Table 3.

Hazard Ratios for Mortality Associated With Total EPA + DHA Intake (Diet + Supplements), by History of Disease, VITAL Study, 2000–2006^a

Cause of Death	Quartile of EPA + DHA Intake, g/day										P for Trend
	Firstb (0–0.082), No. of Deaths	Second (0.083–0.174)			Third (0.175–0.322)			Fourth (>0.322)
		No. of Deaths	HR	95% CI	No. of Deaths	HR	95% CI	No. of Deaths	HR	95% CI
All causesc	935	785	0.95	0.86, 1.06	667	0.87	0.78, 0.97	650	0.82	0.73, 0.93	0.001
No history of CVD or cancer at baseline	404	352	0.96	0.83, 1.12	280	0.83	0.70, 0.98	283	0.81	0.67, 0.98	0.011
History of CVD or cancer at baseline	529	433	0.92	0.80, 1.05	383	0.84	0.72, 0.98	362	0.81	0.69, 0.95	0.006
CVDd	228	183	0.88	0.71, 1.08	165	0.79	0.63, 0.99	189	0.87	0.68, 1.10	0.158
No history at baseline	129	92	0.77	0.58, 1.02	84	0.78	0.57, 1.05	95	0.91	0.66, 1.27	0.799
History at baseline	98	91	1.01	0.74, 1.37	80	0.81	0.58, 1.14	93	0.82	0.57, 1.17	0.167
Ischemic heart diseasee	131	105	0.90	0.68, 1.18	96	0.80	0.59, 1.07	110	0.80	0.58, 1.10	0.120
No history at baseline	76	60	0.87	0.60, 1.26	49	0.71	0.47, 1.08	48	0.62	0.39, 0.99	0.029
History at baseline	54	45	0.92	0.61, 1.40	47	0.86	0.55, 1.35	62	0.96	0.60, 1.52	0.812
Cancerf	453	390	0.94	0.82, 1.09	332	0.82	0.70, 0.96	304	0.77	0.64, 0.92	0.001
No history at baseline	218	202	0.98	0.80, 1.20	162	0.81	0.65, 1.02	166	0.79	0.62, 1.02	0.027
History at baseline	234	188	0.89	0.72, 1.09	168	0.83	0.66, 1.03	138	0.72	0.56, 0.93	0.010
Lung cancerg	142	97	0.81	0.62, 1.06	82	0.72	0.53, 0.97	90	0.77	0.56, 1.07	0.069
No history at baseline	105	76	0.84	0.62, 1.15	63	0.69	0.49, 0.98	79	0.89	0.62, 1.28	0.310
History at baseline	37	21	0.35	0.16, 0.77	18	0.75	0.34, 1.65	11	0.12	0.04, 0.40	0.176
Hematopoietic cancerh	48	52	1.11	0.72, 1.72	29	0.79	0.48, 1.32	35	0.84	0.49, 1.45	0.396
No history at baseline	28	35	1.26	0.73, 2.18	20	0.97	0.52, 1.83	20	0.95	0.52, 1.90	0.736
History at baseline	20	17	0.72	0.32, 1.62	9	0.64	0.12, 0.82	14	0.55	0.21, 1.45	0.100
Colorectal canceri	47	30	0.72	0.44, 1.17	24	0.61	0.35, 1.04	30	0.71	0.40, 1.25	0.194
No history at baseline	23	18	0.79	0.41, 1.54	13	0.71	0.34, 1.50	11	0.60	0.25, 1.40	0.220
History at baseline	24	12	0.49	0.21, 1.12	11	0.47	0.20, 1.10	19	0.73	0.31, 1.74	0.414
Breast cancerj	38	35	1.12	0.68, 1.85	29	1.07	0.61, 1.86	13	0.66	0.32, 1.36	0.391
No history at baseline	7	6	1.05	0.34, 3.29	6	1.27	0.37, 4.31	2	0.51	0.08, 3.13	0.713
History at baseline	30	29	1.11	0.63, 1.94	23	0.96	0.51, 1.79	11	0.61	0.27, 1.39	0.297
Pancreatic cancerk	29	32	1.58	0.91, 2.75	23	1.09	0.58, 2.06	16	0.78	0.36, 1.70	0.505
No history at baseline	26	26	1.17	0.66, 2.08	19	0.95	0.49, 1.86	13	0.65	0.28, 1.51	0.349
History at baseline	3	6	—l	—	4	—	—	3	—	—	—
Other cancersf	133	130	1.08	0.84, 1.40	124	1.01	0.77, 1.33	109	0.90	0.67, 1.23	0.485
Other causesc	244	205	1.02	0.84, 1.25	161	0.92	0.73, 1.14	150	0.84	0.64, 1.08	0.145

Abbreviations: CI, confidence interval; CVD, cardiovascular disease; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; HR, hazard ratio; MET, metabolic equivalent of task; VITAL, Vitamins and Lifestyle.

^a Numbers may not sum to totals because of missing data. All models adjusted for age (as the time scale), sex, race/ethnicity, marital status (married/living together, never married, separated/divorced, widowed, or missing), education (high school graduate or less, some college, or college/advanced degree), body mass index (weight (kg)/height (m)²) at age 45 years (<18.5, 18.5–<25.0, 25.0–29.9, ≥30.0, or missing), average physical activity in the 10 years before baseline (MET-hours/week; tertiles), smoking (never, 1–12.5 pack-years, 12.6–35.0 pack-years, >35.0 pack-years, or missing), average alcohol intake at age 45 years (none, <1 drink/day, 1–2 drinks/day, >2 drinks/day, or missing), total energy intake (kcal/day; continuous), number of servings per day of fruits (quartiles), number of servings per day of vegetables (quartiles), dietary intake of arachidonic acid (g/day; continuous), aspirin use in the past 10 years (none, low, high, or missing), use of nonaspirin nonsteroidal antiinflammatory drugs in the past 10 years (none, low, high, or missing), self-rated health (excellent, very good, good, fair, or poor), sigmoidoscopy in the last 10 years (yes/no), mammogram in the last 2 years (yes/no), prostate-specific antigen test in the last 2 years (yes/no), and current use of cholesterol-lowering medication (yes/no).

^b Reference category (HR = 1).

^c Results were additionally adjusted for morbidity score (see footnote c of Table 2), percentage of calories derived from trans fat (quartiles), percentage of calories derived from saturated fat (quartiles), years of estrogen therapy (none, <5, 5–9, ≥10, or missing), years of estrogen + progestin therapy (none, <5, 5–9, ≥10, or missing), age at menopause (≤39 years, 40–44 years, 45–49 years, 50–54 years, ≥55 years, or missing), age at death of father (≤59 years, 60–69 years, 70–79 years, 80–89 years, or ≥90 years), and age at death of mother (≤59 years, 60–69 years, 70–79 years, 80–89 years, or ≥90 years).

^d Results were additionally adjusted for history of cardiovascular disease (yes/no; defined as history of heart attack, coronary bypass surgery, angioplasty, stroke, congestive heart failure, or diagnosis of angina) family history of heart attack (number of relatives: 0, 1, or ≥2), current use of blood pressure medication (yes/no), percentage of calories derived from trans fat (quartiles), percentage of calories derived from saturated fat (quartiles), years of estrogen therapy (none, <5, 5–9, or ≥10), and years of estrogen + progestin therapy (none, <5, 5–9, or ≥10).

^e Results were additionally adjusted for history of ischemic heart disease (yes/no; defined as history of heart attack, coronary bypass surgery, angioplasty, or diagnosis of angina), family history of heart attack (number of relatives: 0, 1, or ≥2), current use of blood pressure medication (yes/no), percentage of calories derived from trans fat (quartiles), percentage of calories derived from saturated fat (quartiles), years of estrogen therapy (none, <5, 5–9, or ≥10), and years of estrogen + progestin therapy (none, <5, 5–9, or ≥10).

^f Results were additionally adjusted for history of cancer other than nonmelanoma skin cancer (yes/no), family history of cancer (number of relatives: 0, 1, or ≥2), years of estrogen therapy (none, <5, 5–9, or ≥10), years of estrogen + progestin therapy (none, <5, 5–9, or ≥10), age at menopause (≤39, 40–44, 45–49, 50–54, or ≥55 years), age at menarche (≤11, 12, 13, or ≥14 years), and number of servings of red/processed meat per week (quartiles).

^g Results were additionally adjusted for history of lung cancer (yes/no), family history of lung cancer (number of relatives: 0, 1, or ≥2), history of emphysema, chronic bronchitis, or chronic obstructive pulmonary disease (yes/no), years of smoking, and pack-years squared.

^h Results were additionally adjusted for history of leukemia/lymphoma (yes/no), family history of leukemia/lymphoma (number of relatives: 0, 1, or ≥2), history of any cancer (yes/no), history of rheumatoid arthritis (yes/no), and history of fatigue/lack of energy (yes/no).

ⁱ Results were additionally adjusted for history of colorectal cancer (yes/no), family history of colorectal cancer (number of relatives: 0, 1, or ≥2), history of diabetes (yes/no), years of estrogen therapy (none, <5, 5–9, or ≥10), years of estrogen + progestin therapy (none, <5, 5–9, or ≥10), calcium intake from diet, calcium intake from supplements, and number of servings of red/processed meat per week (quartiles).

^j Results were additionally adjusted for history of breast cancer (yes/no), family history of breast cancer (number of relatives: 0, 1, or ≥2), years of estrogen therapy (none, <5, 5–9, or ≥10), years of estrogen + progestin therapy (none, <5, 5–9, or ≥10), age at first birth, history of hysterectomy (none, simple, total), age at menopause (≤39, 40–44, 45–49, 50–54, or ≥55 years), and age at menarche (≤11, 12, 13, or ≥14 years).

^k Results were additionally adjusted for history of pancreatic cancer (yes/no), family history of pancreatic cancer (number of relatives: 0, 1, or ≥2), number of servings of red/processed meat per week (quartiles), and history of diabetes (yes/no).

^l Hazard ratios and 95% confidence intervals were not calculated because of small numbers of deaths.