Hyperaldosteronsim is the most frequent form of hypertension in Czech Republic

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Original Article

Journal of Human Hypertension (2003) 17, 349–352.

doi:10.1038/sj.jhh.1001554

Prevalence of primary hyperaldosteronism in moderate to severe

hypertension in the Central Europe region

B trauch1, T Zelinka1, M Hampf2, R Bernhardt3 and J Widimsky Jr1

13rd Department of Medicine, First Faculty of Medicine,

University, General Faculty Hospital, Prague, Czech Republic

2Max Delbruck Centrum für Molekuläre Medizin, Berlin, Germany

3Universität des Saarlandes, Fachbereich Biochemie, Saarbrücken,

Germany

Correspondence: Dr B trauch, 3rd Department of Medicine, First

Faculty of Medicine, University, General Faculty Hospital, U

Nerocnice 1, Prague 2, 12808, Czech Republic. E-mail:

strauch@...

Received 15 November 2002; Revised 25 January 2003; Accepted 3

February 2003.

Abstract

Recently published studies from different parts of the world report

significantly higher prevalence of primary hyperaldosteronism (PH)

in hypertensives (ranging from 5 to 25%) than the previously

accepted figures. There have been no data so far about the

prevalence of PH in Central Europe. Therefore, we have undertaken

this study to evaluate the prevalence of PH in patients with

moderate to severe hypertension referred to a hypertension unit in

the Czech Republic, together with the determination of the

percentage of different subtypes of PH including familial forms. In

addition to that, we have evaluated the prevalence of other types of

secondary forms of hypertension.

A total of 402 consecutive patients (230 females and 172 males) with

hypertension, referred to our hypertension unit, were studied.

Positive aldosterone/renin ratio (ARR, (ng/100 ml)/(ng/ml/h)) 50 as

a more strict marker of PH was found in 87 patients (21.6%), 30% of

them were normokalaemic. The diagnosis of PH was later confirmed in

77 cases (89%); the total prevalence of PH was thus 19%. PH

consisted of the following forms: idiopathic hyperaldosteronism 42%,

unilateral aldosterone-producing adenoma 36%, unilateral hyperplasia

7%, nonclassifiable PH (refused operation/adrenal venous sampling)

13%, familial hyperaldosteronism type 1.2%. The prevalence of other

types of secondary hypertension was as follows: pheochromocytoma 5%,

renovascular 4.5%, hypercortisolism 2%, renal 0.75%.

In conclusion, we have noted that PH in the Central Europe region

(Czech Republic) is the most frequent form of endocrine hypertension

with a considerably high prevalence in moderate to severe

hypertension. Application of more strict criteria raises the

probability of correct diagnosis of PH including the early

normokalaemic stages of PH.

Keywords: primary aldosteronism, prevalence, aldosterone–renin ratio

Introduction

Conn,1,2 who first described the cure of a patient with primary

hyperaldosteronism (PH) in 1954, recognised that hypokalaemia was

not present in all cases of PH and suggested, that normokalaemic PH

may masquerade as essential hypertension and thus the prevalence

could be higher. This idea was at that time rejected and forgotten

for nearly 40 years and PH was considered to be rare. In the early

1980s Hiramatsu et al3 described the utility of aldosterone/renin

ratio (ARR) and reported a prevalence of 2.6%. The utility of ARR

has been further explored, and in the 1990s many studies were

reported with prevalence ranging from 5 to 25%.4,5,6,7 The apparent

differences in the described prevalences of PH in these studies may

reflect different selection criteria/design and/or potential

geographical differences in the occurrence of PH.

Another important finding is that normokalaemia does not exclude the

diagnosis of PH. In the case of the positive screening test, the

diagnosis must be confirmed by suppression tests (fludrocortisone or

salt loading test) and morphological methods (CT or MRI scan).

Adenomas/hyperplasias <1 cm could be possibly missed on CT scan and

therefore, if suppression tests confirm the diagnosis of PH, adrenal

venous sampling (AVS) is indicated.8 Furthermore, the use of ARR as

the screening test has important clinical implications— more

patients would be diagnosed and possibly cured when surgically

treated. However, the indi-cations for the use of the ARR in all

hypertensive patients still remain controversial—some authors

dispute the validity of such an application.9 Another problem is

that different diagnostic criteria are being used—ARR values ranging

from 20 to 50.

So far there have been no data about the prevalence of PH in Central

Europe (Czech Republic). Therefore, we have undertaken this study to

evaluate the prevalence of primary aldosteronism in patients with

moderate to severe hypertension referred to a hypertension unit in

this area, together with the determination of the percentage of

different subtypes of PH. We have used stricter screening criteria

(ARR 50) for PH. Additionally, we have evaluated the prevalence of

other types of endocrine-mediated and secondary hypertension.

Subjects and methods

We have studied 402 consecutive hypertensive subjects from all

regions of the Czech Republic in 1997–2001, most of them with

moderate to severe hypertension who were examined in our

hypertension unit. The group consisted of 172 men and 230 women of

mean age 51 years. All patients discontinued their usual

antihypertensive therapy at least 14 days before admission to the

hospital and were given only alpha-blockers depen-ding on the blood

pressure (BP) (the medication was withdrawn and patients were

followed up by the GPs). All subjects underwent diagnostic workup

during short hospitalisation (3–5 days), which consisted of a

variety of laboratory and morpho-logical methods to exclude

potential secondary forms of hypertension.

We measured office BP (by a mercury sphygmomanometer in the sitting

position according to ISH recommendations) and also performed 24-h

ambulatory blood pressure monitoring (ABPM) (Spacelabs 90207,

Redmont, CA, USA) in all subjects.

Blood samples were taken for electrolytes as well as for hormonal

tests including PRA and aldosterone in both recumbent and upright

positions. All hormonal parameters were calculated by the usual

commercial methods. Aldosterone and renin concentrations were

measured using commercial RIA methods (Immunotech, France). Our

laboratory's aldosterone normal reference values were 20–150 ng/l

and PRA 0.7–2.6 ng/ml/h. (The conversion between units used for

aldosterone levels is as follows: to get aldosterone in pmol/l,

multiply aldosterone in ng/100 ml by 27.7.) We have calculated the

ARR (ng/100 ml)/(ng/ml/h) in all 402 patients both in recumbent and

upright positions. The criterion for provisional diagnosis of PH was

the ARR 50 (PRA and aldosterone levels measured after 2 h upright

position). The confirmation of the diagnosis of PH was based on (1)

elevated ARR (50 ng/l), (2) suppressed PRA (0.7 ng/ml/h) and

elevated plasma aldosterone (150 ng/l) levels, and (3) the absence

of or mild suppression of plasma aldosterone after saline infusion

(plasma aldo-sterone 85 ng/l) as previously described.10 The

suppression test was performed in the morning after at least 8 h of

recumbent position. In patients who were treated by adrenalectomy,

the diagnosis was also confirmed by histology. The adrenal CT scan

was performed in all the patients screened positive for PH. In all,

20 patients also underwent adrenal venous sampling in order to

further differentiate the subtypes of PH.

Genetic screening for the exclusion of dexamethasone-suppressible

hyperaldosteronism was also performed in patients with PH. The

molecular genetic test can be performed with a single PCR according

to our previously published procedure.11,12

Other potential secondary causes of hypertension were confirmed by

means of the usual morphological and laboratory methods. In case no

secondary cause was elucidated, the patient was considered to

have 'essential' hypertension.

Results

ARR50 was found in 87 patients (21.6%). In all, 30% of them were

normokalaemic. The diagnosis of PH was confirmed by the criteria

described earlier in this text in 77 cases of the 87 (89%); the

total prevalence is hence 19%. The prevalence of PH and other types

of secondary hypertension is shown in Figure 1 (PH 19%,

pheochromocytoma 5%, renal artery stenosis (renovascular) 4%,

hypercortisolism 2%, renal hypertension 1%). Basic characteristics

of the patients with PH are shown in Table 1.

Figure 1.Prevalence of different forms of secondary hypertension in

402 patients with moderate to severe hypertension.

Full figure and legend (81K)

Table 1 - Basic characteristics of patients with confirmed primary

aldosteronism (values are meanss.d.).Full table

Basic characteristics of all the hypertensive patients and

hypertensive patients without PA are shown in Table 2.

Table 2 - Basic characteristics of all 402 patients and 325 patients

without PH with moderate to severe hypertension referred to our

hypertension unit (values are meanss.d.).Full table

The presence of the different forms of PH is shown in Figure 2

(idiopathic hyperaldosteronism 42%, aldosterone-producing adenoma

36%, unilateral hyperplasia 7%, nonclassifiable PA (refused

operation, adrenal venous sampling) 13%, familial hyperaldosteronism

type I 2%).

Figure 2.Presence of different forms of primary aldosteronism in 77

patients (FH I=familial hyperaldosteronism type I).

Full figure and legend (66K)

Discussion

We have demonstrated a relatively high prevalence of PH in patients

with moderate to severe hypertension in our study. Our study is, to

our knowledge, the first one related to the Central Europe region.

In concordance with the results of earlier prevalence

studies,3,4,5,6,7 we have confirmed that PH is not as rare as was

previously thought and appears to be the most frequent form of

endocrine-mediated hypertension. It thus appears that there are no

major geographical differences in the occurrence of PH. As of the

percentage of the subtypes of PH, the majority of our patients had

idiopathic hyperaldosteronism with bilateral overproduction. One-

third of our patients had an aldosterone-producing adenoma later

confirmed by histology. In 7% of patients with PH after diagnosing

unilateral overproduction by AVS, unilateral adrenalectomy was

indicated with the histologic finding of hyperplasia.

Unfortunately, a smaller percentage of our patients rejected further

examination (adrenal venous sampling) after having normal CT scan

and therefore spironolactone therapy was started.

Familial hyperaldosteronism type I (glucocorticoid-remediable

aldosteronism, GRA) was relatively rare. In addition to our

previously described family with GRA,12 we have found only one other

case.

The ARR is a very useful tool as a screening test for diagnosing PA

in patients with moderate to severe hypertension even in the absence

of hypokalaemia. According to previous data, the use of stricter ARR

criteria (ARR50 (ng/100 ml)/(ng/ml/h) increases the probability of

diagnosis of PA.4 We confirmed this observation since in our study

in 89% of patients with ARR equal to or higher than 50 the diagnosis

was confirmed. This stricter screening marker thus appears to be

clinically more reliable than frequently used ARR 20–30.13,14 There

is an ongoing debate about the use of ARR as a screening test in all

hypertensive subjects.9 Our policy to use the ARR in all patients

with moderate to severe hypertension and also in those with

suggestive laboratory/morphological findings was substantiated by

the results of this study. The proportion of normokalaemic patients

in our study was 30% less than previously published—the higher

prevalence of hypokalaemia might be because of some degree of

preselection.

The results of our study also have limitations—the patients referred

to our unit might have been in some way preselected, and it would be

difficult to predict the prevalence in the general hypertensive

population. However, the nonselective hypertensive population is

difficult to define.15 On the other hand, all our patients were

consecutively referred and no patient was rejected. Our data may

thus apply to patients with moderate to severe hypertension.

In conclusion, we have noted that PA is the most frequent form of

endocrine hypertension with a considerably high prevalence in

moderate to severe hypertension in the Czech Republic. Idiopathic

hyperaldosteronism may represent the common form of PH, while

familial hyperaldosteronism ap-pears to be rare. The use of more

strict screening cri-teria raises the probability of correct

diagnosis of PA including the early normokalaemic stages of PA.

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Acknowledgements

This study was supported by Project No J 13198: 11110000-2 of the

Ministry of Education, Youth and Sports of the Czech Republic