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Intermediate endpoints for atherosclerosis in hypertension
1Istituto di Clinica Medica, University of Milan, Ospedale Maggiore, Italy.
Insights
Antihypertensive therapy trials need to measure atherosclerosis progression using carotid intima-media thickness (IMT). This non-invasive ultrasound method helps assess plaque growth in hypertensive patients, offering valuable clinical insights.
Area of Science:
- Cardiovascular Medicine
- Hypertension Research
- Diagnostic Imaging
Background:
- Event-based trials demonstrate antihypertensive therapy benefits for cardiovascular morbidity and mortality.
- However, these trials do not assess the impact of antihypertensive therapy on atherosclerosis development.
- Trials utilizing plaque growth as endpoints are necessary to address this gap.
Purpose of the Study:
- To evaluate the utility of carotid intima-media thickness (IMT) as an endpoint in trials assessing antihypertensive therapy.
- To explore the role of non-invasive ultrasound in monitoring atherosclerosis progression in hypertensive individuals.
Main Methods:
- Quantitative coronary arteriography is unsuitable for uncomplicated hypertensive patients.
- B-mode quantitative ultrasound assessment of carotid artery intima-media thickness (IMT) is a non-invasive and reproducible method.
- Current limitations include uncertainty in normality limits, plaque definition, and IMT growth rates in hypertension.
Main Results:
- Carotid wall lesions are highly prevalent in hypertension, with prevalence dependent on lesion definition criteria.
- Elevated systolic blood pressure is a significant risk factor for carotid lesions.
- Increased carotid IMT correlates with a history of coronary or cerebrovascular disease.
Conclusions:
- Trials of antihypertensive therapy using IMT as an endpoint are likely to yield clinically useful information.
- Non-invasive ultrasound assessment of IMT offers a promising approach to study atherosclerosis progression in hypertension.
- Further research is needed to refine IMT measurement standards and interpretation in hypertensive populations.
Background:
Event-based trials of antihypertensive therapy, although they have been essential in showing the beneficial effects of antihypertensive therapy on cardiovascular morbidity and mortality, could not answer the question whether antihypertensive therapy influences the development of atherosclerosis. Trials using measurements of plaque growth as endpoints are necessary.
Methods:
The traditional approach of using quantitative coronary arteriography for assessing the course of coronary artery disease during treatment cannot obviously be used in uncomplicated hypertensive patients. B-mode quantitative ultrasound assessment of intima-media thickness (IMT) of the carotid artery wall is now being used in several trials comparing different antihypertensive drugs. The major advantage of this approach is that it is non-invasive; it has also been demonstrated that IMT measurements are well reproducible. Limits of normality, definition of plaques and rate of growth of IMT in hypertension are still uncertain, however. Additionally, ultrasonographic techniques do not clearly distinguish between media and intima, and it is difficult to decide how many of the carotid wall lesions observed in hypertension are due to media hypertrophy related to hypertension or to intima changes related to atherosclerosis, although it is likely that the largest lesions have an atherosclerotic component.
Prevalence And Clinical Significance Of Imt:
Baseline data from two recent trials, the VHAS and the ELSA, indicate that carotid wall lesions are highly prevalent in hypertension, but the prevalence level obviously depends on the criteria used for defining these lesions. It is known that elevated systolic blood pressure is an important risk factor for carotid lesions, and epidemiological surveys have shown that increased carotid IMT is more frequently associated with history and signs of coronary artery or cerebrovascular disease. Some evidence from a prospective study is also available, and the VHAS findings support this conclusion. Trials of antihypertensive therapy using IMT as endpoint are, therefore, likely to provide clinically useful information.