Why heart disease mortality is low in France: the time lag explanation.

Malcolm Law, Nicholas Wald

Summary points

Mortality from ischaemic heart disease in France is about a quarter of that in Britain, but the major risk factors are similar

Undercertification of ischaemic heart disease in France could account for about 20% of the difference

The high consumption of alcohol in France, and of red wine in particular, explains little of the difference

We propose that the difference is due to the time lag between increases in consumption of animal fat and serum cholesterol concentrations and the resulting increase in mortality from heart disease--similar to the recognised time lag between smoking and lung cancer. Consumption of animal fat and serum cholesterol concentrations increased only recently in France but did so decades ago in Britain

Evidence supports this explanation: mortality from heart disease across countries, including France, correlates strongly with levels of animal fat consumption and serum cholesterol in the past (30 years ago) but only weakly to recent levels. Based on past levels, mortality data for France are not discrepant

In France mortality from ischaemic heart disease is about a quarter of that in Britain.[1-7] The major risk factors are no more favourable in France, and this so called "French paradox" has not been satisfactorily explained. Table 1 shows the difference in mortality from heart disease between the countries, and table 2 shows the similar levels of animal fat consumption, serum total cholesterol and high density lipoprotein cholesterol concentrations, blood pressure, and (in men) smoking. The French paradox is usually attributed to the higher consumption of alcohol in France, notably of wine,[2-5] and some have suggested a specific effect of red wine. In this article we assess quantitatively the extent to which this and other possible explanations can account for the low rate of heart disease in France. We then consider a novel "time lag" hypothesis, which, we believe, is the main explanation for the paradox.

Table 1 Mortality (No of deaths/100 000) from ischaemic heart disease and poorly specified causes in people aged 55-64 in France and Britain in 1992[7 8]

 
                                              Men 
 
Certified cause of death (ICD-9    France   Britain   Difference 
 code) 
 
Ischaemic heart disease (410-4)      128       487        -359 
All poorly specified or               71         3          68 
 unspecified causes: 
  Unspecified or unknown causes    24        1          23 
   (799.9)(*) 
  Poorly specified cardiac         47        2          45 
   causes(*): 
    Ventricular or unspecified     6         1 
     dysrhythmia (427.1,427.4, 
     427.8, 427.9) 
    Cardiac arrest (427.5)         9         0 
    Heart failure (428)            19        1 
    Unspecified heart or           5         0 
     cardiovascular disease 
     (429.2, 429.9, 440.9) 
    Cardiogenic shock (785.5)      3         0 
    Sudden death (798.1)           4         0 
Ischaemic heart disease plus        199       490        -291 
 poorly specified causes 
 
                                   Men         Women 
 
Certified cause of death (ICD-9    Ratio   France   Britain 
 code) 
 
Ischaemic heart disease (410-4)     1:4       27       153 
All poorly specified or            24:1       25        2 
 unspecified causes: 
  Unspecified or unknown causes              8     0.3 
   (799.9)(*) 
  Poorly specified cardiac                 17        2 
   causes(*): 
    Ventricular or unspecified              2        1 
     dysrhythmia (427.1,427.4, 
     427.8, 427.9) 
    Cardiac arrest (427.5)                  3        0 
    Heart failure (428)                     7        1 
    Unspecified heart or                    2        0 
     cardiovascular disease 
     (429.2, 429.9, 440.9) 
    Cardiogenic shock (785.5)               1        0 
    Sudden death (798.1)                    1        0 
Ischaemic heart disease plus      1:2.5      52       155 
 poorly specified causes 
 
                                         Women 
 
Certified cause of death (ICD-9    Difference   Ratio 
 code) 
 
Ischaemic heart disease (410-4)        -126      1:6 
All poorly specified or                 23      12:1 
 unspecified causes: 
  Unspecified or unknown causes      8 
   (799.9)(*) 
  Poorly specified cardiac          15 
   causes(*): 
    Ventricular or unspecified 
     dysrhythmia (427.1,427.4, 
     427.8, 427.9) 
    Cardiac arrest (427.5) 
    Heart failure (428) 
    Unspecified heart or 
     cardiovascular disease 
     (429.2, 429.9, 440.9) 
    Cardiogenic shock (785.5) 
    Sudden death (798.1) 
Ischaemic heart disease plus          -103       1:3 
 poorly specified causes 

(*) French data provided by Dr Francoise Hatton, INSERM.

Table 2 Average values of risk factors for ischaemic heart disease in France and Britain, 1985-1990

 
                                               France   Britain 
National consumption data 
No of cigarettes (per adult daily)[9]            6.4      6.5 
Animal fat (% of total energy intake)[2]        25.7     27.0 
Fruit and vegetables (% of total energy          5.0      4.3 
 intake)[2] 
Survey data (age 50-70 years) 
Percentage who smoked cigarettes[9-13]: 
  Men                                            32       29 
  Women                                           9       30 
Mean serum total cholesterol concentration 
 (mmol/l)[12-19]: 
  Men                                           6.1       6.2 
  Women                                         6.5       6.7 
Mean high density lipoprotein cholesterol 
 concentration (mmol/l)(14-19):                 1.3       1.3 
  Men                                           1.5       1.5 
  Women 
Mean systolic blood pressure (mm Hg)[12 13]:    150       148 
  Men                                           149       148 
  Women 

This hypothesis arises from the observation that animal fat consumption and serum cholesterol concentration have been similar in France and Britain for a relatively short time--about 15 years. For decades up to 1970, France had lower animal fat consumption (about 21% of total energy consumption v 31% in Britain) and serum cholesterol (5.7 v 6.3 mmol/l), and only between 1970 and 1980 did French values increase to those in Britain.[2 12-25] There must be a time lag between the increase in serum cholesterol concentration and the full effect of the resulting increase in coronary artery atheroma and risk of death from ischaemic heart disease. The observations that Western populations are exposed to high levels of dietary saturated fat and serum cholesterol from childhood, that atheroma progresses slowly throughout life, and that only about 1% of men die from ischaemic heart disease before the age of 50[9] suggest that decades of exposure must elapse. We propose that this is the main explanation for the low mortality from ischaemic heart disease in France. A similar time lag is recognised with smoking and lung cancer, in which it is the smoking habit of 30-40 years ago that is important in determining current risk,[26] and a long incubation period for heart disease has been previously proposed.[27]

Previous explanations of the paradox

Undercertification of ischaemic heart disease

Not all deaths caused by ischaemic heart disease in France are classified as such; French doctors tend to certify some (such as those caused by heart failure and other late complications of myocardial infarction) as poorly specified causes.[5 28] Table 1 shows that poor certification is important but can only partly explain the paradox. The excess attribution of deaths to poorly specified cardiac causes in France is equivalent to 12% of the difference in mortality from heart disease between France and Britain (45/359 in men and 15/126 in women), and to all poorly specified causes is equivalent to 19% (68/359 and 23/126).

Smoking

The prevalence of smoking in men is similar in France (32%) and Britain (29%), but in women it is lower in France (9% v 30%) (table 2). These patterns have persisted for over 30 years[9] and are reflected in mortality from lung cancer (similar in French and British men but lower in French than British women[7]). The low prevalence of smoking in French women is consistent with the fact that the ratio of mortality from ischaemic heart disease in French to British women (1:3) is lower than the equivalent ratio in men (1:2.5) (table 1). Given that the risk of ischaemic heart disease in 55-64 year old smokers is twice that of nonsmokers,[29] the risk in French women ((2 x 9%) + (1 x 91%)) divided by that in British women ((2 x 30%) + (1 x 70%)) is 84%, and 84% of 1:3 (the ratio of mortality in French women to that in British women) is 1:2.5, the same as the ratio in men. The sex difference is explained, but not the residual mortality ratio of 1:2.5 in both sexes.

Alcohol

Figure 1 shows the relative risk of mortality from ischaemic heart disease according to alcohol consumption in the American Cancer Society's cancer prevention study I (the largest cohort study in the world, with 18 771 deaths from ischaemic heart disease),[30] cancer prevention study II (10 252 deaths from ischaemic heart disease),[31] and in the three next largest cohort studies (recording 1061 deaths,[32] 940 deaths,[33] and 611 events[34]). The studies show a consistent reduction in risk of about 20% in people who drink about one unit of alcohol a day than in people who drink none but, taken together, indicate that drinking more than about one unit a day confers little or no further protection. The data are consistent with a dose response relation. The pattern is the same in men and women.[31 33] This non-linear dose-response relation probably reflects a summation of opposing effects of alcohol: the protective effects (mainly the increase in serum concentration of high density lipoprotein cholesterol but also the favourable changes in haemostatic factors) are countered by the higher blood pressure, which increases risk.

[Figure 1 ILLUSTRATION OMITTED]

If all French men and no British men drank at least one unit of alcohol a day, other factors being equal, the difference in ischaemic heart disease would be about 20%. If half of British men drank at least one unit of alcohol daily the difference would be 10%, and if three quarters of British men did so it would be 5%. The …