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Hi All,

The usual method to examine the risk of foods that is used in 4,046 studies in

Medline uses the principal component analysis method. Using a new method termed

reduced rank regression used in only seven studies in Medline, bad foods are

worse

for all-cause mortality prediction.

The below are pdf-available.

van Dam RM.

New approaches to the study of dietary patterns.

Br J Nutr. 2005 May;93(5):573-4. No abstract available.

PMID: 15975154

The relationship between diet and health can be examined at the level of food

components, foods and dietary patterns. Until recently, the study of food

components, particularly nutrients, has been the dominant approach in

nutritional

epidemiology. This approach has clear advantages. If the development of a

disease is

causally related to the intake of a food component, the examination of that food

component will be the approach with the greatest power to identify its effect.

In

addition, results for food components can be compared with associations observed

in

other populations, data from mechanistic studies and health effects found in

intervention studies (Willett & Buzzard, 1998). Knowledge on the level of food

components can then be used to produce foods with higher or lower levels of the

component. For example, reduction of the amount of trans-fatty acids in

margarines

has probably resulted in substantial health benefits for populations (Oomen et

al.

2001). However, the effect of a food component can differ depending on the food

that

it is derived from due to interactions between food components or physical

characteristics of foods. For example, folate from beer may provide less health

benefits than the same amount of folate from bread, because alcohol reduces

intestinal folate uptake, interferes with folate metabolism and increases

urinary

loss of folate (Jiang et al. 2003). Effects of food consumption on disease risk

can

be different from predictions based on known effects of food components, because

our

knowledge on the myriad possible beneficial or detrimental aspects of foods

(s

& Murtaugh, 2000) is still limited. The study of foods and food groups accounts

for

interactions between different components of a food, and for effects of physical

characteristics and unknown components.

In addition to different components of a food, synergy or antagonism may also

exist

for components of different foods and drinks that are included in the dietary

pattern of an individual. As a result, health effects of dietary patterns may be

greater than for individual foods or nutrients. Results from the Dietary

Approaches

to Stop Hypertension (DASH) intervention study illustrate the importance of

considering dietary patterns (Appel et al. 1997). The DASH diet, a diet

characterized by high consumption of vegetables, fruits, low-fat dairy products

and

whole grains, resulted in a greater reduction in blood pressure than had been

found

for individual minerals in these foods. Another advantage of the study of

dietary

patterns in epidemiological studies is that potential dietary confounders are

largely incorporated in the dietary pattern variable.

Different methods have been used to study dietary patterns in epidemiological

studies. Two main approaches can be distinguished. First, an exploratory

approach

can be used that identifies combinations of foods and drinks as they are

consumed in

reality in a particular population. Principal components analysis is a

frequently

used exploratory approach to identify dietary patterns (Hu et al. 2000). This

data

reduction technique constructs new variables that are linear combinations of the

original variables and explain as much of the variation in the original

variables as

possible. Applied to dietary data, new dietary pattern variables are derived on

the

basis of the correlation matrix of the original food variables. The use of

principal

components analysis to derive dietary pattern variables requires several

arbitrary

choices such as the original variables to include and the number of dietary

patterns

to identify (ez et al. 1998). This underlines the importance of conducting

sensitivity analyses to examine the robustness of the findings (Hu et al. 2000).

Dietary patterns identified by the explanatory approach reflect dietary

behaviour

and are not based on known health effects of diet. As a result, the identified

dietary patterns are not necessarily relevant for disease risk. However, results

can

increase insight into possibilities for dietary changes and can provide

information

for setting priorities for changing dietary patterns in a population by public

health initiatives. Second, a hypothesis-oriented approach that uses predefined

criteria to construct dietary pattern scores can be used. These scores reflect

the

degree to which a person's diet conforms to a dietary pattern that was defined a

priori based on presumed health effects. Scores based on dietary recommendations

(McCullough et al. 2002) and characteristics of the traditional Mediterranean

diet

(Trichopoulou et al. 2003) have been used. Deciding what individual components

to

include, the cut-off points and the weights of different components of an a

priori

score still requires subjective choices. This approach does not have the

advantages

related to studying existing dietary behaviour or to the identification of new

dietary patterns that may affect disease risk. However, the approach can capture

the

greater effects of the overall diet as compared with individual components, and

can

be used to test the validity of dietary recommendations.

Hoffmann and colleagues have introduced a new method in nutritional epidemiology

that combines characteristics of the explanatory and hypothesis-oriented

approaches

to dietary patterns (Hoffmann et al. 2004a). This reduced rank regression (RRR)

method has similarities with principal components analysis, but it uses a set of

response variables in addition to a set of food intake variables. The identified

dietary patterns are linear combinations of the original food intake variables

that

maximally explain variation in the response variables (Hoffmann et al. 2004a). A

priori knowledge is introduced by using a set of response variables that is

known to

predict the disease of interest. In a paper in this issue of BJN, Hoffmann et

al.

(2005) have used macronutrient intakes as response variables, resulting in

dietary

pattern variables that are linear combinations of the original food variables

and

maximally explain variation in macronutrient intakes. The identified dietary

pattern

was characterized by higher intakes of meats, poultry, butter, sauces and eggs,

and

lower intakes of bread and fruit, and was associated with a higher risk of

premature

mortality. Although the approach used invites interpretation of this association

in

terms of macronutrients only, other characteristics of the identified dietary

pattern may still have contributed to the observed association. For the RRR

method,

the number of dietary patterns that can be identified is limited by the number

of

response variables. However, arbitrary decisions such as the choice of original

food

intake variables remain necessary, and sensitivity analyses should be conducted.

An

alternative approach that is of potential interest is the use of biomarkers of

dietary intake that are relevant for the disease of interest as response

variables.

This application would identify combinations of foods that maximally explain

variation in biomarkers of dietary intake, avoiding measurement error related to

food composition data or to lack of information on bioavailability for different

combinations of foods.

In a case–control study of coronary heart disease, Hoffmann and colleagues used

biomarkers of disease as response variables in the RRR analysis (Hoffmann et al.

2004b). A dietary pattern characterized by higher intakes of meat, margarine,

poultry and sauce, and lower intakes of vegetarian dishes, wine, vegetables and

whole grains, maximally explained variation in the five selected biomarkers of

CVD

(HDL-cholesterol, LDL-cholesterol, lipoprotein(a), C-peptide and C-reactive

protein

concentrations). The identified dietary pattern was strongly associated with

CHD.

The use of biomarkers of disease as response variables is of interest because it

may

aid the pathophysiological interpretation of observed associations between

dietary

patterns and disease. However, the explorative nature of the approach should be

kept

in mind: in the theoretical situation where the biomarkers used perfectly

predict

the disease, the method simply identifies the combination of food variables that

is

most highly correlated with the disease in the study population. Thus, an

important

consideration is whether findings can be confirmed in diverse populations. After

randomly splitting the sample in half, dietary pattern variables identified in

the

two sub-populations remained associated with CHD in the other sub-population,

but

the associations were much weaker (Hoffmann et al. 2004b).

The RRR method may prove to be a useful tool in nutritional epidemiology,

because it

can provide insight into the pathophysiological pathway that links dietary

patterns

to disease. Use of the same set of response variables in different study

populations

may facilitate the comparison of results from diverse populations. In addition,

confirmation of results for RRR or principal components analyses in other

populations can be performed by calculating a dietary pattern score using the

same

weights and food variables or by using a simplified dietary pattern score

(Schulze

et al. 2003a). An application of dietary pattern analyses is to obtain insight

into

intercorrelations between dietary variables and the potential for confounding.

In

addition, adjustment for dietary pattern scores may be an efficient method to

address confounding by other dietary variables in studies of individual foods

and

food components (Schulze et al. 2003b). The combination of analyses of food

components, foods and dietary patterns is likely to provide most insight into

the

relationship between diet and disease risk.

Hoffmann K, Boeing H, Boffetta P, Nagel G, Orfanos P, Ferrari P, Bamia C.

Comparison of two statistical approaches to predict all-cause mortality by

dietary

patterns in German elderly subjects.

Br J Nutr. 2005 May;93(5):709-16.

PMID: 15975171

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=pubmed & dopt=Abstra\

ct & list_uids=15975171 & query_hl=28

Abbreviations: AIC, Akaike's Information Criterion, EPIC, European Prospective

Investigation into Cancer and Nutrition, PCA, principal component analysis, RRR,

reduced rank regression

.... To study the effect on mortality of a specific food or food group consumed

regularly is neither promising nor scientifically justified because foods are

consumed in combination and intake data are highly correlated. Adjustment for

all

other foods would result in a vast number of regression parameters to estimate.

As a

consequence, multicollinearity of the food intakes and the restricted power of a

study may lead to unstable parameter estimates with wide confidence intervals. A

possible approach is to consider diet-quality scores based on recommended diets

or

dietary guidelines ( et al. 1994; Kennedy et al. 1995; Trichopoulou et

al.

1995, 2003; Huijbregts et al. 1997; Osler & Schroll, 1997; Haines et al. 1999;

Kant

et al. 2000; McCullough et al. 2002; Seymour et al. 2003). However, diet-quality

scores are based on selected dietary components and do not allow for the intake

of

some food groups.

An alternative approach is to construct dietary patterns and to study the

combined

effect of foods differently weighted in pattern scores (Kumagai et al. 1999;

Osler

et al. 2001). Principal component analysis (PCA) is the most widely applied

statistical method to derive dietary patterns in nutritional science (Randall et

al.

1992; Slattery et al. 1998; Hu et al. 2000; Osler et al. 2001; Schulze et al.

2001;

Hu, 2002; Schulze & Hu, 2002; Costacou et al. 2003; Van Dam et al. 2003). PCA,

or

the very similar factor analysis, aims to construct linear combinations of food

intakes, which explain a high proportion of the variation in food intakes. If

the

objective of the study is to describe typical eating patterns in the study

population without reference to health outcomes, PCA is a useful tool. However,

explaining much variation in food intakes by PCA does not necessarily mean that

also

much variation in macronutrients such as fatty acids and carbohydrates will be

explained. From a theoretical point of view, dietary patterns that focus on the

variation in selected nutrients and especially on changes of the mix of energy

sources could be more useful in examining the effects of diet on disease

incidence

or mortality than the classic PCA patterns.

The focus on variation in biologically relevant nutrients was the reason to

introduce reduced rank regression (RRR) in nutritional epidemiology (Hoffmann et

al.

2004a). RRR is a statistical method that is more flexible than PCA because it

works

with two sets of variables. It aims to construct linear combinations of

variables

belonging to one set by maximizing the explained variation in variables of the

other

set. Defining the second set by a few variables that are expected to be related

to

the health outcome of the study should identify dietary patterns that are

possibly

associated with the outcome. In nutritional epidemiology, many previous studies

have

focused on major energy sources because they are quantitatively important in our

diets and differences in the mix of energy sources among human populations are

correlated with striking variation in rates of many diseases (Willett, 1998).

Although large prospective studies on an individual level have not supported an

important role of energy sources on cancer (Willett, 2000b) and stroke (He et

al.

2003), energy intake from specific types of fat appear to be related to the risk

of

CVD (Jakobsen et al. 2004; Tanasescu et al. 2004) and type 2 diabetes (Salmeron

et

al. 2001) that may have small effects on total mortality (Hooper et al. 2001).

Therefore, choosing percentages of total energy intake from different

macronutrients

as a second set of variables in the RRR analysis could be promising in

identifying

dietary patterns that are meaningful for the development of chronic diseases and

for

mortality.

In the present study, we applied the RRR method to food consumption data

collected

by means of a food frequency questionnaire and focused on the variation in

percentages of energy from saturated fat, monounsaturated fat, polyunsaturated

fat,

protein and carbohydrates. We also applied the classic PCA method to the same

data

and compared the performance of the two approaches to predict mortality. We used

data from the European Prospective Investigation into Cancer and Nutrition

(EPIC)

study. This work was involved in the EPIC-Elderly project and considered only

dietary patterns in the German EPIC cohorts.

Subjects and methods

Study population

Study participants were volunteers from the two German cohorts in Potsdam and

Heidelberg of the EPIC study who were aged 60 years or older at baseline.

Participants were recruited between 1994 and 1998. The response rate was 22·7%

in

Potsdam and 38·3% in Heidelberg (Boeing et al. 1999a). ... Four hundred and four

study participants (221 from Potsdam, 183 from Heidelberg) died during the

follow-up

time, which varied between 4 and 8 years. Because of the high number of 287

diseased

who had self-reported prevalent chronic diseases at enrolment we did not exclude

these persons from the analysis, but we adjusted for prevalence of chronic

diseases

in the respective analysis.

Data collection

Dietary intake information was collected by a self-administered scanner-readable

food frequency questionnaire, which included questions on the frequency and

portion

size of 148 food items eaten during the year preceding enrolment (Schulze et al.

1999). Photographs supported the estimation of portion sizes. The frequency of

intake was measured using ten categories, ranging from ‘never’ to ‘five times

per d

or more’ (Boeing et al. 1999b). Foods were classified into twenty-three food

groups

based on nutrient profiles or culinary usage according to the common

classification

of the EPIC project (Slimani et al. 2002). Nutrient intake was calculated using

data

from the German Food Code BLSII.3 that is a slight modification of BLSII.2

(Dehne et

al. 1999). Macronutrient intake estimated from the food frequency questionnaire

was

validated by the mean macronutrient intake obtained from twelve 24 h dietary

recalls. The correlation coefficient between both intakes adjusted for energy

varied

between 0·58 for carbohydrates and 0·84 for protein (Kroke et al. 1999b). ...

.... Results

The factor loadings of the first two patterns obtained by PCA and RRR are

presented

in Table 1. A high positive loading indicates a strong direct association

between

the food group and the pattern, whereas a high negative loading reflects a

strong

inverse association. To make visible what the important food groups for each

pattern

were we omitted all factor loadings between -0·2 and +0·2. The major

contributors to

the first PCA pattern were potatoes, vegetables, legumes, bread, all types of

meat,

eggs, sauces and soups which were all positively correlated with the pattern

score.

These foods are often eaten together at lunch or at supper in German households.

The

second PCA pattern was characterized by high positive loadings of vegetables,

fruits, dairy products, other cereals, vegetable oils and non-alcoholic

beverages,

as well as by a negative loading of alcoholic beverages other than wine. This

pattern reflects prudent nutrition consistent with dietary recommendations. The

first RRR pattern had high positive loadings in all types of meat, butter,

sauces

and eggs, and was inversely associated with bread and fruits. It represents

dietary

habits expected to be detrimental for human health. Finally, legumes, poultry,

fish

and margarine were directly associated and butter, sugar and cakes were

inversely

associated with the second RRR pattern score.

Table 1. Factor loadings* of the dietary patterns obtained by different

statistical

methods in the German cohorts of the European Prospective Investigation into

Cancer

and Nutrition Elderly study (n 9356)

.................................

--------Principal component analysis Reduced rank regression

.................................

Food groups----Pattern 1 Pattern 2 Pattern 1 Pattern 2

.................................

Potatoes and other tubers 0·25 - - -

Vegetables 0·25 0·44 - -

Legumes - 0·23 - c0·20

Fruits - 0·36 -0·20 - -

Dairy products - 0·26 - -

Pasta, rice and other grain

Bread 0·22 - -0·28 -

Other cereals - 0·27 - -

Red meat 0·42 - 0·35 -

Poultry 0·25 - 0·21 0·22

Processed meat 0·35 - 0·51 -

Fish and shellfish - - - 0·20

Eggs and egg products 0·21 - 0·20 -

Vegetable oils - 0·43 - -

Butter - - 0·31 -0·64

Margarine - - - 0·37

Sugar and confectioneary - - - -0·36

Cakes - - - -0·31

Non-alcoholic beverages - 0·31 - -

Wine

Other alcoholic beverages - -0·31 - -

Sauces and condiments 0·38 - 0·26 -

Soups and bouillons 0·21 - - -

.........................

*Factor loadings that are between -0·2 and +0·2 are not shown.

The variation in food groups and energy sources explained by each of the four

dietary patterns is summarized in Table 2. The two PCA patterns explained 11·3

and

8·4% of food intake variation, respectively. In contrast, the first and second

RRR

patterns explained only 4·4 and 6·1% of the total variation in all twenty-three

food

groups. However, the variation in energy sources accounting for the two RRR

patterns

were 30·8 and 15·9% and as expected much higher than the proportion of energy

sources variation explained by the two PCA patterns (together 7%). Table 2 also

gives a more detailed picture of how much variation in every energy source can

be

explained by the patterns. As indicated, RRR patterns performed better than PCA

patterns in explaining the variation in all energy sources. For example, the

first

RRR pattern alone accounted for 39·1% of variation in energy from saturated fat

and

simultaneously for much of the variation in monounsaturated fat and

carbohydrates.

Table 2. Explained variation (%) of food groups and energy sources by dietary

patterns obtained by different statistical methods in the German cohorts of the

European Prospective Investigation into Cancer and Nutrition Elderly study (n

9356)

........................

----Principal component analysis Reduced rank regression

----Pattern 1 Pattern 2 Total* Pattern 1 Pattern 2 Total*

........................

Explained variation (%) of:

All twenty-three food groups 11·3 8·4 19·7 4·4 6·1 10·5

All five energy sources 4·4 2·6 7·0 30·8 15·9 46·7

Energy from saturated fat (%) 1·5 1·2 2·7 39·1 20·4 59·5

Energy from monounsaturated fat (%) 8·0 0·2 8·2 57·7 0·9 58·6

Energy from polyunsaturated fat (%) 1·0 2·9 3·9 12·2 29·2 41·4

Energy from protein (%) 1·5 0·3 1·8 12·0 28·7 40·7

Energy from carbohydrates (%) 10·0 8·4 18·4 33·2 0·1 33·3

...........................

*Proportion of variation explained by pattern 1 and pattern 2 together.

As can be seen in Table 3, mean percentages of energy from different sources

varied

across quintiles of the two PCA and two RRR dietary pattern scores. Because of

the

high number of subjects all trends were statistically significant (P<0·0001).

However, the most striking variation was that of energy from saturated fat,

monounsaturated fat and carbohydrates across quintiles of the first RRR pattern.

A

high score of the first RRR pattern reflected a diet rich in saturated and

monounsaturated fat and poor in carbohydrates. Energy from total fat increased

from

25·9% in the lowest quintile to 37·2% in the highest quintile of the pattern

score,

whereas the proportion of energy from carbohydrates simultaneously decreased

from

48·0 to 37·6%. The energy composition in the highest quintile did not meet

current

dietary recommendations, which advise an intake of less than 35% of energy from

fat

and more than 45% of energy from carbohydrates (Institute of Medicine of the

National Academies, 2002).

Table 3. Mean percentages of energy from different sources according to

quintiles of

dietary pattern scores in the German cohorts of the European Prospective

Investigation into Cancer and Nutrition Elderly study (n 9356)

...............................

----Percentage of energy from: Quintiles of dietary pattern scores

----1 2 3 4 5 Trend*

................................

PCA† Pattern 1

Saturated fat 13·4 13·6 13·7 14·0 14·4 >

Monounsaturated fat 10·9 11·3 11·6 11·9 12·5 >

Polyunsaturated fat 5·6 5·9 5·9 6·0 6·1 >

Total fat 29·9 30·8 31·2 31·9 33·0 ?

Protein 13·4 13·6 13·7 13·8 14·1 >

Carbohydrates 45·8 44·6 43·6 42·6 40·2 <

PCA Pattern 2

Saturated fat 14·1 14·3 13·9 13·6 13·2 <

Monounsaturated fat 11·8 11·9 11·6 11·6 11·4 <

Polyunsaturated fat 5·6 5·8 5·9 6·0 6·2 >

Total fat 31·5 32·0 31·4 31·2 30·8 <

Protein 13·4 13·7 13·8 13·9 13·8 >

Carbohydrates 39·7 42·7 43·9 44·7 45·5 >

RRR‡ Pattern 1

Saturated fat 11·3 12·7 13·7 14·8 16·5 >

Monounsaturated fat 9·5 10·6 11·6 12·5 14·0 >

Polyunsaturated fat 5·1 5·6 5·9 6·3 6·7 >

Total fat 25·9 28·9 31·2 33·6 37·2 >

Protein 12·6 13·3 13·7 14·1 14·8 >

Carbohydrates 48·0 45·8 43·6 41·5 37·6 <

RRR Pattern 2

Saturated fat 16·1 14·4 13·3 12·7 12·6 <

Monounsaturated fat 12·2 11·7 11·3 11·3 11·7 <

Polyunsaturated fat 4·7 5·3 5·8 6·4 7·4 >

Total fat 33·0 31·4 30·4 30·4 31·7 <

Protein 12·0 13·1 13·7 14·4 15·4 >

Carbohydrates 42·1 43·5 44·3 44·2 42·5 >

...............................

PCA, principal component analysis; RRR, reduced rank regression.

*< = decreasing quintiles. > = increasing quintiles. All trends across

quintiles of

dietary patterns were significant (P<0·0001).

†PCA and RRR were applied to twenty-three food groups defined in Table 1.

‡In the RRR analysis the percentages of energy from saturated fat,

monounsaturated

fat, polyunsaturated fat, protein and carbohydrates were used as response

variables.

The relative risks of all-cause mortality associated with an increase in each

pattern score by one standard deviation are presented in Table 4. The relative

risks

adjusted for centre and sex were significantly different from 1·0 for the first

PCA

pattern (relative risk 1·12; 95% CI 1·01, 1·24) and for the first RRR pattern

(relative risk 1·25; 95% CI 1·14, 1·40). After additional adjustment for

prevalent

cancer, prevalent CHD, prevalent diabetes, prevalent hypertension, BMI and

waist:hip

ratio, the first PCA pattern was no more significant. In contrast, the first RRR

pattern remained significant even after further adjustment for smoking status,

educational level, physical activity at work, physical activity at leisure time

and

total energy intake (relative risk 1·20; 95% CI 1·09, 1·31). Comparing the

goodness

of fit of the fully adjusted models by Akaike's Information Criterion (AIC)

suggests

the use of RRR patterns (AIC=5580) instead of PCA patterns (AIC=5592). Also a

fully

adjusted model with percentages of energy from macronutrients chosen as

predictors

had a lower goodness of fit (AIC=5594). Actually, no single energy source had a

significant effect on mortality. Moreover, substituting the RRR patterns by the

Mediterranean diet-quality score (Trichopoulou et al. 1995, 2003) was associated

with a decrease of model fit and a loss of significance (data not shown).

Table 4. Relative risk and 95% CI of mortality according to standardized*

increase

of pattern scores obtained by different statistical methods in the German

cohorts of

the European Prospective Investigation into Cancer and Nutrition Elderly study

(n

9356)

................................

----Principal component analysis (PCA)† Reduced rank regression (RRR)‡

----Pattern 1 Pattern 2 Pattern 1 Pattern 2

Relative risk 95% CI Relative risk 95% CI Relative risk 95% CI Relative

risk

95% CI

................................

Model 1‡‡ 1·12 1·01, 1·24 0·91 0·82, 1·01 1·25 1·14, 1·40 0·98 0·89,

1·07

Model 2 1·11 0·98, 1·23 0·92 0·82, 1·02 1·23 1·12, 1·34 0·94 0·86, 1·04

Model 3 1·10 0·96, 1·28 0·99 0·89, 1·10 1·20 1·09, 1·31 0·96 0·87, 1·06

...............................

*A unit increase of the pattern score is an increment of SD.

†PCA and RRR were applied to twenty-three food groups defined in Table 1.

‡In the RRR analysis the percentages of energy from saturated fat,

monounsaturated

fat, polyunsaturated fat, protein, and carbohydrates were used as response

variables.

‡‡Model 1: adjusted for centre and sex. Model 2: adjusted for centre, sex,

prevalent

cancer, CHD, diabetes and hypertension, BMI and waist:hip ratio. Model 3:

adjusted

for all variables included in model 2 and additionally for smoking status,

education

level, physical activity at work, physical activity at leisure time and total

energy

intake.

Table 5 shows the relative risks of death according to quintiles of dietary

pattern

scores by taking into account all confounders as before. Again, the first RRR

pattern was the only significant predictor of total mortality. The relative

risks

across increasing quintiles of this pattern score were 1·0, 1·01, 0·96, 1·32 and

1·61 (95% CI 1·17, 2·21; P for trend: 0·0004). Interpreting this relationship as

effect of energy composition means that only a simultaneous high proportion of

energy from total fat and protein and low proportion of energy from

carbohydrates

was associated with increased mortality risk.

Table 5. Relative risk* and 95% CI of mortality according to quintiles of

pattern

scores in the German cohorts of the European Prospective Investigation into

Cancer

and Nutrition Elderly study (n 9356)

.........................

--------Quintiles of dietary patterns

--------1 2 2 4 5

Dietary patterns---Relative risk Relative risk 95% CI Relative risk 95% CI

Relative risk 95% CI Relative risk 95% CI P for trend

...........................

PCA pattern 1 1·0 0·83 0·57, 1·22 1·00 0·70, 1·45 1·03 0·70, 1·51 1·06

0·68, 1·65 0·50

PCA pattern 2 1·0 0·91 0·68, 1·22 0·90 0·66, 1·23 1·10 0·81, 1·51 0·80

0·55, 1·15 0·61

RRR pattern 1 1·0 1·01 0·70, 1·46 0·96 0·66, 1·38 1·32 0·95, 1·85 1·61

1·17, 2·21 0·0004

RRR pattern 2 1·0 0·87 0·63, 1·21 0·81 0·57, 1·13 1·07 0·78, 1·48 0·96

0·70, 1·33 0·74

Shortened† RRR 1 1·0 1·07 0·73, 1·58 1·25 0·87, 1·80 1·35 0·94, 1·94

1·34

0·93, 1·94 0·062

Simplified‡ RRR 1 1·0 0·99 0·67, 1·45 1·24 0·86, 1·77 1·26 0·88, 1·79

1·31

0·91, 1·87 0·061

..........................

PCA, principal component analysis; RRR, reduced rank regression.

*Adjusted for centre, sex, prevalent cancer, CHD, diabetes and hypertension,

BMI,

waist:hip ratio, smoking status, education level, physical activity at work,

physical activity at leisure time and total energy intake.

†Derived from the original pattern by neglecting all food groups with factor

loadings between -0·2 and +0·2.

‡Derived from the shortened pattern by setting all positive factor loadings

equal to

+1 and all negative loadings equal to -1.

In Table 6, means and percentages of different baseline characteristics

according to

quintiles of the first RRR pattern are summarized. Individuals with high scores

had

a higher BMI, were more likely to come from the Potsdam centre, tended to smoke,

had

a lower education level and were more likely to be unemployed. Confounding

effects

on relative risk estimates due to these associations were taken into account as

before.

Table 6. Baseline characteristics according to quintiles of the first reduced

rank

regression (RRR) pattern score in the German cohorts of the European Prospective

Investigation into Cancer and Nutrition Elderly study (n 9356)

.........................

----Quintiles of the first RRR pattern

Characteristics 1 2 3 4 5 P for trend

.........................

Mean age (years) 62·5 62·5 62·7 62·7 62·6 0·02

Mean BMI (kg/m2) 27·1 27·3 27·7 27·7 28·2 <0·0001

Mean waist:hip ratio 0·90 0·89 0·89 0·90 0·91 0·0007

Potsdam (%) 0·46 0·53 0·57 0·59 0·57 <0·0001

Male (%) 0·43 0·55 0·56 0·51 0·46 0·59

Current smokers (%) 0·11 0·11 0·12 0·16 0·20 <0·0001

Former smokers (%) 0·42 0·36 0·36 0·37 0·38 0·08

Education level (%)

None/primary school 0·36 0·40 0·41 0·42 0·43 <0·0001

Technical school 0·30 0·31 0·31 0·30 0·30 0·53

University degree 0·34 0·29 0·28 0·28 0·27 <0·0001

Physical activity at work (%)

Unemployed 0·74 0·79 0·81 0·80 0·79 <0·0001

Sedentary occupation 0·16 0·13 0·12 0·11 0·12 <0·0001

Standing occupation 0·07 0·07 0·06 0·07 0·07 0·56

Manual work 0·02 0·01 0·01 0·02 0·02 0·79

Physical activity at leisure time (%)

Minimal 0·23 0·22 0·19 0·21 0·22 0·32

Moderate 0·32 0·32 0·31 0·33 0·31 0·56

Heavy 0·45 0·46 0·50 0·46 0·47 0·17

To examine the robustness of our findings and to reduce the dependency of the

dietary pattern from the data we simplified the first RRR pattern score. At

first,

we shortened the score by neglecting all food groups with loadings between -0·2

and

+0·2. Then we formed a simplified pattern (Schulze et al. 2003) by defining the

coefficients of the remaining food groups as +1 or as -1 depending on the sign

of

the factor loading. The resulting simplified pattern score is simply the sum of

the

standardized food groups of red meat, poultry, processed meat, butter, sauces

and

eggs, minus the sum of the standardized food groups of bread and fruits. The

shortened and the simplified versions of the first RRR pattern were separately

used

as a predictor of mortality (see Table 5). The relative risks for the shortened

and

simplified patterns were attenuated as compared with the full pattern and the

trend

across increasing quintiles of the score was only borderline significant in both

cases (P=0·062 and P=0·061).

As further sensitivity analysis we excluded all participants with prevalent

chronic

diseases (cancer, CHD, diabetes) and prevalent hypertension. The first RRR

pattern

only slightly changed after exclusion. The factor loadings were almost the same

as

before with differences of corresponding loadings varying between -0·01 and

+0·01.

The proportion of variation explained by the first RRR pattern was 30·7%, which

represented a decrease of only 0·1%. The adjusted relative risk associated with

an

increase of the first RRR score by SD was 1·24 (95% CI 1·05, 1·48) and therefore

similar to the result obtained with the total sample, although it was less

precise

because of the exclusion of a relatively large proportion of deaths.

Discussion

In the German cohorts of the EPIC-Elderly study we found a significant

association

between a specific dietary pattern and total mortality. This pattern was derived

by

the statistical RRR method recently introduced in nutritional epidemiology

(Hoffmann

et al. 2004a). The RRR pattern score adequately reflects variation in energy

sources

and corroborates the hypothesis that certain combinations of energy sources

affect

human health. A high RRR pattern score, which was associated with high intake of

fat

and protein and low intake of carbohydrates, increased the risk of death.

Subjects

with a pattern score belonging to the highest quintile obtained on average 37·2%

of

their energy from fat and 37·6% from carbohydrates and thus did not meet current

dietary recommendations (Institute of Medicine of the National Academies, 2002).

Food groups that contributed to this unfavourable pattern of energy sources were

red

meat, poultry, processed meat, butter, sauces and eggs, whereas a high intake of

bread and fruits decreased the pattern score. These food groups did not have

simultaneously high loadings in one of the first two PCA patterns that reflect a

typical German diet and a diet supposed to be prudent.

The most appealing advantage of the new RRR method compared with PCA or

traditional

factor analysis is the capability to incorporate prior information. The type of

prior information needed is the knowledge of diet-related variables that are

expected to be predictive for the health outcome under study. Previous

correlation

and epidemiological studies indicated that the mix of energy sources in diet

could

be important for health (Hu et al. 1997; Willett, 1998; Liu & Manson, 2001;

Salmeron

et al. 2001; Mann, 2002). Evidence clearly suggests that dietary fat affects the

lipid and lipoprotein risk profile (Kris-Etherton et al. 2002; Lichtenstein,

2003;

Wolfram, 2003; Pelkman et al. 2004). Because the number of energy sources is

markedly smaller than the number of foods, focusing on the set of energy sources

as

done in the present RRR analysis results in a reduction of dimension. This

reduction

can be considered gain by prior knowledge since explaining a high proportion of

variation in a smaller set of variables is much easier than in a larger set of

variables. The result of the present study, that in contrast to PCA patterns the

first RRR pattern was significantly associated with all-cause mortality,

confirms

prior knowledge and corroborates the hypothesis that variation in the mix of

energy

sources is meaningful for mortality. However, whether the macronutrient

composition

or other dietary components highly correlated with some macronutrients are

linked to

disease prevention and higher life expectancy remains unclear (Sacks & Katan,

2002).

Randomized clinical trials and intervention studies could help to find out the

crucial components and aspects of diet that could be the response variables in

future RRR analyses.

In the current study several limitations should be considered. First, dietary

data

were collected by food frequency questionnaire and, therefore, were subject to

considerable measurement error. Because dietary patterns use intakes of all

foods

the effect of measurement error on the pattern score will be high but in general

cannot be quantified.

Second, dietary intake assessed by a single food frequency questionnaire

referred to

a period of 1 year and cannot be considered lifetime exposure. Diet may change

over

lifetime and these changes in dietary habits may have an impact on mortality.

Repeated measurements of dietary intake over many years would be necessary to

model

diet history and to explore the short- and long-term effects on life expectancy.

Third, the definition and number of food groups may have an effect on the

results of

a pattern analysis. Because of adherence to the food group classification of the

EPIC project and the necessary consistency and comparability of dietary data

from

both German EPIC cohorts, we chose fewer food groups in the present study than

in

previous studies (Hoffmann et al. 2004a,B). A drawback of a small number of food

groups is that foods with potential different health effects are possibly

combined

in the same group and important variation in dietary intake can possibly not be

reflected by patterns derived subsequently.

Fourth, residual confounding due to insufficient consideration of

socio-demographic,

occupational and other environmental factors may have caused bias in relative

risk

estimation. For example, bias may probably be attributed to modelling the

important

exposures, smoking and physical activity, only by categorical variables with few

categories. Interactions between nutrition, physical activity and obesity were

not

considered in the present study although these risk factors could be components

of

the same sufficient condition for mortality following the concept of Rothman

(1976).

Fifth, the low response rate of the cohort study calls into question whether the

cohort is representative for the German population. Distinctions in dietary

habits

may lead to patterns derived in the study population that are quite different

from

those of the target population.

Sixth, the findings of an RRR analysis are not completely reproducible by other

studies because they depend on the data at hand. The construction of simplified

patterns may be helpful to find more robust results and possibly form a basis

for

dietary recommendations.

Seventh, the choice of response variables is not unique and seems to be somewhat

arbitrary. Two RRR analyses with different sets of responses will, in general

lead

to different patterns.

However, the non-uniqueness of responses can also be considered a strength of

the

RRR method because RRR can allow for new findings in research and additional

information sources by modifying the set of response variables in future

studies.

For example, in the case of available blood samples, biomarkers may be more

informative than nutrients because they can provide the link between diet and

the

health outcome. Thus, choosing appropriate biomarkers as responses in the RRR

analysis is a promising way to quantify indirect effects of diet on chronic

diseases

and mortality by specifying possible pathways (Hoffmann et al. 2004b).

In conclusion, the RRR method is a powerful tool to derive dietary patterns in

nutritional epidemiology. It is a flexible method that combines the strength of

PCA

to consider inter-correlations of dietary intakes and the advantage of

diet-quality

scores to allow for use of biologically plausible prior information. The

application

of RRR in the present study to evaluate the impact of diet on mortality suggests

that a diet rich in fat and poor in carbohydrates decreases life expectancy.

Al Pater, PhD; email: old542000@...

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