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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. We reviewed the literature and performed new analyses of the mortality statistics from Greenland, Canada, and Alaska. 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. 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.
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Low incidence of cardiovascular disease among the Inuit*/what is the
evidence?
Peter Bjerregaard
a,
*, T. Kue Young
b
, Robert A. Hegele
c
a
Division for Research in Greenland, National Institute of Public Health, Svanemøllevej 25 Copenhagen
Ø
, Denmark
b
Department of Public Health Sciences, University of Toronto, Toronto, Canada
c
Robarts Research Institute, London, Canada
Received 8 May 2002; received in revised form 26 September 2002; accepted 3 October 2002
Abstract
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
1. Introduction
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.’[1]. 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’ [2] has attained axio-
matic status in the atherosclerosis literature [3]. 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 [4] and seal or other marine mammals are
not consumed at all.
* Corresponding author. Tel.: /45-3927-12-22; fax: /45-3927-30-
95
E-mail address: p.bjerregaard@dadlnet.dk (P. Bjerregaard).
Atherosclerosis 166 (2003) 351 /357
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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.
2.1. Greenland
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 [5]. Population figures
were obtained from the censuses of 1965 and 1970 [6,7]
and, since 1976, from an annually updated population
register [8]. 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 [9].In
Table 2, mortality from IHD was adjusted as suggested
by Murray and Lopez [10]. 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 [11]. The calculation of confidence
intervals was based on the Poisson distribution.
2.2. Canada
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)[12]. Inuit-specific data require
special data linkage of administrative databases and are
not routinely reported by the various government
agencies.
2.3. Alaska
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)[13]. 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%) [14]. 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.
3. Results
In Alaska, early clinical evidence from before 1950
indicated an almost total absence of cardiovascular
disease [15]. 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
[18] (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
[22], while mortality from IHD among those aged 65
and above was higher in Greenland than in Denmark
[23].
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
[26]. 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
[27,29].
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 [32]. The study, however,
Table 1
Studies of ischaemic heart disease and arteriosclerosis among the Inuit
Author Region Data source Conclusion
Rabinowitch, 1936 [16] Eastern Canadian
Arctic
Clinical examination and
X-ray (n389)
Data definitively disprove the alleged absence of arteriosclerosis
among the Eskimo
Bertelsen, 1940 [1] Greenland Clinical observations Arteriosclerosis and degeneration of the myocardium are quite
common conditions among the Greenlanders
Ehrstro
¨m, 1951 [18] Northwest Green-
land
Clinical examination and
X-ray (n1073)
The incidence of clinical manifestations of arteriosclerosis is
lower than in Korpo, Finland
Rodahl, 1954 [17] Alaska X-ray examination
(n84)
Same degree of arteriosclerosis among Eskimos and white
people
Gottman, 1960 [19] Alaska Autopsy (n57) Cardiovascular disease of an arteriosclerotic type is not
uncommon
Lederman et al., 1962 [20] Canada Autopsy (n90) Eskimos do have atherosclerosis
Maynard et al., 1967 [22] Alaska Death certificates Mortality from heart diseases lower among Alaska Eskimos
than among the general population of USA
Arthaud, 1970 [21] Alaska Autopsy (n339) Notes cases of myocardial infarction and atherosclerosis. No
comparisons with other populations
Clausen, 1974 [23] Greenland Mortality statistics Coronary heart deaths more frequent in Greenland than in
Denmark
Kroman and Green, 1980 [29] Northwest Green-
land
Hospital records Very low incidence of acute myocardial infarction
Bjerregaard, 1988 [24], Bjerre-
gaard and Dyerberg, 1988 [28]
Greenland Mortality statistics Relative risk for IHD compared with Denmark 0.5
Middaugh, 1990 [25] Alaska Mortality statistics Alaska Natives had lower mortality from cardiovascular disease
and atherosclerosis than other Alaskans. Relative risk 0.7
Hansen et al., 1990 [30] Northwest Green-
land
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 [31] Greenland X-ray (n268) Same prevalence of calcified lesions in the abdominal aorta as
among Danes
Young et al., 1993 [27] Northwest Terri-
tories, Canada
Mortality statistics Mortality from IHD lower in NWT (all ethnic groups) than in
all Canada
Davidson et al., 1993 [26] Alaska Mortality statistics Relative risk for IHD 0.5 compared with Alaska whites
Newman et al., 1993 [32] 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
/3 polyunsa-
turated fatty acids (marine diet) and atherosclerosis and
stroke [33].
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 [10]. 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) [12]. 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)[13]. 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
Alaskans.
3.2. Cardiovascular genetics
The genetic component of atherosclerosis is complex,
with the contributions of numerous genes interacting
with environmental determinants [34]. 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
Table 2
Reported mortality from cardiovascular disease in Greenland and
Denmark
Greenland Denmark Ratio CI (95%)
Cerebrovascular disease
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
IHD
a
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
IHD
b
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.
a
ICD-8 410 /414; ICD-10 I20 /I25.9.
b
Adjusted according to Murray 1996 [10].
Table 3
Mortality from cardiovascular diseases among the Inuit in Canada and
Alaska in the 1990s
Indigenous All Ratio CI (95%)
Cerebrovascular disease
Nunavik, Canada, 1995 /
1997
a
200 48 4.13 1.07 /10.68
Nunavut, Canada not available ///
Alaska Natives, 1993 /1998
b
36 27 1.36 1.17 /1.57
Alaska Inuit
c
not available ///
IHD
Nunavik, Canada not available ///
Nunavut, Canada, 1995 /
1997
a
40 136 0.29 0.06 /0.87
Alaska Natives, 1993 /1998
b
79 79 0.99 0.88 /1.11
Alaska Inuit, 1990 /1998
b,c
70 82 0.85 0.74 /0.96
Adjusted to different standard populations.
a
Adjusted to the Canadian population 1991.
b
Adjusted to the US population 1940.
c
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 [34].
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.
4. Discussion
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
coronaries [33].
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
[44]. 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
Table 4
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 [45], but
the genotype of the Inuit does not unequivocally
indicate a population with a high or low predisposition
for atherosclerosis.
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 [13]. 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 [46] compared with 25% in
1991 [47]. 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
[49]. In some studies of general populations fish
consumption appears to be associated with reduced
IHD mortality in high-risk populations only [50] while
other studies show an effect also among those without
evidence of prior cardiovascular disease [51].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.
5. Conclusion
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 [52]. 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
were.
Acknowledgements
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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... Inuit who were originally thought to be relatively immune to CHD because of their n-3 PUFAs consumption ). There also have been increases in the rates of death from IHD and stroke among all indigenous populations that are higher compared with whites (Bjerregaard, Young et al. 2003). This finding indicates that despite several-fold higher intakes of n-3 polyunsaturated fatty acids (n-3 PUFAs) and Se in the Inuit population that are related to improved antioxidant protection, they are not necessarily protected from disease risk relative to the non-indigenous population. ...
... When compared to the Oji-Cree and non-aboriginal Canadian, Inuit had the lower rates of hypertriglycemia, low HDL-C, high and fasting glucose and they ranked as intermediate in terms of abdominal obesity whereas native Cree ranked higher than Inuit (Liu, Hanley et al. 2006). The rate of high blood pressure in Inuit was shown to be similar to non-aboriginal Canadians as previously been demonstrated in Greenlandic Inuit (Bjerregaard, Young et al. 2003). All components of the MetS in Inuit increased with increased obesity. ...
... n-3, omega-3; n-6, omega-6; AA, arachidonic acid (20:4n-6); EPA, eicosapentaenoic acid (20:5n-3); MUFA, monounsaturated fatty acids; PUFA, polyunsaturated Fatty acids; SFA, Saturated fatty acids; TFA, trans fatty acids. The relationship between oxidative stress biomarkers and cardiometabolic risk factors has been sparsely addressed in the Inuit, which is an important to study with respect to the protection against metabolic deteriorations associated with CVD that is indicated in the Inuit population (Bjerregaard, Young et al. 2003;Kuhnlein, Receveur et al. 2004;Young 2007 (Table 3.3). Nevertheless, the range of the measured isoprostanes was well within normal ranges reported in healthy Caucasians (Milne, Yin et al. 2007). ...
Thesis
Full-text available
This doctoral dissertation is the first study to comprehensively assess the oxidative stress status among the Inuit using the gold standard biomarker F2-isoprostanes, and determine its correlates related to cardiometabolic risk factors and the environmental contaminants methylmercury and polychlorinated biphenyls (PCBs) that bioaccumulate in Arctic regions. Greater understanding of oxidative stress status was achieved by quantifying novel isoprostanes isomers that may competitively reduce F2‐isoprostanes generation under various physiological conditions that may be associated with decreased oxygen tension such as smoking; and by nutritional profiles associated with high n-3 polyunsaturated fatty acids (PUFAs) intake. In addition, the simultaneous measurement of these isoprostane isoforms provided mechanistic insights of the “cardioprotective” advantage the Inuit may possess despite environmental contaminant health risks. The quantification of plasma F2‐isoprostanes, F3-isoprostanes and isofurans, provided new evidence to support previous suggestions that despite recurrent concerns over mercury and PCBs environmental‐health risks, the traditional Inuit diet provides nutritional antioxidant benefits that can counteract some environmental contaminant induced health risks. In addition, we showed for the first time direct evidence that the co‐presence of selenium and n‐3 PUFAs in the traditional Inuit foods may be potential risk modifiers of cardiometabolic deterioration. Despite this latter observation, we also showed that the Inuit might not be fully protected from health risks associated with contaminants; especially this is for the younger generation that continues to shift away from consuming traditional foods.
... Type 2 diabetes (T2D) was practically unknown in Greenland in the 1960s (Sagild et al. 1966;Kromann and Green 1980) and observations in the 1970s of supposedly low cardiovascular disease (CVD) prevalence and high intakes of n-3 fatty acids ("fish oils") (Bang and Dyerberg 1972;Dyerberg et al. 1975;Bang et al. 1976) prompted a worldwide research interest in this association (Abdelhamid et al. 2018). However, both T2D and CVD are major burdens in Greenland today (Bjerregaard et al. 2003b;Jørgensen et al. 2012;Fodor et al. 2014), where sedentary jobs have replaced the full-time hunter-fisher lifestyle for many individuals and where imported foods are increasingly replacing the traditional diet. The changing lifestyle is of great concern (Bjerregaard et al. 2002(Bjerregaard et al. , 2004Dahl-Petersen et al. 2011;Jørgensen et al. 2012;Jeppesen et al. 2014); however, genetic research is also gaining increasing interest to explain the high prevalence of lifestyle diseases in Greenland. ...
Article
The Inuit in Greenland have gone through dramatic lifestyle changes during the last half century. More time is spent being sedentary and imported foods replaces traditional foods like seal and whale. The population has also experienced a rapid growth in obesity and metabolic disturbances and diabetes is today common despite being almost unknown few decades ago. In this paper, we describe and discuss the role of lifestyle changes and genetics for Inuit metabolic health. Novelty: Cardiometabolic disease risk has increased in Greenland. Lifestyle changes and possibly gene-lifestyle interactions play a role.
... Accordingly obesity is an increasing problem among Inuit in Greenland with a rise from 15 to 25% over the past two centuries 20 and it is a major risk factor of diabetes 21 . The common myth that Inuit are exempted from CVD [22][23][24] is continuously disproven with recent studies finding that CVDs in Inuit populations are prevalent and relevant public health issues [25][26][27] . Adding to the pool of risk factors for diabetes among Inuit is the unique genetic structure of isolated populations giving rise to common risk alleles with larger effect sizes than in populations with a more diverse genetic composition. ...
Article
Full-text available
Cardiovascular disease (CVD) is a well-known complication of diabetes, but the association has not been studied among Inuit in Greenland. The aim was to examine the association between diabetes and incident CVD among Inuit in Greenland and determine if the common diabetogenic TBC1D4 variant confers increased risk of CVD. We followed an initial study population of 4127 adults in Greenland who had participated in at least one population-based health survey, in national registers. We used Poisson regression to calculate incidence rate ratios (IRR) of cardiovascular endpoints, comparing participants with and without diabetes and comparing homozygous TBC1D4 carriers with heterozygous carriers and non-carriers combined. Close to 10% had diabetes and age range was 18–96 years (45% male). Of the 3924 participants without prior CVD, 362 (~ 9%) had CVD events during a median follow-up of 10 years. Multivariate IRR for the effect of diabetes on CVD was 1.12 (95% CI: 0.80, 1.57) p = 0.50. Using a recessive genetic model, we compared homozygous TBC1D4 carriers with wildtype and heterozygous carriers combined, with a multivariate IRR of 1.20 (95% CI: 0.69, 2.11) p = 0.52. Neither diabetes nor the TBC1D4 variant significantly increased CVD risk among Inuit in Greenland in adjusted models.
... The Inuit diet is exceptionally high in omega-3 fatty acids, which is not characteristic of most low-carbohydrate diets. Also of note, the Inuit do not have exceptional health or longevity and are especially subject, perhaps because of the high omega-3 fat intake, to intracranial hemorrhage (16). Another potential exception is the Paleolithic diet (see below), which is at times invoked as an illustration of low-carbohydrate eating; however, it is not truly low in carbohydrate and differs substantially from most popular versions of the low-carbohydrate diet. ...
Article
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Homelessness is a devastating experience for children and their families. Families, the majority of whose members are children, now comprise more than one-third of the overall homeless population. Most of these children are less than six years old. Various assumptions have driven policy and the allocation of resources to programs serving these families. Although decades of research and field experience suggest strategies for preventing and reducing this problem, perspectives differ, hindering the development of effective solutions. In this article, we explore some of these assumptions, including ( a) definitions of homelessness used to count the numbers of families and determine resource allocation, ( b) the needs of children and responses to the impact of adverse childhood experiences, and ( c) whether services matter and should be integrated with affordable housing. We conclude by suggesting various directions to ensure that these children are protected and have the opportunity to grow and thrive. Expected final online publication date for the Annual Review of Public Health, Volume 41 is April 1, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
... In many populations, the mutant allelic frequency (or the number of individual alleles of a certain type divided by the total number of all alleles at a genetic locus in a given population) was found to be 4.9-13% (Yoshida and Sakane, 1999). For example, the mutant allelic frequency in Europeans is 8%; however, Mongoloids including Inuits, Pima Indians, and Japanese show relatively higher allelic frequencies, reaching more than 30% in Pima Indians and approaching 20% in Japanese (Yoshida and Sakane 1999;Bjerregaard et al. 2003;Takeuchi et al. 2012). ...
Article
Beta3-adrenergic receptor (ADRB3) is a mediator of catecholamine-stimulated lipolysis in humans. The Trp64Arg polymorphism with T/C transition in the ADRB3 gene has been considered to reduce lipolysis and metabolic expenditure. Here, we investigated the hitherto unknown role of the Trp64Arg substitution on food preference among healthy young adults (mean age, 24.3; n = 53, including 25 men). Preference toward four food types (bitter, sour, salty, or sweet) and greasy (high-fat) foods was examined using a self-reported questionnaire. There was no noticeable sex-difference in food preference. Incidentally, only among female subjects, the genotype frequencies of the Trp64Arg polymorphism were in accordance with the Hardy-Weinberg equilibrium. Consequently, female subjects were divided into two groups for further analyses: 18 subjects with TT genotype (Trp64Trp) (wild-type group) and 10 subjects with TC genotype (Trp64Arg) (heterozygous group). No significant difference was observed in preference for four food types between the groups. However, when sweet foods were divided into high-fat and low-fat subgroups, food preference for high-fat sweet foods in heterozygous group was significantly higher than that in wild-type group. Moreover, when subjects were divided into two classes based on preference for greasy foods (like, n = 16 or dislike, n = 12), the preference degree in heterozygous group who liked high-fat foods (n = 5) was significantly higher than that in wild-type group (n = 11), suggesting that the Trp64Arg substitution might genetically enhance high-fat food preference. Thus, understanding the relationship between ADRB3 Trp64Arg substitution and fat preference will be valuable for obesity prevention.
... Interest in omega-3 fatty acids began with reports that Greenland Inuits, who ate a diet of oily fish and seal high in omega-3s, had low rates of cardiovascular disease (72,73). Some researchers have questioned these findings because Bang et al. studied the diets of Inuits and only speculated that eating marine fats reduced cardiovascular disease (74). Other researchers emphasize Inuits had a prevalence of cardiovascular disease similar to non-Inuits; they had high mortality from cerebrovascular strokes; their general death rate was double that of non-Inuit peoples; and their life expectancy was roughly 10 years less than the Danish people Bang et al. used for comparisons (75). ...
Article
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The health of livestock, humans, and environments is tied to plant diversity—and associated phytochemical richness—across landscapes. Health is enhanced when livestock forage on phytochemically rich landscapes, is reduced when livestock forage on simple mixture or monoculture pastures or consume high-grain rations in feedlots, and is greatly reduced for people who eat highly processed diets. Circumstantial evidence supports the hypothesis that phytochemical richness of herbivore diets enhances biochemical richness of meat and dairy, which is linked with human and environmental health. Among many roles they play in health, phytochemicals in herbivore diets protect meat and dairy from protein oxidation and lipid peroxidation that cause low-grade systemic inflammation implicated in heart disease and cancer in humans. Yet, epidemiological and ecological studies critical of red meat consumption do not discriminate among meats from livestock fed high-grain rations as opposed to livestock foraging on landscapes of increasing phytochemical richness. The global shift away from phytochemically and biochemically rich wholesome foods to highly processed diets enabled 2.1 billion people to become overweight or obese and increased the incidence of type II diabetes, heart disease, and cancer. Unimpeded, these trends will add to a projected substantial increase in greenhouse gas emissions (GHGE) from producing food and clearing land by 2050. While agriculture contributes one quarter of GHGE, livestock can play a sizable role in climate mitigation. Of 80 ways to alleviate climate change, regenerative agriculture—managed grazing, silvopasture, tree intercropping, conservation agriculture, and farmland restoration—jointly rank number one as ways to sequester GHG. Mitigating the impacts of people in the Anthropocene can be enabled through diet to improve human and environmental health, but that will require profound changes in society. People will have to learn we are members of nature's communities. What we do to them, we do to ourselves. Only by nurturing them can we nurture ourselves.
... For many years, CVD was considered to be uncommon among Inuit from Greenland, Canada and USA [15]. However, later on, mortality statistics from studies published between 1936 and 1993 have shown that mortality from CVD was higher among Inuit than white comparison populations [32][33][34]. Population-and register-based surveys in Greenlanders from 1999 to 2001 and 2003 to 2012, respectively, showed a similar prevalence of coronary heart disease and ischemic electrocardiographic changes, as observed in Europeans [20,35,36], whereas cerebrovascular events were more common in Inuit [35,36]. In a recent longitudinal study, Canadian Nunavik Inuit had a slightly higher, and Greenlandic Inuit a similar, absolute age-adjusted CVD incidence as a Danish control population [37]. ...
Article
In this review, we describe the extraordinary population of Greenland, which differs from large outbred populations of Europe and Asia, both in terms of population history and living conditions. Many years in isolation, small population size and an extreme environment have shaped the genetic composition of the Greenlandic population. The unique genetic background combined with the transition from a traditional Inuit lifestyle and diet, to a more Westernized lifestyle, has led to an increase in the prevalence of metabolic conditions like obesity, where the prevalence from 1993 to 2010 has increased from 16.4% to 19.4% among men, and from 13.0% to 25.4% among women, type 2 diabetes and cardiovascular diseases. The genetic susceptibility to metabolic conditions has been explored in Greenlanders, as well as other isolated populations, taking advantage of population‐genetic properties of these populations. During the last 10 years, these studies have provided examples of loci showing evidence of positive selection, due to adaption to Arctic climate and Inuit diet, including TBC1D4 and FADS/CPT1A, and have facilitated the discovery of several loci associated with metabolic phenotypes. Most recently, the c.2433‐1G>A loss‐of‐function variant in ADCY3 associated with obesity and type 2 diabetes was described. This locus has provided novel biological insights, as it has been shown that reduced ADCY3 function causes obesity through disrupted function in primary cilia. Future studies of isolated populations will likely provide further genetic as well as biological insights.
... Overall, it is still difficult to draw conclusions about the "antagonist" effect of omega-6 PUFA against omega-3 PUFA in a context of myocardial infarction, since few studies have been published on the subject. However, populations that are large consumers of fish, such as the Inuit and Japanese, have a low mortality rate from ischemic heart disease [62][63][64]. This is also apparent in populations consuming a Mediterranean-type diet [65]. ...
Article
Full-text available
The high-fat diet of North Americans has a major impact on cardiovascular disease occurrence. Notably, fatty acids have been identified as important factors that could modulate such diseases, especially myocardial infarction (MI). Experimentally, omega-3 polyunsaturated fatty acids (PUFA) have demonstrated positive effects on cardiovascular disorders and have also shown cardioprotection by decreasing MI size. Although many animal experiments have clearly established the benefits of omega-3 PUFA, clinical studies have not reached similar conclusions. In fact, the findings of recent clinical investigations indicate that omega-3 PUFA play only a minor role in cardiovascular health. This dichotomy between experimental and clinical studies may be due to different parameters that are not taken into account in animal experiments. We have recently observed that the high consumption of omega-6 PUFA results in significant attenuation of the beneficial effect of omega-3 PUFA on MI. We believe that part of the dichotomy between experimental and clinical research may be related to the quantity of omega-6 PUFA ingested. This review of the data indicates the importance of considering omega-6 PUFA consumption in omega-3 PUFA studies.
... In this respect, due to the putative beneficial role played by LC-PUFAs against cardiovascular diseases, increasing attention has been paid to those populations subsisting on a strict marine diet. However, due to a lack of evidence that the mortality from cardiovascular diseases is lower among those populations (Bjerregaard et al., 2003), opinions that seafood is a unique source of beneficial nutrients remain still controversial. ...
Article
Bivalve molluscs, including oysters and scallops, are hedonic foods that have been a valuable source of vitamins, minerals and proteins in the human diet since the Stone Age. Despite being rich in beneficial compounds, it is still debatable whether bivalves should be regarded as a healthy food since they can accumulate harmful microorganisms, and toxic compounds from the surrounding environment. Currently, there is still no in-depth understanding of the ultimate effect of bivalve consumption on humans. The use of advanced foodomics approaches is beginning to provide a more detailed characterisation of the beneficial and deleterious compounds in these seafood products. In addition to defining bivalve molluscs within an international dietary framework, this review highlights the major nutritional components of their metabolome (foodome) with a focus on several groups of toxicants whose presence can negatively offset their nutritional value. An overview of metabolomics applications to the study of bivalve molluscs is included.
Article
Background and aims: No prospective study have ever assessed if marine n-3 polyunsaturated fatty acids protect Inuit against cardiovascular disease as claimed. It is highly relevant as cardiovascular disease (CVD) incidence rates are rising concurrent with a westernization of diet. We aimed to assess the association between blood cell membrane phospholipid content of eicosapentaenoic acid and docosahexaenoic acid (EPA + DHA) on CVD risk in Inuit. Methods: We used data from a cohort of adult Greenlanders with follow-up in national registers. The main outcome was fatal and non-fatal CVD incidence among participants without previous CVD. The continuous effect of EPA + DHA was calculated as incidence rate ratios (IRRs) using Poisson regression with age as time scale, adjusting for age, sex, genetic admixture, lifestyle and dietary risk factors. Results: Out of 3095 eligible participants, 2924 were included. During a median follow-up of 9.7 years, 216 had their first CVD event (8.3 events/1000 person years). No association between EPA + DHA and CVD risk was seen, with IRR = 0.99 per percentage point EPA + DHA increase (95% CI: 0.95-1.03, p = 0.59). No association was seen with risk of ischemic heart disease (IHD) (IRR = 1.03, 95% CI: 0.97-1.09) and stroke (IRR = 0.98, 95% CI: 0.93-1.03) as separate outcomes or for intake of EPA and DHA. Conclusions: We can exclude that the CVD risk reduction is larger than 21% for individuals at the 75% EPA + DHA percentile compared to the 25% percentile. We need a larger sample size and/or longer follow-up to detect smaller effects and associations with IHD and/or stroke.
Article
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The GNB3 825T allele encodes a product that has enhanced activation of heterotrimeric G proteins in vitro and could play a role in adipogenesis. We therefore evaluated the possibility that the GNB3 825T allele was associated with obesity in a sample of 213 healthy Canadian Inuit. We found that body weight, body mass index, waist girth, hip girth, subscapular skinfold thickness, and triceps skinfold thickness were significantly higher in subjects with the GNB3 825T/T genotype than in subjects with other genotypes. Furthermore, two anthropometric ratios, namely that of waist to hip circumference and that of subscapular to triceps skinfold thickness, were not significantly different across genotypes. This suggested that the increased deposition of fat in subjects with the GNB3 825T/T genotype was generalized and not localized to particular subregions. There was no association of this genetic variation with blood pressure. The GNB3 825T/T genotype accounted for between 1.6% and 3.3% of the total variation (≤13% of attributable variation) of the obesity-related traits. The potential for a genetic marker of obesity creates opportunities for future studies in the Inuit, not just to confirm the associations, but also to examine prospectively the influence of interventions and possible relationships between GNB3 825T and longer term complications of obesity.
Article
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Gas-liquid chromatography analyses have been carried out to investigate the composition of esterified fatty acids in the plasma lipids in 130 Greenland Eskimos, compared with those of 32 Greenland Eskimos living in Denmark and of 31 Caucasian Danes in Denmark. While the Eskimos living in Denmark did not differ substantially from other persons living in Denmark and, from what is found in other studies in Western communities, the Greenland Eskimos showed a completely different pattern. They demonstrated a much higher proportion of palmitic, palmitoleic, and timnodonic acids, while they had a markedly lower concentration of linoleic acid. The total concentration of polyunsaturated fatty acids was lower in Greenland Eskimos than in the other groups. These findings are discussed in the light of the generally accepted opinion of the beneficial effect on plasma lipid levels and on the morbidity of coronary atherosclerosis of a high dietary intake of polyunsaturated fatty acids. As plasma lipid and lipoprotein levels in Greenland Eskimos in a previous study were found markedly lower than those found in Western populations, and as coronary atherosclerosis seems to occur far less commonly among Eskimos in Greenland than among peoples in industrialized countries, it was found difficult to combine these observations with the results from the present study. If dietary differences are the main reason for the differences in plasma lipid concentrations, the results from the present study point more toward qualitative than toward quantitative differences in respect of fatty acid composition of the food.
Article
We discovered that rare mutations in LMNA, which encodes lamins A and C, underlie autosomal dominant Dunnigan-type familial partial lipodystrophy. Because familial partial lipodystrophy is an extreme example of genetically disturbed adipocyte differentiation, it is possible that common variation in LMNA is associated with obesity-related phenotypes. We subsequently discovered a common single nucleotide polymorphism (SNP) in LMNA, namely 1908C/T, which was associated with obesity-related traits in Canadian Oji-Cree. We now report association of this LMNA SNP with anthropometric indexes in 186 nondiabetic Canadian Inuit. We found that physical indexes of obesity, such as body mass index, waist circumference, waist to hip circumference ratio, subscapular skinfold thickness, and subscapular to triceps skinfold thickness ratio were each significantly higher among Inuit subjects with the LMNA 1908T allele than in subjects with the 1908C/1908C genotype. For each significantly associated obesity-related trait, the LMNA 1908C/T SNP genotype accounted for between approximately 10–100% of the attributable variation. The results indicate that common genetic variation in LMNA is an important determinant of obesity-related quantitative traits. We discovered that rare mutations in LMNA, which encodes lamins A and C, underlie autosomal dominant Dunnigan-type familial partial lipodystrophy. Because familial partial lipodystrophy is an extreme example of genetically disturbed adipocyte differentiation, it is possible that common variation in LMNA is associated with obesity-related phenotypes. We subsequently discovered a common single nucleotide polymorphism (SNP) in LMNA, namely 1908C/T, which was associated with obesity-related traits in Canadian Oji-Cree. We now report association of this LMNA SNP with anthropometric indexes in 186 nondiabetic Canadian Inuit. We found that physical indexes of obesity, such as body mass index, waist circumference, waist to hip circumference ratio, subscapular skinfold thickness, and subscapular to triceps skinfold thickness ratio were each significantly higher among Inuit subjects with the LMNA 1908T allele than in subjects with the 1908C/1908C genotype. For each significantly associated obesity-related trait, the LMNA 1908C/T SNP genotype accounted for between approximately 10–100% of the attributable variation. The results indicate that common genetic variation in LMNA is an important determinant of obesity-related quantitative traits.
Article
The third volume of 'Cancer Incidence in Five Continents' contains information from 78 populations in 28 countries, and covers the period 1968-1972. Volumes I and II covered the years 1960-1966 and are now out of print. As in Volume II, there are chapters on the techniques of registration, and the classification used. The chapter on reliability of registration includes tables giving the percentage of cases confirmed histologically by sex and by site and by 5 yr age groups by sex for all sites. Similar tables are presented for cases registered from death certificates only and for the mortality from cancer in the registration area in the period in question expressed as a percentage of incidence. New topics include equivalence tables for the 7th and 8th revision of the International Classification of Diseases, Injuries and Causes of Death (ICD), a commentary on the processing of data and a new measure of age standardized incidence, the cumulative rate; these rates are given for a selection of common sites for the age intervals 0 to 64 and 0 to 74 yr. In addition to the age specific and age standardized rates presented in previous volumes, age standardized rates are given for 46 four digit ICD rubrics: these include subdivisions of the colon and skin and the leukemias. Registries reporting their data according to the 7th revision of the ICD are clearly distinguished from the others. A feature, which it is hoped will be of considerable use, is a cumulated index for the first 3 volumes. The bibliography includes a listing of selected WHO publications concerning cancer. Although the book is now some 584 pages, it is still easy to consult.
Article
Background There is conflicting evidence on the benefits of foods rich in vitamin E (alpha-tocopherol), n-3 polyunsaturated fatty acids (PUFA), and their pharmacological substitutes. We investigated the effects of these substances as supplements in patients who had myocardial infarction. Methods From October, 1993, to September, 1995, 11324 patients surviving recent (less than or equal to 3 months) myocardial infarction were randomly assigned supplements of n-3 PUFA (Ig daily, n=2836), vitamin E (300 mg daily, n=2830), both (n=2830), or none (control, n=2828) for 3.5 years. The primary combined efficacy endpoint was death, non-fatal myocardial infarction, and stroke. Intention-to-treat analyses were done according to a factorial design (two-way) and by treatment group (four-way). Findings Treatment with n-3 PUFA, but not vitamin E, significantly lowered the risk of the primary endpoint (relative risk decrease 10% [95% CI 1-18] by two-way analysis, 15% [2-26] by four-way analysis). Benefit was attributable to a decrease in the risk of death (14% [3-24] two-way, 20% [6-33] four-way) and cardiovascular death (17% [3-29] two-way, 30% [13-44] four-way). The effect of the combined treatment was similar to that for n-3 PUFA for the primary endpoint (14% [1-26]) and for fatal events (20% [5-33]). Interpretation Dietary supplementation with n-3 PUFA led to a clinically important and satistically significant benefit. Vitamin E had no benefit. Its effects on fatal cardiovascular events require further exploration.
Article
An epidemiological survey of several chronic diseases in the Upernavik district, Northwest Greeland, is reported. The study population (ap-prox. 1 800 inhabitants) is one of the remaining whaling and sealing populations in Greenland. It was observed over the 25-year period 1950–74 as to the incidence of the diseases, which was based on all cases diagnosed in hospital during this period. The disease pattern of the Greenlanders differs from that of West-European populations, having a higher frequency of apoplexy and epilepsy but a lower frequency or absence of acute myocardial infarction, diabetes mellitus, thyrotoxicosis, bronchial asthma, multiple sclerosis and psoriasis. The distribution of cancer types differs from that of the Danish population, but the total incidence of cancer is of the same magnitude. Further comparable studies should be performed in Greenlandic districts that are characterized by more profound changes in life style, in order to elucidate the effect of these changes on the disease pattern. Acta Med Scand 208: 401, 1980.
Article
Previous studies in Greenland suggest that death rates from ischemic heart disease [IHD] are lower in Eskimos than in Danes and other Caucasian populations. This has been explained by a high intake of n-3 polyunsaturated fatty acids with beneficial effects on blood lipids and hemostasis. In other populations, lipoprotein(a) [Lp(a)] is associated with IHD, plasma concentrations of Lp(a) being genetically determined to a major extent. We have compared Lp(a) concentrations and apo(a) phenotypes in 120 Greenlandic Eskimos with those in 466 Danish men. The median Lp(a) concentration in Eskimos (8.7 mg/dl;[95% CI 6.5-10.7]) was not significantly different from that in Danes (6.3 mg/dl; [95% CI 5.2-7.0]), whereas the 90th percentile was significantly higher among Danes: 46.36 mg/dl; [95% CI 43.0-54.3] vs. 27.6 mg/dl [95% CI 20.7-36.9]. In 20% of the Danes, but in only 8% of the Eskimos (P = 0.009), the concentration of Lp(a) exceeded 30 mg/dl. The difference is probably explained by a low frequency of the low molecular weight apo(a) phenotypes among Eskimos, since the apo(a) isoforms F and B were absent, and the S1 and S2 types were present in only 3.3% of Eskimos. In contrast, these apo(a) isoforms were present in 26.6% of the Danes in either single-band or double-band phenotypes. The pattern of apo(a) polymorphism found in this study could provide part of a genetic explanation for the putative low rates of IHD in Eskimo populations.