Download Cell Membrane Trans-Fatty Acids and the Risk of Primary Cardiac

Cell Membrane Trans-Fatty Acids and the Risk of Primary
Cardiac Arrest
Rozenn N. Lemaitre, PhD, MPH; Irena B. King, PhD; Trivellore E. Raghunathan, PhD;
Rachel M. Pearce, MS; Sheila Weinmann, PhD; Robert H. Knopp, MD;
Michael K. Copass, MD; Leonard A. Cobb, MD; David S. Siscovick, MD, MPH
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Background—The relation of trans-fatty acid intake to life-threatening arrhythmias and primary cardiac arrest is unknown.
Methods and Results—We investigated the association of trans-fatty acid intake, assessed through a biomarker, with the
risk of primary cardiac arrest in a population-based case-control study. Cases, aged 25 to 74 years, were out-of-hospital
cardiac arrest patients attended by paramedics in Seattle, Washington from 1988 to 1999 (n⫽179). Controls, matched
to cases by age and sex, were randomly identified from the community (n⫽285). Participants were free of previous
clinically diagnosed heart disease. Blood was obtained at the time of cardiac arrest (cases) or at the time of an interview
(controls) to assess trans-fatty acid intake. Higher total trans-fatty acids in red blood cell membranes was associated
with a modest increase in the risk of primary cardiac arrest after adjustment for medical and lifestyle risk factors (odds
ratio for interquintile range, 1.5; 95% CI, 1.0 to 2.1). However, trans isomers of oleic acid were not associated with risk
(odds ratio for interquintile range, 0.8; 95% CI, 0.5 to 1.2), whereas higher levels of trans isomers of linoleic acid were
associated with 3-fold increase in risk (odds ratio for interquintile range, 3.1; 95% CI, 1.7 to 5.4).
Conclusions—These findings suggest that dietary intake of total trans-fatty acids is associated with modest increase and
trans isomers of linoleic acid with a larger increase in the risk of primary cardiac arrest. These associations need to be
confirmed in future studies that distinguish between trans isomers of linoleic acid and trans isomers of oleic acid.
(Circulation. 2002;105:●●●-●●●.)
Key Words: heart arrest 䡲 fatty acids 䡲 epidemiology
S
udden cardiac death is the leading cause of death from
coronary heart disease (CHD), with about half of the
cases occurring in persons without clinically diagnosed heart
disease.1 Although the prevention of sudden cardiac death in
the community remains a challenge, there is growing evidence that the fatty acid composition of the diet can influence
the risk of life-threatening arrhythmias and sudden cardiac
death.2–10
Whether trans-fatty acids influence the risk of sudden
cardiac death is unknown.
Diets enriched in saturated fatty acids increase the risk
of ventricular fibrillation and sudden cardiac death in
primates.4,7 Because trans-fatty acids resemble saturated
fatty acids in their biophysical properties, we hypothesized
that higher levels of dietary trans-fatty acids, assessed by
a biomarker, would be associated with an increased risk of
primary cardiac arrest (sudden cardiac death). Trans isomers of linoleic acid (trans-18:2) represents 25% of total
trans-fatty acids in adipose tissue, suggesting that they
contribute to trans fatty acid intake.16 Trans-18:2 fatty
acids, which have one cis double bond and one trans
double bond, have different biophysical properties than
trans-fatty acids with a single trans double bond (trans18:1).12 For these reasons, we also investigated whether
trans-18:2 fatty acids might differ from trans-18:1 in their
association with primary cardiac arrest (PCA). To examine
these questions, we conducted a population-based casecontrol study.
See p ●●●
Trans-fatty acids are unsaturated fatty acids found in
partially hydrogenated oils, beef, and dairy products.11,12
Trans-fatty acids differ from most naturally occurring
unsaturated fatty acids by the presence of one or more
double bonds in the trans configuration instead of the
usual cis configuration. Like saturated fatty acids, fatty
acids with trans double bonds pack more tightly than cis
fatty acids, allowing the processing of oils into margarine.
Population studies suggest an increased risk of CHD with
higher dietary intake of total trans-fatty acids. 13–15
Received October 19, 2001; revision received December 3, 2001; accepted December 14, 2001.
From the Cardiovascular Health Research Unit, Departments of Medicine (R.N.L., D.S.S., R.M.P., S.W., R.H.K., M.K.C., L.A.C.) and Epidemiology
(D.S.S.), University of Washington, Seattle; Public Health Sciences Division (I.B.K.), Fred Hutchinson Cancer Research Center, Seattle, Wash; and the
Institute for Social Research (T.E.R.), University of Michigan, Ann Arbor.
Correspondence to Rozenn N. Lemaitre, PhD, MPH, University of Washington, Cardiovascular Health Research Unit, Metropolitan Park, East Tower,
Suite 1360, 1730 Minor Ave, Seattle, WA 98101. E-mail [email protected]
© 2001 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org
DOI: 10.1161/hc0602.103583
1
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Circulation
February 12, 2002
Methods
Study Subjects
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Cases were out-of-hospital PCA patients attended by paramedics in
Seattle and suburban King County, Washington, between October
1988 and June 1999. We defined PCA as a sudden pulseless
condition in the absence of evidence of a noncardiac cause of cardiac
arrest. Cases were identified from emergency service incident
reports. In addition to incident reports, we reviewed death certificates, medical examiner reports, and autopsy reports, when available,
to exclude patients with cardiac arrest attributable to a noncardiac
cause.
We restricted PCA cases to married residents of King County,
Washington, between the ages of 25 and 74 years. Cases for whom
the paramedics were unable to draw a blood sample at the time of the
arrest were excluded. We have previously shown that the distributions of risk factors among cases with and without blood samples
were similar.10 Because the focus of the study was on persons who
appeared healthy until their cardiac arrest, we excluded cases with a
history of clinically recognized heart disease or life-threatening
comorbidities. We also excluded users of fish-oil supplements,
because fish oil use would affect red blood cell (RBC) membrane
fatty acid composition.
We were able to contact 89% of the spouses of identified cases.
The spouses of 205 eligible cases (86%) participated in an in-person
interview (n⫽196) or a telephone interview (n⫽9), for an overall
response rate of 77%. Additionally, 26 cases were excluded because
their blood could not be analyzed.
For each case, control subjects matched on age (within 7 years)
and sex were randomly selected from the community by the
sampling technique of random-digit dialing.17 Ninety-seven percent
of known residential households contacted were successfully
screened to determine if residents were eligible for the study. We
obtained blood samples and spouse interviews from 309 eligible
control subjects (61%), for an overall response rate of 59%.
Additionally, 24 controls were excluded because their blood could
not be analyzed. Controls followed the same eligibility criteria as the
cases.
Red Blood Cell Membrane Fatty Acid Measurements
Paramedics obtained blood specimens from the cases in the field
after essential emergency medical care had been provided and either
the patient was clinically stable or resuscitation had proven ineffective, usually within 30 to 45 minutes of the cardiac arrest. Blood
specimens were obtained from controls at the time of the interview.
The University of Washington Human Subjects Review Committee
approved the protocol.
Blood specimens were processed10 and submitted to gas chromatography16 according to published methods. Technicians blinded to
case and control status conducted the laboratory analyses. Quality
control included the use of pooled RBCs and internal standards.
Using gas chromatography, we measured nine trans-fatty acids in
RBC membrane samples: five trans isomers of oleic acid, collectively referred to as trans-18:1 (12 trans-18:1, 11 trans-18:1, 10
trans-18:1, 9 trans-18:1, and mix of 6 to 8 trans-18:1); two trans
isomers of linoleic acid, collectively referred to trans-18:2 (9 cis, 12
trans-18:2 and 9 trans, 12 cis-18:2); and two trans isomers of
palmitoleic acid, collectively referred to trans-16:1 (7 trans-16:1 and
9 trans-16:1). We did not identify any conjugated trans isomer of
linoleic acid. We summed data on the individual trans-fatty acids to
obtain the RBC membrane levels of total trans-fatty acids, trans18:1, trans-18:2, and trans-16:1. Fatty acid levels were expressed as
percentages of total fatty acids.
Validity of Red Blood Cell Trans-Fatty
Acid Measurement
To validate the measurement of RBC membrane level of trans-fatty
acids as a biomarker of dietary intake of trans-fatty acids, we
developed a 17-item food frequency questionnaire. For each food
consumed, spouses as proxy respondents for cases and controls were
asked to estimate usual serving size and frequency of consumption
during the prior month of 17 processed foods, previously found to
contribute the most to dietary intake of trans-fatty acids in a previous
study.16 Using the United States Department of Agriculture’s Special
Purpose Table No. 1,18 we calculated an index of total trans-fatty
acid dietary intake from the trans-fatty acids consumed in the 17
foods. Among 111 controls, RBC membrane total trans-fatty acid
levels were related to the index of total trans-fatty acid intake
(r⫽0.5, P⬍0.001).
Relation of Red Blood Cell Membrane Levels of
Trans-18:1 and Trans-18:2 Fatty Acids to Intake of
Specific Foods
We used the spouse dietary data for 111 controls to perform linear
regression analyses using RBC membrane levels of trans isomers as
dependent variables and consumption frequencies of the 17 foods
listed in the questionnaire as predictors. Higher consumption of
commercially available pizza, fried chicken, and cookies were
independent predictors of higher RBC membrane levels of trans18:2 fatty acids (model Rsq⫽0.33). In contrast, higher intake of
margarine, donuts, and cookies were independent predictors of
higher RBC membrane levels of trans-18:1 fatty acids (model
Rsq⫽0.26), suggesting that different foods might possibly contribute
to the higher intake of trans-18:2 and trans-18:1 fatty acids.
Detailed Nutrient Assessment
On the basis of 4 days of food records completed by 55 controls
themselves, RBC membrane levels of total trans-fatty acids were not
related to total caloric intake (r⫽0.1, P⫽0.5) and to percentage of
energy from saturated fat (r⫽0.1, P⫽0.3) after adjustment for red
cell membrane levels of long-chain n-3 polyunsaturated fatty acids
and linoleic acid.
Assessment of Other Risk Factors
We collected information on demographic factors, medical conditions, lifestyle characteristics, and dietary habits during the in-person
interview or, in the case of 9 case-control pairs, the telephone
interview. Dietary saturated fat intake was assessed with the Northwest Lipid Research Clinic Fat Intake Scale, an index that correlates
with saturated fat intake.10
Statistical Methods
Statistical analyses were carried out using STATA 6.0. We compared
the distribution of risk factors among cases and controls using t test
for continuous variables and ␹2 test for categorical variables. We
compared risk factor distribution across tertiles of trans-fatty acid
levels among controls using ANOVA. We assessed the associations
of trans-fatty acids with other fatty acids among controls from
Pearson correlation coefficients.
We used conditional logistic regression to obtain odds ratios
(estimates of relative risks) of PCA associated with increasing levels
of RBC membrane trans-fatty acids. Statistical significance was
assessed with the likelihood ratio test. In the main analyses,
trans-fatty acids were included as continuous terms. Odds ratios and
95% CIs corresponding to the interquintile range of the control
distribution were then calculated from the regression estimates.
Quadratic terms were not included, because they did not improve the
fit of any of the models. We also present odds ratios associated with
upper quartiles of trans-18:2 fatty acid levels obtained from a model
with indicator variables for the quartiles, using the lowest quartile as
reference.
Information was missing on smoking (1% of controls), hypertension (2% of cases, 1% of controls), education (1% of cases), diabetes
(0.5% of cases), weight (3% of cases, 7% of controls), and family
history (9% of cases, 6% of controls). Fourteen percent of all
subjects had 1 missing value on one of these covariates and 1% had
2 missing values. The missing values were imputed using a multiple
imputation method.19 Results obtained with imputed missing values
are presented in this study. Similar results were obtained when
matched case-control pairs without missing values were examined.
Lemaitre et al
TABLE 1.
Characteristics of Cases and Controls
Controls
(n⫽285)
P
59.5 (10.3)
57.8 (10.3)
0.09
Male sex, %
82.1
80.7
0.70
White race, %
91.1
92.6
0.54
Diabetes, %
12.9
6.7
0.02
Hypertension, %
26.1
15.3
0.004
Family history of myocardial infarction
or sudden cardiac death, %
55.2
44.2
0.03
84.1 (18.0)
82.7 (15.0)
Age, y, mean (SD)
Weight, kg, mean (SD)
Current smokers, %
31.3
7.8
3
TABLE 2. Red Blood Cell Membrane Fatty Acids of Cases
and Controls
Cases
(n⫽179)
Characteristic
Trans-Fatty Acids and Primary Cardiac Arrest
% of Total Fatty Acids
Cases
(n⫽179)
Controls
(n⫽285)
Mean
SD
Mean
SD
P
Total trans-fatty acids
2.10
0.58
2.01
0.51
0.09
Trans-18:1 fatty acids
1.71
0.54
1.64
0.47
0.10
0.64
Trans-18:2 fatty acids
0.22
0.061
0.20
0.050
0.01
⬍0.001
Trans-16:1 fatty acids
0.17
0.042
0.17
0.046
0.47
4.17
1.10
4.66
1.28
0.0001
Fatty Acids
Trans-fatty acids
Long-chain n3 fatty acids
Former smokers, %
43.0
40.2
0.55
High school graduates, %
68.4
76.8
0.04
Leisure-time physical activity, %
87.2
94.4
0.006
Other major fatty acids
0.005
16:0 (palmitic acid)
18.85
1.04
18.68
0.96
0.06
18:0 (stearic acid)
14.27
0.70
14.22
0.69
0.43
10.96
0.84
10.86
0.85
0.19
9.30
1.29
9.11
1.07
0.09
14.01
1.18
13.78
1.16
0.04
Energy expended among exercisers,
kcal, mean (SD)
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Alcohol users, %
Alcohol consumption among drinkers,
g/day, mean (SD)
1034 (1267) 1534 (2008)
DHA⫹EPA
69.3
71.2
0.65
18:1n9 (oleic acid)
22.9 (35.0)
17.2 (26.1)
0.10
18:2n6 (linoleic acid)
20:4n6 (arachidonic acid)
DHA⫹EPA indicates docosahexaenoic acid⫹eicosapentaenoic acid.
Results
Given the matching, mean age and sex distribution were
similar in cases and controls (Table 1). As expected, other
traditional risk factors for PCA, such as present smoking,
diabetes, hypertension, and family history of myocardial
infarction or sudden cardiac death, were more prevalent in
cases than in controls (Table 1). In addition, cases were less
likely to have formal education beyond high school and were
less likely to engage in leisure-time physical activity.
Mean RBC trans-fatty acid levels were higher in cases than
controls. In contrast, mean levels of long-chain n-3 polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were higher in controls (Table 2).
RBC membrane levels of total trans-fatty acids were not
related to age, sex, hypertension, diabetes, or smoking (Table
3). However, they were inversely related to alcohol consumption and education (Table 3), inversely related to RBC
membrane levels of DHA⫹EPA (r⫽⫺0.39, P⬍0.001), and
positively associated with RBC membrane levels of linoleic
acid (r⫽0.33, P⬍0.001). The associations of RBC membrane
levels of trans-18:2 fatty acids with risk factors were similar
except for age (61 years in the lowest tertile of trans-18:2
versus 56 years in other tertiles, P⫽0.0013), weight (from
lowest to highest tertile: 81.3 kg, 82.5 kg, 84.3 kg, P⫽0.03),
and RBC levels of linoleic acid, which were not related to
levels of trans-18:2 fatty acids (r⫽0.05).
After adjustment for traditional PCA risk factors, RBC
membrane levels of total trans-fatty acids were associated
with a modest increase in risk of PCA (Table 4). An increase
in total trans-fatty acids from 1.59% to 2.45% of total fatty
acids, the interquintile range among controls, was associated
with an odds ratio of 1.47 (95% CI, 1.01 to 2.13). However,
the association was reduced by adjustment for RBC membrane levels of DHA⫹EPA (Table 4). The association of
higher levels of trans-18:1 fatty acids with PCA was also
reduced by adjustment for DHA⫹EPA (Table 4). Similar
results were obtained for trans-18:1 isomers mostly from
hydrogenated vegetable oils (9 trans-18:1 and 10 trans-18:1)
or mostly from animal products (11 trans-18:1) (not shown).
In contrast, trans-18:2 fatty acids were strongly associated
with PCA. An increase in trans-18:2 fatty acids from 0.16%
to 0.24% of total fatty acids, the interquintile range among
controls, was associated with an odds ratio of PCA of 2.66
(95% CI, 1.58 to 4.46) after adjustment for risk factors and
DHA⫹EPA (Table 4). Categorical analyses were consistent
with a linear relationship; compared with the lowest quartile
of RBC membrane trans-18:2 levels, levels of trans-18:2
corresponding to the 2nd, 3rd, and 4th quartiles were associated with odds ratios of 1.41 (0.66 to 3.00), 2.39 (1.07 to
5.35), and 4.22 (1.65 to 10.8), respectively (P for trend 0.002)
after adjustment for risk factors and DHA⫹EPA. Furthermore, with both classes of trans-fatty acids included simultaneously in statistical models, trans-18:2 fatty acids were
strongly associated with PCA (odds ratio for interquintile
range, 3.05; 95% CI, 1.71 to 5.44), whereas trans-18:1 fatty
acids were not associated with PCA (odds ratio for interquintile range, 0.77; 95% CI, 0.48 to 1.24) after adjustment for
risk factors and DHA⫹EPA.
Additional adjustments for alcohol consumption, caffeine
consumption, RBC membrane levels of linoleic acid, and
other major fatty acids did not change the results. Subject
characteristics, including sex, age, hypertension, diabetes,
smoking, family history of myocardial infarction or sudden
death, weight, and DHA⫹EPA levels, did not modify the
association of trans-18:2 fatty acids with PCA (not shown).
Discussion
In this population-based study, higher levels of total transfatty acids in RBC membranes were associated with a modest
1.5-fold increase in risk of PCA after adjustment for tradi-
4
Circulation
February 12, 2002
TABLE 3. Risk Factor Distribution Among Tertiles of Red Blood Cell Trans-Fatty
Acids in Controls
Tertile of Red Blood Cell Total Trans-Fatty Acids*
Age, y, mean (SD)
Sex, %
Diabetes, %
P
I
II
III
58.7 (9.2)
57.2 (11.1)
57.8 (10.6)
0.60
82.4
77.3
82.5
0.58
8.8
5.2
6.2
0.59
Hypertension, %
13.5
15.6
16.5
0.84
Family history of CHD, %
44.7
46.1
41.9
0.85
83.3 (16.8)
82.7 (14.55)
82.1 (13.9)
0.17
9.0
7.3
7.3
0.89
1468 (1516)
1441 (2622)
1435 (1612)
0.99
78.0
73.2
62.9
0.06
25.4 (37.2)
14.9 (18.4)
10.3 (12.5)
0.002
80.2
81.4
69.1
0.08
Weight, kg, mean (SD)
Current smokers, %
Leisure-time physical activity,
kcal, mean (SD)
Alcohol users, %
Alcohol consumption among
drinkers, g/day, mean (SD)
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High school graduates, %
*Median (range) of total trans-fatty acid levels in tertiles were, expressed as % of total fatty acids:
1.52 (0.98 –1.75) in I, 1.94 (1.75–2.14) in II, and 2.51 (2.15–3.54) in III.
tional risk factors. However, examination of the main classes
of trans-fatty acids revealed that trans isomers of oleic acid
(trans-18:1) and trans isomers of linoleic acid (trans-18:2)
were not equivalent. Although trans-18:1 fatty acids showed
no association with PCA, an increase in RBC membrane
trans-18:2 fatty acids corresponding to the interquintile range
was associated with nearly 3-fold increase in risk of PCA.
The association was independent of traditional risk factors,
membrane levels of other fatty acids, and levels of trans-18:1
fatty acids.
The strengths of this study include the use of populationbased cases and controls, the objective assessment of transfatty acid intake using a biomarker, and adjustment of results
for other known risk factors. To address the possibility that
cases might have changed their diet as a consequence of poor
health leading to PCA, we restricted the study to cases with
no history of clinically recognized heart disease and no
life-threatening comorbidities.
This study has several limitations. We did not measure all
aspects of diet, and the possibility of residual confounding
TABLE 4.
cannot be eliminated. In particular, we may have incompletely adjusted for saturated fat intake. However, among
control subjects who completed a 4-day food record, we did
not find evidence of a relation of RBC membrane trans-fatty
acids with saturated fat intake. It is therefore unlikely that
differences in saturated fat intake can fully account for the
observed association between trans-18:2 and PCA. For 15%
of the study subjects, 1 or 2 covariate values were imputed;
however, similar study results were obtained with subjects
without any missing values. The use of surrogate respondents
inevitably introduced some misclassification in assessment of
potential confounders; however, the exposure of interest was
measured objectively. Participation rate in the controls was
60%, and the odds ratios associated with higher levels of
trans-18:2 fatty acids could be overestimated if controls who
declined participation in the study ate more foods containing
trans-18:2 than the controls who participated.
The modest association of total trans-fatty acid levels with
PCA when adjusting for traditional risk factors only is
comparable to the association of total trans-fatty acid intake
Association of Trans-Fatty Acids With the Risk of Primary Cardiac Arrest
OR Corresponding to the Interquintile Range (95% CI)
Model Adjusted for Traditional Risk Factors*
and Levels of DHA⫹EPA
Trans-18:1 and Trans-18:2
Assessed Simultaneously
Interquintile
Range, %
Total trans-fatty acids
0.86
1.47 (1.01–2.13)
1.24 (0.84–1.84)
Trans-18:1 fatty acids
0.81
1.41 (0.97–2.06)
1.19 (0.80–1.77)
0.77 (0.48–1.24)
Trans-18:2 fatty acids
0.08
2.97 (1.79–4.91)
2.66 (1.58–4.46)
3.05 (1.71–5.44)
*Traditional risk factors were age, smoking (never, past, current), history of diabetes (yes/no), treated hypertension
(yes/no), education beyond high school (yes/no), family history of MI or sudden death (yes/no), and the continuous
covariates weight, height, index of dietary saturated fat intake, and energy expended in leisure-time physical activity.
DHA⫹EPA indicates docosahexaenoic acid⫹eicosapentaenoic acid.
Lemaitre et al
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with CHD reported in several cohort studies.13–15 A pooled
estimate of the adjusted relative risk of CHD (CHD death and
nonfatal myocardial infarction) associated with an increase of
2% in energy in total trans-fatty acid intake is 1.25 (95% CI,
1.11 to 1.40).15 Intake of total trans-fatty acids was estimated
from a food frequency questionnaire in these studies, and
whether trans-18:2 fatty acids differed from trans-18:1 fatty
acids was not reported.
There is little published information on the possible association of trans-fatty acids with PCA. In an autopsy-based
case-control study of sudden cardiac death with 66 cases,
adipose tissue trans-fatty acids were not associated with risk
of cardiac arrest.20 However, the low prevalence of hypertension and diabetes in the cases, known PCA risk factors,
suggests that these autopsy cases were not representative of
the cases in the population as a whole.
The mechanism by which trans-fatty acids might influence
the risk of PCA is largely unknown. Trans-fatty acids have
similarities to saturated fatty acids, and saturated fatty acids
have been shown to increase the risk of life-threatening
arrhythmias in primates.4,7 Whether trans-fatty acids in general and trans-18:2 fatty acids in particular influence the risk
of arrhythmias in primates has yet to be investigated.
Trans-fatty acids are made during partial-hydrogenation
and frying of vegetable oils21,22 and by bacterial action in
ruminants’ stomachs.23 The trans isomer composition of
processed foods varies with oil type and the specifics of
partial hydrogenation. In a subset of controls, higher consumption of commercially available pizza, fried chicken, and
cookies predicted 33% of the variation in RBC membrane
trans-18:2 levels, suggesting that these common processed
foods might rise trans-18:2 intake. Consumption of margarine was a predictor of trans-18:1 levels, together with donuts
and cookies, but did not predict trans-18:2 levels, suggesting
the possibility that margarine might contribute to total transfatty acid intake but not trans-18:2. This finding needs
confirmation by feeding studies.
In conclusion, we observed a modest association of RBC
membrane levels of total trans-fatty acids with PCA and a
strong positive association of membrane trans-18:2 fatty
acids with PCA. These associations need to be confirmed in
future studies that distinguish between trans-18:1 and trans18:2 fatty acids.
Acknowledgments
The research reported in this article was supported by grants from the
National Heart, Lung, and Blood Institute (HL41993), University of
Washington Clinical Nutrition Research Unit (DK-35816), and
Medic One Foundation, Seattle, Wash. We appreciate the assistance
of the paramedics of the Seattle Medic One Program and SeattleKing County Health Department Emergency Medical Services Divisions with the project. We also thank Sandra Tronsdal, Melinda
Sue Lentz, and Margaret Birdsall for their help with the project.
Trans-Fatty Acids and Primary Cardiac Arrest
5
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Cell Membrane Trans-Fatty Acids and the Risk of Primary Cardiac Arrest
Rozenn N. Lemaitre, Irena B. King, Trivellore E. Raghunathan, Rachel M. Pearce, Sheila
Weinmann, Robert H. Knopp, Michael K. Copass, Leonard A. Cobb and David S. Siscovick
Circulation. published online December 31, 2001;
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