128) and young adult (<40y at diagnosis; JNCI2014 21;106) cancer survivors have a substantially increased risk of CVD when compared to the general population; this is largely attributable to exposure to cardiotoxic therapies (anthracyclines, radiation) at a young age. Less is known regarding the magnitude of risk of CVD in individuals with hematologic malignancies diagnosed at age ≥40y, a population that accounts for the largest proportion of new cancer diagnoses in the U.S. and has a high prevalence of CVRFs. The few studies addressing this issue have been limited by small sample size, short (<1y) follow-up, varying definitions of cardiovascular outcomes, and lack of comparison to non-cancer controls. The current study overcomes these limitations. Methods: Using a retrospective cohort study design, 2,993 2+y survivors of non-Hodgkin lymphoma (NHL), lymphocytic leukemia (LL), and multiple myeloma (MM) diagnosed at age ≥40y between 2000 to 2007 and treated at Kaiser Permanent Southern California (KPSC) were included in the study. KPSC is the largest integrated managed care organization in Southern California, with documented 10-year insurance retention rates for cancer survivors exceeding 70% (JAYAO 2013 2:59). A non-cancer comparison group (N=6,272) was constructed by selecting individuals enrolled in KPSC and matched to cancer survivors (1:2) on age at diagnosis, sex, and zip-code. Cumulative incidence of CVD (ICD-9 definition: congestive heart failure, stroke, or myocardial infarction) was calculated, taking into consideration the competing risk of death. Definition of CVRFs (hypertension, diabetes, dyslipidemia) was per the National Cholesterol Education Program Adult Treatment Panel III criteria. Cox proportional hazards regression analysis was used to calculate hazard ratio (HR) estimates and 95% confidence intervals (CI), adjusted for relevant covariates. Results: Median age at cancer diagnosis was 63y (range: 40-96); 53.6% were male; 68% were non-Hispanic white; diagnoses: NHL (N=1,787 [59.7%]), LL (N=705 [23.6%], MM (N=501 [16.7%]). In cancer survivors, median time from cancer diagnosis to end of follow-up was 6.2 years (range: 2-10), representing 12,622 person-years of follow-up. Comparison with non-cancer cohort: The 8y cumulative incidence of CVD was significantly higher for NHL survivors (17% vs. 14%, p<0.01), LL (19% vs. 16%, p=0.02), and MM (21% vs. 11%, p<0.01), when compared to non-cancer subjects (Figures). Multivariable analysis adjusted for age, sex, race/ethnicity and CVRFs revealed a significantly increased risk of CVD across all cancer diagnoses (NHL: HR=1.3, 95%CI, 1.1-1.6; LL: HR=1.3, 95%CI, 1.0-1.6, MM=1.9, 95%CI, 1.5-2.5) when compared to non-cancer subjects; younger (<65y at diagnosis) MM survivors were at highest risk (HR=3.5, 95%CI, 2.2-5.6). Modifiers of CVD risk among cancer survivors: Hypertension and diabetes were independent modifiers of CVD risk. Hypertension was associated with a 1.9-fold (95%CI,1.1-3.3) increased risk of developing CVD in NHL survivors and a 3.1-fold (95%CI, 1.4-6.7) increased risk in MM survivors. Diabetes was associated with increased CVD risk across all diagnoses (NHL: HR=1.7, 95%CI, 1.2-2.4; LL: HR=1.6, 95%CI, 1.0-2.6; MM: HR=1.6, 95%CI, 1.0-2.3). Conclusions: Survivors of adult-onset NHL, LL and MM are at increased risk for developing cardiovascular disease when compared to a matched non-cancer cohort. Cardiovascular risk factors such as hypertension and diabetes are independent modifiers of risk of delayed cardiovascular disease. Taken together these data form the basis for identifying high-risk individuals for targeted surveillance, as well as aggressive management of cardiovascular risk factors. Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures No relevant conflicts of interest to declare.

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Cardiovascular Disease in Adolescents and Young Adults with Hematologic Malignancies

Blood ◽

10.1182/blood.v126.23.880.880 ◽

2015 ◽

Vol 126 (23) ◽

pp. 880-880

Author(s):

Chun Chao ◽

Lanfang Xu ◽

Cooper Robert ◽

Smita Bhatia ◽

Saro Armenian

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Cardiovascular Risk ◽

Cancer Survivors ◽

Cardiovascular Risk Factors ◽

Cancer Diagnosis ◽

Hematologic Malignancies ◽

Cvd Risk ◽

Increased Risk

Abstract Introduction: Advances in treatment strategies and supportive care have resulted in a growing number of survivors of adolescents and young adults (AYA: diagnosed 15-39y) with hematologic malignancies. In the general U.S. population, cardiovascular disease (CVD: heart failure, stroke, myocardial infarction) is a leading cause of morbidity and mortality, and cardiovascular risk factors (CVRFs: diabetes, hypertension and dyslipidemia) are well-established modifiers of CVD risk. While considerable effort has been made to characterize long-term CVD outcomes in survivors of childhood (<21y) cancer, there is a paucity of information on the magnitude and modifiers of CVD risk, as well as outcomes after onset of CVD in survivors of AYA cancers. AYAs diagnosed with hematologic malignancies may be at a higher risk of CVD when compared to the general population because of exposure to cardiotoxic therapies (anthracyclines, radiation), and the development of new CVRFs as they age. Methods: Using a retrospective cohort study design, 779 2+y survivors of non-Hodgkin lymphoma (NHL: N=274), Hodgkin lymphoma (HL: N=323), and acute leukemia (Leuk: N=182), diagnosed at age 15-39y between 1998 to 2009, and treated at Kaiser Permanent Southern California (KPSC) were included in the study. KPSC is the largest integrated managed care organization in Southern California, with documented 5-year insurance retention rates for AYA cancer survivors approaching 80% (J Adolesc Young Adult Oncol 2013 2:59). A non-cancer comparison group (N=8,062) was constructed by selecting individuals enrolled in KPSC and matched to cancer survivors (1:10) on age at diagnosis, sex, health plan membership and calendar year. Time-dependent Poisson regression was used to derive incidence rate ratio (IRR) estimates and 95% confidence intervals (CI) for CVD (ICD-9 definition: heart failure, stroke, or myocardial infarction), adjusted for relevant covariates. Kaplan-Meier curves were generated for cancer survivors, stratified by CVD status. Definition of CVRFs (hypertension, diabetes, dyslipidemia) was per an algorithm developed by KPSC's case management system, which uses a combination of ICD-9 codes, laboratory test results, and documentation of receipt of medications for these conditions (Am J Epidemiol. 2014 179:27). Results: Median age at cancer diagnosis was 29y (range: 15-39 years); 53.4% were male; 58.2% were non-Hispanic white; diagnoses: HL (41.5%), NHL (35.2%), Leuk (23.4%). In cancer survivors, median time from cancer diagnosis to end of follow-up was 5.4y (range: 2-14.9y), representing 4,961 person-years of follow-up. Comparison with non-cancer controls: Multivariable analysis adjusted for age, sex, race/ethnicity, CVRFs, smoking history and overweight/obesity, revealed a significantly increased risk of CVD across all cancer diagnoses (Overall: IRR=3.5, 95%CI, 2.0-6.1) and by certain cancer types (Leuk: IRR=4.5, 95%CI, 1.8-11.2; HL: IRR=3.0, 95%CI, 1.0-8.9; NHL: IRR=2.0, 95%, 0.7-5.6) when compared to non-cancer controls. Modifiers of CVD risk: Hypertension, diabetes, and dyslipidemia were independent modifiers of CVD risk. Hypertension was associated with a 5.1-fold (95%CI, 2.1-12.1) increased risk, diabetes was associated with a 4.4-fold (95%CI, 1.9-9.9) increased risk, and dyslipidemia was associated with a 2.8-fold (95%CI, 1.2-6.6) increased risk of CVD in AYA survivors when compared to survivors without these CVRFs. Outcomes by CVD status among cancer survivors: Overall survival was significantly worse (5y: 64%, 10y: 56%) among cancer survivors who developed CVD when compared to survivors without CVD (5y: 95%, 10y: 91%), p<0.01 (Figure). Conclusions: Survivors of AYA hematologic malignancies are at increased risk for developing cardiovascular disease when compared to a matched non-cancer controls. In these survivors, overall survival following onset of CVD is especially poor, and cardiovascular risk factors are independent modifiers of delayed cardiovascular disease risk. Taken together these data form the basis for identifying high-risk individuals for population-based targeted surveillance, as well as aggressive management of cardiovascular risk factors. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

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Identification of Biochemical and Molecular Markers of Early Aging in Childhood Cancer Survivors

10.1101/2021.04.01.438017 ◽

2021 ◽

Author(s):

Silvia Ravera ◽

Tiziana Vigliarolo ◽

Silvia Bruno ◽

Fabio Morandi ◽

Danilo Marimpietri ◽

...

Keyword(s):

Cancer Survivors ◽

Childhood Cancer ◽

Childhood Cancer Survivors ◽

Antioxidant Defenses ◽

Elderly Subjects ◽

Cancer Type ◽

Metabolism Regulation ◽

Increased Risk ◽

Early Aging ◽

The Impact

ABSTRACTPurposeSurvival rates of Childhood Cancer Patients have improved tremendously over the past four decades. However, cancer treatments are associated with an increased risk of developing an anticipated onset of chronic diseases typical of aging. Thus, we aimed to identify molecular/metabolic cellular alterations responsible for early aging in Childhood Cancer Survivors (CCS).Patients and MethodsBiochemical, proteomic and molecular biology analyses were conducted on mononuclear cells (MNCs) isolated from peripheral blood of 196 CCS, comparing the results with those obtained on MNCs of 154 healthy subjects.ResultsData demonstrate that CCS-MNCs show: i) inefficient oxidative phosphorylation associated with low energy status and a metabolic switch to lactate fermentation compared with age-matched normal controls; ii) increment of lipid peroxidation due to an unbalance among the oxidative stress production and the activation of the antioxidant defenses; (iii) significantly lower expression of genes and proteins involved in mitochondrial biogenesis and metabolism regulation, such as CLUH, PGC1-α, and SIRT6 in CCS, not observed in the age-matched healthy or elderly subjects. The application of a mathematical model based on biochemical parameters predicts that CCS have a biological age significantly increased by decades compared to the chronological age. Overall, the results show that the impact of chemo/chemoradiotherapy on mitochondria efficiency in 196 CCS was rather homogeneous, irrespective of cancer type, treatment protocols, and time elapsed from the end of the curative period.ConclusionsOur study identifies some biochemical and molecular alterations possibly contributing to the pathophysiology of anticipated aging and metabolic deficiency described in CCS. These results may be useful in identifying approaches to restore the mitochondrial function, slowing down the aging and the associated pathological conditions in CCS.

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Abstract P283: Disparities in Long-term Risk of Cardiovascular Disease by Sexual Orientation and Race/Ethnicity: the National Longitudinal Study of Adolescent Health

Circulation ◽

10.1161/circ.129.suppl_1.p283 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Cari J Clark ◽

Iris W Borowsky ◽

Alvaro Alonso ◽

Rachael A Spencer ◽

Susan A Everson-Rose

Keyword(s):

Cardiovascular Disease ◽

Sexual Orientation ◽

Longitudinal Study ◽

Adolescent Health ◽

Sexual Minorities ◽

P Value ◽

Cvd Risk ◽

National Longitudinal Study ◽

Increased Risk ◽

Race Ethnicity

Background: Risk of cardiovascular disease (CVD) may be higher in sexual minorities, but epidemiologic evidence is sparse. We used a nationally representative sample of young adults to examine sex-specific disparities in global CVD risk by sexual orientation and race/ethnicity. Methods: Data were from National Longitudinal Study of Adolescent Health subjects who participated in wave 4 (2008-09) and who had valid weights and non-missing data (7087 women; 6340 men). Age, race/ethnicity, sexual orientation, education, financial stress, and CVD risk factors (body mass index, smoking, diabetes, systolic blood pressure, and use of antihypertensive medication) were collected via an in-home interview. We calculated the 30-Year risk for total CVD using a Framingham-based prediction model. Sex-specific differences in 30-year risk of CVD by sexual orientation were calculated with weighted linear models adjusted for age, race/ethnicity, education, and financial distress. Sex-specific interactions between race/ethnicity and sexual orientation were tested. Results: Mean age was 28.9 ± .2 years; 93% (n=5912) of male participants were heterosexual, 4% (n=258) were bisexual, and 2% (n=170) were gay. 80% (n=5713) of female participants were heterosexual, 18% (n=1243) were bisexual, and 2% (n=131) were lesbian. Average 30-year risk of CVD was 17.2 ± .5% in men and 9.0 ± .3% in women. Differences in CVD risk by sexual orientation were not detectable for men (p=.59). Compared to heterosexual women, bisexual and lesbian women had a .9% (95% CI: .3, 1.4) and 2.0% (95% CI: .7, 3.2) higher risk of CVD, respectively. In race/ethnicity stratified models (interaction p-value=.01), an increased risk among sexual minorities, especially lesbians, was detectable except among Hispanic women (Figure). Conclusion: Disparities in global CVD risk were observed by sexual orientation for women and persisted across most racial/ethnic groups. Sexual orientation may be a marker of increased risk of CVD but more research on contributing factors is needed.

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The Impact of a Long-Term Rivastigmine and Donepezil Treatment on All-Cause Mortality in Patients With Alzheimer’s Disease

American Journal of Alzheimer s Disease & Other Dementias® ◽

10.1177/1533317518775044 ◽

2018 ◽

Vol 33 (6) ◽

pp. 385-393 ◽

Cited By ~ 3

Author(s):

Jakub Kazmierski ◽

Chaido Messini-Zachou ◽

Mara Gkioka ◽

Magda Tsolaki

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cox Regression ◽

Symptomatic Treatment ◽

Risk Of Death ◽

Increased Risk ◽

Functional Assessments ◽

The Impact

Cholinesterase inhibitors (ChEIs) are the mainstays of symptomatic treatment of Alzheimer’s disease (AD); however, their efficacy is limited, and their use was associated with deaths in some groups of patients. The aim of the current study was to assess the impact of the long-term use of ChEIs on mortality in patients with AD. This observational, longitudinal study included 1171 adult patients with a diagnosis of AD treated with donepezil or rivastigmine. Each patient was observed for 24 months or until death. The cognitive and functional assessments, the use of ChEIs, memantine, antipsychotics, antidepressants, and anxiolytics were recorded. The total number of deaths at the end of the observational period was 99 (8.45%). The patients who had received rivastigmine treatment were at an increased risk of death in the follow-up period. The higher risk of death in the rivastigmine group remained significant in multivariate Cox regression models.

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Western dietary pattern increases risk of cardiovascular disease in Iranian adults: a prospective population-based study

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2016-0508 ◽

2017 ◽

Vol 42 (3) ◽

pp. 326-332 ◽

Cited By ~ 9

Author(s):

Parvin Mirmiran ◽

Zahra Bahadoran ◽

Azita Zadeh Vakili ◽

Fereidoun Azizi

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Dietary Patterns ◽

Dietary Pattern ◽

Regression Models ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Western Dietary Pattern ◽

Increased Risk

Limited data are available regarding the association of major dietary patterns and risk of cardiovascular disease (CVD) in Middle Eastern countries. We aimed to evaluate the association of major dietary patterns, using factor analysis, with the risk of CVD. Participants without CVD (n = 2284) were recruited from the Tehran Lipid and Glucose Study and were followed for a mean of 4.7 years. Dietary intake of participants was assessed at baseline (2006–2008); biochemical variables were evaluated at baseline and follow-up examination. Multivariate Cox proportional hazard regression models, adjusted for potential confounders, were used to estimate risk of CVD across tertiles of dietary pattern scores. Linear regression models were used to indicate association of dietary pattern scores with changes of CVD risk factors over the study period. Two major dietary patterns, Western and traditional, were identified. During a mean 4.7 ± 1.4 years of follow-up, 57 participants experienced CVD-related events. In the fully adjusted model, we observed an increased risk of CVD-related events in the highest compared to the lowest tertile category of Western dietary pattern score (HR = 2.07, 95% CI = 1.03–4.18, P for trend = 0.01). Traditional dietary pattern was not associated with incidence of CVD or CVD risk factors. A significant association was observed between the Western dietary pattern and changes in serum insulin (β = 5.88, 95% CI = 0.34–11.4). Our findings confirm that the Western dietary pattern, characterized by higher loads of processed meats, salty snacks, sweets, and soft drinks, is a dietary risk factor for CVD in the Iranian population.

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Risk Factors for Cardiovascular Disease (CVD) in Adults with Type 1 Diabetes: Findings from Prospective Real-life T1D Exchange Registry

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa015 ◽

2020 ◽

Vol 105 (5) ◽

pp. e2032-e2038 ◽

Cited By ~ 4

Author(s):

Viral N Shah ◽

Ryan Bailey ◽

Mengdi Wu ◽

Nicole C Foster ◽

Rodica Pop-Busui ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Type 1 Diabetes ◽

Diabetic Nephropathy ◽

The United States ◽

Cvd Risk Factors ◽

Cvd Risk ◽

The Impact

Abstract Context Cardiovascular disease (CVD) is a major cause of mortality in adults with type 1 diabetes. Objective We prospectively evaluated CVD risk factors in a large, contemporary cohort of adults with type 1 diabetes living in the United States. Design Observational study of CVD and CVD risk factors over a median of 5.3 years. Setting The T1D Exchange clinic network. Patients Adults (age ≥ 18 years) with type 1 diabetes and without known CVD diagnosed before or at enrollment. Main Outcome Measure Associations between CVD risk factors and incident CVD were assessed by multivariable logistic regression. Results The study included 8,727 participants (53% female, 88% non-Hispanic white, median age 33 years [interquartile ratio {IQR} = 21, 48], type 1 diabetes duration 16 years [IQR = 9, 26]). At enrollment, median HbA1c was 7.6% (66 mmol/mol) (IQR = 6.9 [52], 8.6 [70]), 33% used a statin, and 37% used blood pressure medication. Over a mean follow-up of 4.6 years, 325 (3.7%) participants developed incident CVD. Ischemic heart disease was the most common CVD event. Increasing age, body mass index, HbA1c, presence of hypertension and dyslipidemia, increasing duration of diabetes, and diabetic nephropathy were associated with increased risk for CVD. There were no significant gender differences in CVD risk. Conclusion HbA1c, hypertension, dyslipidemia and diabetic nephropathy are important risk factors for CVD in adults with type 1 diabetes. A longer follow-up is likely required to assess the impact of other traditional CVD risk factors on incident CVD in the current era.

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Comorbidities Impact Survival in Multiple Myeloma: Analysis of the Veterans Health Administration National Database

Blood ◽

10.1182/blood.v120.21.760.760 ◽

2012 ◽

Vol 120 (21) ◽

pp. 760-760

Author(s):

Tanya Wildes ◽

Suhong Luo ◽

Graham A Colditz ◽

Kenneth R. Carson

Keyword(s):

Cardiovascular Disease ◽

Multiple Myeloma ◽

Renal Impairment ◽

Proportional Hazards ◽

First Year ◽

Risk Of Death ◽

Increased Risk ◽

Comorbidity Index ◽

The Impact ◽

Over Time

Abstract Abstract 760 Introduction: The incidence of multiple myeloma (MM) increases with age, and the prognosis worsens. Comorbidities increase in prevalence with age, yet little is known about the impact of comorbid medical conditions on outcomes in MM. Methods: In a retrospectively-assembled cohort study, all patients with MM diagnosed between 1998 and 2009 at a Veterans' Administration (VA) hospital were identified in the VA central cancer registry. Patients who received no treatment within 6 months of diagnosis were excluded, eliminating those with smoldering myeloma or who received supportive care only. Comorbidities were ascertained from ICD-9 codes present prior to the diagnosis of MM, and categorized using the Romano adaptation of the Charlson Comorbidity Index (CCI). The independent effects of age, race and comorbidities were examined using Cox proportional hazards modeling. The impact of individual comorbidities on survival was also examined, controlling for age and race. Results: A total of 2,968 patients were identified. The median age was 69 (range 27–92). The vast majority of patients (98%) were male; 28.6% of the patients were black. The median Charlson Comorbidity Index score was 2 (range 0–13). The frequencies of selected comorbidities were: diabetes (31%), renal impairment (23.8%), cardiovascular comorbidities (38.8%) and pulmonary (26.6%). The median overall survival (OS) for the entire cohort was 28.6 months at a median follow up of 26.8 months (range 0–137 months). On multivariate analysis, age was significantly associated with mortality [Hazard Ratio (HR) 1.03 per year (95% confidence intervals (CI) 1.03–1.04), p<0.0001]. Race was not significantly associated with survival [HR 0.99 (95% CI 0.90–1.09), p=0.81]. The median OS, adjusted for age and race, was 36.5 months for patients with no comorbidities, 33.9 months for patients with a CCI score of 1–2, 25.6 months for patients with a CCI score of 3–4 and 20.2 months for patients with a CCI score ≥5. The impact of comorbidities on survival violated the proportional hazards assumption, with a cut-point at 1 year, indicating that the influence of comorbidities varied over time. Relative to those with no comorbidities, the HR for death among those with a CCI score 1–2 was 1.20 (0.97–1.48) in the first year, and 1.03 (95% CI 0.89–1.18) subsequent to the first year; among those with a CCI score 3–4, the HR for death was 1.67 (95% CI 1.34–2.08) in the first year and 1.23 (95% CI 1.05–1.45) subsequently; among those with a CCI score ≥5, the risk of death in the first year doubled [HR 2.15 (95% CI 1.73–2.67)] and was increased 40% subsequently [HR 1.42 (95% CI 1.19–1.69)]. Individual prevalent comorbidities were then examined. Cardiovascular disease, renal impairment, and pulmonary disease were all significantly associated with mortality. In the first year after diagnosis, cardiovascular disease was associated with a 55% increase in mortality [HR 1.55 (95% CI 1.35–1.78)] while, subsequent to the first year, the risk was only increased about 20% [HR 1.19 (95% CI 1.07–1.39)]. The impact of renal impairment and pulmonary impairment did not vary over time; both were associated with a 25% increased risk of death [renal impairment HR 1.26 (95% CI 1.14–1.38); pulmonary disease HR 1.24 (95% CI 1.13–1.37)]. Diabetes was not associated with survival (HR 1.02, p=0.64) after controlling for age, race and cardiovascular, pulmonary or renal impairment. Conclusion: Age and comorbidities are independently associated with increased risk of mortality in MM. The influence of comorbidities varies over time, with the greatest impact noted in the first year after diagnosis of MM among those with a CCI score ≥3 and with cardiovascular disease. Further study is needed to determine whether this increased early mortality is related to increased risk of toxicity of therapy, inadequate MM therapy or both. Disclosures: No relevant conflicts of interest to declare.

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Prognostic Impact of Transfusions Intensity on Survival and Development of Thrombocytopenia in Newly Diagnosed Lower-Risk MDS Patients Participating in the European Leukemianet EU-MDS Registry

Blood ◽

10.1182/blood.v126.23.1677.1677 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1677-1677

Author(s):

Louise De Swart ◽

Tom Johnston ◽

Alexandra Smith ◽

Pierre Fenaux ◽

Argiris Symeonidis ◽

...

Keyword(s):

Lower Risk ◽

Research Funding ◽

Control Group ◽

Rapid Decline ◽

Prognostic Impact ◽

Platelet Counts ◽

Risk Of Death ◽

Increased Risk ◽

The Impact

Abstract Background The outcome of lower-risk MDS patients with red blood cell transfusions (RBCT) dependency is inferior to that of RBCT independent patients, but whether the intensity of RBCT is important for prognosis is unknown. The EUMDS Registry is a non-interventional, observational longitudinal study enrolling patients with lower-risk MDS from 142 sites in 17 countries as described elsewhere (1). The EUMDS registry has accrued 1,902 patients as of July 21, 2015. We hypothesized that RBCT intensity is an independent prognostic factor for survival. Methods We first assessed the impact of RBCT intensity in the first year post-diagnosis (1yrPD) on progression-free survival among the 1034 patients who survived at least 1yrPD and had potential for a further year of follow-up. Secondly, we developed a longitudinal model of platelet counts throughout follow-up for 1660 patients in the registry with potential for at least one year follow-up. Results Among the 1034 patients, 323 patients had died: 67 after progression to higher-risk MDS/AML and 256 without progression. A further 41 surviving patients had progressed to AML. The overall 5-year survival was 52%. In a proportional hazards regression model (Table), the risk of death or progression increased in a non-linear fashion with age at diagnosis (p<0.001). The risk of death was increased in the intermediate IPSS-R risk group compared to low risk. Patients with RARS and 5q- syndrome had a better outcome compared to RCMD. Increased RBCT intensity in 1yrPD (Table, Figure) was strongly associated with an increased risk of death (p<0.001). In the 1660 patients no significant decline in platelet counts was observed (0.16x109 platelets/l average monthly decline, p=0.16) among patients who were not RBC transfused at any time during follow-up. However platelet counts of patients receiving RBCT declined more quickly (p<0.0001) at an average rate of 1.14x109 platelets/l/month. Among the 920 RBCT dependent patients, lower platelet counts were associated with receiving more RBCT units in the preceding six months. 185 Patients had at least 2 observations both before and after becoming RBCT dependent, defined as 1st RBCT. 50% of these patients had a decreasing trend of platelets prior to their 1st RBCT and 67% had a decreasing slope of platelets after their 1st RBCT. In the control group of RBC untransfused patients, decreasing slopes of platelets occurred in around 50% of the patients throughout the whole observation period of 4 visits. Logistic regression of the risk of having a post-1st RBCT decreasing trend in platelets showed that transfused patients were at a greater risk (OR=1.7, 95% CI: 1.1-2.7) of having a post-1st RBCT decreasing trend in platelets than untransfused patients. Conclusion These multivariate regression models including age, sex, country, IPSS and WHO classification showed that more intensive RBCT treatment is associated with poor prognosis and a more rapid decline of platelets. This indicates that the intensity of RBCT should be incorporated in the regular prognostic scoring systems and the choice of therapeutic interventions. (1): De Swart L et al. Br J Haematol 2015; 170: 372-83. Disclosures Fenaux: NOVARTIS: Honoraria, Research Funding; CELGENE: Honoraria, Research Funding; JANSSEN: Honoraria, Research Funding; AMGEN: Honoraria, Research Funding. Hellström-Lindberg:Celgene Corporation: Research Funding. Sanz:JANSSEN CILAG: Honoraria, Research Funding, Speakers Bureau. Mittelman:Roche: Research Funding; Novartis Pharmaceuticals Corporation: Research Funding; GlaxoSmithKline: Research Funding; Johnson & Johnson: Research Funding, Speakers Bureau; Celgene: Research Funding, Speakers Bureau; Amgen: Research Funding. Almeida:Bristol Meyer Squibb: Speakers Bureau; Shire: Speakers Bureau; Celgene: Consultancy; Novartis: Consultancy. Park:Hospira: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding. Itzykson:Oncoethix: Research Funding. de Witte:Novartis: Research Funding.

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