Eating too much salt raises blood pressure and the risk of having a heart attack or stroke. The investigators do not fully understand why salt raises blood pressure, but storage of sodium in the body, particularly in the skin, may be important. For this reason, the investigators wish to study the link between skin sodium, blood pressure and cardiovascular risk in patients with high blood pressure, of different ethnicities, using techniques such as skin biopsy and magnetic resonance imaging (MRI). The results will provide detailed information on skin sodium storage and help us better understand the effects of blood pressure medications on these mechanisms. Ultimately, the investigators aim to develop personalized treatment guidelines for clinical use.
The physiological basis of salt sensitivity of blood pressure (SSBP) is poorly understood, and determining which patients have SSBP is not straightforward. Furthermore, determining salt sensitivity requires direct intervention tracking changes in blood pressure after salt challenge or depletion over several days. This makes identifying salt-sensitive individuals impractical in a clinical setting, hindering its application. It is crucial that the investigators elucidate the underlying mechanisms of salt-sensitivity, and through this understanding develop a biomarker of SSBP for clinical use. From a review of recent studies it appears that in the short-term, accumulation of skin sodium during high salt intake attenuates the blood pressure response, while in the long-term, high skin sodium levels indicate a tendency for SSBP, hypertension and elevated cardiovascular risk. The reasons for this are not clear and merit further investigation. By refining methods for quantification of skin sodium and expanding its use in hypertension research, the clinicians can improve patient assessment, treatment prescription, and disease monitoring. Using skin biopsy and sodium MRI provides a unique opportunity to study skin sodium handling and SSBP during antihypertensive treatment, and can provide insights into why hypertensives and certain ethnic groups have a higher incidence of SSBP. Sodium MRI may also help increase our understanding of the mechanisms by which diuretics work, both systemically and in the kidney and provide a way to identify salt-sensitive individuals for targeted clinical intervention. Hypotheses: 1. Skin sodium decreases with salt-dependent (diuretic) treatments but not salt-independent (calcium channel blocker) treatments. 2. Diuretic-induced reductions in skin sodium correlate with reductions in blood pressure. 3. Skin sodium is higher in populations traditionally known to be more salt sensitive, such hypertensive patients of black ethnicity. Patients will be enrolled on to a randomised, open-label, two-treatment two-period crossover treatment. The hypertensive medication used in this study are Amlodipine 5 or 10mg and Chlortalidone 25mg. The duration for individual participants will be approximately 16 weeks. Participants will have a total of 7 visits including screening/enrolment (visit 1) and baseline visit (visit 2).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
60
Amlodipine 5mg and Amlodipine 10mg will be one of the study drugs the patients will receive.
Chlortalidone 25mg will be one of the study drugs the patients will receive.
Addenbrooke's Hospital
Cambridge, United Kingdom
St Thomas' Hospital
London, United Kingdom
Concentration of Skin sodium
This is planned for all participants
Time frame: Approximately 8 weeks after receiving each treatment up to week 16 which will be the study completion week
Concentration of Skin Potassium
This is planned for all participants
Time frame: Approximately 8 weeks after receiving each treatment up to week 16 which will be the study completion week
Systolic blood pressure
This is planned for all participants
Time frame: All study visits - every 4 weeks up to week 16 which will be the study completion week
MRI skin sodium concentration
This is planned for all participants
Time frame: Approximately 8 weeks after receiving each treatment up to week 16 which will be the study completion week
Concentration of Skin glycosaminoglycans
This is planned for all participants
Time frame: Approximately 8 weeks after receiving each treatment up to week 16 which will be the study completion week
Diastolic blood pressure
This is planned for all participants
Time frame: All study visits - every 4 weeks up to week 16 which will be the study completion week
Body weight
This is planned for all participants
Time frame: Body weight measurement will be performed at baseline only.
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