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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 decline?  

Research programme: Functional Trajectories and Cardiovascular ageing 

Programme leader: Professor Rebecca Hardy

MRC Studentship: Ahmed Elhakeen

Other LHA scientists: Professor Diana KuhProfessor Marcus Richards, Dr Mai Stafford

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 2014-20 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).

Main objectives

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 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 themes:

  • the predictors of life course body size trajectories, including predictors of healthy trajectories, and their impact on CV ageing and CVD;
  • 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 targeted treatment.

Key Publications

Hardy R, Ghosh, AK, Deanfield, JE, Kuh, D, Hughes, AD. Birth weight, childhood growth and left ventricular structure in a British birth cohort. International Journal of Epidemiology. 1016 July 14. [Epub ahead of print]
This paper finds that childhood overweight is associated with poorer cardiac structure at 60-64 years, over and above what would be expected with normal somatic growth. It illustrates the benefit of the repeated measures of height and weight across the life and is unique in linking these with measures of cardiac structure at older ages.

Ghosh AK, Hardy RJ, Francis DP, Chaturvedi N, Pellerin D, Deanfield J, Kuh D, Mayet J, Hughes AD; on behalf of the MRC NSHD Scientific and Data Collection Team. Midlife blood pressure change and left ventricular mass and remodelling in older age in the 1946 British birth cohort study. European Heart Journal 2014 Dec 7;35(46):3287-95. doi: 10.1093/eurheartj/ehu389.

Ghosh AK, Hughes, AD, Francis D, Chaturvedi N, Pellerin D, Deanfield J, Kuh D, Mayet J, Hardy R; on behalf of the MRC NSHD Scientific and Data Collection Team. Midlife blood pressure and midlife rise in blood pressure predict future diastolic dysfunction independently of current BP: The Medical Research Council National Survey of Health and Development (MRC NSHD). Heart. 2016 Apr 7. pii: heartjnl-2015-308836. doi: 10.1136/heartjnl-2015-308836. [Epub ahead of print]
Together these two papers highlight the impact of a rapid midlife rise in blood pressure  on the cardiac structure and function. They suggest that early identification of individuals with rapid rises in blood pressure may be important for prevention of impaired cardiac function in later life. Since current hypertension guidelines on initiation of treatment tend not to take account of change in BP, this may miss an opportunity to prevent cardiac damage in later life.

Hardy, R, Lawlor, DA, Kuh, D. A life course approach to cardiovascular disease. Future cardiology 2015. Jan;11(1):101-13. doi: 10.2217/fca.14.67.
This paper illustrates how a life course approach has been applied to cardiovascular disease, highlighting the evidence in support of the early origins of disease risk. We suggest that understanding underlying ‘normal’ or ‘healthy’ trajectories and the characteristics that drive deviations from such trajectories offer the potential for early prevention and for identifying means of preventing future disease.

Johnson, W, Li, L, Kuh, D, Hardy, R. How has the age-related process of overweight or obesity development changed over time? Co-ordinated analyses in five United Kingdom birth cohort studies. PLoS Medicine. 2015 May 19;12(5):e1001828. doi: 10.1371/journal.pmed.1001828.
This paper tracks the development of the obesity epidemic in the UK using 5 cohorts from the UK born at different times between 1946 and 2001. Our findings indicate increasing accumulation of lifetime exposure to overweight in increasingly younger generations and demonstrate the dramatic impact of a change to a more obesogenic environment, one that encourages consumption of unhealthy, high calorie diet and discourages activity, around the 1980s. The paper was cited in the Government’s Childhood Obesity Strategy.

Charakida, M, Khan, T, Johnson, W, Woodside, J, Finer, N, Kuh, D, Hardy, R, Deanfield, JE. Lifelong patterns of BMI and cardiovascular phenotype at 60-64 years: The 1946 British birth cohort. Lancet Diabetes & Endocrinology. 2014 Aug;2(8): 648-54. doi: 10.1016/S2213-8587(14)70103-2. Epub 2014 May 20.
This paper shows that increasing length of time spent overweight is associated with greater carotid intima-media thickness (cIMT), a marker of atherosclerosis measured in clinics at age 60-64 years. This has important implications for future generations in the context of the current obesity epidemic where subsequent generations are spending an increasing amount of their lives overweight.

Full list of publications from 2007-2012

For more recent publications please look on our findings page which can be found by clicking here.