Brief Summary The purpose of this study is to investigate how circulating metabolites mediate changes in heart function after exercise intervention.

Condition or disease :Cardiovascular function

Intervention/treatment Cardiovascular: Echocardiography Other: Vascular Stiffness Other: Metabolomics (Blood)

Detailed Description The purpose of the study is to determine the effect of a structured exercise intervention on mitochondrial fuel metabolism and cardiovascular function. Participants with diastolic dysfunction will undergo a structured exercise intervention.

Group A (intervention) will undergo exercise intervention for three months and Group B (control) will not receive the exercise intervention. At the start of the study and upon completion, all participants will undergo cardiovascular tests to measure cardiovascular function, as well bio-specimen (blood and urine) collection for metabolic profiling.

Study Design Study Type : Randomized controlled trial Estimated Enrollment :40 participants Time Perspective:Prospective Official Title:EaRneST: Exercise and CiRculating MetabolomicS: A Pilot Randomized Controlled Study Study Start Date :July 2018 Estimated Primary Completion Date :Nov 2019 Estimated Study Completion Date : Nov 2019

Groups and Cohorts Group/Cohort :Group A Intervention/treatment Visit 1. Baseline procedures

1. Cardiovascular measurements Arterial stiffness assessment by non-invasive brachial blood pressure machine Echocardiography Standard transthoracic echocardiographic examination will be performed according to established laboratory practice using standard commercially available machines.

   Resting electrocardiography will be performed to ascertain sinus rhythm.

2. Biospecimen collection Fresh blood, urine specimens will be collected for metabolomics.

3. Six-minute walk test The Six-Minute Walk Test is a shuttle walk test.

4. Musculoskeletal Analysis Participants will undergo focused examinations that include measurement of height, weight, body mass index, waist circumference, body composition analysis.

Visit 2 to Visit 13. One time per week exercise intervention for a total of three months

Visit 14: End of three months' procedures.

1. Cardiovascular measurements Echocardiography Resting electrocardiography will be performed to ascertain sinus rhythm.
2. Biospecimen collection Fresh blood, urine specimens will be collected for metabolomics.
3. Six-minute walk test
4. Musculoskeletal Analysis

Group B Visit 1. Baseline procedures

1. Cardiovascular measurements Arterial stiffness assessment by non-invasive brachial blood pressure machine Echocardiography Standard transthoracic echocardiographic examination will be performed according to established laboratory practice using standard commercially available machines.

   Resting electrocardiography will be performed to ascertain sinus rhythm.

2. Biospecimen collection Fresh blood, urine specimens will be collected for metabolomics.

3. Six-minute walk test The Six-Minute Walk Test is a shuttle walk test.

4. Musculoskeletal Analysis Participants will undergo focused examinations that include measurement of height, weight, body mass index, waist circumference, body composition analysis.

Visit 2: End of three months' procedures.

1. Cardiovascular measurements Arterial stiffness assessment by non-invasive brachial blood pressure machine Echocardiography Resting electrocardiogram will be performed to ascertain heart rhythm.
2. Biospecimen collection Fresh blood, urine specimens will be collected for metabolomics.
3. Six-minute walk test
4. Musculoskeletal Analysis Outcome Measures

Inclusion Criteria:

• Aged 40 years old and above
• At least Grade 1 Diastolic Dysfunction
• Willing and able to give informed consent for participation for the study

Exclusion Criteria:

• History of cardiovascular disease
• History of cancer
• History of stroke
• Uncontrolled hypertension (systolic blood pressure ≥160mmHg and/or diastolic blood pressure ≥90mmHg) despite being on treatment for hypertension
• Low blood pressure (systolic blood pressure <90mmHg or diastolic blood pressure <40mmHg)
• Acute pulmonary embolus or pulmonary infarction
• Acute myocarditis or pericarditis
• Suspected or known dissecting aneurysm
• Acute systemic infection
• Uncontrolled metabolic disease (e.g. diabetes, thyrotoxicosis or myxedema)
• Neuromuscular, musculoskeletal or rheumatoid disorders that are exacerbated by exercise