Determinants of, and outcomes associated with antihypertensive‐associated incident diabetes and metabolic syndrome in hypertensive patients in the ASCOT‐trial
Author(s)
Gupta, Ajay Kumar
Type
Thesis
Abstract
Controversy exists whether the adverse effects on glucose metabolism and the increased
incidence of new‐onset diabetes (NOD) associated with beta‐blockers and/or diuretics
translate into adverse cardiovascular (CV) events, and thereby seriously detract from the
beneficial effects of the these agents. Furthermore, little is known about the determinants
of NOD among hypertensive patients. Controversy also surrounds the clinical utility of the
metabolic syndrome (MetS) and its role in predicting NOD and CV outcomes. In this thesis I
present an evaluation of these issues using the database of the Anglo‐Scandinavian Cardiac
Outcomes Trial.
Increase in the baseline fasting plasma glucose (FPG), body mass index, serum triglyceride
and systolic blood pressure significantly increased the risk for NOD. In contrast,
randomisation to amlodipine ± perindopril treatment (in comparison with atenolol ±
thiazide), high HDL ‐cholesterol, alcohol use and age over 55 years were significant
protective factors. On further analysis, cumulative‐mean glucose (CMG) and FPG were
found to be independent and significant risk factors for CV outcomes and death. Allocation
to atenolol‐based treatment (vs. amlodipine‐based treatment) was associated with a
significantly greater increase in CMG levels, and a progressive worsening of glycaemic status
(normoglycaemia, impaired glycaemia and NOD) after 1 year of follow‐up. Worsening
glycaemic status was found to have a significant and linear relationship with increased risk
of CV outcomes and death.
The MetS, after adjustment for its constituent components, was found to be an
independent predictor for stroke and death, but not for coronary outcomes. Furthermore,
the MetS was associated with a 22% increased risk of NOD, after adjusting for its individual
components, and was found to be a significantly better predictor of NOD than impaired
fasting glucose.
In summary, these data suggest that among hypertensive patients, antihypertensive agents
are important determinants for the development of NOD, and the antihypertensive-associated
in‐trial glycaemic worsening is associated with increased risk of CV outcomes and
death. I have also shown that, in routine clinical practice, the MetS has an important role as
an easy‐to‐use predictor for the risk of NOD, CV outcomes and death; and that the increased
risk of CV outcomes and death associated with the MetS is independent of the influence of
its constituent components.
incidence of new‐onset diabetes (NOD) associated with beta‐blockers and/or diuretics
translate into adverse cardiovascular (CV) events, and thereby seriously detract from the
beneficial effects of the these agents. Furthermore, little is known about the determinants
of NOD among hypertensive patients. Controversy also surrounds the clinical utility of the
metabolic syndrome (MetS) and its role in predicting NOD and CV outcomes. In this thesis I
present an evaluation of these issues using the database of the Anglo‐Scandinavian Cardiac
Outcomes Trial.
Increase in the baseline fasting plasma glucose (FPG), body mass index, serum triglyceride
and systolic blood pressure significantly increased the risk for NOD. In contrast,
randomisation to amlodipine ± perindopril treatment (in comparison with atenolol ±
thiazide), high HDL ‐cholesterol, alcohol use and age over 55 years were significant
protective factors. On further analysis, cumulative‐mean glucose (CMG) and FPG were
found to be independent and significant risk factors for CV outcomes and death. Allocation
to atenolol‐based treatment (vs. amlodipine‐based treatment) was associated with a
significantly greater increase in CMG levels, and a progressive worsening of glycaemic status
(normoglycaemia, impaired glycaemia and NOD) after 1 year of follow‐up. Worsening
glycaemic status was found to have a significant and linear relationship with increased risk
of CV outcomes and death.
The MetS, after adjustment for its constituent components, was found to be an
independent predictor for stroke and death, but not for coronary outcomes. Furthermore,
the MetS was associated with a 22% increased risk of NOD, after adjusting for its individual
components, and was found to be a significantly better predictor of NOD than impaired
fasting glucose.
In summary, these data suggest that among hypertensive patients, antihypertensive agents
are important determinants for the development of NOD, and the antihypertensive-associated
in‐trial glycaemic worsening is associated with increased risk of CV outcomes and
death. I have also shown that, in routine clinical practice, the MetS has an important role as
an easy‐to‐use predictor for the risk of NOD, CV outcomes and death; and that the increased
risk of CV outcomes and death associated with the MetS is independent of the influence of
its constituent components.
Date Issued
2011-10
Date Awarded
2012-08
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Poulter, Neil
Sever, Peter
Publisher Department
National Heart and Lung Institute
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)