Fatty acids as determinants of in-vivo lipid peroxidation: The EFFGE study in Eastern Finnish hypertensive and non-hypertensive subjects

Figures & data

Table I. Fatty acid characteristics, and age- and sex-adjusted correlations between the different degrees of fatty acid unsaturation and plasma free F_2α-isoprostanes.

	Men (n = 443)		Women (n = 778)			Combined men+ women F2-IsoPs^a
	Mean	SD	Mean	SD	P^b	r	P^c
Plasma free F2-IsoPs, pg/mL^a	21.1	5.8	24.5	8.4	< 0.001
Age, years	60.6	8.5	58.6	8.1	< 0.001
Age range, years	30–85		31–79
Plasma fatty acids
Plasma SFA, mmol/L^a	4.12	2.61	4.21	2.51	0.32	–0.109	< 0.001
Plasma MUFA, mmol/L^a	3.30	1.85	3.27	1.74	0.97	–0.079	0.006
Plasma PUFA, mmol/L^a	4.65	2.72	4.63	2.44	0.72	–0.175	< 0.001
Plasma n6 PUFA, mmol/L^a	4.13	2.58	4.09	2.32	0.86	–0.166	< 0.001
Plasma n3 PUFA, mmol/L^a	0.52	0.25	0.54	0.24	0.08	–0.146	< 0.001
Plasma arachidonic acid (20:4), mmol/L^a	0.45	0.17	0.47	0.17	0.033	0.00	1.00
Plasma PUFA/SFA ratio^a	1.19	0.30	1.16	0.33	0.19	–0.115	< 0.001
Plasma n6/n3 PUFA ratio^a	8.18	4.01	7.91	3.99	0.21	–0.072	0.013
Intake of fatty acids	(n = 379)		(n = 689)
Dietary SFA, E%	9.9	2.6	9.5	2.6	0.009	0.062	0.043
Dietary MUFA, E%	9.2	1.8	9.0	2.1	0.11	–0.03	0.36
Dietary PUFA, E%	4.1	0.9	4.1	1.1	0.64	–0.094	0.002
Dietary n6 PUFA, E%^a	3.1	0.7	3.1	1.0	0.60	–0.079	0.010
Dietary n3 PUFA, E%^a	1.0	0.3	1.0	0.3	0.88	–0.094	0.002
Dietary PUFA/SFA ratio	0.44	0.13	0.46	0.15	0.014	–0.124	< 0.001
Dietary n6/n3 PUFA ratio^a	3.3	0.9	3.3	1.3	0.52	0.02	0.52
Dietary trans-fatty acids, E%	0.25	0.11	0.25	0.11	0.92	0.080	0.009
Dietary SFA+trans-fatty acids, E%	10.2	2.7	9.7	2.7	0.011	0.063	0.041
Dietary SFA+trans-fatty acid intake per total fat intake, %	42.0	5.4	41.3	5.6	0.042	0.117	< 0.001
Dietary total fat intake/n3 PUFA intake ratio^a	30.7	10.5	30.1	9.3	0.36	0.096	0.002

F₂-IsoPs = F_2α-isoprostanes; MUFA = monounsaturated fatty acid; n3 = omega-3; n6 = omega-6; PUFA = polyunsaturated fatty acid; SFA = saturated fatty acid.

Characteristics data are mean ± SD.

^aDue to skewed distribution, the variable was log-transformed prior to the statistical analysis.

^bP for sex difference (t test for independent samples).

^cP for correlation (partial correlation adjusted for age and sex).

Table II. Subject characteristics, and age- and sex-adjusted correlations between the clinical and nutritional risk factors of CVD and plasma free F_2α-isoprostane levels, the plasma free F_2α-isoprostane/20:4 ratio, or plasma free 20:4 concentration.

								Correlations for combined men+ women data
	Men			Women				F2-IsoPs^a		F2-IsoPs/20:4 ratio^a		Plasma 20:4^a
	n	Mean	SD	n	Mean	SD	P ^d	r	P^e	r	P^e	r	P^e
Age, years	433	60.6	8.5	778	58.6	8.1	< 0.001	–0.02	0.61	0.03	0.39	–0.04	0.13
Sex (1 = male, 2 = female)	433	1	0	778	2	0		0.210	< 0.001	0.089	0.002	0.057	0.048
Plasma free F2-IsoPs, pg/mL^a	433	21.1	5.8	778	24.5	8.4	< 0.001
Plasma free F2α-IsoPs, ng/μmol 20:4^a	433	0.054	0.032	778	0.060	0.037	0.002	0.622	< 0.001
Plasma arachidonic acid (20:4), μmol/L^a	433	450	169	778	470	169	0.033	0.00		–0.783	< 0.001
Smoker (0 = no, 1 = yes)	433	0.10	0.30	778	0.07	0.26	0.09	0.04	0.16	0.02	0.41	0.00	0.94
Alcohol use, g/day^b	433	7.38	9.42	778	3.05	5.29	< 0.001	0.01	0.75	–0.04	0.19	0.06	0.05
Duration of weekly physical activity, h^a	433	7.7	7.3	776	6.6	5.5	0.05	–0.096	0.001	–0.01	0.70	–0.062	0.035
Body mass index, kg/m^2a	433	27.1	3.9	778	26.9	4.8	0.19	0.283	< 0.001	0.105	< 0.001	0.091	0.002
Waist-to-hip circumference ratio	433	0.95	0.06	778	0.84	0.07	< 0.001	0.153	< 0.001	–0.01	0.81	0.130	< 0.001
Essential hypertension (1 = no, 2 = yes)	433	1.50	0.50	778	1.50	0.50	0.97	0.066	0.021	–0.02	0.46	0.080	0.005
Systolic blood pressure, mmHg^a	433	135	17	778	132	19	< 0.001	0.072	0.012	0.01	0.67	0.04	0.15
Cardiovascular disease (0 = no, 1 = yes)	433	0.12	0.33	778	0.06	0.25	0.001	0.05	0.08	0.02	0.55	0.02	0.53
Myocardial infarction (0 = no, 1 = yes)	433	0.05	0.22	778	0.01	0.10	0.001	0.071	0.013	0.03	0.27	0.02	0.59
Angina pectoris (0 = no, 1 = yes)	433	0.10	0.31	778	0.06	0.24	0.008	0.05	0.10	0.01	0.77	0.03	0.35
Serum NT-proANP, nmol/L^a	429	1.023	0.745	763	0.998	0.482	0.10	0.01	0.70	0.05	0.07	–0.058	0.044
Serum NT-proBNP, nmol/L^a	429	0.093	0.127	763	0.091	0.076	0.013	0.06	0.06	0.06	0.05	–0.03	0.31
Type 2 diabetes (0 = no, 1 = yes in interview)	433	0.07	0.26	778	0.05	0.21	0.06	0.05	0.08	0.058	0.045	–0.03	0.24
Serum insulin, mU/L^a	433	9.3	9.1	775	7.3	5.8	< 0.001	0.168	< 0.001	0.03	0.35	0.099	0.001
Serum triglycerides, mmol/L^a	433	1.32	0.79	778	1.15	0.60	< 0.001	0.162	< 0.001	–0.04	0.22	0.174	< 0.001
Serum LDL cholesterol, mmol/L	433	3.24	0.89	778	3.35	0.87	0.037	0.02	0.47	–0.101	< 0.001	0.146	< 0.001
Serum HDL cholesterol, mmol/L	433	1.45	0.42	778	1.79	0.47	< 0.001	–0.05	0.10	–0.067	0.019	0.05	0.10
Apolipoprotein A1, g/L	432	1.5	0.3	771	1.8	0.3	< 0.001	0.02	0.56	–0.119	< 0.001	0.165	< 0.001
Apolipoprotein B, g/L	432	1.1	0.3	771	1.1	0.3	0.61	0.05	0.08	–0.133	< 0.001	0.209	< 0.001
Serum CRP, mg/L^c	433	1.9	3.5	778	2.1	3.1	0.09	0.119	< 0.001	0.02	0.41	0.065	0.025
Plasma glucose, mmol/L^a	433	5.95	0.96	778	5.56	0.93	< 0.001	0.135	< 0.001	0.05	0.09	0.04	0.13
Plasma alpha-tocopherol, μmol/L^a	433	30.3	6.9	776	31.6	6.4	0.001	–0.04	0.14	–0.190	< 0.001	0.209	< 0.001
Plasma beta-carotene, μmol/L^a	433	0.30	0.20	776	0.47	0.32	< 0.001	–0.201	< 0.001	–0.05	0.11	–0.100	0.001
Energy intake, kcal/day^a	379	2120	760	689	1930	780	< 0.001	–0.03	0.42	0.05	0.11	–0.082	0.007
Dietary protein intake, E%	379	18.2	2.7	689	18.8	2.7	< 0.001	–0.05	0.10	–0.118	< 0.001	0.110	< 0.001
Dietary fat intake, E%	379	28.3	4.8	689	28.0	5.3	0.36	–0.00	0.93	–0.02	0.60	0.02	0.55
Dietary carbohydrates, E%	379	49.9	6.1	689	50.3	6.5	0.40	–0.01	0.72	0.061	0.047	–0.086	0.005
Dietary fiber, g/MJ	379	3.4	0.9	689	3.9	1.0	< 0.001	–0.03	0.28	0.02	0.49	–0.05	0.09
Dietary sodium, mg/kcal^a	379	1.64	0.32	689	1.61	0.33	0.17	–0.03	0.28	–0.073	0.017	0.067	0.030
Dietary fruit, vegetable and berry intake, g/day^c	379	581	496	689	701	583	< 0.001	–0.03	0.35	0.01	0.87	–0.03	0.35

CRP = highly sensitive C-reactive protein; F₂-IsoPs = F_2α-isoprostanes; HDL = high-density lipoprotein; LDL = low-density lipoprotein; NT-proANP and NT-proBNP = N-terminal fragments of A and B-type natriuretic peptides; 20:4 = arachidonic acid.

Characteristics data are mean ± SD.

^a–cDue to skewed distribution, the variable was either ^alog-transformed, or categorized ^b1 to 3, or ^c1 to 5 prior to the statistical analysis.

^dP for sex difference (t test for independent samples).

^eP for correlation (partial correlation adjusted for age and sex). Due to zero values, the log transformation was carried out for 1191 subjects in NT-proANP and for 1089 subjects in NT-proBNP.

Table III. Linear multivariable regression for the associations between plasma free F_2α-isoprostane levels (pg/mL) and the CVD risk factors.

	B	Beta	P
All of the subjects (n = 1211)
(Constant)	0.583
Body mass index, kg/m^2a	0.517	0.268	< 0.001
Sex (1 = male, 2 = female)	0.062	0.225	< 0.001
Dietary PUFA/SFA ratio	–0.105	–0.105	< 0.001
Serum apolipoprotein A1, g/L	0.044	0.098	0.001
Plasma β-carotene, μmol/L^a	–0.043	–0.097	0.001
Dietary protein intake, E%	–0.003	–0.060	0.026
Plasma n6/n3 PUFA ratio^a	–0.036	–0.058	0.030
Age, years	–0.001	–0.035	0.195
Men (n = 433)
(Constant)	0.479
Body mass index, kg/m^2a	0.313	0.165	0.001
Dietary total fat intake/n3 PUFA intake ratio^a	0.159	0.164	< 0.001
Plasma glucose, mmol/L^a	0.280	0.153	0.003
Serum NT-proBNP, nmol/L^a	0.040	0.139	0.003
Age, years	0.000	–0.023	0.63
Women (n = 778)
(Constant)	0.691
Body mass index, kg/m^2a	0.534	0.284	< 0.001
Dietary PUFA/SFA ratio	–0.105	–0.106	0.002
Plasma n6/n3 PUFA ratio^a	–0.060	–0.094	0.005
Serum apolipoprotein A1, g/L	0.040	0.087	0.013
Plasma β-carotene, μmol/L^a	–0.040	–0.083	0.023
Duration of the weekly physical activity, h	–0.037	–0.072	0.036
Age, years	–0.001	–0.046	0.19

n3 = omega-3; n6 = omega-6; NT-proBNP = N-terminal fragments of B-type natriuretic peptides; PUFA = polyunsaturated fatty acid; SFA = saturated fatty acid.

Values are regression coefficients and standardized regression coefficients indicating the change in F_2α-isoprostanes in pg/mL in response to one unit change in explanatory factor.

^aDue to skewed distribution, the variable was log-transformed prior to the statistical analysis. Regression models contained two steps: Step 1: age and sex, or age alone, were included in the model. Step 2: Step 1 + stepwise regression (P for entry 0.05 and P for removal 0.10) for different CVD risk factors.

Table IV. Linear multivariable regression for the associations between plasma free F_2α-isoprostane levels (ng/μmol 20:4) and the CVD risk factors.

	B	Beta	P
All of the subjects (n = 1211)
(Constant)	–1.313
Serum apolipoprotein B, g/L	–0.138	–0.170	< 0.001
Plasma PUFA/SFA ratio^a	–0.264	–0.152	< 0.001
Plasma n6/n3 PUFA ratio^a	–0.142	–0.146	< 0.001
Sex (1 = male, 2 = female)	0.057	0.130	< 0.001
Body mass index, kg/m^2a	0.387	0.127	< 0.001
Dietary protein intake, E%	–0.009	–0.114	< 0.001
Serum apolipoprotein A1, g/L	–0.077	–0.110	< 0.001
Essential hypertension (1 = no, 2 = yes)	–0.039	–0.093	0.002
Dietary SFA+trans-fatty acids, E%	0.006	0.070	0.011
Serum NT-proBNP, nmol/L^a	0.033	0.056	0.047
Age, years	0.000	0.004	0.90
Men (n = 433)
(Constant)	–1.451
Serum apolipoprotein B, g/L	–0.183	–0.246	< 0.001
Dietary protein intake, E%	–0.013	–0.166	< 0.001
Plasma PUFA/SFA ratio^a	–0.269	–0.159	0.001
Serum apolipoprotein A1, g/L	–0.113	–0.141	0.002
Plasma n6/n3 PUFA ratio^a	–0.121	–0.130	0.005
Dietary SFA+trans-fatty acids, E%	0.008	0.106	0.017
Energy intake, kcal/day^a	0.140	0.097	0.028
Plasma glucose, mmol/L^a	0.295	0.093	0.044
Age, years	0.002	0.065	0.15
Women (n = 778)
(Constant)	–1.403
Body mass index, kg/m^2a	0.492	0.168	< 0.001
Plasma n6/n3 PUFA ratio^a	–0.149	–0.150	< 0.001
Serum apolipoprotein B, g/L	–0.120	–0.142	< 0.001
Plasma PUFA/SFA ratio^a	–0.222	–0.126	0.001
Essential hypertension (1 = no, 2 = yes)	–0.044	–0.102	0.005
Dietary protein intake, E%	–0.007	–0.083	0.017
Serum apolipoprotein A1, g/L	–0.053	–0.072	0.043
Smoker (0 = no, 1 = yes)	0.058	0.070	0.047
Age, years	0.000	–0.014	0.69

n3 = omega-3; n6 = omega-6; NT-proBNP = N-terminal fragments of B-type natriuretic peptides; PUFA = polyunsaturated fatty acid; SFA = saturated fatty acid; 20:4 = arachidonic acid.

Values are regression coefficients and standardized regression coefficients indicating the change in F_2α-isoprostanes in ng/μmol 20:4 in response to one unit change in explanatory factor.

^aDue to the skewed distribution, the variable was log-transformed prior to the statistical analysis. Regression models contained two steps: Step 1: age and sex, or age alone, were included in the model. Step 2: Step 1 + stepwise regression (P for entry 0.05 and P for removal 0.10) for different CVD risk factors.