Life course determinants of cardiovascular ageing

Lead Research Organisation: MRC Unit for Lifelong Health and Ageing

Abstract

Around one in two men and one in three women suffer a cardiovascular event sometime during life, making cardiovascular disease (CVD) a major cause of mortality and morbidity. Heart failure is of increasing importance because of improvements in the prevention and treatment of acute clinical events such as heart attack. Although clinical disease becomes evidence at older ages, the presence of plaque in the arteries is already present by young adulthood and progresses through life. Hence there is increasing interest in the use of measures of changes taking place before disease as tools to predict future clinical events and target treatment.||The overall aim of this programme is to investigate how exposures over the life course are associated with cardiovascular structure and function and the development of disease. The MRC National Survey of Health and Development, a birth cohort study of men and women born in 1946 and followed up ever since, is collecting a comprehensive set of measures of the structure and function of the heart and arteries. Evaluations of this type will be critical to understanding whether risk factor modification from a much earlier age than is routine in current clinical practice could yield benefits for CVD prevention. |

Technical Summary

Approximately one in two men and one in three women suffer a cardiovascular event at sometime during life, making cardiovascular disease (CVD) a major cause of mortality and morbidity. Atrial fibrillation and heart failure are assuming increasing importance as clinical end-points in CVD, due to improvements in primary prevention and treatment of acute clinical events. Although clinical complications of atherosclerosis manifest in later life, atheroma is already present by young adulthood and progresses through life so there is increasing interest in the use of non-invasive measures of subclinical disease as tools to predict future clinical events and target therapies.||The overall aim of this programme is to evaluate the impact of exposures over the life course on cardiovascular structure and function and the development of disease. To do this we are collecting a comprehensive set of measures of arterial and cardiac structure and function as well as repeating measures of cardiovascular risk factors already measured at younger ages. Evaluations of this type will be critical to understanding whether risk factor modification from a much earlier age than is routine in current clinical practice could yield benefits for CVD prevention. ||The main objectives of this programme are to use the MRC National Survey of Health and Development:||To assess the influence of the life course exposure to established CVD risk factors (such as blood pressure and smoking) on arterial and cardiac structure and function, and on preclinical disease ||To investigate whether factors of less certain causal relevance, such as early growth and development and life circumstances, have effects on these outcomes, or modify the impact of the established risk factors on these outcomes.||To study the inter-relationships between the different CVD measurements and establish the range of normality in the UK population aged 60-64 years. Diastolic dysfunction, a condition accounting for an increasing proportion of patients with heart failure, is of particular interest.||To identify genetic factors that predict cardiovascular risk, function and preclinical disease in order to gain better insight into causal mechanisms. For example, to examine the effect on carotid atheroma of common genetic variants with established effects on LDL-cholesterol concentration, to test the hypothesis that carotid atheroma reflects arterial changes on the causal pathway leading to clinical disease. ||To evaluate the role of CVD in the decline of physical and cognitive capability

Publications

10 25 50
 
Description Set for Britain poster event at House of Commons
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Influenced training of practitioners or researchers
 
Description British Cardiovascular Society Annual conference travel award
Amount £2,000 (GBP)
Organisation British Cardiovascular Society 
Sector Private
Country United Kingdom
Start  
 
Description NPRI - Eating behaviours: tracking through the lifecourse and impact on chronic disease
Amount £310,222 (GBP)
Funding ID G0701939 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start  
 
Description UCLEB Consortium of population based studies
Amount £970,230 (GBP)
Organisation British Heart Foundation (BHF) 
Sector Charity/Non Profit
Country United Kingdom
Start  
 
Title metabochip database 
Description The BHF grant and collaborations with MRC Epidemiology have funded a metabochip data on NSHD 
Type Of Material Database/Collection of Data/Biological Samples 
Year Produced 2011 
Provided To Others? Yes  
Impact publications 
 
Title new specialist databses for cardiac and vascular function 
Description latest NSHD data collection which ended in 2011 has created new specialist databases on IMT, PWV, ECG, cardiac parameters etc 
Type Of Material Database/Collection of Data/Biological Samples 
Year Produced 2011 
Provided To Others? Yes  
Impact forthcoming publications with collaborators 
 
Description Collaboration with JD and AH UCL Cardio 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Contributions will include providing NSHD data, data analysis, research advice, publication writing, grant applications, editing manuscripts and knowledge exchange
Collaborator Contribution Contributions will include using NSHD data, data analysis, research advice, publication writing, grant applications, editing manuscripts and knowledge exchange
Impact PMID 25198238 24856161 25246483 Servier Award - European research proposal in the field of hypertension and related diseases with a focus on end-organ damage and other biomarkers.
Start Year 2009
 
Description External Programme co led by CVD Project Management Group 
Organisation Sahlgrenska University Hospital
Country Sweden 
Sector Hospitals 
PI Contribution Providing the data from the NSHD, data analysis and writing up results
Collaborator Contribution CVD PMG was established for the purpose of maximising the scientific potential of the NSHD data on cardiac and vascular structure and function
Impact 21804106, 21909115
Start Year 2008
 
Description External Programme co led by CVD Project Management Group 
Organisation St George's University of London
Country United Kingdom 
Sector Academic/University 
PI Contribution Providing the data from the NSHD, data analysis and writing up results
Collaborator Contribution CVD PMG was established for the purpose of maximising the scientific potential of the NSHD data on cardiac and vascular structure and function
Impact 21804106, 21909115
Start Year 2008
 
Description External Programme co led by CVD Project Management Group 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Providing the data from the NSHD, data analysis and writing up results
Collaborator Contribution CVD PMG was established for the purpose of maximising the scientific potential of the NSHD data on cardiac and vascular structure and function
Impact 21804106, 21909115
Start Year 2008
 
Description External Programme co led by CVD Project Management Group 
Organisation University of Glasgow
Country United Kingdom 
Sector Academic/University 
PI Contribution Providing the data from the NSHD, data analysis and writing up results
Collaborator Contribution CVD PMG was established for the purpose of maximising the scientific potential of the NSHD data on cardiac and vascular structure and function
Impact 21804106, 21909115
Start Year 2008
 
Description Genetics of obesity 
Organisation University of Cambridge
Department MRC Epidemiology Unit
Country United Kingdom 
Sector Multiple 
PI Contribution NSHD data sharing, analysis, scientific papers
Collaborator Contribution Nick Wareham's group has brought genetic experitise to collaboration
Impact 22456663 22654120 22150704 20962026 19880856 25198238
Start Year 2008
 
Description International Consortium for Blood Pressure Genome-wide Association 
Organisation Queen Mary University of London
Department Barts and The London School of Medicine and Dentistry
Country United Kingdom 
Sector Academic/University 
PI Contribution NSHD data sharing, data analysis and contributing to writing of research papers
Collaborator Contribution Coordinating the consortium, providing data and genetics expertise
Impact Numerous research papers 21378095 22100073 21909115
Start Year 2009
 
Description Novel risk markers for CVD disease 
Organisation St George's University of London
Department Division of Population Health Sciences and Education
Country United Kingdom 
Sector Academic/University 
PI Contribution NSHD data sharing - early life exposure data from the cohort database Provision of data on cardiac indices in support of the analysis Advise on analyses taking life course exposures into account. Contribute to the scientific development of the project throughout.
Collaborator Contribution Responsible for overall management of the project, planning of analyses and will supervise the study statistician in conjunction with the other investigators. Drafting of study reports in conjunction with co-investigators. Provision of data on cardiac indices in support of the analysis. Provision of data on vascular indices in support of the analysis. Provision of data on laboratory measurements in support of the analysis.
Impact Grant funding from MRC Grant funding now finished 2016 Papers being completed Elhakeem A. Leisure-time physical activity across adulthood and biomarkers of cardiovascular disease at age 60-64: a prospective cohort study. PMID:29180005 Elhakeem, A, Cooper, R, Whincup, P, Brage, S, Kuh, D, Hardy, R. Physical activity, sedentary time and cardiovascular disease biomarkers at age 60-64. JAHA. 2018 Aug 21;7(16):e007459. doi: 10.1161/JAHA.117.007459. Erratum in: J Am Heart Assoc. 2018 Oct 16;7(20):e004284. PMID: 30369324
Start Year 2011
 
Description Novel risk markers for CVD disease 
Organisation University College London
Department Department of Cardiorespiratory Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution NSHD data sharing - early life exposure data from the cohort database Provision of data on cardiac indices in support of the analysis Advise on analyses taking life course exposures into account. Contribute to the scientific development of the project throughout.
Collaborator Contribution Responsible for overall management of the project, planning of analyses and will supervise the study statistician in conjunction with the other investigators. Drafting of study reports in conjunction with co-investigators. Provision of data on cardiac indices in support of the analysis. Provision of data on vascular indices in support of the analysis. Provision of data on laboratory measurements in support of the analysis.
Impact Grant funding from MRC Grant funding now finished 2016 Papers being completed Elhakeem A. Leisure-time physical activity across adulthood and biomarkers of cardiovascular disease at age 60-64: a prospective cohort study. PMID:29180005 Elhakeem, A, Cooper, R, Whincup, P, Brage, S, Kuh, D, Hardy, R. Physical activity, sedentary time and cardiovascular disease biomarkers at age 60-64. JAHA. 2018 Aug 21;7(16):e007459. doi: 10.1161/JAHA.117.007459. Erratum in: J Am Heart Assoc. 2018 Oct 16;7(20):e004284. PMID: 30369324
Start Year 2011
 
Description Novel risk markers for CVD disease 
Organisation University of Glasgow
Department Institute of Cardiovascular and Medical Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution NSHD data sharing - early life exposure data from the cohort database Provision of data on cardiac indices in support of the analysis Advise on analyses taking life course exposures into account. Contribute to the scientific development of the project throughout.
Collaborator Contribution Responsible for overall management of the project, planning of analyses and will supervise the study statistician in conjunction with the other investigators. Drafting of study reports in conjunction with co-investigators. Provision of data on cardiac indices in support of the analysis. Provision of data on vascular indices in support of the analysis. Provision of data on laboratory measurements in support of the analysis.
Impact Grant funding from MRC Grant funding now finished 2016 Papers being completed Elhakeem A. Leisure-time physical activity across adulthood and biomarkers of cardiovascular disease at age 60-64: a prospective cohort study. PMID:29180005 Elhakeem, A, Cooper, R, Whincup, P, Brage, S, Kuh, D, Hardy, R. Physical activity, sedentary time and cardiovascular disease biomarkers at age 60-64. JAHA. 2018 Aug 21;7(16):e007459. doi: 10.1161/JAHA.117.007459. Erratum in: J Am Heart Assoc. 2018 Oct 16;7(20):e004284. PMID: 30369324
Start Year 2011
 
Description UCLEB cohort collaboration for genetic research 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution NSHD data sharing and epideomiological experitise
Collaborator Contribution Maximising research potential of NSHD Prof Aroon Hinorani brings in CVD and genetic skills and manages the collaboration with several CVD cohort studies at UCL and Edinburgh, including NSHD. Data sharing
Impact UCL Biomedical Research Centre High Impact Grant awarded BHF programme grant under review 23977022 White 26781229 Neusch 25979724 Talmund 25475436
Start Year 2008
 
Description UCLEB cohort collaboration for genetic research 
Organisation University of Bristol
Country United Kingdom 
Sector Academic/University 
PI Contribution NSHD data sharing and epideomiological experitise
Collaborator Contribution Maximising research potential of NSHD Prof Aroon Hinorani brings in CVD and genetic skills and manages the collaboration with several CVD cohort studies at UCL and Edinburgh, including NSHD. Data sharing
Impact UCL Biomedical Research Centre High Impact Grant awarded BHF programme grant under review 23977022 White 26781229 Neusch 25979724 Talmund 25475436
Start Year 2008
 
Description UCLEB cohort collaboration for genetic research 
Organisation University of Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution NSHD data sharing and epideomiological experitise
Collaborator Contribution Maximising research potential of NSHD Prof Aroon Hinorani brings in CVD and genetic skills and manages the collaboration with several CVD cohort studies at UCL and Edinburgh, including NSHD. Data sharing
Impact UCL Biomedical Research Centre High Impact Grant awarded BHF programme grant under review 23977022 White 26781229 Neusch 25979724 Talmund 25475436
Start Year 2008
 
Description CDF's work chosen for you tube video promotion during American College of Cardiology conference 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact CDF's work chosen for you tube video promotion during American College of Cardiology conference. Promoted research findings concerning life course approach to cardiology

Increasing awareness among cardiologists about a life course approach to health care
Year(s) Of Engagement Activity 2012