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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY VOL. 70, NO.

13, 2017

ª 2017 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION ISSN 0735-1097/$36.00

PUBLISHED BY ELSEVIER http://dx.doi.org/10.1016/j.jacc.2017.08.006

REVIEW TOPIC OF THE WEEK

A Test in Context: Lipid Profile,


Fasting Versus Nonfasting
Børge G. Nordestgaard, MD, DMSC

ABSTRACT

Fasting for >8 h, as previously required for lipid profiles, normally only occurs a few hours before breakfast. By contrast,
the nonfasting state predominates most of a 24-h cycle and better captures atherogenic lipoprotein levels. Plasma
contains atherogenic lipoproteins of hepatic origin in the fasting state and additionally those of intestinal origin in the
nonfasting state. Maximal mean changes for random, nonfasting versus fasting levels are þ26 mg/dl for
triglycerides, 8 mg/dl for total cholesterol, 8 mg/dl for low-density lipoprotein cholesterol, þ8 mg/dl for remnant
cholesterol, and 8 mg/dl for non–high-density lipoprotein cholesterol; lipoprotein(a), apolipoprotein B, and
high-density lipoprotein cholesterol are largely unaffected. For patients, laboratories, and clinicians alike, nonfasting lipid
profiles represent a simplification without negative implications for prognostic, diagnostic, and therapeutic options for
cardiovascular disease prevention. Several societies’ guidelines and statements in Denmark, the United Kingdom,
Europe, Canada, Brazil, and the United States endorse nonfasting lipid profiles. (J Am Coll Cardiol 2017;70:1637–46)
© 2017 by the American College of Cardiology Foundation.

F asting for more than 8 h normally only occurs a


few hours before breakfast (Figure 1). By
contrast, the nonfasting state predominates
for most of a 24-h cycle. Therefore, because plasma
statements in Denmark (3), the United Kingdom (4),
Europe (5,6), Canada (7,8), Brazil (9), and the United
States (10–12).
This review first delineates the lipid, lipoprotein,
contains atherogenic lipoproteins of hepatic origin and apolipoprotein components of minimal, stan-
in the fasting state and additionally those of intesti- dard, and expanded lipid profiles, followed by a
nal origin in the nonfasting state, the nonfasting state description of the difference in these measurements
may better capture the total amount of atherogenic li- between the fasting and the random, nonfasting
poproteins in plasma during the majority of a 24-h states. Thereafter, and with focus on the patient, the
period. main goal of this review is to provide a critical eval-
Despite that, lipid profiles have previously been uation of the pros and cons of fasting versus non-
measured in blood drawn in the fasting state, that is, fasting lipid profiles, and the implications for
after 8 to 12 h without food intake, whereas water and prognostic, diagnostic, and therapeutic options for
other nonfatty fluid intake have typically been preventing cardiovascular disease. Finally, the re-
allowed (1,2). However, the tradition of using fasting view mention implications for conducting clinical
lipid profiles is currently changing many places in the trials and provides a short historical overview for the
world, with random, nonfasting lipid profiles being increasing use of nonfasting, rather than fasting, lipid
endorsed by several societies, guidelines and profiles worldwide.
Listen to this manuscript’s
audio summary by
JACC Editor-in-Chief
Dr. Valentin Fuster.
From the Department of Clinical Biochemistry and The Copenhagen General Population Study, Herlev and Gentofte Hospital,
Copenhagen University Hospital, Copenhagen, Denmark; and the Faculty of Health and Medical Sciences, University of Copen-
hagen, Copenhagen, Denmark. Dr. Nordestgaard has reported that he has no relationships relevant to the contents of this paper to
disclose.

Manuscript received June 23, 2017; revised manuscript received August 3, 2017, accepted August 4, 2017.
1638 Nordestgaard JACC VOL. 70, NO. 13, 2017

Lipid Profile, Fasting Versus Nonfasting SEPTEMBER 26, 2017:1637–46

ABBREVIATIONS LIPIDS, LIPOPROTEINS, AND are apolar toward the lipoprotein core, but are polar
AND ACRONYMS APOLIPOPROTEINS MEASURED IN toward the water phase. These molecules are phos-
LIPID PROFILES pholipids, free cholesterol, and apolipoproteins
apoB = apolipoprotein B
(Table 1). Apolipoproteins act as cofactors for en-
CI = confidence interval
Lipids such as cholesterol and triglycerides, zymes in lipid metabolism and as ligands when lipo-
HDL = high-density lipoprotein
measured as total plasma values in lipid proteins are recognized at cell surfaces. Most
IDL = intermediate-density profiles, are important for most cells. important are apolipopteins B (apoB) and E, which
lipoprotein
Cholesterol is an essential component of cell facilitate removal of low-density lipoprotein (LDL)
LDL = low-density lipoprotein
membranes, and also acts as precursor for and chylomicron remnant/intermediate-density
Lp(a) = lipoprotein(a)
bile acids and steroid hormones. Tri- lipoprotein (IDL) from plasma, respectively.
VLDL = very low-density glycerides are important as energy sources Lipoproteins increase in size and decrease in den-
lipoprotein
and, after storage, act as an energy reserve as sity from high-density lipoprotein (HDL) to LDL to
well as for insulation against cold weather. Unlike lipoprotein(a) (Lp[a]) to IDL to very low-density li-
triglycerides, carbohydrates, and proteins, choles- poprotein (VLDL) to chylomicrons (Table 1). Chylo-
terol cannot be degraded by human cells. Cholesterol micron remnants have size and density like IDL and
that is newly synthesized or taken up via the intestine VLDL.
will therefore remain in the body unless it is con- Cholesterol and triglycerides in the diet are
verted to steroid hormones, lost through skin cell absorbed in the small intestine and incorporated into
detachment, or secreted via bile. chylomicrons (Figure 2). Chylomicrons are transferred
Because lipids will not mix with water, plasma has to the bloodstream via lymph, where it comes in
a lipid transport system consisting of water-soluble contact with the triglyceride-degrading enzyme lipo-
lipoproteins. The cores of lipoproteins consist of protein lipase, mainly in fat and muscle tissue. The
apolar lipid triglycerides and cholesterol esters resulting chylomicron remnants are taken up rapidly
(Table 1) (13). Cholesterol esters are free cholesterol by liver cells.
molecules esterified with a fatty acid coming from Cholesterol in the liver is either secreted via bile as
phospholipids; when cholesterol is measured in bile acids or cholesterol, or will, together with tri-
plasma or lipoproteins, it is a measurement of free glycerides, be packed into VLDL particles that are
and esterified cholesterol combined. To keep tri- secreted into the bloodstream (Figure 2). Triglycerides
glycerides and cholesterol esters in a water solution, in VLDL will be degraded in fat and muscle tissue by
the surface of lipoproteins consists of molecules that the enzyme lipoprotein lipase, and the cholesterol-
rich IDL particle is formed. Some IDL particles are
cleared by liver cells, whereas others are converted to
F I G U R E 1 Nonfasting and Fasting Periods During a 24-h Cycle With Intake of LDL particles through the action of the triglyceride-
Typical Meals degrading enzyme hepatic lipase. LDL particles are
taken up via the LDL receptor in the liver and other
Less than 8 hrs tissues.
since last meal
Lipoprotein(a) particles are LDL particles with an
extra apolipoprotein, apo(a) (Table 1); apo(a) has ho-
mology with plasminogen, and therefore may inter-
Non-fasting fere with fibrinolysis and indirectly promote arterial
Noon
thrombosis (14). HDL particles were previously
thought to be important in atherosclerosis and car-
6 am 6 pm diovascular disease, but the evidence to support this
is becoming weaker and weaker (15,16).
Fasting In hyperlipidemia, there is a surplus of atherogenic
Midnight
lipoproteins circulating in the blood, and a fraction of
these will penetrate into the arterial intima via simple
size- and concentration-dependent filtration (Figure 3)
More than 8 hrs (17). Chylomicrons and large VLDL with diameters
since last meal
larger than 75 nm are not able to enter the intima (18),
unlike all other lipoproteins (16,17). LDL, lip-
Fasting for more than 8 h for most individuals only represents a few hours in the early oprotein(a) (Lp(a)), IDL, chylomicron remnants, and
morning. VLDL all enter the intima and are trapped, as they
cannot penetrate the elastic laminas in the media.
JACC VOL. 70, NO. 13, 2017 Nordestgaard 1639
SEPTEMBER 26, 2017:1637–46 Lipid Profile, Fasting Versus Nonfasting

T A B L E 1 Size, Density, and Core and Surface Components of Lipoproteins

Components (% of Dry Weight)

Core Surface
Diameter Molecular Density Main
(nm) Weight  106 (Da) (g/ml) Triglycerides Cholesterol Ester Cholesterol Phospholipid Apolipoproteins Apolipoproteins

Chylomicrons 75–1,200 50–1,000 0.93 86 3 2 7 2 A, B-48, C, E


VLDL 30–80 10–80 0.93–1.006 55 12 7 18 8 B-100, C, E
IDL 25–35 5–10 1.006–1.019 23 29 9 19 19 B-100, C, E
Lipoprotein(a) 25–30 4–5 1.040–1.090 8 30 8 25 29 B-100, a
LDL 18–25 2.3 1.019–1.063 6 42 8 22 22 B-100
HDL 5–12 0.2–0.4 1.063–1.210 4 15 5 34 42 A, C, E

HDL ¼ high-density lipoprotein; IDL ¼ intermediate-density lipoprotein; LDL ¼ low-density lipoprotein; VLDL ¼ very low-density lipoprotein.

All of these apoB-containing lipoproteins can, to some value and may confuse, rather than enlighten, the
degree, transfer back from the intima to the lumen of clinician.
the artery against the blood pressure gradient, but the A minimal lipid profile consists of plasma total
larger triglyceride-rich lipoproteins IDL, chylomicron cholesterol and triglycerides (Table 2). A standard lipid
remnants and VLDL have particular difficulty leaving profile also includes measurements of LDL cholesterol
the intima due to their larger sizes (16,19,20). and HDL cholesterol. Total cholesterol, HDL choles-
In isolated hypercholesterolemia, when tri- terol, and triglycerides are measured directly, whereas
glycerides are below 176 mg/dl (2 mmol/l), LDL LDL cholesterol can either be measured directly
cholesterol is the main atherogenic component in or calculated by the Friedewald equation if
plasma (Figure 4, left). In combined hyperlipidemia, triglycerides are <400 mg/dl (<4.5 mmol/l): total
when triglycerides are 176 to 880 mg/dl (2 to cholesterol  HDL cholesterol  triglycerides/2.2 (all
10 mmol/l), cholesterol in LDL, IDL, chylomicron in mmol/l; or  triglycerides/5 with values in mg/dl)
remnants, and VLDL combined constitute the (21), with direct measurement of LDL cholesterol at
atherogenic plasma component (Figure 4, middle). triglyceride concentrations $400 mg/dl (4.5 mmol/l).
However, when triglycerides are severely elevated Traditionally, the Friedewald equation has been
above 880 mg/dl (10 mmol/l), chylomicrons and large
VLDL are not atherogenic, whereas LDL, IDL, chylo-
micron remnants, and small VLDL are atherogenic F I G U R E 2 Atherogenic Lipoproteins Present in the Blood During Periods of

(Figure 4, right). Fasting and Nonfasting

MINIMAL, STANDARD, AND EXPANDED Nonfasting


LIPID PROFILES
Fasting

The decision of which lipid profile to order for a given


patient depends on the balance between optimal
LDL
diagnostic accuracy and cost, while avoiding unnec-
essary diagnostic noise from measurement of too
Chylomicron
many lipid, lipoprotein, and apolipoprotein compo- Chylomicron
remnant
nents (Table 2). The minimal lipid profile is valuable
VLDL IDL
in countries and situations where cost is a major
issue, whereas standard and expanded lipid
profiles are most commonly used in modern medi-
cine. Single measurements of either total or LDL Lipoprotein lipase Lipoprotein lipase
cholesterol should be avoided, as important elevation
Triglycerides Cholesterol
of triglycerides and remnant cholesterol can then
be overlooked. Finally, many laboratories offer
During fasting, only liver-derived lipoproteins are present in plasma, whereas in the
additional measurements, such as lipoprotein nonfasting state, intestinal-derived lipoproteins are likewise found in plasma.
subfractions, other apolipoproteins, and even IDL ¼ intermediate-density lipoprotein; LDL ¼ low-density lipoprotein; VLDL ¼ very
metabolomics phenotyping, all of which, for the low-density lipoprotein.
majority of patients, are without proven clinical
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Lipid Profile, Fasting Versus Nonfasting SEPTEMBER 26, 2017:1637–46

measurements in the same patient, unless therapeu-


F I G U R E 3 Transfer of Lipoproteins Between Plasma and the Arterial Intima
tic intervention is aimed at reducing Lp(a) concen-
trations. Importantly, the cholesterol content of
Plasma Arterial Wall
Intima Media Adventitia Lp(a), corresponding to approximately 30% of Lp(a)
total mass (32), is included in total, non-HDL, and LDL
HDL cholesterol values and its apoB content is included in
the apoB value.
LDL
Finally, measurements of apoB can be used as an
Lp(a) alternative to non-HDL cholesterol (6,7,10,28), but
this measurement adds extra cost. ApoB is a well-
IDL +
chylomicron
standardized measurement that captures all athero-
remnants genic lipoproteins.
Small
VLDL
DIFFERENCES BETWEEN FASTING AND
NONFASTING LIPID PROFILES
Chylomicrons
+ large VLDL
Plasma contains remnant lipoproteins of hepatic
origin in the fasting state, whereas remnant lipo-
proteins of intestinal origin additionally are present
in the nonfasting state (Figure 2). This means that
This figure depicts the relative speed by which different lipoproteins enter and leave the from 1 to 7 h after a habitual meal, plasma tri-
arterial intima, and thereby which lipoproteins that get trapped preferentially in the intima. glycerides and remnant cholesterol are slightly
First, the larger the lipoprotein diameter, the fewer that will enter into the intima, where elevated (Figure 5). A habitual meal here means
chylomicrons and large VLDL are simply too large to enter. Second, although HDL is small
whatever the person chose to eat before blood sam-
enough to penetrate into the media and leave via the adventitia, other lipoproteins are so
pling, which naturally will differ from person to
large that they can only leave the intima via the lumen of the artery. Because back transport
is against a blood pressure gradient, the largest lipoproteins, such as IDL, chylomicron person and from country to country. The degree of
remnants, and small VLDL, get trapped preferentially in the intima. HDL ¼ high-density plasma triglyceride elevation is related to levels at
lipoprotein; Lp(a) ¼ lipoprotein(a); other abbreviations as in Figure 2. baseline; the lower the baseline triglycerides, the
smaller the postprandial effect and vice versa per
equivalent fat load.
applied to a fasting lipid profile; however, calculated The maximal mean changes as measured in random,
LDL cholesterol determined with this equation at tri- nonfasting versus fasting blood samples are þ26 mg/dl
glyceride concentrations <400 mg/dl (4.5 mmol/l) is (0.3 mmol/l) for triglycerides, 8 mg/dl (0.2 mmol/l)
similar to LDL cholesterol measured directly on both for total cholesterol, 8 mg/dl (0.2 mmol/l) for LDL
fasting and nonfasting lipid profiles (22–24). These 4 cholesterol, þ8 mg/dl (0.2 mmol/l) for remnant
measurements can, without additional cost, be sup- cholesterol, and 8 mg/dl (0.2 mmol/l) for non-HDL
plemented with calculated remnant cholesterol (i.e., cholesterol, whereas lipoprotein(a), apoB, HDL
triglyceride-rich lipoprotein cholesterol) and calcu- cholesterol, and apoA1 are largely unaffected by
lated non-HDL cholesterol (i.e., LDL þ remnant random, nonfasting sampling (Figure 6) (5,33–37).
cholesterol) levels. Calculated remnant cholesterol is Importantly, in individual subjects, the change in tri-
a strong causal risk factor for cardiovascular disease glycerides will depend on baseline triglyceride levels,
(25–27). The use of non-HDL cholesterol for cardio- fat intake, and time since the last meal.
vascular disease risk prediction has been emphasized Interestingly, the slight decrease in total, LDL, and
in several guidelines and consensus papers non-HDL cholesterol after a habitual meal intake
(6,7,10,28); non-HDL cholesterol is currently not a (Figure 6) occurs 0 to 4 h after meals, at the same time
therapeutic target in U.S. guidelines (29). as a reduction in plasma albumin is observed, but not
An expanded lipid profile should be a standard coinciding with the observed increase in triglycerides
one, with inclusion of Lp(a) measurement. This ge- and remnant cholesterol (35,36). This illustrates that
netic, causal cardiovascular risk factor (14,30,31) the slight reduction in levels of total, LDL, and non-
should be measured at least once in all patients HDL cholesterol is due to fluid intake, and not food
screened for cardiovascular risk (30); it is noteworthy intake, and that this phenomenon therefore will likely
that Lp(a) concentrations vary little over time (<10%) also occur during standard fasting for lipid profiles, as
in any individual. Lp(a) determination should not, water and other nonfatty fluid intake is typically
however, be included in repeated lipid profile allowed (1,2).
JACC VOL. 70, NO. 13, 2017 Nordestgaard 1641
SEPTEMBER 26, 2017:1637–46 Lipid Profile, Fasting Versus Nonfasting

F I G U R E 4 Cholesterol in Atherogenic Lipoproteins in Different Types of Hyperlipidemia

Plasma
Cholesterol
mg/dL mmol/L

463 12

309 8
VLDL (+IDL) Chylomicrons
VLDL + IDL
+ large VLDL
+ chylomicron
remnants
Atherogenic
LDL cholesterol Atherogenic
155 4 cholesterol VLDL + IDL
LDL + chylomicron
remnants
Atherogenic
LDL cholesterol
HDL
HDL HDL
0 0

Isolated Hypercholesterolemia Combined Hypercholesterolemia Severe Hypertriglyceridemia


(Triglycerides < 2 mmol/L) (Triglycerides 2-10 mmol/L) (Triglycerides > 10 mmol/L)
(< 176 mg/dL) (176-880 mg/dL) (> 880 mg/dL)

(Top) The visual appearance of the 3 types of hyperlipidemia: isolated hypercholesterolemia; combined hyperlipidemia; and severe hyper-
triglyceridemia. (Bottom) Distribution of atherogenic cholesterol in different lipoproteins, all shown in orange. For severe hypertriglyceridemia,
some cholesterol is found in chylomicrons and large VLDL that likely are not atherogenic (shown in gold), as these lipoproteins are too large to enter
into the intima (see Figure 3). Neutral cholesterol in HDL is shown in green. Abbreviations as in Figures 2 and 3.

T A B L E 2 Minimal, Standard, and Expanded Lipid Profiles, Nonfasting or Fasting

Measurements in Plasma or Serum as


Part of Lipid Profiles
Minimal Lipid Standard Lipid Expanded Lipid Not Advised as Additional
Measurement Lipid Lipoprotein Apolipoprotein Profile Profile Profile Single Measurement Measurements

Advantage Inexpensive Low cost Relatively low cost None None


Disadvantage No lipoprotein None None Overlooked elevated Expensive, largely
measurements triglycerides and remnant unnecessary
cholesterol measurements
Triglycerides O O O O
Total cholesterol O O O O O
LDL cholesterol* O O O O
HDL cholesterol O O O
Remnant cholesterol† O O O
Non-HDL cholesterol‡ O O O
Lipoprotein(a) O O
ApoB O (O) O
ApoA1 O O
Lipoprotein subfractions O O
Other apolipoproteins O O
Metabolomic phenotyping O O O O

*LDL cholesterol can either be measured directly or calculated by the Friedewald equation if triglycerides are <400 mg/dl (4.5 mmol/l): total cholesterol  HDL cholesterol  triglycerides/2.2 (all in mmol/l;
or  triglycerides/5 with values in mg/dl) (21), with direct measurement of LDL cholesterol at triglyceride concentrations $400 mg/dl (4.5 mmol/l). †Remnant cholesterol (¼ triglyceride-rich lipoprotein
cholesterol) is calculated as total cholesterol  LDL cholesterol  HDL cholesterol, using random, nonfasting or fasting lipid profiles; if LDL cholesterol is also calculated, then remnant cholesterol is
equivalent to triglycerides/2.2 in mmol/l and to triglycerides/5 in mg/dl. ‡Non-HDL cholesterol is calculated as total cholesterol  HDL cholesterol and is equivalent to LDL and remnant cholesterol
combined.
ApoA1 ¼ apolipoprotein A1; ApoB ¼ apolipoprotein B; other abbreviations as in Table 1.
1642 Nordestgaard JACC VOL. 70, NO. 13, 2017

Lipid Profile, Fasting Versus Nonfasting SEPTEMBER 26, 2017:1637–46

In patients at Copenhagen University Hospital, re-


F I G U R E 5 Plasma Triglycerides and Remnant Cholesterol as a Function of Time Since
Last Habitual Meal in Individuals in the General Population
sults were similar with triglycerides measured both in
the nonfasting and fasting states (Figure 7) (5). This
Copenhagen General Population Study was even true for those with the highest triglyceride
N = 92,285 levels or with diabetes.
2

PROS AND CONS OF NONFASTING VERSUS


FASTING LIPID PROFILES

Triglycerides Because fasting has previously been the standard


before blood sampling for a lipid profile in most
mmol/L

countries, the shift toward using nonfasting rather


1
than fasting lipid profiles naturally has been debated
over the last few years (5,38–50): many arguments
and novel data for and against have been presented
Remnant cholesterol from the perspective of the patient, laboratory, and
clinician.
With the current evidence base, it could be argued

0
that the use of nonfasting lipid profiles is evidence-
Fasting 0-1 1-2 2-3 3-4 4-5 5-6 6-7 7-8 driven, whereas continued use of fasting lipid pro-
Time Since Last Meal, Hours files is largely belief-driven (Central Illustration).
Indeed, a main argument for keeping fasting lipid
The mean maximal increase in triglycerides of 26 mg/dl (0.3 mmol/l) and in remnant profiles is that “We have always done it that way!”
cholesterol of 8 mg/dl (0.2 mmol/l), compared with fasting levels, occurs 3 to 4 h after when today, prospective evidence from more than
the last meal. 300,000 individuals is available suggesting that
nonfasting lipid profiles are as good as, if not better
than, fasting lipid profiles in predicting future car-
diovascular events (5,51–54).
For example, in the Emerging Risk Factors Collab-
F I G U R E 6 Mean Maximal Change in Lipids, Lipoproteins, oration, the hazard ratio for predicting coronary heart
and Apolipoproteins in Random, Nonfasting Compared With
disease per 43 mg/dl (1.1 mmol/l) higher non-HDL
Fasting Lipid Profiles in Individuals in the General Population
cholesterol was 1.72 (95% confidence interval [CI]:
Copenhagen General Population Study 1.51 to 1.95) in 20 studies combined using nonfasting
N = 92,285 lipid profiles and including 103,354 subjects, of whom
mmol/L mg/dL
3,829 had an event, whereas the corresponding value
Triglycerides +0.3 +26
in 48 studies combined using fasting lipid profiles in
Total cholesterol –0.2 –8 199,076 subjects, of whom 8,956 had an event, was
1.41 (95% CI: 1.30 to 1.53) (51). Similarly, 3 large ran-
LDL cholesterol –0.2 –8
domized trials of statin therapy used nonfasting lipid
Remnant cholesterol +0.2 +8 profiles (5).
NonHDL cholesterol –0.2 –8 The pros and the new evidence for using random,
nonfasting lipid profiles reflect that many new
Lipoprotein(a) No change
guidelines and consensus statements endorse non-
Apolipoprotein B No change fasting lipid profiles for most patients (3–9,11,12),
whereas a few older guidelines still recommend
HDL cholesterol No change
fasting lipid profiles for most patients (Central
Apolipoprotein A1 No change Illustration) (29).
IMPLICATIONS FOR THE PATIENT. From the
Decreased Increased
Maximal Change After Normal Food Intake perspective of the patient, a random, nonfasting lipid
profile is practical compared with a fasting lipid pro-
file because it does not interfere with the patient’s
These changes all are clinically insignificant. Adapted with
permission from Nordestgaard et al. (5). Abbreviations as in normal life and allows going to the laboratory for the
Figures 2 and 3. blood draw at any time of the day (Central
Illustration). Nonfasting sampling will also be safe,
JACC VOL. 70, NO. 13, 2017 Nordestgaard 1643
SEPTEMBER 26, 2017:1637–46 Lipid Profile, Fasting Versus Nonfasting

whereas fasting for some patients with diabetes on


F I G U R E 7 Comparison of Concentrations of Plasma Triglycerides Measured in the
antidiabetic medication may lead to risk of hypogly- Random, Nonfasting, and Fasting States in the Same Patients
cemia (55). Nonfasting lipid profiles will be time-
saving and thus cost-saving for patients, because Copenhagen University Hospital 2011-2015
the need to return another day for a fasting lipid N
profile is eliminated. All 5538
Triglycerides, mmol/L
IMPLICATIONS FOR PROGNOSTIC AND DIAGNOSTIC < 1.1 1793
OPTIONS. From the perspective of the laboratory, a
1.1-1.5 1582
fasting lipid profile is thought to be superior to a
nonfasting one because it can be standardized and 1.6-2.5 1454

leads to slightly less variation in the measured ana- 2.6-4.0 534


lytes (49), most importantly triglycerides. Interest-
> 4.0 175
ingly, however, the median triglyceride values and
Diabetes
95% CIs were similar in 5,538 patients who had tri- No 4711
glycerides measured both in the nonfasting and
fasting states (Figure 7). Also, under nonstandardized, Yes 418

random, nonfasting conditions, plasma triglycerides


0 1 2 3 4 5 6 7
on average only increase by 26 mg/dl (0.3 mmol/l) at
Triglycerides, mmol/L
4 h after a habitual meal (Figures 5 and 6). Such minor
Nonfasting Fasting
changes are clinically unimportant, because a clini-
cian is only interested in whether plasma tri-
The fluctuation in plasma triglycerides is similar in the fasting and nonfasting states, even
glycerides are 176 mg/dl (2 mmol/l) versus say
in those with the highest triglycerides or with diabetes. Most patients were outpatients;
440 mg/dl (5 mmol/l), whereas a difference between
however, a minor fraction were likely inpatients, many of whom may experience reduced
176 mg/dl (2 mmol/l) and 202 mg/dl (2.3 mmol/l) is appetite and, depending upon diagnosis (and state of recovery), were likely receiving
clinically insignificant. clear liquids/soft diet with low fat intake at the time of the nonfasting and/or fasting
Another argument often presented against elimi- blood draw. For such patients, the total fat intake likely is lower than in the free-living
state and, therefore, would not be generalizable to a general population. Adapted with
nation of fasting lipid profiles is that, in many coun-
permission from Nordestgaard et al. (5).
tries, other measurements in the blood also require
fasting before blood sampling. In Denmark, however,
there is no requirement for fasting for any blood
measurements, except for fasting before an oral
F I G U R E 8 Historical Development of Endorsement of Random, Nonfasting Lipid
glucose tolerance test, and random, nonfasting gly-
Profiles by Societies, Guidelines, and Statements
cosylated hemoglobin A 1c is used to diagnose and
monitor diabetes, rather than fasting glucose.
Endorsement of nonfasting lipid profiles by societies, guidelines, & statements
Several publications endorsing use of nonfasting
Year Region Society/guideline/statement
lipid profiles for the majority of patients also mention 2017 US AACE/ACE: American Association of Clinical Endocrinologists
situations where a fasting lipid profile, or at least a & American College of Endocrinology
fasting triglyceride measurement, may theoretically 2016 Brazil Consensus of five medical societies
2016 Europe ESC/EAS: European Society of Cardiology & European
improve diagnostic accuracy (3–7,9,11,12). Although Atherosclerosis Society
each of these suggestions for using fasting lipid pro- 2016 Canada CCS: Canadian Cardiovascular Society
files in certain situations may sound reasonable, none 2016 Canada CHEP: Canadian Hypertension Education Program
2016 Europe EAS/EFLM: European Atherosclerosis Society & European
are supported by strong scientific evidence, but Federation of Clinical Chemistry and Laboratory Medicine
rather are likely driven by beliefs of some of the au-
2014 US VA/DoD: Veterans Affairs & US Department of Defense
thors of the various guidelines and statements. 2014 UK NICE: National Institute for Health and Care Excellence
Therefore, my recommendation is to use nonfasting
2011 US AHA: American Heart Association
lipid profiles widely, whereas any physician, natu-
2009 Denmark DSKB: Danish Society for Clinical Biochemistry
rally, is free to agree with an individual patient to fast
for a given lipid profile. Before 2009 essentially all societies, guidelines, and statements either required
Taken together, and given the higher and higher fasting before lipid profile measurement or did not mention requirements

demands for fast, efficient, and inexpensive health


care services all over the world, it is important that Particularly from 2016 and onwards, the use of nonfasting lipid profiles has been
we consider what is most convenient for patients, endorsed widely.
laboratories, and clinicians alike, while, at the same
1644 Nordestgaard JACC VOL. 70, NO. 13, 2017

Lipid Profile, Fasting Versus Nonfasting SEPTEMBER 26, 2017:1637–46

C E NT R AL IL L U STR AT IO N Comparison of Fasting and Nonfasting Lipid Profiles

Nordestgaard, B.G. J Am Coll Cardiol. 2017;70(13):1637–46.

Direct comparison of arguments for and against use of random, nonfasting, and fasting blood sampling. Nonfasting blood sampling can occur anytime during the 24-h
cycle, irrespective of what and when the individual ate before blood sampling. By contrast, a fasting blood sample can only be drawn after a period without food
intake for 8 or more hours, which often means that a natural small fast of a few hours in the early morning will be extended, possibly until noon, before the blood is
drawn.

time, being perfectly fine clinically, and maybe IMPLICATIONS FOR THERAPEUTIC OPTIONS. Because
focus less on exactly how standardly and precisely statin therapy (and other lipid-lowering therapy)
we can measure an analyte (50). In addition, use is decided on the basis of an individual’s global
of nonfasting lipid profiles will improve patient flow cardiovascular risk, including the presence of car-
in laboratories, as it eliminates large numbers of diovascular disease, familial hypercholesterolemia,
people all coming for blood draws early in the and diabetes, and not just on plasma lipid values in
morning. all major guidelines (4,6,7,11,12,29), minor changes in
JACC VOL. 70, NO. 13, 2017 Nordestgaard 1645
SEPTEMBER 26, 2017:1637–46 Lipid Profile, Fasting Versus Nonfasting

the lipid profile from fasting to nonfasting conditions HISTORICAL DEVELOPMENT OF


(Figures 5 to 7) will only affect a few individuals NONFASTING LIPID PROFILES
regarding the decision to start a statin or not. Also,
many guidelines use total and HDL cholesterol for The Danish Society for Clinical Chemistry recom-
risk calculations, and these measurements are mini- mended nationwide use of nonfasting lipid profiles in
mally affected by nonfasting versus fasting states. 2009 (3), followed by similar endorsement in 2011 by
Nevertheless, many guidelines use LDL cholesterol the American Heart Association (10) and, in 2014, by
to monitor pharmacological treatment and as goals the U.K. National Institute for Health and Care
for treatment. In individuals with borderline LDL Excellence guidelines (4) and guidelines from Veter-
cholesterol, the lower LDL cholesterol observed ans Affairs and U.S. Department of Defense (Figure 8)
mainly 0 to 4 h after a habitual meal due to liberal (11). This was followed by similar recommendations
fluid intake and hemodilution (35), particularly in in 2016 by the European Atherosclerosis Society and
patients with diabetes (36), needs to be considered European Federation of Clinical Chemistry and Lab-
when using nonfasting lipid profiles to decide oratory Medicine, in a joint consensus statement with
whether to commence a statin or titrate its dose; detailed discussion of the evidence, as well as the
however, the same is true for fasting lipid profiles, clinical implications of using nonfasting, rather than
typically with no restrictions on water intake (1,2). fasting lipid profiles (5). Later in 2016, this was fol-
IMPLICATIONS FOR CLINICAL TRIALS. Nonfasting, lowed by a similar endorsement for nonfasting lipid
compared with fasting lipid profiles will also help profiles by the Canadian Hypertension Education
recruit and retain patients in lipid-lowering trials, Program guidelines (8), the Canadian Cardiovascular
and likely will reduce trial costs. This is because Society guidelines (7), the European Society of Car-
ethical committees in many countries do not allow diology and the European Atherosclerosis Society
patients to be asked to fast before the first study visit, guidelines for the management of dyslipidemias (6),
which means an extra study visit simply for the lipid and by consensus of 5 medical societies in Brazil (9).
profile. Also, the use of nonfasting lipid profiles dur- Finally, in 2017, endorsement of the use of nonfasting
ing follow-up visits will be more practical for study lipid profiles came from the American Association of
participants, and will allow study visits at any time of Clinical Endocrinologists and the American College of
the day, whatever suits the individual study partici- Endocrinology (12).
pant. Finally, because nonfasting lipid profile mea-
surements are used more and more commonly in ADDRESS FOR CORRESPONDENCE: Dr. Børge G.
clinical practice, it is equally important that future Nordestgaard, Clinical Biochemistry, Herlev Hospital,
lipid-lowering trials are conducted under nonfasting Herlev Ringvej 75, 2730 Herlev, Denmark. E-mail:
conditions to match the clinical reality of the future. boerge.nordestgaard@regionh.dk.

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