compression of morbidity: new insights in the role of lifestyle factors johan mackenbach & wilma...

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


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


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.


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


30.5 29.526.7

35.8 35.333.0


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.


0

1

2

3


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


30.428.2

26.9

36.434.4

32.9


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


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


30.5.0

28.526.7

33.8 34.5 32.7


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

compression of morbidity: new insights in the role of lifestyle factors johan mackenbach & wilma...

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