TABLE 2.
Characteristics of prospective cohort studies (including nested case-control and case-cohort studies) that evaluated the associations between LA biomarkers and mortality from all causes, CVD, and/or cancer1
| Study name, location | Sampling year | First author, year (ref) | Study design | Mean follow-up, y | Total sample size, n | Total deaths, n | CVD deaths, n | Cancer deaths, n | Mortality type | Age, y | Male, % | Tissue type | Measuring method | Mean/median of LA, %FA | Covariates |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| MP-1, Netherlands | 1987–1991 | de Goede, 2013 (43) | NCC | 12.5 | 444 | — | 222 | — | Fatal CAD | 50.5 | 70 | Cholesteryl esters | GC | 43.8 | Age, gender, cohort, enrollment date, smoking, BMI, educational level, alcohol intake, systolic blood pressure, total cholesterol |
| MP-2, Netherlands | 1993–1997 | de Goede, 2013 (43) | NCC | 12.5 | 114 | — | 57 | — | Fatal CAD | 51.7 | 79 | Cholesteryl esters | GC | 54.4c | Age, gender, cohort, enrollment date, smoking, BMI, educational level, alcohol intake, systolic blood pressure, total cholesterol |
| CHS, USA | 1992–1993 | Wu, 2014 (44) | Cohort | 9 | 2792 | 1994 | 678 | 411 | All-cause, CVD,2 and cancer | 74 | 36 | Phospholipids | GC | 19.7 | Age, sex, race, enrollment site, education, smoking status, prevalent diabetes, atrial fibrillation, and hypertension, leisure-time physical activity, BMI, waist circumference, alcohol use, and plasma phospholipid long-chain n–3 PUFAS (sum of ETA+DPA+DHA, % of total FAs) |
| 1992–1993 | Marklund, 2019 (7) | Cohort | 13 | 2907 | — | 832 | — | CVD | 72.1 | 36 | Phospholipids | GC-FID | 19.7 | Age, sex, race, field or clinical center if applicable, BMI, education, smoking, physical activity, alcohol intake, diabetes status, treated hypertension, treated hypercholesterolemia, regular aspirin use, biomarker concentrations of ALA, ETA, sum of trans-18:1 FAs, and sum of trans-18:2 FAs | |
| 60YO, Sweden | 1997–1999 | Marklund, 2015 (45) | Cohort | 14.5 | 1733 | 459 | — | — | All-cause and CVD2 | 60 | 47.2 | Cholesteryl esters | GC | 48.5 | Age, BMI, smoking, physical activity, education, alcohol intake, diabetes mellitus, drug-treated hypertension, and drug-treated hypercholesterolemia |
| 1997–1998 | Marklund, 2019 (7) | Cohort | 14.5 | 4150 | — | 69 | — | CVD | 60.3 | 48 | Cholesteryl esters | GC | 48.4 | Age, sex, race, field or clinical center if applicable, BMI, education, smoking, physical activity, alcohol intake, diabetes, treated hypertension, treated hypercholesterolemia, regular aspirin use, biomarker concentrations of ALA, ETA, sum of trans-18:1 FAs, and sum of trans-18:2 FAs | |
| TRIUMPH, USA | 2005–2007 | Harris, 2013 (46) | Cohort | 2 | 1144 | 135 | — | — | All-cause | 59.5 | 65.8 | Erythrocytes | GC | 13.3 | GRACE score (based on age, heart rate, systolic blood pressure, renal function, congestive heart failure, ST-segment deviation, cardiac arrest, and elevated biomarkers) |
| ULSAM-70, Sweden | 1991–1995 | Iggman, 2016 (17) | Cohort | 14.8 | 853 | 605 | 251 | — | All-cause and CVD | 71 | 100 | Adipose tissue | GC | 12.7 | Age, analysis occasion, smoking, BMI, alcohol intake, physical activity, diabetes prevalence, systolic blood pressure, dyslipidemia, and hypertension treatment |
| ULSAM-50, Sweden | 1970–1973 | Warensjö, 2008 (47) | Cohort | 30.7 | 2009 | 1012 | 461 | — | All-cause and CVD | 50 | 100 | Cholesteryl esters | GC | 53.9 | Age, total cholesterol, BMI, smoking, physical activity, and hypertension |
| 1970–1973 | Kilander, 2001 (48) | Cohort | > 10 | 1990 | 630 | 301 | 216 | All-cause,2 CVD,2 and cancer | 50 | 100 | Cholesteryl esters | GC | 54 | Age | |
| NSCS-Men, Australia | 1996 | Miura, 2016 (49) | Cohort | 17 (Max) | 444 | 98 | — | — | All-cause | 50 | 100 | Phospholipids | GC | 239.75 μg/mL | Age, sex, smoking status, blood cholesterol, jaundice measure (proxy serum β-carotene concentration), and history of serious medical condition |
| NSCS-Women, Australia | 1996 | Miura, 2016 (49) | Cohort | 17 (Max) | 564 | 81 | — | — | All-cause | 49 | 0 | Phospholipids | GC | 257.25 μg/mL | Age, sex, smoking status, blood cholesterol, jaundice measure (proxy serum β-carotene concentration), and history of serious medical condition |
| WHIMS, USA | 1996 | Harris, 2017 (50) | Cohort | 14.9 | 6501 | 1851 | 617 | 462 | All-cause, CVD, and cancer | 70 | 0 | Erythrocytes | GC | 11.89 | Age, race, hormone therapy assignment, BMI, education, smoking pack-years, physical activity, weekly alcohol intake, waist circumference, region, family history of cancer, family history of CVD, aspirin use, high cholesterol requiring pills, and a history of hypertension, diabetes, CVD, and/or cancer |
| DIA Patient, Sweden | 1996–2010 | Huang, 2012 (51) | Cohort | 1.5 | 222 | 61 | — | — | All-cause | 57 | 61 | Phospholipids | GLC | 19.7 | Age, sex, comorbidities (composite score of diabetes and CVD), dialysis modality and protein-energy wasting (Subjective Global Assessment tool), and IL-6 |
| Old patients, Norway | 1994–1995 | Lindberg, 2008 (52) | Cohort | <3 | 254 | 101 | — | — | All-cause | 82.1 | 35 | Phospholipids | GC | 18.7 | Age, sex, assignment to Geriatric Evaluation and Management Unit treatment, Barthel Index, residence (private home or sheltered housing), current smoking status, history of CVD, and HDL-cholesterol, LDL-cholesterol, prealbumin, and α-tocopherol concentrations |
| KIHD, Finland | 1984–1989 | Virtanen, 2018 (53) | Cohort | 22.4 | 2480 | 1143 | 575 | 317 | All-cause, CVD, and cancer | 53 | 100 | Total serum | GC | 26.39 | Age, examination year, BMI, family history of diabetes, smoking, education, income, leisure-time physical activity, intake of alcohol, serum long-chain n–3 PUFAs, hypertension, family history of CVD, cancer, or diabetes, use of hypercholesterolemia, hypertension, or diabetes medications at baseline or during follow-up, and intakes of SFAs, MUFAs, trans-FAs, fiber, and fruit, berries, and vegetables |
| 1984–1989 | Laaksonen, 2005 (35)2 | Cohort | 14.6 | 1551 | 202 | 69 | — | All-cause and CVD | 52 | 100 | Total serum | GC | 27.9 | Age, year of examination, smoking, alcohol consumption, adult socioeconomic status, moderate to vigorous leisure-time physical activity, plasma lipid-standardized α-tocopherol concentrations, plasma ascorbic acid, dietary total energy and energy-adjusted saturated fat and fiber intake, LDL cholesterol, systolic blood pressure, blood pressure medication, family history of ischemic heart disease, C-reactive protein concentrations, fasting concentrations of insulin and nonesterified FAs, and BMI | |
| LURIC, Germany | 1997–2000 | Delgado, 2017 (54) | Cohort | 10 | 3259 | 975 | 614 | — | All-cause and CVD | 64.9 | 70 | Erythrocytes | GC | 11.5 | Age, gender, BMI, LDL cholesterol, HDL cholesterol, log triglycerides, hypertension, diabetes, smoking, and lipid-lowering therapy |
| EUROASPIRE- Finnish, Finland | 1991–1994 | Erkkila, 2003 (55) | Cohort | 5 | 415 | 35 | 18 | — | All-cause and CAD | 60.7 | 69 | Cholesteryl esters | GC | 48.72 | Age, sex, diagnostic category (coronary artery bypass grafting, or percutaneous transluminal coronary angioplasty compared with acute myocardial infarction or acute myocardial ischemia), energy intake, serum cholesterol, serum triacylglycerol, diabetes, BMI, and education |
| EPIC-Norfolk, UK | 1993–1997 | Marklund, 2019 (7) | Cohort | 17.6 | 7016 | — | 951 | — | CVD | 63.1 | 49 | Phospholipids | GC-FID | 24.3 | Age, sex, race, field or clinical center if applicable, BMI, education, smoking, physical activity, alcohol intake, diabetes status, treated hypertension, treated hypercholesterolemia, regular aspirin use, biomarker concentrations of ALA, ETA, sum of trans-18:1 FAs, and sum of trans-18:2 FAs |
| MCCS, Australia | 1990–1994 | Marklund, 2019 (7) | Cohort | 7.1 | 6265 | — | 282 | — | CVD | 56.3 | 46 | Phospholipids | GLC-FID | 20.1 | Age, sex, race, field or clinical center if applicable, BMI, education, smoking, physical activity, alcohol intake, diabetes status, treated hypertension, treated hypercholesterolemia, regular aspirin use, biomarker concentrations of ALA, ETA, sum of trans-18:1 FAs, and sum of trans-18:2 FAs |
| MESA, USA | 2000–2002 | Marklund, 2019 (7) | Cohort | 8.6 | 2722 | — | 208 | — | CVD | 62.1 | 47 | Phospholipids | GC-FID | 21.5 | Age, sex, race, field or clinical center if applicable, BMI, education, smoking, physical activity, alcohol intake, diabetes status, treated hypertension, treated hypercholesterolemia, regular aspirin use, biomarker concentrations of ALA, ETA, sum of trans-18:1 FAs, and sum of trans-18:2 FAs |
| SHHEC, UK | 1985–1986 | Marklund, 2019 (7) | Cohort | 23.6 | 4391 | — | 308 | — | CVD | 48.7 | 52 | Adipose tissue | GC | 9.2 | Age, sex, race, field or clinical center if applicable, BMI, education, smoking, physical activity, alcohol intake, diabetes status, treated hypertension, treated hypercholesterolemia, regular aspirin use, biomarker concentrations of ALA, ETA, sum of trans-18:1 FAs, and sum of trans-18:2 FAs |
| AGES- Reykjavik, Iceland | 2002–2006 | Marklund, 2019 (7) | Cohort | 10 | 1195 | — | 162 | — | CVD | 76.6 | 39 | Phospholipids | GC-FID | 17.7 | Age, sex, race, field or clinical center if applicable, BMI, education, smoking, physical activity, alcohol intake, diabetes status, treated hypertension, treated hypercholesterolemia, regular aspirin use, biomarker concentrations of ALA, ETA, sum of trans-18:1 FAs, and sum of trans-18:2 FAs |
| HS, Japan | 2002–2003 | Marklund, 2019 (7) | Cohort | 10.2 | 3103 | — | 98 | — | CVD | 60.9 | 42 | Total plasma | GC | 27 | Age, sex, race, field or clinical center if applicable, BMI, education, smoking, physical activity, alcohol intake, diabetes status, treated hypertension, treated hypercholesterolemia, regular aspirin use, biomarker concentrations of ALA, ETA, sum of trans-18:1 FAs, and sum of trans-18:2 FAs |
| ARIC, USA | 1987–1989 | Marklund, 2019 (7) | Cohort | 22.7 | 3749 | — | 289 | — | CVD | 63.9 | 48 | Phospholipids | GC | 22 | Age, sex, race, field or clinical center if applicable, BMI, education, smoking, physical activity, alcohol intake, diabetes status, treated hypertension, treated hypercholesterolemia, regular aspirin use, biomarker concentrations of ALA, ETA, sum of trans-18:1 FAs, and sum of trans-18:2 FAs |
| CCCC, Taiwan, China | 1992–2000 | Marklund, 2019 (7) | Cohort | 14.1 | 1838 | — | 306 | — | CVD | 60.6 | 55 | Total plasma | GC-FID | 15.6 | Age, sex, race, field or clinical center if applicable, BMI, education, smoking, physical activity, alcohol intake, diabetes status, treated hypertension, treated hypercholesterolemia, regular aspirin use, biomarker concentrations of ALA, ETA, sum of trans-18:1 FAs, and sum of trans-18:2 FAs |
| HSS, USA | 2000–2002 | Pottala, 2010 (56) | Cohort | 5.9 | 956 | 237 | — | — | All-cause | 67 | 82 | Whole blood | GC | 22.96 | No |
| PPSII, France | 1981–1985 | Zureik, 1995 (57) | Cohort | 9.3 | 3277 | — | — | 59 | Cancer | 36–52 | 100 | Cholesteryl esters | GC | 48.5 | Age, smoking, alcohol consumption, BMI, and serum cholesterol |
| FHS, USA | 2005–2008 | Harris, 2018 (58) | Cohort | 7.3 | 2500 | 350 | 58 | 146 | All-cause, CVD, and cancer | 66 | 43 | Erythrocytes | GC | 11.3 | Age, sex, BMI, marital status, education, employment, health insurance status, regular aspirin use, prevalent hypertension, cholesterol medication, prevalent diabetes, alcohol consumption, smoking, metabolic equivalents, total to HDL cholesterol ratio, systolic blood pressure, C-reactive protein, omega-3 index |
| 3C, France | 1999–2001 | Satizabal, 2018 (25) | Cohort | 8.1 | 1406 | 251 | — | — | All-cause | 74.6 | 39.4 | Total plasma | GC | 24.9 | Age, sex, systolic blood pressure, antihypertensive medications, BMI, smoking, diabetes mellitus, and atrial fibrillation |
| MRFIT, USA | 1973–1976 | Simon, 1998 (59) | NCC | 6.9 | 323 | — | — | 108 | Fatal cancer | 35–57 | 100 | Cholesteryl esters | GLC | 51.66 | Age, smoking status, date of randomization, clinical center, treatment assignment, alcohol intake, plasma cholesterol concentration, and diastolic blood pressure |
| 1973–1976 | Simon, 1998 (59) | NCC | 6.9 | 323 | — | — | 108 | Fatal cancer | 35–57 | 100 | Phospholipids | GLC | 21.24 | Age, smoking status, date of randomization, clinical center, treatment assignment, alcohol intake, plasma cholesterol concentration, and diastolic blood pressure | |
| InCHIANTI, Italy | 1998–2000 | Lelli, 2019 (42) | Cohort | < 9 | 927 | 318 | 114 | — | All-cause and CVD | 75 | 44 | Total serum | GC | 24.2 | Age, sex, education, BMI, estimated glomerular filtration rate (CKD-EPI), caloric intake/body weight, smoke, hypertension, diabetes, alcohol, and oleic acid consumption |
1AGES-Reykjavik, Age, Gene/Environment Susceptibility–Reykjavik Study; ALA, α-linolenic acid; ARIC, Atherosclerosis Risk in Communities; CCCC, Chin-Shan Community Cardiovascular Cohort Study; CHS, Cardiovascular Health Study; CVD, cardiovascular disease, CAD, coronary artery disease; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; DIA Patient, a small cohort of dialysis patients in Sweden; DPA, docosapentaenoic acid; EPIC, European Prospective Investigation into Cancer and Nutrition; ETA, eicosatetraenoic acid; EUROASPIRE-Finnish, Finnish cohort of EUROASPIRE (European Action on Secondary and Primary Prevention by Intervention to Reduce Events); FA, fatty acid; FHS, Framingham Heart Study; FID, flame-ionization detection; GRACE, Global Registry of Acute Coronary Events; HS, Hisayama Study; HSS, Heart and Soul Study; InCHIANTI, longitudinal InCHIANTI study; KIHD, Kuopio Ischemic Heart Disease Risk Factor Study; LA, linoleic acid; LURIC, Ludwigshafen Risk and Cardiovascular Health Study; MCCS, Melbourne Collaborative Cohort Study; MESA, Multi-Ethnic Study of Atherosclerosis; MP-1 and MP-2, Monitoring Project on Cardiovascular Disease Risk Factors; MRFIT, Multiple Risk Factor Intervention Trial; NCC, nested case-control; NSCS, Nambour Skin Cancer Study; PPSII, Paris Prospective Study II; ref, reference; SHHEC, Scottish Heart Health Extended Cohort; TRIUMPH, Translational Research Investigating Underlying disparities in acute Myocardial Infarction Patients’ Health status study; ULSAM-50, Uppsala Longitudinal Study of Adult Men investigations, recruitment at 50 y old; ULSAM-70, Uppsala Longitudinal Study of Adult Men investigations, recruitment at 70 y old; WHIMS, Women's Health Initiative Memory Study; 3C, Three-City Study; 60YO, Stockholm old men and women; Old patients, A small cohort of frail, old patients in Norway.
2Have more updated/completed data shown in other articles and thus these records were not used in analyses.