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Int J Mol Epidemiol Genet 2012;3(1):66-76

Original Article
Biomarker-based score to predict mortality in persons aged 50 years and
older: a new approach in the Swedish AMORIS study

Mieke Van Hemelrijck, Danielle Harari, Hans Garmo, Niklas Hammar, Goran Walldius, Mats Lambe, Ingmar Jungner, Lars
Holmberg

King’s College London, School of Medicine, Division of Cancer Studies, Cancer Epidemiology Group, London, UK; Department
of Ageing and Health, Guys and St Thomas’ Foundation Trust and King’s College London, Division of Health and Social Care
Research; Regional Cancer Centre, Uppsala University, Uppsala, Sweden; Department of Epidemiology, Insitute of
Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; AstraZeneca R&D, Södertalje, Sweden; 6Department of
Medicine and Department of Epidemiology, Insitute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden;
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; 8Department of Medicine,
Clinical Epidemiological Unit, Karolinska Institutet and CALAB Research, Stockholm, Sweden

Received February 8, 2012; Accepted February 23, 2012; Epub February 28, 2012; Published March 15, 2012

Abstract: Background: Management of frailty is the cornerstone of geriatric medicine, but there remains a need to identify
biomarkers that can predict early death, and thereby lead to effective clinical interventions. We aimed to study the combination
of C-reactive protein (CRP), albumin, gamma-glutamyl transferase (GGT), and HDL to predict mortality. Methods: A total of
44,457 persons aged 50+ whose levels of CRP, albumin, GGT, and HDL were measured at baseline were selected from the
Swedish Apolipoprotein MOrtality RISk (AMORIS) study. A mortality score, ranging from 0 to 4, was created by adding the
number of markers with abnormal values according to the clinical cut-off (CRP > 10 mg/L, albumin < 35 mg/L, GGT > 36 kU/L,
HDL < 1.04 mmol/L). Mortality was studied with multivariate Cox proportional hazards models. Results: 2,245 persons died
from cancer, 3,276 from circulatory disease, and 1,860 from other causes. There was a positive trend between mortality score
and all-cause mortality as well as cancer and circulatory disease-specific death (e.g. HR for all-cause mortality: 1.39 (95%CI:
1.32-1.46), 2.04 (1.89-2.21), and 3.36 (2.87-3.93), for score=1, 2, and 3+, compared to score=0). Among cancer patients with no
other co-morbidities (n=1,955), there was a positive trend between the score and mortality (HR: 1.24 (95%CI: 1.0.-1.49), 2.38
(95%CI: 1.76-3.22), and 5.47 (95%CI: 2.98-10.03) for score=1, 2, and 3+ compared to score=0). Conclusions: By combining
biomarkers of different mechanisms contributing to patient frailty, we found a strong marker for mortality in persons aged 50+.
Elevated risks among cancer patients with no other co-morbidities prior to biomarker assessment call for validation in other
cohorts and testing of different combinations and cut-offs than those used here, in order to aid decision-making in treatment of
older cancer patients. (IJMEG1112002).

Keywords: Frailty, mortality, albumin, HDL-cholesterol, C-reactive protein, gamma-glutamyltransferase


Address all correspondence to:
Dr. Mieke Van
Hemelrijck, King’s College London, School of Medicine
Division of Cancer Studies, Cancer Epidemiology Group, Research Oncology
3rd Floor, Bermondsey Wing, Guy’s Hospital, London SE1 9RT,
UK.
Tel: +44(0)20 3287 9815;
E-mail: mieke.vanhemelrijck@kcl.ac.uk