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| ID | Type | Description | Link |
|---|---|---|---|
| 95309 | Other Identifier | Northumberland Tyne and Wear CLRN |
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Normal aging is characterized by altered cardiovascular function. Our preliminary data with MR imaging and spectroscopy in normal subjects without cardiovascular disease or hypertension show that age-related cardiac dysfunction is characterized initially by impaired relaxation of the heart (40 - 60 years), and then at > 60 years altered contraction and impaired myocardial energetics. For the first time, the investigators will test whether the functional and energetic effects of normal aging can be reversed by acutely reducing stiffness of peripheral blood vessels using an ACE inhibitor. This will potentially have important insights into how normal aging affects the heart, and how potential treatments could be used to attenuate this process.
Normal aging is characterized by altered cardiovascular function. Our preliminary data with MR imaging and spectroscopy in normal subjects without cardiovascular disease or hypertension show that age-related cardiac dysfunction is characterized initially by diastolic dysfunction (40 - 60 years), and then at > 60 years altered systolic strains and impaired myocardial energetics. The investigators propose to study the mechanism of these findings in subjects with normal aging without any cardiovascular disease, hypothesizing that increased vascular stiffening contributes to impaired energetics and left ventricular function. For the first time, the investigators will test whether the functional and energetic effects of normal aging can be reversed by acutely reducing afterload using an ACE inhibitor. This will be tested at 2 ages (40-60 and > 60 years), so that the intervention tests the hypothesis soon after the abnormalities develop (40-60 years - diastolic dysfunction; > 60 years energetics and altered strains). This will potentially have important insights into how normal aging affects the heart, and how potential treatments could be used to attenuate this process.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ramipril | Experimental | Those who are 40 years and older receive an ACE inhibitor to determine if this reduces age-related changes in left ventricular energetics and function |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ramipril | Drug | Ramipril in one dose to reduce vascular stiffness to determine effects of this on left ventricular function and energetics |
|
| Measure | Description | Time Frame |
|---|---|---|
| Vascular Stiffness | There are 3 principal measures of vascular stiffness, and these are central pulse pressure, central systolic pressure, and the augmentation index. These are correlated against the 3 principal measures of left ventricular function and energetics that are known to change with age: torsion to shortening ratio, early to late diastolic filling ratio, and the ratio of phosphocreatine to adenosine triphosphate (listed as separate Primary Outcome Measures). | 2 Hours - Acute study with no follow-up |
| Left Ventricular Energetics | Left ventricular energetics is measured as the ratio of phosphocreatine to adenosine triphosphate | 2 hours - Acute Study, no follow-up |
| Left Ventricular Function | Left ventricular function is measured with the 2 parameters that are known to change with age: ratio of early to late diastolic filling, and ratio of torsion to shortening ratio. | 2 hours - Acute Study, no follow-up |
| Measure | Description | Time Frame |
|---|---|---|
| Effects of ACE inhibitor on left ventricular energetics and function in those subjects aged 40 and over | A single dose of ACE inhibitor is given to reduce vascular stiffness, and we then measure the effects of this on the measures of left ventricular function and energetics which are the torsion to shortening ratio, diastolic early to late filling ratio, and the phosphocreatine to adenosine triphosphate ratio. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Guy A MacGowan, MD | Freeman Hospital, Newcastle upon Tyne and Newcastle University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Campus for Ageing and Vitality | Newcastle upon Tyne | NE4 6BE | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22180656 | Background | Hollingsworth KG, Blamire AM, Keavney BD, Macgowan GA. Left ventricular torsion, energetics, and diastolic function in normal human aging. Am J Physiol Heart Circ Physiol. 2012 Feb 15;302(4):H885-92. doi: 10.1152/ajpheart.00985.2011. Epub 2011 Dec 16. | |
| 26892669 | Derived | Parikh JD, Hollingsworth KG, Kunadian V, Blamire A, MacGowan GA. Measurement of pulse wave velocity in normal ageing: comparison of Vicorder and magnetic resonance phase contrast imaging. BMC Cardiovasc Disord. 2016 Feb 19;16:50. doi: 10.1186/s12872-016-0224-4. |
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| ID | Term |
|---|---|
| D017257 | Ramipril |
| ID | Term |
|---|---|
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| 6 hours - Acute study, no follow-up |