Obese individuals have a higher prevalence of nocturnal hypertension and non-dipping blood pressure (BP). These conditions are associated with an increased risk of cardiovascular (CV) events and death. Natriuretic Peptides (NPs) are hormones produced by the heart which directly regulate BP by causing dilation of blood vessels and by removing sodium and water from the body. NPs have a 24-hour day-night rhythm and this controls the day-night rhythm of BP as well. The NP-BP rhythm relationship is broken down in obese individuals. Obese individuals also have lower circulating NP levels. Lower circulating levels of NPs and elevated renin hormone (a part of the Renin-Angiotensin-Aldosterone System \[RAAS\]) at nighttime may contribute to the high nocturnal blood pressure in obese individuals which puts them at a higher risk of developing CV events. This current study seeks to determine the biological implications of chronopharmacology for synchronizing NP-RAAS-based blood pressure therapy with the physiological diurnal rhythms to restore the normal diurnal rhythm of blood pressure in obese individuals.
Age more than or equal to 18 years of age
Body Mass Index between 30 to 45 kg/m²
Blood pressure: Systolic BP more than or equal to 130mmHg and less than or equal to 160mmHg and diastolic blood pressure more than or equal to 80mmHg and less than or equal to 100mmHg. Individuals with hypertension as per the 2017 ACC/AHA Guidelines will be eligible for enrollment
Age less than 18, at screening.
Systolic BP <130 or >160mmHg at baseline, or diastolic BP <80 or >100 mmHg at baseline
BMI <30 kg/m² or >45 kg/m²
History of pulmonary hypertension
Factorial
Sacubitril-Valsartan 49 Mg-51 Mg Oral Tablet
DrugThe subject will be randomized, in a double-blind manner to sacubitril/valsartan 49/51 mg once in the morning or once in the evening for a period of 28 days.
Valsartan 80 mg Oral Tablet
DrugThe subject will be randomized, in a double-blind manner to valsartan 80 mg once in the morning or once in the evening for a period of 28 days.
Change in mean nocturnal systolic blood pressure
Change in mean nocturnal systolic blood pressure will be analyzed in the two study arms (morning vs. evening dose of sacubitril/valsartan or valsartan) from baseline and after 28 days of intervention.
Change in percent nocturnal dipping blood pressure
Change in percent nocturnal dipping blood pressure will be analyzed in the two study arms (morning vs. evening dose of sacubitril/valsartan or valsartan) from baseline and after 28 days of intervention.
Change in 24-hour mean systolic blood pressure
Change in 24-hour mean systolic blood pressure will be analyzed in the two study arms (morning vs. evening dose of sacubitril/valsartan or valsartan) from baseline and after 28 days of intervention.
Change in 24-hour mean diastolic blood pressure
Change in 24-hour mean diastolic blood pressure will be analyzed in the two study arms (morning vs. evening dose of sacubitril/valsartan or valsartan) from baseline and after 28 days of intervention.
Change in mean daytime systolic blood pressure
Change in mean daytime systolic blood pressure will be analyzed in the two study arms (morning vs. evening dose of sacubitril/valsartan or valsartan) from baseline and after 28 days of intervention.
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University of Alabama at Birmingham
Lead sponsor
National Heart, Lung, and Blood Institute (NHLBI)
Collaborator
