Table 2. Association Between Fish Intake and Clinical Events in Each Study^a.

Event	Category of fish intake, HR (95% CI)				P value for trend
	<50 g/mo	50 g/mo to <175 g/wk	175 to <350 g/wk	≥350 g/wk
PURE trial (n = 147 541)
Intake, median (IQR), g/wk	0.1 (0.0-7.0)	67.9 (32.9-109.9)	231.0 (197.4-273.7)	593.6 (450.1-1050.0)
Composite of death or major CVD
No. of participants	37 428	62 391	22 502	25 324
No. (%) of events (n = 15 019)	4338 (11.6)	6331 (10.2)	1799 (8.0)	2551 (10.1)
Age and sex adjusted	1 [Reference]	0.98 (0.94-1.02)	0.87 (0.81-0.92)	0.90 (0.84-0.96)	<.001
Multivariable	1 [Reference]	1.00 (0.95-1.04)	0.93 (0.88-1.00)	0.96 (0.89-1.03)	.08
No history of CVD	1 [Reference]	1.00 (0.95-1.05)	0.94 (0.88-1.01)	0.97 (0.90-1.04)	.18
History of CVD	1 [Reference]	0.96 (0.84-1.09)	0.89 (0.74-1.06)	0.90 (0.74-1.09)	.17
Total mortality
No. of participants	37 428	62 391	22 502	25 324
No. (%) of deaths (n = 10 076)	3131 (8.4)	4069 (6.5)	1140 (5.1)	1736 (6.9)
Age and sex adjusted	1 [Reference]	1.00 (0.95-1.05)	0.89 (0.83-0.96)	0.91 (0.84-0.99)	.005
Multivariable	1 [Reference]	1.02 (0.96-1.08)	0.98 (0.90-1.07)	0.96 (0.88-1.05)	.35
No history of CVD	1 [Reference]	1.02 (0.96-1.08)	0.98 (0.90-1.07)	0.97 (0.88-1.06)	.48
History of CVD	1 [Reference]	0.94 (0.79-1.11)	0.92 (0.73-1.16)	0.91 (0.71-1.16)	.36
Major CVD events
No. of participants	37 428	62 391	22 502	25 324
No. (%) of events (n = 8201)	2215 (5.9)	3524 (5.6)	1001 (4.4)	1461 (5.8)
Age and sex adjusted	1 [Reference]	0.98 (0.92-1.04)	0.85 (0.78-0.92)	0.90 (0.83-0.99)	.001
Multivariable	1 [Reference]	1.00 (0.94-1.07)	0.89 (0.82-0.97)	0.95 (0.86-1.04)	.06
No history of CVD	1 [Reference]	1.00 (0.94-1.08)	0.91 (0.83-1.00)	0.97 (0.88-1.08)	.24
History of CVD	1 [Reference]	0.97 (0.83-1.13)	0.83 (0.67-1.03)	0.86 (0.69-1.08)	.08
Myocardial infarction
No. of participants	37 428	62 391	22 502	25 324
No. (%) of events (n = 3806)	1146 (3.1)	1486 (2.4)	456 (2.0)	718 (2.8)
Age and sex adjusted	1 [Reference]	0.97 (0.89-1.06)	0.90 (0.80-1.02)	0.88 (0.77-1.00)	.03
Multivariable	1 [Reference]	1.01 (0.92-1.11)	0.97 (0.85-1.10)	0.90 (0.78-1.04)	.15
No history of CVD	1 [Reference]	1.01 (0.91-1.12)	0.97 (0.84-1.12)	0.96 (0.82-1.11)	.46
History of CVD	1 [Reference]	0.95 (0.76-1.18)	0.96 (0.71-1.29)	0.71 (0.51-0.99)	.07
Stroke
No. of participants	37 428	62 391	22 502	25 324
No. (%) of events (n = 3925)	986 (2.6)	1827 (2.9)	478 (2.1)	634 (2.5)
Age and sex adjusted	1 [Reference]	0.95 (0.87-1.04)	0.80 (0.71-0.90)	0.91 (0.80-1.03)	.01
Multivariable	1 [Reference]	0.97 (0.88-1.06)	0.81 (0.72-0.92)	0.95 (0.83-1.08)	.09
No history of CVD	1 [Reference]	0.96 (0.87-1.06)	0.84 (0.73-0.96)	0.97 (0.84-1.11)	.22
History of CVD	1 [Reference]	1.00 (0.80-1.25)	0.75 (0.55-1.03)	0.91 (0.66-1.27)	.22
Sudden cardiac death
No. of participants	37 428	62 391	22 502	25 324
No. (%) of events (n = 371)	109 (0.3)	189 (0.3)	30 (0.1)	43 (0.2)
Age and sex adjusted	1 [Reference]	0.84 (0.64-1.09)	0.91 (0.57-1.46)	1.03 (0.64-1.65)	.79
Multivariable	1 [Reference]	0.78 (0.58-1.05)	0.83 (0.49-1.40)	0.99 (0.59-1.68)	.69
No history of CVD	1 [Reference]	0.78 (0.56-1.08)	0.75 (0.41-1.36)	1.10 (0.64-1.89)	.91
History of CVD	1 [Reference]	0.31 (0.11-0.87)	0.80 (0.18-3.68)	0.67 (0.02-19.2)	.50
CVD death
No. of participants	37 428	62 391	22 502	25 324
No. (%) of events (n = 3102)	993 (2.6)	1206 (1.9)	317 (1.4)	586 (2.3)
Age and sex adjusted	1 [Reference]	1.02 (0.93-1.12)	0.87 (0.76-1.01)	0.90 (0.78-1.04)	.07
Multivariable	1 [Reference]	1.06 (0.96-1.18)	0.94 (0.81-1.10)	0.94 (0.80-1.10)	.33
No history of CVD	1 [Reference]	1.07 (0.96-1.20)	0.97 (0.82-1.15)	0.99 (0.84-1.20)	.84
History of CVD	1 [Reference]	0.95 (0.75-1.19)	0.81 (0.57-1.13)	0.72 (0.51-1.03)	.047
Non-CVD death
No. of participants	37 428	62 391	22 502	25 324
No. (%) of events (n = 5904)	1820 (4.9)	2414 (3.9)	707 (3.1)	963 (3.8)
Age and sex adjusted	1 [Reference]	0.98 (0.92-1.05)	0.91 (0.82-1.00)	0.94 (0.85-1.04)	.11
Multivariable	1 [Reference]	1.00 (0.93-1.07)	1.00 (0.90-1.11)	1.00 (0.90-1.12)	.99
No history of CVD	1 [Reference]	1.00 (0.92-1.07)	0.98 (0.88-1.10)	0.99 (0.88-1.10)	.76
History of CVD	1 [Reference]	0.96 (0.74-1.23)	1.05 (0.75-1.49)	1.09 (0.75-1.58)	.17
ONTARGET and TRANSCEND (n = 31 491)b,c
Intake, median (IQR), g/d	2.8 (0 to 9.2)	119.7 (55.3-119.7)	240.1 (200.2-249.9)	450.1 (359.8-720.3)
Composite of death or major CVD
No. of participants	2801	16 377	7252	5061
No. (%) of events	642 (22.9)	3434 (21.0)	1395 (19.2)	979 (19.3)
Age and sex adjusted	1 [Reference]	0.94 (0.86-1.03)	0.85 (0.77-0.93)	0.84 (0.75-0.93)	<.001
Multivariable	1 [Reference]	0.96 (0.88-1.05)	0.88 (0.80-0.97)	0.88 (0.79-0.98)	.002
Total mortality
No. of participants	2801	16 377	7252	5061
No. (%) of events	404 (14.42)	2005 (12.24)	825 (11.38)	537 (10.61)
Age and sex adjusted	1 [Reference]	0.90 (0.80-1.00)	0.82 (0.72-0.92)	0.75 (0.66-0.86)	<.001
Multivariable	1 [Reference]	0.92 (0.82-1.02)	0.86 (0.76-0.98)	0.81 (0.70-0.92)	<.001
Major CVD events
No. of participants	2801	16 377	7252	5061
No. (%) of events	504 (18.0)	2752 (16.8)	1116 (15.4)	810 (16.0)
Age and sex adjusted	1 [Reference]	0.96 (0.87-1.06)	0.86 (0.77-0.96)	0.87 (0.78-0.98)	.001
Multivariable	1 [Reference]	0.97 (0.88-1.08)	0.89 (0.80-1.00)	0.91 (0.81-1.03)	.02
Myocardial infarction
No. of participants	2801	16 377	7252	5061
No. (%) of events	151 (5.4)	791 (4.8)	360 (5.0)	250 (4.9)
Age and sex adjusted	1 [Reference]	0.86 (0.72-1.02)	0.85 (0.70-1.03)	0.84 (0.68-1.04)	.22
Multivariable	1 [Reference]	0.86 (0.72-1.03)	0.86 (0.71-1.05)	0.86 (0.69-1.06)	.34
Stroke
No. of participants	2801	16 377	7252	5061
No. (%) of events	118 (4.2)	740 (4.5)	285 (3.9)	252 (5.0)
Age and sex adjusted	1 [Reference]	1.07 (0.87-1.30)	0.93 (0.75-1.16)	1.15 (0.91-1.44)	.64
Multivariable	1 [Reference]	1.11 (0.91-1.36)	0.99 (0.80-1.24)	1.25 (1.00-1.58)	.20
Sudden cardiac death
No. of participants	2801	16 377	7252	5061
No. (%) of events	43 (1.5)	221 (1.4)	101 (1.4)	66 (1.3)
Age and sex adjusted	1 [Reference]	1.04 (0.74-1.47)	1.03 (0.71-1.48)	0.93 (0.62-1.39)	.30
Multivariable	1 [Reference]	1.04 (0.74-1.46)	1.05 (0.72-1.52)	0.94 (0.63-1.42)	.72
CVD death
No. of participants	2801	16 377	7252	5061
No. (%) of events	243 (8.7)	1199 (7.3)	497 (6.8)	326 (6.4)
Age and sex adjusted	1 [Reference]	0.91 (0.79-1.04)	0.83 (0.71-0.98)	0.76 (0.64-0.91)	<.001
Multivariable	1 [Reference]	0.92 (0.80-1.06)	0.87 (0.74-1.02)	0.80 (0.67-0.96)	.01
Non-CVD death
No. of participants	2801	16 377	7252	5061
No. (%) of events	161 (5.8)	806 (4.9)	328 (4.5)	211 (4.2)
Age and sex adjusted	1 [Reference]	0.87 (0.73-1.03)	0.78 (0.64-0.94)	0.73 (0.59-0.90)	.001
Multivariable	1 [Reference]	0.89 (0.75-1.06)	0.83 (0.68-1.01)	0.79 (0.64-0.98)	.02
ORIGIN trial (n = 12 422)b,c
Intake, median (IQR), g/d	2.2 (0 to 8.8)	64.5 (28.0-119.7)	248.5 (211.4-319.2)	567.7 (445.2-874.3)
Composite of death or major CVD
No. of participants	3572	5049	1995	1806
No. (%) of events	866 (24.2)	1022 (20.2)	395 (19.8)	391 (21.6)
Age and sex adjusted	1 [Reference]	0.76 (0.70-0.84)	0.70 (0.62-0.79)	0.77 (0.69-0.87)	<.001
Multivariable	1 [Reference]	0.81 (0.74-0.89)	0.81 (0.72-0.92)	0.88 (0.77-0.99)	.02
Total mortality
No. of participants	3572	5049	1995	1806
No. (%) of events	650 (18.2)	707 (14.0)	259 (13.0)	261 (14.4)
Age and sex adjusted	1 [Reference]	0.73 (0.66-0.81)	0.65 (0.57-0.75)	0.73 (0.63-0.85)	<.001
Multivariable	1 [Reference]	0.79 (0.71-0.88)	0.77 (0.66-0.90)	0.86 (0.74-1.00)	.01
Major CVD events
No. of participants	3572	5049	1995	1806
No. (%) of events	656 (18.4)	781 (15.5)	286 (14.3)	297 (16.4)
Age and sex adjusted	1 [Reference]	0.80 (0.72-0.89)	0.72 (0.62-0.82)	0.82 (0.72-0.95)	<.001
Multivariable	1 [Reference]	0.81 (0.73-0.90)	0.77 (0.66-0.89)	0.87 (0.76-1.01)	.02
Myocardial infarction
No. of participants	3572	5049	1995	1806
No. (%) of events	155 (4.34)	224 (4.44)	101 (5.06)	111 (6.15)
Age and sex adjusted	1 [Reference]	0.96 (0.79-1.18)	1.06 (0.82-1.36)	1.28 (1.00-1.63)	.04
Multivariable	1 [Reference]	0.90 (0.73-1.11)	0.97 (0.74-1.25)	1.16 (0.90-1.49)	.21
Stroke
No. of participants	3572	5049	1995	1806
No. (%) of events	173 (4.8)	211 (4.2)	75 (3.8)	74 (4.1)
Age and sex adjusted	1 [Reference]	0.83 (0.67-1.01)	0.72 (0.55-0.95)	0.79 (0.60-1.04)	.03
Multivariable	1 [Reference]	0.83 (0.68-1.02)	0.75 (0.57-1.00)	0.82 (0.62-1.09)	.09
Sudden cardiac death
No. of participants	3572	5049	1995	1806
No. (%) of events	202 (5.6)	170 (3.4)	63 (3.2)	72 (4.0)
Age and sex adjusted	1 [Reference]	0.56 (0.46-0.69)	0.51 (0.38-0.68)	0.64 (0.49-0.84)	<.001
Multivariable	1 [Reference]	0.61 (0.49-0.75)	0.60 (0.45-0.81)	0.73 (0.55-0.98)	.006
CVD death
No. of participants	3572	5049	1995	1806
No. (%) of events	416 (11.6)	433 (8.6)	138 (6.9)	148 (8.2)
Age and sex adjusted	1 [Reference]	0.70 (0.61-0.80)	0.55 (0.45-0.66)	0.65 (0.54-0.79)	<.001
Multivariable	1 [Reference]	0.76 (0.66-0.87)	0.66 (0.54-0.80)	0.78 (0.64-0.94)	<.001
Non-CVD death
No. of participants	3572	5049	1995	1806
No. (%) of events	234 (6.6)	274 (5.4)	121 (6.1)	113 (6.3)
Age and sex adjusted	1 [Reference]	0.78 (0.66-0.93)	0.84 (0.68-1.05)	0.88 (0.70-1.10)	.23
Multivariable	1 [Reference]	0.84 (0.70-1.01)	0.97 (0.77-1.22)	1.00 (0.79-1.26)	.86

Abbreviations: CVD, cardiovascular disease; IQR, interquartile range; ONTARGET, Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial; ORIGIN, Outcome Reduction With Initial Glargine Intervention; PURE, Prospective Urban Rural Epidemiology; TRANSCEND, Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease.

^aAdjusted for age, sex and study center (latter as random effect). Multivariable model is adjusted for age, sex, study center (random effect), body mass index, educational level (primary or less; secondary; trade, college, or university), smoking status (never, former, or current), alcohol intake, physical activity (low, <600; moderate, 600-3000; high, >3000 metabolic equivalent of task per minute per week), urban or rural location, history of diabetes, cancer, use of statin or antihypertension medications, and intake of fruit, vegetables, red meat, poultry, dairy, and total energy.

^bIn ONTARGET and TRANSCEND combined and in the ORIGIN trial, physical activity categories were: mainly sedentary (reference standard); 1 to 4 times per week; and more than 4 times per week.

^cONTARGET and TRANSCEND combined and the ORIGIN trial also adjusted for treatment allocation.