Cardiac Energetics and Function in Normal Human Ageing

Conditions

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

Keywords

Energy Metabolism, Ageing, left ventricle, energetics, function

Brief summary

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

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.

Jehill Parikh, Kieren G. Hollingsworth, Vijay Kunadian, Andrew M. Blamire, Guy A. MacGowan

BMC Cardiovascular Disorders2016-02-1840 citations

10.1186/s12872-016-0224-4

Interventions

DRUGRamipril

Ramipril in one dose to reduce vascular stiffness to determine effects of this on left ventricular function and energetics

Study design

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

BASIC_SCIENCE

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

20 Years to 80 Years

Healthy volunteers

Yes

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.

Design outcomes

Primary

Measure	Time frame	Description
Vascular Stiffness	2 Hours - Acute study with no follow-up	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).
Left Ventricular Energetics	2 hours - Acute Study, no follow-up	Left ventricular energetics is measured as the ratio of phosphocreatine to adenosine triphosphate
Left Ventricular Function	2 hours - Acute Study, no follow-up	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.

Secondary

Measure	Time frame	Description
Effects of ACE inhibitor on left ventricular energetics and function in those subjects aged 40 and over	6 hours - Acute study, no follow-up	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.

Countries

United Kingdom

Outcome results

None listed