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© 2008 American Society for Nutrition J. Nutr. 138:946-953, May 2008

Nutritional Epidemiology

The French National Nutrition and Health Program Score Is Associated with Nutritional Status and Risk of Major Chronic Diseases1–3,

Carla Estaquio4,*, Katia Castetbon5, Emmanuelle Kesse-Guyot4, Sandrine Bertrais4, Valérie Deschamps5, Luc Dauchet4, Sandrine Péneau4, Pilar Galan4 and Serge Hercberg4–6

4 UMR U557 INSERM, U1125 INRA and Paris 13 University, CNAM, Centre de Recherche en Nutrition Humaine-IdF, 93017 Bobigny, France and 5 Unité de Surveillance et d'Epidémiologie Nutritionnelle, Institut de Veille Sanitaire; PARIS 13 University, CNAM, Centre de Recherche en Nutrition Humaine-IdF, 93017 Bobigny, France and 6 Département de Santé Publique, Hôpital Avicenne, 93017 Bobigny, France

* To whom correspondence should be addressed. E-mail: c.estaquio{at}uren.smbh.univ-paris13.fr.


   ABSTRACT
TOP
 ABSTRACT
Introduction
 Materials and Methods
 Results
 Discussion
 LITERATURE CITED
 
Few studies have found that adherence to dietary guidelines reduces the incidence of chronic disease. In 2001, a National Nutrition and Health Program (Program National Nutrition Santé) was implemented in France and included 9 quantified priority nutritional goals involving fruit, vegetable, and nutrient intakes, nutritional status, and physical activity. We developed an index score that includes indicators of these public health objectives and examined the association between this score and the incidence of major chronic diseases in the Supplémentation en Vitamines et Minéraux AntioXydants cohort. Data from middle-aged adults free of major chronic diseases and who provided at least 3 24-h dietary records during the first 2 y of follow-up have been included in the present analysis (n = 4,976). Major chronic disease, documented during the 8-y follow-up period (n = 455), was defined as the combination of cardiovascular disease (n = 131), cancer (n = 261), or death (n = 63), whichever came first. In fully adjusted Cox models, men in the top tertile score compared with those in the lowest one had a 36% lower risk of major chronic diseases (hazard ratio = 0.64; 95% CI: 0.44–0.96). No association was found in women. Healthy diet and lifestyle were associated with a lower risk of chronic diseases, particularly in men, thereby underlying relevance of the French nutritional recommendations.


   Introduction
TOP
 ABSTRACT
 Introduction
Materials and Methods
 Results
 Discussion
 LITERATURE CITED
 
Poor nutritional status is one of the greatest risk factors in several chronic diseases, including cardiovascular disease (CVD),7 certain cancers, obesity, diabetes, and osteoporosis (1–3). Epidemiological studies evaluating the relationship between diet and chronic disease often focus on a single group of foods or nutrients. It would be of a great benefit for public health to be able to pinpoint this relationship taking into account diet as a whole and including other nutritional risk factors such as body mass, blood pressure (BP), and biochemical markers of nutritional status.

Recently, dietary patterns have been developed by using a priori methods (4–6). Greater adherence to healthy dietary patterns has been associated with lower mortality (7–9) and a lower incidence of CVD in various populations (10–13). Whereas most indexes are based on food groups (and some include nutrients), one published index score included both dietary (groups of foods and nutrients) and nondietary components [physical activity (PA) and BMI] (14) and found a significantly reduced risk of cancer in postmenopausal women.

In France in 2001, the French National Nutrition and Health Program [Program National Nutrition Santé (PNNS)] was implemented under the aegis of the Ministry of Health. Its general goal is to improve the health status in the general population by intervening at the level of one of its determinants, nutrition (15). Among the 9 nutritional goals targeted for the 2001–10 period, 5 are related to diet [fruits and vegetables (F&V), calcium and vitamin D, lipids, carbohydrate and fibers, and alcohol intake), 1 concerns PA in daily life, and 3 involve nutritional markers (serum cholesterol, BP, and BMI). Whereas some national surveys are being conducted to describe the nutritional situation according to PNNS indicators, this is also worth evaluating the possible benefit in prevention of chronic diseases.

We have developed an index score that includes all indicators used to define PNNS objectives. The aim of our study was to examine the relationship between this score and the incidence of major chronic diseases in a cohort of French adults.


   Materials and Methods
TOP
 ABSTRACT
 Introduction
 Materials and Methods
Results
 Discussion
 LITERATURE CITED
 
Study population

The design, methods, and rationale of the Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) study have been described elsewhere (16). Briefly, the SU.VI.MAX study was initially designed as a randomized, double-blind, placebo-controlled, primary prevention trial to test the efficacy of daily supplementation with antioxidant vitamins and minerals at nutritional doses [120 mg of ascorbic acid, 30 mg of vitamin E ({alpha}-tocopherol), 6 mg of β-carotene, 100 µg of selenium, and 20 mg of zinc] in reducing the incidence of ischemic heart diseases and cancer. Women were 35–60 y of age and men were 45–60 y of age at enrollment. The lower age in women was based on the incidence of breast and uterine cancers and ischemic CVD (16). The SU.VI.MAX study was approved by the Ethical Committee for Studies with Human Subjects at Paris-Cochin Hospital and the Commission Nationale Informatique et Liberté. Throughout the study, respondents completed dietary records and health and demographic questionnaires, provided blood samples, and underwent physical examinations.

Subjects who completed at least 3 24-h dietary records during the first 24 mo of follow-up, were free of cancer or ischemic CVD during that period, and had no missing covariables were included in the present analyses.

Data collection

Information on gender, age, smoking habits, education level, occupation, and marital status was collected by a self-administrated questionnaire at enrollment. Each subject underwent a yearly visit involving either biochemical sampling (at y 0, 2, 5, and 7) or clinical examination (at y 1, 3, and 7).

Dietary assessment

Subjects were asked to provide 24-h dietary records every 2 mo for a total of 6 records per year; each day of the week and all seasons were represented (16). Participants used a validated reference manual for coding food portions (17). Nutrient intakes, including vitamins, minerals, and alcohol, were estimated using food composition tables validated for the usual French foods (18).

Assessment of PA

PA was assessed using the French self-administered version of the Modifiable Activity Questionnaire (19). Briefly, information was collected about the type, frequency, and duration of activity performed. Using published compendiums (20,21), metabolic equivalent tasks were assigned to each leisure activity reported and summary scores were computed, including the mean metabolic equivalent task-hours per week of PA.

Blood sampling

At baseline, a 35-mL venous blood sample was obtained from participants who had been fasting for 12 h. Some nutritional biomarkers were measured (22).

Clinical examination

Height, weight, and BP were measured at each clinical examination. Weight was measured using an electronic scale with subjects wearing indoor clothing and no shoes. Height was measured under the same conditions to the nearest 0.5 cm using a wall-mounted stadiometer. BMI was calculated as weight (kg) divided by height-squared (m2). BP was measured using a standardized procedure with a mercury sphygmomanometer. It was taken once from each arm in subjects who had been lying down for 10 min. The mean of these 2 measurements was used for analyses. If systolic BP (SBP) was ≥160 mm Hg or diastolic BP ≥ 110 mm Hg, BP was remeasured after another rest period of 10 min and the lowest value was retained.

Follow-up of major chronic diseases

Participants were asked to complete a monthly questionnaire summarizing treatment compliance and health events. Information about health outcomes was obtained from subjects' reports and from data collected at yearly visits. If there was no contact with a participant for a long period or if a participant did not attend the yearly scheduled visit, an investigation was launched to determine the reasons. Once an adverse event was suspected, all relevant records, including results of diagnostic tests and procedures (imaging, biopsy, etc.) were collected from physicians and hospitals involved or directly from participants. Each event was reviewed by expert committees who did not know the supplementation assignment. Cancers were validated by histologic reports; ischemic CVD were confirmed by radiologic reports or by meeting a combination of clinical, biological, and electrocardiographic criteria when appropriate. Causes of death were confirmed by information from relatives or physicians. Vital status of all subjects and causes of death were verified with the national death registry.

Construction of the French score of indicators of PNNS objectives

    Indicator definition. Construction of the French score of indicators of the PNNS objectives (FSIPO) was primarily based on indicators used to define the 9 priority PNNS public health objectives (Supplemental Table 1). A "healthy" threshold was identified for each indicator using the statement of the objective itself or an external reference like the French national recommended dietary allowances (RDA) (23) or distribution observed within the SU.VI.MAX study. For instance, the indicator concerning the F&V group was defined according to the PNNS definition of "low consumers" i.e. <3.5 servings per day (24). The indicator was therefore the intake of F&V around this threshold. The next step was to identify foods included in the F&V group. According to detailed information provided in PNNS dietary guidelines, this group includes all fruits (excluding dried fruits), vegetables (excluding potatoes and legumes), 100% juices, and mixed foods containing F&V. French recipes validated by dieticians were used to assess amounts consumed from mixed foods. The number of servings was defined as total weight of F&V (g/d) divided by a standard serving size, i.e. 80 g. Thresholds for indicators of calcium, fibers, and simple carbohydrates were defined according to the French RDA (23). Thresholds for BP and cholesterol components were defined by means observed in the SU.VI.MAX study. The intake of simple sugars was assessed by the contribution of total simple sugars to total energy intake (EI; excluding alcohol) with respect to the French RDA (23). The same approach was used for assessing consumption of complex carbohydrates. Because only a subsample of subjects had available vitamin D status measurements, it was not included in the component corresponding to the calcium and vitamin D objective.

    Index scoring. Scoring decisions were made a priori and based on the national program objectives (Supplemental Table 1) or epidemiological or clinical evidence (1–3) that had been evaluated by a task group, which included nutrition researchers, epidemiologists, statisticians, and dieticians.

The general approach (Table 1) consisted of attributing 1 point (maximum score) to subjects who reached the PNNS indicator threshold, with the exception of PA, for which an additional one-half point was given to subjects who exceeded current guidelines. For each component, intermediate points (0.5 points) were attributed to those who did not entirely attain the threshold but whose nutritional status was considered "fair." The rest of the subjects did not receive any point. PNNS priority objectives are not ranked according to their public health importance. The task group chose to apply a weighing scheme to capture specific dietary patterns and nutritional status indicators that have been consistently associated with lower risks of chronic disease (Table 1). A priori weightings and internal weightings were chosen on this basis.


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  		TABLE 1 Public health objectives, points, thresholds, and weightings for the FSIPO

 
    Point deductions regarding EI. Points were deducted for individuals with an EI greater than their estimated needs according to basal metabolic rate (BMR) and PA levels. Schofield's equations (25) were used to estimate each individual's BMR. PA data were used to classify subjects into 3 categories: sedentary, moderate, and vigorous. Next, PA level values for each category were used (26). Individual energy expenditures (BMR x PA level) were then compared with EI reported in the 24-h dietary records. If reported EI were >5% of the calculated energy needs, the total score was reduced by the same proportion. For example, if a volunteer reported EI 15% higher than his or her actual energy expenditure, the total score was reduced by 15%.

In total, the FSIPO consisted of 13 components based on indicators of the 9 priority objectives described in the PNNS. The overall FSIPO ranged from 0 to 17.5 points; higher scores reflected dietary patterns that approached indicators used for defining national objectives.

Statistical analyses

Statistical analyses were performed by gender to account for the study design. The mean of all 24-h dietary records assessed during the recording period was used in the analyses. Some serum or plasma nutrient concentrations were log-transformed to improve normality. We used ANOVA to investigate the relationship between the FSIPO tertile distribution and demographic and socioeconomic status. Multivariate linear regression models controlled for age (continuous) and total EI (continuous) were used to examine associations of nutrient intake or biomarkers to the FSIPO and included a linear contrast to test for trend. We analyzed relationships between the FSIPO and major chronic disease events by survival analyses. Follow-up time was the time between the end of the first 2 y of follow-up (1996–97) and the first CVD or cancer event, death, last contact, or the day the subject completed a total of 10 y of follow-up (2004–05). Initially, the design of the study defined primary outcomes as major fatal and nonfatal ischemic CVD [International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) codes 120–125, 163, 165, 166, 170, 171, 174] and cancer of any kind (ICD-10-CM codes C00-C97, D00-D09, D37-D48), except for basal cell carcinoma of the skin (ICD-10-CM codes C44 and M809-M811) (27). A secondary outcome was all-cause mortality. In our study, the primary endpoint was a major chronic disease event defined as combination of CVD, cancer, or death, whichever came first. Hazard ratios (HR) and their 95% CI were estimated using Cox proportional hazards models (28). All Cox models were adjusted for age (continuous). Models were controlled for smoking status (never, former, current), education level (primary school, secondary school, high school or equivalent), and total EI (continuous). In women, menopausal status (yes/no) and number of children (0, 1–2, ≥3) were also included. All Cox models included a linear contrast to test for trend. The multivariate-adjusted model also included daily supplementation (placebo, intervention group) to account for the study design. We verified that independent variables used in multivariate models were not colinear. Graphic methods and time-extended Cox models were used to check the proportional hazards assumption for this study. This assumption did not appear to be violated. Values in the text are means ± SD unless otherwise indicated. Differences were considered significant at P < 0.05. All analyses were performed using SAS software (SAS Institute, version 8.2).


   Results
TOP
 ABSTRACT
 Introduction
 Materials and Methods
 Results
Discussion
 LITERATURE CITED
 
The present analyses included 4,976 subjects (2,095 men and 2,881 women) among 12,741 subjects participating in the SU.VI.MAX study (Fig. 1). During the 8-y follow-up period, 455 major chronic disease endpoints were documented. They included 261 cancers (106 in men and 155 in women), 131 CVD events (103 in men and 28 in women), and 63 deaths (33 in men and 30 in women). At baseline, men were 52.0 ± 4.7 y old and women were 47.3 ± 6.6 y old. Men's score was 8.9 ± 2.3 (range: 1.4–15.4) and that of women was 9.2 ± 2.2 (range: 0.9–15.3). The FSIPO was normally distributed for each gender.


Figure 1
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  		FIGURE 1  Flow of subjects included in the FSIPO analyses.

 
The FSIPO was significantly associated with age, occupational category, and smoking habits in men (Table 2). Among men, those older than 55 had higher scores compared with other age groups. The mean score increased among occupational categories from farmers, self-employed to retired and unemployed men (Table 2). Men who never smoked had a higher score compared with former smokers and current smokers. Women with a higher score were more likely not to smoke and to have a higher education level (Table 2). In addition, women with a higher score were younger and more likely to hold a management or professional job (Table 2).


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  		TABLE 2 FSIPO by social and demographic characteristics12

 
Age- and energy-adjusted mean nutrient intake increased with higher FSIPO tertile in men and women (Table 3). This was especially apparent in both genders for macronutrients and vitamins (except for vitamin D) as well as minerals, with the exception of iron in men and sodium in women. The relationship between FSIPO tertiles and most nutritional biomarkers was also significant (Table 3), excluding apoprotein (Apo)-A lipoprotein in men and women, serum zinc and retinol in men, and serum selenium in women.


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  		TABLE 3 Daily nutrient intakes and nutritional biomarkers by FSIPO tertiles

 
After adjusting for age (Table 4), the FSIPO was inversely associated with the risk of major chronic disease in men. In multivariate-adjusted models, men in the top FSIPO tertile compared with those in the lowest tertile had a 36% lower risk of major chronic disease (Table 4). The test for trend P-value was at the limit of significance. No significant association was found in women (Table 4).


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  		TABLE 4 HR estimates of major chronic disease by FSIPO tertiles and gender12

 
When the point deduction taking into account excessive EI was not applied, the correlation between this modified index and the original FSIPO was 0.93 (P < 0.0001). However, the association with risk of chronic disease in men was no longer significant.


   Discussion
TOP
 ABSTRACT
 Introduction
 Materials and Methods
 Results
 Discussion
LITERATURE CITED
 
In this middle-aged cohort, nutritional status that corresponded to PNNS indicators was found to be associated with a 36% reduced risk of chronic disease or mortality after 8 y of follow-up in men. In contrast, this prognostic value of the FSIPO was not observed in women. Higher scores were found to be associated with better nutrient intakes and biomarkers in both sexes.

A significant protective association has been observed in most studies that analyzed the relationship between diet-based indexes and total cardiovascular and cancer mortality, regardless of whether they included nutrient intakes (8,9,29) or not (7). For example, Kant et al. (9) found that the Recommended Food Score was associated with a decreased risk of cancer mortality. However, the Recommended Food Score was heavily weighted by the F&V component, which contributed 15 of a total of 23 points. Nevertheless, this result supports the demonstrated protective role of F&V against certain cancers.

Only a few studies have examined the relationship between dietary guidelines and the incidence of chronic diseases. Two cohort studies investigated the association between the incidence of CVD and cancer (10,11) and the Healthy Eating Index (HEI) (30). HEI had a moderate inverse association with major chronic diseases and with CVD in men after 8 y of follow-up (10). HEI and CVD were weakly associated in women who were followed over 12 y. No association with cancer incidence was found. Although the scores are not directly comparable due to their different components, our results follow the same trend.

Several hypotheses might explain the absence of an association between the FSIPO and major chronic disease events in women in our study. First, the most common female cancer occurring during the SU.VI.MAX follow-up was breast cancer. The relationship between diet and breast cancer remains inconclusive in the literature (31,32). However, associations between breast cancer in postmenopausal women and alcohol intake, weight gain in adulthood, and PA have recently been widely acknowledged (1–3). Small variations of these lifestyle factors were observed in our study except for PA; moreover, the low number of postmenopausal breast cancers and insufficient duration of follow-up could have led to insufficient statistical power. In our study, cases of cancer were 5.5 times as high as CVD occurrences in women, whereas in men, the number of cancer and CVD cases was similar. This probably had an incidence on differences in associations of the FSIPO with major chronic diseases.

In a study conducted among postmenopausal women (14) with nondietary components removed from the index, a nonsignificant effect on cancer incidence was observed. We did not find a significant effect on the incidence of major chronic diseases in men when the same approach was used (data not shown). The nutritional markers measured in our study might be viewed as intermediate factors in the relationship between diet and chronic disease occurrence. However, cholesterol level, BP, and body mass are probably insufficient to ensure protective effects. The combination of an adequate diet, nutritional markers, and PA may work synergistically to enhance chronic disease prevention.

The Dietary Guidelines for Americans Adherence Index (33) includes a penalty system as in our analyses. In France, the recommended number of servings per day is not adjusted for age, gender, or EI compared with the United States. However, excessive EI is of interest when analyzing diet quality (6,33). Our penalty approach had an impact on our results: mean EI were similar across tertiles when the deduction was applied in women, whereas this was not the case in men. However, the prognostic value of the FSIPO was no longer significant in men when the penalty was not applied, although men with or without penalty were ranked in the same fashion.

The exclusion of a large number of subjects limited the external validity of our results (34). Moreover, our study included subjects recruited on a voluntary basis (16) who may have been more interested in health and nutrition than the typical study participant. The choices made a priori regarding the points attributed to each indicator can be discussed. Such categories may conceal the true variability in intake data and reduce the range of scores (6). The FSIPO cut-off values (with 3 possible values) discriminate individuals according to their adherence to the guidelines (data not shown). Because PNNS guidelines were not disseminated at the time of the study, we used the FSIPO retrospectively in the SU.VI.MAX cohort. The FSIPO should now be applied to populations willing to comply with PNNS recommendations. Studies analyzing methods of diet description that fit with the score approaches should also be developed. The inaccurate estimation of portion sizes or underreporting of "unhealthy" food consumption are inherent with 24-h dietary records. We minimized these limitations by using at least 3 d of records.

Several strengths of our study should also be stressed. Higher FSIPO scores were related to both healthy lifestyle components (nonsmokers, normal BMI) and nutritional status (dietary and biochemical markers). The use of 3 24-h records during 2 y of follow-up enables a satisfactory dietary estimation, limits misclassification by decreasing intra-individual variation (35), and could be considered as more reliable and precise for assessing intakes compared with FFQ, which were used in previous studies (10,11,14). Diet was very stable over the study period in this cohort (data not shown) and these measures can be considered as representative of the usual diet. Finally, this score includes both dietary and biochemical markers measured using standardized procedures in a large population sample and many potentially confounding factors were included in the analyses.

The significant association between the FSIPO and nutrient intake and nutritional biomarkers could be taken as an intermediate validation of our approach. As expected, subjects with higher scores had better nutritional status, as assessed through biological markers. Although the associations were consistent in men and women, analyses were stratified on gender, because inclusion criterion related to age varied across gender in the SU.VI.MAX study. Moreover, gender-stratified analyses showed better diet and nutritional status in women than in men, resulting in a higher FSIPO score.

Age and healthy dietary habits were associated; older men had slightly better mean scores than middle-aged men. This result is consistent with the literature (30,33,36). For women, however, the younger women had better scores, which could be related to their higher education and occupation levels compared with seniors in the SU.VI.MAX study. Our analyses also confirm an association between smoking and less favorable diet, nutritional status, and PA summarized by lower scores (37).

Cohort studies with a long follow-up are necessary to identify the relationship between diet and development of chronic diseases. In the future, CVD, cancer, and mortality will be analyzed as separate outcomes in the SU.VI.MAX cohort due to continuing follow-up. In middle-aged men, healthy diet and lifestyle were related to a reduction in major chronic disease incidence after an 8-y follow-up. These results demonstrate the potential for improving the health status of the French population, particularly that of men, when PNNS nutritional guidelines are followed by changes in habits. They also support the validity of pursuing public health nutrition programs such as the PNNS.


   FOOTNOTES
 
1 Supported by a grant from the Direction Générale de la Santé, Ministère de la Santé et des Solidarités, France. C. Estaquio was supported in part by the Fondation Louis Bonduelle, France. Back

2 Author disclosures: C. Estaquio, K. Castetbon, E. Kesse-Guyot, S. Bertrais, V. Deschamps, L. Dauchet, S. Péneau, P. Galan, and S. Hercberg, no conflicts of interest. Back

3 Supplemental Table 1 is available with the online posting of this paper at jn.nutrition.org. Back

7 Abbreviations used: Apo, apoprotein; BMR, basal metabolic rate; BP, blood pressure; CVD, cardiovascular disease; EI, energy intake; F&V, fruit and vegetable; FSIPO, French score of indicators of the PNNS objectives; HEI, Healthy Eating Index; HR, hazard ratio; ICD-10-CM, International Classification of Diseases, 10th Revision, Clinical Modification; PA, physical activity; PNNS, Programme National Nutrition Santé; RDA, recommended dietary allowance; SBP, systolic blood pressure; SU.VI.MAX, Supplémentation en Vitamines et Minéraux AntioXydants. Back

Manuscript received 15 October 2007. Initial review completed 13 November 2007. Revision accepted 27 February 2008.


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 ABSTRACT
 Introduction
 Materials and Methods
 Results
 Discussion
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