Plasma phospholipid trans fatty acids and risk of heart failure1–3
Oluwabunmi A Tokede, Andrew B Petrone, Naomi Q Hanson, Michael Y Tsai, Natalie A Weir, Robert J Glynn,
J Michael Gaziano, and Luc Djousse´
ABSTRACT
Background: Although trans fatty acids (TFAs) may increase the
risk of dyslipidemia and coronary artery disease (CAD), limited
data are available on their association with heart failure (HF).
Objective: Our goal was to assess associations of plasma and di-
etary TFAs with HF and CAD.
Design: We used a prospective, nested case-control design to select
788 incident HF cases and 788 matched controls from the Physi-
cians’ Health Study for biomarker analyses and a prospective
cohort for the dietary analyses. Plasma fatty acids were assessed by
using gas chromatography, and dietary intake was estimated by
using a food-frequency questionnaire. Self-reported HF was
ascertained by using annual follow-up questionnaires with
validation in a sub- sample. We used conditional logistic (or Cox)
regression to estimate multivariable-adjusted ORs (or HRs) for HF
and CAD.
Results: Multivariable-adjusted ORs (95% CIs) for HF across con-
secutive quintiles of plasma trans 18:2 (linoleic acid) fatty acids
were 1.0 (reference), 1.10 (0.79, 1.54), 0.88 (0.62, 1.25), 0.71 (0.49,
1.02), and 0.67 (0.45, 0.98) (P-trend = 0.01). Each SD of plasma
trans 18:2 was associated with a 22% lower risk of HF (95% CI:
6%, 36%). Plasma trans 16:1 and 18:1 were not associated with
risk of HF (P . 0.05). Dietary trans fats were not associated
with in- cident HF or CAD.
Conclusions: Our data are consistent with a lower risk of HF with
higher concentrations of plasma trans 18:2 but not with trans 16:1
or trans 18:1 fatty acids in male physicians. Dietary TFAs were not
related to incident HF or CAD. Am J Clin Nutr 2013;97:698–
705.
INTRODUCTION
Cardiovascular disease (CVD)4 remains a major public health
concern in both developed and developing countries (1–3). Data
from the Framingham Heart Study suggest that 1 in 5 adults will
develop heart failure (HF) over the course of their lifetime (4).
Approximately half of those diagnosed with HF will die within 5
y (5). In the United States, health care costs due to HF are
projected to reach $97.0 billion by 2030 (6). In the United
Kingdom, the “direct” cost of health care for HF patients was
estimated to be £716 million (1.83% of total National Health
Service expenditure), additional costs associated with long-term
nursing home care and secondary HF admissions accounted for
another £751 million (2.0% of total National Health Service
expenditure) (7).
Previous studies have shown the importance of dietary
factors on CVD and its risk factors. For example, trans fatty
acid (TFA) intake decreases HDL cholesterol and increases
LDL cholesterol
698 Am J Clin Nutr 2013;97:698–705. Printed in USA. © 2013 American Society for Nutrition
(8) and could lead to a higher risk of coronary artery disease
(CAD) (9), a major risk factor for HF. Consumption of TFAs
has also been shown to increase the risk of other major
predictors of HF including type 2 diabetes (10), obesity (11),
dyslipidemia (12), and hypertension (13). However, not all
studies have re- ported deleterious effects with TFAs. The
consumption of TFAs was not associated with risk of diabetes
among male health professionals (14) and among women in D
Iowa (15). Another study also reported no association between o
w
TFAs and dyslipi- demia (16). The role of TFAs in the nl
development of HF has similarly not been fully elucidated. oa
Hence, the primary purpose of this study was to examine the de
relation between various plasma phospholipid TFAs d
fro
(biomarkers for habitual TFA consumption) and the risk of HF
m
in US male physicians. In a secondary aim, we evaluated the aj
association of dietary TFA consumption [estimated by a food- cn
frequency questionnaire (FFQ)] with incident HF and CAD. .n
utr
iti
on
SUBJECTS AND METHODS .or
g
Subjects by
gu
Participants in the primary analyses are members of the es
Physicians’ Health Study (PHS) I, a completed, randomized, t
on
N
1
ov
From the Divisions of Aging (OAT, ABP, JMG, and LD) and Preventive e
Medicine (RJG and JMG), Department of Medicine, Brigham and Women’s m
Hospital, Boston, MA; the Departments of Advanced Research and Diag- be
nostic Laboratory (NQH) and Laboratory Medicine and Pathology (MYT
and NAW), University of Minnesota, Minneapolis, MN; the Department of
Biostatistics, Harvard School of Public Health, Boston, MA (RJG); the Mas-
sachusetts Veterans Epidemiology and Research Information Center and
Geriatric Research, Education, and Clinical Center, Boston, MA (JMG and
LD); and Harvard Medical School, Boston, MA (RJG, JMG, and LD).
2
Supported by grants R01HL092946 and HL092946S1 (LD) from the
National Heart, Lung, and Blood Institute and the Office of Dietary Supple-
ment, Bethesda, MD. The Physicians’ Health Study is supported by grants
CA-34944, CA-40360, and CA-097193 from the National Cancer Institute
and grants HL-26490 and HL-34595 from the National Heart, Lung, and
Blood Institute.
3
Address correspondence to L Djousse´, 1620 Tremont Street, Boston,
MA 02120. E-mail: ldjousse@partners.org.
4
Abbreviations used: CAD, coronary artery disease; CVD, cardiovascular
disease; FFQ, food-frequency questionnaire; HF, heart failure; PHS, Physi-
cians’ Health Study; TFA, trans fatty acid.
Received August 29, 2012. Accepted for publication January 29, 2013.
First published online February 27, 2013; doi: 10.3945/ajcn.112.050120.
 PLASMA TFAS AND RISK OF HEART FAILURE
double-blind, placebo-controlled trial designed to study low-
dose aspirin and b-carotene for the primary prevention of CVD
and cancer. A detailed description of the PHS I has been pub-
lished (17). Briefly, this was a 2 3 2 factorial trial of low-dose
aspirin and b-carotene. A total of 22,071 US male physicians
(mostly white), aged 40–84 y, were enrolled in 1982. Each
participant provided written informed consent, and the in-
stitutional review board at Brigham and Women’s Hospital ap-
proved the study protocol.
In our secondary analyses, we analyzed data on participants
from PHS I and II who provided an FFQ collected between
1997 and 2001. Of note, the PHS II was a randomized
controlled trial in 14,641 subjects (7000 newly recruited
physicians and 7641 members of the original PHS I). A detailed
description of the PHS II has been previously published (18).
Case and control selection for the primary aim
All incident HF cases among participants who provided
baseline blood samples were eligible to serve as cases in this
study. We used a risk set technique to randomly select one
control subject, free of HF at the time of the index case’s
diagnosis of HF. Each control was matched to the respective
case on race (white compared with nonwhite), age (62 y), year
of birth (62 y), and time of blood collection (6288 d) as
described previously (19). A total of 788 matched pairs were
selected for the current analyses.
Blood collection
Between August 1982 and December 1984, kits for blood
sampling were sent to participants with instructions to have their
blood drawn and returned to Brigham and Women’s Hospital
using a prepaid overnight courier. The kit included a cold pack
to keep the specimens cool (but not frozen) until receipt the
following morning, when they were processed, separated into
aliquots, and stored at 2808C. A total of 15,700 baseline blood
samples were collected. There was virtually no loss to follow-up
of the cohort; 100% were followed up for vital status, and .
99% were followed up for nonfatal outcomes.
Ascertainment of HF and CHD in the PHS
Ascertainment of endpoints including HF in the PHS was
achieved by using yearly follow-up questionnaires. A detailed
description of HF validation in the PHS using self-reported in-
formation and the Framingham criteria (20) as well as against
review of medical records has been published elsewhere (21).
Incident cases of coronary artery bypass grafting or
percutaneous transluminal coronary angioplasty were validated
by the PHS Endpoint Committee, Brigham and Women’s
Hospital. Di- agnoses of nonfatal myocardial infarction were
confirmed by using WHO criteria (22). Fatal myocardial
infarction was con- firmed by death certificates, hospital
records, and (for death outside the hospital) observers’
accounts.
Measurement of plasma phospholipid TFAs
Fatty acid profile was measured in plasma by using the
method previously described by Cao et al (23). Lipids were
extracted from plasma with a mixture of chloroform and
methanol.
699
Cholesteryl ester, triglycerides, and phospholipid subclasses
were separated on a silica thin-layer chromatography plate in a
solvent mixture of petroleum ether, diethyl ether, and glacial
acetic acid. This phospholipid band was harvested and used for
the formation of methyl esters by using 14% boron trifluoride in
methanol and then extracted with petroleum ether. The final
product was dissolved in heptane and injected onto a 100-m
Varian capillary column (FAME CP7420, high-polarity 100%
bonded phase; Agilent Technologies) in a Hewlett-Packard gas
chromatograph with a flame ionization detector and
interfaced with HP Chemstation software (Hewlett-Packard).
Adequate separation of fatty acid methyl esters was obtained
over an 80-min period with an initial temperature of 1908C for
25 min. The temperature was increased to 2408C at a rate of
28C/min and held for 5 min. Fatty acid methyl esters from 14:0
through 24:1n–9 were separated, identified, and expressed as
percentage of total fatty acids. The following CVs were
obtained on 20 blind duplicates: 16:1n–7 trans (t) = 20.0%;
18:1n–7-9t = 2.4%; 18:1n–6t = 2.8%; 18:2cis
D
(c)/t, 18:2t/c, and 18:2t/t = 8.5%. o
w
Assessment of other variables nl
oa
At baseline, each study participant provided information on de
smoking (never, former, and current smoker), exercise (How d
fro
often do you exercise vigorously enough to work up sweat?
m
Possible answers included rarely/never, 1–3 times/mo, 1 time/ aj
wk, 2–4 times/wk, 5–6 times/wk, and daily), and alcohol intake cn
(rarely/never, 1–3 drinks/mo, 1 drink/wk, 2–4 drinks/wk, 5–6 .n
drinks/wk, daily, and $2 drinks/d). Self-reported baseline utr
iti
weight and height were used to compute BMI (calculated as on
weight in kilograms divided by height in meters squared). Co- .or
morbidity in this cohort has been ascertained through annual g
questionnaires. by
gu
es
Assessment of dietary TFA intake t
on
Information on dietary fatty acid consumption was obtained N
by using an FFQ administered between 1997 and 2001. ov
Nutrients were computed by using the food composition e
database from the Harvard School of Public Health and m
manufacturers’ in- formation. The validity and reproducibility be
of FFQs have been published elsewhere (24). The residual
method was used to adjust nutrients for energy intake (25).
Statistical analysis
We initially examined the distribution of plasma or dietary
TFAs for normality. For the primary analyses, we created
quintiles of each exposure (16:1, 18:1, and 18:2 TFAs) by using
the distribution of TFAs among control series. We used condi-
tional logistic regression to compute multivariable-adjusted ORs
as estimates of RR with corresponding 95% CIs. We also ex-
amined each exposure as a continuous variable and estimated
the RR associated with each SD of higher exposure. On the
basis of prevailing knowledge, we assessed confounding by
BMI (con- tinuous), smoking (never, past, current), alcohol
intake (rarely, monthly, weekly, daily), exercise to sweat
weekly or more (yes or no), previous type 2 diabetes (yes or
no), and atrial fibrillation (yes or no). Because TFAs have been
shown to increase LDL cholesterol and lower HDL cholesterol,
we considered hyper- tension and CHD as potential intermediate
factors between TFAs
700 TOKEDE ET AL

and HF. Possible interactions between each TFA and

TABLE 1
confounding variables in each model were assessed by
Characteristics of 788 heart failure cases and 788 matched controls in US
including product terms in the model. male physicians1
The initial model accounted for matching factors only (age, Cases Controls P
race, date of blood collection, and year of birth). A Characteristics (n = 788) (n = 788) value
parsimonious model also adjusted for BMI, smoking, and
alcohol consumption; and a final model contained further
adjustment for exercise, diabetes, and atrial fibrillation. Total trans fat (% of 2.0 6 0.62 2.1 6 0.03
A P value for linear trend was obtained by creating a new total fatty acids) 0.6
variable that was assigned the median TFA value from the BMI (kg/m2) 25.8 6 3.2 24.6 6 ,
control series in each quintile, and then by using that new var- 2.5 0.0
iable in the conditional logistic regression model. 1
Age (y) 58.7 6 8.0 58.7 6 0.48
For the secondary analyses, we used a Cox proportional 8.1
hazards model to assess the relation of dietary TFA with History of atrial 5. 2.4 ,
incident CAD and HF. We created quintiles of TFAs by using 5 0.0
the lowest quintile as the reference category. Proportional 1
fibrillation (%)
hazards as- sumption was tested by including an interaction with
History of CABG (%) 2. 0.9 0.02
logarithmic person-time in the model. The models were 4
adjusted for age, smoking, alcohol, and exercise. Potential History of CAD (%) 4. 2.3 0.02
mediation was exam- 3 D
History of type 2 7. 3.3 , o
ined by including BMI, diabetes, atrial fibrillation, and hyper- 9 0.0 w
tension in the model. To obtain P values for linear trend, 1 nl
we diabetes (%) oa
Alcohol (%) 0.053
created a new variable that was assigned the median value of the Rarely 17.0 14.9 de
TFA for each quintile and fitted the variable in each regression Monthly d
11.4 8.1
model. fro
Weekly 44.7 46.8
m
All analyses were completed by using SAS, version 9.2 (SAS Daily 26.4 30.0 aj
Institute). All P values were 2-tailed, and significance was set at 1
Except for BMI and age, data for other characteristics were not pro- cn
an a of 0.05. vided by all individuals. CABG, coronary artery bypass grafting; CAD, .n
coronary artery disease. utr
iti
2
Mean 6 SD (all such values).
on
RESULTS
.or
g
Relation of plasma phospholipid TFAs and HF risk with incident HF: multivariable-adjusted HRs (95% CIs) across by
Characteristics of HF cases and matched controls are shown consecutive quintiles of dietary TFAs were 1.0 (reference), 1.13 gu
in Table 1. The distribution of participants and covariates across (0.90, 1.42), 1.03 (0.82, 1.30), 1.18 (0.94, 1.48), and 1.11 (0.88, es
1.39) (Table 5). t
quintiles of individual TFAs are shown in Table 2. on
Higher plasma concentrations of trans 16:1 fatty acids were In a subanalysis, we also evaluated the relation of dietary N
associated with a lower prevalence of hypertension. Plasma TFAs with CAD and found no meaningful relation: ov
concentrations of trans 18:1 fatty acids were inversely associ- multivariable-ad- justed HRs (95% CIs) across consecutive e
quintiles were 1.0 (reference), 0.91 (0.78, 1.07), 0.86 (0.74, m
ated with hypertension, high cholesterol, and current smoking, be
whereas higher concentrations of trans 18:2 fatty acids were 1.01), 0.94 (0.81, 1.10),
associated with a lower prevalence of hypercholesterolemia and 0.86 (0.73, 1.01) (Table 6).
(Table 2).
Multivariable-adjusted ORs (95% CIs) for HF were 1.0 (ref-
erence), 1.10 (0.79, 1.54), 0.88 (0.62, 1.25), 0.71 (0.49, 1.02), DISCUSSION
and In this study, higher concentrations of plasma phospholipid
0.67 (0.45, 0.98) across consecutive quintiles of trans 18:2 fatty trans linoleic acid (trans 18:2) were significantly associated
acids (P-trend = 0.01) (Table 3). Each SD of higher plasma with a lower risk of HF after adjustment for potential
trans 18.2 fatty acids was associated with a 22% lower risk of confounders. This lower risk was observed in all of the models,
HF (95% CI: 6%, 36%). Additional adjustment for CAD and regardless of the inclusion or exclusion of any potential
hypertension had minimal effect on the OR (OR per SD: 0.79; confounders or me- diating factors. In contrast, no association
95% CI: 0.65, 0.96). Analyses for plasma trans 16:1 and trans was found between plasma trans 16:1 or trans 18:1 fatty acids
18:1 isomers did not show any meaningful association (P-trend and risk of HF. In a secondary analysis, we did not find any
0.23 and 0.37, respectively; Table 3). association between dietary TFAs and incident HF or CAD
after an average follow-
up of w10 y.
Relation of dietary TFAs (from the FFQ) and incident HF Fat is one of the most challenging dietary components to
and CAD accurately measure, making it difficult to identify associations
The average age at the time of dietary assessment was 66 y, between dietary fat and health. Although many previous studies
and mean follow-up was w10 y. Baseline characteristics by have examined the role of fat consumption on CAD risk, their
quintiles of total dietary TFAs are provided in Table 4. In a conclusions are potentially hampered because assessment of
multivariable- adjusted model, we found no association dietary fat by commonly used methods is limited by recall
between dietary TFAs biases and measurement errors (26). Consequently, biomarkers
are
TABLE 2
Baseline characteristics of 1576 US male physicians across quintiles of plasma phospholipid TFAs1

Plasma trans 16:1 Plasma trans 18:1 Plasma trans 18:2

Characteristics Q1 (low) Q3 Q5 P- Q1 Q3 Q5 P- Q1 Q3 Q5 P-
(high) trend (low) (high) trend (low) (high) tren
d
n 2 326 292 332 312 298 323 314 282 P
9 L
5 A
Plasma TFAs (% 0.05 (0.02, 0.06) 0.08 (0.08, 0.09) 0.12 (0.11, 0.26) 0.98 (0.60, 1.16) 1.57 (1.44, 1.70) 2.37 (2.08, 4.10) 0.24 (0.15, 0.28) 0.36 (0.33, 0.39) 0.51 (0.45, 2.71) S
of total fatty acids)2 M
BMI (kg/m2) 24.9 6 25.1 6 25.0 6 0.98 25.5 6 25.2 6 24.8 6 , 25.4 6 25.0 6 25.0 6 0. A
2.53 2.9 2.6 3.1 2.9 2.5 0.01 2.9 2.8 2.8 0 T
6 F
Age (y) 58.5 6 7.6 59.5 6 58.0 6 0.46 58.5 6 58.8 6 59.1 6 0.5 58.9 6 58.2 6 58.3 6 0. AS
8.3 7.7 7.7 8.1 8.1 6 7.8 8.0 7.9 0 A
5
Prevalent atrial 3. 3.4 3.8 0.78 5.1 2.9 3.7 0.5 2.5 3.8 2.1 0.
N
7 8 7 D
3 RI
fibrillation (%) S
History of CABG 1. 1.5 1.4 0.78 1.2 0.3 1.0 0.7 2.8 2.9 0.7 0. K
(%) 7 0 0 O
6 F
History of CAD 3. 3.1 3.1 1.00 3.3 0.6 4.0 0.7 5.0 4.5 2.5 0. H
(%) 1 3 0 E
7
Prevalent type 2 4. 6.4 5.5 0.34 8.1 4.2 4.0 0.0 6.2 6.1 5.0 0.
A
4 5 4
9
diabetes (%)
Hypertension (%) 3 31.3 26.7 ,0.01 36.8 28.2 25.5 , 36.5 26.8 32.3 0.
5 0.01 1
. 3
9
High cholesterol 1 10.4 13.7 0.02 16.9 12.8 9.7 , 18.9 13.4 11.7 0.
(%) 6 0.01 0
. 1
6
Exercise (%) 7 74.2 73.3 0.35 64.5 76.3 78.2 , 67.5 75.5 75.5 0.
0 0.01 0
. 1
5 70
Smoking status (%)
1
Never 3 46.6 52.1 ,0.01 34.3 46.2 56.4 , 41.2 46.5 48.9 0.
6 0.01 0
Downloaded from ajcn.nutrition.org by guest on November 10,
 . 2
6
Past 4 43.3 38.4 ,0.01 50.3 41.7 34.6 , 50.2 42.4 39.7 0.
9 0.01 0
. 1
2
Current 1 10.1 9.3 0.0 15.1 12.2 9.1 0.0 8.4 11.2 11.0 0.
3 8 3 5
. 5
9
Alcohol (%)
Rarely 6. 15.3 26.0 ,0.01 6.0 15.7 27.5 , 9.9 17.5 22.0 ,
8 0.01 0.01
Monthly 6. 9.5 12.3 0.01 7.5 8.3 11.7 0.0 10.2 8.9 9.9 0.
8 3 9
5
Weekly 4 47.9 43.5 0.26 41.3 48.1 46.0 0.2 48.3 43.3 43.3 0.
0 7 2
. 1
3
Daily 4 26.7 17.8 ,0.01 44.9 26.9 14.1 , 31.0 29.6 24.5 0.
6 0.01 0
. 7
1
1
Except for BMI and age, data for other characteristics were not provided by all individuals; quintiles were created by using TFA distribution in the control series. CABG, coronary artery bypass grafting;
CAD, coronary artery disease; Q, quintile; TFA, trans fatty acid.
2
Values are medians; ranges in parentheses.
3
Mean 6 SD (all such values).
702 TOKEDE ET AL

increasingly being used in nutritional epidemiology to assist in

djusted for matching factors; model 2 adjusted as for model 1 with additional adjustment for BMI, smoking, alcohol, exercise, diabetes, and atrial fibrillation analyzed by using conditional logistic regression. PHS I, Physicians’
1.10 (0.79, 1.54) 1
Model 2
dietary measurement and to deal with problems inherent in self-
reported intakes (27).
Although many previous studies have focused on the relation
of TFAs with CAD and intermediate phenotypes, little is known
about the association of TFAs with HF in the literature. In
earlier related studies, higher plasma concentrations of trans
trans 18:2

1.15 (0.84, 1.58) 1

Model 1
18:2 fatty acids were associated with a higher risk of primary
cardiac arrest (28) and fatal ischemic heart disease among
older adults (29). In rodent models of HF, however, a diet high
in fat and low in carbohydrate prevented the development and
progression of HF compared with low-fat/high-carbohydrate
diets (30, 31). Although underlying mechanisms for such
Quintile range2

protection are unclear, it is increasingly being recognized that

the type of fats consumed appears to be far more relevant for
cardiometabolic health than the proportion of energy con-
sumed from total fat (32, 33).
A significant amount of investigation has been done on the
(0.159–0.274)

relation of fat consumption with CVD (34, 35). Some studies

3

have reported increased risk of type 2 diabetes (36), obesity D

ORs (95% CIs) of heart failure according to quintiles of individual plasma phospholipid TFAs in 1576 male physicians from the PHSTABLE

0.88 (0.63, 1.23) 1

2

(11), dyslipidemia (12), and hypertension (13) with TFAs. o

Q1Model
I1

However, other studies did not find deleterious effects of TFAs w

with di- abetes (14), dyslipidemia (37), and CAD (16). Few of nl
oa
the above- mentioned studies evaluated individual TFAs. de
Various types of TFAs are produced during partial d
hydrogenation of vegetable and seed oil. These include trans
Health Study I; Q, quintile; ref, reference; TFA, trans fatty acid.

fro
trans 18:1

isomers of oleic (trans 18:1) and linoleic (trans 18:2) acids. A m

0.93 (0.68, 1.26) 1
Model 1

third major group—palmitoleic acid (trans 16:1)—is usually aj

cn
produced by bacterial metabolism of unsaturated fatty acids in .n
ruminant animals and found in beef, lamb, and dairy products utr
(38). Divergent reports suggest the importance of studying iti
individual TFAs because their effects may be heterogeneous. on
.or
xNutrients derived from FFQs are widely used in epidemio- g
logic studies despite the potential for measurement errors and by
recall biases. We examined the relation of dietary TFAs gu
(assessed es
t
on
N
ov
e
m
be
 PLASMA TFAS AND RISK OF HEART FAILURE 703
TABLE 4
Characteristics of 18,750 individuals by quintiles of total dietary TFAs (from FFQs)1
Dietary TFAs

Characteristics Q1 (low) Q2 Q3 Q4 Q5 (high) P-trend

n 3750 3750 3750 3750 3750
Total dietary TFAs (g/d)2 0.88 (0.02, 1.35 (1.14, 1.70 (1.53, 2.05 (1.87, 2.61 (2.28,
1.14) 1.53) 1.87) 2.28) 6.10)
BMI (kg/m2) 25.0 6 3.23 25.6 6 3.3 26.0 6 3.5 26.2 6 3.6 26.6 6 3.9 ,0.01
Age (y) 65.9 6 8.5 66.0 6 8.9 66.1 6 9.2 66.4 6 9.5 66.6 6 9.9 ,0.01
Total energy intake (kcal) 1674.6 6 1686.3 6 1705.9 6 1714.2 6 1656.1 6 0.74
542.1 524.4 528.2 509.8 503.7
History of atrial fibrillation (%) 6.3 6.8 7.0 7.2 7.8 0.01
History of type 2 diabetes (%) 5.0 5.5 5.1 5.9 7.9 ,0.01
Hypertension (%) 39.2 42.0 43.0 43.6 44.0 ,0.01
Exercise (%) 70.4 64.7 62.2 60.1 54.1 ,0.01
Smoking status (%)
Never 56.8 53.7 54.7 55.3 53.5 0.05
Past 41.2 43.5 42.3 40.5 41.6 0.36
Current 2.0 2.8 3.0 4.2 4.9 ,0.01
Alcohol (%)
Rarely 20.1 14.6 14.6 16.2 20.5 0.23 D
Monthly 6.4 7.1 7.2 7.4 10.1 ,0.01 o
Weekly 36.1 37.1 37.4 40.2 39.4 ,0.01 w
Daily 37.4 41.2 40.8 36.3 30.0 ,0.01 nl
1 oa
Some participants had missing data on smoking (n = 13), exercise (n = 319), diabetes (n = 21), hypertension (n = 90), and alcohol use (n = 99). FFQ,
de
food-frequency questionnaire; Q, quintile; TFA, trans fatty acid.
2
d
Values are medians; ranges in parentheses. fro
3
Mean 6 SD (all such values). m
aj
cn
.n
by FFQ) with incident HF and CAD in our study. Contrary to study by Hu et al (44) included only women, the present study utr
previous reports, we found no association between dietary TFAs consisted exclusively of men. Finally, whereas Hu et al (44) an- iti
and incident HF. This null finding was also observed across in- alyzed probable and confirmed cases of CAD, the present study on
dividual TFAs (ie, 16:1, 18:1, and 18:2; data not shown). Our .or
included only confirmed cases of CAD. g
finding of no association between dietary TFAs and incident Our study has some limitations. The measurement of by
CAD is consistent with 2 previously completed studies in male plasma phospholipid TFA concentrations was performed on gu
cohorts (42, 43). In contrast, a prospective study in women (44) baseline blood samples and therefore may not fully represent es
reported a 27% (95% CI: 3%, 56%) higher risk of CAD among habitual patterns of dietary TFA consumption. Also, whereas t
women in the highest quintile of dietary TFA consumption on
plasma concentrations of TFAs are biomarkers of dietary TFA N
compared with the lowest quintile. Differences in study design, con- sumption, it is important to note that there are other ov
subject characteristics, and other factors may partially explain nondietary factors that may influence measured fatty acid e
the divergent results. The biomarkers, for example, metabolism, endogenous synthesis, m
average age of participants in that study was w46 y (compared and sample handling/storage, and diseases (diabetes,
be
with a mean age of 66 y in our cohort). In addition, whereas the malabsorption). In

TABLE 5
HRs (95% CIs) of heart failure according to quintiles of dietary TFAs (from FFQs) 1
No. of
Quintile of TFA (g/d) cases/person- Model 1 Model 2 Mod
years el 3
Q1 (ref): 0.87 (0.025, 1.12) 144/40, 1.00 1.00 1.00
378
Q2: 1.33 (1.13, 1.50) 165/39, 1.14 (0.91, 1.10 (0.88, 1.13 (0.90,
830 1.42) 1.38) 1.42)
Q3: 1.69 (1.51, 1.84) 156/39, 1.04 (0.83, 0.99 (0.79, 1.03 (0.82,
469 1.30) 1.25) 1.30)
Q4: 2.04 (1.85, 2.26) 184/38, 1.26 (1.01, 1.12 (0.90, 1.18 (0.94,
610 1.57) 1.40) 1.48)
Q5: 2.60 (2.27, 5.32) 182/37, 1.21 (0.97, 1.03 (0.82, 1.11 (0.88,
857 1.51) 1.29) 1.39)
P-trend — 0.05 0.80 0.39
Modeled as continuous — 1.07 (1.00, 1.01 (0.94, 1.03 (0.96,
variable2 1.15) 1.08) 1.10)
1
Quintile values are medians; ranges in parentheses. Number of subjects per model: model 1, 19,768; model 2,
19,301; and model 3, 19,214. Model 1 adjusted for age; model 2 adjusted as for model 1 plus additionally adjusted for
diabetes, smoking, alcohol, exercise, BMI, and atrial fibrillation; and model 3 adjusted as for model 2 plus additionally
adjusted for coronary artery disease and hypertension. Analyses were performed by using proportional hazards regression.
FFQ, food- frequency questionnaire; Q, quintile; ref, reference; TFA, trans fatty acid.
2
ORs per SD increase in dietary TFAs (0.69 g/d).
704 TOKEDE ET AL
TABLE 6
HRs (95% CIs) of CAD according to quintiles of dietary TFAs (from FFQs) 1
No. of
Quintile of dietary TFA (g/d) cases/person- Model 1 Model 2 Mod
years el 3
Q1 (ref): 0.88 (0.02, 1.13) 331/36, 1.00 1.00 1.00
911
Q2: 1.35 (1.14, 1.52) 308/36, 0.94 (0.81, 0.92 (0.78, 0.91 (0.78,
567 1.10) 1.07) 1.07)
Q3: 1.70 (1.53, 1.86) 299/36, 0.90 (0.77, 0.87 (0.74, 0.86 (0.74,
391 1.05) 1.01) 1.01)
Q4: 2.05 (1.87, 2.27) 327/35, 1.00 (0.86, 0.94 (0.81, 0.94 (0.81,
569 1.17) 1.10) 1.10)
Q5: 2.61 (2.28, 6.10) 306/34, 0.95 (0.81, 0.87 (0.74, 0.86 (0.73,
894 1.10) 1.02) 1.01)
P-trend — 0.73 0.17 0.13
Modeled as continuous — 0.99 (0.94, 0.96 (0.92, 0.96 (0.91,
variable2 1.04) 1.02) 1.01)
1
Quintile values are medians; ranges in parentheses. Number of subjects per model: model 1, 18,750; model 2,
18,321; and model 3, 18,302. Model 1 adjusted for age; model 2 adjusted as for model 1 plus additionally adjusted for
smoking, alcohol, exercise, and BMI; model 3 adjusted as for model 2 plus additionally adjusted for diabetes and atrial
fibrillation. Analyses were performed by using proportional hazards regression. CAD, coronary artery disease; FFQ, food-
frequency questionnaire; Q, quintile; ref, reference; TFA, trans fatty acid. D
2
ORs per SD increase in dietary TFAs (0.69 g/d). o
w
nl
oa
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