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NUTRITION (A. GARG, SECTION EDITOR)
Role of cis-Monounsaturated Fatty Acids in the Prevention
of Coronary Heart Disease
Peter J. Joris
1
&Ronald P. Mensink
1
Published online: 24 May 2016
#The Author(s) 2016. This article is published with open access at Springerlink.com
Abstract The effects of cis-monounsaturated fatty acids (cis-
MUFAs) on the risk of coronary heart disease (CHD) and on
CHD mortality are not clear. Also, dietary recommendations
for cis-MUFA as derived by various organizations are not in
agreement. Earlier studies have mainly focused on the effects
of cis-MUFA on serum lipids and lipoproteins. More recent
studies, however, have also addressed effects of cis-MUFA on
other non-traditional CHD risk markers such as vascular func-
tion markers, postprandial vascular function, and energy in-
take and metabolism. Although well-designed randomized
controlled trials with CHD events as endpoints are missing,
several large prospective cohort studies have recently been
published on the relationship between cis-MUFA and CHD
risk. The aim of this paper is to review these new studies that
have been published in the last 3 years on the effects of cis-
MUFA on cardiovascular risk markers and CHD.
Keywords Monounsaturated fatty acids .Oleic acid .Risk
markers .Coronary heart disease .Cardiovascular disease
Introduction
Optimizing dietary fatty-acid intake is an integral part of die-
tary guidelines to prevent coronary heart disease (CHD) [1]. In
fact, unequivocal evidence exists that eliminating trans-fatty
acids from hydrogenated oils in the diet lowers the prevalence
of CHD [2]. A decrease in the intake of saturated fatty acids
(SFA) is also recommended, but in this respect, the type of
macronutrient that replaces SFA is important. Replacement of
SFA by carbohydrates from refined starches/added sugars
may not decrease CHD risk, while replacement by carbohy-
drates from whole grains or cis-polyunsaturated fatty acid (cis-
PUFA) does [3•,4]. The effects of cis-monounsaturated fatty
acids (MUFA; Fig. 1) on CHD risk and CHD mortality are
however less clear [5]. Also, dietary recommendations as de-
rived by various health agencies for trans-fatty acids, SFA,
and cis-PUFA are generally more in agreement than those
for cis-MUFA. For example, no specific dietary reference
values for cis-MUFA have been formulated in the very recent
2015–2020 Dietary Guidelines for Americans [6], while other
organizations have set reference values for cis-MUFA [7]. In
2012, Schwingshackl and Hoffmann have reviewed the avail-
able evidence from systemic reviews and meta-analyses re-
garding cis-MUFA intake and cardiovascular risk [8]. It was
concluded that there was no clear justification to formulate
specific dietary recommendations for cis-MUFA for the pri-
mary and secondary prevention of cardiovascular disease
(CVD). On the other hand, as no harmful effects of cis-
MUFA-rich diets are known, more longer term intervention
studies were suggested to clarify potential benefits of cis-
MUFA-rich diets. Since then, several new studies have been
published during the last 3 years on the relationship between
cis-MUFAs and cardiovascular risk markers or CHD, which
will be discussed in the present review.
Food Sources Of cis-Monounsaturated Fatty Acids
Worldwide,themeanintakeofcis-MUFA ranges from 3.5 %
of total energy in certain regions of China to about 22 % in
This article is part of the Topical Collection on Nutrition
*Ronald P. Mensink
r.mensink@maastrichtuniversity.nl
1
Department of Human Biology, NUTRIM School of Nutrition and
Translational Research in Metabolism, Maastricht University
Medical Center, PO Box 616, Maastricht 6200 MD, The Netherlands
Curr Atheroscler Rep (2016) 18: 38
DOI 10.1007/s11883-016-0597-y
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Greece. Oleic acid (18:1; n-9) is the predominant cis-MUFA,
accounting for more than 92 % of all MUFAs consumed.
Other cis-MUFAs are also present in the diet, but only in very
small amounts (Table 1). Except for erucic acid (22:1; n-9),
their health effects have hardly been studied. Animal studies
have suggested that erucic acid at high intakes may cause
myocardial lipidosis due to poor mitochondrial β-oxidation.
However, rapeseed oil varieties low in erucic acid are nowa-
days part of the food chain. Therefore, cis-MUFA intakes in
the studies discussed mainly refer to intakes of oleic acid.
Some vegetable oils, such as olive oil (≈75 %), mid-oleic
sunflower oil (≈70 %), and rapeseed oil (≈65 %), consist of
more than 50 % of cis-MUFA, followed by other products
such as palm oil, nuts and seeds, avocados, and animal fats
[9]. In fact, animal fats are the main source of cis-MUFA in a
typical American diet, and high cis-MUFA and SFA intakes
may thus be correlated. The six food groups with the highest
contribution to total MUFA intake among US adults based on
the National Health and Nutrition Examination Survey
(NHANES) 2003–2006 were other fats and oils (10.5 %), beef
(9.2 %), cakes/cookies/quick bread/pastry/pie (8.9 %), frank-
furters/sausages/luncheon meats (7.5 %), cheese (6.6 %), and
margarine and butter (6.4 %) [10].
cis-Monounsaturated Fatty Acid
and Cardiovascular Risk Markers
cis-MUFA may affect cardiovascular health through effects on
a wide variety of markers associated with CHD [11]. This
paragraph reviews current evidence on the effects of cis-
MUFA on serum lipids and lipoproteins, vascular function
markers, postprandial vascular function, and energy intake
and metabolism.
Serum Lipids and Lipoproteins
Data from the many earlier well-controlled randomized inter-
vention studies have shown that cis-MUFA has a favorable
effect on the serum lipoprotein profile. In studies that replaced
fats or oils high in SFAwith oils rich in cis-MUFA, significant
decreases were found in serum concentrations of total choles-
terol, LDL-cholesterol, and apoB100 and the total to HDL-
cholesterol ratio. Serum HDL-cholesterol, apo-AI, and triac-
ylglycerol concentrations hardly changed. Overall, the effects
of oils rich in cis-PUFA were slightly more favorable than
those of oils rich in cis-MUFA, especially on LDL-
cholesterol and the total to HDL-cholesterol ratio. In these
studies, the diets were enriched with cis-MUFA from different
sources such as olive oil, high-oleic acid sunflower oil, high-
oleic acid safflower oil, and rapeseed oil. More recently, other
intervention trials have been carried out specifically focusing
on cis-MUFA. Gilmore et al. reported that in 17 postmeno-
pausal women, consumption of high-MUFA or low-MUFA
ground beef for 6 weeks had comparable effects on the serum
lipoprotein profile [12]. However, the difference in cis-MUFA
intake provided by the two types of ground beef was less than
2 g/day, which may have been too small to observe any ef-
fects. In a randomized, double-blind, crossover design with
131 abdominally obese volunteers, five oils with comparable
amounts of SFA, but differing in the amounts of oleic acid,
linoleic acid, α-linolenic acid, or docosahexaenoic acid
(DHA) were consumed for 4-week periods [13••]. Effects on
serum LDL-cholesterol, HDL-cholesterol, and triacylglycerol
concentrations were comparable, confirming the findings that
Fig. 1 Monounsaturated fatty acids (MUFAs) are chemically classified
as fatty acids that have one double bond in the carbon chain. In the cis-
configuration, the hydrogen atoms attached to the double bond point into
the same direction (top:oleicacid,acis-MUFAwith18carbonatoms),
while in the trans-configuration, the hydrogen atoms are located on op-
posite sides (bottom:elaidicacid,atrans-MUFA with 18 carbon atoms)
Tabl e 1 Overview of different types of cis-monounsaturated fatty acids
cis-MUFA Food sources
Caproleic acid (10:1) Ruminant fats
Lauroleic acid (12:1; n-3) Ruminant fats
Myristoleic acid (14:1; n-5) Ruminant fats
Palmitoleic acid (16:1; n-7) Ruminant fats, fats from fish and
marine mammals, macadamia oil,
sea buckthorn oil and milkweed
seed oil
Oleic acid (18:1; n-9) Vegetable oils such as olive oil,
mid-oleic sunflower oil and
low-erucic acid rapeseed oil, nuts
and seeds, avocados, palm oil,
and animal fats
Gadoleic acid (20:1; n-11) Fish oils such as ray, shark and
cod, and mustard oil
Erucic acid (22:1; n-9) Mustard oil
Nervonic acid (24:1; n-9) Mustard oil, fish oils such as salmon
Oleic acid is the predominant cis-MUFA in the diet, accounting for more
than 92 % of all MUFAs consumed
MUFA monounsaturated fatty acid
38 Page 2 of 7 Curr Atheroscler Rep (2016) 18: 38
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
cis-unsaturated fatty acids with 18 carbon atoms have compa-
rable effects on serum lipids. An oil rich in cis-MUFA and
DHA, however, increased LDL-cholesterol and HDL-
cholesterol and lowered serum triacylglycerol concentrations
as compared with the other four oils [13••]. In a subset of the
population, no evidence was found that consumption of the
oils had an adverse effect on LDL proteoglycan binding [14],
as observed in animal studies after consumption of oils rich in
cis-MUFA [15]. As expected, a high-palmitic acid diet in-
creased concentrations of total LDL-cholesterol and HDL-
cholesterol and had no effects on serum triacylglycerol as
compared with a high-oleic acid diet in 18 healthy subjects
[16]. Also, olive oil and rapeseed oil were found to have
similar effects on the serum lipoprotein profile [17]. In a 24-
week parallel study in individuals with type 2 diabetes, a
peanut-enriched American Diabetic Association (ADA) meal
plan had similar effects on the serum lipoprotein profile com-
pared with a nut-free ADA meal plan [18]. Dietary SFA and
total fat intakes between the two groups were not different. In
the Dietary Intervention and Vascular Function (DIVAS) trial,
a randomized, single-blind, parallel-group intervention study
with 195 adults at moderate CVD risk, three groups of sub-
jects consumed for 16 weeks a diet that was rich in SFA, cis-
MUFA, or cis-PUFA. Except for commercially available
foods, specially formulated oils and spreads were used high
in cis-MUFA (refined olive oil and rapeseed oil) and cis-
PUFA (safflower oil). The high-SFA group received butter.
As compared with the high-SFA groups, serum total and
LDL-cholesterol concentrations were reduced to the same ex-
tent on the high-MUFA and high-PUFA diets. Effects on se-
rum HDL-cholesterol and triacylglycerol were comparable
[19••]. Overall, these recent studies are in line with the earlier
studies.
The mechanistic aspects of cis-MUFA were examined by
Labonté and colleagues [20]. In a randomized parallel study,
the effects of exchanging carbohydrates for cis-MUFA as part
of an experimental portfolio diet on apolipoprotein kinetics
were investigated in 16 dyslipidemic subjects. The experimen-
tal diets were fed for 4 weeks after a 4-week run-in period. The
high-MUFA diet increased apo-AI pool size, mainly due to a
reduced apo-AI fractional catabolic rate. LDL apoB100 pool
size tended to be reduced on the cis-MUFA diet through an
increase in LDL apoB100 fractional catabolic rate.
Vascular Function Markers
The DIVAS study was adequately powered to investigate the
long-term impact of replacing SFAs with cis-MUFAs on var-
ious fasting vascular function markers [19••]. It was found that
replacing dietary SFAs with cis-MUFAs did not affect fasting
flow-mediated vasodilation (FMD) of the brachial artery
[19••]. These findings are in agreement with those of
Sanders and colleagues, who replaced 5.2 % of energy from
dietary SFAs by cis-MUFAs for 24 weeks in 121 insulin-
resistant men and women [21••]. Furthermore, replacement
of SFAs had no effect on arterial stiffness, supporting the
earlier findings of Sanders et al. reporting no change in
carotid-to-femoral pulse wave velocity (PWV
c-f
)whenSFAs
were replaced with cis-MUFAs [21••]. Of the secondary out-
come measures, substitution of dietary SFAs by cis-MUFAs
significantly reduced circulating E-selectin concentrations by
7.8 %, suggesting an improvement in endothelial activity,
while night systolic blood pressure was reduced by 4.9 mm
of Hg. As discussed by the authors [19••], the large range of
recorded daily activity levels may have masked any effects of
the intervention on 24-h or daytime ambulatory blood pres-
sure recordings.
Postprandial Vascular Function
Postprandial vascular responses were compared between
normal-weight and obese men following three isocaloric
high-fat challenges differing in fatty-acid composition [22].
For this, 18 normal-weight and 18 obese middle-aged men
received in a random order a milkshake providing 95 g of
fat, which was either high in SFAs, cis-MUFAs, or n-3long-
chain PUFAs. Compared with the SFA and n-3PUFA shakes,
it was found that the cis-MUFA milkshake resulted in a more
pronounced decrease in the augmentation index (AIx)—a
measure of the arterial pressure waveform that depends on
the tone of peripheral resistance arteries—and blood pressure.
Milkshake consumption resulted in increased plasma
sICAM1, sICAM3, and sVCAM1 concentrations 4 h post-
prandially, with no differences in responses between the
shakes for these and other (E-selectin and vWF) plasma bio-
markers of endothelial function. Lithander et al. [23] com-
pared the effects of a test meal rich in oleic acid with an
isoenergetic meal rich in palmitic acid on postprandial vascu-
lar function in younger male participants. No differences in
PWV
c-f
, AIx or blood pressure were found between the two
test meals providing 56 g of fat. Except for subject character-
istics, the difference in findings with the study of Esser and
colleagues [22] may also be explained by meal composition,
because the mixed meal provided by Lithander was higher in
carbohydrates and lower in dietary fat (56 g of fat versus 95 g
of fat).
Energy Intake and Metabolism
Mennella and colleagues fed 15 healthy normal-weight sub-
jects in random order 30 mL of high-oleic acid sunflower oil,
virgin olive oil, or sunflower oil plus 30 g of bread. After
consumption of the oils rich in oleic acid, energy intake was
reduced at the subsequent self-chosen lunch, possible related to
the increased postprandial concentrations of
oleoylethanolamide (OEA), a compound produced by the small
Curr Atheroscler Rep (2016) 18: 38 Page 3 of 7 38
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intestine that is involved in appetite regulation. However, ener-
gy intake over the next 24 h as assessed by food diaries was
comparable between the three treatments [24]. Total energy
intake as measured during 4 days was lower in a randomized
controlled trial (RCT) with 24 healthy elderly overweight par-
ticipants following consumption of high-oleic acid peanuts and
regular peanuts compared with isoenergetic amounts of a high-
carbohydrate snack (potato crisps). Despite these reductions in
energy intake, no differences in hunger and satiety that were
assessed following snack consumption using visual analog
scales were observed [25]. Comparable results were reported
in another study with high-oleic acid peanuts [26].
In their recent review [27], Krishnan and Cooper conclud-
ed that acute-meal studies suggested that diet-induced thermo-
genesis and fat oxidation were increased on high unsaturated-
fat diets as compared with SFA-rich diets. In this respect, no
differences were found between MUFA and PUFA. It was
further concluded that also long-term dietary interventions
may suggest that MUFA-rich diets induced a greater energy
expenditure, diet-induced thermogenesis or fat oxidation as
compared with SFA-rich diets [27]. More recently, however,
Clevenger et al. found no differences in the effects of SFA,
MUFA, and PUFA on diet-induced thermogenesis or post-
prandial substrate oxidation in obese women [28]. On the
other hand, Kien and colleagues reported in healthy volunteers
a higher rate of fat oxidation during the fasted state on a
palmitic-acid rich diet as compared with an oleic-acid rich
diet. Diets were provided for 3 weeks [29••]. Overall, there
is no unanimous agreement that cis-MUFA affects energy
metabolism compared with other dietary fatty acids. The few
short-term studies that used peanuts are more consistent in this
respect and effects may therefore not necessarily be related to
cis-MUFA intake. Also, it is not known if the effects are
sustained on the longer term and are ultimately translated into
a lower body weight and an improved cardiometabolic profile.
cis-Monounsaturated Fatty Acid
and Cardiovascular Disease
The Mediterranean diet is well known for its high cis-
MUFA content (16 to 29 % of energy) with olive oil being
the predominant source of fat and intakes of SFA below 8 %
[30]. The Mediterranean dietary pattern is associated with a
reduced cardiovascular risk. Even though not designed to
specially evaluate the effects of cis-MUFA, the
PREvención con DIEeta MEDiterraneá (PREDIMED) trial
found that a Mediterranean diet supplemented with extra-
virgin olive oil (50 g/day) or mixed nuts (30 g/day) reduced
in individuals at high cardiovascular risk the incidence of
major cardiovascular events (a composite of myocardial in-
farction, stroke, or death from CVD causes) as compared
with a control diet low in fat [31••]. A meta-analysis of 15
RCTs, that involved more than 50,000 participants, aimed to
estimate the effect of replacing dietary SFA for carbohy-
drates, cis-PUFA, cis-MUFA, or protein on cardiovascular
morbidity and mortality [5]. It was concluded that the effects
of cis-MUFA were unclear as only one small trial from 1965
was identified [32], in which no effects were observed. In
this respect, the results of recently published large prospec-
tive cohort studies evaluating the association between cis-
MUFA intake with the risk of CVD and cardiovascular
death may be more informative (Table 2).
Subjects within the PREDIMED trial were also prospec-
tively studied. While the trial was conducted from 2003 to
2010, the present data were based on an expanded follow-up
until 2012 [33•]. The mean intake of cis-MUFAs (expressed as
percentage of energy) was high: 13.4 % in the lowest quintile
compared with 26.1 % in the top quintile. After 6 years of
follow-up, 336 CVD cases and 414 total deaths were reported.
It was found that higher intakes of cis-MUFA were inversely
associated with CVD, cardiovascular death, and all-cause
death. In fact, isocaloric substitution of 5 % of energy from
SFAs or trans-FAs with cis-MUFAs was associated with a 37
and 40 % lower risk of total CVD events. In agreement, an
updated analysis of the Nurses’Health Study (1980–2010; 84,
628 US women) and the Health Professional Follow-Up
Study (1986–2010; 42,908 US men) showed a reduction in
CHD risk when SFA was exchanged for cis-MUFA [3•]. In
these two large, independent prospective cohorts of men and
women, 7667 cases of CHD (4931 nonfatal myocardial infarc-
tions and 2736 CHD deaths) were documented over 24 to
30 years of follow-up. Replacing 5 % of energy from dietary
SFAwithanequivalentamountofcis-MUFA was associated
with a 15 % (95 % CI, 3 to 26 %) lower risk of CHD. In a large
prospective cohort study carried out within the Alpha-
Tocopherol, Beta-Carotene Cancer Prevention Study
(ATBC), the associations between glycemic index, substitu-
tions of total, low-, medium-, and high-glycemic-index carbo-
hydrates for dietary fat and the risk of CHD were examined
[34•]. During a 19-year follow-up, 4379 CHD cases, including
a total of 2377 non-fatal myocardial infarctions and 2002
CHD deaths, were documented among approximately 22,
000 middle-aged Finnish male smokers. Substituting carbo-
hydrates for cis-MUFAs was associated with a decreased risk.
It was estimated that isoenergetic replacements of 2 % of
energy from total, low-, or high-glycemic-index carbohy-
drates for cis-MUFAs were associated with 8 % (95 % CI, 1
to 16 %), 9 % (95 % CI 2 to 16 %), and 8 % (95 % CI 1 to
15 %) lower CHD risks. The isocaloric replacement of
medium-glycemic-index carbohydrates with cis-MUFA
tended to decrease the risk of CHD by 7 % (95 % CI 0 to
15 %). Dietary fiber intake modified the association between
the replacement of carbohydrates with cis-MUFA and the risk
of CHD in the stratified analyses. In fact, increasing cis-
MUFA intake at the expense of carbohydrates was more
38 Page 4 of 7 Curr Atheroscler Rep (2016) 18: 38
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beneficial among the subjects with a higher fiber intake. In
patients with type 2 diabetes, the association between dietary
carbohydrate intake and substitution for cis-MUFA with car-
diovascular and all-cause mortality was also investigated
[35•]. A total of 6192 type 2 diabetic patients from 15 cohorts
of the European Prospective Investigation into Cancer and
Nutrition (EPIC) were included. After a mean follow-up of
about 9 years, 268 CVD deaths and 791 total deaths were
reported. Substituting 5 % of energy from carbohydrates with
cis-MUFA may be associated with a lower all-cause mortality
risk (HR, 0.87; 95 % CI, 0.76 to 1.00), while no effects were
reported for CVD mortality risk.
Surprisingly, a lower CHD risk with a higher intake of
SFAs was recently observed that did not depend on the
type of substituting macronutrient [36•]. The EPIC-
Netherlands (EPIC-NL) cohort included 35,597 Dutch
men and women. In this prospective cohort study, a total
of 1807 incident CHD cases and 158 CHD deaths (8.7 %)
occurred over a median follow-up time of 12 years. After
full adjustment, the substitution of 5 % of energy from SFA
with cis-MUFA was associated with 30 % (95 % CI: 2 %
to 65 %) increased risk to develop CHD. These results,
however, should be interpreted with caution. As discussed
by the authors [36•], residual confounding by unmeasured
initiation of cholesterol-lowering therapy during follow-up
may explain these findings as adults with high SFA intake
have high serum cholesterol concentrations and will be-
come eligible for lipid-lowering therapy during follow-up,
which would reduce CHD risk. In addition, the limited
variation in dietary SFA intake or the source of SFA may
also have attributed to the observed risk differences in this
Dutch population.
Conclusions
In summary, recent studies are in line with the earlier studies
showing that cis-MUFAs have a favorable effect on the serum
lipoprotein profile as compared with a mixture of SFA, while
effects are comparable to those of linoleic and α-linolenic acid.
Effects on fasting and postprandial vascular function have not
been studied extensively and no consistent differences between
the various fatty acids are evident. Longer-term studies should
address whether products rich in cis-MUFA affect energy intake
and metabolism compared with other macronutrients. In fact,
studies addressing the effects of food sources and matrices are
of interest, as this may impact the results. Well-designed RCTs
with CVD events as endpoints are lacking. Evidence from large
prospective cohort studies regarding effects of cis-MUFA on the
risk to develop CHD is limited, but several studies do suggest
that replacements of SFA or high-glycemic index foods for cis-
MUFA lowers CHD risk. In this respect, however, cis-MUFA is
not more beneficial than linoleic acid. More research is thus
required on the long-term effects of cis-MUFA as compared
with other macronutrients on CHD risk markers as well as on
clinical endpoints to clarify the potential role of cis-MUFAs in
the primary and secondary prevention of CHD.
Compliance with Ethical Standards
Conflict of Interest Peter J. Joris declares no conflict of interest.
Ronald P. Mensink declares grant support from Top Institute for Food
and Nutrition (Wageningen, the Netherlands) and from Unilever
Research and Development (Vlaardingen, the Netherlands).
Human and Animal Rights and Informed Consent This article does
not contain any studies with human or animal subjects performed by any
of the authors.
Tabl e 2 Summary of recent studies assessing the effects of cis-MUFAs on cardiovascular disease
Study Research question Study design Results
PREDIMED Study [33•] Dietary fat intake and risk of total
CVD events in a population at
high risk of CVD
Prospective cohort study Dietary SFA for cis-MUFA
(5 % of energy) HR 0.63
(95 % CI 0.43–0.94)
NHS and the HPFS [3•] Dietary fat intake and risk of CHD
in men and women free of
diabetes, CVD, and cancer
Prospective cohort study Dietary SFA for cis-MUFA
(5 % of energy) HR 0.85
(95 % CI 0.74–0.97)
ATBC Cancer Prevention
Study [34•]
Carbohydrate substitution for
dietary fat and risk of CHD in
Finnish male smokers
Prospective cohort study Total carbohydrates for cis-
MUFA (2 % of energy)
RR 0.92 (95 % CI 0.84–0.99)
EPIC Study [35•] Carbohydrate substitution for
dietary fat on mortality risk in
patients with type 2 diabetes
Prospective cohort study Carbohydrates for cis-MUFA
(5 % of energy) HR 0.87
(95 % CI 0.76–1.00). No
effects on CVD mortality risk
EPIC-NL Study [36•] Dietary fat intake and risk of
CHD in a Dutch population
Prospective cohort study Dietary SFA for cis-MUFA
(5 % of energy) HR 1.30
(95 % CI 1.02–1.65)
CVD cardiovascular disease, CHD coronary heart disease, N/A not applicable, SFA saturated fatty acid, MUFA monounsaturated fatty acid, HR hazards
ratio, RR relative risk
Curr Atheroscler Rep (2016) 18: 38 Page 5 of 7 38
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Curr Atheroscler Rep (2016) 18: 38 Page 7 of 7 38
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