Life course epidemiology is concerned with understanding how risk factors occurring during development and degenerative periods combine to affect disease risk.(1) Central to this approach is an understanding that many physiological processes reach a peak level (their highest functional level) early in life, remain relatively stable through mid-life, and then decline during older age. For example, there is evidence that greatest lung volume is usually attained in late adolescence / early adulthood in humans, that it then remains constant into the 6th/7th decade of life in healthy non-smokers and then begins to decline.(2) Similarly, peak bone mass, though achieved somewhat earlier in females compared to males, is achieved by the end of the second decade in both genders, remains constant through middle-age, before declining, particularly post-menopause in women.(3) Peak vascular and metabolic health appears to be reached by late adolescence and begins to decline in healthy individuals during their 60s/70s.(4, 5) Disease risk, related to sub-optimal levels of physiological function, may result from attaining lower than average peak levels of function (most likely due to risk factors early in life during developmental periods), earlier decline from the peak level or more rapid decline in older age.(2) The importance of the developmental period in determining the level of the peak function has been emphasised in relation to bone health by describing the actual value of peak bone mass achieved by late 20s as the "bone bank for the remainder of life".(3)

This underlying theory suggests that ideal life course studies will have repeat measurements of key physiological functions across life in large cohorts of individuals and will be able to examine the relative importance of level of peak function, age at decline and speed of decline in relation to future health risk as well as key risk factors for these different aspects of functional trajectories. To our knowledge, no existing study has such repeat life course measurements from early age into late adulthood and it will be some decades before existing birth cohorts that do have repeat infant and childhood measurements reach older age. One potential alternative to examining life course trajectories in markers of physiological function in a single cohort study is to use multiple cohorts that cover different life course stages. The aim of this study is to examine the extent to which this might be possible.

We have chosen blood pressure as our measurement of an important marker of physiological function since it is an important risk factor for cardiovascular disease and is likely to have been measured in most cohort studies. Textbook descriptions of age related changes in blood pressure are based on series of cross-sectional studies of different age groups.(6) These show marked increases in systolic blood pressure from birth to age 1 (from on average 70mmHg to 95mmHg), followed by steady increases of 1-2mmHg per year to late 20s after which the rise is more marked to age 80 when it begins to level off, but never appears to decline with increasing age.(6) A very different pattern is observed for diastolic blood pressure, which appears to have a more gentle increase in early life, rising by just 2mmHg in the first year of life and then 0.5-1mmHg per year to age 40, where they remain relatively stable until the 6th decade and then show a very gradual decline.(6) On top of these average age-related changes are gender differences with little evidence of a gender difference until adolescence, at which time increases in both systolic and diastolic blood pressure become more gentle in females compared to males, so that mean blood pressure is greater in males than females by age 18.(6) On average systolic blood pressure is 10mmHg in males than females at age 18.6 However, in middle-age the increase in systolic blood pressure is greater in females than males so that by age 70 year systolic blood pressure is on average 10mmHg higher in females than males.(6) Whether these age-related differences in blood pressure from cross-sectional studies are found in prospective studies of the same individuals with repeat measurements is unclear.

The specific objectives of this study are:

1. To develop statistical methods to model the average population age related trajectory of blood pressure by combining information from cohorts of different ages with repeat measures of blood pressure.

2. To apply these models to MRC funded cohorts in order to investigate the sociodemographic differences in such trajectories.

3. To apply latent class analysis to individual cohort to identify groups of individuals with different trajectories and to investigate the risk factors for such groups.

Methods

Cohort selection

Cohorts are selected on the basis of (i) receiving core funds from the UK Medical Research Council (the first objective of our grant was to identify such cohorts and because funding is from MRC public health network the focus is primarily on MRC funded cohorts (though we hope to extend this if possible in the future); (ii) general population cohort studies; (iii) have at least three examinations on study participants where blood pressure was assessed.

To date 5 cohorts fulfiling these criteria have been identified of which ALSPAC is one

Statistical methods

Analyses will be undertaken within each individual cohort using Bayesian models and latent class analyses as appropriate.

Variables required from ALSPAC

Gender

Month & Year of birth

Whether singleton/twin/triplet

Mothers education

Fathers education

Head of household social class

Age at each clinic measurement 7, 8, 9, 10, 11, 13, 15

Systolic blood pressure at each clinic measurement 7, 8, 9, 10, 11, 13, 15

Diastolic blood pressure at each clinic measurement 7, 8, 9, 10, 11, 13, 15

History of blood pressure medication

Height and weight at age clinic measurement 7, 8, 9, 10, 11, 13, 15

Birth weight

Gestational age

References

(1) Kuh D, Ben-Shlomo Y, Lynch J, Hallqvist J, Power C. Life course epidemiology. J Epidemiol Community Health 2003 October;57(10):778-83.

(2) Strachan DP, Sheikh A. A life course approach to respiratory and allergic diseases. In: Kuh D, Ben-Shlomo Y, editors. A life course approach to chronic disease epidemiology. 2nd Edition. 2 ed. Oxford: Oxford University Press; 2004. p. 240-59.

(3) Mora S, Gilsanz V. Establishment of peak bone mass. Endocrinol Metab Clin North Am 2003 March;32(1):39-63.

(4) McGill HC, Jr., McMahan CA, Herderick EE, Malcom GT, Tracy RE, Strong JP. Origin of atherosclerosis in childhood and adolescence. Am J Clin Nutr 2000 November;72(5 Suppl):1370S-15S.

(5) Lawlor DA, Chaturvedi N. Treatment and prevention of obesity--are there critical periods for intervention? Int J Epidemiol 2006 January 5;35:3-9.

(6) Bazzano LA, He J, Whelton PK. Blood pressure in westernized and isolated populations. In: Lip GYH, Hall JE, editors. Comprehensive Hypertension.Philadelphia: Mosby, Elsevier; 2007. p. 21-30.