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COMPRESSION OF MORBIDITY: COMPRESSION OF MORBIDITY: NEW INSIGHTS IN THE ROLE OF NEW INSIGHTS IN THE ROLE OF
LIFESTYLE FACTORSLIFESTYLE FACTORS
JOHAN MACKENBACH & WILMA NUSSELDERJOHAN MACKENBACH & WILMA NUSSELDERDEPARTMENT OF PUBLIC HEALTHDEPARTMENT OF PUBLIC HEALTH
ERASMUS MCERASMUS MC
FRIES JF. ‘Aging, natural death, and the FRIES JF. ‘Aging, natural death, and the compression of morbidity’. NEJM 1981compression of morbidity’. NEJM 1981
Syllogism:Syllogism:
- the human life span is fixed (and average life - the human life span is fixed (and average life expectancy is rapidly approaching this limit)expectancy is rapidly approaching this limit)
- the age at first infirmity will increase- the age at first infirmity will increase
- therefore, the average duration of infirmity - therefore, the average duration of infirmity will decreasewill decrease
FRIES (2)FRIES (2)
Average life expectancy is rapidly approaching its Average life expectancy is rapidly approaching its biological limit:biological limit:
- increases in life expectancy reflect mortality declines - increases in life expectancy reflect mortality declines at younger ages: rectangularization of survival curvesat younger ages: rectangularization of survival curves
- further rectangularization is likely to occur, around - further rectangularization is likely to occur, around mean age at death of 85 yearsmean age at death of 85 years
FRIES (3)FRIES (3)
Age at first infirmity will increase:Age at first infirmity will increase:
- frequency of some chronic illnesses is - frequency of some chronic illnesses is already declining (e.g. cardiovascular)already declining (e.g. cardiovascular)
- further reduction is possible and likely to- further reduction is possible and likely to
occur as a result of lifestyle improvementoccur as a result of lifestyle improvement
Life expectancy at birth plateaued in the 1970s, after rapid increases since 1850
OMRAN AR. The epidemiologic OMRAN AR. The epidemiologic transition. Milbank Mem F Q 1971transition. Milbank Mem F Q 1971
Pandemics of infection are gradually Pandemics of infection are gradually displaced by degenerative and man-made displaced by degenerative and man-made diseases, in three stages:diseases, in three stages:
- age of pestilence and famine- age of pestilence and famine
- age of receding pandemics- age of receding pandemics
- age of degenerative and man-made - age of degenerative and man-made diseasesdiseases
Historical decline of mortality from infectious disease
… and rise of mortality from ischemic heart disease and other chronic diseases
…partly due to the rise of cigarette smoking and other lifestyle risk factors
UNANSWERED QUESTIONSUNANSWERED QUESTIONS
Was the epidemiologic transition accompanied Was the epidemiologic transition accompanied historically by an expansion of morbidity (cf. historically by an expansion of morbidity (cf. Myers’ ‘disability transitions’)?Myers’ ‘disability transitions’)?
If so, did higher exposure to modern lifestyle If so, did higher exposure to modern lifestyle factors historically contribute to an expansion factors historically contribute to an expansion of morbidity?of morbidity?
Will reduced exposure to modern lifestyle Will reduced exposure to modern lifestyle factors contribute to a compression of factors contribute to a compression of morbidity in the future?morbidity in the future?
OUTLINE OF PRESENTATIONOUTLINE OF PRESENTATION
Conceptual and empirical progress since Fries’ Conceptual and empirical progress since Fries’ 1981 paper1981 paper
Results Dutch research programme on Results Dutch research programme on compression of morbiditycompression of morbidity
Conclusions, and implications for research Conclusions, and implications for research and public health policyand public health policy
CONCEPTUAL AND CONCEPTUAL AND EMPIRICAL PROGRESSEMPIRICAL PROGRESS The ‘remarkable plasticity of human longevity’: The ‘remarkable plasticity of human longevity’:
rapid declines of mortality among the elderly rapid declines of mortality among the elderly
Distinction between ‘morbidity’, ‘functional Distinction between ‘morbidity’, ‘functional ability’, ‘disability’, ‘health care use’, …ability’, ‘disability’, ‘health care use’, …
New methods for quantification of New methods for quantification of compression: Sullivan, multistate, ….compression: Sullivan, multistate, ….
Morbidity and mortality do not change Morbidity and mortality do not change independently independently
DUTCH RESEARCH PROGRAMME DUTCH RESEARCH PROGRAMME COMPRESSION OF MORBIDITY COMPRESSION OF MORBIDITY
Collaboration between Erasmus MC and Collaboration between Erasmus MC and Groningen UniversityGroningen University
Funded by Netherlands Organization for Funded by Netherlands Organization for Scientific ResearchScientific Research
3 PhD theses (Mamun, Janssen, Franco 3 PhD theses (Mamun, Janssen, Franco Duran), 30 papers in international scientific Duran), 30 papers in international scientific journalsjournals
COMPREHENSIVE ANALYSISCOMPREHENSIVE ANALYSISDATA AND METHODS (1)DATA AND METHODS (1)
Framingham Heart Study, individuals aged 50 Framingham Heart Study, individuals aged 50 and olderand older
3 non-overlapping 12 year follow-up periods 3 non-overlapping 12 year follow-up periods starting 1956-58, 1969-73, and 1985-89starting 1956-58, 1969-73, and 1985-89
Self-reported smoking, time spent on physical Self-reported smoking, time spent on physical activity; measured weight and blood pressureactivity; measured weight and blood pressure
Physician evaluated cardiovascular disease; Physician evaluated cardiovascular disease; death death
9304 observation intervals used in analysis9304 observation intervals used in analysis
COMPREHENSIVE ANALYSISCOMPREHENSIVE ANALYSISDATA AND METHODS (2)DATA AND METHODS (2)
Pooling of Repeated Observations methodPooling of Repeated Observations method Poisson regression, Hazard Ratios for 3 Poisson regression, Hazard Ratios for 3
transitions (no CVD to CVD, no CVD to Death, transitions (no CVD to CVD, no CVD to Death, CVD to Death)CVD to Death)
Confounders selected according to variable of Confounders selected according to variable of interest (age, sex, education, marital status, interest (age, sex, education, marital status, comorbidity), start of follow-up period, other comorbidity), start of follow-up period, other cardiovascular risk factors)cardiovascular risk factors)
STATA version 8.2STATA version 8.2
COMPREHENSIVE ANALYSISCOMPREHENSIVE ANALYSISDATA AND METHODS (3)DATA AND METHODS (3)
Period multistate life tables, starting at age 50 Period multistate life tables, starting at age 50 and closed at age 100, by genderand closed at age 100, by gender
3 states (free from CVD, history of CVD, death), 3 states (free from CVD, history of CVD, death), no backflowsno backflows
By level of exposure to risk factor, transition By level of exposure to risk factor, transition rates as estimated in Poisson regressionrates as estimated in Poisson regression
Confidence intervals estimated by parametric Confidence intervals estimated by parametric bootstrapping with @RISKbootstrapping with @RISK
COMPREHENSIVE ANALYSISCOMPREHENSIVE ANALYSISSUMMARY OF RESULTSSUMMARY OF RESULTS
Smoking and lack of physical activity increase all 3 Smoking and lack of physical activity increase all 3 transition rates transition rates -- therefore are neutral w.r.t. compression -- therefore are neutral w.r.t. compression
Hypertension and obesity primarily increase Hypertension and obesity primarily increase incidence rates incidence rates -- therefore lead to expansion of morbidity-- therefore lead to expansion of morbidity
In the right mix, prevention of these risk factors In the right mix, prevention of these risk factors may produce compression of (cardiovascular) may produce compression of (cardiovascular) morbiditymorbidity
SmokingSmokingRate Ratios for 3 transitionsRate Ratios for 3 transitions
Corrected for age, sex, hypertension, BMI, physical activity, co(morbidity), start follow-up. Corrected for age, sex, hypertension, BMI, physical activity, co(morbidity), start follow-up.
Source: Our analyses of the Framingham Heart StudySource: Our analyses of the Framingham Heart Study
0.00
1.00
2.00
3.00
No CVD toCVD
No CVD toDeath
CVD to Death
Never Former Current
Corrected for age, sex, hypertension, BMI, physical activity, co(morbidity), start follow-up. Source: Our analyses of the Framingham Heart Study.
SmokingSmokingHealth expectancies from age 50Health expectancies from age 50
Effect of Smoking between Age 50 to 80
22.9 23.518.9
28.4 27.224.9
7.1 6.1
7.0
6.36.2
5.7
0.0
5.0
10.0
15.0
20.0
25.0
30.0
35.0
40.0
Never Former Current Never Former Current
Men Women
Smoking status (by sex)
Nu
mb
er
of y
ea
rs
Free of CVD With CVD
30.029.7.1
25.8
34.8 33.4
30.6
Source: Our analyses of the Framingham Heart Study
HypertensionHypertensionRate Ratios for 3 transitionsRate Ratios for 3 transitions
Corrected for age, sex, hypertension, BMI, physical activity, co(morbidity), start follow-up. Corrected for age, sex, hypertension, BMI, physical activity, co(morbidity), start follow-up.
Source: Our analyses of the Framingham Heart StudySource: Our analyses of the Framingham Heart Study
0
1
2
3
No CVD to CVD No CVD toDeath
CVD to Death
Normal Pre-hypertension Hypertension
Corrected for age, sex, smoking, BMI, physical activity, co(morbidity), start follow-up . Source: Our analyses of the Framingham Heart Study
HypertensionHypertensionHealth expectancies from age 50Health expectancies from age 50
Figure 1. Effect of Hypertension at age 50 and over
26.822.7
19.2
32.529.2
26.0
3.86.8
7.5
3.36.1
7.0
0.0
5.0
10.0
15.0
20.0
25.0
30.0
35.0
40.0
Normal Pre-hypertension Hypertension Normal Pre-hypertension Hypertension
Men Women
Hypertension status (by sex)
Num
ber
of y
ear
s
Free of CVD With CVD
30.5 29.526.7
35.8 35.333.0
Source: Our analyses of the Framingham Heart Study
Physical activityPhysical activityRate Ratios for 3 transitionsRate Ratios for 3 transitions
Corrected for age, sex, hypertension, BMI, physical activity, co(morbidity), start follow-up.Corrected for age, sex, hypertension, BMI, physical activity, co(morbidity), start follow-up.
Source: Our analyses of the Framingham Heart StudySource: Our analyses of the Framingham Heart Study
0
1
2
3
No CVD to CVD No CVD toDeath
CVD to Death
High Moderate Low
Corrected for age, sex, smoking, co(morbidity), start follow-up. Source: Our analyses of the Framingham Heart Study.
Physical activityPhysical activityHealth expectancies at age 50Health expectancies at age 50
LEsLEs RRsRRs
Effect of Physical Activity between Age 50 to 80
23.0 21.0 19.8
29.7 27.9 26.5
7.47.2
7.1
6.66.6
6.5
0.0
5.0
10.0
15.0
20.0
25.0
30.0
35.0
40.0
High Moderate Low High Moderate Low
Men Women
Level of Physical Activity (by sex)
Num
ber
of y
ears
Free of CVD With CVD
30.428.2
26.9
36.434.4
32.9
Source: Our analyses of the Framingham Heart Study
OverweightOverweightRate Ratios for 3 transitionsRate Ratios for 3 transitions
Corrected for Corrected for age, sex, smoking, co(morbidity), start follow-up.age, sex, smoking, co(morbidity), start follow-up. Source: Our analyses Source: Our analyses
of the Framingham Heart Studyof the Framingham Heart Study
0
1
2
3
No CVD to CVD No CVD toDeath
CVD to Death
Normal Overweight Obesity
OverweightOverweightHealth expectancies from age 50Health expectancies from age 50
Figure 1. Effect of overweight between Age 50 to 80
22.2 20.8 18.9
28.2 27.1 25.1
5.9 7.77.8
5.6 7.47.6
0.0
5.0
10.0
15.0
20.0
25.0
30.0
35.0
40.0
Normal Overweight Obese Normal Overweight Obese
Men Women
BMI status (by sex)
Num
ber
of y
ear
s
Free of CVD With CVD
30.5.0
28.526.7
33.8 34.5 32.7
Source: Our analyses of the Framingham Heart Study
COMPREHENSIVE ANALYSISCOMPREHENSIVE ANALYSISSUMMARY OF RESULTSSUMMARY OF RESULTS
Smoking and lack of physical activity increase all 3 Smoking and lack of physical activity increase all 3 transition rates transition rates -- therefore are neutral w.r.t. compression -- therefore are neutral w.r.t. compression
Hypertension and obesity primarily increase Hypertension and obesity primarily increase incidence ratesincidence rates-- therefore lead to expansion of morbidity-- therefore lead to expansion of morbidity
In the right mix, prevention of these risk factors In the right mix, prevention of these risk factors may produce compression of (cardiovascular) may produce compression of (cardiovascular) morbiditymorbidity
COMPREHENSIVE ANALYSISCOMPREHENSIVE ANALYSISLIMITATIONSLIMITATIONS
Uncertainty about internal validity of empirical Uncertainty about internal validity of empirical relationships, e.g. observational study, relationships, e.g. observational study, sampling error, confounding, …sampling error, confounding, …
Uncertainty about external validity of empirical Uncertainty about external validity of empirical relationships, e.g. only one data-set, only from relationships, e.g. only one data-set, only from age 50, only cardiovascular morbidity, …age 50, only cardiovascular morbidity, …
Uncertainty of modelling exercise, e.g. no Uncertainty of modelling exercise, e.g. no backflows and memory, not dynamic, …backflows and memory, not dynamic, …
CONCLUSIONS (1)CONCLUSIONS (1)
It is theoretically possible, but by no means It is theoretically possible, but by no means inevitable, to achieve compression of inevitable, to achieve compression of (cardiovascular) morbidity by lifestyle changes(cardiovascular) morbidity by lifestyle changes
It is likely that lifestyle changes have It is likely that lifestyle changes have contributed to expansion of (cardiovascular) contributed to expansion of (cardiovascular) morbidity during the epidemiologic transition morbidity during the epidemiologic transition
CONCLUSIONS (2)CONCLUSIONS (2)
Fries’ paper was imprecise in many respects, Fries’ paper was imprecise in many respects, but probably correct on possibility of but probably correct on possibility of compression by lifestyle change compression by lifestyle change
Firmer conclusions require strengthening of Firmer conclusions require strengthening of empirical foundations: pooling observational empirical foundations: pooling observational studies, and doing experimental studiesstudies, and doing experimental studies
FURTHERFURTHERREADINGREADING Powerpoint presentation Powerpoint presentation
will be posted on my will be posted on my personal webpage, personal webpage, where references to where references to published papers can be published papers can be found too:found too:
http://mgzlx4.erasmusmc.nl/http://mgzlx4.erasmusmc.nl/pwp?jpmackenbachpwp?jpmackenbach