Table 1.

Selected studies using biomarkers from multiple systems to predict all-cause mortality^a

Study; Dataset; Country	Sample Size/Ages; Number Deaths; Mean follow up/ End of observation	Biomarkers Included				Control Variables	AUC (Controls Only)	AUC gain (Add Biomarkers)
		Cardiovacular/ Metabolic	Inflammatory	Neuro-endocrine	Other
Studies Using Individual Biomarkers Representing Multiple Systems
Rosero-Bixby & Dow (2012); CRELES; Costa Rica	n=2313 aged 60+; n=564 deaths; 5 years ending 2010	SBP DBP TC HDL Ratio TC/HDL LDL TG HbA1c GLU Waist BMI WHR Knee height	CRP	DHEAS U. CORT U. EPI U. NE	CrCl Grip strength Walking   speed PEF	Sex Age Region Disability Cancer Involuntary weight   loss Smoker SAH	0.72	0.06
Haring et al. (2011); Study of Health in Pomerania; Germany	n=4261 aged 20–79; n=456 deaths; 9.7 years ending 12/15/2009	HbA1c	Fbg		U. Albumin GGT	Age Sex Cohabitation Education Occupation Income Smoking Alcohol use Physical activity Diet SAH Perceived QoL Hx of:   Hypertension   MI   Stroke   Diabetes Waist	0.88	0.004
Goldman et al. (2009); SEBAS 2000; Taiwan	n=933 aged 54+; n=162 deaths; 6 years ending 12/31/2006	Hypertension TC HDL BMI Waist HbA1c	WBC % NEUT IL-6	DHEAS U. CORT U. EPI U. NE	CrCl Albumin IGF-1	Age Sex Mainlander Urban Education Smoking # Current chronic   conditions Mobility Cognitive function CES-D SAH Use of:   BP meds   Diabetic meds	0.79	0.06
Goldman et al. (2006b); SEBAS 2000; Taiwan	n=927 aged 54+; n=61 deaths; 3 years ending in 2003	SBP DBP TC Ratio TC/HDL HbA1c BMI	IL-6	DHEAS U. CORT U. EPI U. NE U. DOP	IGF-1	Age Sex Urban Smoking # Current chronic   conditions Mobility   limitations Cognitive function CES-D SAH Pain level	0.79	0.08
Stork et al. (2006); Zoetermeer, Netherlands	n=403 men aged 70+; n=75 deaths; 4 years ending in 2000	Included in "Controls"	CRP IL-6		# Carotid plaques	Age SBP Pulse Smoking Use of:   BP meds   Diabetic meds Hx of MI BMI	0.62	0.15
Newson et al. (2010); Rotterdam Study; Netherlands	n=2008 aged 55–85; n=639 deaths before 85th birthday; 7.9 years ending 1/1/2007	DBP	CRP		Albumin Uric acid Femoral   neck bone   mineral   density Ankle   brachial   index # carotid   plaques	Age Sex Smoking Left ventricular   function SAH Cognitive status Any IADL   limitations Body weight   stable past year	0.75	N/A
Studies Using Multi-System Biomarker Summary Scores
Borrell et al. (2010); NHANES III; U.S.	n=13,715 aged 25+; n=2491 deaths; 8.7 years ending 12/31/2000	SBP DBP Pulse TC HDL HbA1c WHR	CRP		Albumin	Age Sex Race/Ethnicity Education Income	N/A	N/A
Crimmins et al. (2009); NHANES III; U.S.	n=14,443 aged 20+; n=2134 deaths; 8.3 years ending 12/31/2000	SBP DBP Pulse TC HDL HbA1c BMI	CRP		Albumin	Age Sex Race Poor Smoking Heavy Drinking Exercise BMI	N/A	N/A
Goldman et al. (2006a); SEBAS 2000; Taiwan	n=935 aged 54+; n=72 deaths; 3 years ending in 2004	SBP DBP TC Ratio TC/HDL TG GLU HbA1c BMI WHR	IL-6		IGF-1	Age Sex Urban # Chronic   conditions Mobility CES-D Cognitive function Smoking	N/A	N/A
Gruenewald et al. (2006); MacArthur Study of Successful Aging; U.S.	n=1189 aged 70–79; n=492 deaths; 12 years ending in 2000	SBP DBP HDL Ratio TC/HDLHbA1c	IL-6 CRP Fbg	DHEA U. CORT U. EPI U. NE	Albumin	Modeled separately by sex	N/A	N/A
Karlamangla et al. (2006); MacArthur Study of Successful Aging; U.S.	n=171 aged 70–79; n=19 deaths; 4.5 years ending in 1995	SBP DBP TC HDL HbA1c WHR		DHEAS U. CORT U. EPI U. NE		Age	N/A	N/A
Wang et al. (2006); Framingham Heart Study; U.S.	n=3209 mean age 59; n=207 deaths; 7.4 years (date follow up ended is not stated)		CRP		B-type   natriuretic   peptide Renin Hcy UACR	Age Sex Smoking Hypertension TC HDL Diabetes BMI SCr Presence of CVD	0.80	0.02
Seeman et al. (2004); MacArthur Study of Successful U.S.	n=657 aged 70–79; n=141 deaths; 7.5 years ending 12/31/1995	SBP DBP HDL Ratio TC/HDL HbA1c WHR	IL-6 CRP Fbg	DHEAS U. CORT U. EPI U. NE	Albumin CrCl PEF	Age Sex Race Education # Chronic   conditions	N/A	N/A
Seeman et al. (2001) MacArthur Study of Successful Aging; U.S.	n=720 aged 70–79; n=153 deaths; 7 years ending in 1997	SBP DBP HDL Ratio TC/HDL HbA1c WHR		DHEAS U. CORT U. EPI U. NE		Age Sex Ethnicity Education Income Hx of chronic   conditions (MI, stroke, diabetes, hypertension, cancer, hip fracture, other broken bones)	N/A	N/A
Levine et al. (2013); NHANES III; U.S.	n=9389 aged 30–75; n=1843 deaths; 18 years ending 12/31/2006	SBP TC HbA1c	CRP CMV optical density		SCr Albumin S. ALP FEV SUN	Age Sex	0.83	N/A

Abbreviations: BMI = body mass index; BP = blood pressure; CES-D = Center for Epidemiologic Studies Depression scale; CMV = cytomegalovirus; CrCl = creatinine clearance; CRP = c-reactive protein; DBP = diastolic blood pressue; DHEA = dehydroepiandrosterone; DHEAS = dehydroepiandrosterone sulfate; Fbg = fibrinogen; FEV = forced expiratory volume; GGT = gamma glutamyltransferase; GLU = fasting glucose; HbA1c = glycosylated hemoglobin; Hcy = homocysteine; HDL = high-density lipoprotein cholesterol; Hx = history; IADL = instrumental activities of daily living; IGF-1 = insulin-like growth factor 1; MI = myocardial infarction; NEUT = neutrophils; PEF = peak expiratory flow; QoL = quality of life; SAH = self-assessed health status; S. ALP = serum alkaline phosphatase; SBP = systolic blood pressure; SCr = serum creatinine; SUN = serum urea nitrogen; TC = total cholesterol; TG = triglycerides; UACR = urinary albumin-to-creatinine ratio U. CORT = urinary cortisol; U. EPI = urinary epinephrine; U. NE = urinary norepinephrine; WHR = waist-hip ratio.

^aFor studies of individual biomarkers, we list in this table only those that: 1) included at least one standard cardiovascular/metabolic markers (e.g., blood pressure, lipids, measures of glucose metabolism, and obesity) as well as at least one inflammatory marker (e.g., interleukin-6, IL-6; C-reactive protein, CRP); and 2) assessed the discriminatory ability of the set of biomarkers. For studies using a multi-marker summary score, we included all studies that used a summary score based on markers from multiple systems to predict all-cause mortality.