Dietary Polyunsaturated Fatty Acids Intake Is Not Associated with Framingham Risk Score: Analysis of Korean National Health and Nutrition Examination Survey 2013

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INTRODUCTION

Polyunsaturated fatty acids (PUFAs) have a hydrocarbon chain pos- sessing two or more carbon-carbon double bonds. Essential PUFAs for health are omega-3 (n-3) and omega-6 (n-6), and must be ingested by hu- mans and other animals, since they are not naturally synthesized.¹⁾

The n-3 has a cardio-protective effect and reduces cardiovascular disease (CVD) event.^2-5) The American Heart Association (AHA), the American College of Cardiology, and the European Society of Cardiolo- gy have recommended an intake of n-3 fatty acid for the prevention of CVDs.^6,7) However, studies have not examined the effects of increased or decreased n-6 levels on CVD clinical endpoints and there is insufficient

Original Article

https://doi.org/10.21215/kjfp.2017.7.4.575 eISSN 2233-9116

Korean J Fam Pract. 2017;7(4):575-580

KJFP

Korean Journal of Family Practice

고도불포화지방산의 섭취와 프레밍험 위험도와의 관계:

국민건강영양조사 2013년도 분석을 통한 연구

정석인, 나경민, 주남석*

아주대학교병원 가정의학과

Received July 13, 2016 Revised October 11, 2016 Accepted October 13, 2016

Corresponding author Nam-Seok Joo Tel: +82-31-219-5959, Fax: +82-31-219-5218 E-mail: jchcmc@daum.net

This is an open-access article distributed under the terms of the Creative Commons At- tribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Dietary Polyunsaturated Fatty Acids Intake Is Not Associated with Framingham Risk Score:

Analysis of Korean National Health and Nutrition Examination Survey 2013

Suk-In Jung, Kyung-Min Nah, Nam-Seok Joo*

Department of Family Medicine, Ajou University Hospital, Suwon, Korea

Background: The influence of dietary polyunsaturated fatty acid intake on cardiovascular risk is contested. We explored the relationship of dietary polyunsaturated fatty acid intake with the Framingham risk score (FRS) in Koreans.

Methods: From 8,018 participants in the 2013 Korean National Health and Nutrition Examination Survey, the relevant data of 4,242 participants (1,753 males and 2,489 females) were selected and cross-sectionally analyzed. The FRS was compared by the tertiles of dietary polyunsaturated fatty acids, including daily dietary omega-6 fatty acid intake (n-6), daily dietary omega-3 fatty acid intake (n-3), and the ratio of dietary n-6 and n-3 fatty acid intake (n-6:n-3) after adjustment for relevant variables (age, systolic blood pressure, hypertension, diabetes mellitus, dyslipidemia, myocardial infarction, angina, alcohol consumption, smoking, moderate activity, occupation, waist circumference, body mass index, calorie intake, total cholesterol, and high-density lipoprotein).

Results: Mean age was 44.3 and 46.0 years in males and females, respectively. Dietary n-6 intake in males and females was 11.91 g and 1.89 g, respectively, while dietary n-3 intake in males and females was 8.31 g and 1.42 g, respectively. Mean FRS was 6.6 and 6.1 in males and females, respectively. FRS before adjustment was negatively correlated with dietary n-6 and n-3 intake, but positively correlated with n-6:n-3. However, FRS showed no differences after adjustment.

Conclusion: FRS showed no differences in the comparison according to the tertiles of dietary polyunsaturated fatty acids. This could indicate that dietary polyunsaturated fatty acids were not significantly associated with FRS.

Keywords: Fatty Acids, Polyunsaturated; Fatty Acids, Essential; Cardiovascular Diseases

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Suk-In Jung, et al. Dietary PUFAs Is Not Associated with FRS Score

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evidence showing the effect of either increased or decreased n-6 intake on CVD risk factors, such as blood lipids and blood pressure, in the Co- chrane review.⁸⁾ However, the AHA states that n-6 PUFA reduces the risk of coronary heart disease (CHD) relative to lower intakes.⁹⁾

The ratio of n-6:n-3 is important. A low ratio is more desirable in reducing the risk of many chronic diseases, including CVD.^10,11) However, recent studies have not associated n-3 intake with a lower CVD risk.^12-14)

The Framingham risk score (FRS) was developed based on data ob- tained from the Framingham Heart Study, and has been used globally to evaluate CVD risk. The FRS is a sex-specific, simple coronary disease prediction algorithm that estimates the 10-year risk of developing CHD using sex, age, total cholesterol (TC), smoking, high-density lipoprotein (HDL), and systolic blood pressure (SBP).^15,16) The FRS performs well even in different ethnic groups.¹⁷⁾

In South Korea, as diet has become more westernized, interest has grown in foods that can best aid in disease prevention. Hence, it is important to address the controversy over PUFA consumption. We are in- terested in verifying the efficacy of n-3 and n-6 for CHD prevention in Koreans. To investigate the protective influence of PUFAs on CHD, we explored the relationship of dietary PUFA intake using the FRS on the Korean population after extracting data from Korean National Health and Nutritional Examination Survey (KNHANES).

METHODS

1. Participants

KNHANES is an ongoing surveillance system in the Republic of Ko- rea that assesses the health and nutritional status of Koreans, monitors trends in health risk factors and the prevalence of major chronic diseases, and provides data for the development and evaluation of national health policies and programs. Data from the first year of the sixth KNHANES survey that included dietary n-3 and n-6 PUFAs, age, SBP, TC, HDL, and smoking were used in this cross-sectional analysis. The initial number of participants was 8,018 (3,645 males and 4,373 females). Of these, 4,242 participants (1,753 males and 2,489 females) were evaluated after 2,209 participants were excluded due to age (0 to 19 years and over 80 years) not suitable for FRS analysis, and 1,556 participants were excluded due to missing data. All participants provided written informed consent before the survey.

2. Laboratory, Physical, and Nutritional Assessments Blood samples were collected annually after an 8-hour fast. Each sample was immediately processed, refrigerated, and transported in cold storage to the central testing institute (NeoDin Medical Institute, Seoul, Korea) for analysis within 24 hours. Serum TC and HDL concentration were measured enzymatically using a Hitachi Automatic Analyzer 7600 (Hitachi, Tokyo, Japan). Blood pressure was measured by a nurse, using a Baumanometer Wall Unit 33 (W.A. Baum Co., Inc., Copiague, NY, USA);

three measurements were taken, with the average of the second and third measurements reported. Nutrient intake, including total calorie and PU- FAs, was assessed using a 24-hour dietary recall questionnaire, adminis- tered by a dietician.

3. Lifestyle Questionnaires

Current smokers were defined as those who were currently smoking and had smoked more than five packs of cigarettes throughout their life.

Moderate activity was assessed by a questionnaire and categorized as whether occurring or not. In KNHANES, moderate activity means an increased amount of activity compared to activities of everyday living, or activity that causes some shortness of breath, with the activity performed once for at least 30 minutes, five days a week or more. Alcohol consumption assessed by a questionnaire was categorized as cumulative alcohol consumption if consumption was at least once a month annually.

4. Assessment of Cardiovascular Disease Risk

The FRS was used to determine CHD. In the Framingham/ATP III criteria, FRS was calculated using scoring of age, TC, smoking, serum HDL, SBP, and use of hypertension (HTN) medication to estimate the 10-year CHD risk. Because scores are known to differ according to sex, sex-specific analysis was performed.

5. Statistical Analyses

The complex sample analysis used for the KNHANES data weighted all values, and followed statistical guidance from the Korea Centers for Disease Control and Prevention. The participants were divided into male and female groups and stratified into three tertiles, according to the amount of dietary PUFA intake (n-3, n-6, and the n-6:n-3 ratio). General characteristics such as age, body mass index (BMI), waist circumference (WC), TC, HDL, low-density lipoprotein (LDL), triglyceride (TG), dietary PUFA, SBP, diastolic blood pressure (DBP), HTN, diabetes mellitus

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정석인 외. 고도불포화지방산의 섭취와 프레밍험 위험도와의 관계 Korean Journal of Family Practice

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(DM), myocardial infarction (MI), alcohol consumption, and FRS were evaluated by a descriptive method after data weighting. In this study, previous diagnosis and medical prescription was used to define HTN, diabetes and dyslipidemia while MI, angina was defined following medical diagnoses. ANOVA was used for the comparison of general characteristics between men and women, and for the characteristics comparison among the dietary uptake tertile groups in the sex. We compared FRS according to the daily dietary uptake tertile group, using the ANCOVA test, after adjustment for age, SBP, HTN, DM, dyslipidemia, MI, angina, alcohol consumption, smoking, moderate activity, occupation, WC, BMI, calorie intake, TC, and HDL after data weighting. The results represented the adjusted FRS.

P<0.05 was considered significantly statistical different. Data was analyzed using IBM SPSS Statistics for Windows, version 22.0 (IBM Corp., Armonk, NY, USA).

RESULTS

All data were analyzed after data weighting. The mean age was 44.3 years in males and 46.0 years in females. Dietary n-6 intake in males and females were 11.91 g and 1.89 g, respectively, while n-3 was 8.31 g and 1.42 g, respectively. The mean FRS was 6.6 in males and 6.1 in females. The general characteristics of the participants are presented in Table 1.

Age was significantly different in males (P for trend <0.001), while age and SBP were significantly different in females (P for trend <0.001 and

Table 1. General characteristics of male and female subjects Characteristic Male

(n=1,753)

Female

(n=2,489) P-value

Age (y) 44.3 (0.5) 46.0 (0.5) 0.002^*

BMI (kg/m²) 24.4 (9.6) 23.3 (10.0) <0.001^*

WC (cm) 84.0 (0.3) 77.2 (0.3) <0.001^*

TC (mg/dL) 187.1 (1.0) 188.5 (0.9) 0.318

HDL (mg/dL) 48.9 (0.3) 55.6 (0.3) <0.001^*

LDL (mg/dL) 112.5 (1.8) 120.3 (2.3) 0.007^*

TG (mg/dL) 162.5 (4.0) 112.3(1.9) <0.001^*

Calorie intake (kcal) 2,490.5 (32.8) 1,775.1 (18.6) <0.001^*

n-3 (g) 1.89 (0.06) 1.42 (0.04) <0.001^*

n-6 (g) 11.91 (0.30) 8.31 (0.19) <0.001^*

n-6:n-3 8.06 (0.15) 7.95 (0.12) 0.531

SBP (mmHg) 119.1(0.4) 113.7(0.5) <0.001^*

DBP (mmHg) 78.2 (0.3) 72.88 (0.3) <0.001^*

HTN (%) 14.2 (0.9) 15.1 (0.9) 0.402

DM (%) 6.7 (0.7) 5.9 (0.6) 0.327

Dyslipidemia (%) 5.7 (0.5) 8.7 (0.6) <0.001^*

MI, angina (%) 2.1 (0.3) 1.5 (0.2) 0.191

Alcohol consumption (%) 75.4 (1.3) 42.6 (1.2) <0.001^* Current smoker (%) 41.8 (1.5) 5.2 (0.6) <0.001^* Moderate activity (%) 8.7 (0.9) 4.3 (0.4) <0.001^*

FRS 6.55 (0.22) 6.06 (0.25) 0.101

Values are presented as weighted mean (standard error).

BMI, body mass index; WC, waist circumference; TC, total cholesterol; HDL, high density lipoprotein; TG, triglyceride; n-3, daily dietary omega-3 fatty acid intake;

n-6, daily dietary omega-6 fatty acid intake; SBP, systolic blood pressure; HTN, hypertension; DM, diabetes mellitus; MI, myocardial infarction; Alcohol consumption, monthly alcohol consumption; FRS, Framingham risk score.

Analysis was performed using ANOVA after date weighting following statistical guidance from the Korea Centers for Disease Control and Prevention.

*P<0.05 was considered significantly statistical different.

Table 2. General characteristics of subjects by tertile of daily dietary n-3 intake for FRS and correlation of dietary n-3 intake and FRS

Characteristic Male (n=1,753) Female (n=2,489)

T1 (n=584) T2 (n=585) T3 (n=584) P for trend T1 (n=829) T2 (n=830) T3 (n=830) P for trend

Age (y) 46.9 (0.7) 44.4 (0.8) 42.0 (0.6) <0.001 49.1 (0.8) 45.0 (0.6) 44.0 (0.6) <0.001

SBP (mmHg) 119.7 (0.7) 119.3 (0.7) 118.2 (0.7) 0.343 115.7 (0.7) 113.1 (0.7) 112.3 (0.7) 0.001

TC (mg/dL) 184.3 (1.8) 187.6 (1.7) 189.2 (1.9) 0.131 191.3 (1.6) 186.7 (1.3) 187.5 (1.3) 0.053

HDL (mg/dL) 48.1 (0.5) 48.6 (0.6) 49.8 (0.5) 0.088 54.8 (0.5) 55.7 (0.5) 56.3 (0.5) 0.098

Smoking (%) 42.4 (2.4) 43.1 (2.4) 39.9 (2.5) 0.589 5.3 (0.9) 4.4 (0.9) 6.0 (1.0) 0.459

n-3 (g) 0.51 (0.01) 1.32 (0.01) 3.62 (0.13) <0.001 0.36 (0.01) 0.98 (0.01) 2.93 (0.09) <0.001

n-6 (g) 5.11 (0.17) 10.1 (0.20) 19.5 (0.61) <0.001 3.52 (0.08) 7.39 (0.15) 14.01 (0.41) <0.001

n-6:n-3 10.83 (0.35) 7.74 (0.15) 5.98 (0.14) <0.001 10.73 (0.25) 7.69 (0.17) 5.45 (0.12) <0.001

FRS 7.58 (0.36) 6.71 (0.37) 5.49 (0.34) <0.001 7.75 (0.40) 5.44 (0.35) 5.04 (0.33) <0.001

FRS (adjusted) 9.39 (0.19) 9.57 (0.17) 9.31 (0.22) 0.595 11.99 (0.17) 11.62 (0.20) 12.18 (0.22) 0.184

SBP, systolic blood pressure; TC, total cholesterol; HDL, high density lipoprotein; smoking, current smoker; n-3, daily dietary omega-3 fatty acid intake; n-6, daily dietary omega-6 fatty acid intake; FRS, Framingham risk score.

FRS (adjusted) was adjusted by age, systolic blood pressure, diastolic blood pressure, hypertension, diabetes mellitus, hyperlipidemia, myocardial infarction, angina, alcohol consumption, smoking, moderate activity, employment, waist circumference, body mass index, calorie intake, total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglyceride.

Analysis was performed using ANOVA and ANCOVA (for adjusted FRS) after date weighting following statistical guidance from the Korea Centers for Disease Control and Prevention.

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<0.001, respectively) within data required for the calculation of FRS from the n-3 tertile. Significant negative relationships were evident between FRS and tertile group of dietary n-3 PUFA intake in males and females (P for trend <0.001; Table 2). Age and SBP differed significantly for the calculation of the FRS in the n-6 tertile of males and in the n-6:n-3 tertile of both sexes. However, for the n-6 tertile of females, age, SBP, TC, and HDL were significantly different (P for trend <0.01). There were significant negative relationships between FRS and the n-6 tertile (P for trend

<0.001), but significant positive relationships between FRS and the n-

6:n-3 tertile in both males and females (Tables 3, 4).

After adjustments for age, SBP, DBP, HTN, DM, hyperlipidemia, MI, angina, alcohol consumption, smoking, moderate activity, employment, WC, BMI, caloric intake, TC, HDL, LDL, and TG, there was no significant relationship between FRS and the n-3, n-6, and n-6:n-3 tertile groups in both sexes (Tables 2–4).

Table 3. General characteristics of subject by tertile of daily dietary n-6 intake for FRS and correlation of dietary n-6 intake and FRS

Age (y) 50.5 (0.7) 44.5 (0.7) 39.4 (0.6) <0.001 52.3 (0.81) 45.2 (0.56) 41.2 (0.63) <0.001

SBP (mmHg) 121.4 (0.8) 118.7 (0.7) 117.6 (0.6) 0.001 117.8 (0.8) 113.2 (0.7) 110.4 (0.7) <0.001

TC (mg/dL) 185.9 (1.7) 187.5 (1.6) 187.8 (1.8) 0.664 192.4 (1.7) 188.9 (1.3) 184.5 (1.2) <0.001

HDL (mg/dL) 48.2 (0.6) 48.4 (0.5) 49.8 (0.5) 0.664 54.1 (0.5) 56.3 (0.5) 56.2 (0.5) 0.001

Smoking (%) 41.5 (2.3) 42.5 (2.4) 41.3 (2.3) 0.913 5.5 (0.9) 4.0 (0.7) 6.2 (0.1) 0.081

n-3 (g) 0.85 (0.04) 1.56 (0.07) 2.98 (0.13) <0.001 0.62 (0.03) 1.19 (0.07) 2.37 (0.08) <0.001

n-6 (g) 3.60 (0.08) 8.58 (0.08) 21.30 (0.52) <0.001 2.51 (0.05) 6.22 (0.05) 15.66 (0.34) <0.001

n-6:n-3 7.27 (0.23) 7.70 (0.18) 8.99 (0.26) <0.001 7.33 (0.23) 8.11 (0.17) 8.33 (0.17) 0.001

FRS 8.89 (0.33) 6.75 (0.39) 4.56 (0.32) <0.001 9.20 (0.42) 5.64 (0.31) 3.66 (0.34) <0.001

FRS (adjusted) 9.37 (0.23) 9.52 (0.18) 9.39 (0.22) 0.863 11.77 (0.20) 12.17 (0.18) 11.85(0.24) 0.286

Table 4. General characteristic of subject by tertile of daily dietary n-6:n-3 intake for FRS and correlation of dietary n-6:n-3 intake and FRS

Age (y) 49.7 (0.7) 42.7 (0.8) 41.3 (0.6) <0.001 49.9 (0.6) 44.7 (0.7) 43.6 (0.6) <0.001

SBP (mmHg) 121.1 (0.7) 118.3 (0.7) 118.1 (0.6) <0.001 115.3 (0.8) 113.8 (0.7) 112.0 (0.7) 0.004

TC (mg/dL) 188.3 (1.7) 188.0 (1.8) 185.3 (1.7) 0.403 189.7 (1.4) 187.9 (1.5) 188.0 (1.4) 0.597

HDL (mg/dL) 48.4 (0.6) 48.9 (0.5) 49.1 (0.5) 0.642 54.8 (0.4) 55.9 (0.5) 56.1 (0.5) 0.101

Smoking (%) 38.8 (2.3) 44.0 (2.3) 42.0 (2.4) 0.233 4.1 (0.9) 4.5 (0.9) 7.1 (1.2) 0.109

n-3 (g) 2.73 (0.16) 1.88 (0.07) 1.16 (0.06) <0.001 2.17 (0.11) 1.39 (0.04) 0.75 (0.03) <0.001

n-6 (g) 8.49 (0.39) 13.80 (0.54) 12.99 (0.58) <0.001 6.34 (0.23) 9.98 (0.29) 8.56 (0.35) <0.001 n-6:n-3 3.63 (0.07) 7.31 (0.03) 12.68 (0.28) <0.001 3.49 (0.06) 7.22 (0.32) 12.81 (0.19) <0.001

FRS 8.49 (0.34) 6.02 (0.35) 5.38 (0.33) <0.001 7.82 (0.34) 5.42 (0.37) 5.04 (0.35) <0.001

FRS (adjusted) 9.53 (0.21) 9.18 (0.19) 9.58 (0.16) 0.302 11.93 (0.19) 11.72 (0.19) 12.14 (0.21) 0.372 Values are presented as weighted mean (standard error).

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정석인 외. 고도불포화지방산의 섭취와 프레밍험 위험도와의 관계 Korean Journal of Family Practice

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DISCUSSION

In this cross-sectional analysis, the intake of n-3 and n-6 PUFAs and the n-6:n-3 intake ratio was significantly related to the FRS prior to adjustment, but not after adjustment, in both sexes.

Both the negative correlation of n-3 and n-6 intake with FRS, and the positive correlation of the n-6:n-3 intake ratio with FRS in both sexes, respectively, prior to adjustment was consistent with previous studies that reported on the relationship of PUFAs with CVD, except for n-6. Co- chrane review studies have not examined the effects of either increased or decreased n-6 on CVD risk.⁸⁾ After adjustments, we did not observe any correlations between PUFA intake and FRS that was consistent with previous studies.8,12-14,18)

Sohn et al.¹⁹⁾ performed a cross-sectional study with participants who underwent an annual health examination and voluntarily participated in a dietary modification program conducted at Bundang Seoul National University Health Promotion Center and Iksan Public Health Center in 2012. In this study, the relationship of FRS and PUFAs was analyzed, using the same Framingham/ATP III criteria as Sohn et al.,¹⁹⁾ to calculate the FRS. Before adjustment, dietary PUFAs displayed negative relationships with FRS, and these were maintained after adjustment for dietary factors and interleukin 6 (IL-6). These differences likely reflect the factors used for correction. To determine the precise relationship between dietary PUFA and FRS, more than two control variables may be necessary, as in the present study.

The n-3 fatty acids may reduce the risk for CVD through reduced sus- ceptibility of the heart to ventricular arrhythmia and through an anti- thrombogenic effect. The n-3 PUFA has fasting and postprandial hypo- triglyceridemic effects and is mildly hypotensive.²⁾ These effects may slow the growth of atherosclerotic plaque by reducing adhesion molecule ex- pression, reducing platelet-derived growth factors, and promoting an anti-inflammatory effect. Considering these mechanisms, intake of n-3 PUFA may aid in the prevention of CVD. In regards to anti-inflammatory properties, a study on vascular endothelial cells demonstrated that n-6 fatty acids suppressed all key mediators of the atherosclerotic process²⁰⁾; while higher plasma n-6 was correlated to decreased serum pro-inflammatory markers, including IL-6 and IL-1 receptor antagonist, and increased anti-inflammatory marker, transforming growth factor-beta.²¹⁾ There is concern that a n-6 enriched fatty acid diet may be more influen- tial than n-3 in the production of 2-series prostaglandins (PG) (such as

PGE2 and PGI2), thromboxane A2, and 4-series leukotrienes (such as leukotriene 4). Because 2- and 4-series PGs have a potent pro-inflammatory effect, an n-6 PUFA enriched diet may be more atherogenic. There- fore, the dietary n-6:n-3 ratio is increasingly recognized as being more important than absolute intake.²²⁾

A question arises as to why n-3 PUFA has been effective in the past, given the absence of correlation in recent studies, including the present study. Kromhout et al.²³⁾ suggested one possibility. Recent results have been affected by improvement in cardio-protective drug treatment, such as the use of statins. The authors opined that statin use might reduce the beneficial effect of n-3. In our study, 7.8% of participants were taking medication for hyperlipidemia. Because the FRS is calculated using TC and HDL, the results could have been affected by hyperlipidemia treatment.

The n-3 PUFA was reported to increase mortality in angina patients than decreasing malignant arrhythmia during regional myocardial isch- emia.¹⁴⁾ In heart failure patients, n-3 is elevated in red blood cells and can aid in predicting the risk of ventricular arrhythmias.²⁴⁾ Men diagnosed with angina who are advised to eat oily fish particularly those taking fish oil capsules are reported to have a higher risk of cardiac death.²⁵⁾ PUFAs are typically consumed by eating fish. Men in Eastern Finland, who con- sume a large amount of fish, have an exceptionally high CHD mortality.

Salonen et al.²⁶⁾ explained this was due to the high mercury content in fish. When considering these results, increasing the intake of n-3 PUFA may not necessarily be beneficial in preventing CVDs. Our study results are also consistent with a prior finding that dietary n-3 and n-6 PUFAs are not significantly associated with FRS after adjustment for relevant variables.

There are some limitations in our study. First, this study was cross- sectional and not prospective. Secondly, KNHANES data for one year (2013) were used instead of data from multiple years. Thirdly, dietary n-3 and n-6 PUFAs were assessed using a one-day dietary questionnaire.

Nonetheless, this is the first study to evaluate the association of dietary n-3 and n-6 PUFAs and FRS in Koreans. The results provide preliminary data for more detailed research into the relationship of dietary n-3 and n-6 PUFAs and CV risk factor assessments, such as FRS.

In conclusion, FRS showed no differences in the comparison according to the tertiles of dietary n-3 and n-6 PUFAs. Dietary PUFAs may not be significant in the association with FRS.

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