Project Lead(s): (John) David Spence
Issue
Hypertension is a major health issue in Africa, with retention of salt and water for hereditary reasons being more common. Two particular causes of resistant hypertension are more common in the region: renal sodium channel mutations (variants of Liddle’s syndrome) and primary aldosteronism, due to bilateral adrenocortical hyperplasia.
Current approaches to management of hypertension assume that all patients are the same, yet patients with mutations of the renal epithelial sodium channel account for 6% of cases and require specific treatment; primary aldosteronism with bilateral hyperplasia due to mutations of aldosterone synthase (CYP11B2) account for 20% of hypertension cases in Africa, and also require specific treatment with spironolactone, eplerenone (or amiloride for men if eplerenone is not available).
Solution
This project tested the hypothesis that using individualized treatment based on the patient’s physiology (assessed by measuring plasma renin and aldosterone) would be superior to usual care. The project involved patients with resistant hypertension in three countries – Kenya, Nigeria and South Africa.
A total of 101 patients with resistant hypertension were enrolled at three sites in Africa and randomized to usual care versus physiologically individualized care; 89 patients completed the study.
Therapy for hypertension was tailored to the underlying cause of hypertension (as determined by laboratory testing) and the patients were followed for one year.
Patients with low renin and high aldosterone (primary aldosteronism) were treated primarily with spironolactone, eplerenone, and amlodipine; those with low renin and low aldosterone (Liddle’s variants) were treated with diuretics (amiloride where available) and amlodipine; those with high renin and high aldosterone were treated primarily with angiotensin receptor blockers, thiazide and amlodipine.
Individualized therapy significantly improved blood pressure control. Systolic blood pressure was reduced to the target (<140 mmHg) in 75% of patients randomized to individualized therapy versus 25% of those randomized to usual care (p = 0.001). Diastolic control to <90 mmHg was achieved in 60% of individualized versus 40% of usual care participants (p = 0.09).
Five candidate genes thought to cause hypertension by causing salt and water retention were sequenced in two subgroups of patients (suspected primary aldosteronism and suspected Liddle syndrome variants). Five single nucleotide polymorphisms (SNPs) that appear to be promising were found.
Outcome
The researchers intend to finalize and publish the results of the study and use the results to support larger randomized clinical trials in Canada and elsewhere.
Investigators in Africa were informed about the advantages of individualized therapy for resistant hypertension and, as they are all leaders in their countries, it is expected that the investigators will educate other physicians in Africa about the advantages of this approach.
Follow-up studies of the promising SNPs are planned in larger hypertension clinic populations in Africa and Canada, and family studies will be carried out if feasible and if funding is obtained.