as a country develops , the types of diseases that affect its population shift from primarily infectious , such as diarrhea and pneumonia , to primarily noncommunicable diseases , such as cardiovascular disease ( cvd ) , obesity , and cancer.1 the global burden of cvd has increased , mostly in wealthy countries .
however , many low and middleincome countries now face a growing burden from the modern health risks ( physical inactivity , tobacco ) , while still fighting an unfinished battle with traditional health risks ( undernutrition , sanitation).1 , 2 , 3 cvds are now the leading cause of mortality in the world , causing 17.5  million deaths in 2012 , which represented 31% of total global mortality.4 in france , cvds are the second major cause of mortality  the first among women  and represent nearly one third ( 28% ) of total mortality.5 
  optimistically , simple and costeffective measures such as dietary changes could reduce the obesity epidemic and the resultant cvd burden , as it has been estimated that lifestyle choices can account for up to 40% of premature cvd deaths.5 in the past few decades , associations between individual nutritional factors and chronic diseases , especially cvd , have been widely investigated .
more recently , alternative approaches that consider the whole diet ( for example , dietary indices reflecting diet quality ) have been used , making it feasible to capture nutrient interactions in the food matrix.6 , 7 in particular , the adherence to a traditional mediterranean dietary pattern , including a high consumption of plant foods and olive oil , low intakes of saturated fat and sugar , and a low / moderate consumption of wine , has been associated with a lower risk of cvd and mortality in many epidemiological studies,8 , 9 as well as with lower levels of inflammation.10 , 11 , 12 indeed , the association between inflammatory mechanisms and the development of cvd has been largely brought to light.13 , 14 , 15 inflammatory pathways promote thrombosis , a late complication of atherosclerosis responsible for myocardial infarctions ( mi ) and most strokes.14 
  to assess the adherence to a dietary pattern , several dietary scores or indices have been developed , such as the dietary inflammatory index ( dii ) .
this index was developed in 200916 and then updated in 2014.17 the dii aims to measure the inflammatory potential of the diet based on the pro and antiinflammatory properties of its various components , including macronutrients , vitamins , minerals , flavonoids , specific food items , and energy intake , according to the existing literature based on tissue culture , and animal and human studies . to our knowledge
, only 3 published studies have investigated the association between the dii and the risk of cardiovascular disease .
all 3 studies reported a protective role of a more antiinflammatory diet.18 , 19 , 20 these recent studies have begun to fill an important gap in understanding the relationship between systemic inflammation  a phenomenon with multiple underlying causes  and cardiovascular disease , by focusing specifically on diet , which appears to be a key modifiable factor involved in inflammatory pathways.10 , 11 , 12 additionally , to the best of our knowledge , no study has yet investigated the association of the dii with the incidence of specific cvd subtypes . in order to contribute to filling this research gap , we assessed the prospective association between the inflammatory potential of the diet , as measured by the dii , and the incidence of overall cvd and subtypes of cvd  namely , mi ; strokes ; angina pectoris and revascularization interventions  in a large cohort of french adults with a longterm followup .
subjects were selected from the  supplmentation en vitamines et minraux antioxydants  ( su.vi.max ) study .
the su.vi.max study was a randomized , doubleblind , placebocontrolled primary prevention trial conducted between 1994 and 2002 .
it included 12  741 french adults ( women aged 3560  years and men aged 4560  years ) .
its primary aim was to evaluate the potential efficacy of daily supplementation with antioxidant vitamins and minerals ( ascorbic acid , vitamin e , carotene , selenium , and zinc ) delivered at nutritional ( ie , nonpharmacologic ) doses on the prevention of cancer , ischemic heart disease , and overall mortality.21 the trial phase ended in 2002 and health events monitoring was pursued until september 2007 .
the su.vi.max study was registered at clinicaltrials.gov ( number nct00272428 ) and was conducted according to the guidelines laid down in the helsinki declaration of 1975 as revised in 1983 , and was approved by the ethics committee for studies with human participants of pariscochin hospital ( ccpprb no .
all subjects provided written informed consent . in this analysis , we selected men and women who provided at least 3 valid 24hour dietary records during the first 2  years of followup ( n=8108 ) and who had no missing data for covariables ( 7743 ) to be included in the models ( figure ) . selection of participants for our analyses , su.vi.max study , france
. cvd indicates cardiovascular diseases ; dii , dietary inflammatory index ; su.vi.max , supplmentation en vitamines et minraux antioxydants . throughout the entire su.vi.max study trial phase ( 19942002 ) , participants were asked to provide a 24hour dietary record every 2  months , for a total of 6 records per year covering all days of the week and all seasons of the year . for these analyses ,
mean dietary intakes were calculated across all available , valid 24hour dietary records obtained during the first 2  years of followup , in order to obtain a proxy for habitual dietary intakes .
dietary records were considered invalid if energy intake was < 100 or > 6000  kcal / day .
additionally , men reporting < 800  kcal / day and women reporting < 500  kcal / day across one third or more of records were excluded to account for energy underreporting .
an instruction manual including validated photographs of generic foods and portion sizes was provided to facilitate coding food portions.22 a food composition table was used to estimate nutrient intake.23 we used the dii to determine the  inflammatory potential  of the diet .
this index relies on information contained in 1943 published studies reporting association between nutritional factors and inflammatory markers.17 briefly , points were assigned to every food parameter on the basis of relevant articles found in the literature , according to whether each food parameter increased ( + 1 ) , decreased ( 1 ) , or had no ( 0 ) effect on 6 inflammatory biomarkers : interleukin1b , interleukin4 , interleukin6 , interleukin10 , tumor necrosis factor , and creactive protein .
the dii computed from the 24hour records in this study includes data on 36 of the 45 food parameters comprising the dii : carbohydrate , protein , total fat , energy , alcohol , fiber , cholesterol , saturated fatty acids , monounsaturated fatty acids , polyunsaturated fatty acids , omega 3 , omega 6 , niacin , thiamin , riboflavin , vitamin b6 , vitamin b12 , iron , magnesium , vitamin a , vitamin c , vitamin d , vitamin e , folic acid , carotene , anthocyanidins , flavan3ol , flavonols , flavonones , flavones , isoflavones , garlic , ginger , pepper , onion , and tea .
dietary intakes for these parameters were first standardized using a  world  mean and sd , derived from nutritional databases from 11 populations around the world , then transformed to percentiles and multiplied by literaturederived inflammatory points for each food parameter , then summed up .
dii scores were computed on the basis of participantspecific mean nutrient and food intakes , which were obtained by averaging intakes across all available dietary records , as explained in the first paragraph of the dietary data section ( ie , dii scores were not first calculated per day and then averaged ) .
more details on the score computation can be found elsewhere.17 
  information about health was selfreported via a monthly questionnaire during the followup .
other sources of information regarding outcome included yearly clinical examinations . in case of no contact with a participant for a long period , or nonattendance at the yearly visit ,
an investigation was launched to determine the reasons . in case of a suspected event ,
investigations were conducted to obtain relevant medical data ( clinical , biochemical , histological , and radiological reports ) from participants , physicians , and/or hospitals .
all cardiovascular events were reviewed and validated by an independent expert committee , unaware of the supplementation group assignment , and then classified using the international classification of diseases , 10th revision , clinical modification ( codes i20i24 , i64).24 first , we considered as outcome the occurrence of all cvds .
sociodemographic data , including sex , date of birth , education ( primary education only , up to secondary education , higher education ) , as well as information on marital status ( couple or single ) , smoking status ( neversmoked , former or current smoker ) , and physical activity level were obtained by a ( nonvalidated ) baseline questionnaire .
the items concerning physical activity inquired whether a participant had a regular physical activity , and if yes , whether they estimated this activity to be equivalent to 1  hour of walking per day .
body mass index was calculated using baseline weight and height measurements performed by trained personnel according to standardized procedures , using an electronic scale ( seca , hamburg , germany ) and a wallmounted stadiometer .
subjects contributed persontime up to the date of the cardiovascular event ( n=292 ) , death ( n=193 ) , the last completed questionnaire or last contact ( n=1704 ) or september 1 , 2007 ( n=5554 ) , whichever occurred first . for analyses concerning subclasses of cvd , participants who reported another cvd event than the one studied during followup were included as noncases for the studied cvd and censored at the date of that diagnosis .
nutritional intakes were energyadjusted using the residual method,25 and thus presented as adjusted ( least squares ) means with 95% ci .
values for all other quantitative variables were presented as means ( sd ) , and values for qualitative variables as percentages .
we estimated hazard ratio ( hr ) of cvd risk and 95% cis both for the continuous dii score and for quartiles of dii scores , using cox proportional hazard models.26 graphic methods ( log  log [ survival ] versus log  time plots ) were used to check for proportional hazards assumptions for this study . the lowest quartile of dii score ( q1 , reflecting the most antiinflammatory diet ) was used as the reference category .
the first model was crude ( model 0 ) , with only age as the timescale in the cox model .
a second model was adjusted for age ( timescale in the cox model ) , sex , and daily energy intake without alcohol ( continuous , in kcal / day ) ( model 1 ) .
a multivariate model was further adjusted for number of available 24hour dietary records ( continuous ) , smoking status , physical activity , education level , marital status , and treatment allocation group ( placebo or active ) ( model 2our main model ) .
two additional models ( 3a and 3b ) were created in order to verify whether our results would remain stable even when adjusting for baseline body mass index ( continuous , in kg / m ) and for alcohol intake ( continuous , in g / day ) , respectively .
the reason why model 3b was , in addition to body mass index , further adjusted for alcohol intake is that alcohol consumption is considered in a linear manner for the computation of the dii score while only moderate alcohol consumption is associated with a reduced cvd risk.27 the same models were used for both overall cvds and analyses focused on cvd subtypes . in order to verify the robustness of our findings
first , we reanalyzed our data after removing participants who developed a cardiovascular event during the first 2  years of followup .
second , we selected only participants with at least six 24hour records during the first 2  years of followup in order to improve the accuracy of nutritional estimates .
finally , we repeated our analyses with a dii score in which dietary intakes for all parameters were first adjusted for overall energy intake , using the energy density method ( [ crude intakes / total energy intake]1000 ) , named  dii 2  .
all tests were 2sided and p<0.05 was considered statistically significant , except for interaction tests for which statistical power is often weak in observational studies.28 thus , p<0.10 was applied for these models .
interactions between the dii score ( modeled both as a continuous variable and as quartiles ) and sex and intervention group were investigated .
all analyses were performed using sas software ( version 9.3 ; sas institute inc , cary , nc ) .
subjects were selected from the  supplmentation en vitamines et minraux antioxydants  ( su.vi.max ) study .
the su.vi.max study was a randomized , doubleblind , placebocontrolled primary prevention trial conducted between 1994 and 2002 .
it included 12  741 french adults ( women aged 3560  years and men aged 4560  years ) .
its primary aim was to evaluate the potential efficacy of daily supplementation with antioxidant vitamins and minerals ( ascorbic acid , vitamin e , carotene , selenium , and zinc ) delivered at nutritional ( ie , nonpharmacologic ) doses on the prevention of cancer , ischemic heart disease , and overall mortality.21 the trial phase ended in 2002 and health events monitoring was pursued until september 2007 .
the su.vi.max study was registered at clinicaltrials.gov ( number nct00272428 ) and was conducted according to the guidelines laid down in the helsinki declaration of 1975 as revised in 1983 , and was approved by the ethics committee for studies with human participants of pariscochin hospital ( ccpprb no .
in this analysis , we selected men and women who provided at least 3 valid 24hour dietary records during the first 2  years of followup ( n=8108 ) and who had no missing data for covariables ( 7743 ) to be included in the models ( figure ) .
cvd indicates cardiovascular diseases ; dii , dietary inflammatory index ; su.vi.max , supplmentation en vitamines et minraux antioxydants .
throughout the entire su.vi.max study trial phase ( 19942002 ) , participants were asked to provide a 24hour dietary record every 2  months , for a total of 6 records per year covering all days of the week and all seasons of the year . for these analyses ,
mean dietary intakes were calculated across all available , valid 24hour dietary records obtained during the first 2  years of followup , in order to obtain a proxy for habitual dietary intakes .
dietary records were considered invalid if energy intake was < 100 or > 6000  kcal / day .
additionally , men reporting < 800  kcal / day and women reporting < 500  kcal / day across one third or more of records were excluded to account for energy underreporting .
an instruction manual including validated photographs of generic foods and portion sizes was provided to facilitate coding food portions.22 a food composition table was used to estimate nutrient intake.23 we used the dii to determine the  inflammatory potential  of the diet .
this index relies on information contained in 1943 published studies reporting association between nutritional factors and inflammatory markers.17 briefly , points were assigned to every food parameter on the basis of relevant articles found in the literature , according to whether each food parameter increased ( + 1 ) , decreased ( 1 ) , or had no ( 0 ) effect on 6 inflammatory biomarkers : interleukin1b , interleukin4 , interleukin6 , interleukin10 , tumor necrosis factor , and creactive protein .
the dii computed from the 24hour records in this study includes data on 36 of the 45 food parameters comprising the dii : carbohydrate , protein , total fat , energy , alcohol , fiber , cholesterol , saturated fatty acids , monounsaturated fatty acids , polyunsaturated fatty acids , omega 3 , omega 6 , niacin , thiamin , riboflavin , vitamin b6 , vitamin b12 , iron , magnesium , vitamin a , vitamin c , vitamin d , vitamin e , folic acid , carotene , anthocyanidins , flavan3ol , flavonols , flavonones , flavones , isoflavones , garlic , ginger , pepper , onion , and tea .
mean and sd , derived from nutritional databases from 11 populations around the world , then transformed to percentiles and multiplied by literaturederived inflammatory points for each food parameter , then summed up .
dii scores were computed on the basis of participantspecific mean nutrient and food intakes , which were obtained by averaging intakes across all available dietary records , as explained in the first paragraph of the dietary data section ( ie , dii scores were not first calculated per day and then averaged ) .
other sources of information regarding outcome included yearly clinical examinations . in case of no contact with a participant for a long period , or nonattendance at the yearly visit ,
an investigation was launched to determine the reasons . in case of a suspected event ,
investigations were conducted to obtain relevant medical data ( clinical , biochemical , histological , and radiological reports ) from participants , physicians , and/or hospitals .
all cardiovascular events were reviewed and validated by an independent expert committee , unaware of the supplementation group assignment , and then classified using the international classification of diseases , 10th revision , clinical modification ( codes i20i24 , i64).24 first , we considered as outcome the occurrence of all cvds .
sociodemographic data , including sex , date of birth , education ( primary education only , up to secondary education , higher education ) , as well as information on marital status ( couple or single ) , smoking status ( neversmoked , former or current smoker ) , and physical activity level were obtained by a ( nonvalidated ) baseline questionnaire .
the items concerning physical activity inquired whether a participant had a regular physical activity , and if yes , whether they estimated this activity to be equivalent to 1  hour of walking per day .
body mass index was calculated using baseline weight and height measurements performed by trained personnel according to standardized procedures , using an electronic scale ( seca , hamburg , germany ) and a wallmounted stadiometer .
subjects contributed persontime up to the date of the cardiovascular event ( n=292 ) , death ( n=193 ) , the last completed questionnaire or last contact ( n=1704 ) or september 1 , 2007 ( n=5554 ) , whichever occurred first . for analyses concerning subclasses of cvd
, participants who reported another cvd event than the one studied during followup were included as noncases for the studied cvd and censored at the date of that diagnosis .
nutritional intakes were energyadjusted using the residual method,25 and thus presented as adjusted ( least squares ) means with 95% ci .
values for all other quantitative variables were presented as means ( sd ) , and values for qualitative variables as percentages .
we estimated hazard ratio ( hr ) of cvd risk and 95% cis both for the continuous dii score and for quartiles of dii scores , using cox proportional hazard models.26 graphic methods ( log  log [ survival ] versus log  time plots ) were used to check for proportional hazards assumptions for this study .
the lowest quartile of dii score ( q1 , reflecting the most antiinflammatory diet ) was used as the reference category .
the first model was crude ( model 0 ) , with only age as the timescale in the cox model .
a second model was adjusted for age ( timescale in the cox model ) , sex , and daily energy intake without alcohol ( continuous , in kcal / day ) ( model 1 ) .
a multivariate model was further adjusted for number of available 24hour dietary records ( continuous ) , smoking status , physical activity , education level , marital status , and treatment allocation group ( placebo or active ) ( model 2our main model ) .
two additional models ( 3a and 3b ) were created in order to verify whether our results would remain stable even when adjusting for baseline body mass index ( continuous , in kg / m ) and for alcohol intake ( continuous , in g / day ) , respectively .
the reason why model 3b was , in addition to body mass index , further adjusted for alcohol intake is that alcohol consumption is considered in a linear manner for the computation of the dii score while only moderate alcohol consumption is associated with a reduced cvd risk.27 the same models were used for both overall cvds and analyses focused on cvd subtypes . in order to verify the robustness of our findings
first , we reanalyzed our data after removing participants who developed a cardiovascular event during the first 2  years of followup .
second , we selected only participants with at least six 24hour records during the first 2  years of followup in order to improve the accuracy of nutritional estimates . finally , we repeated our analyses with a dii score in which dietary intakes for all parameters were first adjusted for overall energy intake , using the energy density method ( [ crude intakes / total energy intake]1000 ) , named  dii 2  .
all tests were 2sided and p<0.05 was considered statistically significant , except for interaction tests for which statistical power is often weak in observational studies.28 thus , p<0.10 was applied for these models .
interactions between the dii score ( modeled both as a continuous variable and as quartiles ) and sex and intervention group were investigated .
all analyses were performed using sas software ( version 9.3 ; sas institute inc , cary , nc ) .
these analyses included a total of 7743 participants ( 3197 men and 4546 women ) .
mean age at baseline ( sd ) was 51.94.7 and 47.16.6  years for men and women , respectively .
baseline characteristics of the study population are presented by sexspecific quartiles of the dii in table  1 . given the relatively large size of our sample , the following comparisons of characteristics across quartiles should be interpreted with caution , as not every statistically significant result is biologically and clinically meaningful .
compared to those with a lower dii score ( q1 ) , reflecting an antiinflammatory diet , participants with higher dii scores ( q4 ) , ( ie , more proinflammatory ) were slightly younger , less educated , less physically active , smokers , and less often postmenopausal women .
a higher dii score also was associated with slightly higher glycemia , slightly higher total blood cholesterol concentration , and slightly higher blood pressure , both systolic and diastolic .
in addition , a higher dii score was associated with lower total daily energy intake , as well as a lower fruit and vegetable consumption , a lower intake of mono and polyunsaturated fatty acids  including n3 and n6vitamins ( c , e , b6 , b9 , and b12 ) , carotene , calcium , magnesium , sodium , iron , iodine , potassium , phosphorus , and fibers but a higher intake of saturated fatty acids and a higher alcohol consumption ( table  2 ) .
baseline characteristics across sexspecific quartiles of the dii score , su.vi.max study , france ( n=7743 ) values for quantitative variables are means ( sd ) , except for the dii where mean ( interquartile range ) is presented .
dii indicates dietary inflammatory index ; hdl , highdensity lipoprotein ; htm , hormonal treatment for menopause ; ldl , lowdensity lipoprotein ; su.vi.max , supplmentation en vitamines et minraux antioxydants . 

oral contraceptive use : 3621 ; postmenopausal women : 4197 ; htm medication : 1092 ; glycemia : 7514 ; cholesterol : 7669 ; hdl and ldl cholesterol : 7618 ; systolic and diastolic blood pressure : 6422 .
nutritional data across sexspecific quartiles of the dii score , su.vi.max study , france ( n=7743 ) values are means ( sds ) or least squares means ( 95% ci ) , as specified .
dii indicates dietary inflammatory index ; mufa , monounsaturated fatty acids ; pufa , polyunsaturated fatty acids ; sfa , saturated fatty acids ; su.vi.max , supplmentation en vitamines et minraux antioxydants .
carbohydrate , fat , and protein are presented as percentage of total daily energy intake .
data were energyadjusted using the residual method , and thus presented as least squares means ( 95% cis ) . during the 13year followup ( mean duration was 11.4  years , corresponding to 87  932  personyears of observation ) ,
the distribution was as follows : 93 mi , 58 strokes , 128 angina pectoris and revascularization interventions , and 13 sudden deaths . in the crude model 0 ,
we observed a positive association between the dii score , reflecting a proinflammatory diet , and risk of cvd ( hrq4 versus q1=1.73 , 95% ci=1.252.39 ) ( table  3 ) .
however , this association was no longer observed after adjustment for confounding factors in any of the models ( 1 , 2 , 3a , or 3b ) .
interactions tested between the dii score and sex or intervention group were not significant , whether the dii was modeled as a continuous variable or as quartiles .
association between the dii and incidence of overall cardiovascular disease , su.vi.max study , france ( n=7743 ) the values listed next to 
model 0model 3b  are hazard ratio ( 95% cis ) , estimated through cox proportional hazard models , corresponding to sexspecific quartiles of the dii .
model 2 : model 1+supplementation group , number of 24h records , education level , marital status , smoking status , and physical activity .
dii indicates dietary inflammatory index ; iqr , interquartile range ; q , sexspecific quartile ; su.vi.max , supplmentation en vitamines et minraux antioxydants . 

p for trend ( obtained by modeling dii quartiles as an ordinal variable ) . when separating cvds into subclasses ( table  4 ) , being in the highest dii score quartile was associated with a higher incidence of mi , as compared to being in the lowest quartile ( hrquartile 4 versus quartile 1=2.24 , 95% ci : 1.084.67 ) in the fully adjusted model ( model 2 ) , although the hr for a onepointincrease in dii was not statistically significant ( hr continuous dii=1.11 , 95% ci=0.971.27 ) .
no significant relationship was found regarding incidence of cerebrovascular accident or angina pectoris and revascularization intervention .
association between the dii and incidence of subclasses of cardiovascular disease , su.vi.max study , france ( n=7743 ) values are hazard ratio ( 95% cis ) , estimated through cox proportional hazard models , corresponding to sexspecific quartiles of the dii .
persontime per quartile ( q ) in days : q1 , 22  432 ; q2 , 22  117 ; q3 , 21  912 ; q4 , 21  471 .
model 2 : model 1+supplementation group , number of 24h records , education level , marital status , smoking status , and physical activity .
ap indicates angina pectoris ; dii , dietary inflammatory index ; mi , myocardial infarction ; q , sexspecific quartile ; ri , revascularization intervention ; su.vi.max , supplmentation en vitamines et minraux antioxydants . 

three sets of supplemental analyses were conducted in order to investigate the stability of our results concerning mi .
first , when removing participants with cardiovascular events declared during the first 2  years of followup ( n=7602 ) , findings were very similar ( table  5 ) .
next , when selecting participants with at least six 24hour records ( n=6362 ) , findings were strengthened ( hrq4 versus q1 for mi risk=3.23 , 95% ci=1.377.62 ) , and the hr for a onepointincrease in dii was significantly different from 1.00 ( hr continuous=1.18 , 95% ci=1.011.38 ) ( table  6 ) .
finally , in analyses using a dii score based on energyadjusted nutritional parameters , the results were broadly consistent with those of our main analysis , although the observed association was weaker ( table  7 ) .
association between the dii and incidence of myocardial infarction among participants without early cardiovascular events , su.vi.max study , france ( n=7602 ) values are hazard ratio ( 95% cis ) , estimated through cox proportional hazard models , corresponding to sexspecific quartiles of the dii .
model 2 : model 1+supplementation group , number of 24h records , education level , marital status , smoking status , and physical activity .
dii indicates dietary inflammatory index ; iqr , interquartile range ; q , sexspecific quartile ; su.vi.max , supplmentation en vitamines et minraux antioxydants . 

association between the dii and incidence of myocardial infarction among participants with at least six 24h dietary records , su.vi.max study , france ( n=6362 ) values are hazard ratio ( 95% cis ) , estimated through cox proportional hazard models , corresponding to sexspecific quartiles of the dii .
model 2 : model 1+supplementation group , number of 24h records , education level , marital status , smoking status , and physical activity .
dii indicates dietary inflammatory index ; iqr , interquartile range ; q , sexspecific quartile ; su.vi.max , supplmentation en vitamines et minraux antioxydants . 

association between a dii calculated on the basis of energyadjusted nutritional parameters ( dii 2 ) and incidence of myocardial infarction , su.vi.max study , france ( n=7743 ) values are hazard ratio ( 95% cis ) , estimated through cox proportional hazard models , corresponding to sexspecific quartiles of the dii .
model 2 : model 1+supplementation group , number of 24h records , education level , marital status , smoking status , and physical activity .
dii indicates dietary inflammatory index ; iqr , interquartile range ; q , sexspecific quartile ; su.vi.max , supplmentation en vitamines et minraux antioxydants . 

in this large cohort study of middleaged french adults , a prospective association was found between a proinflammatory diet , as reflected by higher dii scores , and the incidence of myocardial infarction over a 13year period , even after adjusting for a wide range of potential confounders including sociodemographic data and lifestyle habits .
no statistically significant relationship was observed for overall cvd risk , stroke , or angina pectoris and revascularization intervention incidence . to the best of our knowledge
, no previous study had investigated the association between the dii score and different subtypes of cvd . as indicated by the distribution of nutrient intakes by dii quartiles in our study ( table  2 )
, lower dii scores do not simply reflect diets with a higher antiinflammatory potential , but also diets that are generally healthier .
thus , our findings also should be interpreted in the light of studies that have found a preventive role of diets with an overall high quality with respect to mi incidence .
for example , lower risks of mi were found among individuals exhibiting a healthy diet , as defined by a score above 27 points on a slightly modified version of the smartdiet index in the troms study,29 and defined by being in the top quintile of recommended food score in a prospective cohort of swedish men.30 the mediterranean diet  also has been related to a lower mi incidence.31 
  the dii was associated with increased mi risk but not with other cvd outcomes in our study .
a possible explanation could be that inflammation is more strongly linked to mi than other subtypes of cvd .
indeed , the infiltration and retention of lowdensity lipoprotein cholesterol in the arterial intima initiates an inflammatory response in the artery wall , involving the binding of blood cells , especially monocytes , which then differentiate into macrophages and internalize a broad range of molecules including oxidized lowdensity lipoprotein particles .
ultimately , the macrophages are transformed into foam cells , the prototypical cells in atherosclerosis .
several endogenous and microbial molecules can ligate patternrecognition receptors ( tolllike receptors ) on these cells , leading to the release of proinflammatory cytokines and ultimately to tissue damage .
as activated macrophages produce inflammatory cytokines that can destabilize lesions and initiate thrombus formation , all of these inflammatory reactions can finally lead to the activation and rupture of plaques , and mi.13 , 14 , 15 
  angina pectoris and revascularization interventions  which are generally conducted among highrisk people before any cardiovascular event  might reflect the early stages of inflammatory mechanism,14 compared to mi , which reflects the cumulative effect of advancedstage inflammation in the artery . on the other hand , ischemic or hemorrhagic
strokes may or may not be linked to mechanisms of inflammation32 ; nevertheless , it was hard to separate the 2 types in our study . to the best of our knowledge , only 3 other studies have investigated the association between the dii score and overall cvd risk using a prospective design .
two of these studies that were based on the spanish cohorts predimed ( prevencin con dieta mediterrnea)18 and sun ( seguimiento universidad de navarra)19 have investigated quartiles of the dii , and have found a positive association , showing a linear dose  response trend , with overall cvd risk .
the respective hr , comparing the fourth with the first quartile , were 1.73 ( 95% ci=1.152.60),18 and 2.03 ( 1.063.88),19 respectively .
another study , conducted in a cohort of australian men,20 has investigated the dii as a binary variable ( negative versus positive scores ) ; it also found positive dii scores to be associated with an elevated overall cvd risk : odds ratio=2.07 ( 1.20 , 3.55 ) . other studies have focused on other dietary indexes . for instance , a higher level of adherence to the french dietary guidelines , as reflected in programme national nutrition santguideline score ( pnnsgs ) , was associated with a lower risk of cvd.33 this result is consistent with those obtained examining other diet quality indexes.34 , 35 nevertheless , these dietary indices do not focus on the inflammatory potential of the diet , and thus the measured association may reflect different mechanisms of action . some limitations of this study should be acknowledged .
first , the subjects in our analysis , who were volunteers participating in a nutritional intervention study,21 generally had a higher educational level than the general population , and probably a higher general interest in nutrition .
furthermore , we included only participants who had completed at least 3 dietary records during the first 2  years of the study ; thus , they may have been particularly compliant and health conscious .
moreover , participants of the su.vi.max cohort were aged between 35 ( women ) or 45 ( men ) and 60  years old at baseline .
thus , any generalization of these results to younger or older subjects should be done cautiously ; further studies may be needed in other populations .
additionally , the limited number of cases may have impaired our ability to detect some of the hypothesized associations , especially for specific cvd subtypes . finally ,
these findings are based on observational data ; thus , residual confounding can not be ruled out .
strengths of the present study include its large sample size and its prospective design , allowing us to assess the association between baseline inflammatory potential of the diet and cvd risk through a long followup period of 13  years .
in addition , our clinical and dietary data exhibited a high level of accuracy , with a mean of nine 24hour dietary records per participant .
finally , we used an index that was specifically designed to measure the inflammatory potential of any diet : the dii was based on peerreviewed literature focusing specifically on inflammation ; furthermore , this index can be adapted to virtually any dietary assessment method that provides estimates of nutrient intake ; and it is standardized to dietary intakes from representative populations around the world , thus facilitating easy quantitative comparisons across studies .
the results of this study provide new arguments for dietary prevention of mi , suggesting that favoring antiinflammatory nutritional compounds and limiting proinflammatory foods and nutrients may contribute to lower the risk of mi .
this is in line with the major role of inflammation in the development of atherosclerosis , the most important contributor to the growing burden of cvd .
the authors responsibilities were as follows : galan , hercberg , and kesseguyot were responsible for developing the concept , design , and protocol of the study and for coordinating data collection ; neufcourt performed the statistical analysis and wrote the article ; kesseguyot provided methodological guidance and had primary responsibility for the final content ; neufcourt , assmann , fezeu , touvier , graffouillre , shivappa , hbert , wirth , hercberg , galan , julia , and kesseguyot were involved in interpreting results and editing the manuscript for important intellectual content .
this work was supported by grants from the fondation coeur et artres , the french national research agency ( agence nationale de recherche , anr ) ( grant no .
anr05pnra010 ) and the french ministry of health ( direction gnrale de sant , dgs ) .
assmann was supported by a doctoral fellowship from the ecole doctorale galile , university of paris 13 , sorbonne paris cit .
drs shivappa , hbert , and wirth were supported by the united states national institute for diabetes , digestive and kidney diseases ( grant no .
dr james r. hbert owns controlling interest in connecting health innovations llc ( chi ) , a company planning to license the right to his invention of the dietary inflammatory index ( dii ) from the university of south carolina in order to develop computer and smartphone applications for patient counseling and dietary intervention in clinical settings .
 backgroundcardiovascular diseases ( cvd ) are the leading cause of death in the world , and diet plays a major role in cvd incidence , especially through lipid oxidation mechanisms . 
 this , in turn , leads to tissue inflammation and formation of atheromatous plaques.methods and resultsour objective was to evaluate the association between the inflammatory potential of the diet and the incidence of overall cvd or its subclasses . 
 we included 7743 participants from the supplmentation en vitamines et minraux antioxydants ( su.vi.max ) cohort . 
 all cardiovascular events were recorded using selfreported information or clinical visits , and were validated . the dietary inflammatory index ( dii ) 
 was computed using repeated 24hour dietary records ( mean=9.53.4 records / subject ) . 
 hazard ratio and 95% ci for outcomes ( cvd and subclasses ) were estimated across sexspecific quartiles of the dii using cox proportional hazard models . 
 a total of 292 cardiovascular events were recorded and validated during an average of 11.4  years of followup : 93 myocardial infarctions , 58 strokes , 128 angina pectoris and revascularization interventions , and 13 sudden deaths . when considering cvd subclasses , a diet with proinflammatory properties , as expressed by higher dii scores , was significantly associated with a higher risk of myocardial infarction ( hazard ratioquartile 4 versus quartile 1=2.24 , 95% ci : 1.084.67 ) . 
 no significant association was observed between the dii score and stroke or both angina pectoris and revascularization intervention.conclusionsa proinflammatory diet , as measured by a higher dii score , was prospectively associated with a higher risk of myocardial infarction . 
 promotion of a diet exhibiting antiinflammatory properties may help prevent myocardial infarctions . 