Low incidence of cardiovascular disease among the Inuit*/what is the
*, T. Kue Young
, Robert A. Hegele
Division for Research in Greenland, National Institute of Public Health, Svanemøllevej 25 Copenhagen
Department of Public Health Sciences, University of Toronto, Toronto, Canada
Robarts Research Institute, London, Canada
Received 8 May 2002; received in revised form 26 September 2002; accepted 3 October 2002
Background: The notion that the incidence of ischemic heart disease (IHD) is low among the Inuit subsisting on a traditional
marine diet has attained axiomatic status. The scientific evidence for this is weak and rests on early clinical evidence and uncertain
mortality statistics. Methods: We reviewed the literature and performed new analyses of the mortality statistics from Greenland,
Canada, and Alaska. Findings: The evidence for a low mortality from IHD among the Inuit is fragile and rests on unreliable
mortality statistics. Mortality from stroke, however, is higher among the Inuit than among other western populations. Based on the
examination of 15 candidate gene polymorphisms, the Inuit genetic architecture does not obviously explain putative differences in
cardiovascular disease prevalence. Interpretation: The mortality from all cardiovascular diseases combined is not lower among the
Inuit than in white comparison populations. If the mortality from IHD is low, it seems not to be associated with a low prevalence of
general atherosclerosis. A decreasing trend in mortality from IHD in Inuit populations undergoing rapid westernization supports
the need for a critical rethinking of cardiovascular epidemiology among the Inuit and the role of a marine diet in this population.
#2002 Elsevier Science Ireland Ltd. All rights reserved.
Keywords: Inuit; Cardiovascular disease; Ischemic heart disease; Stroke; Atherosclerosis; Marine diet; Mortality
Bertelsen in his classic 1940 description of the disease
and mortality pattern among the Inuit of Greenland
stated that ‘arteriosclerosis and degeneration of the
myocardium are quite common conditions among the
Inuit, in particular considering the low mean age of the
population.’. Bertelsen, who is considered the father
of epidemiology in Greenland, based his opinion both
on many years of clinical practice in Greenland and on
the reports of medical officers since 1838. Despite this
historical background, the unreferenced 1975 statement
‘coronary atherosclerosis is almost unknown among
these people [the Greenland Eskimos] when living in
their own cultural environment’  has attained axio-
matic status in the atherosclerosis literature . The
present article will explore whether this latter widely
accepted opinion of the medical research community is
valid in the light of current knowledge.
The Inuit are a numerically small people scattered
along the coastline of Alaska, Northern Canada, and
Greenland with a small contingent in eastern Siberia.
They traditionally subsisted on marine mammals and
fish but post World War 2 development has impelled
their lifestyle and diet to that of the industrialized world.
The consumption of marine species is, however, still
much higher than in USA, Canada, and Denmark. Our
own unpublished studies from Greenland show that in
1993, 62% of the Inuit in Greenland consumed seal meat
and 64% fish at least once a week; by 1999 these
proportions had decreased to 46 and 58%, respectively.
In Denmark, the proportion of people who consumed
fish at least once a week remained stable at 45% from
1995 to 2001  and seal or other marine mammals are
not consumed at all.
* Corresponding author. Tel.: /45-3927-12-22; fax: /45-3927-30-
E-mail address: firstname.lastname@example.org (P. Bjerregaard).
Atherosclerosis 166 (2003) 351 /357
0021-9150/02/$ - see front matter #2002 Elsevier Science Ireland Ltd. All rights reserved.
PII: S 0 0 2 1 - 9 1 5 0 ( 0 2 ) 0 0 3 6 4 - 7
2. Material and methods
Literature about cardiovascular disease among the
Inuit was identified in MEDLINE and existing biblio-
graphies on Inuit health. Additional information was
obtained by tracing the primary references cited in these
publications. We furthermore attempted to collect and
analyze officially collected mortality data in three
jurisdictions with large Inuit populations, i.e. Green-
land, Northern Canada, and Alaska and compare these
with mortality statistics from Denmark, Canada and the
USA, respectively. Due to the use of different standard
populations (1940 USA population for Alaska Natives;
1991 Canada population for Canadian Inuit; and the
IARC World Population for Greenlanders), the three
regions are not directly comparable. Without access to
raw data from Alaska and Canada with which to
compute age-standardization using a single standard,
comparison is only valid between the regional Inuit
population and the respective national populations of
USA, Canada, and Denmark.
Mortality analyses were based on the mortality
register for Greenland at the Danish National Institute
of Public Health. This computerized register covers all
deaths in Greenland since 1968 and has information
among other things on causes of death and place of birth
as a proxy measure of ethnicity. For 1968 /1993, causes
of death were coded according to ICD-8; from 1994
ICD-10 was used. Ischemic heart disease (IHD) was
defined as ICD-8 codes 410 /414 or ICD-10 codes I20/
I25.9; stroke as 430 /438 and I60/I69.9, respectively.
For the years 1965/1967, we used published mortality
information from the annual reports of the Chief
Medical Officer in Greenland . Population figures
were obtained from the censuses of 1965 and 1970 [6,7]
and, since 1976, from an annually updated population
register . This register is based on the population
register of Denmark, in which each individual is
assigned a unique identification number that follows
the individual from birth to death. It is very compre-
hensive and accurate. The analyses included only
persons born in Greenland, as a proxy for Inuit
ethnicity, with permanent residence in Greenland at
the time of death. Greenlanders who were permanent
residents in Denmark, and Danes living in Greenland
were excluded. Mortality analyses for Denmark were
based on the Danish mortality register at the Danish
National Institute of Public Health and on population
figures from the population register of Denmark .In
Table 2, mortality from IHD was adjusted as suggested
by Murray and Lopez . The adjustment is based on
the finding that, in many countries, a high proportion of
cardiovascular deaths are attributed to ill-defined causes
such as heart failure, general atherosclerosis, or unde-
fined heart disease /so-called ‘garbage codes’/while in
other countries with a supposedly high validity of
mortality statistics this proportion is much lower. In
order to correct for the likely undercoding of IHD in the
former countries a standard algoritm was applied to
increase the estimate of mortality from IHD. Rates were
age-standardized by the direct method to the World
Standard Population . The calculation of confidence
intervals was based on the Poisson distribution.
While Canadian Inuit (or any ethnic group) cannot be
identified in death certificates in Canada, Inuit consti-
tute over 85% of the population of the Nunavut
Territory (formerly part of the Northwest Territories)
and 90% of the Nunavik region in the province of
Que´bec. Age-standardized mortality rates for cardiovas-
cular diseases are available online for these two health
regions in Statistics Canada’s Health Indicators 2001
(http://www.statcan.ca). Inuit-specific data require
special data linkage of administrative databases and are
not routinely reported by the various government
Mortality statistics for Alaska are generally reported
under the broad rubric of ‘American Indians and Alaska
Natives’. Further breakdown of the Alaska Native
category into specific Indian tribes, Eskimos (Yupik
and Inupiat) and Aleuts is not consistently available
from either the State of Alaska or the US Indian Health
Service. However, it is also possible, as in Canada, to
obtain online age-standardized mortality rates for
cardiovascular disease in specific census areas in Alaska,
which have a predominantly Eskimo population (http://
www.hss.state.ak.us). There are six such areas where
Eskimos constitute over 90% of the Native population
and more than 65% of the total all-race population:
Bethel (83% of total all-race population), Dillingham
(69%), Nome (78%), North Slope (72%), Northwest
Arctic (84%), and Wade Hampton (88%) . IHD was
defined as ICD-9 codes 402, 410 /414, and 429.2 and
accordingly included some unspecific diagnoses con-
trary to the data from Greenland.
In Alaska, early clinical evidence from before 1950
indicated an almost total absence of cardiovascular
disease . In contrast, early clinical evidence from
Canada and Greenland indicated that the incidence of
arteriosclerosis and cardiovascular diseases was similar
P. Bjerregaard et al. / Atherosclerosis 166 (2003) 351 /357352
to that of western countries or higher [1,16,17], while
one study from Greenland reported a lower incidence
 (Table 1). A total of 486 autopsies taken from three
studies from Alaska and Canada during the 1960s and
70s concluded that arteriosclerosis and myocardial
infarction were present among the Eskimos, but the
authors were reluctant to draw any conclusion about the
relative incidence due to small numbers [19 /21]. Mor-
tality statistics and studies based on death certificates
from 1955/1965 showed a low mortality from all
cardiovascular diseases among the Alaska Eskimos
compared with the general population of the USA
, while mortality from IHD among those aged 65
and above was higher in Greenland than in Denmark
More recent studies from Alaska, Canada, and
Greenland based on routine reporting of causes of
death concurred that age-adjusted IHD mortality was
lower among the Inuit than among white comparison
populations [24/27]. The relative risk for IHD mortality
was /0.5 in Alaska Eskimos compared with US whites
. Our own studies, which have been extensively cited
in support of a low IHD mortality in Greenland,
compared mortality among the Greenland Inuit from
1968 to 1983 with the general population in Denmark in
1980 and found relative risks of /0.5 for men and
women [24,28]. Mortality from other heart diseases was
higher than in the white comparison populations in both
Alaska, Canada, and Greenland. Cerebrovascular dis-
ease mortality was similar among the Inuit in Alaska
and Canada and the white populations with which they
were compared, while it was significantly higher among
Greenlanders than among Danes. Hospital records from
Greenland and Canada likewise showed low incidences
of IHD and high incidences of cerebrovascular disease
X-ray and ultrasound studies showed that Inuit had
almost the same degree and extent of atherosclerosis in
the abdominal, femoral, and carotid arteries as the white
comparison populations [16,17,30,31]. However, an
autopsy study designed to specifically study coronary
atherosclerosis showed significantly higher proportions
of raised lesions in the coronary arteries of mostly
forensic cases among Alaska non-natives than among
Alaska Natives, while the differences were not signifi-
cant for the abdominal aorta . The study, however,
Studies of ischaemic heart disease and arteriosclerosis among the Inuit
Author Region Data source Conclusion
Rabinowitch, 1936  Eastern Canadian
Clinical examination and
Data definitively disprove the alleged absence of arteriosclerosis
among the Eskimo
Bertelsen, 1940  Greenland Clinical observations Arteriosclerosis and degeneration of the myocardium are quite
common conditions among the Greenlanders
¨m, 1951  Northwest Green-
Clinical examination and
The incidence of clinical manifestations of arteriosclerosis is
lower than in Korpo, Finland
Rodahl, 1954  Alaska X-ray examination
Same degree of arteriosclerosis among Eskimos and white
Gottman, 1960  Alaska Autopsy (n57) Cardiovascular disease of an arteriosclerotic type is not
Lederman et al., 1962  Canada Autopsy (n90) Eskimos do have atherosclerosis
Maynard et al., 1967  Alaska Death certificates Mortality from heart diseases lower among Alaska Eskimos
than among the general population of USA
Arthaud, 1970  Alaska Autopsy (n339) Notes cases of myocardial infarction and atherosclerosis. No
comparisons with other populations
Clausen, 1974  Greenland Mortality statistics Coronary heart deaths more frequent in Greenland than in
Kroman and Green, 1980  Northwest Green-
Hospital records Very low incidence of acute myocardial infarction
Bjerregaard, 1988 , Bjerre-
gaard and Dyerberg, 1988 
Greenland Mortality statistics Relative risk for IHD compared with Denmark 0.5
Middaugh, 1990  Alaska Mortality statistics Alaska Natives had lower mortality from cardiovascular disease
and atherosclerosis than other Alaskans. Relative risk 0.7
Hansen et al., 1990  Northwest Green-
Ultrasound (n61) Native Greenlanders had almost the same degree and extent of
atherosclerosis in the carotid and femoral arteries as the Danes
Ingeman-Nielsen, 1990  Greenland X-ray (n268) Same prevalence of calcified lesions in the abdominal aorta as
Young et al., 1993  Northwest Terri-
Mortality statistics Mortality from IHD lower in NWT (all ethnic groups) than in
Davidson et al., 1993  Alaska Mortality statistics Relative risk for IHD 0.5 compared with Alaska whites
Newman et al., 1993  Alaska Autopsy (n103) Fewer raised lesions in coronary arteries and aorta of Alaska
Natives compared with whites
P. Bjerregaard et al. / Atherosclerosis 166 (2003) 351 /357 353
tells us little about the clinically important differences in
the older age groups. Autopsy studies from Greenland
led to the hypothesis that there is a U-shaped dose-
response association between fat tissue n
turated fatty acids (marine diet) and atherosclerosis and
3.1. An update of mortality analyses
Table 2 shows cardiovascular mortality rates in
Greenland and Denmark age-adjusted to the World
Standard Population. The population of Denmark is a
homogeneous Caucasian population and the vital regis-
tration is comprehensive and reliable. The mortality
from all non-stroke cardiovascular diseases was similar
in Greenland and Denmark while mortality from stroke
was higher in Greenland Inuit throughout. In the
absence of autopsies, it is risky to analyze cause-specific
mortality, but the table indicates that the reported
mortality from IHD was consistently lower in Green-
land than in Denmark. A decreasing secular trend was
most obvious for IHD.
A substantial proportion of non-stroke cardiovascu-
lar deaths was attributed to unspecific ‘garbage’ codes:
32% compared with B/15% in countries with good
mortality statistics . This suggests that there may be
a rather large number of hidden deaths from IHD. After
adjustment for this the IHD mortality in Greenland was
not significantly lower than in Denmark in 1965 /1974
and 1995/1998, and only slightly lower in 1975/1994.
In Canada’s two regions with predominantly Inuit
populations, Nunavik and Nunavut, the age-adjusted
mortality rates in 1995/1997 for all cardiovascular
diseases were 431 (95% CI: 223, 639) per 100 000
person-years and 216 (141, 290), respectively, which
was not significantly different from the all-Canadian
rate of 246 (245, 247) . Because of the small
population size and low number of events, further
breakdown into IHD and stroke deaths in Nunavut
and Nunavik results in very wide confidence intervals
(Table 3). There is, however, some support based on
vital statistics, that relative to all-Canadians, IHD
mortality is lower among the Inuit whereas for stroke
the mortality rate is higher.
Alaska Natives (50% of whom are Eskimos) had an
age-adjusted mortality rate for IHD that was not
different from that of all Alaskans, but a stroke rate
that was higher (Table 3). Figures are not available
for Inuit separately, but in 1990 /1998 among the six
predominantly Eskimo census areas the age-adjusted
mortality rate for IHD was slightly lower than for all
3.2. Cardiovascular genetics
The genetic component of atherosclerosis is complex,
with the contributions of numerous genes interacting
with environmental determinants . Alleles of many
different candidate genes havebeenvariably shown to
be associated with atherosclerosis and its intermediate
traits. Given the caveats of genetic association studies
for complex diseases, and for atherosclerosis in parti-
cular, we nonetheless examined whether ‘deleterious
Reported mortality from cardiovascular disease in Greenland and
Greenland Denmark Ratio CI (95%)
1965 /1974 135 55 2.45 2.14 /2.81
1975 /1984 106 45 2.36 2.08 /2.65
1985 /1994 111 41 2.71 2.44 /3.00
1995 /1998 105 39 2.69 2.28 /3.15
Non-stroke cardiovascular disease (IHD and other )
1965 /1974 270 253 1.07 0.97 /1.18
1975 /1984 195 201 0.97 0.89 /1.06
1985 /1994 179 170 1.05 0.97 /1.14
1995 /1998 159 137 1.16 1.01 /1.32
1965 /1974 179 211 0.85 0.75 /0.96
1975 /1984 84 161 0.52 0.45 /0.60
1985 /1994 74 126 0.59 0.51 /0.67
1995 /1998 65 90 0.72 0.58 /0.89
1965 /1974 206 211 0.98 0.87 /1.09
1975 /1984 120 161 0.75 0.66 /0.84
1985 /1994 112 126 0.89 0.80 /0.99
1995 /1998 98 90 1.09 0.91 /1.29
Adjusted to the World Standard Population by direct standardiza-
tion. Mortality rates per 100 000 person-years.
ICD-8 410 /414; ICD-10 I20 /I25.9.
Adjusted according to Murray 1996 .
Mortality from cardiovascular diseases among the Inuit in Canada and
Alaska in the 1990s
Indigenous All Ratio CI (95%)
Nunavik, Canada, 1995 /
200 48 4.13 1.07 /10.68
Nunavut, Canada not available ///
Alaska Natives, 1993 /1998
36 27 1.36 1.17 /1.57
not available ///
Nunavik, Canada not available ///
Nunavut, Canada, 1995 /
40 136 0.29 0.06 /0.87
Alaska Natives, 1993 /1998
79 79 0.99 0.88 /1.11
Alaska Inuit, 1990 /1998
70 82 0.85 0.74 /0.96
Adjusted to different standard populations.
Adjusted to the Canadian population 1991.
Adjusted to the US population 1940.
Six census areas with predominantly Inuit population.
P. Bjerregaard et al. / Atherosclerosis 166 (2003) 351 /357354
alleles’ of candidate genes for atherosclerosis and related
traits varied in frequency between Inuit and geographi-
cally matched Canadians of European descent as con-
trols. Of 15 alleles examined, we found that in Inuit
compared with Canadians of European descent, five
were significantly less frequent, five were significantly
more frequent, and five were not different in frequency,
consistent with, respectively, decreased risk, increased
risk, and no difference in risk [34 /43] (Table 4). This
suggested that differences in genetic architecture do not
clarify possible differences in cardiovascular disease
prevalence, although such an analysis is admittedly
very preliminary and limited. The genetic variants tested
may have had little biological association with disease in
the Inuit, while unmeasured genomic variants could be
playing a more important role. In addition, genetic
associations can be ‘context dependent’ and it cannot be
determined whether certain of the genetic variants
studied might be relatively more important determinants
of cardiovascular disease in the Inuit. Full understand-
ing of the genetic component of cardiovascular disease
in the Inuit will require more effort because of con-
founding factors such as context-dependency, small
genetic effects, non-mendelian inheritance, gene /gene
interactions and gene /environment interactions .
Even if there was more confidence in the Inuit ‘genetic
profile’ as being consistent with either susceptibility or
resistance to atherosclerosis, it is very possible that
lifestyle factors could either attenuate or amplify the
influence of the complex genetic component.
The evidence in the 1970s for a low IHD incidence
among the Inuit was based on scattered clinical ob-
servations and the routine mortality statistics from
Alaska [15,22], while similar observations from Canada
and Greenland indicated an incidence of IHD that was
similar to white populations [1,16,17,23]. This weak
evidence has been substantiated only to a certain degree
in later studies. The current scientific evidence from
clinical, X-ray and ultrasound studies seem to allow the
cautious conclusion that atherosclerosis has been pre-
sent among the Inuit at levels by and large similar to
those of white populations of North America and
Europe, at least in the Eastern Arctic. However, autopsy
studies from Greenland showed a poor correlation
between arteriosclerosis of the large arteries and the
Our updated analyses of mortality indicate that the
mortality from IHD was similar among the Inuit and
the southern comparison populations or slightly lower.
Mortality from stroke was higher among the Inuit in all
three areas, in particular in Greenland. A serious
argument against the validity of the results concerning
mortality is the low autopsy rate and the assumed low
general validity of the diagnoses at least in Greenland
. It is questionable to what extent the differentiation
among the specific cardiovascular diagnoses is based on
solid clinical evidence and to what extent it is mere
conjecture*/possibly influenced by the presupposition
that IHD is rare among the Inuit. Adjustment for
Allele frequencies of atherosclerosis candidate genes in Canadian Inuit and white controls
gene Allele Inuit (N175) Europeans (N92)
Consistent with decreased risk in Inuit
ACE angiotensin converting enzyme intron 16 deletion 0.31* 0.46
F5 clotting factor V Q506 0* 0.02
MTHFR methylenetetra-hydrofolate reductase 677T 0.06* 0.24
HFE hemochromatosis Y282 0* 0.09
MBL mannose binding lectin non-A 0.09* 0.23
Consistent with increased risk in Inuit
AGT angiotensinogen T235 0.82* 0.45
APOE apolipoprotein E E4 0.23* 0.13
PON1 paraoxonase-1 R192 0.70* 0.35
FABP2 intestinal fatty acid binding protein T54 0.35* 0.25
ADRB3 beta-3 adrenergic receptor R64 0.30* 0.08
Consistent with no difference in risk among Inuit
HL hepatic lipase 480C 0.60 0.68
APOC3 apolipoprotein CIII 455C 0.47 0.44
PON2 paraoxonase-2 G148 0.29 0.25
PPP1R3 protein phosphatase-1 (skeletal muscle) deletion 0.33 0.29
GNB3 G-protein beta-3 subunit 825T 0.50 0.44
*, allele frequency is significantly different (PB0.05).
P. Bjerregaard et al. / Atherosclerosis 166 (2003) 351 /357 355
‘garbage codes’ reduced the difference between IHD
mortality in Greenland and Denmark considerably.
Based on the above, we find the hypothesis that
mortality from IHD is low among the Inuit compared
with western populations insufficiently founded. Since
mortality from stroke was higher among the Inuit and
Alaska Natives than in the white comparison popula-
tions, a general statement that mortality from cardio-
vascular disease is high among the Inuit seems more
warranted than the opposite.
In addition to our own genetic studies among the
Canadian Inuit, studies in Greenland have shown a low
prevalence of certain apolipoprotein (a) isoforms con-
sistent with a low genetic disposition for IHD , but
the genotype of the Inuit does not unequivocally
indicate a population with a high or low predisposition
The decrease in mortality from IHD in Greenland
since 1965 is surprising in view of the rapid westerniza-
tion of the country during the same period. A similar
trend was present among Alaska Natives . If this
represents a real decrease in the incidence of IHD and
not just a change in diagnostic habits or improved
possibilities for treatment, it will be difficult to maintain
the importance of the traditional marine diet for a low
incidence of atherosclerosis and IHD in these popula-
tions. Studies from 1952 estimated that 54% of the daily
energy intake in the villages of Northwest Greenland
came from traditional food  compared with 25% in
1991 . During the same period, according to the
censuses, the proportion of the Greenlandic population
living in the villages, where the consumption of tradi-
tional food is considerably higher than in towns,
decreased from 51 to 21%. However, assuming that
westernization reduces the proportion of individuals
with a very high intake of traditional food, the findings
are consistent with the hypothesis that the association
between dietary intake of marine lipids and athero-
sclerosis is U-shaped. Although the genetic changes
must be small over the time span considered, what little
change that has been is likely to be towards greater
European admixture and thus implicitly higher inci-
dence of IHD.
Clinical trials in non-aboriginals indicate a cardiovas-
cular survival benefit that is associated with dietary
supplementation with fish or marine oils among patients
surviving a recent myocardial infarction [48,49]. The
pathophysiological basis is probably not through an
anti-atherogenic but through an anti-arrhytmic effect
. In some studies of general populations fish
consumption appears to be associated with reduced
IHD mortality in high-risk populations only  while
other studies show an effect also among those without
evidence of prior cardiovascular disease .Itis
obvious that the epidemiology of cardiovascular disease
among the Inuit and the complicated interactions
among marine lipids, other environmental factors, and
genetic factors are not yet fully understood.
Mortality from stroke is similar or probably higher
among the Inuit than among other western populations.
The evidence for a low mortality from IHD is fragile
and rests on unreliable mortality statistics. If present, it
seems not to be associated with a low prevalence of
general atherosclerosis. The life style of the Inuit is
rapidly changing towards an increased cardiovascular
risk factor profile . Physical activity declines, obesity
is widespread, the reliance on imported food increases,
and the smoking rates are alarmingly high. We may still
obtain a picture of the determinants of the traditional
Inuit cardiovascular disease and mortality pattern by
studying the life style of the elders in an historical
perspective and following their disease and mortality
pattern over the coming years, but time is running out.
In a few years from now we may not be able to find out
why the Inuit were protected against IHD /if ever they
Kue Young is a Senior Investigator of the Canadian
Institutes of Health Research. R.A. Hegele holds a
Canada Research Chair in Human Genetics and a
Career Investigator Award from the Heart and Stroke
Foundation of Ontario. General support from the
Canadian Institutes of Health Research and the Black-
burn Group are acknowledged.
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