Cardiac Energetics and Function in Normal Human Ageing

Study Overview
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Brief Summary
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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.

Detailed Description
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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 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.

Official Title
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Cardiac Energetics and Function in Normal Human Ageing

Conditions
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Left Ventricular Function Systolic Dysfunction, Left Ventricular Function Diastolic Dysfunction, Ageing

Intervention / Treatment
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* Drug: Ramipril


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects between the ages of 20 and 80 years Exclusion Criteria: Any cardiovascular condition including hypertension, or on any cardiovascular therapy. Blood Pressure > 150 mmHg systolic, and/or > 90 mmHg diastolic Claustrophobia Implanted metal prosthesis Chronic renal failure requiring dialysis Diabetes mellitus.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ramipril<br>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 | Drug: Ramipril<br>* Ramipril in one dose to reduce vascular stiffness to determine effects of this on left ventricular function and energetics<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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. | 6 hours - Acute study, no follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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energetics, Energy Metabolism, Ageing, left ventricle, function