Primary Aldosteronism in General Practice: Organ Damage, Epidemiology and Treatment

Primary aldosteronism (PA) is the most frequent form of secondary hypertension. It is caused by autonomous secretion of aldosterone, encompassing a group of disorders which is for 99% predominated by unilateral aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia (BAH). Diagnosis of PA is relevant for two reasons:

1. independent of the level of blood pressure, hypertension due to autonomous aldosterone secretion causes more cardiovascular damage than essential hypertension;
2. PA requires specific treatment: adrenalectomy in case of APA and mineralocorticoid receptor antagonists (MRA) in case of BAH.

Although previously presumed a rare condition (prevalence \<1%), PA is now estimated to affect 6 to 20% of the hypertensive population. Given this high prevalence of PA, as well as the amount of cardiovascular damage and the available specific treatment, the question is raised whether screening of PA should be introduced in Dutch general practice. To answer this important question, several issues with regard to PA need to be elucidated:

1. International studies report a prevalence of PA in general practice of 6-13%. Prevalence in the Dutch population is still unknown;
2. Because of underdiagnosis of PA and long delay in diagnosis of PA after recognition of hypertension (mean eight years), data on characteristics of early diagnosed PA are lacking. Proof of early cardiovascular damage would strengthen the case of screening for PA and needs to be studied;
3. Consequently, the diagnostic delay has lead to lack of data on optimal treatment in early PA. In the current guideline (NHG-guideline 'Cardiovascular risk management') a regimen of antihypertensive drugs is advised, and only if hypertension is refractory for \>6 months patients are referred. It is unknown if hypertension is resistant to therapy in the initial phase of PA. If not, this would also argue for early biochemical screening for PA, because even if blood pressure is controlled, the detrimental effect of aldosterone itself will go on unopposed. It is therefore required to study the response to antihypertensive drugs (not MRA) in these patients.

Rationale: Primary aldosteronism (PA) is the most frequent form of secondary hypertension. It is caused by autonomous secretion of aldosterone, encompassing a group of disorders which is for more than 99% predominated by unilateral aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia (BAH). Diagnosis of PA is relevant for two reasons: 1) independent of the level of blood pressure, hypertension due to autonomous aldosterone secretion causes more cardiovascular damage than essential hypertension; 2) PA requires specific treatment: adrenalectomy in case of APA and mineralocorticoid receptor antagonists (MRA) in case of BAH.

Although previously presumed a rare condition (prevalence \<1%), PA is now estimated to affect 6 to 20% of the hypertensive population. Given this high prevalence of PA, as well as the amount of cardiovascular damage and the available specific treatment, the question has been raised whether screening of PA should be introduced in Dutch general practice. To answer this important question, several issues with regard to PA need to be elucidated:

1. International studies report a prevalence of PA in general practice of 6-13%. Prevalence in the Dutch population is still unknown;
2. Up to now, the laboratory test for screening for PA, the aldosterone/renin ratio (ARR), is primarily used in secondary care. The relation between the ARR and outcomes in primary care is unknown;
3. Because of underdiagnosis of PA and long delay in diagnosis of PA after recognition of hypertension (mean eight years), data on characteristics of early diagnosed PA are lacking. Indications of early cardiovascular damage would strengthen the case of screening for PA and needs to be studied.

Eligibility Criteria:
Inclusion Criteria:

Part 1:

1. Newly diagnosed hypertensive patients (according to the NHG-guideline 'Cardiovascular risk management');
2. 18 years or older;
3. No use of antihypertensive medication.

Part 2:

1. Patients with increased aldosterone/renin ratio;
2. Positive sodium loading test;
3. Written informed consent.

Part 2 + 3:

1. Patients with normal aldosterone/renin ratio;
2. Normal ARR;
3. Written informed consent.

Part 3:

1. Patients with increased aldosterone/renin ratio;
2. Positive sodium loading test;
3. Normokalemic;
4. Written informed consent.

Exclusion Criteria:

1. Use of antihypertensive medication;
2. Heart failure class II, III or IV (according to the New York Heart Association);
3. Pregnancy or breastfeeding.