Supplemental Table 1. Characteristics of the Studies Included in the Meta-Analysis

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Supplemental Table 1. Characteristics of the studies included in the meta-analysis

Source / Males,
% / Age at
baseline,
year / Duration
of follow-up,
year / No.
of individuals
/Person- Years / No.
of cases / Exposure
assessment / Exposure
categories
Incidence
CVD
(18) de Oliveira Otto et al.,2012,
MESA,
USA / 47.3 / 61.8±10.3 / 6.2 / 5,285 /
32,767 / 279 / Semi-quantitative FFQ / Quintiles of heme iron (mg/d):
≤0.45, 0.46-0.63, 0.64-0.80, 0.81-1.08, ≥1.09
Quintiles of nonheme iron (mg/d):
≤8.5, 8.6-9.9, 10.0-11.3, 11.4-13.3, ≥13.4
IHD
(8) Galan et al., 2006,
SU.VI.MAX,
France / 32.5 / 48.6±6.5
(35-60) / 7.5
(median) / 9,917 /
74,774 / 187 / Serum ferritin concentration measured by using automatic nephelometry (BNII nephelometer; Dade Behring, Paris La De´fence, France). / Quartiles of serum ferritin (µg/L):
< 30, 30-70, 70-160, >160.
CHD
(36) Liao et al., 1994,
NHANES I,
USA / 43.6 / 58.5±11.0
(40-74) / 13
(0-16) / 4,237 /
55,081 / 1,151 / Serum iron and TIBC determinations were made in the Nutritional Biochemistry Section of the CDC. / Quartiles of serum iron,TIBC, and transferrin saturation, details: NA.
(35) Sempos et al., 1994, NHANES I and NHEFS,
USA / 44.8 / 61
(25-74) / 14.6 / 4,518 / 65,962.8 / 842 / Serum iron and TIBC were determined by a modification of the automated Technicon AAH-25 method, which is based on the procedure of Giovanniello and Ramsey. / Quartiles of transferrin saturation (%):
White men: < 22.1, 22.1-27.2, 27.3-32.3,
32.4-39.4, ≥39.5.
White women: <20.4, 20.4-25.0,
25.1- 29.3, 29.4-35.3, ≥35.4.
Tertiles of transferrin saturation (%):
Black men: <24.4, 24.4-31.5, ≥31.6.
Black women: <22.0, 22-27.8, ≥27.9.
(34) Gartside et al., 1995,
NHANES I,
USA / NA
(including both genders) / 44.4±16.5
(20-72) / 10 / 8,251 / NA / 492 / Semi-quantitative FFQ. / Tertiles of dietary iron (mg/d):
<8.4, 8.4-13.0, ≥13.1
(19) Fox et al., 2002,
Australia / 52.2 / 50±13
(20-79) / 4 / 2,031/ NA / 235 / Serum iron levels were measured by a standard colorimetric method, and serum transferrin levels were determined by rate immunoturbidimetry on an automated analyzer (model 917, Hitachi, Tokyo, Japan).
Serum ferritin levels were measured by chemiluminescence immunoassay (ACS-180, Chiron Diagnostics, Norwood, Mass.). / Ferritin (µg/l): ≤300, >300
Transferrin saturation (%): <45, ≥45
(16) Van der A et al., 2005,
Prospect-EPIC,
Netherlands / 0 / 56
(52-62) / 4.3
(median) / 16,136 / 69,600 / 252 / Semi-quantitative FFQ / Quartiles of iron intake (mg/day):
Total iron:
<9.56, 9.57-10.50, 10.50-11.43, >11.43.
Heme iron:
<1.28, 1.28-1.76, 1.76-2.27, >2.27.
Non-heme iron:
<7.88, 7.88-8.73, 8.73-9.56, >9.56.
MI
(6) Salonen et al., 1992,
KIHDRFS,
Finland / 100 / ≥42 / 3 / 1,931 / 5,793 / 51 / Ferritin concentrations were measured with a radioimmunoassay using a Multigamma model 1261 gamma counter (LKB Wallac, Turku, Finland). / Serum ferritin (µg/l): <200, ≥200.
(37) Ascherio et al.., 1994,
HPFS,
USA / 100 / 40-75 / 4 / 44, 933 / 157,010 / 249 / Semi-quantitative FFQ / Quintiles of dietary iron
( mg/d, median):
Total iron: 11, 13, 15, 18, 37;
Heme iron: 0.7, 1.0, 1.3, 1.6, 2.1
(5) Klipstein-Grobush et al., 1999,
Rotterdam Study,
Netherlands / NA
(including both genders) / ≥55 / 4
(3-7) / 4,802 / 19,208 / 124 / Semi-quantitative FFQ / Tertiles of dietary iron (mg/d):
Total iron: <10.6, 10.6-12.4, >12.4.
Heme iron: <0.70, 0.70-1.00, >1.00.
(11) Marniemi et al., 2005,
Finland / 47.81 / 65-99 / 10 / 755/ NA / 130 / Dietary history interview, serum iron concentration was analyzed spectrophotometrically by the ferrozine method. / Tertiles of dietary iron, serum iron and serum ferritin, details: NA.
Mortality
CVD
(35) Sempos et al., 1994, NHANES I and NHEFS,
USA / 44.8 / 61
(25-74) / 14.6 / 744 /
10,862.4 / 164 / Serum iron and TIBC were determined by a modification of the automated Technicon AAH-25 Method, which is based on the procedure of
Giovanniello and Ramsey. / Tertiles of transferrin saturation (%):
Black men: <24.4, 24.4-31.5, ≥31.6.
Black women: <22.0, 22-27.8, ≥27.9.
(32)Marniemi et al., 1998,
Finland / 52.9 / ≥65 / 13 / 344 / NA / 142 / Serum iron concentration was determined spectrophotometrically by the ferrozine method.
Serum ferritin concentration was determined by solid phase radioimmunoassay.
Serum transferrin concentrations were analyzed by radial immune diffusion plates. / Tertiles of serum iron, ferritin, and transferrin, details: NA.
(23) Wells et al., 2004,
NH2MS,
USA / 45.7 / 30-75 / >12.83 / 3,410 / 43,761 / NA / Serum iron and TIBC were determined by a modification of the automated Technicon AAH-25 Method, which is based on the procedure of
Giovanniello and Ramsey. / Transferrin Saturation (%): <55, >55
(20) Lee et al., 2005,
IWHS,
USA / 0 / 61.5
(55-69) / 15 / 34,492 / NA / 1,767 / Semi-quantitative FFQ / Quintiles of dietary iron (mg/d, median):
Heme iron:
Q1: 0.057, Q3:1.37, Q5:2.43.
Non-heme iron:
Q1: 6.9, Q3:12.8, Q5: 24.4.
(22) Kim et al., 2012,
NHANES III,
USA / 50.8 / 67.1 / 15.5 / 5,695 / NA / 1,361 / Serum ferritin was measured by single-incubation two-site immunoradiometric assay; serum iron and total iron-binding capacity were measured by a modified automated AAII-25 colorimetric method using an RFA or RFA-200 automated ferrozine colorimetric analyzer system. / Quintiles of serum ferritin (ng/mL):
Men: ≤68.0, 69.0-118.0, 119.0-181.0, 182-288.0, ≥289.0.
Women: ≤46.0, 47.0-80.0, 81.0-123.0, 124.0-193.0, ≥194.0.
Quintiles of transferrin saturation (%):
Men: ≤18.0, 18.1-23.1, 23.2-28.2, 28.3-35.1, ≥35.2.
IHD
(33)Van Asperen et al., 1995,
Netherlands / 49.6 / 70.7±4.9
(64-87) / 17 / 260/ 2,845 / 50 / Serum iron was measured by spectrophotometry and TIBC by the method of Ramsay. / Tertiles of transferrin saturation (%):
Men: ≤24.1, 24.2-31.8, >31.8
Women: ≤22.8, 22.9-29.8, >29.8
Tertiles of TIBC (µmol/l):
Men: ≤64.8, 64.9-72.2, >72.2
Women: ≤63.4, 63.5-75.2, >75.2
(21) Morkedal et al., 2011,
HUNT 2 study,
Norway / 46.0 / 49.5±16.5 / 11.4 / 60, 798/ 608,748 / 1,034 / Serum iron was measured on a Hitachi 911 analyzer using a ferrozin-method with reagents from Boehringer Mannheim, Germany. Serum transferrin concentration was measured on the same Hitachi 911 analyzer using an immunoturbidimetric method with reagents from DAKO A/S, Denmark. / Quartiles of TIBC (µmol/l):
Men: 19-55, 56-60, 61-65, 66-165
Women: 21-56, 57-61, 62-68, 69-129
CHD
(37) Ascherio et al., 1994,
HPFS,
USA / 100 / 40-75 / 4 / 44,933 / 157,010 / 137 / Semi-quantitative FFQ / Quintiles of dietary iron
( mg/d, median):
Total iron: 11, 13, 15, 18, 37.
Heme iron : 0.7, 1.0, 1.3, 1.6, 2.1.
(39) Reunanen et al., 1995,
Finland / 49.9 / 45-64 / 13.8 / 12,188 / 168,194.4 / 984 / Serum iron and TIBC were determined with a colorimetric assay method applied to Technicon Auto Analyzer. / Quintiles of serum iron, TIBC and transferrin saturation, details: NA.
(10) Corti et al., 1997,
EPESE,
USA / 35.2 / 78.8
(≥71) / 4.4
(median) / 3,936 /
16,250 / 209
(CAD) / Serum iron was measured with standard colorimetric method using ferrozine as chromogen. / Quartiles of serum iron (median, µg/ dl):
Men: 50.5, 73.9, 92.4, 127.3.
Women: 46.3, 68.3, 84.9, 114.7.
(9) Zhang et al., 2012,
JACC Study,
Japan / 39.4 / 56.1 / 14.7
(median) / 58,615 / 859,450 / 557 / Semi-quantitative FFQ / Quintiles of iron intake ( mg/day, median):
Total iron: 5.12, 6.60, 7.65, 8.78, 10.58.
Heme iron 0.07, 0.16, 0.22, 0.28, 0.44.
Non-heme iron: 3.84, 6.05, 7.23, 8.40. 10.19.
MI
(5) Klipstein-Grobusch et al., 1999,
Rotterdam Study,
Netherlands / NA
(including both genders) / ≥55 / 4 / 4,802 /
19,208 / 30 / Semi-quantitative FFQ / Tertiles of dietary (mg/d):
Total iron: <10.6, 10.6-12.4, >12.4
Heme iron: <.70, .70-1.00, >1.00.
(7) Morrison et al., 1994,
Nutrition Canada Survey,
Canada / 42.7 / 35-79 / 10.2 / 9,920 / 103,142 / 224 / Serum iron and unsaturated iron binding capacity were determined using a Beckman DSA 560 discrete sample analyzer. / Tertiles of serum iron (µg / dl): <120, 120- 174, ≥175

Abbreviations: CAD, coronary artery disease; CDC, Center for Disease Control and Prevention; CHD, coronary heart disease; CVD, cardiovascular disease; EPESE, Established Populations for Epidemiologic Studies of the Elderly; EPIC, European Prospective Investigation of Cancer; FFQ, food frequency questionnaire; HPFS, Health Professionals Follow-up Study; HUNT, Nord-Trøndelag Health Study; IHD, ischemic heart disease; IWHS, Iowa Women’s Health Study; JACC, Japan Collaborative Cohort; KIHDRFS, Kuopio Ischemic Heart Disease Risk Factor Survey; MESA, Multi-Ethnic Study of Atherosclerosis; MI, myocardial infarction; NA, not available; NHANES, National Health and Nutrition Examination Survey; NH2MS, NHANES II Mortality Study; NHEFS, NHANES 1 Epidemiologic Followup Study; NHS, Nurses’ Health Study; SU.VI.MAX, Supplementation en Vitamines et Mineraux Antioxydants (Supplementation in Vitamin and Mineral Antioxidants); TIBC, total iron binding capacity.

Supplemental Table 1. Characteristics of the studies included in the meta-analysis (Continued)

Source / Outcome assessment / Adjusted variables
Incidence
CVD
(23) Wells et al., 2004
NHANES II, NH2MS
USA / Obtained from death certificate.
ICD-9 codes: 391-448.9 / No adjustment.
(18) de Oliveira Otto et al., 2012,
MESA,
USA / Obtained from cohort clinic visits, telephone calls to participants, medical records, or obituaries. Self-reported diagnoses, death certificates, autopsy reports, and medical records were reviewed by medical endpoints committee. / Gender, race-ethnicity, education, study center, physical activity, cigarette smoking, ratio of polyunsaturated intake to saturated fat intake, and intakes of alcohol, energy, , magnesium, antioxidant, zinc, beta-carotene, vitamin C, vitamin E, and mutual adjustment for non-heme and heme iron .
IHD
(8) Galan et al., 2006,
SU.VI.MAX,
France / Review of medical records by an expert committee.
ICD-10 codes: I20-24 / Age, smoking, BMI, total cholesterol, serum triglycerides, and group of supplementation.
CHD
(36) Liao et al., 1994,
NHANES I,
USA / Survivors and proxy respondents interviewed. Information obtained from death certificates or hospital records.
ICD-9 codes: 410-414. / Baseline age, SBP, serum cholesterol, education, and cigarette smoking.
(35) Sempos et al., 1994,
NHANES I and NHEFS,
USA / Obtained from death certificate or by hospital discharge diagnoses.
ICD-9 codes: 410-414. / Age, history of diabetes, smoking status, serum total cholesterol, serum albumin, SBP, and level of education.
(34) Gartside et al., 1995,
NHANES I,
USA / Obtained from death certificate or by hospital discharge diagnoses.
ICD-9 codes: 410-414. / Age, sex, alcohol, cigarette smoking, maximum weight, physical activity, diet riboflavin, serum magnesium, sedimentation rate, and Quetelet index.
(19) Fox et al., 2002,
Australia / Obtained from Western Australian Hospital Morbidity Data System.
ICD-9 codes: 410-459. / Age, gender, BMI, BP treat, BP, diabetes treatment, total cholesterol, HDL cholesterol, smoking, alcohol consumption, and hemoglobin.
(16)Van der A et al., 2005,
Prospect-EPIC,
Netherlands / Obtained from death certificate. Underlying cause of death coded by National Vital Statistics. / Age at intake, total energy intake, BMI, smoking, physical activity, hypertension, diabetes, hypercholesterolemia, energy-adjusted intakes of saturated fat , carbohydrate, fiber, alcohol, beta carotene, vitamin E, and vitamin C.
MI
(6) Salonen et al., 1992,
KIHDRFS,
Finland / Obtained from AMI registry. / BMI, smoking, maximal oxygen uptake, SBP, DBP, blood hemoglobin and leukocyte count, serum HDL2 and LDL cholesterol, triglycerides , apolipoprotein B, insulin, glucose, and copper, plasma fibrinogen, ischemic exercise ECG and family history of IHD.
(37) Ascherio et al., 1994,
HPFS,
USA / Self-report or reported by next-of-kin, coworkers, postal authorities, or the National Death Index; confirmed using medical records, autopsy reports, or death certificates. / Only age or ”age, BMI, smoking habits, alcohol consumption, history of hypertension, diabetes, hypercholesterolemia, family history of MI, profession, and quintiles of intake of total energy and vitamin E”.
(36) Liao et al., 1994,
NHANES I,
USA / Survivors and proxy respondents interviewed. Information obtained from death certificates or hospital records.
ICD-9 codes: 410-414. / Baseline age, SBP, serum cholesterol, education, and cigarette smoking.
(5) Klipstein-Grobusch et al., 1999,
Rotterdam Study,
Netherlands / Classified independently by two research physicians; Any disagreement was settled by a discussion. All events were verified by a CVD expert finally.
ICD-10 codes: I21-24. / Age, gender, BMI, pack-years of smoking, equivalent household income, education, alcohol intake, categories of energy-adjusted beta-carotene, vitamin C, vitamin E, and use of antioxidative vitamin supplements.
(11) Marniemi et al., 2005,
Finland / Mortality and cause of death obtained from National Register of Causes of Death.
ICD-9 codes: 410, 412, 414 / Age, gender, smoking, and functional capacity.
Mortality
CVD
(35) Sempos et al., 1994,
NHANES I and NHEFS,
USA / Obtained from death certificate or by hospital discharge diagnoses.
ICD-9 codes: 390-448. / Age, history of diabetes, smoking status, serum total cholesterol, serum albumin, SBP, and level of education.
(32) Marniemi et al., 1998,
Finland / Obtained from National Death Register. / Age, sex, alcohol use, BMI, CHD, hypertension, diabetes, serum cholesterol, HDL cholesterol, and triglycerides
(20) Lee et al., 2005,
IWHS,
USA / Identified from State Health Registry of Iowa or National Death Index. Underlying cause of death determined from state vital registry.
ICD-9 codes: 390-459;
ICD-10 codes: I00-99. / Age, BMI, waist-hip ratio, physical activity, cigarette smoking, alcohol consumption, hormone replacement therapy, HBP, intakes of energy, saturated fat, trans fat, polyunsaturated fat, folate, beta-carotene, vitamin E, Vitamin C, zinc and mutual adjustment of heme and non-heme iron intake.
(22) Kim et al., 2012,
NHANES III,
USA / Obtained from death certificate.
ICD-10 codes: I00-78;
I80-99 for CVD death. / Age, race-ethnicity, poverty income ratio, years of education, cigarette smoking, alcohol consumption, BMI, physical activity, and Charlson comorbidity index.
IHD
(33) Van Asperen et al., 1995,
Netherlands / Obtained from Central Bureau of Statistics in the Netherlands.
ICD-9 codes: 410-414. / Age, smoking, alcohol intake, SBP, serum total cholesterol, BMI, prevalence of IHD and diabetes mellitus.
(21) Morkedal et al.,2011,
HUNT 2 study,
Norway / Obtained from National Cause of Death Registry.
ICD-9 codes: 410-414;
ICD-10 codes: I20-25. / Attained age, SBP, level of smoking, diabetes mellitus, total / HDL cholesterol ratio, waist-hip ratio, time since last meal.
CHD
(37) Ascherio et al., 1994,
HPFS,
USA / Reported by next-of-kin, coworkers, postal authorities, or the National Death Index; confirmed using medical records, autopsy reports, or death certificates. / Only age or ”age, BMI, smoking habits, alcohol consumption, history of hypertension, diabetes, hypercholesterolemia, family history of MI, profession, and quintiles of intake of total energy and vitamin E”.
(39)Reunanen et al., 1995,
Finland / Obtained from death certificates.
ICD-8 codes: I410.00-412.99. / Age, serum cholesterol, hypertension, smoking, diabetes and obesity, and parity in women.
(10) Corti et al., 1997,
EPESE,
USA / Mainly obtained from death certificate. <1% of participants from proxy, obituaries or other sources.
ICD-9 codes: 410-414 for CAD. / Age, level of education, race, use of iron supplementation, HDL cholesterol, total cholesterol, serum albumin, anemia, elevated creatinine, BMI, BP level, smoking, use of alcohol, and history of diabetes, hypertension, stroke, heart attack, and cancer.
(9) Zhang et al., 2012,
JACC Study,
Japan / Obtained from death certificates.
ICD-9 codes 410-414;
ICD-10 codes I20–25. / BMI, smoking status, ethanol intake, history of hypertension, history of diabetes mellitus, sports time, walking time, educational status, perceived mental stress, dietary sodium intake, and for women, menopausal status and hormone replacement therapy.
MI
(5) Klipstein-Grobusch et al., 1999,
Rotterdam Study
Netherlands / Classified independently by two research physicians; Any disagreement was settled by a discussion. All events were verified by a CVD expert finally.
ICD-10 codes: I21-24. / Age, gender, BMI, pack-years of smoking, equivalent household income, education, alcohol intake, categories of energy-adjusted beta-carotene, vitamin C, vitamin E, use of antioxidative vitamin supplements.
(7) Morrison et al., 1994,
Nutrition Canada Survey,
Canada / Obtained from Statistics Canada’s National Mortality Database for the years of 1970-1987.
ICD-8 codes used; Details: NA. / Age, cigarette smoking, hypertension, serum cholesterol, and diabetes status.

Abbreviations: BMI, body mass index; BP, blood pressure; CAD, coronary artery disease; CHD, coronary heart disease; CVD, cardiovascular disease; DBP, diastolic blood pressure; EPIC, European Prospective Investigation of Cancer; HBP, high blood pressure; HDL, high-density lipoprotein; HPFS, Health Professionals Follow-up Study; HUNT, Nord-Trøndelag Health Study; ICD, International Classification of Diseases; IHD, ischemic heart disease; IWHS, Iowa Women’s Health Study; JACC, Japan Collaborative Cohort; KIHDRFS, Kuopio Ischemic Heart Disease Risk Factor Survey; LDL, low-density lipoprotein; MESA, Multi-Ethnic Study of Atherosclerosis; MI, myocardial infarction; NA, not available; NHANES, National Health and Nutrition Examination Survey; NH2MS, NHANES II Mortality Study; NHEFS, NHANES 1 Epidemiologic Followup Study; NHS, Nurses’ Health Study; SBP, systolic blood pressure; SU.VI.MAX, Supplementation en Vitamines et Mineraux Antioxydants (Supplementation in Vitamin and Mineral Antioxidants)