data were derived from the third national health and nutrition examination survey ( nhanes iii , 19881994 ) , a representative survey of the civilian , noninstitutionalized us population conducted by the national center for health statistics ( nchs ) of the center for disease control and prevention . details of the survey design and methodology are available elsewhere ( nchs , 2006a ) . briefly , individuals were interviewed at home , then invited to a mobile examination centre ( mec ) for further interviews , tests and examinations . details of the oral health component of nhanes iii are published elsewhere ( drury et  al . 1996 ) . the teeth were divided into two maxillary and two mandibular halves and measurements were taken from two sites per tooth ( midbuccal and mesiobuccal ) for all teeth ( excluding third molars ) in one randomly chosen upper and lower quadrant . these measurements included periodontal probing depth ( ppd ) , gingival recession and bleeding on probing ( bop ) . clinical attachment loss ( cal ) was calculated as the sum of the recession and ppd . individuals receiving renal replacement therapy ( through dialysis or kidney transplant ) were excluded from periodontal examination . periodontitis was defined using the 2007 cdc / aap ( centre for disease control and prevention / american academy of periodontology ) classification ( page & eke 2007 ) . in addition , continuous periodontal parameters were also employed such as mean ppd , mean cal , cumulative periodontal probing depth ( cppd ) , number of teeth present and proportion of sites that bled upon probing . cumulative ppd was calculated as the sum of the maximum probing pocket depths 4  mm of each tooth and as such is a surrogate measure of the potential extent of biofilm exposed connective tissues ( dietrich et  al . edentulous individuals were included in the analyses but formed a group distinct from individuals with periodontitis . the serum creatinine levels recorded in the nhanes iii survey were recalibrated to be traceable to an isotopederived mass spectroscopy method using the equation  below ( nchs , 2006b ) : 
 standardized creatinine=(0.960serum creatinine)0.18 
  age , sex , ethnicity and standardized serum creatinine were incorporated in the ckd epidemiology collaboration ( ckdepi ) equation  to calculate estimated glomerular filtration rate ( egfr ) ( levey et  al . this equation  improves mortality risk stratification in individuals with ckd compared with the modification of diet in renal disease ( mdrd ) equation  ( shafi et  al . 2012 ) . based on an egfr<60  ml / min/1.73  m , individuals were classified as having stage 35 ckd , hitherto referred to as urinary albumin and creatinine levels were employed to calculate the albumincreatinine ratio ( acr ) . albuminuria was classified as acr < 30  mg / g ; acr    30  mg / g and < 300  mg / g ; and acr    300  mg / g . individuals were classed as hypertensive if their mean ( of three consecutive measurements ) systolic blood pressure ( bp ) was 140  mmhg or mean diastolic bp was 90  mmhg . individuals were classed as diabetic by selfreporting ( excluding gestational diabetes ) or if their glycated haemoglobin ( hba1c ) was 6.5% . individuals ' smoking status was determined from selfreporting and classified into current , former or never smokers ( cigarettes only ) . data on covariates employed in the statistical analyses included information on age , sex , ethnicity ( nonhispanic white , nonhispanic black , mexican american or other ) , alcohol consumption ( never , not in last year , between 014 drinks / week , more than 14 drinks / week ) and selfreported history of previous cardiovascular events ( stroke , heart attack or heart failure ) . pulse pressure was calculated as the difference between the mean systolic and diastolic bp . self reported measures of socioeconomic status ( household income , marital status and educational attainment ) were coded as follows . household income ( less than $ 20,000 or $ 20,000 or more ) ; marital status ( married or living as married , never married , divorced or separated or widowed ) ; educational attainment ( less than high school , high school diploma or more than high school ) . body mass index ( bmi ) was coded  as a categorical variable with bmi < 18.5  kg / m as underweight ;   18.5  kg / m and < 25  kg / m as normal ;  25  kg / m and < 30  kg / m as overweight and 30  kg / m as obese . laboratory tests including serum cholesterol ( total and highdensity lipoprotein / hdl ) were performed . serum cholesterol levels were classified into binary variables ( total serum cholesterol 24  mg / l or < 24  mg / l and serum hdl cholesterol 3.5  mg physical activity was selfreported by individuals and reclassified as  recommended or more  if they reported moderate activity five or more times a week or vigorous activity three or more times a week . physical activity was also classified as  recommended or more  if individuals reported moderate physical activity four or more times a week and vigorous activity one or more times a week or reported moderate activity three or more times a week and vigorous activity two or more times a week . individuals ' physical activity was classified as  none  if they reported no leisure time physical activities . individuals who reported some level of physical activity but less than recommended were classed as the nchs provide mortality data for nhanes iii participants up to 31st december 2006 , linked by probabilistic record matching with the national death index ( ndi ) . the publicly available data set contains information on the mortality status of individuals aged 17  years or older . for individuals who are classified as assumed deceased  , information is available on 113 underlying cause of death categories , based on the ninth and tenth revisions of the international classification of diseases ( icd9 and icd10 ) . cvd mortality was limited to cases where the underlying cause of death was coded between 53 and 75 ( inclusive ) ( anderson et  al . 2001 ) . details of the linked mortality data have been published elsewhere ( nchs , 2010 ) . analyses performed followed guidelines for nhanes iii ( nchs , 1996 ) , accounting for the complex survey design and sampling weights to yield estimates generalizable to the us population . differences in categorical and continuous data were assessed for statistical significance using pearson chisquare , ttest , fisher 's exact test and analysis of variance ( anova ) as appropriate . cox proportional hazards ( ph ) regression models were fitted to evaluate the association between periodontal status , traditional risk factors ( diabetes , hypertension and smoking status ) and allcause and cvd mortality , independent of potential confounders . the fully adjusted model adjusted for age , sex , ethnicity , ckd status , periodontal status , diabetic status , hypertensive status , smoking status , pulse pressure , history of cvd ( heart attack or stroke or heart failure ) , alcohol consumption , acr , hypercholesterolaemia and lowhdl , bmi , physical activity and measures of socioeconomic status ( household income , marital status and educational attainment ) . the ph assumption was tested using schoenfeld residuals , scaled schoenfeld residuals and graphical methods . were not included in the analyses ( listwise deletion ) . thus out of a possible 13,784 individuals eligible for analyses , 1379 ( 10% ) individuals were excluded due to incomplete covariate data ( table  s1 ) . we considered the effect measure modification of mortality ( allcause and cardiovascular ) in individuals with ckd according to their periodontal health status . we conducted formal tests of interaction between periodontal variables and ckd case definition by entering interaction terms in the model . further formal tests of interactions between ckd , periodontitis or edentulism and age , gender and ethnicity were also carried out . analyses were carried out using stata / ic version 12.1 ( statacorp lp , college station , tx , usa ) . data were derived from the third national health and nutrition examination survey ( nhanes iii , 19881994 ) , a representative survey of the civilian , noninstitutionalized us population conducted by the national center for health statistics ( nchs ) of the center for disease control and prevention . details of the survey design and methodology are available elsewhere ( nchs , 2006a ) . briefly , individuals were interviewed at home , then invited to a mobile examination centre ( mec ) for further interviews , tests and examinations . details of the oral health component of nhanes iii are published elsewhere ( drury et  al . 1996 ) . the teeth were divided into two maxillary and two mandibular halves and measurements were taken from two sites per tooth ( midbuccal and mesiobuccal ) for all teeth ( excluding third molars ) in one randomly chosen upper and lower quadrant . these measurements included periodontal probing depth ( ppd ) , gingival recession and bleeding on probing ( bop ) . clinical attachment loss ( cal ) individuals receiving renal replacement therapy ( through dialysis or kidney transplant ) were excluded from periodontal examination . periodontitis was defined using the 2007 cdc / aap ( centre for disease control and prevention / american academy of periodontology ) classification ( page & eke 2007 ) . in addition , continuous periodontal parameters were also employed such as mean ppd , mean cal , cumulative periodontal probing depth ( cppd ) , number of teeth present and proportion of sites that bled upon probing . cumulative ppd was calculated as the sum of the maximum probing pocket depths 4  mm of each tooth and as such is a surrogate measure of the potential extent of biofilm exposed connective tissues ( dietrich et  al . edentulous individuals were included in the analyses but formed a group distinct from individuals with periodontitis . the serum creatinine levels recorded in the nhanes iii survey were recalibrated to be traceable to an isotopederived mass spectroscopy method using the equation  below ( nchs , 2006b ) : 
 standardized creatinine=(0.960serum creatinine)0.18 
  age , sex , ethnicity and standardized serum creatinine were incorporated in the ckd epidemiology collaboration ( ckdepi ) equation  to calculate estimated glomerular filtration rate ( egfr ) ( levey et  al . 2009 ) . this equation  improves mortality risk stratification in individuals with ckd compared with the modification of diet in renal disease ( mdrd ) equation  ( shafi et  al . based on an egfr<60  ml / min/1.73  m , individuals were classified as having stage 35 ckd , hitherto referred to as urinary albumin and creatinine levels were employed to calculate the albumincreatinine ratio ( acr ) . albuminuria was classified as acr < 30  mg / g ; acr    30  mg / g and < 300  mg / g ; and acr    300  mg / g . individuals were classed as hypertensive if their mean ( of three consecutive measurements ) systolic blood pressure ( bp ) was 140  mmhg or mean diastolic bp was 90  mmhg . individuals were classed as diabetic by selfreporting ( excluding gestational diabetes ) or if their glycated haemoglobin ( hba1c ) was 6.5% . individuals ' smoking status was determined from selfreporting and classified into current , former or never smokers ( cigarettes only ) . data on covariates employed in the statistical analyses included information on age , sex , ethnicity ( nonhispanic white , nonhispanic black , mexican american or other ) , alcohol consumption ( never , not in last year , between 014 drinks / week , more than 14 drinks / week ) and selfreported history of previous cardiovascular events ( stroke , heart attack or heart failure ) . self reported measures of socioeconomic status ( household income , marital status and educational attainment ) were coded as follows . household income ( less than $ 20,000 or $ 20,000 or more ) ; marital status ( married or living as married , never married , divorced or separated or widowed ) ; educational attainment ( less than high school , high school diploma or more than high school ) . body mass index ( bmi ) was coded  as a categorical variable with bmi  < 18.5  kg / m as underweight ;   18.5  kg / m and < 25  kg / m as normal ;  25  kg / m and < 30  kg / m as overweight and 30  kg / m as obese . laboratory tests including serum cholesterol ( total and highdensity lipoprotein / hdl ) were performed . serum cholesterol levels were classified into binary variables ( total serum cholesterol 24  mg / l or < 24  mg / l and serum hdl cholesterol 3.5  mg physical activity was selfreported by individuals and reclassified as  recommended or more  if they reported moderate activity five or more times a week or vigorous activity three or more times a week . if individuals reported moderate physical activity four or more times a week and vigorous activity one or more times a week or reported moderate activity three or more times a week and vigorous activity two or more times a week . individuals ' physical activity was classified as  none  if they reported no leisure time physical activities . individuals who reported some level of physical activity but less than recommended were classed as the nchs provide mortality data for nhanes iii participants up to 31st december 2006 , linked by probabilistic record matching with the national death index ( ndi ) . the publicly available data set contains information on the mortality status of individuals aged 17  years or older . for individuals who are classified as assumed deceased  , information is available on 113 underlying cause of death categories , based on the ninth and tenth revisions of the international classification of diseases ( icd9 and icd10 ) . cvd mortality was limited to cases where the underlying cause of death was coded between 53 and 75 ( inclusive ) ( anderson et  al . details of the linked mortality data have been published elsewhere ( nchs , 2010 ) . analyses performed followed guidelines for nhanes iii ( nchs , 1996 ) , accounting for the complex survey design and sampling weights to yield estimates generalizable to the us population . differences in categorical and continuous data were assessed for statistical significance using pearson chisquare , ttest , fisher 's exact test and analysis of variance ( anova ) as appropriate . cox proportional hazards ( ph ) regression models were fitted to evaluate the association between periodontal status , traditional risk factors ( diabetes , hypertension and smoking status ) and allcause and cvd mortality , independent of potential confounders . the fully adjusted model adjusted for age , sex , ethnicity , ckd status , periodontal status , diabetic status , hypertensive status , smoking status , pulse pressure , history of cvd ( heart attack or stroke or heart failure ) , alcohol consumption , acr , hypercholesterolaemia and lowhdl , bmi , physical activity and measures of socioeconomic status ( household income , marital status and educational attainment ) . the ph assumption was tested using schoenfeld residuals , scaled schoenfeld residuals and graphical methods . any individuals with missing covariate data were not included in the analyses ( listwise deletion ) . thus out of a possible 13,784 individuals eligible for analyses , 1379 ( 10% ) individuals were excluded due to incomplete covariate data ( table  s1 ) . we considered the effect measure modification of mortality ( allcause and cardiovascular ) in individuals with ckd according to their periodontal health status . we conducted formal tests of interaction between periodontal variables and ckd case definition by entering interaction terms in the model . further formal tests of interactions between ckd , periodontitis or edentulism and age , gender and ethnicity were also carried out . analyses were carried out using stata / ic version 12.1 ( statacorp lp , college station , tx , usa ) . we analysed data from individuals in nhanes iii aged 20  years and older with complete data on serum creatinine , periodontal status and mortality followup ( n  =  13,784 ) and with a median followup time of 14.3  years ( mean 13.5  years , range 1  month18.2  years ) . of the 13,794 individuals included in the analyses , 861 ( 6% ) were classified as ckd and 12,923 as nonckd . individuals with ckd were more likely to be older , have different ethnic and socioeconomic mix , nonsmokers ( never or ex smokers ) , diabetic , hypertensive , with higher total serum cholesterol and lower levels of serum hdl , report lower levels of physical activity and consume less alcohol and report a history of cvd ( stroke , heart attack and congestive heart failure ) compared to those without ckd . individuals with ckd were more likely to suffer from periodontitis ( or be edentulous ) and have fewer teeth compared to individuals without ckd . when examining continuous variables of periodontal health , patients with ckd were more likely to have a greater mean cal and greater bop ( table  1 ) . values are percentages ( standard error ) unless stated acr , albumincreatinine ratio ; bmi , body mass index ; bop , percentage of sites that bleed on probing ; cal , clinical attachment loss ; cppd , cumulative probing depth ; egfr , estimated glomerular filtration rate ; hdl , highdensity lipoprotein ; ppd , periodontal probing depth . comparing no ckd and ckd . within individuals with ckd , comparing healthy and periodontitis . among individuals with ckd , those with periodontitis were more likely to be older , of nonwhite ethnicity , current smokers , diabetic and hypertensive and have a lower egfr compared to periodontally healthy individuals . these individuals also had lower household incomes and educational attainments compared to periodontally healthy individuals . periodontally healthy individuals were similar to those with periodontitis in terms of their sex , alcohol consumption , marital status , physical activity , history of cvd events and bmi ( table  1 ) . after adjusting for covariates , individuals with ckd had a 44% ( 95% ci : 2863% ) increased rate of allcause mortality compared to those without ckd ( table  2 ) . individuals with periodontitis had a 36% ( 2251% ) increased rate of allcause mortality compared to individuals who were periodontally healthy . results from cox proportional hazards regression analyses for allcause and cardiovascular mortality using an age and sexadjusted and a fully adjusted model bop , proportion of sites that bleed on probing ; cal , clinical attachment loss ; ckd , chronic kidney disease ; cppd , cumulative periodontal probing depth ; ppd , periodontal probing depth . fully adjusted model adjusted for age , sex , ethnicity , ckd status , periodontal status , diabetic status , hypertensive status , smoking status , pulse pressure , history of cvd ( heart attack or stroke or heart failure ) , alcohol consumption , acr , hypercholesterolaemia and lowhdl , bmi , physical activity and measures of socioeconomic status ( household income , marital status and educational attainment ) . the association between periodontitis and allcause mortality was similar between individuals with or without ckd ( pvalue for interaction  =  0.57 ) . similarly , the associations between ckd and allcause mortality did not vary by age , sex or diabetes status ( pvalues for interaction 0.14 , 0.99 and 0.09 respectively ) . furthermore , the association between periodontitis and allcause mortality did not vary by age , gender or diabetes status ( pvalues for interaction 0.73 , 0.51 and 0.51 respectively ) . in edentulous individuals edentulous individuals under the age of 65 had a significantly increased rate of allcause mortality compared to edentulous individuals 65  years and older , hazard ratio ( hr ) 1.85 ( 1.412.44 ) and 1.18 ( 1.041.33 ) respectively ( tables s2 , s3 and fig . for example a 1  mm increase in mean ppd was associated with a 17% ( 628% ) increase in incident rate of allcause mortality ( table  2 ) . edentulousness was associated with a 32% ( 1750% ) increased rate of allcause mortality compared with periodontally healthy dentate individuals . diabetes ( hr 1.41 ; 1.271.57 ) , hypertension ( hr 1.06 ; 0.931.20 ) and current smoking ( hr 2.12 ; 1.822.48 ) were associated with an increased rate of allcause mortality although this increase was not significant for hypertension ( table  2 ) . the 10year allcause mortality for individuals with ckd ( but without periodontitis or other traditional risk factors ) was 32% ( 2935% ) . addition of periodontitis to the risk profile increased 10year mortality to 41% ( 3647% ) . this increase in mortality was comparable with that seen in individuals with ckd who had diabetes instead of periodontitis ( 43% ; 3849% ) . a similar cumulative effect on mortality is seen with periodontitis and other traditional risk factors ( table  3 ) . these estimates are based on the demographic features of individuals with ckd within nhanes iii ( e.g. a mean age of 73  years ) . estimated survival curves for individuals with ckd and different risk factor profiles is given in fig .  1 . tenyear allcause mortality ( percentages ) of individuals with ckd by risk factors ( along with the addition of periodontitis to the risk factor ) fully adjusted model adjusted for age , sex , ethnicity , ckd status , periodontal status , diabetic status , hypertensive status , smoking status , pulse pressure , history of cvd ( heart attack or stroke or heart failure ) , alcohol consumption , acr , hypercholesterolaemia and lowhdl , bmi , physical activity and measures of socioeconomic status ( household income , marital status and educational attainment ) . cox proportional hazard regression graphs ( adjusting for age , sex , ethnicity , pulse pressure , history of cvd , alcohol consumption , acr , hypercholesterolaemia and lowhdl , bmi , physical activity , household income , marital status and educational attainment ) of survival in patients with ckd stratified using periodontitis and other traditional risk factors ( diabetes , hypertension and smoking ) . individuals with ckd had a 60% ( 3295% ) increased rate of cvd mortality compared to those without ckd ( table  2 ) , independent of confounders specified . individuals with periodontitis had a 38% ( 1665% ) increased rate of cvd mortality compared to individuals who were periodontally healthy . the association between periodontitis and cvd mortality was similar between individuals with or without ckd ( pvalue for interaction  =  0.27 ) . the associations between ckd and cvd mortality did not vary by age , sex or diabetes status ( pvalues for interaction 0.39 , 0.82 and 0.34 respectively ) . the association between periodontitis and cvd mortality did not vary by gender or diabetes status ( pvalues for interaction 0.77 and 0.17 respectively ) . there was a trend in patients with ckd and periodontitis to have an increased hr of cvd mortality if they were under the age of 65 compared with 65 and over but this was not significant . edentulous individuals under the age of 65 having a significantly increased rate of cvd mortality , hr 2.03 ( 1.313.13 ) , compared to edentulous individuals 65  years and older who had comparable rates of cvd mortality compared to periodontally healthy individuals , hr 0.89 ( 0.711.10 ) ( tables s4 , s5 and fig . mean ppd and percentage of sites that bleed on probing were associated with a statistically significant increase in the rate of cvd mortality ( table  2 ) . edentulous and periodontally healthy dentate individuals had comparable rates of cvd mortality ( table  2 ) . diabetes ( hr 1.45 ; 1.241.70 ) , hypertension ( hr 1.32 ; 1.061.63 ) and current smoking ( hr 2.10 ; 1.692.62 ) were associated with an increased rate of cvd mortality ( table  2 ) . the 10year cvd mortality for individuals with ckd ( and combinations of risk factors ) highlights the similarity in the magnitude of increase in cvd mortality associated with diabetes ( 24% ; 1930% ) compared with periodontitis ( 22% ; 1927% ) ( table  4 ) . estimated cvd survival for individuals with ckd and different risk factor profiles is given in fig .  2 . tenyear cvd mortality ( percentages ) of individuals with ckd by risk factors ( along with the addition of periodontitis to the risk factor ) fully adjusted model adjusted for age , sex , ethnicity , ckd status , periodontal status , diabetic status , hypertensive status , smoking status , pulse pressure , history of cvd ( heart attack or stroke or heart failure ) , alcohol consumption , acr , hypercholesterolaemia and lowhdl , bmi , physical activity and measures of socioeconomic status ( household income , marital status and educational attainment ) . for cardiovascular mortality . cox proportional hazard regression graphs ( adjusting for age , sex , ethnicity , pulse pressure , history of cvd , alcohol consumption , acr , hypercholesterolaemia and lowhdl , bmi , physical activity , household income , marital status and educational attainment ) of survival in patients with ckd stratified using periodontitis and other traditional risk factors ( diabetes , hypertension and smoking ) . we analysed data from individuals in nhanes iii aged 20  years and older with complete data on serum creatinine , periodontal status and mortality followup ( n  =  13,784 ) and with a median followup time of 14.3  years ( mean 13.5  years , range 1  month18.2  years ) . of the 13,794 individuals included in the analyses , 861 ( 6% ) were classified as ckd and 12,923 as nonckd . individuals with ckd were more likely to be older , have different ethnic and socioeconomic mix , nonsmokers ( never or ex smokers ) , diabetic , hypertensive , with higher total serum cholesterol and lower levels of serum hdl , report lower levels of physical activity and consume less alcohol and report a history of cvd ( stroke , heart attack and congestive heart failure ) compared to those without ckd . individuals with ckd were more likely to suffer from periodontitis ( or be edentulous ) and have fewer teeth compared to individuals without ckd . when examining continuous variables of periodontal health , patients with ckd were more likely to have a greater mean cal and greater bop ( table  1 ) . values are percentages ( standard error ) unless stated acr , albumincreatinine ratio ; bmi , body mass index ; bop , percentage of sites that bleed on probing ; cal , clinical attachment loss ; cppd , cumulative probing depth ; egfr , estimated glomerular filtration rate ; hdl , highdensity lipoprotein ; ppd , periodontal probing depth . comparing no ckd and ckd . within individuals with ckd , comparing healthy and periodontitis . among individuals with ckd , those with periodontitis were more likely to be older , of nonwhite ethnicity , current smokers , diabetic and hypertensive and have a lower egfr compared to periodontally healthy individuals . these individuals also had lower household incomes and educational attainments compared to periodontally healthy individuals . periodontally healthy individuals were similar to those with periodontitis in terms of their sex , alcohol consumption , marital status , physical activity , history of cvd events and bmi ( table  1 ) . after adjusting for covariates , individuals with ckd had a 44% ( 95% ci : 2863% ) increased rate of allcause mortality compared to those without ckd ( table  2 ) . individuals with periodontitis had a 36% ( 2251% ) increased rate of allcause mortality compared to individuals who were periodontally healthy . results from cox proportional hazards regression analyses for allcause and cardiovascular mortality using an age and sexadjusted and a fully adjusted model bop , proportion of sites that bleed on probing ; cal , clinical attachment loss ; ckd , chronic kidney disease ; cppd , cumulative periodontal probing depth ; ppd , periodontal probing depth . fully adjusted model adjusted for age , sex , ethnicity , ckd status , periodontal status , diabetic status , hypertensive status , smoking status , pulse pressure , history of cvd ( heart attack or stroke or heart failure ) , alcohol consumption , acr , hypercholesterolaemia and lowhdl , bmi , physical activity and measures of socioeconomic status ( household income , marital status and educational attainment ) . the association between periodontitis and allcause mortality was similar between individuals with or without ckd ( pvalue for interaction  =  0.57 ) . similarly , the associations between ckd and allcause mortality did not vary by age , sex or diabetes status ( pvalues for interaction 0.14 , 0.99 and 0.09 respectively ) . furthermore , the association between periodontitis and allcause mortality did not vary by age , gender or diabetes status ( pvalues for interaction 0.73 , 0.51 and 0.51 respectively ) . in edentulous individuals , there was a significant difference in allcause mortality by age . edentulous individuals under the age of 65 had a significantly increased rate of allcause mortality compared to edentulous individuals 65  years and older , hazard ratio ( hr ) 1.85 ( 1.412.44 ) and 1.18 ( 1.041.33 ) respectively ( tables s2 , s3 and fig . for example a 1  mm increase in mean ppd was associated with a 17% ( 628% ) increase in incident rate of allcause mortality ( table  2 ) . edentulousness was associated with a 32% ( 1750% ) increased rate of allcause mortality compared with periodontally healthy dentate individuals . diabetes ( hr 1.41 ; 1.271.57 ) , hypertension ( hr 1.06 ; 0.931.20 ) and current smoking ( hr 2.12 ; 1.822.48 ) were associated with an increased rate of allcause mortality although this increase was not significant for hypertension ( table  2 ) . the 10year allcause mortality for individuals with ckd ( but without periodontitis or other traditional risk factors ) was 32% ( 2935% ) . addition of periodontitis to the risk profile increased 10year mortality to 41% ( 3647% ) . this increase in mortality was comparable with that seen in individuals with ckd who had diabetes instead of periodontitis ( 43% ; 3849% ) . a similar cumulative effect on mortality is seen with periodontitis and other traditional risk factors ( table  3 ) . these estimates are based on the demographic features of individuals with ckd within nhanes iii ( e.g. a mean age of 73  years ) . estimated survival curves for individuals with ckd and different risk factor profiles is given in fig .  1 . tenyear allcause mortality ( percentages ) of individuals with ckd by risk factors ( along with the addition of periodontitis to the risk factor ) fully adjusted model adjusted for age , sex , ethnicity , ckd status , periodontal status , diabetic status , hypertensive status , smoking status , pulse pressure , history of cvd ( heart attack or stroke or heart failure ) , alcohol consumption , acr , hypercholesterolaemia and lowhdl , bmi , physical activity and measures of socioeconomic status ( household income , marital status and educational attainment ) . for allcause mortality . cox proportional hazard regression graphs ( adjusting for age , sex , ethnicity , pulse pressure , history of cvd , alcohol consumption , acr , hypercholesterolaemia and lowhdl , bmi , physical activity , household income , marital status and educational attainment ) of survival in patients with ckd stratified using periodontitis and other traditional risk factors ( diabetes , hypertension and smoking ) . after adjusting for covariates , individuals with ckd had a 60% ( 3295% ) increased rate of cvd mortality compared to those without ckd ( table  2 ) , independent of confounders specified . individuals with periodontitis had a 38% ( 1665% ) increased rate of cvd mortality compared to individuals who were periodontally healthy . the association between periodontitis and cvd mortality was similar between individuals with or without ckd ( pvalue for interaction  =  0.27 ) . the associations between ckd and cvd mortality did not vary by age , sex or diabetes status ( pvalues for interaction 0.39 , 0.82 and 0.34 respectively ) . the association between periodontitis and cvd mortality did not vary by gender or diabetes status ( pvalues for interaction 0.77 and 0.17 respectively ) . there was a trend in patients with ckd and periodontitis to have an increased hr of cvd mortality if they were under the age of 65 compared with 65 and over but this was not significant . edentulous individuals under the age of 65 having a significantly increased rate of cvd mortality , hr 2.03 ( 1.313.13 ) , compared to edentulous individuals 65  years and older who had comparable rates of cvd mortality compared to periodontally healthy individuals , hr 0.89 ( 0.711.10 ) ( tables s4 , s5 and fig . mean ppd and percentage of sites that bleed on probing were associated with a statistically significant increase in the rate of cvd mortality ( table  2 ) . edentulous and periodontally healthy dentate individuals had comparable rates of cvd mortality ( table  2 ) . diabetes ( hr 1.45 ; 1.241.70 ) , hypertension ( hr 1.32 ; 1.061.63 ) and current smoking ( hr 2.10 ; 1.692.62 ) were associated with an increased rate of cvd mortality ( table  2 ) . the 10year cvd mortality for individuals with ckd ( and combinations of risk factors ) highlights the similarity in the magnitude of increase in cvd mortality associated with diabetes ( 24% ; 1930% ) compared with periodontitis ( 22% ; 1927% ) ( table  4 ) . estimated cvd survival for individuals with ckd and different risk factor profiles is given in fig . tenyear cvd mortality ( percentages ) of individuals with ckd by risk factors ( along with the addition of periodontitis to the risk factor ) fully adjusted model adjusted for age , sex , ethnicity , ckd status , periodontal status , diabetic status , hypertensive status , smoking status , pulse pressure , history of cvd ( heart attack or stroke or heart failure ) , alcohol consumption , acr , hypercholesterolaemia and lowhdl , bmi , physical activity and measures of socioeconomic status ( household income , marital status and educational attainment ) . for cardiovascular mortality . cox proportional hazard regression graphs ( adjusting for age , sex , ethnicity , pulse pressure , history of cvd , alcohol consumption , acr , hypercholesterolaemia and lowhdl , bmi , physical activity , household income , marital status and educational attainment ) of survival in patients with ckd stratified using periodontitis and other traditional risk factors ( diabetes , hypertension and smoking ) . in this large cohort , representative of the us population from which it was derived , ckd was associated with increased rates of allcause mortality and cvd mortality , independent of periodontitis , traditional risk factors and other confounders . periodontitis was associated with increased rates of allcause and cvd mortality comparable with , but independent of , that associated with diabetes ( tables  2 , 3 , 4 ; figs  1 and 2 ) . there was an increased rate of allcause mortality but not cvd mortality in edentulous individuals with ckd compared with periodontally healthy dentate individuals . the association between edentulousness and cvd mortality was significant in a subgroup of edentulous individuals under the age of 65 . given the high prevalence of chronic periodontitis in patients with ckd ( chambrone et  al . 2013 ) , our results suggest that periodontitis may be an important nontraditional risk factor for cvd and allcause mortality in these patients , and interestingly contributing to the increased risk to a similar extent as diabetes . the strengths of this study are its large populationbased sampling with robust sampling methodology which allow the results from this analysis to be generalized to the us population . the detailed clinical , demographic and anthropomorphic data collected allows for many of the known covariates to be accounted for in the cox proportional hazards regression model , generating more accurate point estimates . the length of followup for this study is its final strength and allows for the pragmatic assessment of long term , hard outcomes ( allcause and cvd mortality ) . the limitations of this study include the  lack of longitudinal examination of individuals . unfortunately , in nhanes , the longitudinal data is limited to the mortality status of patients derived from the national death index . data on variables were only gathered at inception and therefore changes in variables ( periodontal , diabetes , smoking status , etc ) are not ascertainable . analyses were carried out on the assumption that characteristics did not change between inception and time to death or censoring . some individuals with periodontitis are likely to have received treatment and/or lost teeth during followup , resulting in disease misclassification over time . furthermore , periodontal measurements from nhanes iii are known to underestimate the prevalence of periodontitis by 13.4% ( absolute ) or 60% ( relative ) ( eke et  al . the results of this study may therefore underestimate the association between periodontitis and mortality in ckd . also , as with any multivariable regression analysis , the issue of residual confounding from inaccurate measurement or categorization of variables or confounding from variables not included in the analysis can not be ruled out . previous studies investigating the link between mortality and periodontitis in patients with ckd have done so in patients on haemodialysis ( kshirsagar et  al . 2009 , chen et  al . apart from the small sample sizes ( 122253 patients ) and shorter followup period ( 18  months to 6  years ) , these studies differed significantly from the present analysis as individuals receiving rrt ( through chronic dialysis or a functioning kidney transplant ) were not included in the present analysis ( rrt was an exclusion criteria for periodontal examination in nhanes iii ) . hence , even though these studies demonstrate an association between periodontitis and mortality , thereby lending support to the current findings , the results can not be directly compared . a putative mechanism for a possible link between periodontitis and increased allcause and cvd mortality is via the increased systemic acutephase and oxidative stress burden . this increased burden is seen in individuals with periodontitis and ckd ( ioannidou et  al . 2011 ) and individuals with periodontitis who do not have ckd ( d'aiuto et  al . 2004 , chapple & genco 2013 ) . increased systemic inflammatory and oxidative stress burdens increase the incidence of cvd events in patients with ckd ( arici & walls 2001 , mathew et  al . this mechanism is supported by the association demonstrated here between increased risk of cvd mortality and measures of active periodontitis ( periodontitis case definition , mean ppd and bop ) , as opposed to measures of historical periodontitis ( edentulousness and mean cal ) , where there was a lack of association ( table  2 ) . however , at least part of the association between periodontitis and cvd may also be due to common risk factors such as smoking and diabetes ( dietrich et  al . the increase in allcause mortality in edentulous individuals compared to periodontally healthy dentate individuals , as reported here and also by other investigators in nonckd cohorts ( brown 2009 ) , may be due to several factors . patients are rendered edentulous for a variety of reasons including periodontitis , with approximately 50% of teeth being extracted due to periodontal disease ( phipps & stevens 1995 ) . as approximately half of all tooth extractions are for reasons other than periodontal disease , edentulousness may act as a surrogate marker of general health attitudes and/or behaviours , limited healthcare access or other socioeconomic measures ( joshipura & ritchie 2005 ) . this might also explain the association between edentulousness and cvd mortality in patients under the age of 65 who might have such characteristics and attitudes towards healthcare that render them edentulous before the age of 65 . the biological mechanisms underpinning the relationship between periodontitis and increased mortality in individuals with ckd form a promising area of research and may produce mechanistic targets leading to risk stratification and novel interventions . ongoing longitudinal studies ( stringer et  al . 2013 ) investigating large cohorts of patients with predialysis ckd may provide confirmation of this association and shed light upon explanatory mechanisms . successful treatment of periodontitis has been shown to improve surrogate markers of cvd risk , including serum markers of systemic inflammation ( crp , il6 ) ( d'aiuto et  al . 2004 ) , endothelial function as measured by flowmediated dilatation ( fmd ) and endothelialactivation markers such as soluble eselectin and von willebrand factor ( tonetti et  al . two randomized controlled trials of periodontal interventions in patients with ckd have been carried out but limited to cohorts of haemodialysis patients . these have produced conflicting results either not demonstrating changes in inflammatory markers following periodontal intervention ( wehmeyer et  al . 2013 ) or demonstrating that significant reductions in inflammatory markers can be achieved following periodontal therapy ( fang et  al . currently , patients with ckd are managed to strict targets concerning glycaemic control ( diabetes ) and control of hypertension and smoking cessation to improve outcomes . if a causal link is established between periodontitis and increased rates of adverse outcomes in ckd patients , then establishing and maintaining periodontal health may become an important part of the care pathway of patients with ckd . figure  s1 . cox ph regression graphs for allcause mortality in individuals with periodontitis / edentulism and ckd by age category click here for additional data file . 
 figure  s2 cox ph regression graphs for cvd mortality in individuals with periodontitis / edentulism and ckd by age category . table  s1 numbers of participants ( and percentage ) with missing data in variables included in statistical model . table  s2 exploring the interactions between ckd ( stage 35 ) , periodontal variables and age , gender and diabetes status for allcause mortality . table  s3 hazard ratios ( 95% ci ) and 10year survival ( 95% ci ) of allcause mortality by subgroups of age ( < 65  years of age and 65  years of age ) . table  s4 exploring the interactions between ckd ( stage 35 ) , periodontal variables and age , gender and diabetes status for cvd mortality . table  s5 hazard ratios ( 95% ci ) and 10year survival ( 95% ci ) of cvd mortality by subgroups of age ( < 65  years of age and 65  years of age ) .