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

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

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

Brief Summary:

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 'Cardiovascula

    Detailed Summary:

    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.

    Sponsor: Radboud University

    Current Primary Outcome:

    • PAGODE part 1: prevalence [ Time Frame: 4 months ]
      Prevalence of primary aldosteronism in newly diagnosed hypertensive patients in Dutch general practice.
    • PAGODE part 2: organ damage [ Time Frame: 4 weeks ]

      Difference in cardiorenovascular damage in patients with versus without primary aldosteronism, based on a composite of the following parameters:

      1. Left ventricular mass index in g/m2;
      2. Intima-media thickness of carotid artery in mm;
      3. Pulse wave velocity in m/s;
      4. Central aortic blood pressure in mmHg;
      5. Flow-mediated dilation in %;
      6. Albuminuria in mg albumin per mmol creatinin.
    • PAGODE part 3: blood pressure regulation [ Time Frame: 4 months ]
      Difference in reduction of daytime systolic ambulatory blood pressure measurement (ABPM) in patients with normokalemic primary aldosteronism versus patients with essential hypertension in a standardized treatment regimen during conventional antihypertensive therapy.


    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • PAGODE part 2: organ damage [ Time Frame: 4 weeks ]

      To observe differences between newly diagnosed hypertensive patients with versus without primary aldosteronism in:

      1. Serum potassium;
      2. Low density lipoprotein;
      3. Total cholesterol to high density lipoprotein ratio.
    • PAGODE part 3: blood pressure regulation [ Time Frame: 4 months ]

      To observe differences between newly diagnosed hypertensive patients with versus without primary aldosteronism in:

      1. Reduction of daytime systolic ABPM in patients with primary aldosteronism versus patients with essential hypertension in a standardized treatment regimen during spironolactone (or eplerenone);
      2. Serum potassium response using conventional antihypertensive medication;
      3. Adverse effects using conventional antihypertensive medication;
      4. Serum potassium response using spironolactone (or eplerenone);
      5. Adverse effects using spironolactone (or eplerenone).


    Original Secondary Outcome: Same as current

    Information By: Radboud University

    Dates:
    Date Received: November 13, 2012
    Date Started: September 2013
    Date Completion:
    Last Updated: April 5, 2016
    Last Verified: April 2016