Skip to main content
Top
Published in: Population Health Metrics 1/2012

Open Access 01-12-2012 | Research

Predicting mortality with biomarkers: a population-based prospective cohort study for elderly Costa Ricans

Authors: Luis Rosero-Bixby, William H Dow

Published in: Population Health Metrics | Issue 1/2012

Login to get access

Abstract

Background

Little is known about adult health and mortality relationships outside high-income nations, partly because few datasets have contained biomarker data in representative populations. Our objective is to determine the prognostic value of biomarkers with respect to total and cardiovascular mortality in an elderly population of a middle-income country, as well as the extent to which they mediate the effects of age and sex on mortality.

Methods

This is a prospective population-based study in a nationally representative sample of elderly Costa Ricans. Baseline interviews occurred mostly in 2005 and mortality follow-up went through December 2010. Sample size after excluding observations with missing values: 2,313 individuals and 564 deaths. Main outcome: prospective death rate ratios for 22 baseline biomarkers, which were estimated with hazard regression models.

Results

Biomarkers significantly predict future death above and beyond demographic and self-reported health conditions. The studied biomarkers account for almost half of the effect of age on mortality. However, the sex gap in mortality became several times wider after controlling for biomarkers. The most powerful predictors were simple physical tests: handgrip strength, pulmonary peak flow, and walking speed. Three blood tests also predicted prospective mortality: C-reactive protein (CRP), glycated hemoglobin (HbA1c), and dehydroepiandrosterone sulfate (DHEAS). Strikingly, high blood pressure (BP) and high total cholesterol showed little or no predictive power. Anthropometric measures also failed to show significant mortality effects.

Conclusions

This study adds to the growing evidence that blood markers for CRP, HbA1c, and DHEAS, along with organ-specific functional reserve indicators (handgrip, walking speed, and pulmonary peak flow), are valuable tools for identifying vulnerable elderly. The results also highlight the need to better understand an anomaly noted previously in other settings: despite the continued medical focus on drugs for BP and cholesterol, high levels of BP and cholesterol have little predictive value of mortality in this elderly population.
Appendix
Available only for authorised users
Literature
1.
go back to reference Vaupel J: Lively questions for demographers about death at older ages. Popul Dev Rev. 2009, 35: 347-356. 10.1111/j.1728-4457.2009.00281.x.CrossRef Vaupel J: Lively questions for demographers about death at older ages. Popul Dev Rev. 2009, 35: 347-356. 10.1111/j.1728-4457.2009.00281.x.CrossRef
2.
go back to reference Doblhammer G, Hoffman R, Muth E, Westphal C, Kruse A: A systematic literature review of studies analyzing the effects of sex, age, education, marital status, obesity, and smoking on health transitions. Demogr Res. 2009, 20: 37-64.CrossRef Doblhammer G, Hoffman R, Muth E, Westphal C, Kruse A: A systematic literature review of studies analyzing the effects of sex, age, education, marital status, obesity, and smoking on health transitions. Demogr Res. 2009, 20: 37-64.CrossRef
4.
go back to reference Goldman N, Turra C, Rosero-Bixby L, Weir D, Crimmins T: Do biological measures mediate the relationship between education and health: A comparative study. Soc Sci & Med. 2010, 72: 307-315.CrossRef Goldman N, Turra C, Rosero-Bixby L, Weir D, Crimmins T: Do biological measures mediate the relationship between education and health: A comparative study. Soc Sci & Med. 2010, 72: 307-315.CrossRef
5.
go back to reference Christensen K: Human biodemography: Some challenges and possibilities for aging research. Demogr Res. 2004, 19: 1575-1586.CrossRef Christensen K: Human biodemography: Some challenges and possibilities for aging research. Demogr Res. 2004, 19: 1575-1586.CrossRef
6.
go back to reference Kannel WB, McGee D, Gordon T: A general cardiovascular risk profile: the Framingham Study. Am J Cardiol. 1976, 38: 46-51. 10.1016/0002-9149(76)90061-8.CrossRefPubMed Kannel WB, McGee D, Gordon T: A general cardiovascular risk profile: the Framingham Study. Am J Cardiol. 1976, 38: 46-51. 10.1016/0002-9149(76)90061-8.CrossRefPubMed
7.
go back to reference D’Agostino RB, Grundy S, Sullivan LM, Wilson P, Group CRP: Validation of the Framingham coronary heart disease prediction scores: results of a multiple ethnic groups investigation. JAMA. 2001, 286: 180-187. 10.1001/jama.286.2.180.CrossRefPubMed D’Agostino RB, Grundy S, Sullivan LM, Wilson P, Group CRP: Validation of the Framingham coronary heart disease prediction scores: results of a multiple ethnic groups investigation. JAMA. 2001, 286: 180-187. 10.1001/jama.286.2.180.CrossRefPubMed
8.
go back to reference D’Agostino RB, Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM, Kannel WB: General Cardiovascular Risk Profile for Use in Primary Care. The Framingham Heart Study. Circulation. 2008, 117: 743-753. 10.1161/CIRCULATIONAHA.107.699579.CrossRefPubMed D’Agostino RB, Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM, Kannel WB: General Cardiovascular Risk Profile for Use in Primary Care. The Framingham Heart Study. Circulation. 2008, 117: 743-753. 10.1161/CIRCULATIONAHA.107.699579.CrossRefPubMed
9.
go back to reference ERICA Research Group: Prediction of coronary heart disease in Europe. The 2nd report of the WHO-ERICA project. Europe Heart Journal. 1991, 12: 291-297. ERICA Research Group: Prediction of coronary heart disease in Europe. The 2nd report of the WHO-ERICA project. Europe Heart Journal. 1991, 12: 291-297.
10.
go back to reference Koenig W, Lowel H, Baumert J, Meisinger C: C-reactive protein modulates risk prediction based on the Framingham Score: implications for future risk assessment: results from a large cohort study in southern Germany. Circulation. 2004, 109: 1349-1353. 10.1161/01.CIR.0000120707.98922.E3.CrossRefPubMed Koenig W, Lowel H, Baumert J, Meisinger C: C-reactive protein modulates risk prediction based on the Framingham Score: implications for future risk assessment: results from a large cohort study in southern Germany. Circulation. 2004, 109: 1349-1353. 10.1161/01.CIR.0000120707.98922.E3.CrossRefPubMed
11.
go back to reference Sattar N, Murray HM, Welsh P, de Craen AJ, Lowe GD, Jukema JW, Macfarlane PW, Murphy MB, Stott DJ, Westendorp RG, et al: Are markers of inflammation more strongly associated with risk for fatal than for nonfatal vascular events?. Plos Medicine. 2009, 6: 1-10.CrossRef Sattar N, Murray HM, Welsh P, de Craen AJ, Lowe GD, Jukema JW, Macfarlane PW, Murphy MB, Stott DJ, Westendorp RG, et al: Are markers of inflammation more strongly associated with risk for fatal than for nonfatal vascular events?. Plos Medicine. 2009, 6: 1-10.CrossRef
12.
go back to reference Gruenewald TL, Seeman TE, Ryff CD, Karlamangla AS, Singer BH: Combinations of biomarkers predictive of later life mortality. PNAS. 2006, 103: 14158-14163. 10.1073/pnas.0606215103.CrossRefPubMedPubMedCentral Gruenewald TL, Seeman TE, Ryff CD, Karlamangla AS, Singer BH: Combinations of biomarkers predictive of later life mortality. PNAS. 2006, 103: 14158-14163. 10.1073/pnas.0606215103.CrossRefPubMedPubMedCentral
13.
go back to reference Goldman N, Turra C, Glei DA, Splaki C, Lin YH, Weinstein M: Predicting mortality from clinical and nonclinical biomarkers. J Gerontology, Series A: Med Sci Biological Sci. 2006, 61: 1070-1074. 10.1093/gerona/61.10.1070.CrossRef Goldman N, Turra C, Glei DA, Splaki C, Lin YH, Weinstein M: Predicting mortality from clinical and nonclinical biomarkers. J Gerontology, Series A: Med Sci Biological Sci. 2006, 61: 1070-1074. 10.1093/gerona/61.10.1070.CrossRef
14.
go back to reference Katz D, Foxman B: How well do prediction equations predict? Using receiver operating characteristic curves and accuracy curves to compare validity and generalizability. Epidemiology. 1993, 4: 319-326. 10.1097/00001648-199307000-00007.CrossRefPubMed Katz D, Foxman B: How well do prediction equations predict? Using receiver operating characteristic curves and accuracy curves to compare validity and generalizability. Epidemiology. 1993, 4: 319-326. 10.1097/00001648-199307000-00007.CrossRefPubMed
15.
go back to reference Wald NJ, Simmonds M, Morris JK: Screening for future cardiovascular disease using age alone compared with multiple risk factors and age. PLoS One. 2011, 6: e18742-10.1371/journal.pone.0018742.CrossRefPubMedPubMedCentral Wald NJ, Simmonds M, Morris JK: Screening for future cardiovascular disease using age alone compared with multiple risk factors and age. PLoS One. 2011, 6: e18742-10.1371/journal.pone.0018742.CrossRefPubMedPubMedCentral
16.
go back to reference Behrman JR, Behrman JA, Perez MN: Out of sync? Demographic and other social science research on health conditions in developing countries. Demogr Res. 2011, 24: 45-78.CrossRefPubMedPubMedCentral Behrman JR, Behrman JA, Perez MN: Out of sync? Demographic and other social science research on health conditions in developing countries. Demogr Res. 2011, 24: 45-78.CrossRefPubMedPubMedCentral
17.
go back to reference Rosero-Bixby L, Dow W: Surprising SES gradients in mortality, health and biomarkers in a Latin American population of adults. J Gerontology Social Sci. 2009, 64: 105-117.CrossRef Rosero-Bixby L, Dow W: Surprising SES gradients in mortality, health and biomarkers in a Latin American population of adults. J Gerontology Social Sci. 2009, 64: 105-117.CrossRef
19.
go back to reference Buettner D: The Blue Zones: Lessons for Living Longer From the People Who’ve Lived the Longest. 2010, National Geographic Society, Washington, D. C. Buettner D: The Blue Zones: Lessons for Living Longer From the People Who’ve Lived the Longest. 2010, National Geographic Society, Washington, D. C.
20.
go back to reference Méndez-Chacón E, Rosero-Bixby L, Fernández-Rojas X, Barrantes-Jiménez K: Comparación de los resultados de pruebas de laboratorio seleccionadas de un estudio poblacional de adultos mayores de Costa Rica. Población y Salud en Mesoamérica. 2007, 5: Article N. 4- Méndez-Chacón E, Rosero-Bixby L, Fernández-Rojas X, Barrantes-Jiménez K: Comparación de los resultados de pruebas de laboratorio seleccionadas de un estudio poblacional de adultos mayores de Costa Rica. Población y Salud en Mesoamérica. 2007, 5: Article N. 4-
21.
go back to reference Missov TI, Lenart A: Linking period and cohort life-expectancy linear increases in Gompertz proportional hazards models. Demogr Res. 2011, 24: 455-468.CrossRef Missov TI, Lenart A: Linking period and cohort life-expectancy linear increases in Gompertz proportional hazards models. Demogr Res. 2011, 24: 455-468.CrossRef
22.
go back to reference Goldman N, Glei DA, Lin YH, Weinstein M: Improving mortality prediction using biosocial surveys. Am J Epidemiol. 2009, 169: 769-779. 10.1093/aje/kwn389.CrossRefPubMedPubMedCentral Goldman N, Glei DA, Lin YH, Weinstein M: Improving mortality prediction using biosocial surveys. Am J Epidemiol. 2009, 169: 769-779. 10.1093/aje/kwn389.CrossRefPubMedPubMedCentral
23.
go back to reference Rosero-Bixby L, Collado-Chaves A: Tablas de mortalidad, jubilación e invalidez, Costa Rica 2000–2005.Población y Salud en Mesoamérica. Revista electrónica. 2007, 6 (1): 5- Rosero-Bixby L, Collado-Chaves A: Tablas de mortalidad, jubilación e invalidez, Costa Rica 2000–2005.Población y Salud en Mesoamérica. Revista electrónica. 2007, 6 (1): 5-
24.
go back to reference Kaufman JS, MacLehose RF, Kaufman S: A further crtique of the analytic strategy of adjusting for covariates to identify biologic mediation. Epidemiologic Perspectives & Innovations. 2004, 1 (1): 4-10.1186/1742-5573-1-4.CrossRef Kaufman JS, MacLehose RF, Kaufman S: A further crtique of the analytic strategy of adjusting for covariates to identify biologic mediation. Epidemiologic Perspectives & Innovations. 2004, 1 (1): 4-10.1186/1742-5573-1-4.CrossRef
25.
go back to reference Rehkopf D, Dow W, Rosero-Bixby L: Differences in the association of cardiovascular risk factors with education: a comparison of Costa Rica (CRELES) and the United States (NHANES). J Epidemiology Community Health. 2009, 64: 821-828.CrossRef Rehkopf D, Dow W, Rosero-Bixby L: Differences in the association of cardiovascular risk factors with education: a comparison of Costa Rica (CRELES) and the United States (NHANES). J Epidemiology Community Health. 2009, 64: 821-828.CrossRef
27.
go back to reference Turra CM, Goldman N, Seplaki CL, Glei DA, Lin YH, Weinstein M: Determinants of mortality at older ages: The role of biological markers of chronic disease. Popul Dev Rev. 2005, 31: 675-698. 10.1111/j.1728-4457.2005.00093.x.CrossRef Turra CM, Goldman N, Seplaki CL, Glei DA, Lin YH, Weinstein M: Determinants of mortality at older ages: The role of biological markers of chronic disease. Popul Dev Rev. 2005, 31: 675-698. 10.1111/j.1728-4457.2005.00093.x.CrossRef
28.
go back to reference Cooper R, Kuh D, Hardy R: Objectively measured physical capability levels and mortality: systematic review and meta-analysis. BMJ. 2010, 341: c4467-10.1136/bmj.c4467.CrossRefPubMedPubMedCentral Cooper R, Kuh D, Hardy R: Objectively measured physical capability levels and mortality: systematic review and meta-analysis. BMJ. 2010, 341: c4467-10.1136/bmj.c4467.CrossRefPubMedPubMedCentral
29.
go back to reference Phillips AC, Carroll D, Gale CR, Lord JM, Arlt W, Batty GD: Cortisol, DHEA sulphate, their ratio, and all-cause and cause-specific mortality in the Vietnam Experience Study. Eur J Endocrinol. 2010, 163: 285-292. 10.1530/EJE-10-0299.CrossRefPubMed Phillips AC, Carroll D, Gale CR, Lord JM, Arlt W, Batty GD: Cortisol, DHEA sulphate, their ratio, and all-cause and cause-specific mortality in the Vietnam Experience Study. Eur J Endocrinol. 2010, 163: 285-292. 10.1530/EJE-10-0299.CrossRefPubMed
30.
go back to reference Cappola AR, Xue Q-L, Walston JD, Leng SX, Ferrucci L, Guralnik J, Fried LP: DHEAS Levels and Mortality in Disabled Older Women: The Women’s Health and Aging Study I. J Gerontology, Series A: Medical Sci Biological Sci. 2006, 61: 957-962. 10.1093/gerona/61.9.957.CrossRef Cappola AR, Xue Q-L, Walston JD, Leng SX, Ferrucci L, Guralnik J, Fried LP: DHEAS Levels and Mortality in Disabled Older Women: The Women’s Health and Aging Study I. J Gerontology, Series A: Medical Sci Biological Sci. 2006, 61: 957-962. 10.1093/gerona/61.9.957.CrossRef
31.
go back to reference Glei DA, Goldman N: Dehydroepiandrosterone sulfate (DHEAS) and risk for mortality among older Taiwanese. Ann Epidemiol. 2006, 16: 510-515. 10.1016/j.annepidem.2005.09.010.CrossRefPubMed Glei DA, Goldman N: Dehydroepiandrosterone sulfate (DHEAS) and risk for mortality among older Taiwanese. Ann Epidemiol. 2006, 16: 510-515. 10.1016/j.annepidem.2005.09.010.CrossRefPubMed
32.
go back to reference Currie CJ, Poole CD, Conway P: Evaluation of the association between the first observation and the longitudinal change in C-reactive protein, and all-cause mortality. Heart. 2008, 94: 457-462.CrossRefPubMed Currie CJ, Poole CD, Conway P: Evaluation of the association between the first observation and the longitudinal change in C-reactive protein, and all-cause mortality. Heart. 2008, 94: 457-462.CrossRefPubMed
33.
go back to reference Marsik C, Kazemi-Shirazi L, Schickbauer T, Winkler S, Joukhadar C, Wagner O, Endler G: C-reactive protein and all-cause mortality in a large hospital-based cohort. Clin Chem. 2007, 54: 343-349.CrossRefPubMed Marsik C, Kazemi-Shirazi L, Schickbauer T, Winkler S, Joukhadar C, Wagner O, Endler G: C-reactive protein and all-cause mortality in a large hospital-based cohort. Clin Chem. 2007, 54: 343-349.CrossRefPubMed
34.
go back to reference Harris TB, Ferrucci L, Tracy RP, Corti MC, Wacholder S, Ettinger WH, Heimovitz H, Cohen HJ, Wallace R: Associations of elevated Interleukin-6 and C-Reactive protein levels with mortality in the elderly. Am J Med. 1999, 106: 506-512. 10.1016/S0002-9343(99)00066-2.CrossRefPubMed Harris TB, Ferrucci L, Tracy RP, Corti MC, Wacholder S, Ettinger WH, Heimovitz H, Cohen HJ, Wallace R: Associations of elevated Interleukin-6 and C-Reactive protein levels with mortality in the elderly. Am J Med. 1999, 106: 506-512. 10.1016/S0002-9343(99)00066-2.CrossRefPubMed
35.
go back to reference Khaw K-T, Wareham N, Luben R, Bingham S, Oakes S, Welch A, Day N: Glycated haemoglobin, diabetes, and mortality in men in Norfolk cohort of European Prospective Investigation of Cancer and Nutrition (EPIC-Norfolk). BMJ. 2001, 322: 15-10.1136/bmj.322.7277.15.CrossRefPubMedPubMedCentral Khaw K-T, Wareham N, Luben R, Bingham S, Oakes S, Welch A, Day N: Glycated haemoglobin, diabetes, and mortality in men in Norfolk cohort of European Prospective Investigation of Cancer and Nutrition (EPIC-Norfolk). BMJ. 2001, 322: 15-10.1136/bmj.322.7277.15.CrossRefPubMedPubMedCentral
36.
go back to reference Schatz IJ, Masaki K, Yano K, Chen R, Rodriguez BL, Curb JD: Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study. Lancet. 2001, 358: 351-355. 10.1016/S0140-6736(01)05553-2.CrossRefPubMed Schatz IJ, Masaki K, Yano K, Chen R, Rodriguez BL, Curb JD: Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study. Lancet. 2001, 358: 351-355. 10.1016/S0140-6736(01)05553-2.CrossRefPubMed
37.
go back to reference Song YM, Sung J, Kim JS: Which Cholesterol Level Is Related to the Lowest Mortality in Population with Low Mean Cholesterol Level: A 6.4-Year Follow-up Study of 482,472 Korean Men. Am J Epidemiol. 2000, 151: 739-747. 10.1093/oxfordjournals.aje.a010272.CrossRefPubMed Song YM, Sung J, Kim JS: Which Cholesterol Level Is Related to the Lowest Mortality in Population with Low Mean Cholesterol Level: A 6.4-Year Follow-up Study of 482,472 Korean Men. Am J Epidemiol. 2000, 151: 739-747. 10.1093/oxfordjournals.aje.a010272.CrossRefPubMed
38.
go back to reference Weverling-Rijnsburger AW, Blauw GJ, Lagaay AM, Knook DL, Meinders AE, Westendorp RG: Total cholesterol and risk of mortality in the oldest old. Lancet. 1997, 350: 1119-1123. 10.1016/S0140-6736(97)04430-9.CrossRefPubMed Weverling-Rijnsburger AW, Blauw GJ, Lagaay AM, Knook DL, Meinders AE, Westendorp RG: Total cholesterol and risk of mortality in the oldest old. Lancet. 1997, 350: 1119-1123. 10.1016/S0140-6736(97)04430-9.CrossRefPubMed
39.
go back to reference Krumholz HM, Seeman T, Merrill SS, de Leon CF Mendes, Vaccarino V, Silverman DI, Tsukahara R, Ostfeld AM, Berkman LF: Lack of association between cholesterol and coronary heart disease mortality and morbidity and all-cause mortality in persons older than 70 years. JAMA. 1994, 272: 1335-1340. 10.1001/jama.1994.03520170045034.CrossRefPubMed Krumholz HM, Seeman T, Merrill SS, de Leon CF Mendes, Vaccarino V, Silverman DI, Tsukahara R, Ostfeld AM, Berkman LF: Lack of association between cholesterol and coronary heart disease mortality and morbidity and all-cause mortality in persons older than 70 years. JAMA. 1994, 272: 1335-1340. 10.1001/jama.1994.03520170045034.CrossRefPubMed
40.
go back to reference Kronmal RA, Cain KC, Ye Z, Omenn G: Total serum cholesterol levels and mortality risk as a function of age. A report based on the Framingham data. Arch Intern Med. 1993, 153: 1065-1073. 10.1001/archinte.1993.00410090025004.CrossRefPubMed Kronmal RA, Cain KC, Ye Z, Omenn G: Total serum cholesterol levels and mortality risk as a function of age. A report based on the Framingham data. Arch Intern Med. 1993, 153: 1065-1073. 10.1001/archinte.1993.00410090025004.CrossRefPubMed
41.
go back to reference Kalantar-Zadeh K, Kilpatrick RD, Kuwae N, Wu DY: Reverse epidemiology: A spurious hypothesis or a hardcore reality. Blood Purification. 2005, 23: 57-63. 10.1159/000082012.CrossRefPubMed Kalantar-Zadeh K, Kilpatrick RD, Kuwae N, Wu DY: Reverse epidemiology: A spurious hypothesis or a hardcore reality. Blood Purification. 2005, 23: 57-63. 10.1159/000082012.CrossRefPubMed
42.
go back to reference Rosero-Bixby L: The decline in adult mortality in Costa Rica. Adult Mortality in Latin America. Edited by: Timaeus IM, Chackiel J, Ruzicka L. 1996, Clarendon, Oxford, U.K, 166-195. Rosero-Bixby L: The decline in adult mortality in Costa Rica. Adult Mortality in Latin America. Edited by: Timaeus IM, Chackiel J, Ruzicka L. 1996, Clarendon, Oxford, U.K, 166-195.
Metadata
Title
Predicting mortality with biomarkers: a population-based prospective cohort study for elderly Costa Ricans
Authors
Luis Rosero-Bixby
William H Dow
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Population Health Metrics / Issue 1/2012
Electronic ISSN: 1478-7954
DOI
https://doi.org/10.1186/1478-7954-10-11

Other articles of this Issue 1/2012

Population Health Metrics 1/2012 Go to the issue