Functional Trajectories and Cardiovascular Ageing
Which factors from across the life course promote
good adult cardiovascular function and prevent disease onset, and
which increase vulnerability to accelerated
Research programme: Functional
Trajectories and Cardiovascular ageing
Programme leader: Professor Rebecca Hardy
MRC Studentship: Ahmed Elhakeen
Other LHA scientists: Dr Will Johnson, Professor Diana Kuh, Professor Marcus Richards, Dr Mai Stafford (Programme Leader
Understanding the pathways to cardiovascular (CV) ageing is
important: although deaths from heart and circulatory disease are
falling, cardiovascular disease (CVD) remains the main cause of
death in the UK. Ageing of the CV system, through its impact on
physical and mental functioning in older people, also impairs
quality of life and the ability of individuals to carry out the
tasks of everyday life. Obesity and blood pressure are two of the
major modifiable risk factors for CVD. While the obesity epidemic
has prompted concerns over the health effects of early onset
obesity, there is also a growing recognition that blood pressure
history should be taken into account when considering CVD risk. The
purpose of this programme is to provide evidence on timing and type
of intervention which may prevent or delay the onset of disease,
extend the healthy lifespan and improve wellbeing and quality of
life in older age. This programme addresses the MRC strategic
research priority for 2009-14 to improve the chances of living a
long and healthy life.
This programme investigates biological and social factors
from across the life course that influence CV function in later
life using data from the MRC National Survey of Health and
Development, and other cohort studies. It builds on previous work
which has shown how birth weight, childhood and adolescent growth,
age at puberty and adult changes in body size are related to CV
risk factors, such as blood pressure and cholesterol. We have also
shown how life course influences, from genetics to lifetime
socioeconomic position, influence body size and blood pressure
trajectories and have conducted inter-cohort comparisons of blood
pressure through the MRC cross-unit collaboration: Function
Across the Life Course (FALCon). Cross cohort
comparisons of biological structure and function is currently being
continued through the ESRC/MRC funded project CLOSER (Cohort and
Longitudinal Studies Enhancement Resource).
This research programme focuses on questions which make the best
use of unique life course data to address the causes and
consequences of CV ageing and disease. The new set of measures of
arterial and cardiac structure and function, collected at 60-64
years, provide detailed information on the presence of pre-clinical
changes in the CV system. We carry out research across four related
- the predictors of life course body size trajectories, including
predictors of healthy trajectories, and their impact on CV ageing
- the predictors of adult BP and life course resting heart rate
(RHR) trajectories, including predictors of healthy trajectories,
and their impact on CV ageing;
- the biological pathways and mechanisms underlying CV ageing and
relationships with ageing of other body systems and, in the longer
term, the predictive power of the vascular and cardiac phenotypes
and life course CV risk factors on CHD and heart failure;
- the social and behavioural causes and, in the longer term,
consequences of CV ageing.
This programme has the potential to have a major impact in
regard to refinement of clinical guidelines for the management of
CVD risk by providing evidence on early identification and better
Wills AK, Lawlor DA, Matthews F, Aihie Sayer A, Bakra E,
Ben-Shlomo Y, Benzeval M, Brunner E, Cooper R, Kivimaki M, Kuh D,
Muniz-Terrera G, Hardy R. Life course trajectories of systolic blood
pressure using longitudinal data from UK cohorts.
PLoS Medicine 2011; 8(6):
This paper describes life course trajectories
in SBP using the novel approach of modelling multiple longitudinal
cohorts from different periods of the life course. It was published
in a high ranking general medical journal, was one of the “most
viewed” articles in the week it was published, and was reported on
in the BMJ. It provides evidence on which to base future research
on the importance of the midlife rise in BP.
Wills AK, Hardy RJ, Black S, Kuh D. Trajectories of overweight and body mass
index in adulthood and blood pressure at age 53: the 1946 British
Birth Cohort study. Journal of
Hypertension 2010; 28: 679-686.
As well as
showing the importance of BMI across adulthood and high BP, this
paper illustrated the extent of tracking in BMI across adulthood.
This finding was covered widely in the media. The paper also
outlined, for the first time, the different approaches to the
modelling of BMI across adulthood; approaches which have been
applied in subsequent NSHD papers.
Hardy R, Wills AK, Wong A, Elks CE, Wareham NJ, Loos RJF,
Kuh D, Ong KK. Life course
variations in the associations between FTO and MC4R gene variants
and body size. Human Molecular Genetics
2010; 19: 545-52.
This was one of the first
studies to investigate the longitudinal changes in the association
between gene variants identified as associated with adult BMI. We
showed associations varied with age. We have published two
subsequent papers using a similar approach.
Hardy R, Lawlor DA, Black S, Mishra GD, Kuh D.
Age at parenthood and coronary heart
disease risk factors at age 53 years in men and women.
Journal of Epidemiology and Community Health 2009; 63:
This is one of the few papers to
investigate the impact of age at parenthood on CV risk factors in
men as well as women as a way of distinguishing social and
lifestyle effects of childrearing and the biological effects of
Li L, Hardy R, Kuh D, Lo Conte R, Power C.
Child-to-adult BMI and height
trajectories: a comparison of two British birth
cohorts. American Journal of Epidemiology
2008; 168: 1008-1015.
This paper illustrated
that the 1958 cohort had a faster rate of BMI gain in early
adulthood than the 1946 cohort and had on average a greater BMI by
mid-life. It raises important questions about future trends for
mortality and morbidity, particularly in cohorts who experienced
the obesity epidemic in childhood.
For a full list of publications from 2007-2012 please click
For more recent publications please look on our findings page which
can be found by clicking here.