Determinants of long-term trajectories in cardiovascular risk clusters
Lead Research Organisation:
University College London
Department Name: Epidemiology and Public Health
Abstract
Risk factors for heart disease, such as high blood pressure, obesity, elevated cholesterol levels and pre-diabetes, have a tendency to occur simultaneously in the same individuals. This is called the metabolic syndrome, and having it increases a person?s risk of diabetes, or a heart attack. In addition to these known risk factors, it is thought that other mechanisms, such as inflammation, and the state of fat tissue may also contribute to the risk of heart disease. However it is not known if disturbances in these systems truly cause heart disease, or if they merely mirror the disease process or disturbances in the known risk factors. If these disturbances are truly a cause of heart disease, treating them may help reduce a person?s risk. If they simply follow disturbances in the known risk factors, treatments and preventive measures should remain focused on the risk factors we know. A powerful way to study this question is to examine known and new risk factors at several points in time in the same individuals to determine if changes in one set of risk factors occur before, at the same time or after changes in other sets of risk factors.
We aim to study these questions using information gathered in the Whitehall II study, complemented with new measurements. The Whitehall II study includes over 7000 participants (70% men) who have undergone 3 rounds of screening for known heart disease risk factors at 5 year intervals, and have answered questionnaires about exercise, diet, work, stress, and social status at each round. We have followed participants up to 2004, to see who developed diabetes and heart disease. Participants have also given blood samples at each round, which have been kept in frozen storage. We aim to use these frozen samples to study novel markers of inflammation and the state of fat tissue. The combination of these new measures with the extensive existing data, will allow us to study the change in the components of the metabolic syndrome over time, and to determine if these changes are related as cause or consequence to changes in inflammation, blood clotting and the state of fat tissue. Our extensive data on diet, exercise and socioeconomic status will allow us to study if the way the known and new risk factors work together is different in different segments of society and in people with different health behaviours.
We aim to study these questions using information gathered in the Whitehall II study, complemented with new measurements. The Whitehall II study includes over 7000 participants (70% men) who have undergone 3 rounds of screening for known heart disease risk factors at 5 year intervals, and have answered questionnaires about exercise, diet, work, stress, and social status at each round. We have followed participants up to 2004, to see who developed diabetes and heart disease. Participants have also given blood samples at each round, which have been kept in frozen storage. We aim to use these frozen samples to study novel markers of inflammation and the state of fat tissue. The combination of these new measures with the extensive existing data, will allow us to study the change in the components of the metabolic syndrome over time, and to determine if these changes are related as cause or consequence to changes in inflammation, blood clotting and the state of fat tissue. Our extensive data on diet, exercise and socioeconomic status will allow us to study if the way the known and new risk factors work together is different in different segments of society and in people with different health behaviours.
Technical Summary
The metabolic syndrome, a cluster of central obesity, hypertension, dyslipidaemia and glucose metabolism disturbance, is currently seen as a key risk indicator for cardiovascular disease and diabetes. Using three sequential examinations of the Whitehall II cohort, we have recently shown that; first: impaired glucose tolerance is remarkably unstable over a 10-year period and second: that over 50% of individuals with the metabolic syndrome proceed to normal after 5 years of follow up. This calls into question whether the metabolic syndrome has the same aetiological and prognostic significance in all individuals. It is unclear what determines the speed and course of metabolic deterioration, whether different trajectories of change have different health implications and whether it is possible to predict the course of metabolic deterioration.
In recent years novel biomarkers of CVD risk have emerged, including markers of inflammation and lipid and fat tissue metabolism. Individual relations between diabetes, CVD, the metabolic syndrome and several novel biomarkers have been reported. However, it remains unclear whether these relations are truly causal, or if they can be explained by confounding or reverse causation. A powerful way of assessing causality is to study the sequence of change in serial measurements.
We propose to address these questions using the Whitehall II study, in which over 7000 participants (70% men) have undergone 3 rounds of cardiovascular screening at 5 year intervals. The extant data include all conventional CVD risk factors and a 75g oral glucose tolerance test at each round, complemented with extensive information on risk behaviours and socioeconomic status, as well as non-invasive measures of atherosclerosis at the latest phase and follow-up for validated incident CVD events. These data uniquely enable us to track the course of change in the components of the metabolic syndrome and to study the determinants of metabolic deterioration. We further aim to use available frozen serum from each screening round to measure additional biomarkers of inflammation and fat tissue metabolism. This will allow us to study how novel risk markers cluster amongst each other and with components of the metabolic syndrome; and to address the question of causality in the relation between novel biomarkers, incident diabetes and CVD. Moreover we will be able to study whether differences in clustering or rates of change are related to differences in diet, exercise, other health behaviours, and socio-economic status.
In recent years novel biomarkers of CVD risk have emerged, including markers of inflammation and lipid and fat tissue metabolism. Individual relations between diabetes, CVD, the metabolic syndrome and several novel biomarkers have been reported. However, it remains unclear whether these relations are truly causal, or if they can be explained by confounding or reverse causation. A powerful way of assessing causality is to study the sequence of change in serial measurements.
We propose to address these questions using the Whitehall II study, in which over 7000 participants (70% men) have undergone 3 rounds of cardiovascular screening at 5 year intervals. The extant data include all conventional CVD risk factors and a 75g oral glucose tolerance test at each round, complemented with extensive information on risk behaviours and socioeconomic status, as well as non-invasive measures of atherosclerosis at the latest phase and follow-up for validated incident CVD events. These data uniquely enable us to track the course of change in the components of the metabolic syndrome and to study the determinants of metabolic deterioration. We further aim to use available frozen serum from each screening round to measure additional biomarkers of inflammation and fat tissue metabolism. This will allow us to study how novel risk markers cluster amongst each other and with components of the metabolic syndrome; and to address the question of causality in the relation between novel biomarkers, incident diabetes and CVD. Moreover we will be able to study whether differences in clustering or rates of change are related to differences in diet, exercise, other health behaviours, and socio-economic status.
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| Daniel Witte (Principal Investigator) |