(Hypertension. 1999;34:478-483.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
From the Institute of Community Medicine, University of Tromsø (S.G., K.H.B., B.K.J.), and the Department of Clinical Chemistry, Regional Hospital, University of Trondheim (K.S.B.), Norway.
Correspondence to Sameline Grimsgaard, Institute of Community Medicine, University of Tromsø, N-9037 Tromsø, Norway. E-mail sameline.grimsgaard{at}ism.uit.no
| Abstract |
|---|
|
|
|---|
Key Words: fatty acids blood pressure human
| Introduction |
|---|
|
|
|---|
Blood levels of fatty acids may be used to examine the relationship between individual fatty acids and blood pressure. There are reports of positive associations between blood pressure and blood levels of saturated and monounsaturated fatty acids,8 9 10 whereas polyunsaturated fatty acids have been both positively and inversely associated with blood pressure.8 10 Most previous studies included selected study groups9 10 or few subjects.8 10 On the basis of experimental data in animals and humans, 1 review found that n-6 polyunsaturated fatty acids decrease blood pressure in hypertensive individuals.11 However, 2 reviews of observational data and clinical trials concluded that dietary fats do not influence blood pressure levels.12 13
Plasma levels of essential polyunsaturated fatty acids reflect dietary
intake,14 15 whereas plasma levels of nonessential fatty
acids are less reliable indicators of dietary fat. Nevertheless, plasma
levels of palmitic acid (16:0) and stearic acid (18:0) and
monounsaturated fatty acids correlated with dietary
saturated fat.14 15 In addition, high levels of
dihomo-
-linolenic acid (20:3n-6) may reflect a diet rich in
saturated fat.16
We analyzed the association between plasma levels of phospholipid fatty acids and blood pressure in 4033 men 40 to 42 years old. The large sample size provided enough information to evaluate the independent associations of total fatty acids and individual fatty acids with blood pressure.
| Methods |
|---|
|
|
|---|
The health screening invitation included a questionnaire on cardiovascular disease, smoking habits, and leisure time physical activity (3 levels).18 A second questionnaire, which included questions on alcohol consumption,19 was distributed at the screening and returned via mail by 3483 men. Data on alcohol consumption were available for 3396 men. The study was approved by the Norwegian Data Inspectorate, which considered the legal and ethical issues of the study, and the subjects gave informed consent.
Body weight was measured on an electronic scale with subjects dressed in lightweight clothing. Height was measured in centimeters. Body mass index (BMI) was calculated as the body weight in kilograms divided by the square of the height in meters (kg/m2). We measured blood pressure by the oscillometric method20 with an automatic device (Dinamap, Critikon).17 After the subject had rested for 2 minutes, 3 recordings were made at 1-minute intervals with the individual sitting. The lowest blood pressure value was used in the analysis.
A nonfasting blood sample was analyzed for serum cholesterol at the Central Laboratory, Ulleval Hospital, Oslo.21 Plasma phospholipid fatty acids (myristic acid [14:0], 16:0, 18:0, arachidic acid [20:0], behenic acid [22:0], lignoceric acid [24:0], palmitoleic acid [16:1], oleic acid [18:1], gondoic acid [20:1], erucic acid [22:1], nervonic acid [24:1], eicosatrienoic acid [20:3n-9], linoleic acid [18:2n-6], eicosadienoic acid [20:2n-6], 20:3n-6, arachidonic acid [20:4n-6], adrenic acid [22:4n-6], linolenic acid [18:3n-3], eicosapentaenoic acid [20:5n-3], docosapentaenoic acid [22:5n-3, 22:5n-6], and docosahexaenoic acid [22:6n-3]) were quantified by gas-liquid chromatography as described previously.22 The coefficients of variation for individual fatty acids estimated from replicate analyses (n=55) ranged from 3.3% to 6.6%. Fatty acids were measured as µmol/L and relative concentrations, mol%. Trans-fatty acids were not measured.
Statistical Analysis
All variables were normally distributed except 20:5n-3,
which was log-transformed. Pearson and Spearman correlation
coefficients were computed to evaluate unadjusted relationships between
fatty acids and blood pressure, BMI, total cholesterol,
daily smoking, physical activity, and alcohol consumption. Total fatty
acids and individual fatty acids that showed significant
univariate associations with blood pressure were included
in multiple regression analyses. We included fatty acids
associated with dietary saturated fat (16:0, 16:1, and 20:3n-6),
dietary n-6 (18:2n-6), and dietary n-3 polyunsaturated fat (20:5n-3)
and also examined possible contributions of other fatty acids. Finally,
we adjusted for BMI, daily smoking, physical activity, and alcohol
consumption. Residual analyses confirmed the model assumptions.
Logistic regression was used to estimate the odds ratio for
hypertension (defined as systolic blood pressure
160
mm Hg and/or diastolic blood pressure
95 mm Hg) by
a 2-SD change in fatty acid concentrations. Two-sided
P<0.05 was considered statistically significant. The SAS
software package was used (SAS Corp).23
| Results |
|---|
|
|
|---|
|
|
Blood pressure was positively associated with total fatty acids (Table 2). Mean systolic blood pressure increased by 10 mm Hg from the bottom to the top decile of total fatty acid concentration, without any evidence of a threshold level below which or a plateau above which there was no association (Figure 1, top left). Levels of 18:2n-6 were inversely associated with blood pressure: mean systolic blood pressure decreased by 6 mm Hg from the bottom to the top decile of the 18:2n-6 concentration (Figure 1, bottom left). Systolic blood pressure was also positively associated with levels of 16:0, 16:1, 18:1, 20:3n-9, 20:3n-6, and 20:5n-3 (Table 2 and Figure 1, right).
|
Total fatty acids and relative concentrations of 16:0 and 18:2n-6 were independently associated with blood pressure in multiple regression analysis (Table 3, model 1). Models 2 to 4 show the relationship between systolic blood pressure and fatty acids when we substituted 16:0 with 16:1 and 20:3n-6, which also are considered to reflect dietary saturated fat. All 3 fatty acids showed highly significant independent positive relationships with systolic blood pressure. When fatty acids were added one at a time, no fatty acids other than 16:0, 16:1, and 20:3n-6 were significantly associated with systolic blood pressure when total fatty acids and 18:2n-6 were already included in the regression models. In addition, total fatty acids, 16:0, and 18:2n-6 remained significantly associated with blood pressure when we controlled for BMI, physical activity, smoking, and alcohol consumption (Table 3, model 5). Fatty acids were similarly associated with systolic and diastolic blood pressure (data not shown). The regression model, which included total fatty acids, 16:0, and 18:2n-6, explained 6% and 9% of the variability in systolic and diastolic blood pressure, respectively. The association between levels of 18:2n-6 and diastolic blood pressure was stronger than that of systolic blood pressure and remained significant after adjustment for BMI.
|
Figure 2 (top) illustrates the independent association of total fatty acids and BMI with blood pressure. The prevalence of hypertension was 23% among the 605 men in the top tertile of total fatty acids and BMI. In contrast, 3% of the 576 men in the bottom tertile of total fatty acids and BMI were hypertensive. Total fatty acids and 18:2n-6 were independently associated with blood pressure (Figure 2, bottom). The prevalence of hypertension was 21% among 532 men in the top tertile of total fatty acids and bottom tertile of 18:2n-6. In contrast, 4% were hypertensive among the 528 men in the bottom tertile of total fatty acids and top tertile of 18:2n-6. By multiple logistic regression in which we controlled for BMI, daily smoking, alcohol consumption, and physical activity, the odds ratio for hypertension was 2.2 (95% CI, 1.7 to 2.7) for a 2-SD increase in total fatty acids and 0.6 (95% CI, 0.5 to 0.8) for a 2-SD increase in 18:2n-6.
|
| Discussion |
|---|
|
|
|---|
The association between plasma phospholipid fatty acids and blood pressure was independent of BMI. A positive relationship between dietary saturated fat and blood pressure independent of BMI has been found in some2 3 4 but not all6 7 population studies. Earlier clinical trials were small and had methodological problems.12 However, a recent controlled trial [the Dietary Approaches to Stop Hypertension (DASH) study]24 reported a modest reduction in blood pressure independent of BMI in subjects who were fed a diet formulated to reduce saturated fat (although intake of cholesterol, calcium, and protein were slightly altered versus the other experimental diet). BMI is a strong determinant of blood pressure.1 Part of the association between BMI and blood pressure may depend on dietary fat. Therefore, it can be questioned whether adjustment for BMI is appropriate when assessing the strength of the relationship between dietary fat, as reflected in plasma fatty acids, and blood pressure.
We found that plasma concentrations of 16:0, 16:1, and 20:3n-6 were positively associated with blood pressure. Observational studies from Finland,25 France,9 and US10 also found positive associations between blood levels of 16:0 and 16:1 and blood pressure, and the ratio of 20:3n-6 to 18:2n-6 was increased in erythrocyte membranes of hypertensive subjects.26 Both 16:0 and 16:1 may be obtained from a diet high in saturated fat.27 Although 20:3n-6 is a polyunsaturated fatty acid, blood levels may increase on a saturated fat diet,16 possibly because dietary fat can influence enzymes involved in the metabolism of 20:3n-6.28
Blood pressure was inversely associated with 18:2n-6. Other investigators have found dietary5 and plasma8 10 25 levels of 18:2n-6 to be inversely associated with blood pressure, but the results are inconsistent.2 9 29 The possibility of detecting a relationship between 18:2n-6 and blood pressure may be limited by low interindividual variation, imprecise measures of dietary 18:2n-6, small sample size, and the degree of statistical control for potential confounders.
We found that plasma levels of n-3 fatty acids were positively associated with blood pressure in crude analysis, but no consistent relationship existed in the multivariate analyses. Blood pressure was positively associated with plasma 20:5n-3 concentrations in a small study of Finnish men.8 In contrast, blood pressure was inversely associated with plasma 20:5n-3 in mildly hypertensive individuals.30 A meta-analysis concluded that marine n-3 fatty acids in pharmacological doses have a hypotensive effect, which is restricted to hypertensive subjects and individuals with atherosclerosis.31
Plasma levels of 18:2n-6 and n-3 polyunsaturated fatty acids reflect dietary intake.14 15 32 However, levels of saturated and monounsaturated fatty acids may reflect both dietary fat and endogenous fat synthesis. The concentrations of saturated fatty acids displayed little variation among the men in our study and indicated that levels of saturated fat in plasma phospholipids are actively regulated. Nevertheless, in populations that consume diets high in saturated fat, blood levels of saturated and monounsaturated fatty acids were associated with dietary saturated fat,14 15 probably because of their common sources in milk products and animal fat.27 Blood levels of 20:3n-6 increased on a diet high in saturated fat and low in 18:2n-6.16 These data suggest that high levels of 16:0, 16:1, and 20:3n-6 reflect a diet high in saturated fat relative to polyunsaturated fat.
A limitation when interpreting relative concentrations of fatty acids
is that if the dietary intake of 1 fatty acid increases, the relative
concentrations of some other fatty acids may decrease. However, in the
present analysis, the associations of saturated and
polyunsaturated fatty acids with blood pressure remained significant in
multivariate analyses, which suggests that we
observed true independent associations. Given the lack of dietary data
and the crude measures of physical activity and alcohol used in the
present study, we cannot exclude the possibility of residual
confounding by lifestyle variables. However, the question of
physical activity segregated groups according to physical
fitness,18 and the measure of alcohol use was strongly
associated with levels of
-glutamyltransferase19 and
usual alcohol consumption34 in a population study
conducted in the same geographical area as the present study.
The extent to which total plasma phospholipid fatty acids reflect fat metabolism or dietary fat is unknown. There was a strong positive association between the concentration of total fatty acids and total cholesterol, and dietary saturated fat is the main lifestyle determinant of total cholesterol levels.1 We hypothesize that total fatty acids partly reflect dietary total fat and saturated fat intake.
The mechanisms by which fatty acids may influence blood pressure remain unknown. In humans, blood pressure and cardiac ß-adrenergic receptor responsiveness decreased on a low-fat diet with a high P/S ratio.34 A high fat meal reduced brachial artery reactivity, which suggested that fatty acids influence blood pressure by modulating endothelial function.35 Dietary saturated fat may also promote atherosclerosis and arterial stiffening and thereby increase blood pressure. Carotid intima thickness was positively associated with blood levels of saturated fat.36 Animal studies suggest that 18:2n-6 may reduce blood pressure by serving as a substrate for vasoactive prostaglandins11 and promote relaxation of vascular smooth muscle cells.37
This study showed that plasma phospholipid total fatty acids and the proportions of saturated fatty acids and 18:2n-6 were independently associated with blood pressure and suggested that fatty acids are involved in blood pressure regulation. Additional studies are needed to determine whether these associations reflect cause-and-effect relations and whether blood pressure can decrease on a diet low in total and saturated fat and high in polyunsaturated 18:2n-6.
| Acknowledgments |
|---|
Received September 10, 1998; first decision October 14, 1998; accepted May 12, 1999.
| References |
|---|
|
|
|---|
2.
Salonen JT, Salonen R, Ihanainen M, Parviainen M,
Sëppanen R, Kantola M, Sëppanen K, Rauramaa R. Blood
pressure, dietary fats, and antioxidants. Am J Clin
Nutr. 1988;48:12261232.
3.
Stamler J, Caggiula A, Grandits GA, Kjelsberg M,
Cutler JA. Relationship to blood pressure of combinations of dietary
macronutrients: findings of the Multiple Risk Factor Intervention Trial
(MRFIT). Circulation. 1996;94:24172423.
4. Beegom R, Singh RB. Association of higher saturated fat intake with higher risk of hypertension in an urban population of Trivandrum in south India. Int J Cardiol. 1997;58:6370.[Medline] [Order article via Infotrieve]
5. Oster P, Arab L, Schellenberg B, Kohlmeier M, Schlierf G. Linoleic acid and blood pressure. Prog Food Nutr Sci. 1980;4:3940.[Medline] [Order article via Infotrieve]
6.
Witteman JC, Willett WC, Stampfer MJ, Colditz GA,
Sacks FM, Speizer FE, Rosner B, Hennekens CH. A prospective study of
nutritional factors and hypertension among US women.
Circulation. 1989;80:13201327.
7.
Ascherio A, Rimm EB, Giovannucci EL, Colditz GA,
Rosner B, Willett WC, Sacks F, Stampfer MJ. A prospective study of
nutritional factors and hypertension among US men.
Circulation. 1992;86:14751484.
8. Miettinen TA, Naukkarinen V, Huttunen JK, Mattila S, Kumlin T. Fatty-acid composition of serum lipids predicts myocardial infarction. Br Med J (Clin Res Ed).. 1982;285:993996.
9.
Cambien F, Warnet JM, Vernier V, Ducimetiere P,
Jacqueson A, Flament C, Orssaud G, Richard JL, Claude JR. An
epidemiologic appraisal of the associations between the fatty acids
esterifying serum cholesterol and some
cardiovascular risk factors in middle-aged men.
Am J Epidemiol. 1988;127:7586.
10.
Simon JA, Fong J, Bernert JT Jr. Serum fatty acids and
blood pressure. Hypertension. 1996;27:303307.
11. Iacono JM, Dougherty RM. Effects of polyunsaturated fats on blood pressure. Annu Rev Nutr. 1993;13:243260.[Medline] [Order article via Infotrieve]
12. Sacks FM. Dietary fats and blood pressure: a critical review of the evidence. Nutr Rev. 1989;47:291300.[Medline] [Order article via Infotrieve]
13. Morris MC. Dietary fats and blood pressure. J Cardiovasc Risk. 1994;1:2130.[Medline] [Order article via Infotrieve]
14. Nikkari T, Luukkainen P, Pietinen P, Puska P. Fatty acid composition of serum lipid fractions in relation to gender and quality of dietary fat. Ann Med. 1995;27:491498.[Medline] [Order article via Infotrieve]
15.
Ma J, Folsom AR, Shahar E, Eckfeldt JH, the
Atherosclerosis Risk in Communities (ARIC) Study
Investigators. Plasma fatty acid composition as an indicator of
habitual dietary fat intake in middle-aged adults. Am J Clin
Nutr. 1995;62:564571.
16.
Lasserre M, Mendy F, Spielmann D, Jacotot B. Effects of
different dietary intake of essential fatty acids on C20:3
6 and
C20:4
6 serum levels in human adults. Lipids. 1985;20:227233.[Medline]
[Order article via Infotrieve]
17. Jacobsen BK, Stensvold I, Fylkesnes K, Kristiansen IS, Thelle DS. The Nordland Health Study. Design of the study, description of the population, attendance and questionnaire response. Scand J Soc Med. 1992;20:184187.[Medline] [Order article via Infotrieve]
18. Løchen ML, Rasmussen K. The Tromsø Study: physical fitness, self reported physical activity, and their relationship to other coronary risk factors. J Epidemiol Community Health. 1992;26:103107.
19.
Nilssen O, Førde OH, Brenn T. The Tromsø Study:
distribution and population determinants of
-glutamyltransferase. Am J Epidemiol. 1990;132:318326.
20. Meldrum SJ. The principles underlying Dinamap: a microprocessor based instrument for the automatic determination of mean arterial pressure. J Med Eng Technol. 1978;2:243246.[Medline] [Order article via Infotrieve]
21. Röschlau P, Bernt E, Gruber W. [Enzymatic determination of total cholesterol in serum (author's translation)] Enzymatische Bestimmung des Gesamt-Cholesterins im Serum. Z Klin Chem Klin Biochem. 1974;12:403407.[Medline] [Order article via Infotrieve]
22.
Bjerve KS, Fischer S, Alme K.
-Linolenic acid deficiency in man: effect of ethyl
linolenate on plasma and erythrocyte fatty acid composition and
biosynthesis of prostanoids. Am J Clin Nutr. 1987;46:570576.
23. SAS Institute Inc. SAS/STAT User's Guide. Cary, NC: SAS Institute Inc; 1990.
24.
Appel LJ, Moore TJ, Obarzanek E, Vollmer WM, Svetkey
LP, Sacks FM, Bray GA, Vogt TM, Cutler JA, Windhauser MM, Lin P,
Karanja N. A clinical trial of the effects of dietary patterns on blood
pressure. N Engl J Med. 1997;336:11171124.
25. Uusitupa MI, Sarkkinen ES, Torpström J, Pietinen P, Aro A. Long-term effects of four fat-modified diets on blood pressure. J Hum Hypertens. 1994;8:209218.[Medline] [Order article via Infotrieve]
26.
Russo C, Olivieri O, Girelli D, Guarini P, Pasqualini
R, Azzini M, Corrocher R. Increased membrane ratios of metabolite to
precursor fatty acid in essential hypertension.
Hypertension. 1997;29:10581063.
27. Gunstone FD, Harwood JL, Padley FB. Occurrence and characteristics of oils and fats. In: Padley FB, Gunstone FD, Harwood JL, eds. The Lipid Handbook. New York, NY: Chapman & Hall; 1994:47223.
28. Bezard J, Blond JP, Bernard A, Clouet P. The metabolism and availability of essential fatty acids in animal and human tissues. Reprod Nutr Dev. 1994;34:539568.
29. De Backer G, De Craene I, Rosseneu M, Vercaemst R, Kornitzer M. Relationship between serum cholesteryl ester composition, dietary habits and coronary risk factors in middle-aged men. Atherosclerosis. 1989;78:237243.[Medline] [Order article via Infotrieve]
30. Bønaa KH, Bjerve KS, Straume B, Gram IT, Thelle D. Effect of eicosapentaenoic and docosahexaenoic acids on blood pressure in hypertension: a population-based intervention trial from the Tromsø Study. N Engl J Med. 1990;322:795801.[Abstract]
31.
Morris MC, Sacks F, Rosner B. Does fish oil lower blood
pressure? A meta-analysis of controlled trials.
Circulation. 1993;88:523533.
32.
Zock PL, Mensink RP, Harryvan J, de Vries JH, Katan MB.
Fatty acids in serum cholesteryl esters as quantitative biomarkers of
dietary intake in humans. Am J Epidemiol. 1997;145:11141122.
33.
Nilssen O, Førde OH. The Tromsø Study: the positive
predictive value of
-glutamyltransferase and an alcohol
questionnaire in the detection of early-stage risk drinkers.
J Intern Med. 1991;229:497500.[Medline]
[Order article via Infotrieve]
34. Straznicky NE, Howes LG, Barrington VE, Lam W, Louis WJ. Effects of dietary lipid modification on adrenoceptor-mediated cardiovascular responsiveness and baroreflex sensitivity in normotensive subjects. Blood Press. 1997;6:96102.[Medline] [Order article via Infotrieve]
35. Vogel RA, Corretti MC, Plotnick GD. Effect of a single high-fat meal on endothelial function in healthy subjects. Am J Cardiol. 1997;79:350354.[Medline] [Order article via Infotrieve]
36.
Ma J, Folsom AR, Lewis L, Eckfeldt JH. Relation of
plasma phospholipid and cholesterol ester fatty acid
composition to carotid artery intima-media thickness: the
Atherosclerosis Risk in Communities (ARIC) Study.
Am J Clin Nutr. 1997;65:551559.
37.
Pomposiello SI, Alva M, Wilde DW, Carretero OA.
Linoleic acid induces relaxation and
hyperpolarization of the pig coronary
artery. Hypertension. 1998;31:615620.
This article has been cited by other articles:
![]() |
W. S. Harris, D. Mozaffarian, E. Rimm, P. Kris-Etherton, L. L. Rudel, L. J. Appel, M. M. Engler, M. B. Engler, and F. Sacks Omega-6 Fatty Acids and Risk for Cardiovascular Disease: A Science Advisory From the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Cardiovascular Nursing; and Council on Epidemiology and Prevention Circulation, February 17, 2009; 119(6): 902 - 907. [Full Text] [PDF] |
||||
![]() |
O. A. Gudbrandsen, M. Hultstrom, S. Leh, L. Monica Bivol, O. Vagnes, R. K. Berge, and B. M. Iversen Prevention of Hypertension and Organ Damage in 2-Kidney, 1-Clip Rats by Tetradecylthioacetic Acid Hypertension, September 1, 2006; 48(3): 460 - 466. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Foldes, S. Vajda, Z. Lako-Futo, B. Sarman, R. Skoumal, M. Ilves, R. deChatel, I. Karadi, M. Toth, H. Ruskoaho, et al. Distinct modulation of angiotensin II-induced early left ventricular hypertrophic gene programming by dietary fat type J. Lipid Res., June 1, 2006; 47(6): 1219 - 1226. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Mancia, R. Facchetti, M. Bombelli, H. P. Friz, G. Grassi, C. Giannattasio, and R. Sega Relationship of Office, Home, and Ambulatory Blood Pressure to Blood Glucose and Lipid Variables in the PAMELA Population Hypertension, June 1, 2005; 45(6): 1072 - 1077. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. G. Warner Complementary and Alternative Therapies for Hypertension Complementary Health Practice Review, October 1, 2000; 6(1): 11 - 19. [PDF] |
||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Hypertension Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search Copyright © 1999 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited. |