Author
Catherine M. Tangen
Other affiliations: Johns Hopkins University
Bio: Catherine M. Tangen is an academic researcher from Fred Hutchinson Cancer Research Center. The author has contributed to research in topics: Prostate cancer & Finasteride. The author has an hindex of 10, co-authored 14 publications receiving 13129 citations. Previous affiliations of Catherine M. Tangen include Johns Hopkins University.
Papers
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TL;DR: This study provides a potential standardized definition for frailty in community-dwelling older adults and offers concurrent and predictive validity for the definition, and finds that there is an intermediate stage identifying those at high risk of frailty.
Abstract: Background: Frailty is considered highly prevalent in old age and to confer high risk for falls, disability, hospitalization, and mortality. Frailty has been considered synonymous with disability, comorbidity, and other characteristics, but it is recognized that it may have a biologic basis and be a distinct clinical syndrome. A standardized definition has not yet been established.
Methods: To develop and operationalize a phenotype of frailty in older adults and assess concurrent and predictive validity, the study used data from the Cardiovascular Health Study. Participants were 5,317 men and women 65 years and older (4,735 from an original cohort recruited in 1989-90 and 582 from an African American cohort recruited in 1992-93). Both cohorts received almost identical baseline evaluations and 7 and 4 years of follow-up, respectively, with annual examinations and surveillance for outcomes including incident disease, hospitalization, falls, disability, and mortality.
Results: Frailty was defined as a clinical syndrome in which three or more of the following criteria were present: unintentional weight loss (10 lbs in past year), self-reported exhaustion, weakness (grip strength), slow walking speed, and low physical activity. The overall prevalence of frailty in this community-dwelling population was 6.9%; it increased with age and was greater in women than men. Four-year incidence was 7.2%. Frailty was associated with being African American, having lower education and income, poorer health, and having higher rates of comorbid chronic diseases and disability. There was overlap, but not concordance, in the cooccurrence of frailty, comorbidity, and disability. This frailty phenotype was independently predictive (over 3 years) of incident falls, worsening mobility or ADL disability, hospitalization, and death, with hazard ratios ranging from 1.82 to 4.46, unadjusted, and 1.29-2.24, adjusted for a number of health, disease, and social characteristics predictive of 5-year mortality. Intermediate frailty status, as indicated by the presence of one or two criteria, showed intermediate risk of these outcomes as well as increased risk of becoming frail over 3-4 years of follow-up (odds ratios for incident frailty = 4.51 unadjusted and 2.63 adjusted for covariates, compared to those with no frailty criteria at baseline).
Conclusions: This study provides a potential standardized definition for frailty in community-dwelling older adults and offers concurrent and predictive validity for the definition. It also finds that there is an intermediate stage identifying those at high risk of frailty. Finally, it provides evidence that frailty is not synonymous with either comorbidity or disability, but comorbidity is an etiologic risk factor for, and disability is an outcome of, frailty. This provides a potential basis for clinical assessment for those who are frail or at risk, and for future research to develop interventions for frailty based on a standardized ascertainment of frailty.
16,255 citations
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University of Washington1, Fred Hutchinson Cancer Research Center2, National Institutes of Health3, German Cancer Research Center4, Kaiser Permanente5, American Cancer Society6, Washington University in St. Louis7, Harvard University8, Brigham and Women's Hospital9, Case Western Reserve University10, University of Melbourne11, Cancer Council Victoria12, New York University13, Karolinska Institutet14, University of Hawaii15, University of Virginia16, Indiana University – Purdue University Indianapolis17, St. John's University18, Massey University19, University of Pittsburgh20, University of Utah21, Markey Cancer Center22, University of Kentucky23, Uppsala University24, Memorial University of Newfoundland25
TL;DR: In this article, a combined analysis of 16 studies of colorectal cancer was conducted to examine the shape of the alcohol-CRC association, investigate potential effect modifiers of the association, and examine differential effects of alcohol consumption by cancer anatomic site and stage.
Abstract: Alcohol consumption is an established risk factor for colorectal cancer (CRC). However, while studies have consistently reported elevated risk of CRC among heavy drinkers, associations at moderate levels of alcohol consumption are less clear. We conducted a combined analysis of 16 studies of CRC to examine the shape of the alcohol-CRC association, investigate potential effect modifiers of the association, and examine differential effects of alcohol consumption by cancer anatomic site and stage. We collected information on alcohol consumption for 14,276 CRC cases and 15,802 controls from 5 case-control and 11 nested case-control studies of CRC. We compared adjusted logistic regression models with linear and restricted cubic splines to select a model that best fit the association between alcohol consumption and CRC. Study-specific results were pooled using fixed-effects meta-analysis. Compared to non-/occasional drinking (≤1 g/day), light/moderate drinking (up to 2 drinks/day) was associated with a decreased risk of CRC (odds ratio [OR]: 0.92, 95% confidence interval [CI]: 0.88-0.98, p = 0.005), heavy drinking (2-3 drinks/day) was not significantly associated with CRC risk (OR: 1.11, 95% CI: 0.99-1.24, p = 0.08) and very heavy drinking (more than 3 drinks/day) was associated with a significant increased risk (OR: 1.25, 95% CI: 1.11-1.40, p < 0.001). We observed no evidence of interactions with lifestyle risk factors or of differences by cancer site or stage. These results provide further evidence that there is a J-shaped association between alcohol consumption and CRC risk. This overall pattern was not significantly modified by other CRC risk factors and there was no effect heterogeneity by tumor site or stage.
74 citations
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University of Oxford1, University of California, San Francisco2, Fred Hutchinson Cancer Research Center3, Philippine Institute for Development Studies4, National Institutes of Health5, University of Western Australia6, University of Melbourne7, Cancer Council Victoria8, Harvard University9, German Cancer Research Center10, National Institute for Health and Welfare11, University of Hawaii12, University of Occupational and Environmental Health Japan13, University of Cambridge14, University of Tennessee Health Science Center15, Kyoto Prefectural University of Medicine16, Radiation Effects Research Foundation17, Johns Hopkins University18, National Cancer Research Institute19, University of Southern California20, Uppsala University21, Hokkaido University22, University of Texas Health Science Center at San Antonio23, University of Ioannina24, Imperial College London25, University of Oslo26, Norwegian University of Science and Technology27, University of Washington28, Fiona Stanley Hospital29
TL;DR: Men with low circulating free testosterone may have a lower risk of overall prostate cancer; this may be due to a direct biological effect, or detection bias.
63 citations
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University of Bristol1, International Agency for Research on Cancer2, Fred Hutchinson Cancer Research Center3, National Institutes of Health4, University of Leeds5, German Cancer Research Center6, Royal Melbourne Hospital7, University of Melbourne8, Kaiser Permanente9, University of Virginia10, University of Barcelona11, University of Hamburg12, Imperial College London13, Ohio State University14, University of Southern California15, Cedars-Sinai Medical Center16, Lunenfeld-Tanenbaum Research Institute17, American Cancer Society18, Monash University, Clayton campus19, Cancer Council Victoria20, Dresden University of Technology21, University of Washington22, Johns Hopkins University23, University of North Carolina at Chapel Hill24, Chonnam National University25, University of Hawaii26, Karolinska University Hospital27, Karolinska Institutet28, University of León29, Utrecht University30, Memorial Sloan Kettering Cancer Center31, Cornell University32, Rappaport Faculty of Medicine33, University of Pittsburgh34, University of Utah35, University of Ioannina36, Huntsman Cancer Institute37, Wageningen University and Research Centre38, Umeå University39, Charles University in Prague40, Academy of Sciences of the Czech Republic41, First Faculty of Medicine, Charles University in Prague42, Memorial University of Newfoundland43, Vanderbilt University44
TL;DR: Adiposity was associated with numerous metabolic alterations, but none of these explained associations between adiposity and CRC, and it is suggested that higher BMI more greatly raises CRC risk among men, whereas higher WHR more greatly rises CRCrisk among women.
Abstract: Higher adiposity increases the risk of colorectal cancer (CRC), but whether this relationship varies by anatomical sub-site or by sex is unclear. Further, the metabolic alterations mediating the effects of adiposity on CRC are not fully understood. We examined sex- and site-specific associations of adiposity with CRC risk and whether adiposity-associated metabolites explain the associations of adiposity with CRC. Genetic variants from genome-wide association studies of body mass index (BMI) and waist-to-hip ratio (WHR, unadjusted for BMI; N = 806,810), and 123 metabolites from targeted nuclear magnetic resonance metabolomics (N = 24,925), were used as instruments. Sex-combined and sex-specific Mendelian randomization (MR) was conducted for BMI and WHR with CRC risk (58,221 cases and 67,694 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry). Sex-combined MR was conducted for BMI and WHR with metabolites, for metabolites with CRC, and for BMI and WHR with CRC adjusted for metabolite classes in multivariable models. In sex-specific MR analyses, higher BMI (per 4.2 kg/m2) was associated with 1.23 (95% confidence interval (CI) = 1.08, 1.38) times higher CRC odds among men (inverse-variance-weighted (IVW) model); among women, higher BMI (per 5.2 kg/m2) was associated with 1.09 (95% CI = 0.97, 1.22) times higher CRC odds. WHR (per 0.07 higher) was more strongly associated with CRC risk among women (IVW OR = 1.25, 95% CI = 1.08, 1.43) than men (IVW OR = 1.05, 95% CI = 0.81, 1.36). BMI or WHR was associated with 104/123 metabolites at false discovery rate-corrected P ≤ 0.05; several metabolites were associated with CRC, but not in directions that were consistent with the mediation of positive adiposity-CRC relations. In multivariable MR analyses, associations of BMI and WHR with CRC were not attenuated following adjustment for representative metabolite classes, e.g., the univariable IVW OR for BMI with CRC was 1.12 (95% CI = 1.00, 1.26), and this became 1.11 (95% CI = 0.99, 1.26) when adjusting for cholesterol in low-density lipoprotein particles. Our results suggest that higher BMI more greatly raises CRC risk among men, whereas higher WHR more greatly raises CRC risk among women. Adiposity was associated with numerous metabolic alterations, but none of these explained associations between adiposity and CRC. More detailed metabolomic measures are likely needed to clarify the mechanistic pathways.
59 citations
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Roswell Park Cancer Institute1, Fred Hutchinson Cancer Research Center2, National Institutes of Health3, Johns Hopkins University4, University of Southern California5, James Cook University6, Columbia University7, University of Texas MD Anderson Cancer Center8, University of Texas Health Science Center at San Antonio9
TL;DR: The findings confirm those from previous studies that there are no associations of serum estrogen with prostate cancer risk in untreated men and finasteride results in a modest increase in serum estrogen levels, which are not related to prostate cancerrisk.
Abstract: Objective
Finasteride reduces prostate cancer risk by blocking the conversion of testosterone to dihydrotestosterone. However, whether finasteride affects estrogens levels or change in estrogens affects prostate cancer risk is unknown.
47 citations
Cited by
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TL;DR: Authors/Task Force Members: Piotr Ponikowski* (Chairperson) (Poland), Adriaan A. Voors* (Co-Chair person) (The Netherlands), Stefan D. Anker (Germany), Héctor Bueno (Spain), John G. F. Cleland (UK), Andrew J. S. Coats (UK)
13,400 citations
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TL;DR: The European Working Group on Sarcopenia in Older People (EWGSOP) developed a practical clinical definition and consensus diagnostic criteria for age-related sarcopenia as discussed by the authors.
Abstract: The European Working Group on Sarcopenia in Older People (EWGSOP) developed a practical clinical definition and consensus diagnostic criteria for age-related sarcopenia. EWGSOP included representatives from four participant organisations, i.e. the European Geriatric Medicine Society, the European Society for Clinical Nutrition and Metabolism, the International Association of Gerontology and Geriatrics-European Region and the International Association of Nutrition and Aging. These organisations endorsed the findings in the final document. The group met and addressed the following questions, using the medical literature to build evidence-based answers: (i) What is sarcopenia? (ii) What parameters define sarcopenia? (iii) What variables reflect these parameters, and what measurement tools and cut-off points can be used? (iv) How does sarcopenia relate to cachexia, frailty and sarcopenic obesity? For the diagnosis of sarcopenia, EWGSOP recommends using the presence of both low muscle mass + low muscle function (strength or performance). EWGSOP variously applies these characteristics to further define conceptual stages as 'presarcopenia', 'sarcopenia' and 'severe sarcopenia'. EWGSOP reviewed a wide range of tools that can be used to measure the specific variables of muscle mass, muscle strength and physical performance. Our paper summarises currently available data defining sarcopenia cut-off points by age and gender; suggests an algorithm for sarcopenia case finding in older individuals based on measurements of gait speed, grip strength and muscle mass; and presents a list of suggested primary and secondary outcome domains for research. Once an operational definition of sarcopenia is adopted and included in the mainstream of comprehensive geriatric assessment, the next steps are to define the natural course of sarcopenia and to develop and define effective treatment.
8,440 citations
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TL;DR: ACCF/AHAIAI: angiotensin-converting enzyme inhibitor as discussed by the authors, angio-catabolizing enzyme inhibitor inhibitor inhibitor (ACS inhibitor) is a drug that is used to prevent atrial fibrillation.
Abstract: ACC/AHA
: American College of Cardiology/American Heart Association
ACCF/AHA
: American College of Cardiology Foundation/American Heart Association
ACE
: angiotensin-converting enzyme
ACEI
: angiotensin-converting enzyme inhibitor
ACS
: acute coronary syndrome
AF
: atrial fibrillation
7,489 citations
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Istanbul University1, Heidelberg University2, University of Liège3, Karolinska University Hospital4, University of Southampton5, Catholic University of the Sacred Heart6, University of Toulouse7, Newcastle upon Tyne Hospitals NHS Foundation Trust8, University of Erlangen-Nuremberg9, First Faculty of Medicine, Charles University in Prague10, University of Antwerp11, Public Health Research Institute12, University of Verona13
TL;DR: An emphasis is placed on low muscle strength as a key characteristic of sarcopenia, uses detection of low muscle quantity and quality to confirm the sarc Openia diagnosis, and provides clear cut-off points for measurements of variables that identify and characterise sarc openia.
Abstract: Background in 2010, the European Working Group on Sarcopenia in Older People (EWGSOP) published a sarcopenia definition that aimed to foster advances in identifying and caring for people with sarcopenia. In early 2018, the Working Group met again (EWGSOP2) to update the original definition in order to reflect scientific and clinical evidence that has built over the last decade. This paper presents our updated findings. Objectives to increase consistency of research design, clinical diagnoses and ultimately, care for people with sarcopenia. Recommendations sarcopenia is a muscle disease (muscle failure) rooted in adverse muscle changes that accrue across a lifetime; sarcopenia is common among adults of older age but can also occur earlier in life. In this updated consensus paper on sarcopenia, EWGSOP2: (1) focuses on low muscle strength as a key characteristic of sarcopenia, uses detection of low muscle quantity and quality to confirm the sarcopenia diagnosis, and identifies poor physical performance as indicative of severe sarcopenia; (2) updates the clinical algorithm that can be used for sarcopenia case-finding, diagnosis and confirmation, and severity determination and (3) provides clear cut-off points for measurements of variables that identify and characterise sarcopenia. Conclusions EWGSOP2's updated recommendations aim to increase awareness of sarcopenia and its risk. With these new recommendations, EWGSOP2 calls for healthcare professionals who treat patients at risk for sarcopenia to take actions that will promote early detection and treatment. We also encourage more research in the field of sarcopenia in order to prevent or delay adverse health outcomes that incur a heavy burden for patients and healthcare systems.
6,250 citations
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TL;DR: Developing more efficient methods to detect frailty and measure its severity in routine clinical practice would greatly inform the appropriate selection of elderly people for invasive procedures or drug treatments and would be the basis for a shift in the care of frail elderly people towards more appropriate goal-directed care.
5,456 citations