Download Differences in Coronary Mortalit Can Be Explained by

2771
Differences in Coronary Mortalit Can Be
Explained by Differences in Cholesterol and
Saturated Fat Intakes in 40 Countries but
Not in France and Finland
A Paradox
Sabine M. Artaud-Wild, BS, RD; Sonja L. Connor, MS, RD;
Gary Sexton, PhD; William E. Connor, MD
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Background. For decades, the coronary heart disease (CHD) mortality rate has been four or more times
higher in Finland than in France despite comparable intakes of dietary cholesterol and saturated fat. A
potential answer to this paradox is provided by this study of 40 countries and the analyses of other
nutrients in the diets besides cholesterol and saturated fat.
Medhds and Resuls. CHD death rates for men aged 55 to 64 years were derived from the World Health
Organization annual vital statistics. Dietary intakes were gathered from the Food and Agriculture
Organization of the United Nations database. Forty countries at various levels of economic development
and 40 dietary variables were investigated, including a lipid score that combined the intakes of cholesterol
and saturated fat (Cholesterol-Saturated Fat Index (CSIJ). The CSI was significantly and positively
related to CHD mortality in the 40 countries. The countries with low CSIs had low CHD death rates.
Countries with high CSIs had a wide range of CHD death rates. France, Finland, and other Western
industrialized countries had similar CSIs. After adjusting for cholesterol and saturated fat, milk and
many components of milk (butterfat, milk protein, calcium from milk, and riboflavin) and total calcium
remained positively related to CHD mortality for all 40 countries. There were differences in the
consumption of these foods and nutrients in France and Finland. Milk and butterfat (fat from milk,
cream, cheese, and butter) consumption was higher in Finland than in France. The consumption of plant
foods, recently shown to be protective against CHD (vegetables and vegetable oils containing monounsaturated and polyunsaturated fatty acids), was greater in France than in Finland.
Conchusions. Over the years, France and Finland, with similar intakes of cholesterol and saturated fat,
consistently have had very different CHI) mortality rates. This paradox may be explained as follows. Given a
high intake of cholesterol and saturated fat, the country in which people also consume more plant foods,
including small amounts of liquid vegetable oils, and more vegetables (more antioxidants) had lower rates of
CHD mortality. On the other hand, milk and butterfat were associated with increased CHD mortality, possibly
through their effects on thrombosis as well as on atherosclerosis. (Ciulaion. 1993;88:2771-2779.)
KEY WORDs * thrombosis * diet * cholesterol * heart disease * mortality
In the late 1950s, an epidemiological paradox was
observed. There were large geographical differences in mortality from coronary heart disease
(CHD) among European countries, particularly between France and Finland, despite their having comparable intakes of dietary fat.' Finland had the highest
rate of CHD mortality, and France was at the lower end
of the range. Finland also stood out as having the
highest CHD mortality in the Seven Countries Study.2
In a study of 24 countries in 1961, the correlation
between dietary cholesterol and CHD was high (r=.83).
Received January 12, 1993; revision accepted July 26, 1993.
From the Division of Endocrinology, Diabetes, and Clinical
Nutrition, Department of Medicine, The Oregon Health Sciences
University, Portland, Ore.
Correspondence to Dr William E. Connor, Department of
Medicine, L-465, Oregon Health Sciences University, 3181 SW
Sam Jackson Park Rd, Portland, OR 97201-3098.
However, with comparable intakes of dietary cholesterol in France and Finland, the CHD mortality rate for
men aged 55 to 59 was four times higher in Finland than
in France.3 The same mortality difference was reported
in 1982 by Liu et a14 using data from 1954 and 1965 and
a lipid score based on the Keys equation.
Dietary cholesterol and saturated fat are the two
nutrients most associated with CHD. We combined
their impact into a lipid score, the Cholesterol-Saturated Fat Index (CSI) and then compared the relation
of this index with the coronary mortality in 40 countries
as previously published.5 France and Finland continued
to exhibit very different coronary mortality rates while
having comparable CSIs. The CHD mortality in France,
strikingly lower than observed in comparably developed
countries, has been noted by others as well.6'7
Whenever epidemiological paradoxes exist, a reason
should ultimately be found for them. A classic example
2772
Circulation Vol 88, No 6 December 1993
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is that of marine oils and the Eskimos. Early Arctic
explorers and subsequent medical observers found that
cardiovascular disease was rare in the Eskimos despite
their consuming a diet almost exclusively derived from
animal foods, which clearly had a very high fat and
cholesterol content.8 Bang and Dyerberg9 later explained this discrepancy by noting the differences in the
types of dietary fat eaten by the Eskimos and by the
people in Western countries. The fat consumed by the
Eskimos was almost completely derived from food from
the sea: seal, whale, and fish. These fats all contain large
quantities of the highly polyunsaturated w-3 fatty acids,
which are both hypolipidemic and antithrombotic.
A popular view is that the French have a lower
coronary mortality because of their consumption of red
wine, goose liver pate, and cheese. In our view, this
hypothesis requires scientific validation. Using data that
represent the 1950s through the 1980s, we examined the
relations of coronary mortality to the intakes of foods
and nutrients in 40 countries. We focused specifically on
France, with a relatively low coronary mortality, and
Finland, with the highest coronary mortality. There was
a greater consumption of vegetables and unsaturated fat
in France. There was greater consumption of milk and
butterfat in Finland. These relations occurred after
appropriate adjustment for the intakes of cholesterol
and saturated fat and suggested the possibility of effects
of other dietary factors in influencing the development
of CHD.
Methods
All countries with populations of more than 1 million
and for which both CHD mortality rates and food
supply data could be obtained were included in the
study. The 40 countries meeting these criteria covered
all areas of the globe and nations in differing stages of
industrial development: Austria, Belgium, Denmark,
Finland, France, Hungary, Ireland, The Netherlands,
Norway, Poland, Sweden, Switzerland, the United
Kingdom, West Germany, Bulgaria, Egypt, Greece,
Israel, Italy, Portugal, Romania, Spain, Yugoslavia,
Canada, the United States, Argentina, Chile, Costa
Rica, Cuba, the Dominican Republic, Ecuador, Mexico,
Nicaragua, Paraguay, Uruguay, Venezuela, Australia,
New Zealand, Hong Kong, and Japan. We did not
consider other risk factors for CHD such as cigarette
smoking or hypertension. However, it is generally accepted that cigarette smoking is prevalent in many of
the countries where a low-fat diet is consumed and that
people in these countries generally have low plasma
lipid and lipoprotein levels. Also, Japan, with a low-fat
diet and a low CHD mortality rate, has a high incidence
of hypertension. Still, the fact that the data from
analyses presented in this article fit so well with metabolic data from both human and animal studies suggests
that diet is a major factor in determining coronary
mortality rates throughout the world.10
World Health Organization reports were used as the
source of CHD mortality statistics, ischemic heart disease (International Classification of Diseases, 410-414,
"A" list, A83, 8th revision) being taken as the term
equal to CHD.1" Mortality data were collected for 1977
before the latest changes in the international classification of diseases were introduced.12 These data represent
the more typical picture for the 1950s through the
1980s. CHD mortality rates were expressed as deaths
100 000 population in men aged 55 to 64 years in the
40 countries. To determine the consistency over time,
we compared CHD mortality rates in women and men
at different ages in France and Finland for 1977 as well
as in men age 55 to 64 for every year between 1961 and
1988.
Average food disappearance data for years 1975
through 1977 were collected for each country from the
Food Balance Sheets of the Food and Agriculture
Organization (FAO) of the United Nations.13 Correlation coefficients computed using food data from either
1967 or 1977 and coronary mortality yielded similar
results. Because there were food data for more countries in 1977, we elected to use that year. The FAO data
listing the amounts of specific food items in grams
available per day per inhabitant for each country were
used in this study.
Food Balance Sheets provide a reasonable picture of
food or nutrients available for consumption. No allowance is made for spoilage and table waste, nor are
indications given about differences that may exist in the
diet consumed by different age, sex, or socioeconomic
groups within a country. However, these data (based on
food produced plus food imported minus food exported
and divided by the number of inhabitants and by the
number of days in the year) provide an estimate of per
person per day food supply for each country. While it is
recognized that they may give only crude approximations of actual individual intake, food disappearance
data are useful for allowing intercountry comparisons of
dietary patterns. Furthermore, food disappearance data
are useful in generating hypotheses about dietary factors associated with disease' and have been widely used
in published studies.3,415-'7 Imputed intakes taken directly from the FAO books were used as the basis for
dietary intake in the analyses for fish, cheese, milk, rice,
eggs, wine, and calories from both animal and vegetable
foods. Because we wanted to examine the relation of
nutrients known to be associated with coronary mortality, we used the extensive database of the Nutrition
Coordinating Center (NCC) at the University of Minnesota to compute nutrient intakes using the amounts of
foods consumed by each of the 40 countries as listed in
the FAO books.'819 The energy, fat, and protein intakes
estimated for each country using the NCC database
were similar to the intakes listed in the FAO tables,
which led us to think that other nutrient intakes computed using the NCC database were reliable. The
saturated fat and other nutrient intakes in France were
similar to those reported in a number of studies.4'6'7
Because of the wide range of energy intakes among the
countries, we elected to express all nutrients as some
function of energy intake, either as a percentage of
calories or as an amount per 1000 kcal.
We considered two lipid scores. One was computed
using the Hegsted equation,20 which includes saturated
and polyunsaturated fat as well as cholesterol (as does
the Keys equation21'22). The second was computed using
the equation for the CSI: CSI=(1.01xg saturated
fat)+ (0.05 xmg cholesterol).5 The correlation of the two
lipid scores for all 40 countries was .98. The lipid score
computed using the CSI was selected for the analyses
instead of the score using the Hegsted equation for
three reasons. First, a high CSI indicates a high intake
per
Artaud-Wild et al Coronary Mortality in France and Finland
of cholesterol and saturated fat. These nutrients have
the greatest elevating effect on the total plasma and
low-density lipoprotein (LDL) cholesterol through their
effects in decreasing LDL receptor activity in the liver.2324 Second, the primary effect of polyunsaturated fat
is to lower plasma total and LDL cholesterol by enhancing excretion of sterols from the body.25 These fatty
acids do not affect LDL receptor activity. Third, the
powerful effects of cholesterol and saturated fat might
mask any effect of polyunsaturated and monounsaturated fat on CHD mortality.
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Statistical Analysis
The raw nutrient data for 40 countries were converted into nutrient density data, and Pearson productmoment correlation coefficients were calculated between CHD mortality and each of the nutrients. In a
study such as this, one might expect to find strong
intercorrelations among variables known from previous
studies to be strongly related. In this context, the 40
dietary and food variables presented do not represent
variables that are unrelated. Intercorrelations among
groups of food-related variables were strong enough to
suggest multicollinearity. For example, calories from
animal and vegetable sources were strongly and inversely correlated (r= -.98). Intercorrelations between
milk and components of milk (calcium, protein, and
butterfat) were .85 and higher. This was also true for the
components of meat as well as total fat and its components (saturated, monounsaturated, and polyunsaturated). Except for polyunsaturated fat, the measures of fat
intake were also strongly related to CSI (r>.76).
To account for interrelations among these variables,
further analyses were completed. Partial correlation
coefficients were computed relating CHD mortality and
dietary variables including foods as well as nutrients as
independent variables.26'27 Dietary cholesterol and saturated fat are such strong determinants of CHD mortality that they could mask any other dietary effects. To
examine relations between CHD mortality and dietary
variables apart from cholesterol and saturated fat, we
first adjusted the data for cholesterol and saturated fat
(CSI per 1000 kcal) by computing partial correlation
coefficients between CHD mortality and dietary variables. The primary correlation analyses were done using
data from all 40 countries. Because France and Finland
may be regarded as anomalies and might unduly influence the relations of dietary factors and CHD mortality,
the correlational studies were repeated using the data
from 38 countries excluding France and Finland. The
results of these analyses were similar to those of the 40
countries. Differences that occurred when France and
Finland were excluded from the analysis are discussed
in the text. Even though calories from vegetable foods
and calories from animal foods were highly correlated
with CHD mortality, both of these were excluded from
further analyses to allow for the identification of specific
foods and nutrients related to CHD mortality.
The data presented in Tables 1 and 2 and Fig 2A and
2B include all 40 countries. The data presented in Table
3 include France, West Germany, the United Kingdom,
and Finland. The data presented in Fig 1 include only
France and Finland.
A somewhat surprising finding, based on simple correlation coefficients, was a positive association with
2773
TABLE 1. Relation of Coronary Heart Disease Mortality
Rates and 40 Dietary Variables In Men Aged 55 to 64
Years for 40 Countries (Year 1977)
Significant
Item
Calories from animal foods
Cholesterol-saturated fat index/1 000 kcal
Cholesterol, mg/1000 kcal
Saturated fat, % kcal
Monounsaturated fat, % kcal
Total fat, % kcal
Total protein, % koal
Alcohol, g/1 000 kcal
Milk, g/1000 koal
Milk calcium, mg/1000 kcal
Milk protein, g/1000 kcal
Butterfat, g/1000 kcal
Eggs, g/1 000 kcal
Meat calcium, mg/1 000 kcal
Meat protein, g/1 000 kcal
Meat fat, g/1 000 kcal
Riboflavin, mg/1000 kcal
Sodium, mg/1000 kcal
Calcium, mg/1000 kcal
Phosphorus, mg/1000 kcal
Calories from vegetable foods
Total carbohydrates, % kcal
Starch, g/1 000 kcal
Rice, g/1 000 kcal
Fiber, g/1 000 kcal
Thiamin, mg/1000 kcal
Folic acid, ,ug/1 000 kcal
Vitamin E, mg/1000 kcal
Iron, mg/1000 kcal
co-3 Fatty acids, % kcal
Polyunsaturated fat, % kcal
Sucrose, g/1 000 kcal
Fish, seafood, g/1000 kcal
Cheese, g/1 000 kcal
Wine, g/1000 kcal
Vitamin C, mg/1000 kcal
Niacin, mg/1000 kcal
Vitamin A, IU/1000 kcal
Magnesium, mg/1000 kcal
Potassium, mg/1000 kcal
*P<.001; tP<.01; 4P<.05.
Positive
Correlations
.79*
.78*
.69*
.77*
.46t
.62*
.37*
.35*
.76*
.83*
.77*
.80*
.35*
.56*
.62*
.64*
.51t
.63*
.68*
.39*
Significant
Negative
Correlations
-80*
-.62*
-.69*
-.48t
-44t
-48t
-46t
-.44t
-72*
Nonsignificant
Correlations
-.12
-.03
.19
-.10
+27
-.16
-.19
-23
-.14
+.26
-.05
Circulation Vol 88, No 6 December 1993
2774
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TABLE 2. All Significant Associations of Nutrients and
Foods With CHD Mortality After Adjustment for
Cholesterol and Saturated Fat (CSI/1000 kcal) for
40 Countries
CHD Mortality, r
Food or Nutrient
.51 *
Milk, 9/1000 kcal
.44*
Butterfat, g/1 000 kcal
.58t
Calcium from milk, mg/1 000 kcal
.41 *
Protein from milk, g/1000 kcal
.38*
Riboflavin, mg/1000 kcal
kcal
.36*
Calcium, mg/1000
-.34*
Fat, % kcal
-.33*
Monounsaturated fat, % kcal
Polyunsaturated fat, % kcal
-.33*
CHD indicates coronary heart disease and CSI, CholesterolSaturated Fat Index.
*P<.01; tP<.001; *P<.05.
A
CHD mortality and alcohol consumption. To examine
an interaction between alcohol and dietary fat and
cholesterol, we subdivided the 40 countries into those
with CSI per 1000 kcal less than 20 and those with CSI
per 1000 kcal more than or equal to 20. Partial correlation coefficients were again calculated (adjusting for
CSI per 1000 kcal) specifically looking for a relation
between alcohol consumption and CHD mortality
within each group. All analyses were done using SAS
version 6.04 (SAS Institute, Cary, NC).
B
Results
We looked at coronary mortality over time and by sex
in France and Finland. In 1977, the mortality from
CHD in Finland was three to five times higher than in
France. This was true for all age groups for both men
and women, even though women in both countries had
a lower coronary mortality rate than men (Fig 1). Data
from prospective studies have established that the lower
coronary mortality in France was not the result of
300
_ 0
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2000
b.
or0
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0
40
50
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0
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0
0ID 800
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.;0 =4
O
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0 0
60
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0
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00
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00
0a
200
France
0.
r=0.78
X0
o0
-200
0
15
20
25
10
5
Cholesterol Saturated Fat Index
per 1000 kcal/day
0
1200mr
t
Finland *
1000-
0
0
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to
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00
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-200~
__1
.50
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100 150 200 250
Milk Intake g per 1000 keal/day
50
300
FIG 2. A, Plot of death rate from coronary heart disease
(1977) correlated with daily dietary intake (1976 through
1978) of cholesterol and saturated fat as expressed by
the Cholesterol-Saturated Fat Index (CSI) per 1000 kcal.
(To convert to amounts per MJ, divide values by 4.184.)
The death rate is expressed as deaths per 100000
population for men aged 55 to 64 for 40 countries. CSI
was computed from Food and Agriculture Organization
Food Balance Sheets. B, Plot of death rate from coronary
heart disease correlated with daily milk consumption in
grams per 1000 kcal.
Finnish men
o Finnish women
* French men
French women
*
a
1200
CD
60
70
80
Age in years
FIG 1. Plot of comparison of coronary heart disease
mortalities in France and Finland at different ages in both
sexes. The death rate is expressed as deaths per
100 000 population. Values chosen for age are midpoints
of each 10-year period as listed in the World Health
Organization Annual Vital Statistics.
inadequate or incomplete certification of the cause of
death.1s Comparable differences in coronary mortality
persisted from 1950 through 1987 even though there
were changes in the international classification of death
from CHD. This dispels the possibility that 1977 was an
anomalous year.3 Over a span of 27 years, from 1960 to
1987, the mean ratio of coronary mortality per 100 000
men 55 to 64 years old in Finland versus France was
4.6±0.4 (SD). Between 1961 and the mid 1970s, the
Artaud-Wild et al Coronary Mortality in France and Finland
2775
TABLE 3. Consumption of Foods in France, West Germany, the United Kingdom, and Finland Based on
Nutrients and Foods That Were Correlated With CHD Mortality After Adjustment for CSI In 40 Countries
West
France
198
24
Germany
463
United
Kingdom
710
24
Finland
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CHD mortality*
1031
CSIt, per 1000 kcalt
24
26
Food Items§
74
Milk, g/1000 kcal
69
136
254
Milk protein, g/1000 kcal
7
6
5
12
Butterfat, g/1000 kcal11
12
9
12
18
1
1
Olives, olive oil, peanuts,
3
0.1
peanut oil, g/1 000 kcal¶
Liquid vegetable oils,
8
4
5
1
g/1 000 kcal**
Vegetables, g/1000 kcal
81
45
51
19
CHD indicates coronary heart disease and CSI, Cholesterol-Saturated Fat Index.
*Per 100 000 men ages 55-64 years.'1
tCholesterol-Saturated Fat Index (CS1).5
*To convert to amounts per MJ, divide by 4.184.
§include those with significant correlations with CHD mortality (adjusted for CSI) and vegetables.
IlFat from milk, cream, cheese, and butter.
¶Foods containing mostly monounsaturated fats.
**Oils containing mostly polyunsaturated fats.
coronary mortality rate per 100 000 men rose from 193
to 227 in France and from 837 to 1037 in Finland. For
both countries, the rates decreased steadily to a level of
166 for France and 687 for Finland in 1987, but the ratio
of mortality between the two countries remained constant during those years.
Of the 40 dietary variables considered for the univariate analysis in the 40 countries, 20 dietary variables had
significant positive correlations, 9 had significant negative correlations; and 11 had no significant correlations
with CHD mortality (Table 1). The variables that had
significant positive correlations with CHD mortality
generally consisted of animal foods and nutrients associated with animal foods. Significant negative correlations occurred from either plant foods or nutrients
found predominantly in plant foods (total carbohydrate,
fiber, starch, rice, thiamin, folic acid, and vitamin E).
Iron, which is found in both animal and plant foods, was
negatively correlated. Calories from vegetable foods
were negatively correlated with CHD mortality,
whereas calories from animal foods were positively
correlated. Alcohol had a significant positive correlation
with coronary mortality (r=.35, P=.03), but wine was
not significantly correlated (r= -.16, P=.32). When
France and Finland were excluded from the analyses,
cheese was positively related (r=.35, P=.03) and phosphorus was not related to CHD mortality (r=.30,
P=.07).
The paradox of the vastly different coronary mortality
rates between France and Finland is displayed in Fig 2.
The relation between the CSI and CHD mortality (per
100 000 men aged 55 to 64) for all 40 countries is shown
in Fig 2A. Countries with CSIs of less than 15 per 1000
kcal had CHD mortality rates of 90 to 190. The Mediterranean countries had CSIs of approximately 15 per
1000 kcal and had CHD mortality rates from 200 to 350.
Countries that had CSIs of 24 to 26 per 1000 kcal had
very divergent rates of CHD mortality. France had a
Ratio
Finland/France
5.2
1.1
3.4
2.0
1.5
0.03
0.13
0.23
CSI of 24 per 1000 kcal and a CHD mortality rate of
198. Finland had a CSI of 26 per 1000 kcal and a CHD
mortality rate of 1031. Eating styles currently proposed
to treat and prevent CHD would have a CSI of 8 to 17
per 1000 kcal.5,14,29.30
The differences in CHD mortality rates between
France and Finland could not be explained by their
CSIs because they were almost the same. Could they be
explained by other dietary factors? The correlation of
milk intake with CHD mortality was r=.76 (Fig 2B).
Note the new relative positions of France and Finland
for CHD mortality rates in relation to milk consumption; these two countries no longer stood apart from the
other countries. The difference in milk intakes better
explained the differences in CHD mortality for these
two countries than did the CSI.
Dietary cholesterol and saturated fat were such
strong determinants of CHD mortality that they could
mask any other dietary effects. When we adjusted for
dietary cholesterol and saturated fat intakes for all 40
countries, nine nutrients and foods were significantly
associated with CHD mortality (Table 2). Positive associations with CHD mortality included butterfat (fat
from milk, cream, cheese, and butter), milk, milk protein, riboflavin, calcium, and calcium from milk. These
items were all highly intercorrelated, both before and
after adjustment for CSI. Monounsaturated, polyunsaturated, and total fats were negatively associated with
CHD mortality. Alcohol was not related to CHD mortality after adjustment for CSI.
The strong association of milk and many of its components with CHD mortality, both before and after
adjustment for CSI, suggested that something about
milk must be strongly related to CHD mortality. This
was especially convincing because all variables related
to milk except riboflavin were significantly correlated
with CSI (r=.75 to .84); yet, they remained significantly
correlated with CHD mortality after adjustment for
2776
Circulation Vol 88, No 6 December 1993
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CSI. Was it possible to determine the components most
likely to be associated with CHD mortality? We then
adjusted for CSI and butterfat. Only milk and calcium
from milk remained positively associated with CHD
mortality. When we adjusted for CSI and milk, only
calcium from meat was positively associated with CHD
mortality.
France and Finland were then excluded, and the
analyses adjusting for CSI per 1000 kcal were repeated.
Butterfat, riboflavin, calcium, calcium from milk, and
meat protein remained positively related to CHD mortality. Then, w-3 fatty acids were inversely related to
CHD mortality (r= -.38, P=.02). Milk (r=.30, P=.08)
and milk protein (r=.23, P=.18) appeared to have a
lesser effect on CHD mortality.
To examine the question about the interaction of
alcohol and fat intakes with CHD mortality, the 40
countries were divided into two groups: (1) the countries with CSIs of 20 or more per 1000 kcal and (2) the
countries with CSIs of less than 20 per 1000 kcal. For
the countries with the higher CSIs, the relation of milk
and its components and fat and its components with
CHD mortality after adjustment for CSI were largely
unchanged. The relation of wine (r= -.67, P=.003) and
alcohol (r= -.43, P=.09) was strengthened. In addition,
cheese was inversely related (r= -.69, P=.002). The
interrelation of wine and alcohol was r=.60, P=.01, and
for wine and cheese was r=.48, P=.05. The relations of
milk and its components with CHD mortality (after
adjustment for CSI) were unchanged in the countries
with the lower CSIs. The notable exceptions were total
fat (r=.02), monounsaturated fat (r= -.06), polyunsaturated fat (r= -.02), to-3 fatty acids (r= -.55, P=.01),
wine (r=.18), and alcohol (r=.03).
We then looked at differences in the consumption of
foods and nutrients that were significantly associated
with CHD mortality in the 40 countries after adjustment
for CSI. We included France, Finland, and two other
countries with similar CSIs -the United Kingdom and
West Germany (Table 3). Milk consumption was three
times larger in Finland than in France. There was also a
larger intake of milk protein and butterfat in Finland.
The consumption of liquid vegetable oils, rich in monounsaturated and polyunsaturated fatty acids, was eight
times greater in France. The consumption of olives,
peanuts, olive oil, and peanut oil was 30 times larger in
France than in Finland. The consumption of these foods
in the United Kingdom and West Germany was intermediate between those of France and Finland; so were
their CHD mortality rates: 463 and 710 per 100 000
men, respectively. Vegetable foods were strongly and
negatively correlated with CHD mortality observed on
univariate analysis (r= -.80, P<.001). Thus, we examined the consumption of vegetables among the four
countries. There was four times greater consumption of
vegetables in France than in Finland and intermediate
consumptions for the United Kingdom and West
Germany.
Discussion
Dietary cholesterol and saturated fat were clearly
important determinants of coronary mortality, as might
be expected from the well-known effects of these two
variables on plasma lipids, lipoproteins, and coronary
disease. However, differences in cholesterol and satu-
rated fat intakes, since they were similar, could not
explain why Finland has had a four to five times higher
CHD mortality rate than France. Only differences in
the consumption of other nutrients and foods might
help explain this disparity.
We were initially surprised that alcohol was positively
related to CHD mortality, because of the common
perception that the decreased mortality from CHD in
France may be ascribed to alcohol intake and, in
particular, to the intake of wine.31,32 Also, the results of
some epidemiological studies have shown negative associations for moderate intakes of alcohol and positive
associations for higher intakes.33-35
Although alcohol was positively associated with CHD
mortality univariately, this relation did not remain
significant after adjustment for cholesterol and saturated fat. The countries in our study that had the
greatest intakes of cholesterol and saturated fat generally had the greatest intakes of alcohol, and the differences in alcohol consumption could not explain the
disparity between coronary mortality rates in France
and Finland. However, when we considered only the 18
countries with the higher CSIs and adjusted for CSI, a
different picture emerged. Wine and alcohol were then
inversely and wine was significantly related to CHD
mortality. This finding is in keeping with other reports
of studies involving similar countries.33-35
The picture is not complete without considering the
fact that in the 22 countries with the lower CSIs in which
many of the countries had lower intakes of alcohol,
neither wine nor alcohol was related to CHD mortality
even after adjustment for CSI. Our interpretation of
these findings is that wine (containing antioxidants and
possibly other beneficial factors) and alcohol may be
somewhat protective against CHD mortality when people also consume larger amounts of cholesterol and
saturated fat and smaller amounts of plant foods. Nevertheless, when people consume less cholesterol and
saturated fat and more plant foods (more antioxidants),
drinking wine appears to be unrelated to CHD mortality. This low-CSI, high-plant food pattern is similar to
the eating style proposed to protect people, nutritionally, against coronary disease.5,14,29,30
There were striking differences between France and
Finland in the consumption of major classes of foods
and nutrients that this study showed to be significantly
associated with CHD mortality after adjustments for
cholesterol and saturated fat in the 40 countries: they
were milk, butterfat, monounsaturated and polyunsaturated fats, and, finally, vegetables. Milk and butterfat
were associated with a higher coronary mortality rate,
and plant foods containing the unsaturated fats and
vegetables were associated with a lower coronary mortality rate.
Milk intake was 3.5 times greater in Finland than in
France. The analyses showed that several of the constituents of milk (butterfat, protein, calcium, etc.) were
strongly associated and suggested that milk must be
related in some way to CHD mortality. There are
scattered epidemiological, animal, and human studies
about constituents in milk and coronary disease. Causal
inferences cannot be made from these few studies.
Turpeinen36 previously showed a correlation between
dairy fat and CHD mortality rates (r=.75) for 22
industrialized countries. There
was a
positive correla-
Artaud-Wild et al Coronary Mortality in France and Finland
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tion (r=.78) between coronary mortality rates and the
consumption of dairy fat (excluding fat from cheese) in
19 countries reported by Renaud and de Lorgeril.37 In
our study of 40 countries, the correlation coefficients
between coronary mortality and the consumption of
butterfat including or excluding cheese fat were comparable: r=.80 versus r=.79. Joossems and colleagues38
found a distinct difference in CHD mortality between
southern Belgium and northern Belgium. In southern
Belgium, butterfat consumption was far lower than in
northern Belgium. The coronary mortality was lower in
southern Belgium.38 Likewise, France had a contrasting
pattern of cultures regarding food. Butter consumption
was high in the northern regions such as Moselle, where
the incidence of cardiovascular disease was high.37 Olive
oil was the chief fat consumed in southern France
(along with some peanut oil), and the cardiovascular
disease incidence was low in the South of France,
department of Var.39
In experimental animals, butterfat has been the fat
par excellence that produced thrombosis, a major event
in coronary disease. The experiments of Thomas and
Hartroft4O and Hornstra41 in rats demonstrated that
butterfat in the diet induced myocardial infarction from
the thrombotic obstruction of coronary arteries without
much atherosclerosis. Impairment of fibrinolysis from
butterfat has also occurred in humans.42 The aggregating activity of platelets has been shown to be directly
related to the intake of saturated fatty acids (12 to 18
carbon atoms in length) in free living populations.43
Saturated fatty acids constitute more than 50% of total
fatty acids in butterfat. The potential of butterfat to
increase the arachidonic acid content of platelets in
rabbits may be a significant factor in its thrombogenic
effect since arachidonic acid is a precursor to thromboxane A2.44 Similarly, soft atherosclerotic plaques, which
are more inclined to rupture and thrombose, developed
in monkeys and rabbits fed butterfat.45 Therefore, the
high CHD mortality observed in Finland might have
been related to two factors: (1) the hypercholesterolemic and atherogenic effect of the cholesterol and
saturated fat in milk and (2) the thrombotic tendency
produced by the saturated fat in milk.
As for milk protein, there are studies showing that
casein was hypercholesterolemic in animals compared
with soy protein.46 However, the positive correlation of
milk protein with CHD mortality was no longer significant after adjusting for the combination of cholesterol,
saturated fat, and butterfat in the 40 countries. The
correlation remained positive for milk per se. The high
intake of milk in Finland as shown in Table 3 may have
been contributory to CHD; France had a low intake of
milk.
France had a higher consumption of olives, olive oil,
peanuts, and peanut oil than Finland; its position was
close to that of the other Mediterranean countries that
consumed substantial amounts of monounsaturated
fatty acids and had relatively low rates of CHD mortality. In most epidemiological studies,15-17'47 including the
present one, monounsaturated fat was positively associated with coronary mortality using univariate analysis.
However, in metabolic studies, monounsaturated fatty
acids have an LDL cholesterol-lowering effect similar to
that of polyunsaturated fatty acids but without a corresponding lowering of high-density lipoprotein choles-
2777
terol when substituted for saturated fatty acids48'49 or
complex carbohydrates.50'51 After adjusting for saturated fat and cholesterol, as we have done in our
analyses, there was a significant negative association of
monounsaturated fat with CHD mortality. Keys and
colleagues in the Seven Countries Study also showed,
with multiple regression analyses, that the CHD death
rate was negatively correlated with the percentage of
calories from monounsaturated fatty acids.52
The consumption of polyunsaturated fatty acids contained in liquid vegetable oils was eight times larger in
France than in Finland. However, most epidemiological
studies have not shown a significant inverse correlation
between polyunsaturated fat consumption and CHD
mortality rates.15-17'47 Metabolic studies have shown that
polyunsaturated fat in the diet has a plasma total and
LDL cholesterol-lowering effect49 and that it tends to
prevent thrombosis,5354 thus potentially providing a
protective role against CHD. The narrow range of
polyunsaturated fat intakes the world over and the
overwhelming influence of cholesterol and saturated fat
may mask any significant connection between this nutrient and coronary mortality. In our study, however,
the negative correlation between polyunsaturated fat
and CHD mortality was significant after adjusting for
cholesterol and saturated fat intakes. This observation
may help account for the divergent rates of CHD
mortality. There was a marked difference between the
consumption of liquid vegetable oils between France
and Finland. Interestingly, West Germany and the
United Kingdom occupy intermediate positions with
regard to both consumption of liquid vegetable oils and
coronary mortality.
The consumption of w-3 fatty acids from seafood was
related to coronary disease in Greenland Eskimos, the
Dutch, and the Japanese.55-57 In our study, the amount
of dietary co-3 fatty acids had an inverse relation to
CHD mortality in 38 countries (France and Finland
excluded). This same relation occurred in the 22 countries with CSIs less than 20 per 1000 kcal.
For the 40 countries, calories from animal foods
correlated positively with CHD mortality rates, r=.79
(P<.001), and calories from vegetable foods correlated
negatively, r= -.80 (P<.001); this replicates earlier
findings.10 We also found that, generally, nutrients
associated with animal foods correlated positively with
CHD mortality rates, whereas nutrients associated with
vegetable foods and vegetable oils correlated negatively.
These results are in accordance with earlier international data using assorted food commodities and CHD
mortality.15'16'47 Diets high in cereals, legumes, and
vegetables have been consistently associated with low
plasma cholesterol levels and a low incidence of CHD.
Keys reported, "Fruits and vegetables other than roots
and tubers are much more prominent in the average
diets in Italy and Greece than in those of Finland, the
Netherlands, and the United States."2 This has been
shown in populations as diverse as American vegetarians,59-61 Japanese,62'63 the Tarahumara Indians of Mexico,64 or the Ugandans of East Africa.65 Some support
for a cardiovascular protective role of vegetable foods
comes from clinical trials and feeding studies as
well.66-68 Our data suggest that the higher consumption
of vegetables in France may also have helped to account
for a lower CHD mortality rate compared with Finland.
2778
Circulation Vol 88, No 6 December 1993
Factors in plants that might be protective have not been
fully identified but could include soluble fiber,69 saponins,70 and antioxidants.71,72 Soluble fiber promotes
plasma cholesterol lowering by binding bile acids in the
gut and promoting their excretion in the stool.69 Saponins block absorption of cholesterol.70 Antioxidants
such as beta carotene, ascorbic acid, a-tocopherol, and
phenolic compounds could help prevent LDL from
becoming oxidized; the strong atherogenicity of oxidized LDL has been demonstrated.71-73 A recent study
suggests that CHD mortality rates in middle-aged men
from 16 European countries were inversely related to
plasma vitamin E levels.74
Summary and Conclusions
Differences in coronary mortality
rates the world
could largely be explained by differences in dietary
cholesterol and saturated fat intakes. However, the
difference in coronary mortality rates between France
and Finland has, over many decades, puzzled scientists
because both have had similar intakes of cholesterol and
saturated fat. This paradox led us to take as broad a
look as possible at other dietary factors and CHD
mortality. Our study of 40 countries suggested that
disparate CHD mortality rates could be partly explained in 1977 by intakes of milk, butterfat, and
vegetable foods (particularly, vegetable oils and vegetables). The greater consumption of vegetable foods in
France compared with Finland illustrated that point.
Current scientific evidence gives credence to these
associations in 1993, although further studies are
needed to test the hypotheses suggested by this study.
Finally, this study has stressed that the association of
dietary factors with CHD mortality is very complex, and
differences in coronary mortality cannot be ascribed to
one nutrient or to one food only. It is necessary to
consider the total diet.
over
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Acknowledgments
This study was supported by research grants HL-20910,
HL-37940, and DK-40566 (Clinical Nutrition Research Unit)
and RR-334 (Clinical Research Center), all from the National
Institutes of Health.
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Differences in coronary mortality can be explained by differences in cholesterol and saturated
fat intakes in 40 countries but not in France and Finland. A paradox.
S M Artaud-Wild, S L Connor, G Sexton and W E Connor
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Circulation. 1993;88:2771-2779
doi: 10.1161/01.CIR.88.6.2771
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