Table 2.

Risk of incident CVD according to objective biomarker levels of linoleic acid (18:2n6) and arachidonic acid (20:4n6) in 30 pooled prospective cohort studies

				Multivariable-adjusted hazard ratio (95% CI) per interquintile range†
Outcome	Biomarker	Studies (n)	Cases (n)	Linoleic acid	Arachidonic acid
Total CVD	Phospholipid	14	6 853	1.00 (0.92–1.09)	0.95 (0.87–1.03)
	Total plasma	6	2 742	0.90 (0.78–1.03)	0.81 (0.70–0.94)
	Cholesterol esters	4	1 300	0.74 (0.63–0.88)	1.03 (0.88–1.20)
	Adipose tissue	2	1 412	0.87 (0.75–1.01)	0.98 (0.87–1.10)
	Overall‡	21	10 477	0.93 (0.88–0.99)	0.95 (0.90–1.01)
CVD mortality	Phospholipid	9	3 057	0.89 (0.79–1.00)	0.93 (0.83–1.05)
	Total plasma	4	679	0.66 (0.50–0.86)	0.85 (0.66–1.09)
	Cholesterol esters	3	473	0.56 (0.43–0.73)	0.99 (0.76–1.29)
	Adipose tissue	2	418	0.60 (0.44–0.82)	1.02 (0.84–1.23)
	Overall‡	17	4 508	0.78 (0.70–0.85)	0.94 (0.86–1.02)
Total CHD	Phospholipid	14	6 075	1.01 (0.93–1.10)	0.96 (0.90–1.03)
	Total plasma	7	2 430	0.86 (0.74–1.00)	0.86 (0.74–1.01)
	Cholesterol esters	5	1 178	0.78 (0.65–0.94)	1.02 (0.85–1.23)
	Adipose tissue	3§	3 255	0.88 (0.74–1.03)	1.10 (0.98–1.23)
	Overall‡	26§	11 857	0.94 (0.88–1.00)	0.99 (0.94–1.04)
Ischemic stroke	Phospholipid	12	2 327	0.95 (0.82–1.10)	0.98 (0.85–1.13)
	Total plasma	6	1 105	0.84 (0.66–1.06)	0.93 (0.73–1.18)
	Cholesterol esters	4	598	0.67 (0.51–0.88)	1.13 (0.89–1.43)
	Adipose tissue	2	405	0.87 (0.65–1.15)	0.91 (0.74–1.11)
	Overall‡	21	3 705	0.88 (0.79–0.98)	0.99 (0.90–1.10)

^*AA, arachidonic acid; CHD, coronary heart disease; CI, confidence interval; CVD, cardiovascular disease; LA, linoleic acid.

^†Based on harmonized, de novo individual-level analyses in each cohort, pooled using inverse-variance weighted meta-analysis. Risk was assessed according to the interquintile range (i.e., range between the midpoint of the bottom quintile [10th percentile] and the top quintile [90th percentile]) of each fatty acid, corresponding to the difference between the midpoint of the first and fifth quintiless. Study-specific analyses were adjusted for age (years), sex (male/female), race (Caucasian/non-Caucasian, or study-specific), field or clinical center if applicable (study-specific categories), body-mass index (BMI, kg/m2), education (less than high school graduate, high school graduate, some college or vocational school, college graduate), smoking (current, former, or never; if former not assessed, then current or not current), physical activity (quintiles of metabolic equivalents (METs) per week; or if METs unavailable, quintiles of study-specific definitions of physical or leisure activity), alcohol intake (none, 1–6 drinks/week, 1–2 drink/day, >2 drink/day [14 g alcohol=1 standard drink]), diabetes mellitus (yes/no; defined as treatment with oral hypoglycemic agents, insulin, or fasting plasma glucose >126 mg/dL), treated hypertension (yes/no; defined as hypertension drug use; or if unavailable, as diagnosed/history of hypertension according to study-specific definitions), treated hypercholesterolemia (yes or no; defined as lipid-lowering drug use; if unavailable, as diagnosed/history of hypercholesterolemia according to study-specific definitions), regular aspirin use (yes/no), biomarker concentrations of α-linolenic acid (ALA; 18:3n-3), eicosapentaenoic acid (EPA; 20:5n-3), sum of trans-18:1 fatty acids, and sum of trans-18:2 fatty acids (each expressed as % total fatty acids).

^‡For studies that assessed LA and AA levels in more than one biomarker compartment, the primary compartment for that study was pre-selected for pooled analyses based on the following order: 1) adipose tissue, 2) erythrocyte phospholipid, 3) plasma phospholipid 4) cholesterol ester, and 5) total plasma.

^§Because the Diet, Cancer and Health study assessed associations of AA, but not LA, with total CHD (n cases=2138), a total of, 2 studies (n cases= 1117) evaluated adipose tissue LA and 25 studies (n cases=9719) assessed any biomarker level of LA in relation to total CHD.