Ischemic heart disease and alcohol-related causes of death: A view of the French paradox

ELSEVIER

Ischemic Heart Disease and AlcohoLRelated of the French Paradox

Causes of Death:

BEVERLEY BALKAU,

AND EVELINE ESCHWEGE,

PHD,

FRANCOIS

ESCHWEGE,

MD,

A View

MD

PURPOSE: In France the low rates of death due to ischemic heart disease have been attributed

to the high consumption of alcohol. However, the question remains: are the higher death rates for causes associated with akohol consumption an explanation? METJAODS: Diseases were defined according to the International Classification of Diseases, revision 9. World Health Organization data on country- and age-specific death rates were used. RESULTS: Official causes-of-death statistics for men 40-74 years of age show that in 1990 French men under 50 years old had low death rates from ischemic heart disease but a relatively high all-cause mortality rate, in contrast to low rates for men 60 to 74 years of age. Among French men aged 40-44 years in 1960,34% had died before reaching the age of 70-74 years. In comparison, 37% in the United States and 36% in England and Wales, had died by this age, with 4.5%, 14.19/o, and 15.2% of deaths, respectively, due to ischemic heart disease. If all of the men who died early of causes associated with alcohol had died of ischemic heart disease, there would still b e a lower rate in France (21%) than in the United States (26%) or in Engtand and Wales (25%). CONCLUSION: Thus, although some of the chronic heavy drinkers in France die early of causes associated with,excessive alcohol consumption, this is not the only reason for the low ischemic heart disease death rates. 0 1997 Elsevier Science inc. Ann Epidemiol 1997;7:490-497 KEY WORDS:

Alcohol,

lschemic

Heart

Disease, Neoplasms,

INTRODUCTION The debate continues as to why the French population has a low mortality from coronary heart disease. St. Leger, Cochrane and Moore f 1 ), using data from 18 countries, showed that for the year 1970 death rates from ischemic heart disease were negatively correlated with the consumption of pure alcohol and of wine per inhabitant per year and positively correlated with the intake of both saturated and monounsaturated fats. The French diet has a high intake of saturated fats, but ischemic heart disease is less frequent in France despite the fact that serum cholesterol concentrations are similar to those in countries with higher rateshence the French paradox (2). Renaud and de Lorgeril(2) used a cross-country correlation analysis to relate rates of coronary heart disease mortality with the consumption of dairy fat and wine; with dairy fat alone, 53% of the intercountry variation was explained, when wine was added this percentage increased to 76%. They proposed that wine had

From the INSERM U21, Facult6 de Medecine Paris&d (B.B., E.E.): and the Radiotherapy Department, Institut Gustave-Roussy (F.E.). Address reprint requests to: Beverley Balkau, INSERM U21, FacultC de Medecine Paris-&d, 16 Avenue Paul Vaillant Couturier, 94807 Villejuif Cedex, France. Received January 31, 1997; accepted June 17, 1997. 0 1997 Elsevier Science Inc. All rights reserved. 655 Avenue of rhe Americas, New York, NY 10010

Epidemiology,

Mortality,

French

beneficial effects on hemostatic factors. Criqui and Ringel (3) provided the most recent ecological analysis of this question, using data from 21 “developed” countries for the years 1965, 1970, 1980, and 1988. After adjustment for ethanol intake, animal fat did not have a significant effect on longevity in any of the years studied, nor did it have an effect on cardiovascular mortality in 1980 or 1988. They concluded that in the populations studied, ethanol, particularly ethanol in wine, was inversely related to cardiovascular mortality but not to longevity. Few studies have been published of causes of death in cohorts with very high alcohol consumption. In two Chicago cohorts (4), the problem drinkers (flagged by the employer’s medical department) and heavy drinkers (3 6 glasses per day) had coronary heart disease mortality risk ratios of 3.99 and 1.91 respectively, in comparison with the remainder of their cohort; these ratios were significantly different from I.00 even after adjustment for age and cigarette smoking. A study of 1536 rural Italian men (5) with a very high alcohol consumption (above the fourth quintile where the alcohol intake was more than 114 g per day, representing > 29% of energy intake) showed a significantly higher cardiovascular mortality among the heavy drinkers than among the men whose alcohol consumption was between the second and fourth quintiles, with death rates similar to those from cancer. The low frequency of ischemic heart disease in France 1047-2797/97/$17.00 PI1 SlO47~2797(97)0~85.9

AEP Vei 7, No. 7 Ocro~ f997: 490-497

Selected Abbreviations KID-9 = International

and Acronyms

Classification of Diseases, 9th edition

is not paralleled by a low all-cause death rate: “Aurres pays, awes moeurs” (6). We used cross-country ecological studies of 40-74.year-old men to explore whether early death from alcohol-related causes explains the French paradox.

“European Old” standard age distribution (8). The eight countries studied, during 1960-1990, had different ischemic heart diseasemortality rates (Table 2) and alcohol consumption habits (9) (Table 3). The eight countries were France, Australia, England and Waies, Finland, Italy, Northern Ireland, Scotland and the United States. If data were not available for a given year, the closest year for which data were available was used in the anaivsis.

RESULTS MATERIALS

AND METHODS

The definitions used for the various causes of death are regroupings from the International Classification of Diseases (7) revision 9 (ICD-9) (Table 1); correspondences were made for revisions 6, 7, and 8 of the ICD. The country- and age-specific death rates for the various causesof death were provided by the World Health Organization (Geneva) and were agestandardized according to the

1. Coding of causes of death according to the International Classification for Diseases.Revision 9

TABLE

Disease category

ICD-9 code

Malignant neoplasms Neoplasms associated with alcohol Malignant neoplasms of tongue, gum, floor of mouth, other and unspecified parts of mouth, orepharynx. hypopharynx, oesophagus Malignant neoplasms liver, primary; intmhepatic bile ducts Neoplasms of trachea, bronchus, lung Other tobacco-related neoplasms Malignant neoplasms of nasopharynx, ill-defined sites within the lip, oral cavity and pharynx Maligmant neoplasm of pancreas Malignant neoplasm of respiratory and inttathoracic organs Malignant neoplasm of bladder Malignant neoplasm of kidney and other unspecified urinary organs Neoptasms associated wrth tobacco smoking

189 Ahove two groupings

Diseases of the circulun~ry system Ischemrc heart disease Ccrehrovascular disease

390-459 410-414 430-438

L&cases of the respiratory system

460-519

Diseases of the digestwe system Chronic liver disease and curhosi\

520-579 571

140-208

141,~43-146,148,15~ 155.0,155.1 162

147,149 I57 (BO96) 160,161,163-I65 188

Sigm, qmpt~rms, ill-dehned ccrnditions

780-799

injury rind pc&clnrng Transport accidents Surcrdes and &f-mflicted

E800-E999 EBOO-E848 E950-E959

injuries

Cross-Sectional Study of Death Rates among Men Aged 40-74 Years in 1990 The 1990 age-standardized all-cause death rates among men aged 40-74 years were lower in France than in all but two of the other countries studied (Table 2). For the category “diseases of the circulatory system,” France had a low death rate. In contrast, France had a high death rate from “malignant neoplasms,” in particular for “malignant neoplasms associated with alcohol,” an intermediate rare f& the major single category of fatal neoplasms (Le., those of the “trachea, bronchus, lung,” associated with smoking), and the highest rate for “other malignant tobacco related neoplasms.” For the other major causes of death according to the ICD-9, mortality from “diseases of the respiratory system” was low in France, but for “diseasesof the digestive system,” both France and Italy had relatively high rates, due principally to “chronic liver disease and cirrhosis”; in France in 1990, 98% of these deaths in men in the 4O-74year age group were due to cirrhosis or were linked with alcohol (10). France had a particularly high rate of death from “signs, symptoms, ill-defined conditions.” In 1990 13% of such deaths were classified as “sudden death, cauLwunknown,” and 69% as “other ill-defined and unknown causes of morbidity and mortality” (IO). Sudden death and death of unknown causesare often considered to be death from ischemic heart disease (11); even if these deaths were all reclassified to ischemic heart disease, the resulting death rare would still be lower in France than in all other countries studied. For causes listed in the final chapter of the ICD-9. “injury and poisoning,” France had the second highest mte, following Finland. In France in 1990, the main causes were from motor vehicle traffic accidents (20%), accidental falls (lo%), and suicide (34%) (IO), all of which ~~~tlit be .associ-. ated with excessive consumption of alcohol. In c’trmparison, in Finland, the suicide rate was 50% higher than in France, and there was a high rate of accidental poisoning; in the United States, which had the next highest rare f&r these causes of death, the suicide and accidental f;tlls clead~rates were lower than in France, but the hrlmici&’ r::te was very high. Age-standardized rates can mask differenuea 11-j death mtes between age groups. In 1990 French me11;~ceici40-,50

492

AEP Vol. 7, Nu. 7 October 1997: 490-497

Ralkau et al. THE FRENCH PARAMI)X

TABLE 2. 1990 &e-standardized

death rates per l~,~ France

Disease category

men aged 40-74 years in eight countries USA

Italy

Australia

England/Wakes

Finland

Scotland

N. Ire1

Malignant neoplasms Associated with alcohol Trachea, bronchus, lung Other tobacco related neoplasms

5i04 83 132 103

484 46 166 76

418 27 164 49

383 30 111 49

430 31 148 55

366 20 132 55

491 41 185 61

435 21 140 68

Diseases of the circulatory system Ischemic heart disease Cerebrovascu1ar disease

285 124 58

379 187 87

536 318

54

460 322 64

609 447 86

733 510 119

763 562 123

740 565 88

Diseases of the respiratory system

54

62

96

82

97

85

127

158

Diseases of the digestive system Chronic liver disease and cirrhosis

84 56

87 64

58 33

42 23

39 14

69 36

59 28

35 11

signs, symptoms, ill-defined conditions Injury and poisoning Transport accidents Suicide and self-inflicted

injury

Other causes AH causes

4s

10

11

2

2

6

3

2

118 24 41

66 26 15

87 25 25

64 19 25

48 12 15

195 31 60

72 21

75 16 21

109

89

136

82

77

84

80

66

1199

1177

1342

1115

1302

1538

1595

1511

a Boldface numbers are totals for entire category, only several of which are listed individually

years had a higher mortality rate than men in most of the studied countries (Figure 1). In contrast, French men aged 65-74 years had the lowest death rate of all countries. Causes of death will differ by age, according to country. For the category “ischemic heart disease,” in 1990 the death rate at all ages was the lowest in France (Figure 2A); until the age of 50-54 years, in all seven other countries, this death rate increased more rapidly with age than in France. In contrast, at all ages French men had high death rates for “malignant neoplasms associated with alcohol” (Figure 2B), for “chronic liver disease and cirrhosis” (Figure 2C), and, until the age of 60 years, from deaths from tobaccorelated malignant neoplasms, including those of the “trachea, bronchus, lung” (Figure 2D). Death from “signs, symptoms, ili-defined conditions” was more common in France than in other countries (data not shown), and in 1990 accounted for 7% of deaths for young

TABLE 3. Alcohol consumption (in liters) and type of alcoholic beverage, per capita by country for 2 years: 1961 and 1991 (9). (Total alcohol includes cider) Counttv France Italy United States Australia United Kingdom Finland

Total pure alcohol” 17.7, 11.9b 12.3, 8.4 5.1, 7.0 6.4, 7.7 4.5, 7.4 2.0, 1.4

Wine

Beer

126,67 108, 57 3.6, 7.2 5, 19 12, 12 1. 7

37.40 6, 22 57, a7 99, 102 89, 106 22. 85

Spirits pure alcohol 2.2, 1.2, 2.1, 0.8, 0.8, 1.4.

2.5 1.0 2.1 1.1 1.6 2.6

’ Conversion of volumes of wine and beer to pure alcohol was made according to the country specific figures. h The first number given refers to 1961; the second number, to 1991.

14

in column at left.

men aged 40-44 years and for 3% among men 70-74 years old (9). Another ~mpo~ant cause of death, particularly in younger men, was “injury and poisoning”; in 1990 in France, in the 40-44year age group, 28% of deaths were due to this cause (lo), in comparison with 26% from all forms of “malignant neoplasms” and 15% from “diseases of the circulatory system.” In 1990 French men under 50 years of age had a relatively high mortality rate, and although they had a lower risk of death from ischaemic heart disease, they had higher risks of death from cirrhosis, neoplasms associated with both alcohol and tobacco, ill-defined conditions, and “injuries and poisonings”; over the age of 60 years they had a lower all-cause death rate. Prospective Study of the Cohort of Men Born in 1916-1920 For the men aged 40-44 years in 1960 (who were born in 1916-1920 and stilf living), we estimated the percentages surviving to each age group, using the country and agespecific death rates. Figure 3 shows the difference in cumulative mortality, in comparison with France, between the ages of 40-44 and 70-74 years in this cohort. Of the French men aged 4044 years in 1960, 2.1% had died in the following 5 years, 1960-1965, 5.4% between 1960 and 1970, and corresponding to the oldest age group, 33.8% between 1960 and 1990. The French men had, up until the age of 50-54 years, a relatively high mortality and at age 70-74 years, the lowest cumulative death rate. For the various countries rates of death due to “ischaemic heart disease,” showed a cumulated difference with reference

1751

FIGURE 1. Age-specific all-cause male death rates in 1990 for the eight studied countries, in comparison to France (lC@%). French death rates (% per-year) are given by age group.

s s2 ISOB Lt! ; 125*= 92 3 c = z 4 x z” = <

loo

SO’

to France that increased with age (Figure 4A). For “malignant neoplasms associated with alcohol” (Figure 4B), France had the highest cumulative mortality at all ages; nearly 3% died of “chronic liver disease and cirrhosis” in both France and Italy (Figure 4C) before the age of 70-74 years. For neoplasms associated with tobacco smoking, the French men had a lower cumulative mortality (Figure 4D). For “signs, symptoms, ill-defined conditions,” (data not shown) French men, at all ages, had a higher cumulative death rate than those in other countries, and it is estimated that 2.1% of the French men died from this cause before the age of 70-74 years, in comparison to 0.6% in America and 0.02% in England and Wales. Before 50-54 years of age, these figures were 0.5%, 0.1% and 0.0050/o,respectively. Finally for “injuries and poisonings,” (data not shown), the cumulative frequency of this cause of death was high in France; by the age of 70-74 years, 4.2% of French men died of this cause, in comparison with 3.3% in the United States and 1.6% in England and Wales. The corresponding percentages for men aged 50-54 years were 1.4%, l.l%, and 0.5%, respectively. The cumulative mortalities for “ischemic heart disease”, up until the ageof 70-74 years,was 4.5Ohin France in comparison with 14.1% in the United States and 15.2Ohin England and Wales. Causesof death related to heavy chronic alcohol consumption (malignant neoplasms and cirrhosis) were 2.8% and 4.0% higher, respectivefy, while those associated with illdefined conditions, “injuries and poisonings,” and “malignant neoplasms associated with tobacco smoking” were higher by 2.1% and 3.4%. If all of these alcohol-related deaths were instead deaths due to ischemic heart disease, the associated cumulative ischemic heart disease mortality

,

i

I

i

t

i

I

404-S

45-49

50-5-t

55-59

60-64

M-69

'70-74

Age

0.33

0.49

0.75

1.15

1.72

2.42

3.54

Frenchram 5%Pry=

in France would still be lower (21.4%) than in the United States (26.2%) or in England and Wales (24+8%f. By the age of 50-54 years, the corresponding percentages would be 3.2%, 3.8%, and 2.30/o,respectivefy. --DISCUSSION In both the cross-sectional and cohort studies of death caused by ischemic heart disease that are presented here, French men had lower death rates than men in other countries, but relatively more deaths from causes associated with excessive alcohol consumption (i.e., malignant neoplasms, cirrhosis, poorly defined causes, and accidents). The mortality rate for French men over 60 years of age was comparatively low. Under 50 years of age, the excess mortality from causes related principally or in part to excessive alcohol consumption partly counterbalanced the low mortality due to cardiovascular disease, yielding a relatively high mortality rate. A recent French study estimated a 29% attributabie risk of premature mortality in men aged 35-64 years, for an alcohot consumptjon of > 25 ml per day (~~~~r<~xirnately two glasses per day), after adjusrmenr for age, body mass index, and smoking habits (12). For younger men under 40 years of age, the all causedeath rates in the United States and Finland were higher than in France in 1990. In this age group, c>neof the most frequent causes of death was by accidents, some of which would be caused by excessive alcohol consumption; Finland had the highest death rate, followed by France and the United States, which had similar rates. In all countries studied, death due to ischemic heart disease was rat’s hefore the age

0.03

0.02

I 0.07

I 0.05 0.09

1 0.09

I

0.29

I

0.18

1

0.10

0.06

,

0.03

,

0.02

,

So-54 55-59 60-64 a-69

,

40-44 45-49

,

.*..*.........-....*...*..*..“............-

-------~~~---

0.09

1

0.43

lo.14

,

mm a per year

French

N. Irclmd

French r&s % pc’ year

4s

Fmncc

Italy

t 50-54 0.16

t 45-49 0.09 0.04

t

0.06

45149 s&4 0.04

4-M

0.02

d44

t

0.14

6660

t 0.27

0.38

55-59 6049

0.11

&9

0.48

Cl-69

I

0.14

t 0.57

Age French mes %ptrye=

Age F;;;yy;

FnnCe AttSUdii

Italy N. Ireland Engl& W&s Finland USA

70-74

0.17

65169 70174

Scotland

causes, in comparison to France (100%). French death rates by cause (% per year) are given by age group. A, ischemic heart disease; B, malignant neoplasms associated with alcohol; C, cirrhosis; D, malignant neoplasms associated with tobacco smoking.

FIGURE 2. Age-specific male death rates in 1990, for various

p,

c

I_----e------

USA

Australia

I;inltnct Ettgl& Wnles

N. lrcland Scotland

AEP vol. 7, No. 7 October 1997: 490-4Y7

FlGXXE 3. Difference in cumulated all-cause mortality in comparison to France, in the cohort of men aged40-44 yearsin 1960 (born in 19161920). The cumulated French male morrality (%) is given for each age class.

2

z = 2.5 .g E

B L a

0

2.1

5.4

9.8

16.1

24,l

3 3.8

Cumulative French

mortality (46)

of 40 years. Xncfusion of rhese younger men in our study would change the age standardized death rates and the cumulative percentages surviving; however, the conclusions would be similar. Although moderate alcohol consumption appears to be protective for ischemic heart disease (13, 14), it has been associated with an important risk factor: high blood pressure (15-17). In the INTERSALT study, compared with nondrinkers, men whose alcohol intake was 34-57 g per day had an average increase of systolic~di~tolic blood pressures of 2.711.6 mmHg, and those who drank > 57 g per day had an average increase of 4.61’3.0tnmHg (15). This observation may explain the higher cardiovascular death rates among heavy drinkers (4, 5). In addition, men who consume alcohol to excess tend to be smokers, to be phys~caily inactive, and perhaps to consume a high-fat diet. Thus death due to ischemic heart disease and to alcohol-related causes may well be competing causes of death. The published studies provide no conclusive results on whether the type of alcoholic beverage is important (18). Many of the studies have been done in countries with a relatively low alcohol consumption, where it is more difficult to show significant associations; others were conducted within population groups where there is a strong preference for one type of alcoholic beverage (Table 3), and cultural differences may explain apparent beneficial effects ( 19). The low ischemic heart diseasedeath rates seen in official French mortality statistics are not only due to countryspecific practices in the certification and coding of death certificates (20, 2 1). Results from the MONICA study con firm that even with well-standardized definitions of coronary events, France retains a low incidence rate for fatal and nonfatal events: for men and women aged 35 to 64 years,

the age-standardized rates were on average, 297 per 100,000 in France, 288 in Italy, 492 in Australia, SO8in the United States, 777 in Finland, 781 in Northern Ireland, and 823 in Scotland (22). Nevertheless, there was a wide variation within France, from 240 in Toulouse, to 314 in Lille and 336 in Strasbourg (22); these variations may be related to differences in dietary habits. Differences are likely to exist in the certification of other causes of death+ The medical training of the certifying doctors will differ from country to country as will the cultural acceptability of certifying a death as being due to cirrhosis or suicide. As we have shown, officiat death rates may depend on the method of coding the certified causesof dearb (20). While the cause-specific death rates may be disputed, the intercount~ comparisons of the all-cause mortality rates are not: French men have relatively high death rates at younger ages, and relatively low rates over the age of 60 years; this was true in both 1990 and in the cohort of men born in 1916-l 920 and followed from the age of 40-44 years. Ducimetiere and Richard analyzed mortality and dietary habits in France, in comparison with neighboring countries to the north, i.e., ReIgium and western Germany, and to the south, Italy and Spain (23). In terms of the north-south gradient, France did not take an intermediate position; it had lower-than-expected death rates due to cardiovascular disease,particularly ischemic heart disease, but higher-thanexpected intakes of butter, cheese, mitk, diary products, with a 100% higher-than-expected intake of wine and a 46% lower.than=expected intake of beer. These isuthors concluded that the low rate of ischemic heart disease in France “could be more readily explained by alcohol drinking habits than by any other dietary peculiarity.” In France the high per-capita alcohol consw-nprion is

496

m

Balkau ec al. THE FRENCH PARADOX

AEP Vol. 7, No. 7 OcmbeT1997: 4w-497

497

likely to be due to the fact that a large percentage of the population drinks in moderation while there is a small percentage of heavy chronic drinkers who carry a high risk of early death from causes associated with a chronic alcohol consumption and from cardiovascular diseases. Early death from alcohol-related causes among these heavy chronic drinkers does not account for the low ischemic heart disease mortality in France.

We thank Maryse Prud’homme, Anne Forhan, and Patricia Grand for asststance in Jata analysis and manuscript preparation and Georgina Kramer, of the World Health Organization, Geneva, for providing the dara on cause-specific death rates.

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8. World Health Statistics Annual 1991. lYY2. 19Y’:i. (lenev,l: World Health Organization, 1992, 1993, 1994. 9. Produktschap voor Gedistilleerde Dranken: World I &nk Trends I99 3. Henley-on-Thames: NTC Publications, 1994. 10. Lion 1, Hatton F, Maguin P, et al. Statistiques de, cause? medicale\ de de& 1990. Paris: Les Editions INSERM, 190 q 11. Armstrong DL, Wing SB, Tyroler HA. Uruted State> morrahry from IIIdefined causes, 19681988: Potentiel effects on heart disease rnonalitv trends. Int J Epidemiol. 1995;24:522-527 12. Zureik M, Ducimetiere P. Hugh alcohol-related premarurc mortality in France: Concordant estimates from a prospective cohort study and national mortality statistics. Alcohol Chn Exp Res. 1996;20:428-433, 13. Marmot M, Brunner E. Alcohol and cardiovascular disease: The status of the U-shaped curve. Br Med J. 1991;703:565--Vd 14. Poikolainen K. Alcohol and mortality: A revieiv. 1 tllm Eptdemiol 1995;48:455-465. 15. Marmot MG, Elliot P, Shipley M], et al. Alcohol and blood pressure: The INTERSALT study. Br Med J. 1994;308:126--- 1267. 16. Lip GYH, Beevers DG. Alcohol, hypertension. coronary heart &case and stroke. Clin Exp Pharmacol Physiol. 1995:22:18Y-194. 17. Kaplan NM. Alcohol and hypertension. Lance1 19Y5; 345: 1588-I 589. 18. Rimm EB, Klatsky A, Grobbee D, Stampfer MJ. Review of moderate alcohol consumption and reduced risk of coronary bean disea.se: Is the effect due to beer, wine, or spirits? Br Med J 1996;312:731-736. consumption and coronary 19. Rimm EB. Invited commentary-Alcohol heart disease: Good habits may be more imporranr than rust good wine. Am J Epidemiol. 1996;143:1094-1098. 20. Balkau B, Jougla E, Papoz L and the EURODIAB Subarea 1.: Study Group. European study of the certification and coding of causes ot death of six clinical case histories of diabetic picnts. lnt I Epidcmiol. 1993;22:116-126. 21. Stehbens WE. The quahty of eptdemtologtcal dara u-r ccrninary heart disease and atherosclerosis. J Clin Epidcmiol. 19Y <:46: I3 37 -1346 22. Tunstall-Pedoe H, Kuulasmaa K, Amouyel I’, et ,ri. Myocardial infarction and coronary deaths in the World Health Orgaruzartr 111MONICA project. Circulation. 1994;90:583-612. 23 Ducimetierr P, Richard JL. Dietary lipids and coronary heart disease: Is there a French paradox? Nutr Metnh ihdio~ x’r.rhr RIS 1992;2: 195-201.