Fatty acids linked to cardiovascular mortality are associated with risk factors

Figures & data

Table I. Population characteristics, Genetics of Coronary Artery Disease in Alaska Natives

	Women				Men
	N	Mean	SD	Median	N	Mean	SD	Median
CVD risk factors
Systolic BP (mmHg)	419	120.60	(16.8)	118	336	122.35	(14.2)	122
Diastolic BP (mmHg)	420	75.20	(9.2)	74	337	78.46	(9.58)	79
Mean arterial BP (mmHg)	419	105.47	(12.9)	104	336	106.94	(107.71)	107.3
BMI (kg/m^2)	419	28.65	(6.2)	27.6	334	26.69	(5.1)	25.6
Waist (cm)	414	89.25	(14.2)	87.63	330	88.77	(12.0)	86.36
HDL-C (mg/dL)	419	66.94	(18.7)	65	337	57.39	(19.0)	54
LDL-C (mg/dL)	419	122.43	(35.1)	117	337	123.11	(36.6)	119
Triglyceride (mg/dL)	419	133.55	(77.8)	114	337	125.32	(70.8)	107
HbA1c (%)	421	5.51	(0.46)	5.41	337	5.53	(0.54)	5.5
Fasting glucose (mg/dL)	421	96.79	(17.8)	92	337	96.81	(25.1)	93
Fasting insulin (µU/mL)	420	10.86	(7.9)1	8.85	335	9.62	(9.2)	7.21
2-hour glucose (mg/dL)	282	107.54	(42.4)	102	237	93.35	(38.4)	88
2-hour insulin (µU/mL)	280	44.86	(41.9)	31.65	237	28.40	(37.4)	16.4
Heart rate (beats/minute)	383	73.75	(10.4)	72	324	71.19	(13.1)	70
C-reactive protein	420	0.426	(1.7)	0.12	337	0.338	(0.7)	0.11
Covariates
METS	337	56.62	(58.1)	37.51	289	68.95	(66.1)	49.27
Age (year)	421	51.97	(12.2)		337	51.01	(11.7)
Current smoking (%)	421	53			337	60
Cholesterol medication (%)	421	9.5			337	7.4
BP medication (%)	421	22			337	19
ApoE (n)	421				337
ApoE2 (%)	1				2
ApoE3 (%)	73				66
ApoE4 (%)	32				28

Abbreviations: ApoE=apolipoprotein E; BP=blood pressure; BMI=body mass index; CRP=C-reactive protein; HDL-C=high-density lipoprotein cholesterol; LDL-C=low-density lipoprotein cholesterol; METS=metabolic equivalents.

Table II. Fatty acid proportions (% of total fatty acids) as measured in plasma (bold) and red blood cells (black), Genetics of Coronary Artery Disease in Alaska Natives

	Male (age in years)					Female (age in years)
Fatty acid	35–44	45–54	55–64	65–74	p	35–44	45–54	55–64	65–74	p
Total omega 3	4.86 9.92	5.34 10.76	5.94 12.79	5.96 12.47	0.1428 <0.0001	5.29 11.21	5.57 11.81	5.77 12.85	7.14 15.37	0.0097 <0.0001
18:3-3	0.56 0.21	0.55 0.22	0.57 0.21	0.61 0.24	0.8893 0.8758	0.6 0.23	0.57 0.22	0.56 0.24	0.64 0.22	0.4561 0.6777
20:5-3	1.13 1.57	1.3 1.91	1.44 2.56	1.88 2.65	0.0444 0.0003	1.14 1.93	1.36 2.17	1.35 2.56	1.78 3.45	<0.0001 <0.0001
22:5-3	0.56 2.33	0.59 2.44	0.6 2.69	0.58 2.61	0.3165 0.0018	0.59 2.51	0.54 2.48	0.51 2.58	0.67 2.91	0.0527 0.0042
22:6-3	2.14 5.81	2.47 6.18	2.57 7.34	2.7 6.97	0.0948 <0.0001	2.45 6.53	2.67 6.94	2.72 7.48	3.52 8.78	0.0020 <0.0001
C20-C22	4.19 9.71	4.71 10.53	5.15 12.58	5.27 12.23	0.2125 <0.0001	4.41 10.97	4.92 11.59	4.93 12.61	6.55 15.14	0.0001 <0.0001
Total omega 6	35.06 35.34	29.35 34.23	27.81 32.93	32.32 32.98	0.3833 0.0003	30.17 34.16	31.27 33.12	35.34 31.56	29.27 29.53	0.7880 <0.0001
18:2-6	28.64 18.39	28.04 18.17	26.82 17.84	25.48 17.28	0.0153 0.2971	27.57 18.08	26.78 17.21	24.76 16.52	23.84 15.3	<0.0001 <0.0001
20:4-6	1 13.06	1.07 12.59	0.94 11.96	1.08 12.37	0.2567 0.0013	1 12.5	1.05 12.35	1.02 11.95	1.13 11.49	0.4566 0.0053
Total MUFA	22.95 16.47	22.78 16.83	24.28 16.86	23.21 17.13	0.8910 0.0709	22.34 16.64	22.79 17.07	23.81 17.34	23.38 17.15	0.5446 0.0617
16:1-7	2.11 0.58	2.29 0.7	2.3 0.72	2.54 0.8	0.0010 0.0031	2.57 0.84	2.67 0.94	2.76 1.04	2.83 1.06	0.0509 0.0094
18:1-9	18.96 15.2	19.29 15.5	19.62 15.47	20.1 15.65	0.3088 0.2088	18.82 15.17	18.9 15.43	18.85 15.66	18.81 15.49	0.9951 0.1887
20:1-9	0.13 0.24	0.18 0.18	0.17 0.2	0.19 0.21	0.3633 <0.0001	0.14 0.2	0.13 0.2	0.13 0.18	0.11 0.15	0.6349 <0.0001
24:1-9	0.37 0.45	0.3 0.45	0.4 0.48	0.2 0.46	0.8989 0.7724	0.41 0.44	0.38 0.49	0.52 0.46	0.42 0.45	0.5477 0.1418
Total SFA	31.9 35.06	31.14 35.19	31.15 34.42	31.74 34.36	0.3279 0.3815	32.24 34.98	32.51 35.09	33.57 35.38	33.34 35.22	0.0375 0.3801
14:0	0.89 0.34	0.88 0.39	0.79 0.34	0.86 0.38	0.4904 0.1697	0.98 0.42	0.97 0.41	1.05 0.44	1.11 0.46	0.1615 0.2431
16:0	23.81 20.49	23.09 20.82	23.15 20.34	23.81 20.51	0.2858 0.2305	24.14 21	24.29 21.02	25.15 21.37	24.87 21.37	0.0767 0.0766
18:0	7.19 14.23	7.17 13.97	7.21 13.73	7.07 13.47	0.9178 0.1867	7.12 13.56	7.24 13.65	7.38 13.57	7.35 13.4	0.4019 0.942
Total trans FAs	1.61 2.24	1.48 2.08	1.39 2.09	1.45 2.17	0.1042 0.1144	1.53 2.14	1.7 2.04	1.58 2.03	1.44 1.92	0.1539 0.0869

Table III. Associations^a between CVD risk factors and total plasma fatty acids (µg/ml), Genetics of Coronary Artery Disease in Alaska Natives

0	14:0 Myristic	16:0 Palmitic	16:1-7 Palmitoleic	18:3-6 γ-Linolenic	20:3-6 Dihomo-γ-linolenic	18:0 Stearic	18:1 Oleic	18:2-6 Linoleic	20:4-6 Arachidonic	18:3-3 α-Linolenic	20:5-3 Eicosapentaenoic	22:6-3 Docosahexaenoic
Mortality	+	+	+	+	+	NS	+	–	NS	NS	NS	NS
Triglyceride	0.587 (5.2E^−29)	0.440 (7.9E^−16)	0.469 (1.8E^−23)	0.250 (1.4E^−06)	0.344 (3.3E^−13)	0319 (4.7E^−09)	0.377 (1.4E^−15)	0.209 (8.9E^−06)	0	0.421 (4.5E^−15)	0.119 (0.047)	0
LDL-C	0.115 (0.03)	0.169 (0.002)	0.205 (0.000)	NS	0.113 (0.031)	0.235 (0.0000)	0.198 (0.0001)	0.249 (1.2E^−06)	0.217 (0.0000)	0	0.254 (4.5E^−06)	0.337 (8.9E^−10)
HDL-C	−0.263 (4.0E^−7)	NS	−0 (0.028)	NS	NS	NS	−0.137 (0.009)	NS	NS	−0.146 (0.017)	NS	NS
CRP	NS	NS	NS	NS	NS	NS	NS	NS	NS	NS	−0.108 (0.026)	NS
SBP	0.096 (0.031)	0.097 (0.029)	NS	0.110 (0.023)	0.137 (0.002)	NS	NS	NS	NS	NS	NS	NS
DBP	0.114 (0.013)	NS	NS	0.115 (0.021)	0.107 (0.021)	NS	0.091 (0.048)	NS	NS	NS	NS	NS
ABP	0.107 (0.018)	0.101 (0.024)	NS	0.118 (0.015)	0.143 (0.002)	NS	0.096 (0.031)	NS	NS	NS	NS	NS
HR	NS	NS	NS	NS	NS	NS	0	NS	−0.168 (0.0002)	NS	−0.209 (0.0000)	−0.219 (0.0000)
BMI	0.255 (1.2E^07)	0.199 (0.0000)	0.172 (0.001)	0.174 (0.001)	0.197 (0.0001)	0.190 (0.0001)	0.161 (0.001)	NS	0.123 (0.012)	0.175 (0.003)	NS	NS
Waist	0.280 (1.5E^−08)	0.209 (0.0000)	0.187 (0.0000)	0.204 (0.0002)	0.193 (0.0001)	0.189 (0.0001)	0.180 (0.0002)	NS	0.137 (0.006)	0.166 (0.005)	NS	NS
% fat	0.268 (1.2E^−07)	0.183 (0.0004)	NS	0.207 (0.0001)	0.198 (0.0001)	0.159 (0.0018)	NS	NS	NS	NS	NS	NS
2-hour glucose	0.175 (0.0021)	0.166 (0.004)	0.200 (0.0005)	NS	0.181 (0.001)	NS	0.159 (0.005)	NS	NS	NS	NS	NS
2-hour insulin	0.160 (0.007)	0.138 (0.023)	(0.0001)	0.146 (0.026)	0.165 (0.005)	NS	0.119 (0.046)	NS	NS	0.150 (0.018)	NS	NS
Fasting glucose	0.100 (0.035)	NS	NS	NS	NS	NS	NS	NS	NS	NS	NS	NS
Fasting insulin	0.282 (2.88E^09)	0.195 (0.0000)	NS	0.137 (0.0065)	0.23 (0.0000)	0.186 (0.0001)	NS	NS	NS	NS	NS	NS
HbA1c	0.141 (0.003)	NS	NS	0.191 (0.003)	NS	NS	NS	NS	NS	NS	NS	NS

^aResults are presented as phenotypic correlation estimate (p-value). Negative associations are shown in bold. All phenotypes are adjusted for age, age², sex, age×sex, age²×sex, BMI and physical activity. BMI was not used as a covariate for the BMI analysis. Additional covariates were used as follows: lipid medications for lipids, antihypertensive medication for HR and SBP and smoking for CRP.

Mortality data are from Warensjo et al. (3).

BMI=body mass index; BP=blood pressure; CRP=C-reactive protein; DBP=diastolic blood pressure; HDL-C=high-density lipoprotein cholesterol; HR=heart rate; LDL-C=low-density lipoprotein cholesterol; MAP=mean arterial pressure; SBP=systolic blood pressure; NS=not significant.

Table IV. Associations between CVD risk factors and% of total fatty acids in RBCs^a, Genetics of Coronary Artery Disease in Alaska Natives

	14:0 Myristic	16:0 Palmitic	16:1-7 Palmitoleic	18:3-6 γ-Linolenic	20:3-6 Dihomo-γ-linolenic	18:0 Stearic	18:1 Oleic	18:2-6 Linoleic	20:4-6 Arachidonic	18:3-3 α-Linolenic	20:5-3 Eicosapentaenoic	22:6-3 Docosahexaenoic
Mortality	+	+	+	+	+	NS	+	–	NS	NS	NS	NS
Triglyceride	0.31 (0.0000)	0.33 (0.0000)	0.26 (0.0000)	0.28 (0.000)	0.211 (0.0000)	NS	0.231 (0.0000)	NS	NS	0.17 (0.003)	−0.315 (0.0000)	−0.20 (0.0005)
LDL-C	NS	NS	NS	−0.146 (0.008)	−0.228 (0.0000)	NS	NS	NS	−0.177 (0.001)	NS	0.20 (0.0002)	0.173 (0.002)
HDL-C	NS	NS	NS	NS	NS	NS	NS	0.122 (0.026)	NS	NS	NS	NS
CRP	NS	0.091 (0.045)	NS	NS	0.158 (0.0004)	NS	NS	NS	0.100 (0.037)	NS	−0.106 (0.018)	−0.113 (0.011)
SBP	NS	0.146 (0.006)	NS	NS	0.175 (0.0000)	NS	0.109 (0.042)	NS	NS	NS	NS	NS
DBP	NS	0.126 (0.0024)	NS	NS	0.195 (0.0000)	0.144 (0.010)	NS	NS	NS	NS	−0.152 (0.007)	−0.117 (0.039)
MAP	NS	0.148 (0.006)	NS	NS	0.191 (0.0000)	NS	NS	NS	NS	NS	NS	NS
HR	NS	0.178 (0.0001)	0.137 (0.002)	NS	0.244 (0.0000)	NS	NS	NS	NS	NS	−0.116 (0.010)	−0.113 (0.012)
BMI	0.128 (0.009)	0.146 (0.003)	NS	0.103 (0.039)	0.091 (0.066)	NS	NS	−0.127 (0.009)	NS	NS	NS	NS
Waist	0.161 (0.001)	0.187 (0.0002)	0.124 (0.014)	0.124 (0.015)	0.100 (0.048)	NS	NS	−0.135 (0.007)	NS	NS	NS	NS
2-hour glucose	NS	0.216 (0.0001)	0.215 (0.0001)	NS	0.118 (0.033)	NS	NS	−0.157 (0.005)	NS	NS	NS	NS
2-hour insulin	NS	0.115 (0.048)	NS	0.149 (0.008)	0.168 (0.004)	NS	NS	NS	NS	NS	−0.150 (0.009)	NS
Fasting glucose	NS	NS	NS	NS	NS	NS	NS	−0.103 (0.032)	NS	NS	NS	NS
Fasting insulin	0.171 (0.0003)	NS	NS	0.124 (0.010)	NS	NS	NS	NS	−0.106 (0.028)	NS	NS	NS

^aResults are presented as phenotypic correlation estimate (p-value). Negative associations are shown in bold. All phenotypes are adjusted for age, age², sex, age×sex, age²×sex, BMI and physical activity. BMI was not used as a covariate for the BMI analysis. Additional covariates were used as follows: lipid medications for lipids, antihypertensive medication for HR and SBP and smoking for CRP.

Mortality data are from Warensjo et al. (3).

ABP=average blood pressure; BMI=body mass index; CRP=C-reactive protein; DBP=diastolic blood pressure; HDL-C=high-density lipoprotein cholesterol; HR=heart rate; LDL-C=low-density lipoprotein cholesterol; SBP=systolic blood pressure; NS=not significant.

Warensjö E, Sundsröm J, Vessby B, Cederholm T, Risérus U. Markers of dietary fat quality and fatty acid desaturation as predictors of total and cardiovascular mortality: a population-based prospective study. Am J Clin Nutr. 2008; 88: 203–9.

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