Primary Aldosteronism Screening and Diagnosis in Primary Health Care

Arterial hypertension is a very common disorder. In most cases the cause is unknown and therefore classified as essential or primary hypertension. Primary aldosteronism (PA), characterized by an inappropriate aldosterone secretion, has traditionally been estimated to account for approximately 1 % of all hypertensive cases. By using the aldosterone to renin ratio (ARR) as a screening tool, the detection of patients with PA has been facilitated. Recent international screening studies have found a high prevalence of the disease accounting for up to 10 % of hypertensive individuals. Thus, PA is recognized to be the most common cause of secondary hypertension. However, the prevalence of PA varies between study populations and the frequency among hypertensive patients in primary health care remains uncertain. When we planned these studies, no studies had previously been done in Swedish primary health care. Confirmatory tests are necessary in the evaluation of patients with increased ARR. The fludrocortisone suppression test (FST) is considered to be a reliable method for the diagnosis of PA since it confirms an autonomous aldosterone production. However, the investigational procedure varies between centres. The cut off level for aldosterone depends on the analytical methods applied and there is no consensus on supplementation with NaCl. Furthermore, the optimal duration of the test is unknown. The test is somewhat cumbersome for the patients, and has traditionally been performed as an in-patient procedure. It is not without risks, especially due to the accumulation of extracellular fluid and hypokalemia. The oral captopril suppression test has less side effects compared to the FST, and could potentially be useful as a confirmatory test for PA, especially in primary health care. The evaluation of the test has previously been based on decreasing concentrations of aldosterone. However, the evaluation of the test with the ARR for the diagnosis of PA has not been assessed. Moreover, the reliability of the captopril suppression test for the diagnosis of PA remains uncertain. The general aim of this thesis is to estimate the prevalence of PA among patients with hypertension in a Swedish primary care setting, and to evaluate the performance of confirmatory tests in the diagnosis of PA, using modern methods for the analysis of serum aldosterone and plasma renin. Reference values for different confirmatory diagnostic tests for PA were obtained as part of the research project. In paper I and IV hypertensive patients were screened for PA by the aldosterone to renin ratio (ARR). Patients with a high ARR were referred for confirmatory testing. In paper I, 17 of 200 patients (8.5%) with previously diagnosed and medically treated hypertension were found to have PA. In paper IV, 11 of 200 newly diagnosed and untreated hypertensive patients (5.5%), were diagnosed with PA. Thus, both screening investigations confirmed a high prevalence of the disease. In paper II, reference values for aldosterone and renin were obtained for the FST in healthy subjects. The cut off value for S-aldosterone was 225 pmol/L after four days with FST or 305 pmol/L if the test was restricted to three days. Furthermore, the investigation showed that FST can be shortened to three days and that a 500 mg NaCl supplementation equivalent to the obligatory daily losses is sufficient for a reliable outcome for the test. The specific time during the day for blood sampling was not of particular importance. In paper III, reference values for a 25 mg Captopril test for aldosterone, renin and ARR were obtained in healthy subjects. The results were then applied in hypertensive patients screened for PA with a high ARR. The evaluation showed that the captopril test is not reliable as a confirmatory test in the diagnosis of PA. The specificity for the discrimination between PA and patients with primary hypertension was very low, especially for patients with alterations in the renin angiotensin regulatory system. In the clinical setting, the post captopril ARR is only marginally better for the diagnosis of PA, compared to the basal ARR. However, an ARR at 120 min within the normal range strongly argues against PA. On the other hand, a high ARR (> 130 pmol/mIU) after the captopril test not only supports the diagnosis of PA, but also suggests the possibility of an aldosterone secreting adrenal adenoma. In conclusion, the prevalence of PA among hypertensive patients in a Swedish primary health care area is higher than previously known. Thus, the family practitioner should consider incorporating ARR screening for PA in the evaluation of patients with hypertension, not only among those with traditional signs for PA, but especially in patients who have been newly diagnosed

Primary aldosteronism among newly diagnosed and untreated hypertensive patients in a Swedish primary care area

Abstract Objective. To evaluate the prevalence of primary aldosteronism (PA) in newly diagnosed and untreated hypertensive patients in primary care using the aldosterone/renin ratio (ARR), and to assess clinical and biochemical characteristics in patients with high and normal ARR. Design. Patient survey study. Setting and subjects. A total of 200 consecutive patients with newly diagnosed and untreated hypertension from six primary health care centres in Sweden were included. Main outcome measures. ARR was calculated from serum aldosterone and plasma renin concentrations. The cut-off level for ARR was 65. Patients with an increased ARR were considered for confirmatory testing with the fludrocortisone suppression test (FST), followed by adrenal computed tomographic radiology (CT) and adrenal venous sampling (AVS). Results. Of 200 patients, 36 patients had an ARR > 65. Of these 36 patients, 11 patients had an incomplete aldosterone inhibition during FST. Three patients were diagnosed with an aldosterone producing adenoma (APA) and eight with bilateral adrenal hyperplasia (BHA). Except for moderately lower level of P-K in patients with an ARR > 65 and in patients with PA, there were no biochemical or clinical differences found among hypertensive patients with PA compared with patients without PA. Conclusion. Eleven of 200 evaluated patients (5.5%) were considered to have PA. The diagnosis of PA should therefore be considered in newly diagnosed hypertensive subjects and screening for the diagnosis is warranted

Captopril suppression: Limitations for confirmation of primary aldosteronism.

INTRODUCTION: : The aldosterone/renin ratio (ARR) is the first line screening test for primary aldosteronism (PA). However, in hypertensive patients with an increased ARR, PA needs to be confirmed by other means. METHODS: : A 25 mg oral captopril test was performed in 16 healthy subjects to obtain reference values for aldosterone and ARR at 120 minutes after the test. Subsequently these data were applied to 46 hypertensive patients screened for PA with an increased ARR. RESULTS: : At 120 minutes after the captopril test ARR decreased in healthy subjects within a narrow range, but remained high in patients with PA and in patients with primary hypertension, especially for those with low renin characteristics. At 120 minutes after captopril, the range of ARR in primary hypertensive patients overlapped in 88% of the cases with the range of the ARR in the PA patients. Sensitivity and specificity of basal ARR and ARR after the captopril test to diagnose PA, calculated as receiver operator characteristics, showed an area under the curve of 0.595 for basal ARR and 0.664 for ARR at 120 minutes after the test. CONCLUSION: : The ARR at 120 minutes after the captopril test is only marginally better than basal ARR in diagnosing PA in hypertensive patients screened with an increased ARR. Owing to an overall limited capacity to clearly discriminate PA from primary hypertension, the test could not therefore be recommended for the confirmatory diagnosis of PA

High frequency of primary hyperaldosteronism among hypertensive patients from a primary care area in Sweden

Objective. To search for primary hyperaldosteronism (PHA) among previously known hypertensive patients in primary care, using the aldosterone/renin ratio (ARR), and to evaluate clinical and biochemical characteristics in patients with high or normal ratio. Design. Patient survey study. Setting and subjects. The study population was recruited by written invitation among hypertensive patients in two primary care areas in Sweden. A total of 200 patients met the criteria and were included in the study. Main outcome measures. The ARR was calculated from serum aldosterone and plasma renin concentrations. The cut-off level for ARR was set to 100, as confirmed in 28 healthy subjects. Patients with increased ARR were considered for a confirmatory test, using the fludrocortisone suppression test. Results. Of 200 patients, 50 patients had ARR >100; 26 patients were further evaluated by fludrocortisone suppression test. Seventeen of these patients had an incomplete aldosterone inhibition. Conclusion. In total 17 of 200 evaluated patients (8.5%) had an incomplete suppression with fludrocortisone. This confirms previous reports on a high frequency of PHA. No significant biochemical or clinical differences were found among hypertensive patients with PHA compared with the whole sample

Re-evaluation of the fludrocortisone test: duration, NaCl supplementation and cut-off limits for aldosterone

Objective. Primary aldosteronism (PA) is the most common form of secondary hypertension. Thus, the aims of this study were: (1) to clarify whether the fludrocortisone suppression test (FST), which confirms autonomous aldosterone secretion, is reliable when carried out during a shorter period of time and (2) to confirm the importance of NaCl supplementation. The cut-off limits already obtained for aldosterone in healthy subjects during the FST were applied in hypertensive patients with a high aldosterone to renin ratio (ARR). Material and methods. The healthy subjects were allocated to three groups. Fludrocortisone was administered 4 times daily over 4 days and sodium chloride was supplemented in 3 different doses. The result was applied in 24 hypertensive patients, in 24 healthy subjects (10 women (23-38 years old) and 14 men (23-58 years old)) and in 24 patients with hypertension and high ARR (16 women (45-74 years old) and 8 men (56-73 years old)). Blood pressure, aldosterone, renin, potassium and sodium were measured. Results. After three days of FST, there was a significant decrease in the serum level of aldosterone in the healthy subjects, regardless of high or low sodium chloride supplementation (p0.001). The decrease in serum aldosterone was significantly less pronounced in patients with PA than in healthy subjects and hypertensive patients without PA (p0.001). The 95th percentile of plasma aldosterone at the end of the test was 225 pmol/L. Conclusions. The FST can be shortened to 3 days and a daily 500 mg NaCl supplementation is sufficient. A cut-off value for aldosterone of 225 pmol/L after 4 days with FST is appropriate

Family history as a predictor of hospitalization for hypertension in Sweden.

Hypertension clusters in families. However, no nationwide study has investigated the family history as a predictor of hospitalization for hypertension, which was the purpose of this study

Morbidity and mortality risk among patients with screening-detected severe hypertension in the Malmo Preventive Project

OBJECTIVE: Screening of hypertension has been advocated for early detection and treatment. Severe hypertension (grade 3 hypertension) is a strong predictor for cardiovascular disease. This study aimed to evaluate not only the risk factors for developing severe hypertension, but also the prospective morbidity and mortality risk associated with severe hypertension in a population-based screening and intervention programme.RESEARCH DESIGN AND METHODS: In all, 18,200 individuals from a population-based cohort underwent a baseline examination in 1972-1992 and were re-examined in 2002-2006 in Malmö, Sweden. In total, 300 (1.6%) patients with severe hypertension were identified at re-examination, and predictive risk factors from baseline were calculated. Total and cause-specific morbidity and mortality were followed in national registers in all severe hypertension patients, as well as in age and sex-matched normotensive controls. Cox analyses for hazard ratios were used.RESULTS: Men developing severe hypertension differed from matched controls in baseline variables associated with the metabolic syndrome, as well as paternal history of hypertension (P < 0.001). Women with later severe hypertension were characterized by elevated BMI and a positive maternal history for hypertension at baseline. The risk of mortality, coronary events, stroke and diabetes during follow-up was higher among severe hypertension patients compared to controls. For coronary events, the risk remained elevated adjusted for other risk factors [hazard ratio 2.31, 95% confidence interval (CI) 1.22-4.40, P = 0.011].CONCLUSION: Family history and variables associated with metabolic syndrome are predictors for severe hypertension after a long-term follow-up. Severe hypertension is associated with increased mortality, cardiovascular morbidity and incident diabetes in spite of treatment. This calls for improved risk factor control in patients with severe hypertension