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. 2023 Jan 20;21(1):e07704. doi: 10.2903/j.efsa.2023.7704

Study name

Country

Reference

Follow‐up

Study design

Funding

Original Cohort (N total)

Exclusion criteria

Study population (n, sex and age at baseline(a))

Ascertainment of outcome

Exposure groups(a)

n/person‐years

N deaths Model covariates Results

MPP

Sweden

Schomburg et al. (2019)

9.3 yr (median)

Prospective cohort

Mixed

N = 33,346

Population sampled: General population

Excluded: CVD event prior to baseline

n = 4,366

Sex (% F): 31

Ethnicity: Caucasian

Age (yr): 70

Death ascertained through record linkage with the Swedish Hospital Discharge Register, the Swedish Cause of Death Register, the Stroke in Malmö Register, and the Swedish Coronary Angiography and Angioplasty Registry.

N per quintile of plasma Sepp1 (mg/L, median (range))

Q1 3.7 (0.4–4.3): 873

Q2: 4.7 (4.3–5.1): 873

Q3: 5.5 (5.1–5.9): 874

Q4: 6.3 (5.9–6.9): 873

Q5: 7.7 (6.9–20): 873

N, per quintile

Q1(ref): 314

Q2: 214

Q3: 193

Q4: 175

Q5: 215

Age, gender, current smoking, systolic blood pressure, use of antihypertensive medication, diabetes mellitus,

LDL‐cholesterol, HDL‐cholesterol, and body mass index

HR (95% CI)

Q1(ref): 1

Q2: 0.73 (0.61, 0.87)

Q3: 0.66 (0.55, 0.79)

Q4: 0.57 (0.48, 0.69)

Q5: 0.69 (0.58, 0.82)

ilSIRENTE

Italy

Giovannini et al. (2018)

10 yr

Prospective cohort

Public

N = 364

Population sampled: General population

Excluded: insufficient blood sample

n = 347

Sex (% F): 67

Ethnicity: Caucasian

Age (yr): 85

Survival status was obtained from general practitioners and confirmed by the National Death Registry.

N above/below median serum Se (μg/L)

Low Se ≤ 105.3: 175

High Se > 105.3: 172

N, per group

Low Se: 135

High Se: 113

Model 1: crude

Model 2: age, gender, IADL scale score, BMI, Cancer

Model 3: age, gender, IADL scale score, BMI, Cancer, HDL‐cholesterol, IL‐6, CRP

HR (95% CI), high Se vs low Se

Model 1: 0.66 (0.51, 0.85)

Model 2: 0.69 (0.53, 0.89)

Model 3: 0.71 (0.54, 0.92)

Rivalta + Reggio Emilia

Italy

Vinceti et al. (2016a)

27 yr

Prospective cohort

Mixed

N = 97,780

Population sampled: subjects continuously residing in Rivalta from 1974 to 1985, exposed to high‐Se‐contaminated tap water (n = 2,065) and unexposed municipal population as controls (n = 95,715)

n = 97,780

Sex (% F):

Exposed: 51

Unexposed: 53

Ethnicity: Caucasian

Age (yr): 5–95+

Death ascertained using Reggio Emilia mortality register

person‐years, per group of Se in tap water (inorganic Se) (μg/L)

Exposed 8–10: 46,268

Unexposed < 1: 2,067,862

N, per group

Exposed: 663

Unexposed: 34,598

age and calendar year

HR (95% CI), exposed vs unexposed

0.99 (0.91, 1.05)

SWHS/SMHS

China

Sun et al. (2016)

13.9 yr (F)/8.37 y r (M) (mean)

Prospective cohort

Public

N = 136,421

Population Sampled: General population, without history of cancer, resident in Shanghai

Excluded: immediately lost to follow‐up after study enrolment, missing data, extreme energy intake

n = 133,957 (F 73,854/M 60,103)

Ethnicity: Asian

Age (yr): 40–70

Annual record linkage with the Shanghai Vital Statistics Registry. All possible matches identified through the linkage were verified by home visits

Energy‐adjusted quintile of Se intake (b) (μg/1,000 kcal per d, median) assessed through SFFQ

F/M

Q1 16: 14,771/12,021

Q2 21: 14,771/12,022

Q3 25: 14,769/12,022

Q4 30: 14,771/12,016

Q5 42: 14,772/12,022

N, per quintile

F/M

Q1(ref): 1,863/1,136

Q2: 1,285/885

Q3: 1,033/819

Q4: 892/745

Q5: 676/632

age, birth cohort, education, income, marital status, occupation, BMI, physical activity, total energy intake, dietary fat intake, supplement use, smoking status, drinking status, history of hypertension, diabetes, CHD or stroke and family history of cancer

HR (95% CI)

Females

Q1(ref): 1

Q2: 0.96 (0.89, 1.03)

Q3: 0.92 (0.84, 1.00)

Q4: 0.90 (0.82, 0.99)

Q5: 0.79 (0.71, 0.88)

Males

Q1(ref): 1

Q2: 0.91 (0.83, 0.99)

Q3: 0.86 (0.78, 0.95)

Q4: 0.82 (0.73, 0.91)

Q5: 0.79 (0.70, 0.89)

PREDIMED

Spain

Henríquez‐Sánchez et al. (2016)

4.3 yr (median)

Prospective cohort

Public

N = 7,447

Population sampled: Participants of the PREDIMED RCT, without CVD at enrolment and with either T2DM or ≥3 risk factors (smoking, hypertension, dyslipidemia, overweight or obesity, or family history of premature CVD)

Excluded: no follow‐up; total energy intake < 800 or > 4,000 kcal/d

n = 7,015

Sex (% F): 58

Ethnicity: Caucasian

Age (yr): 55–80

Survival status obtained

from the continuous contact with participants and their families (during trial phase), contact with family physicians, yearly comprehensive review of all medical records and yearly consultation of the National Death Index

Quintile of Se intake assessed through SFFQ

NR

Person‐years

Q1: 6,070

Q2: 6,190

Q3: 6,210

Q4: 6,333

Q5: 6,273

N, per quintile

Q1(ref): 73

Q2: 73

Q3: 62

Q4: 53

Q5: 58

Recruitment center, intervention group, age, sex, education, marital status, BMI, smoking habit, alcohol consumption, total energy intake, energy‐adjusted intake of saturated fatty acids, polyunsaturated fatty acids, monounsaturated fatty acids and glycaemic index and medical history of hypertension, diabetes, dyslipidemia and cancer

HR (95% CI)

Q1(ref): 1

Q2: 0.75 (0.53, 1.05)

Q3: 0.88 (0.62, 1.25)

Q4: 0.72 (0.49, 1.06)

Q5: 0.74 (0.49, 1.10)

p trend 0.212

SES

Sweden

Alehagen et al. (2016)

6.8 yr

Prospective cohort

Mixed

N = 449

Population sampled: General population from a rural municipality

n = 449

Sex (% F): 52

Ethnicity: Caucasian

Age (yr): 70–80

The mortality information was obtained from

the National Board of Health and Welfare in Sweden, which registers all deaths of Swedish citizens.

N, per quartile of serum Se (μg/L)

Q1 < 57.2: 107

Q2 57.2–67.1: NR

Q3 67.1–76.1: NR

Q4 > 76.1: 111

N, per quartile

Q1: 41

Q2‐4: 81

Model 1: crude

Model 2: male gender, smoking, ischemic heart disease, diabetes, chronic obstructive pulmonary disease and ejection fraction < 40% (echocardiography)

HR (95% CI), Q1 vs Q2‐4 (ref)

Model 1: 1.67 (1.15, 2.44)

Model 2: 1.43 (1.02, 2.00)

NHANES III

(1988–1994)

USA

Eaton et al. (2010)

13.4 yr

Prospective cohort

Public

N = 10,531

Population Sampled: General population, ≥ 35 yr

Excluded: missing serum Se and serum creatinine; renal insufficiency

n = 9,304

Sex (% F):

Low Se: 64

Normal Se: 52

Ethnicity: 78% non‐Hispanic, white

Age (yr):

Low Se: 56.4 ± 1.3

Normal Se: 52.1 ± 0.4

Survival status obtained

through the National Death Index

N above/below median serum Se (μg/L)

Low Se (≤ 98 ng/mL): 418

Normal Se (> 98 ng/mL): 8,886

Age‐standardised death rate per 100,000 person‐years

Low Se (≤ 98 ng/mL): 3,509

Normal Se (> 98 ng/mL): 2,305

Model 1: age‐adjusted

Model 2: age, gender, race, geography, smoking, BMI, systolic BP, diabetes, total‐to‐HDL cholesterol ratio, physical activity, lifetime alcohol use, history of CHD or stroke, and family history of CHD

HR (95% CI), low vs normal Se

Model 1: 1.67 (1.4, 1.91)

Model 2: 1.65 (1.41, 1.93)

NHANES

(1996–2006)

USA

Li et al. (2020b)

10.2 yr (median)

Prospective cohort

Public

N = 41,474

Population sampled: General population

Excluded: missing Se data, aged < 18 yr

n = 2,903

Sex (% F): 51

Ethnicity: 56% White, 44% Non‐White

Age (yr): 61.94 ± 13.73

Mortality data extracted from the 1999–2006 NHANES public‐use linked mortality files

n, per quartile of serum Se (μg/L)

Q1 ≤ 124.0: 696

Q2 125.0–135.0: 746

Q3 136.0–147.0: 721

Q4 ≥ 148.0: 740

N, per quartile

Q1: 244

Q2: 208

Q3: 197

Q4: 209

Model 1: age, gender and BMI

Model 2: Model 1 + systolic blood pressure, total cholesterol, C‐reactive protein, alcohol consumption, smoking, race, history of hypertension, cardiovascular disease, diabetes, estimated glomerular filtration rate, use of lipid‐lowering and antiplatelet drugs.

HR (95% CI)

Model 2

Q1(ref): 1

Q2: 0.69 (0.57, 0.84)

Q3: 0.63 (0.52, 0.77)

Q4: 0.64 (0.53, 0.77)

p for trend < 0.01

Model 3

Q1(ref): 1

Q2: 0.62 (0.47, 0.81)

Q3: 0.57 (0.42, 0.75)

Q4: 0.60 (0.45, 0.78)

p for trend < 0.01

NDNS

UK

Bates et al. (2011)

14 yr

Prospective cohort

Public

N = 1,054

Population Sampled: General population aged ≥ 65 years; community living participants

Excluded: missing plasma Se; lost to follow up

n = 826

Sex (% F): 48

Ethnicity: Caucasians

Age (yr): 76.6 ± 7.4

Death registries. All participants agreed to be flagged to the National Register of Births and Deaths, and whose status (i.e. as still alive or registered as having died) was known in September 2008.

Plasma Se (μmol/L)

Males

950 ± 218 (375–2,376)

Females

924 ± 211 (461–1,786)

NR

Model 1: Age and sex

Model 2: Model 1 + other significantly predictive nutrient variables

Model 3: Model 2+ inclusion of a1‐antichymotrypsin, plasma creatinine, total and HDL‐cholesterol and albumin concentrations, BMI, systolic blood pressure, current smoking index, number of prescribed drugs being taken, self‐reported health score, physical activity score and index of poverty

HR (95% CI), per SD plasma Se

Model 1: 0.76 (0.69, 0.84)

Model 2: 0.82 (0.73, 0.91)

Model 3: 0.83 (0.73, 0.94)

InCHIANTI

Italy

Lauretani et al. (2008)

6 yr

Prospective cohort

Public

N = 1,155

Population sampled: General population, aged ≥ 65 yr

Excluded: missing blood sample or incomplete data

n = 1,042

Sex (% F): 57

Ethnicity: Caucasians

Age (yr): 75.6 ± 7.4

Mortality data collected from the General Mortality Registry of the Tuscany Region and death certificates deposited at the municipality of residence.

Quartiles of plasma Se (μmol/L)

Q1: < 0.839

Q2: 0.839–0.934

Q3: 0.935–1.037 Q4: > 1.037

n per quartile NR

N, per quartile

Q1: 98

Q2: 64

Q3: 43

Q4: 32

Model 1: age and sex

Model 2: age, sex, education, BMI,

congestive heart failure, peripheral artery disease, stroke, Parkinson's

disease and chronic obstructive pulmonary disease

HR (95% CI)

Model 1

Q1: 1.82 (1.20, 2.75)

Q2: 1.48 (0.96, 2.29)

Q3: 1.14 (0.72, 1.81)

Q4 (ref): 1

Model 2

Q1: 1.62 (1.06, 2.43)

Q2: 1.42 (0.94, 2.18)

Q3: 1.09 (0.68, 1.74)

Q4 (ref): 1

WHAS I and II

USA

Ray et al. (2006)

5 yr

Prospective cohort

Public

N WHAS I = 1,002

N WHAS II = 436

Population sampled: Community living women with and without physical disabilities

Excluded: missing serum Se, aged < 70 or > 79 yr

n = 632

Sex: females

Ethnicity: NR

Age (yr):

Died 75

Lived 73.9

Vital status determined through follow‐up interviews with proxies, obituaries, and matching with the National

Death Index

Serum Se (μmol/L geometric mean (95% CI))

1.52

Died: 1.43 (1.38–1.49)

Lived: 1.54 (1.52–1.57)

Total = 89

Model 1: age and education

Model 2: age, education, current smoking, alcohol use, BMI, fair‐to‐poor appetite, diabetes mellitus,

cardiovascular disease, and renal disease

HR (95% CI), per 1 SD of Log e Se

Model 1: 0.68 (0.55, 0.83)

Model 2: 0.71 (0.56, 0.9)

Asturias

Spain

González et al. (2007)

6 yr (mean 4.3 yr)

Prospective cohort

Mixed

N = 304

Population sampled: Elderly living in institutions

Excluded: previous history of cancer, mental impairment or CVD, in a wheelchair, with terminal disease, missing biochemical parameters, use of vitamin and/or mineral supplements or following a special diet

n = 215

Sex (% F): 59

Ethnicity: Caucasians

Age: ≥ 60 y

Vital status obtained from the institutions the participants were residing at every year

N, per quintile of serum Se (μmol/L, range)

Q1 ≤ 0.92: 47

Q2 0.93–1.04: 37

Q3 1.05–1.14: 45 Q4 1.15–1.25: 43

Q5 > 1.26: 43

N, per quintile

Q1: 17

Q2: 14

Q3: 10

Q4: 11

Q5: 8

Age, sex, smoking habit, BMI and cognitive score

RR (95% CI)

Q1(ref): 1

Q2: 1.13 (0.54, 2.39)

Q3: 0.69 (0.29, 1.60)

Q4: 0.81 (0.36, 1.82)

Q5: 0.56 (0.23, 1.40)

p for trend = 0.158

EVA

France

Akbaraly et al. (2005)

9 yr

Prospective cohort

Mixed

N = 1,389

Population sampled: General population, residents in Nantes, aged 59–71 y

Excluded: NA

n = 1,389

Sex (% F): 59

Ethnicity: Caucasians

Age (yr):

Died 65.4 ± 3.0

Lived 65.0 ± 3.0

Vital status collected from town hall civil registries

N, per quartile of plasma Se (μmol/L, median (range))

Q1: 0.87 (0.18–0.95): 337

Q2: 1.03 (0.96–1.09): 350

Q3: 1.15 (1.10–1.21): 286 Q4: 1.32 (1.22–1.97): 361

Total = 101

N per quartile NR

Age, sex, smoking,

alcohol consumption, medication, obesity, diabetes, dyslipidaemia and vascular disease

RR (95% CI)

Q1: 3.34 (1.71, 6.53)

Q2: 2.49 (1.25, 4.94)

Q3: 1.67 (0.78, 3.56)

Q4 (ref): 1

General Population Trial

China

Wei et al. (2004)

15 yr

Prospective cohort

Public

N = 29,584

Population sampled: healthy individuals aged 40–69 yr from 4 Linxian communes, participants of the General Population Trial

Excluded: NR

n = 1,103 (sub‐sample from the trial)

Sex (% F): 45

Ethnicity: Asian

Age (yr): 56.6 ± 8.0

Village doctors ascertained mortality among participants through monthly follow‐up

Quartiles of serum Se

(μmol/L)

Q1: ≤ 0.77

Q2: > 0.77–0.91

Q3: > 0.91–1.06 Q4: > 1.06

n per quartile of Se

NR

Total = 516

N per quartile of Se NR

Sex, age, cholesterol, smoking, drinking, and BMI

Assignment to treatment during trial period not included as did not affect estimates

RR (95% CI)

Q1(ref): 1

Q2: 1.01 (0.79, 1.30)

Q3: 0.96 (0.75, 1.23) Q4: 0.93 (0.72, 1.19)

p for trend = 0.57

Uppsala

Sweden

Kilander et al. (2001)

25.7 yr

Prospective cohort

Public

N = 2,322

Population sampled: men aged 50 yr resident in Uppsala

Excluded: died within 2 yr of baseline

n = 2,285

Sex: M

Ethnicity: Caucasians

Age (yr): 48.6–51.1 y

Ascertainment of deaths from the Swedish death register

Serum Se (μg/L), by education level

Low: 73.3

Medium: 77.7

High: 83.0

Total = 630 age

RR (95% CI), per 1 SD of serum Se increase

0.87 (0.80, 0.95)

Finnish Rural

Finland

Virtamo et al. (1985)

5 yr

Prospective cohort

Public

N = 1,710

Population sampled: men from rural areas of eastern and western Finland

Excluded: serum Se ≥ 45 μg/L

n = 328

East 84

West 244

Sex: males

Ethnicity: Caucasians

Age: 55–74 y

Data on deaths obtained from the National Death Certificate Register

Serum Se < 45 μg/L

NR

Model 1: age and area

Model 2: Model 1 + smoking, serum cholesterol, diastolic blood pressure, previous CHD, blood haemoglobin, FEV0.7 S, alcohol consumption

RR (95% CI)

Model 1 1.5 (1.1–2.0)

Model 2 1.4 (1.0–2.0)

Among men initially free of CHD

Model 1: 1.4 (0.9, 2.4)

Model 2: 1.5 (0.9, 2.4)

BMI: body mass index; BP: blood pressure; CI: confidence interval; CRP: c‐reactive protein; CVD: cardiovascular disease; CHD: coronary heart disease; EVA: Etude du Vieillissement Arte'riel study; F: females; FEV: forced expiratory volume; HDL: high density lipoprotein; HR: hazard ratio; IADL: Instrumental Activities of Daily Living; ilSIRENTE: Invecchiamento e Longevità nel Sirente; InCHIANTI: Invecchiare in Chianti; LDL: low density lipoprotein; M: males; MPP: The Malmö Preventive Project; NDNS: National Diet and Nutrition Survey; NHANES: National Health and Nutrition Examination Survey; NR: not reported; PREDIMED: Prevención con Dieta Mediterránea (Prevention with Mediterranean Diet); PY: person‐years; Qx: quartile/quintile x; RCT: randomised controlled trial; RR: relative risk; SD: standard deviation; Se: selenium; SES: South‐East Sweden cohort; SFFQ: semi‐quantitative food frequency questionnaire; SMHS: Shanghai Men's Health Study; SWHS: Shanghai Women's Health Study; UK: United Kingdom; USA: United States of America; WHAS: Women's Health and Aging Study; yr: year.

(a) Mean ± SD (range), unless specified otherwise.

(b): Dietary intakes were adjusted for energy intake using the nutrient density method and expressed as per μg/4184 kJ (1,000 kcal) per day (Willett al., 1997).