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J Am Coll Cardiol, 2005; 45:1716-1722, doi:10.1016/j.jacc.2005.01.060
© 2005 by the American College of Cardiology Foundation
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EXPEDITED REVIEW

Dietary Linolenic Acid and Adjusted QT and JT Intervals in the National Heart, Lung, and Blood Institute Family Heart Study

Luc Djoussé, MD, DSc, MPH*,*, Pentti M. Rautaharju, MD, PhD{dagger}, Paul N. Hopkins, MD, MSPH{ddagger}, Eric A. Whitsel, MD, MPH§, Donna K. Arnett, PhD, MSPH||, John H. Eckfeldt, MD, PhD, Michael A. Province, PhD#, R. Curtis Ellison, MD* Investigators of the NHLBI Family Heart Study

* Section of Preventive Medicine & Epidemiology, Evans Department of Medicine, Boston University School of Medicine, Boston, Massachusetts
{dagger} Department of Community Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina
{ddagger} Department of Cardiovascular Genetics, University of Utah, Salt Lake City, Utah
§ Department of Medicine and Epidemiology, University of North Carolina, Chapel Hill, North Carolina
|| Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama
Department of Laboratory Medicine and Pathology, Fairview-University Medical Center, Minneapolis, Minnesota
# Division of Biostatistics, Washington University, St. Louis, Missouri

Manuscript received October 29, 2004; revised manuscript received December 16, 2004, accepted January 11, 2005.

* Reprint requests and correspondence: Dr. Luc Djoussé, Boston University School of Medicine, Room B-612, 715 Albany Street, Boston, Massachusetts 02118 (Email: ldjousse{at}bu.edu).


   Abstract
Top
 Abstract
Methods
 Results
 Discussion
 References
 
OBJECTIVES: The goal of this study was to examine whether higher consumption of total linolenic acid was associated with rate-adjusted QT and JT intervals (QTrr and JTrr, respectively).

BACKGROUND: Higher intake of fish omega-3 fatty acids and plant omega-3 such as alpha-linolenic acid is associated with lower risk of myocardial infarction. While long-chain omega-3 can inhibit ventricular arrhythmia, it is not known whether alpha-linolenic acid influences ventricular repolarization.

METHODS: We studied 3,642 subjects from the National Heart, Lung, and Blood Institute Family Heart study who were free of myocardial infarction, left ventricular hypertrophy, pacemaker, and with QRS <120 ms. We used the 95th percentile of the gender-specific distribution of QTrr and JTrr to define abnormally prolonged repolarization. Within each gender, we created age- and energy-adjusted tertiles of linolenic acid and used regression models for analyses.

RESULTS: Mean age was 50 years, and average intake of total linolenic acid was 0.74 g/day. There was an inverse association between consumption of linolenic acid and QTrr and JTrr (p for trend 0.001 and 0.0005, respectively). From the lowest (reference) to the highest gender-, age-, and energy-adjusted tertile of linolenic acid, multivariable adjusted odds ratios for prolonged QTrr were 1.0, 0.74 (95% confidence interval [CI] 0.57 to 0.96), and 0.59 (95% CI 0.44 to 0.77), respectively (p for trend 0.0003). Corresponding values for JTrr were 1.0, 0.73 (95% CI 0.52 to 1.03), and 0.59 (95% CI 0.40 to 0.87), respectively (p for trend 0.009). Exclusion of subjects taking drugs known to influence QT did not influence this association.

CONCLUSIONS: Higher intake of dietary linolenic acid might be associated with a reduced risk of abnormally prolonged repolarization in men and women.

Abbreviations and Acronyms
  AA = arachidonic acid
  CAD = coronary artery disease
  CI = confidence interval
  DHA = docosahexaenoic acid
  ECG = electrocardiogram/electrocardiographic
  EPA = eicosapentaenoic acid
  JTrr = rate-adjusted JT interval as JT – 176·[(60/HR) – 1] + 14 for men (HR = heart rate)
  NHLBI = National Heart, Lung, and Blood Institute
  QTc = rate-adjusted QT interval as QT/RR1/2
  QTrr = rate-adjusted QT interval as QT – 185·[(60/HR) – 1] + 6 for men (HR = heart rate)

Coronary artery disease (CAD) remains the leading cause of death in the U.S. While several studies have demonstrated the beneficial effects of dietary linolenic acid on myocardial infarction (1–5), limited data are available on possible underlying physiologic mechanisms. Reducing inflammation (6) and lowering triglycerides (7,8) and, perhaps, blood pressure (9) have been suggested as possible pathways. The role of linolenic acid on ventricular repolarization in humans has not been investigated. A small percentage of linolenic acid can be converted to long-chain omega-3 fatty acids such as eicosapentaenoic fatty acid (EPA) and, in lesser amounts, to docosahexaenoic acid (DHA) (10). Both EPA and DHA have been shown to reduce the risk of sudden cardiac death, possibly through antiarrhythmic effects (11,12). In an animal model, EPA and DHA prevented ventricular fibrillation compared with a control group (13). To date, no study has investigated whether dietary linolenic acid influences the ventricular repolarization phase in humans as measured by rate-adjusted QT and JT intervals (QTrr and JTrr, respectively) (14,15). Linoleic acid—an omega-6 fatty acid—competes with linolenic acid as substrates for desaturase and elongase enzymes. Because the Western diet is rich in linoleic acid, it has been suggested that a lower ratio of linoleic/linolenic acid (e.g., below 6) would maximize the conversion of linolenic acid to DHA (16). Dietary linolenic acid in foods is predominantly alpha-form, and a small amount of gamma-form is found mostly in fatty meat. Dietary linolenic acid is found mainly in flaxseed, linseed, and canola oil, and, to a lesser extent, in soybean oil and green leafy vegetables (16).

We used data collected on 3,642 Caucasian participants of the National Heart, Lung, and Blood Institute (NHLBI) Family Heart study to assess whether dietary consumption of higher amounts of total linolenic acid (alpha- and gamma-form) was associated with QTrr and JTrr. In addition, we evaluated whether such association was modified by the ratio of linoleic-to-linolenic fatty acid.


   Methods
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 Methods
Results
 Discussion
 References
 
Study population.   Subjects in this project were participants of the NHLBI Family Heart study. A detailed description of the NHLBI Family Heart study has been published (17). Briefly, families in the study had been chosen randomly (a random group n = 2,673) or based on a higher than expected risk of CAD from previously established population-based cohort studies (a high-risk group n = 3,037). A family risk score, which related the family’s age- and gender-specific incidence of CAD to that expected in the general population (18), was used to identify families for the high-risk group. Of the 5,710 Caucasian subjects, we excluded 2,068 from the main analyses for the following reasons: 1) missing data on electrocardiogram (ECG) (n = 21), or on dietary linolenic acid (n = 827), or covariates (n = 119); 2) unreliable food frequency questionnaire (n = 149); 3) energy intake outside a priori ranges (n = 140); 4) myocardial infarction (n = 498) or major ventricular conduction defect (n = 308); and 5) QRS interval above 120 ms (n = 6).We did not have an adequate sample on non-Caucasians (n = 265) for separate analyses. Each participant gave informed consent, and the study protocol was reviewed and approved by each of the participating institutions.

Dietary assessment.   We used a staff-administered semiquantitative food frequency questionnaire (19) to obtain data on dietary linolenic acid and other nutrients. The reproducibility and validity of this food frequency questionnaire have been described previously (20). Nutrients were obtained by multiplying the frequency of consumption of an item by the nutrient content of specified portions. Composition values for total linolenic acid and other nutrients were obtained from the Harvard University Food Composition Database derived from U.S. Department of Agriculture sources (21) and manufacturer information.

ECG methodology.   All ECGs in the study were recorded using strictly standardized methods for ECG acquisition and processing. These methods have been described previously (22). Briefly, during the clinic visit, standard 12-lead ECGs were recorded using MAC-PC electrocardiographs (Marquette Electronics, Inc., Milwaukee, Wisconsin), and 10-s records were digitized using a sampling rate of 250 samples/s per lead. All QT measurements were visually verified, and occasional errors were corrected using interactive graphics terminals. The QT and JT intervals were rate-adjusted as a linear function of the RR interval using the algorithms described by Rautaharju et al. (15): QTrr = QT – 185·(60/heart rate – 1) + [6 ms in men] and JTrr = JT – 176·(60/heart rate – 1) + [14 ms in men], where JT = QT – QRS. This method of adjustment eliminates the strong residual correlation between the adjusted QT and heart rate observed repeatedly for the Bazett’s QTc (23–25).

Other variables.   Resting blood pressure was measured three times on sitting participants after a 5-min rest using a random zero sphygmomanometer by trained technicians. Information on cigarette smoking, alcohol intake, education, and level of physical activity during the previous year was obtained by interview. Diabetes mellitus was present if a subject was taking hypoglycemic agents, or if a physician had told him/her that he/she has diabetes mellitus, or if fasting glucose levels were above 7.0 mmol/l. Prevalent CAD was assessed by self-reported history of myocardial infarction, percutaneous transluminal coronary angioplasty, or coronary artery bypass graft. Use of digoxin, diuretic, antiarrhythmic drugs, and other prescription drugs were assessed through medication inventory.

Statistical analyses.   Because higher energy intake is associated with higher linolenic acid and energy intake and dietary patterns differ between men and women and by age, we created gender-, age-, and energy-specific tertiles of linolenic acid. Within each gender, we created four-year age groups (seven categories) and quintiles of energy intake. Then, within each of the 35 groups, we created tertiles of linolenic acid (referred to as gender-, age-, and energy-specific tertiles of linolenic acid). To estimate adjusted mean values of QTrr and JTrr, we used generalized estimating equations to account for familial clustering and confounding factors. The minimal adjusted model controlled for age, body mass index, systolic and diastolic blood pressure, and serum potassium. The full model also controlled for diabetes mellitus, exercise, class Ia and class III antiarrhythmic drugs, and other drugs known to prolong QT intervals or increase the risk of Torsades de Pointes (i.e., antipsychotic, antimalarial, macrolide antibiotics, opiate agonist, and so on). Further adjustment for center, education, diuretic use, risk group (random vs. high-risk group), long-chain omega-3 fatty acids, and waist-hip ratio did not alter the results (data not shown). We also used the 95th percentile of the gender-specific distribution of QTrr (446.9 for men and 455.0 for women) and JTrr (359.0 for men and 363.7 for women) to define abnormal QTrr and abnormal JTrr and used a generalized estimating equation to compute the prevalence odds ratios. In addition, we used linolenic acid as a continuous variable and related it to QTrr and JTrr. We conducted sensitivity analyses by: 1) excluding subjects who were using digoxin or antiarrhythmic drugs; and 2) using subjects previously excluded in the initial analyses. Because linoleic and linolenic acids are competitive substrate for desaturase, we assessed whether the linoleic/linolenic ratio modified the association through: 1) stratified analyses using gender-specific median values of linolenic acid to create two groups; and 2) including main effects and product term in the regression model. Alpha level was set at 0.05, and all analyses were completed using windows SAS version 5.1.2, release 8.02 (SAS Institute, Cary, North Carolina).


   Results
Top
 Abstract
 Methods
 Results
Discussion
 References
 
Characteristics of participants.   Of the 3,642 Caucasian participants included in the analyses, 1,477 were men and 2,165 were women. The mean age was 48.6 ± 13.4 years for men and 51.1 ± 13.4 years for women. The average daily consumption of total dietary linolenic acid was 0.81 ± 0.35 g for men (range 0.21 to 3.48 g/day) and 0.69 ± 0.29 g for women (range 0.13 to 2.45 g/day). Table 1 presents the baseline characteristics by gender-, age-, and energy-adjusted tertiles of dietary linolenic acid.


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  		Table 1. Characteristics of the 3,642 Participants of the NHLBI Family Heart Study According to Gender-, Age-, and Energy-Adjusted Tertiles of Dietary Linolenic Acid*
 
Association between dietary linolenic acid and QTrr and JTrr intervals.   Dietary linolenic acid was inversely associated with QTrr in men in a multivariable adjusted model (p for linear trend 0.0009) (Table 2). In women, a nonstatistically significant inverse association between dietary linolenic acid and QTrr was observed (p for trend 0.12) (Table 2). In a multivariable model, both men and women showed an inverse association between linolenic acid and JTrr in a dose-response fashion (p for linear trend 0.002 for men and 0.04 for women) (Table 2). We observed a similar association using dietary linolenic acid as a continuous variable. For men and women combined, the regression coefficients (SE) for QTrr were –0.5479 (0.1888) for the crude model and –0.835 (0.3061) for the multivariate-adjusted regression model. Corresponding values for JTrr were –0.4945 (0.2437) for the crude and –0.9994 (0.4224) for the multivariable model.


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  		Table 2. Crude and Adjusted Mean Values ± SE of the Rate-Adjusted QT and JT Intervals by Gender and Tertiles of Dietary Linolenic Acid in 3,642 Participants of the NHLBI Family Heart Study
 
There was evidence for a reduced risk for the prolonged repolarization in both men and women. From the lowest to the highest tertile of linolenic acid, multivariable adjusted prevalence odds ratios for prolonged repolarization based on QTrr were 1.0 (reference), 0.81 (95% confidence intervals [CI] 0.46 to 1.44), and 0.51 (95% CI 0.27 to 0.98), respectively, for men (p for trend 0.04) (Table 3). Corresponding values for women were 1.0, 0.71 (95% CI 0.53 to 00.95), and 0.60 (95% CI 0.44 to 0.82), respectively (p for trend 0.003) (Table 3). Similar reduced risk of prolonged repolarization using JTrr was observed, and the results were stronger in women than in men (Table 4). In both men and women combined, the risk of abnormally prolonged repolarization was 41% lower in the highest tertile of linolenic acid compared with the lowest tertile in a multivariable adjusted model (Table 4).


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  		Table 3. Crude and Adjusted Odds Ratios (95% Confidence Intervals) for Abnormal Rate-Adjusted QT According to Gender-, Age-, and Energy-Adjusted Tertiles of Dietary Linolenic Acid in 3,642 Participants of the NHLBI Family Heart Study*
 

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  		Table 4. Crude and Adjusted Odds Ratios (95% Confidence Intervals) for Abnormal Rate-Adjusted JT by Gender-, Age-, and Energy-Adjusted Tertiles of Dietary Linolenic Acid in 3,642 Participants of the NHLBI Family Heart Study*
 
The ratio of linoleic-to-linolenic acid did not influence the results, and there was no evidence for interaction between linoleic and linolenic acid on abnormal QTrr (p = 0.21) or JTrr (p = 0.23).

Sensitivity analyses.   Exclusion of subjects currently receiving digoxin and/or antiarrhytmic drugs did not change the results. From the lowest to the highest tertile of linolenic acid, multivariable adjusted odds ratios for prolonged repolarization using QTrr in the combined data set were 1.0 (reference), 0.75 (95% CI 0.57 to 0.98), and 0.61 (95% CI 0.45 to 0.82), respectively (p for trend 0.0012). Corresponding values were 1.0, 0.64 (95% CI 0.45 to 0.91), and 0.53 (95% CI 0.35 to 0.80), respectively, using JTrr (p for trend 0.003). In a sample (n = 4,504) that included subjects excluded in the initial analyses (i.e., prevalent CAD, left ventricular hypertrophy, and so on), the observed association persisted (i.e., p for trend 0.0017 using QTrr to define abnormal repolarization), and further adjustment for left ventricular hypertrophy, T-negativity, ST-segment depression/elevation did not change the results.


   Discussion
Top
 Abstract
 Methods
 Results
 Discussion
References
 
In this cross-sectional study, higher intake of dietary total linolenic acid (alpha- and gamma-form) was inversely associated with heart-rate-adjusted QT and JT intervals in a dose-response manner in both men and women. This association was not modified by the ratio of n-6 to n-3 fatty acids.

n-3 fatty acids and arrhythmia.   While epidemiologic studies have shown the beneficial effects of linolenic acid on fatal and nonfatal CAD (1–5), triglycerides (8), and carotid wall thickness (26), no data are available on the effects of linolenic acid on myocardial repolarization in humans. Evidence of beneficial effects of EPA and DHA on ventricular arrhythmia has been shown in animal models and in humans. Infusion of EPA (12,13), DHA (12,13), and alpha-linolenic acid (12) in dogs was associated with a significant reduction in ventricular fibrillation. Rats fed with a tuna fish oil diet had a significantly lower incidence rate and severity of arrhythmias and lower risk of ventricular fibrillation compared with rats on a diet enriched with sunflower oil (27). In a study of monkeys, fish oil was associated with significantly raised ventricular fibrillation threshold (33.3 mA) compared with sunflower oil (14.3 mA) after a 16-week intervention (28). Siscovick et al. (29) demonstrated that, compared with no intake of dietary EPA and DHA, monthly intake of 5.5 g of n-3 fatty acid was associated with a 50% reduction in the risk of primary cardiac arrest in 334 patients. In a randomized control trial, a diet rich in EPA and DHA was associated with a 48% decrease in ventricular premature complexes compared to only 25% reduction in the placebo group (sunflower oil) after 16 weeks of intervention (30). Nevertheless, little is known about the relation between dietary linolenic acid and ventricular repolarization or arrhythmia. The only evidence showing antiarrhythmic effects of alpha-linolenic acid has been provided from animal study. In a dog model of cardiac sudden death, alpha-linolenic acid infusion prevented fatal ventricular fibrillation in six of eight dogs (12), an effect similar to infusion of DHA or EPA in the same study. To our knowledge, no previous study has examined the relation between dietary linolenic acid and heart-rate-adjusted QT or JT intervals.

Physiologic mechanisms.   Modification of the eicosanoid system by dietary fatty acids is one of the suggested mechanisms by which EPA and DHA protect against ventricular arrhythmia. The Western diet is rich in linoleic acid, which is a precursor of arachidonic acid (AA); AA is metabolized to generate (n-2) series of prostanoids such as thromboxane A2 and leukotrienes. Alpha-linolenic acid is a precursor of prostaglandin I3 (a vasodilator) and thromboxane A3, which is less active (9). A limited amount of linolenic acid is converted to EPA in vivo; EPA competes with AA as a substrate for cyclooxygenase, thus inhibiting the production of thromboxane A2 that causes vasoconstrictor and platelet aggregation. A reduced ratio of AA/EPA favors the production of (n-3) series of prostanoids and less thromboxane A2 and, thus, reduces the risk of ventricular fibrillation and cardiac arrest (31). Another possible mechanism is the modulation of L-type calcium channels in the sarcolemma of cardiac myocytes by DHA (32). However, additional research is needed to elucidate biologic mechanisms underlying antiarrhythmic effects of n-3 fatty acids.

Other investigators have suggested that a diet rich in n-3 fatty acids (such as linolenic acid) could suppress plasma levels of metabolites of linoleic acid such as thromboxane A2, which stimulates vasoconstriction and platelet aggregation (33). This has been the basis to favor a lower ratio of linoleic-to-linolenic acid (below 6). In the present study, the association between linolenic acid and QT intervals was not modified by the ratio of linoleic-to-linolenic acid.

Study limitations.   In the present study, nutrients were derived from a food frequency questionnaire that has been shown to underestimate energy intake when compared with the doubly-labeled water technique (34). Therefore, our estimate of daily intake of linolenic acid and other nutrients might have been biased. We did not have data separately on alpha- and gamma-linolenic acid. In addition, the cross-sectional design of our study limits our ability to infer causality between linolenic acid intake and QT/JT. However, the large sample size, the availability of data on several risk factors, the wide range of age and linolenic acid, the consistency of our findings with other published reports, and the multicenter design are strengths of our study.

In conclusion, our data suggest that higher consumption of dietary linolenic acid is associated with a reduced risk of prolonged repolarization in both men and women. While this might be one of the underlying mechanisms by which dietary linolenic acid decrease the risk of cardiovascular disease, future studies are needed to confirm our findings.


   Acknowledgments
 
The authors thank the FHS participants and staff for their valuable contributions.


   Footnotes
 
Support was partially provided by the National Heart, Lung, and Blood Institute cooperative agreement grants U01 HL56563, U01 HL56564, U01 HL56565, U01 HL56566, U01 HL56567, U01 HL56568, U01 HL56569, and grant K01-HL70444.


   References
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  1. de Lorgeril M, Renaud S, Mamelle N, et al. Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease Lancet 1994;343:1454-1459.[CrossRef][ISI][Medline]
  2. Hu FB, Stampfer MJ, Manson JE, et al. Dietary intake of alpha-linolenic acid and risk of fatal ischemic heart disease among women Am J Clin Nutr 1999;69:890-897.[Abstract/Free Full Text]
  3. Djoussé L, Pankow JS, Eckfeldt JH, et al. Relation between dietary linolenic acid and coronary artery disease in the National Heart, Lung, and Blood Institute Family Heart study Am J Clin Nutr 2001;74:612-619.[Abstract/Free Full Text]
  4. Baylin A, Kabagambe EK, Ascherio A, Spiegelman D, Campos H. Adipose tissue alpha-linolenic acid and nonfatal acute myocardial infarction in Costa Rica Circulation 2003;107:1586-1591.[Abstract/Free Full Text]
  5. Rastogi T, Reddy KS, Vaz M, et al. Diet and risk of ischemic heart disease in India Am J Clin Nutr 2004;79:582-592.[Abstract/Free Full Text]
  6. Rallidis LS, Paschos G, Liakos GK, Velissaridou AH, Anastasiadis G, Zampelas A. Dietary alpha-linolenic acid decreases C-reactive protein, serum amyloid A and interleukin-6 in dyslipidaemic patients Atherosclerosis 2003;167:237-242.[CrossRef][ISI][Medline]
  7. Kris-Etherton PM, Yu S. Individual fatty acid effects on plasma lipids and lipoproteins: human studies Am J Clin Nutr 1997;65:1628S-1644S.[Abstract/Free Full Text]
  8. Djoussé L, Hunt CS, Arnett DK, Province MA, Eckfeldt JH, Ellison RC. Dietary linolenic acid is inversely associated with plasma triacylglycerol: the National Heart, Lung, and Blood Institute Family Heart study Am J Clin Nutr 2003;78:1098-1102.[Abstract/Free Full Text]
  9. Salonen JT, Salonen R, Ihanainen M, et al. Blood pressure, dietary fats, and antioxidants Am J Clin Nutr 1988;48:1226-1232.[Abstract/Free Full Text]
  10. Gerster H. Can adults adequately convert alpha-linolenic acid (18:3n-3) to eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3)? Int J Vit Nutr Res 1988;68:159-173.
  11. Kang JX, Leaf A. Prevention of fatal cardiac arrhythmias by polyunsaturated fatty acids Am J Clin Nutr 2000;71:202S-207S.[Abstract/Free Full Text]
  12. Billman GE, Kang JX, Leaf A. Prevention of sudden cardiac death by dietary pure omega-3 polyunsaturated fatty acids in dogs Circulation 1999;99:2452-2457.[Abstract/Free Full Text]
  13. Billman GE, Hallaq H, Leaf A. Prevention of ischemia-induced ventricular fibrillation by omega 3 fatty acids Proc Natl Acad Sci U S A 1994;91:4427-4430.[Abstract/Free Full Text]
  14. Rautaharju PM, Zhang ZM. Linearly scaled, rate-invariant normal limits for QT interval: eight decades of incorrect application of power functions J Cardiovasc Electrophysiol 2002;13:1211-1218.[CrossRef][ISI][Medline]
  15. Rautaharju PM, Zhang ZM, Prineas R, Heiss G. Assessment of prolonged QT and JT intervals in ventricular conduction defects Am J Cardiol 2004;93:1017-1021.[CrossRef][ISI][Medline]
  16. Kris-Etherton PM, Taylor DS, Yu-Poth S, et al. Polyunsaturated fatty acids in the food chain in the United States Am J Clin Nutr 2000;71:179S-188S.[Abstract/Free Full Text]
  17. Higgins M, Province M, Heiss G, et al. NHLBI Family Heart study: objectives and design Am J Epidemiol 1996;143:1219-1228.[Abstract/Free Full Text]
  18. Hunt SC, Williams RR, Barlow GK. A comparison of positive family history definitions for defining risk of future disease J Chronic Dis 1986;39:809-821.[CrossRef][ISI][Medline]
  19. Willett WC, Sampson L, Stampfer MJ, et al. Reproducibility and validity of a semiquantitative food frequency questionnaire Am J Epidemiol 1985;122:51-65.[Abstract/Free Full Text]
  20. Rimm EB, Giovannucci EL, Stampfer MJ, Colditz GA, Litin LB, Willett WC. Reproducibility and validity of an expanded self-administered semiquantitative food frequency questionnaire among male health professionals Am J Epidemiol 1992;135:1114-1126.[Abstract/Free Full Text]
  21. US Department of Agriculture Composition of Foods: Raw, Processed, and Prepared, 1963–1988. Washington DC: U.S. Government Printing Office; 1989Agriculture handbook no. 8.
  22. Hong Y, Rautaharju PM, Hopkins PN, et al. Familial aggregation of QT-interval variability in a general population: results from the NHLBI Family Heart study Clin Genet 2001;59:171-177.[CrossRef][ISI][Medline]
  23. Kawataki M, Kashima T, Toda H, Tanaka H. Relation between QT interval and heart rate. Applications and limitations of Bazett’s formula J Electrocardiol 1984;17:371-375.[ISI][Medline]
  24. Rautaharju PM, Warren JW, Calhoun HP. Estimation of QT prolongation. A persistent, avoidable error in computer electrocardiography J Electrocardiol 1990;23(Suppl):111-117.
  25. Sagie A, Larson MG, Goldberg RJ, Bengtson JR, Levy D. An improved method for adjusting the QT interval for heart rate (the Framingham Heart study) Am J Cardiol 1992;70:797-801.[CrossRef][ISI][Medline]
  26. Djoussé L, Folsom AR, Province MA, Hunt SC, Ellison RC. Dietary linolenic acid and carotid atherosclerosis: the National Heart, Lung, and Blood Institute Family Heart study Am J Clin Nutr 2003;77:819-825.[Abstract/Free Full Text]
  27. McLennan PL, Abeywardena MY, Charnock JS. Dietary fish oil prevents ventricular fibrillation following coronary artery occlusion and reperfusion Am Heart J 1988;116:709-717.[CrossRef][ISI][Medline]
  28. McLennan PL, Bridle TM, Abeywardena MY, Charnock JS. Comparative efficacy of n-3 and n-6 polyunsaturated fatty acids in modulating ventricular fibrillation threshold in marmoset monkeys Am J Clin Nutr 1993;58:666-669.[Abstract/Free Full Text]
  29. Siscovick DS, Raghunathan TE, King I, et al. Dietary intake and cell membrane levels of long-chain n-3 polyunsaturated fatty acids and the risk of primary cardiac arrest JAMA 1995;274:1363-1367.[Abstract]
  30. Sellmayer A, Witzgall H, Lorenz RL, Weber PC. Effects of dietary fish oil on ventricular premature complexes Am J Cardiol 1995;76:974-977.[CrossRef][ISI][Medline]
  31. Coker SJ, Parratt JR, Ledingham IM, Zeitlin IJ. Evidence that thromboxane contributes to ventricular fibrillation induced by reperfusion of the ischaemic myocardium J Mol Cell Cardiol 1982;14:483-485.[CrossRef][ISI][Medline]
  32. Hallaq H, Smith TW, Leaf A. Modulation of dihydropyridine-sensitive calcium channels in heart cells by fish oil fatty acids Proc Natl Acad Sci U S A 1992;89:1760-1764.[Abstract/Free Full Text]
  33. Salonen R, Nikkari T, Seppanen K, et al. Effect of omega-3 fatty acid supplementation on platelet aggregability and platelet produced thromboxane Thromb Haemost 1987;57:269-272.[ISI][Medline]
  34. Trabulsi J, Schoeller DA. Evaluation of dietary assessment instruments against doubly labeled water, a biomarker of habitual energy intake Am J Physiol Endocrinol Metab 2001;281:E891-E899.[Abstract/Free Full Text]



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Am. J. Clinical Nutrition, June 1, 2006; 83(6): S1477 - 1482S.
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C. M. Albert, K. Oh, W. Whang, J. E. Manson, C. U. Chae, M. J. Stampfer, W. C. Willett, and F. B. Hu
Dietary {alpha}-Linolenic Acid Intake and Risk of Sudden Cardiac Death and Coronary Heart Disease
Circulation, November 22, 2005; 112(21): 3232 - 3238.
[Abstract] [Full Text] [PDF]

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