Abstract
BACKGROUND
Few previous studies have reported the association of aortic stiffness with marine n-3 fatty acids (Fas) in the general population. The aim of this study was to determine the combined and independent associations of 2 major marine n-3 FAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), with aortic stiffness evaluated using carotid–femoral pulse wave velocity (cfPWV) in Korean, white, and Japanese American men.
METHODS
A population-based sample of 851 middle-aged men (299 Koreans, 266 whites, and 286 Japanese Americans) was examined for cfPWV during 2002–2006. Serum FAs, including EPA and DHA, were measured as a percentage of total FAs using gas chromatography. Multiple regression analysis was used to examine the association of EPA and DHA with cfPWV after adjusting for blood pressure and other confounders.
RESULTS
Mean EPA and DHA levels were 1.9 (SD = 1.0) and 4.8 (SD = 1.4) for Koreans, 0.8 (SD = 0.6) and 2.4 (SD = 1.2) for whites, and 1.0 (SD = 1.0) and 3.2 (SD = 1.4) for Japanese Americans. Both EPA and DHA were significantly higher in Koreans than in the other 2 groups (P < 0.01). Multiple regression analyses in Koreans showed that cfPWV had a significant inverse association with total marine n-3 FAs and with EPA alone after adjusting for blood pressure and other potential confounders. In contrast, there was no significant association of cfPWV with DHA. Whites and Japanese Americans did not show any significant associations of cfPWV with total marine n-3 FAs, EPA, or DHA.
CONCLUSIONS
High levels of EPA observed in Koreans have an inverse association with aortic stiffness.
Keywords: aortic stiffness, blood pressure, carotid femoral pulse wave velocity, docosahexaenoic acid, eicosapentaenoic acid, fish oil, hypertension.
Aortic stiffness is being recognized as a predictor of cardiovascular disease (CVD) and all-cause mortality independent of blood pressure (BP), age, and other CVD risk factors.1 Aortic stiffness can be measured noninvasively by carotid–femoral pulse wave velocity (cfPWV), which is considered the gold standard method. In fact, the European Society of Hypertension/European Society of Cardiology added cfPWV as a factor to assess future CVD risk in recently published guidelines for the management of arterial hypertension.2
A recent meta-analysis reported that supplementation of marine n-3 fatty acids (FAs) improved aortic stiffness.3 The randomized clinical trials (RCTs) in the meta-analysis4–12 and 1 more recent RCT13 have several characteristics. First, subjects in these RCTs were individuals with type 2 diabetes,5,9 metabolic syndrome,10 hyperlipidemia,11,12 or individuals who were obese or overweight.4,6–8 Thus, the result may not be extrapolated to the general population. Second, although the differential effect of 2 major marine n-3 FAs: eicosapentaenoic (EPA; 20:5 n-3) and docosahexaenoic acids (DHA; 22:6 n-3), on CVD risk factors is a current research topic,14 only 1 RCT11 reported the effect of each of DHA and EPA on aortic stiffness separately. Third, although cfPWV is regarded as the gold standard to evaluate aortic stiffness, these RCTs, except for one study,13 used other methods. Finally, most of these RCTs examined the effect of >1 gram of fish oil on aortic stiffness,4–7,9–11,15 as compared with <1 gram of fish oil used in recent RCTs of fish oil on incident CVD.16–18
Observational studies reported the association of marine n-3 FAs with aortic stiffness. Two studies in the 1980s with relatively small sample sizes (i.e., 94 and 55, respectively) suggested that fish consumption was associated with lower aortic stiffness.19,20 More recently, 2 cross-sectional studies reported the association. Anderson et al. reported an inverse association of cfPWV with plasma DHA in 174 healthy subjects,21 although it was not reported whether the association was independent of BP. Tomiyama et al. reported no significant associations of PWV with either serum EPA or DHA in 2,206 subjects who participated in health check-ups.22 However, as the authors stated as 1 limitation, PWV was not evaluated using the standard method (i.e., cfPWV).
In this study, we aimed to determine the association of serum total marine n-3 FAs with aortic stiffness using cfPWV in population-based samples of Korean, white, and Japanese American men. We also aimed to examine the independent associations of serum EPA and DHA with cfPWV. We examined these associations in the ERA JUMP (Electron-Beam Tomography, Risk Factor Assessment Among Japanese and US Men in the Post–World War II Birth Cohort) study, a population-based, cross-sectional study of 851 middle-aged Korean, white, and Japanese American men.
METHODS
The ERA JUMP study is a population-based study of men aged 40–49 years without CVD or other severe disease during 2002–2006, as previously described in detail.23,24 The study examined 310 white Americans in Allegheny County, Pennsylvania; 313 Japanese in Kusatsu, Shiga, Japan; 303 Japanese Americans in Honolulu, Hawaii; and 302 Koreans in Ansan, Gyeonggi-do, South Korea. Our study excluded Japanese men in Japan because cfPWV was not measured. Additionally, we excluded 64 subjects (7.0 %) who had missing cfPWV and other data. The final sample size for our study was 851 (266 white Americans, 299 Koreans, and 286 Japanese Americans). Informed consent was obtained from all participants. The study was approved by the institutional review boards of the University of Pittsburgh, Pittsburgh, Pennsylvania; Korea University, Seoul, South Korea; and Kuakini Medical Center, Honolulu, Hawaii.
All participants underwent a physical examination and laboratory assessment and completed a lifestyle questionnaire, as described previously.23 The lifestyle questionnaire included a question about whether the participant took fish or cod liver oil as a supplement. Venipuncture was performed early in the morning during the clinic visit after a 12-hour fast. The samples were stored at –80 °C and shipped on dry ice to the University of Pittsburgh to determine lipids, glucose, insulin, and FAs. Serum lipids were determined using standardized methods by the Centers for Disease Control and Prevention. Serum glucose was determined by an enzymatic assay, and insulin was determined by a radioimmunoassay. Serum EPA, DHA, and other FAs were determined by capillary gas chromatography, as previously described.23 Total marine n-3 FAs were defined as the sum of EPA, docosapentaenoic acid, and DHA. The coefficients of variation between tests for EPA and DHA were 4.5% and 7.2%, respectively.
BP and heart rate were measured in the right arm of the seated participant after the participant emptied his bladder and sat quietly for 5 minutes, using an appropriate-sized cuff, with an automated sphygmomanometer (BP-8800; Colin Medical Technology, Komaki, Japan).23 The average of the 2 measurements was used for analysis. Hypertension was defined as systolic BP ≥ 140mm Hg, diastolic BP ≥ 90mm Hg, or use of antihypertensive medications. Diabetes mellitus was defined as fasting serum glucose level ≥ 7 mmol/L or use of antidiabetic medications.
cfPWV
Before the study started, staff from the Ultrasound Research Laboratory, University of Pittsburgh trained sonographers from Honolulu and South Korea to measure cfPWV at the Honolulu facility. cfPWV was measured using a noninvasive, automated waveform analyzer (VP2000; Omron, Kyoto, Japan).24 This device recorded the carotid and femoral pulse waveform using multiarray tonometers. It also recorded the phonocardiogram, electrocardiogram, and both the volume pulse form and arterial BP from the right and left brachial and tibial arteries. The pulse volume waveforms were recorded using a semiconductor pressure sensor. Sonographers palpated the left femoral artery and the left carotid artery and placed the handheld tonometers over these 3 pulse areas to obtain femoral and carotid pulse waveforms simultaneously. A foot pedal was used to start the recording. Data were collected 2 times for each participant, and the values were averaged. cfPWV was calculated by time-phase analysis using volume waveforms of the respective arteries (carotid and femoral arteries). cfPWV was calculated as (distance between arterial sites)/(time between the foot of the respective waveforms). Distance between tonometers placed over left carotid and left femoral arteries was measured over the surface of the body. Intraclass correlation for reexamination of cfPWV was 0.84.
Statistical analysis
Participant characteristics for categorical variables were calculated as percentages, whereas continuous variables were calculated as means with SDs. To compare risk factors among the 3 groups, analysis of variance and χ2 test were used for continuous and categorical variables, respectively. As post hoc analyses, we used the Fisher least significant difference. Multiple linear regression analyses were performed to examine the associations of each of total marine n-3 FAs, EPA, and DHA with cfPWV. Because an interaction between race and total marine n-3 FAs in predicting cfPWV was statistically significant (P < 0.01), race-specific analyses were performed. Based on the previous report,25 model 1 adjusted for age, systolic BP, and heart rate. Model 2 further adjusted for body mass index, current smoking, alcohol drinking, and medication for BP. Model 3 additionally adjusted for low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), triglycerides, diabetes, glucose, and medications for diabetes and lipids. Multiple regression models were used to examine the age- and BP-adjusted correlations between cfPWV and risk factors. Assumptions of multiple linear regression were satisfied in all these models. All P values were 2-tailed and considered significant at P < 0.01 for multiple comparison and P < 0.05, otherwise. IBM SPSS Statistics (version 20; IBM, New York, US) software was used for all statistical analyses.
RESULTS
Table 1 shows a profile of risk factors for Koreans, whites, and Japanese Americans. The profile was generally favorable in Koreans compared with whites and Japanese Americans. Exceptions to this trend included HDL-C and rates of current smokers; Koreans had significantly lower levels of HDL-C and higher rate of cigarette smokers as compared with the other 2 groups. Additionally, Koreans had higher prevalence of diabetes and higher levels of diastolic BP as compared with whites but not Japanese Americans. No Koreans took fish oil supplement, whereas >10% of both whites and Japanese Americans did. Mean cfPWV in Koreans was significantly lower than that in the other 2 groups.
Table 1.
Characteristics of the study participants in 2002–2006
| Characteristic | Koreans (n = 299) | Whites (n = 266) | Japanese Americans (n = 286) | P value |
|---|---|---|---|---|
| Age, y | 44.8 (2.8) | 45.0 (2.8) | 46.1 (2.8) | **, *** |
| Systolic blood pressure, mm Hg | 121.6 (14.1) | 122.6 (11.2) | 127.7 (12.5) | **,*** |
| Diastolic blood pressure, mm Hg | 76.2 (11.1) | 73.1 (8.6) | 77.8 (9.2) | *,** |
| Heart rate, per min | 66.3 (9.2) | 64.7 (9.6) | 67.2 (9.0) | ** |
| Body mass index, kg/m2 | 24.7 (2.7) | 27.9 (4.3) | 28.0 (4.6) | *,*** |
| LDL-cholesterol, mmol/L | 2.98 (0.83) | 3.49 (0.87) | 3.14 (0.81) | ** |
| Triglycerides, mmol/L | 1.81 (1.18) | 1.71 (1.13) | 2.08 (1.61) | **,*** |
| HDL-cholesterol, mmol/L | 1.18 (0.30) | 1.24 (0.33) | 1.31 (0.32) | **,*** |
| Glucose, mmol/L | 5.68 (1.00) | 5.64 (0.85) | 6.23 (2.27) | **,*** |
| Insulin, ρmol/L | 70.1 (31.3) | 175.7 (57.6) | 104.9 (63.9) | *,*** |
| Ethanol consumption, g/day | 21.2 (32.2) | 10.0 (14.0) | 17.8 (32.9) | *,*** |
| Hypertension, % | 15.6 | 15.2 | 33.0 | **,*** |
| Diabetes mellitus, % | 9.6 | 3.6 | 13.9 | *,** |
| Current cigarette smokers, % | 37.9 | 7.7 | 12.9 | *,*** |
| Alcohol drinker, % | 44.2 | 44.2 | 37.3 | |
| Hypertension medications, % | 4.7 | 8.7 | 20.5 | **,*** |
| Lipid-lowering medications, % | 1.3 | 12.3 | 23.1 | *,**,*** |
| Diabetes medications, % | 0.3 | 1.0 | 6.6 | **,*** |
| Fish oil liver supplement, % | 0 | 10.9 | 12.6 | *,*** |
| cfPWV, cm/second | 810 (130) | 863 (213) | 902 (208) | *,**,*** |
Values are means (SD) except for proportional variables with percentages.
Abbreviations: cfPWV, carotid femoral pulse wave velocity; HDL, high-density lipoprotein; LDL, low-density lipoprotein.
*P < 0.01 between Koreans and whites; **P < 0.01 between whites and Japanese Americans; ***P < 0.01 between Koreans and Japanese Americans.
The levels of total marine n-3 FAs, EPA, and DHA were significantly higher in Koreans than in the other two groups (Table 2). There were little overlaps in the distributions of marine n-3 FAs between Koreans and the other 3 groups. For example, the lower 25th percentile of EPA in Koreans (1.45%) was higher than the upper 25th percentile in whites (1.00%) and Japanese Americans (1.20%). The levels of total n-6 FAs in Koreans were significantly lower than those in the other 2 groups. In contrast, the levels of saturated FAs in Koreans were significantly higher than those in the other 2 groups. Serum concentrations of FAs were not statistically different among the 3 groups (mean = 243.9, SD = 67.8 for Koreans; mean = 236.2, SD = 51.1 for whites; mean = 242.5, SD = 85.7 for Japanese Americans).
Table 2.
Serum levels of fatty acids in Koreans, whites, and Japanese Americans in 2002–2006
| Fatty acids proportion, % | Koreans (n = 299) | Whites (n = 266) | Japanese Americans (n = 286) | P value |
|---|---|---|---|---|
| Marine-derived n-3 fatty acids | 7.5 (2.4) | 3.8 (1.7) | 4.9 (2.2) | *,**,*** |
| Eicosapentaenoic acid | 1.9 (1.0) | 0.8 (0.6) | 1.0 (1.0) | *,**,*** |
| Docosahexaenoic acid | 4.8 (1.4) | 2.4 (1.2) | 3.2 (1.4) | *,**,*** |
| Alpha linolenic fatty acid | 1.0 (0.8) | 0.3 (0.3) | 0.4 (0.4) | *,**,*** |
| Total n-6 fatty acids | 33.4 (4.5) | 41.3 (4.2) | 41.2 (4.3) | *,*** |
| Saturated fatty acids | 34.3 (2.9) | 30.9 (2.5) | 30.9 (2.2) | *,*** |
| Monounsaturated fatty acids | 18.6 (3.6) | 18.9 (3.1) | 18.1 (3.5) | ** |
| Trans-fatty acids | 1.2 (1.6) | 1.0 (0.5) | 0.9 (0.4) | *** |
Values are means (SD). Marine-derived n-3 fatty acids were calculated as a sum of eicosapentaenoic acid (20:5n-3), docosapentaenoic acid (22:5n-3), and docosahexaenoic acid (22:6n-3). Total n-6 fatty acids were calculated as a sum of linoleic acid (18:2n-6), gamma-lenoleic acid (18:3n-6), dihomo-gamma-lenolenic acid (20:3n-6), and arachidonic acid (20:4n-6). Saturated fatty acids were calculated as a sum of tetradecanoic acid (14:0), palmitic acid (16:0), and stearic acid (18:0. Monosaturated fatty acids were calculated as a sum of palmitoleic acid (16:1n-7), 9-octadecanoic acid (18:1n-9), and vaccenic acid (18:1n-7). Trans-fatty acids were calculated as a sum of palmitelaidic acid (16:1t), trans-9 octadecaenoic acid (18:1t), and linolelaidic acid (18:2tt).
*P < 0.01 between Koreans and whites; **P < 0.01 between whites and Japanese Americans; ***P < 0.01 between Koreans and Japanese Americans.
We examined the age- and BP-adjusted correlations between cfPWV and each risk factor. Generally, we did not observe significant correlations. Exceptions were triglycerides in Koreans (standardized coefficient = 0.146; P < 0.01), body mass index and HDL-C in whites (standardized coefficients = 0.268 and −0.163, respectively; P < 0.01), and body mass index in Japanese Americans (standardized coefficient = 0.289; P < 0.01). We also examined age- and BP-adjusted correlations between cfPWV and FAs. We observed significant correlations between EPA and monounsaturated FAs in Koreans (standardized coefficients = −0.155 and 0.177, respectively; P < 0.01) as well as alpha linolenic acids and trans FAs in Japanese Americans (standardized coefficients == 0.175 and 0.150, respectively; P < 0.01).
In multiple linear regression analyses adjusting for age, BP, and heart rate in each of the 3 groups, total marine n-3 FAs in Koreans, but not in whites or Japanese Americans, had a significant inverse association with cfPWV (Table 3, Model 1). The significant inverse association in Koreans remained after further adjusting for other potential confounders including body mass index, low-density lipoprotein cholesterol, HDL-C, and diabetes (Table 3, Models 2 and 3). The significant association was not altered after further adjusting for other FAs, including alpha-linolenic and trans-FAs (data not shown).
Table 3.
Multivariable adjusted association of combined serum eicosapentaenoic and docosahexaenoic acid with carotid–femoral pulse wave velocity
| Model | Koreans (n = 299) | Whites (n = 266) | Japanese Americans (n = 286) | |||
|---|---|---|---|---|---|---|
| Standardized beta | P value | Standardized beta | P value | Standardized beta | P value | |
| Model 1 | −0.137 | 0.01 | 0.009 | 0.89 | −0.077 | 0.17 |
| Model 2 | −0.132 | 0.02 | 0.043 | 0.47 | −0.038 | 0.49 |
| Model 3 | −0.132 | 0.02 | 0.044 | 0.47 | −0.025 | 0.66 |
Model 1 adjusted for age, systolic blood pressure, and heart rate. Model 2 further adjusted for body mass index, current smoking, alcohol drinking, and medication for blood pressure. Model 3 further adjusted for low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, diabetes, and medication for lipids.
We further examined the independent association of EPA and DHA with cfPWV in each of the 3 groups. In Koreans, EPA but not DHA showed a significant inverse association with cfPWV after adjusting for age, BP, and heart rate (Table 4, Model 1). The significant inverse association remained after further adjusting for potential confounders (Table 4, Models 2 and 3) and after further adjusting for other FAs, including DHA, alpha-linolenic and trans-FAs (data not shown). We also entered mean arterial BP instead of systolic BP, and the significant association remained. Neither EPA nor DHA showed a significant association with cfPWV in whites or Japanese Americans (Table 4).
Table 4.
Multivariable adjusted association of serum eicosapentaenoic and docosahexaenoic acid with carotid–femoral pulse wave velocity
| Model | Koreans (n = 299) | Whites (n = 266) | Japanese Americans (n = 286) | |||
|---|---|---|---|---|---|---|
| Standardized beta | P value | Standardized beta | P value | Standardized beta | P value | |
| EPA | ||||||
| Model 1 | −0.141 | 0.01 | 0.018 | 0.76 | −0.069 | 0.21 |
| Model 2 | −0.140 | 0.01 | 0.039 | 0.50 | −0.047 | 0.39 |
| Model 3 | −0.149 | 0.008 | 0.043 | 0.47 | −0.031 | 0.58 |
| DHA | ||||||
| Model 1 | −0.087 | 0.11 | 0.012 | 0.84 | −0.066 | 0.24 |
| Model 2 | −0.086 | 0.12 | 0.053 | 0.37 | −0.021 | 0.70 |
| Model 3 | −0.087 | 0.11 | 0.060 | 0.33 | −0.006 | 0.91 |
Model 1 adjusted for age, systolic blood pressure, and heart rate. Model 2 further adjusted for body mass index, current smoking, alcohol drinking, and medication for blood pressure. Model 3 further adjusted for low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, diabetes, and medication for lipids.
DISCUSSION
This study has shown that serum levels of total marine n-3 FAs had a significant inverse association with aortic stiffness after adjusting for BP and other confounders in Koreans who had much higher serum levels of marine n-3 FAs than whites and Japanese Americans. This study has also shown that EPA but not DHA had a significant inverse association with cfPWV in Koreans after adjusting for BP and other confounders. No significant associations of cfPWV with total marine n-3 FAs, EPA or DHA in whites or Japanese Americans.
We observed that total marine n-3 FAs had a significant inverse association with cfPWV only in Koreans, not in whites or Japanese Americans. RCTs that reported beneficial effects of EPA on aortic stiffness administered ≥1.8g/day of fish oil,9−12 which is much higher than dietary intake of fish oil in typical Western diet (i.e., 0.1g/day).26 We have recently reported that dietary intake of fish is substantially higher in Koreans than in Americans based on national nutrition surveys (i.e., 74g/day vs. 7g/day, respectively).27 Our observation that serum levels of marine n-3 FAs in Koreans were >100% higher than levels of whites is consistent with the fact that dietary intake of fish in Koreans is much higher than Americans. Thus the observed significant inverse association in Koreans may be attributed to their high dietary intake of fish.
A recent systemic review of effects of marine n-3 FAs on CVD risk factors28 showed that marine n-3 FAs significantly reduce triglycerides, increase HDL-C, and reduce BP. The inverse association of cfPWV with marine n-3 FAs in Koreans remained significant after adjusting for these factors, indicating that the association was unlikely to be medicated through these factors.
RCTs reporting the beneficial effect of fish oil on aortic stiffness examined its short-term effect (i.e., 6 weeks to 6 months).4–12 This short-term effect is likely to be due to functional rather than structural changes and may be partly due to increases in nitric oxide production, endothelium-related arterial relaxation, and mitigation of vasoconstrictive responses to norepinephrine and angiotensin II by marine n-3 FAs.29,30 Because Koreans are very likely to be exposed to high serum levels of marine n-3 FAs for many years, we cannot deny the possibility that long-term exposure to high marine n-3 FAs preserves the structure of the aorta. Degradation of compliant elastin fibers and deposition of stiffer collagen is considered a key cause of age-related aortic stiffness.31 Marine n-3 FAs may stimulate healthy collagen production through the nuclear factor-kappa B pathway.32 In addition, we and others recently reported that aortic calcification is positively associated with aortic stiffness.24,33 Marine n-3 FAs may inhibit vascular calcification by the p38-mitogen-acitivated protein kinase pathway.34
This study has shown that EPA but not DHA had a significant inverse association with cfPWV in Koreans. Although the reason for this independent association of EPA but not DHA with cfPWV remains to be elucidated, generally our results are consistent with the results from RCTs of marine n-3 FAs on aortic stiffness. Most RCTs of EPA on aortic stiffness reported a significant improvement of aortic stiffness in individuals with hyperlipidemia,12 obesity,10 and type 2 diabetes.9 Two RCTs of DHA on aortic stiffness reported no significant improvement of aortic stiffness in individuals with hyperlipidemia4 or obesity.7 Only 1 RCT reported the effect of each of EPA and DHA on aortic stiffness.11 Nestel et al. reported that 3g of EPA and 3g of DHA similarly but nonsignificantly improved aortic stiffness evaluated using systemic arterial compliance.11 Although independent effects of EPA and DHA on CVD risk factors (e.g., BP, low-density lipoprotein cholesterol, vascular function, and endothelial function)14 have been reported in selected populations, our study is the first to show the independent association of EPA with aortic stiffness.
We observed that cfPWV in Koreans was significantly lower than in whites despite similar prevalence of hypertension between the 2 groups and significantly higher levels of diastolic BP in Koreans than in whites. Although this study was not intended to investigate the difference in aortic stiffness among ethnicities, it is possible that lifelong exposure to high marine n-3 FAs in Koreans partly contributed to their lower cfPWV compared with whites. It is also possible that the difference in cfPWV is partly due to genetic differences (e.g., polymorphisms of angiotensin II type 1 receptor, angiotensin-converting enzyme, angiotensinogen, and β1-adrenergic receptor)35 as well as gene–environmental interaction.
We observed that prevalence of diabetes was significantly higher in Koreans and Japanese Americans than in whites. This observation is consistent with the results from previous studies.36 It is well known from migrant studies of Asians to the United States that Asians, including Koreans, are more susceptible to developing diabetes than whites.36
This study has several strengths. This study included population-based samples from three different ethnicities. This enabled us to look at the difference in associations between fish oil and aortic stiffness across the multiple ethnicities. Using standardized methods in all measurements across the ethnicities increased the validity. Our study had several limitations. The cross-sectional study prevented the assessment of causality between fish oil and aortic stiffness. Our study included only men and those aged 40–49 years. Thus, the results may not be generalizable to other age groups or women. Serum marine n-3 FAs reflect short-term dietary intake and may not reflect long-term dietary intake. However, it is likely that a single measurement of EPA and DHA is reflective of the habitual dietary intake in Korea where fish intake is known to be high.37 We did not have data on types of hypertension medications, although some hypertension medications (e.g., angiotensin-converting enzyme inhibitor) are reported to improve aortic stiffness.38 However, actual number of individuals under hypertension medications was small in our study. Moreover, the results did not change materially after excluding those individuals (data not shown).
Aortic stiffness is being recognized as a predictor of CVD and all-cause mortality independent of BP, age, and other CVD risk factors.1 Total marine n-3 FAs had significant inverse association with aortic stiffness evaluated using cfPWV in Koreans, a population with >100% higher serum levels of total marine n-3 FAs than whites. The association was not observed in the 2 other populations with lower serum levels of marine n-3 FAs. Although the differential effect of EPA and DHA on CVD risk factors has been intensely investigated, only 1 previous study examined their independent effect on aortic stiffness, which reported similar nonsignificant improvement of arterial compliance between EPA and DHA. Our study has shown that EPA but not DHA had a significant inverse association with cfPWV in Koreans. These findings may suggest that high serum levels of marine n-3 FAs, mainly EPA, have inverse associations with aortic stiffness. The independent effect of EPA and DHA on aortic stiffness, including its mechanisms, is to be confirmed in future studies.
DISCLOSURE
The authors declared no conflict of interest.
ACKNOWLEDGMENTS
This work was supported by grants HL68200 and HL071561 from the National Institutes of Health, United States; Korea Centers for Disease Control and Prevention (government budget code: 2004-E71001-00, 205-E71001-00); and by B 16790335 and A 13307016, 17209023, and 21249043 from the Japanese Ministry of Education, Culture, Sports, Science and Technology.
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