Aldosterone and stroke PUBMED last 8 years.

[Guest guest]

1: Int J Cardiol. 2008 Sep 13. [Epub ahead of print]

Bilateral adrenal hyperplasia complicated with severe ischemic stroke

in a young

patient.

Triantafyllidi H, Arvaniti C, Katsiva V, Lekakis I, Kremastinos D.

2nd Department of Cardiology, University of Athens, Medical School,

Attikon

Hospital, Athens, Greece.

A young patient suffered from acute right hemiparesis, facial

weakness and

Broca's aphasia with multiple brain lesions due to severe

hypertension. His

evaluation for secondary causes of hypertension revealed

hyperaldosteronism due

to bilateral adrenal hyperplasia. Treatment is based primarily on

spironolactone

and ACE inhibitors. Two years later he was in an outstanding clinical

condition

with few remained neurological symptoms and his blood pressure well

controlled.

PMID: 18793812 [PubMed - as supplied by publisher]

2: Bull Acad Natl Med. 2007 Nov;191(8):1745-54; discussion 1754-5.

[Hypertensive disease in subjects born in sub-Saharan Africa or in

Europe

referred to a hypertension unit: a cross-sectional study]

[Article in French]

Gombet T, Steichen O, Plouin PF.

Unité d'hypertension artérielle, Hôpital Européen s

Pompidou, 20 rue

Leblanc, 75908 Paris cedex 15.

Hypertensive disease is reported to be more severe in black patients

than in

white patients, but most available data concern African-Americans. We

studied

blood pressure history and levels, the prevalence of associated risk

factors,

renal and cardiovascular complications, and secondary forms of

hypertension in

patients born in sub-Saharan Africa and managed in France, by

comparison with up

to five control patients born in Europe and matched for age and sex.

Compared to

European hypertensive women, African hypertensive women had a higher

body-mass

index (28.8 vs 26.3 kg/m2, p<0.001) and were more often diabetic (12

vs 5%,

p<0.001). Hypertensive men and women born in sub-Saharan Africa had

higher

systolic blood pressure (152 vs 148 mmHg, p<0.001), were more likely

to have a

history of stroke (11.7 vs 6.7%, p<0.001) and were less likely to

have a history

of smoking or hyperlipidemia than European controls. Sub-Saharan

Africans were

more frequently given antihypertensive medication than their paired

controls (84

vs 74%, p<0.001), and their antihypertensive regimens were more

likely to include

a diuretic (54 vs 46%, p=0.001) or a calcium channel antagonist (58

vs 49%,

p=0.001). Compared to European controls, patients born in sub-Saharan

Africa had

more frequent proteinuria (test strip positivity : 32 vs 18%, p<0.001),

irrespective of blood pressure and diabetes. The overall prevalence

of secondary

hypertension was similar in the two populations. However, patients

born in

sub-Saharan Africa were more likely than their European controls to

have primary

hyperaldosteronism (12 vs 7%, p=0.001) and less likely to have

renovascular

disease (1 vs 5%, p=0.001). Thus, the higher prevalence of

cardiovascular and

renal complications at referral among patients born in sub-Saharan

Africa

relative to age- and sex-matched European patients does not seem to

be explained

solely by observed differences in blood pressure or associated risk

factors. The

difference in the distribution of secondary hypertension warrants

further study.

Publication Types:

English Abstract

PMID: 18666471 [PubMed - indexed for MEDLINE]

3: Arch Intern Med. 2008 Jan 14;168(1):80-5.

Cardiovascular outcomes in patients with primary aldosteronism after

treatment.

Catena C, Colussi G, Nadalini E, Chiuch A, Baroselli S, Lapenna R,

Sechi LA.

Hypertension and Cardiovascular Unit, Division of Internal Medicine,

Department

of Experimental and Clinical Pathology and Medicine, University of

Udine, Udine,

Italy.

BACKGROUND: Experimental and human studies demonstrate that long-term

exposure to

elevated aldosterone levels results in cardiac and vascular damage.

METHODS: We

investigated long-term cardiovascular outcomes in patients with primary

aldosteronism after surgical or medical treatment. Fifty-four

patients with or

without evidence of adrenal adenomas were prospectively followed up

for a mean of

7.4 years after treatment with adrenalectomy or spironolactone.

Patients with

primary aldosteronism were compared with patients with essential

hypertension and

were treated to reach a blood pressure of less than 140/90 mm Hg. The

main

outcome measure was a combined cardiovascular end point comprising

myocardial

infarction, stroke, any type of revascularization procedure, and

sustained

arrhythmias. RESULTS: At baseline, the prevalence of cardiovascular

events was

greater in primary aldosteronism (35%) than in essential hypertension

(11%) (odds

ratio, 4.61; 95% confidence interval, 2.38-8.95; P< .001), with odds

ratios of

4.93, 4.36, and 2.80 for sustained arrhythmias, cerebrovascular

events, and

coronary heart disease, respectively. Blood pressure during follow-up

was

comparable in the primary aldosteronism and essential hypertension

groups. Ten

patients in the primary aldosteronism group and 19 in the essential

hypertension

group reached the primary end point (P= .85). analysis indicated

that older

age and longer duration of hypertension were factors independently

associated

with the cardiovascular end point. Cardiovascular outcome was

comparable in

patients with aldosteronism treated with adrenalectomy vs aldosterone

antagonists

(P= .71). CONCLUSION: Primary aldosteronism is associated with a

cardiovascular

complication rate out of proportion to blood pressure levels that

benefits

substantially from surgical and medical treatment in the long term.

Publication Types:

Comparative Study

Research Support, Non-U.S. Gov't

PMID: 18195199 [PubMed - indexed for MEDLINE]

4: Exp Clin Endocrinol Diabetes. 2007 Mar;115(3):171-4.

Detecting and treating primary aldosteronism: primary aldosteronism.

Mantero F, Mattarello MJ, Albiger NM.

Division of Endocrinology, Department of Medical and Surgical Sciences,

University of Padua, Italy. franco.mantero@...

Primary aldosteronism (PA) is the most common cause of mineralocorticoid

hypertension. Different studies, using the plasma aldosterone

concentration to

plasma renin activity ratio (PAC/PRA) for the screening of patients with

hypertension, have shown a marked increase in the detection rate of PA.

Idiopathic bilateral adrenal hyperplasia (IHA) and aldosterone-

producing adrenal

adenoma (APA), are the leading causes of primary aldosteronism.

Glucocorticoid-remediable aldosteronism (GRA), also called familial

hyperaldosteronism type I, familial hyperaldosteronism type II and

carcinomas are

rare causes of PA. Patients with hypertension and hypokalemia, those

with a

family history of hypertension and stroke at an early age, or

patients with

medication-resistant hypertension should be screened for PA using the

PAC/PRA

ratio. If a high ratio is found, a sodium loading test or a captopril

test is

warranted to confirm the diagnosis. Adrenal gland imaging is

important in subtype

differentiation (APA vs IHA). Adrenal venous sampling should be used

when other

tests prove inconclusive. Genetic testing has facilitated detection

of GRA.

Surgery is considered the treatment of choice for patients with APA,

while

bilateral hyperplasia subtypes are treated medically. Normalization of

aldosterone levels or aldosterone receptor blockade are necessary to

prevent the

morbidity and mortality associated with hypertension, hypokalemia, and

cardiovascular damage.

Publication Types:

Review

PMID: 17427105 [PubMed - indexed for MEDLINE]

5: J Vet Intern Med. 2005 Sep-Oct;19(5):725-31.

Results of diagnostic investigations and long-term outcome of 33 dogs

with brain

infarction (2000-2004).

Garosi L, McConnell JE, Platt SR, Barone G, Baron JC, de Lahunta A,

Schatzberg

SJ.

Animal Health Trust, Centre for Small Animal Studies, Lanwades Park,

Kentford,

Newmarket, UK. lsg@...

Medical records of 33 dogs presented for acute onset, nonprogressive,

intracranial dysfunction that had a magnetic resonance imaging

diagnosis of brain

infarction were reviewed. Postmortem confirmation of brain infarction

was

available in 10 dogs. All dogs were evaluated by CBC, serum

biochemistry, thyroid

and adrenal testing, urinalysis, thoracic and abdominal imaging, and

cerebrospinal fluid analysis. Results of coagulation profile and

arterial blood

pressure were available in 32/33 and 28/33 dogs, respectively. On the

basis of

the imaging findings, infarcts were classified depending on their type

(territorial or lacunar) and location within the brain

(telencephalic, 10/33;

thalamic/midbrain, 8/33; cerebellar, 15/33). No marked associations

among

location or type of infarct and patient age and sex, occurrence of

systemic

hypertension, and the presence or absence of a concurrent medical

condition were

identified. Small breed dogs (< or =15 kg) were significantly more

likely to have

territorial cerebellar infarcts, whereas large breed dogs (>15 kg) were

significantly more likely to have lacunar thalamic or midbrain

infarcts. A

concurrent medical condition was detected in 18/33 dogs with brain

infarcts, with

chronic kidney disease (8/33) and hyperadrenocorticism (6/ 33) being

most

commonly encountered. Of 33 dogs, 10 were euthanized because of the

severity and

lack of improvement of their neurologic status or the severity of their

concurrent medical condition. No association was identified between

type or

location of infarct and patient outcome. Dogs with concurrent medical

conditions

had significantly shorter survival times than those with no

identifiable medical

condition and were significantly more likely to suffer from recurrent

neurologic

signs because of subsequent infarcts.

PMID: 16231718 [PubMed - indexed for MEDLINE]

6: J Am Coll Cardiol. 2005 Apr 19;45(8):1243-8.

Comment in:

J Am Coll Cardiol. 2005 Apr 19;45(8):1249-50.

Evidence for an increased rate of cardiovascular events in patients

with primary

aldosteronism.

Milliez P, Girerd X, Plouin PF, Blacher J, Safar ME, Mourad JJ.

Department of Cardiology, Lariboisière Hospital, Paris, France.

OBJECTIVES: The aim of this report was to show that the rate of

cardiovascular

events is increased in patients with either subtype of primary

aldosteronism

(PA). BACKGROUND: Primary aldosteronism involves hypertension (HTN),

hypokalemia,

and low plasma renin. The two major PA subtypes are unilateral

aldosterone-producing adenoma (APA) and bilateral adrenal

hyperplasia. METHODS:

During a three-year period, the diagnosis of PA was made in 124 of

5,500 patients

referred for comprehensive evaluation and management. Adenomas were

diagnosed in

65 patients and idiopathic hyperaldosteronism in 59 patients. During

the same

period, clinical characteristics and cardiovascular events of this

group were

compared with those of 465 patients with essential hypertension (EHT)

randomly

matched for age, gender, and systolic and diastolic blood pressure.

RESULTS: A

history of stroke was found in 12.9% of patients with PA and 3.4% of

patients

with EHT (odds ratio [OR] = 4.2; 95% confidence interval [CI] 2.0 to

8.6]).

Non-fatal myocardial infarction was diagnosed in 4.0% of patients

with PA and in

0.6% of patients with EHT (OR = 6.5; 95% CI 1.5 to 27.4). A history

of atrial

fibrillation was diagnosed in 7.3% of patients with PA and 0.6% of

patients with

EHT (OR = 12.1; 95% CI 3.2 to 45.2). The occurrence of cardiovascular

complications was comparable in both subtypes of PA. CONCLUSIONS:

Patients

presenting with PA experienced more cardiovascular events than did

EHT patients

independent of blood pressure. The presence of PA should be detected,

not only to

determine the cause of HTN, but also to prevent such complications.

Publication Types:

Clinical Trial

Randomized Controlled Trial

PMID: 15837256 [PubMed - indexed for MEDLINE]

7: No Shinkei Geka. 2003 Nov;31(11):1223-7.

[Multiple intracerebral microhemorrhages associated with primary

aldosteronism: a

case report]

[Article in Japanese]

Miyata K, Imaizumi T, Horita Y, Hashimoto Y, Tanno K, Koide A, Niwa J.

Emergency Care Unit, Hakodate Municipal Hospital, Japan.

We have observed dot-like low intensity spots (a dot-like hemosiderin

spot:

dotHS) on T2*-weighted (T2*-w) MRI, subsequently diagnosed

histologically as

previous microbleeds associated with lipohyalinosis, amyloid

angiopathy and

cerebral small vessel disease (SVD) including an intracerebral

hematoma (ICH) and

a lacunar infarction. According to the literature, primary

aldosteronism (PA),

characterized by hypertension, is related to SVD. A 49-year-old

female with a

long history of untreated hypertension secondary to PA was admitted

to our

hospital for medical examinations on July 18th, 2000. She had the

stepwise

development of dementia, dysarthria and gait disturbance (right

hemiparesis). CT

and MRI demonstrated multiple lacunar infarctions. She was readmitted

to our

hospital on Jan 23rd, 2002. A neurological examination revealed right

hemiparesis, dysarthria and consciousness disturbance. CT on admission

demonstrated ICH in the left midbrain. Six days after the hemorrhage,

T2*-w MRI

showed thirty-two dotHSs in the basal ganglias and the cortical-

subcortical

regions. The incidence of ICH in patients with hypertension secondary

to PA is

reported to be higher than in patients with essential hypertension.

Multiple

dotHS may be associated with ICH, lacunar infarction, and severe

microangiopathy

related to hypertension secondary to PA.

Publication Types:

Case Reports

English Abstract

PMID: 14655595 [PubMed - indexed for MEDLINE]

8: Cardiol Rev. 2004 Jan-Feb;12(1):44-8.

Glucocorticoid-remediable aldosteronism.

McMahon GT, Dluhy RG.

Division of Endocrinology, Diabetes & Hypertension, Brigham & Women's

Hospital,

and Harvard Medical School, Boston, Massachusetts 02115, USA.

gmcmahon@...

Glucocorticoid remediable aldosteronism (GRA) appears to be the most

common

monogenic form of human hypertension. As a result of chimeric gene

duplication,

aldosterone is ectopically synthesized in the zona fasciculata of the

adrenal

gland under the control of adrenocorticotropin (ACTH). Affected

individuals are

typically hypertensive, often with onset in youth, and demonstrate

refractoriness

to standard antihypertensives such as angiotensin-converting enzyme

inhibitors

and beta-blockers. GRA subjects are normokalemic but often develop

hypokalemia

when treated with a potassium-wasting diuretic. Analysis of affected

kindreds has

demonstrated a high prevalence of early cerebral hemorrhage, largely

as a result

of aneurysms. Identification of affected individuals should allow direct

neurovascular screening and targeted antihypertensive therapy.

Publication Types:

Review

PMID: 14667264 [PubMed - indexed for MEDLINE]

9: Rev Med Chil. 2002 Dec;130(12):1399-405.

[Primary aldosteronism and pregnancy: report of 2 cases]

[Article in Spanish]

Germain AM, Kottman C, Valdés G.

Departamentos de Nefrología y Obstetricia/Ginecología, Facultad de

Medicina,

Pontificia Universidad Católica, Santiago.

Based on two patients, we discuss the difficulties in diagnosing and

managing

primary aldosteronism in pregnancy, which derive from changes of the

renin-angiotensin-aldosterone axis, from the uncertainty regarding

blood pressure

control along gestation and postpartum, and from the contraindication

to the use

of spironolactone. The first case is a 27 years old woman with a long

standing

refractory hypertension, a hemorrhagic stroke with left brachial

hemiplegia and

crural hemiparesia, two miscarriages, one stillbirth and one

offspring with

intrauterine growth retardation. Due to hypokalemia, a plasma

aldosterone/renin

activity ratio of 91, and a negative genetic screening for

glucocorticoid

remediable aldosteronism (GRA), a primary hyperaldosteronism with

normal adrenals

in CT scan was diagnosed, and good blood pressure control was

attained with

spironolactone. After two and a half years of normotension, a fifth

pregnancy,

managed with methyldopa evolved with satisfactory blood pressures,

plasma

potassium, fetal growth, uterine and umbilical arterial resistance

indexes, and

maternal endothelial function. At 37 1/2 weeks of pregnancy the

patient delivered

a healthy newborn weighing 2,960 g. Blood pressure rose during the 48

hours of

postpartum in the absence of proteinuria and required i.v.

hydralazine. The

second patient is a 37 years old woman, with known refractory

hypertension for 7

years, hypokalemia, plasma aldosterone/renin activity ratio greater

than 40,

normal adrenals in the CAT scan, and a negative genetic screening for

GRA. She

had normotensive pregnancies 5 and 3 years prior to the detection of

hypertension, with hypertensive crisis in both postpartum periods,

retrospectively considered as expressions of primary hyperaldosteronism.

Publication Types:

Case Reports

English Abstract

Research Support, Non-U.S. Gov't

PMID: 12611241 [PubMed - indexed for MEDLINE]

10: Hypertens Res. 2002 Sep;25(5):737-42.

Dietary sodium restriction restores nocturnal reduction of blood

pressure in

patients with primary aldosteronism.

Takakuwa H, Shimizu K, Izumiya Y, Kato T, Nakaya I, Yokoyama H,

Kobayashi K, Ise

T.

Department of Gastroenterology and Nephrology, Kanazawa University

Graduate

School of Medical Science, Kanazawa, Japan. takakuwa@...-

u.jp

The purpose of this study was to elucidate the effects of dietary sodium

restriction on diurnal blood pressure (BP) variation in primary

aldosteronism. We

studied the diurnal variation in the systemic hemodynamic indices and in

baroreflex sensitivity (BRS). In 13 subjects with aldosterone-

producing adenomas

(2 males; mean age, 39+/-2 years), intra-arterial pressure was monitored

telemetrically on a normal salt diet (NaCl 10-12 g/day). Non-dippers

were defined

as those with a nocturnal reduction in systolic BP (SBP) of less than

10% of

daytime SBP. Ten subjects showed a non-dipper pattern. Six of these

" non-dippers "

underwent repetitive hemodynamic studies on the last day of a 1-week

low salt

diet regimen (NaCl 2-4 g/day). Stroke volume was determined using

Wesseling's

pulse contour method, calibrated with indocyanine green dilution. BRS

was

calculated every 30 min as delta pulse interval/delta SBP on spontaneous

variations. Nocturnal reduction of SBP was 4.1% on the normal salt

diet. With

sodium restriction, urinary sodium excretion decreased from 187+/-8

to 46+/-8

mmol/day, and body weight decreased from 57.9+/-2.1 to 56.6+/-1.9 kg.

Night-time

BP significantly decreased with dietary modification from 154+/-7/88

+/-4 to

140+/-6/78+/-4 mmHg, whereas daytime BP was unaltered. With sodium

restriction,

cardiac index and stroke index decreased throughout the day. No

significant

difference was seen in either daytime or nighttime BRS between the

two diets. We

conclude that the non-dipper pattern is common in patients with an

aldosterone-producing adenoma on a normal salt intake, and under such

conditions,

volume expansion appears to play a major role in the impairment of

nocturnal BP

reduction.

PMID: 12452327 [PubMed - indexed for MEDLINE]

11: J Clin Endocrinol Metab. 2002 Jul;87(7):3187-91.

Glucocorticoid remediable aldosteronism: low morbidity and mortality

in a

four-generation italian pedigree.

Mulatero P, di Cella SM, TA, Milan A, Mengozzi G, Chiandussi L,

Gomez- CE, Veglio F.

Department of Medicine and Experimental Oncology, Hypertension Unit,

San Vito

Hospital, University of Turin, Strada San Vito 34, 10133 Turin, Italy.

paolo.mulatero@...

Glucocorticoid remediable hyperaldosteronism (GRA) is a monogenic

form of

inherited hypertension caused by a chimeric gene originating from an

unequal

cross-over between the 11 beta-hydroxylase (CYP11B1) and aldosterone

synthase

(CYP11B2) genes. GRA is characterized by high plasma levels of

aldosterone

(regulated by ACTH) with suppressed plasma renin activity and the

production of

two rare steroids, 18hydroxycortisol and 18oxocortisol. Affected

patients usually

show severe hypertension and an elevated frequency of stroke at a

young age.

Affected women have a high risk of developing preeclampsia during

pregnancy.

Here, we describe a 5-generation pedigree from Sardinia in which the

presence of

the chimeric gene is demonstrated in 4 generations. This family

displays a mild

phenotype with average blood pressure levels of 131/86 mm Hg for GRA+

patients.

The occurrence of stroke is very low, and preeclampsia was not

observed in 29

pregnancies from 8 GRA+ mothers. We investigated whether the cross-

over site

(between the CYP11B1 and CYP11B2 genes) or biochemical

characteristics could

explain this phenotype. The cross-over site was located at the end of

intron 3,

in the same region as described in other families. We found a

significant

correlation between blood pressure and 18hydroxycortisol,

18oxocortisol, and

plasma aldosterone levels, but not with kallikrein. However, none of the

biochemical or genetic parameters investigated could explain the mild

phenotype

of the family.

PMID: 12107222 [PubMed - indexed for MEDLINE]

12: J Pediatr. 2001 May;138(5):715-20.

Glucocorticoid-remediable aldosteronism is associated with severe

hypertension in

early childhood.

Dluhy RG, B, Harlin B, Ingelfinger J, Lifton R.

Division of Endocrinology and Hypertension, Brigham and Women's

Hospital, Harvard

Medical School, Boston, Massachusetts 02115, USA.

OBJECTIVES: To review the childhood course of glucocorticoid-remediable

aldosteronism (GRA) in order to provide management guidelines for

hypertension in

children. METHODS: Records for 20 children with GRA (aged 1 month to

18 years; 16

with hypertension) were retrospectively reviewed. RESULTS: Of the 16

children

with GRA who developed hypertension, 50% had moderate-severe

hypertension (blood

pressure [bP] >99th centile for age and sex); 32% had mild

hypertension (BP >95th

and <99th centile), and 18% had borderline normal BP (BP >90th and <95th

centile). Eight of 16 children with hypertension who received directed

monotherapy (glucocorticoid suppression or aldosterone receptor/

sodium epithelial

channel antagonists) maintained BP below the 90th centile. Three

additional

subjects receiving a combination of directed therapies or a

combination of

directed therapies and nifedipine were unable to achieve BP control.

At GRA

diagnosis, 5 of 8 children were normokalemic, and plasma renin

activity was

suppressed in 5 of 5 subjects. CONCLUSIONS: Clinicians should have a

high index

of suspicion for GRA, especially in children with severe hypertension

and a

positive family history of early-onset hypertension and/or premature

hemorrhagic

stroke. Directed monotherapy is often successful in controlling BP in

GRA.

PMID: 11343049 [PubMed - indexed for MEDLINE]

13: J Clin Endocrinol Metab. 2000 Jun;85(6):2160-6.

Comment in:

J Clin Endocrinol Metab. 2000 Jun;85(6):2158-9.

Severity of hypertension in familial hyperaldosteronism type I:

relationship to

gender and degree of biochemical disturbance.

Stowasser M, Bachmann AW, Huggard PR, Rossetti TR, Gordon RD.

University Department of Medicine, Greenslopes Hospital, Brisbane,

Australia.

In familial hyperaldosteronism type I (FH-I), inheritance of a hybrid

11beta-hydroxylase/aldosterone synthase gene causes ACTH-regulated

aldosterone

overproduction. In an attempt to understand the marked variability in

hypertension severity in FH-I, we compared clinical and biochemical

characteristics of 9 affected individuals with mild hypertension

(normotensive or

onset of hypertension after 15 yr, blood pressure never >160/100 mm

Hg, < or = 1

medication required to control hypertension, no history of stroke,

age >18 yr

when studied) with those of 17 subjects with severe hypertension

(onset before 15

yr, or systolic blood pressure >180 mm Hg or diastolic blood pressure

>120 mm Hg

at least once, or > or = 2 medications, or history of stroke). Severe

hypertension was more frequent in males (11 of 13 males vs. 6 of 13

females; P <

0.05). All 4 subjects still normotensive after age 18 yr were

females. Of 10

other affected, deceased individuals (7 males and 3 females) from a

single

family, all six who died before 60 yr of age (4 by stroke) were males.

Biochemical studies were conducted in 6 mild and 16 severe subjects.

The 2 groups

were similar in terms of urinary sodium excretion. Mild subjects

tended, although

not significantly, to have lower urinary 18-oxo-cortisol (mean +/-

SD, 27.4 +/-

9.0 vs. 35.2 +/- 12.9 nmol/mmol creatinine x day), higher plasma

potassium (4.0

+/- 0.3 vs. 3.6 +/- 0.4 mmol/L), and lower recumbent (0800 h after

overnight

recumbency) plasma aldosterone levels (498 +/- 279 vs. 744 +/- 290

pmol/L).

Upright (midmorning after 2-3 h of upright posture) plasma

aldosterone levels

were similar (mild, 485 +/- 150; severe, 474 +/- 188 pmol/L). In 1

normotensive

female, upright PRA was much higher, and the upright aldosterone/PRA

ratio was

much lower than that in the other subjects. The remaining mild

subjects had

similar upright PRA levels (mild, 2.8 +/- 1.4; severe, 3.7 +/- 3.2

pmol/ L x min)

and aldosterone/PRA ratios (mild, 199.5 +/- 133.4; severe, 200.6 +/-

150.9) as

severe subjects. During angiotensin II (AII) infusion studies (n = 6

mild and 10

severe), performed during recumbency, aldosterone levels were lower

in the mild

group both basally (404 +/- 144 vs. 843 +/- 498 pmol/L; P < 0.05) and

after 60

min AII (2 ng/kg x min; 261 +/- 130 vs. 520 +/- 330 pmol/L; P < 0.05).

Aldosterone was unresponsive (rose by <50%) to AII in all subjects.

Day curve

studies (blood collected every 2 h for 24 h; n = 2 mild and 7 severe)

demonstrated abnormal regulation of aldosterone by ACTH rather than

by AII in

both groups. In conclusion, in this series of patients with FH-I,

males had more

severe hypertension, and the degree of hybrid gene-induced aldosterone

overproduction may have contributed to the severity of hypertension.

Publication Types:

Research Support, Non-U.S. Gov't

Research Support, U.S. Gov't, Non-P.H.S.

PMID: 10852446 [PubMed - indexed for MEDLINE]

14: Mayo Clin Proc. 2000 Mar;75(3):278-84.

Erratum in:

Mayo Clin Proc 2000 May;75(5):542.

Comment in:

Mayo Clin Proc. 2000 Jun;75(6):655-6.

Management of difficult-to-control hypertension.

Graves JW.

Division of Hypertension and Internal Medicine, Mayo Clinic

Rochester, MN 55905,

USA.

Hypertension is a primary risk factor for heart disease and stroke,

the first and

third most common causes of death in the United States. The National

Health and

Nutrition Examination Survey (NHANES) revealed an increase in

awareness of

hypertension from 51% to 73%, and, among persons with hypertension,

the treatment

rate has increased from 31% to 55% (from 1976-1980 vs 1988-1991). Of

importance,

the rate of those achieving goal blood pressure (< 140/90 mm Hg) has

only

improved from 10% in NHANES-II (1976-1980) to 29% in NHANES-III

(1988-1991).

Thus, more than 70% of persons with hypertension in whom good blood

pressure

control has not been achieved are termed " difficult hypertensives. "

Failure to

achieve treatment blood pressure goals of less than 140/90 mm Hg is

usually

attributed to the presence of resistant hypertension, a resistant

physician,

secondary causes of hypertension such as renovascular disease,

medication adverse

effects, or a nonadherent patient. A practical understanding of the

pathophysiology of resistant hypertension, appropriate screening

techniques for

secondary forms of hypertension, and alternative management

strategies for a

chronic disease such as hypertension can result in treatment goals

being achieved

in most difficult hypertensives.

Publication Types:

Review

PMID: 10725955 [PubMed - indexed for MEDLINE]

15: Med Clin (Barc). 1999 Nov 6;113(15):579-82.

[Remediable glucocorticoid hyperaldosteronism: molecular diagnosis]

[Article in Spanish]

Lurbe E, Chaves FJ, Torró I, Armengod ME, Alvarez V, Redon J.

Unidad de Nefrología Pediátrica, Hospital General, Valencia.

BACKGROUND: The first family diagnosed in Spain of glucocorticoid

remediable

aldosteronism (GRA) is reported. SUBJECTS AND METHODS: We described the

phenotype, biochemical values and genetic diagnosis of a GRA

pedigree. DNA

analysis was performed by using Southern-blot and polymerase chain

reaction.

RESULTS: We reported a 14-year-old boy who presented with severe

hypertension,

and strong family history of early-onset hypertension. His suppressed

plasmatic

renin activity, family history and failure to respond to conventional

antihypertensive therapy raised GRA as a potential etiology. The

diagnosis was

confirmed by genetic testing, in the index case and in one of family

members,

which demonstrated the chimeric gene duplication, which was a

resultant of a

crossing-over between the proximal portion of 11 beta-hydroxylase

gen, CYP11B1,

and the distal portion of aldosterone synthetase gene CYP11B2. Two

other family

members, who died, suffered hyporeninemic severe hypertension. The

cause of death

in one of them was hemorrhagic stroke. Amiloride, which blocks sodium

transport

in the distal nephron, plus hydroclorothiazide was an effective

treatment option.

CONCLUSIONS: The role of molecular diagnosis techniques is essential

for the

rapid diagnosis of cases of arterial hypertension secondary to familial

glucocorticoid remediable aldosteronism.

Publication Types:

English Abstract

Review

PMID: 10605685 [PubMed - indexed for MEDLINE]

16: J Cardiovasc Nurs. 1999 Jul;13(4):59-77; quiz 127-8.

Genetic determinants of blood pressure regulation.

Ambler SK, Brown RD.

Division of Cardiology, Denver Health Medical Center, University of

Colorado

Health Sciences Center, USA. kelly.ambler@...

Blood pressure homeostasis in humans reflects the coordinate

interactions of

cardiac output, peripheral vascular resistance, renal volume control,

and CNS

integration in response to short- and long-term environmental

stimuli. Variations

in mean arterial pressure within the population include a significant

hereditary

component. The clearest examples of this genetic contribution occur

in rare forms

of monogenic hypertension (glucocorticoid remediable aldosteronism,

apparent

mineralocoid excess, Liddle's syndrome) or hypotension

(pseudohypoaldosteronism

type I, Bartter's syndrome, Gitelman's syndrome). Primary

hypertension, which

comprises approximately 95% of hypertensives and is a major risk

factor for

coronary heart disease, stroke, and renal disease in the U.S.,

represents a

multifactorial and polygenic disease with incremental contributions

from genetic

and environmental determinants. Efforts to date have identified

several candidate

genes involved in primary hypertension, including angiotensinogen

(AGT), a

vasoactive peptide; alpha-adducin, a protein that regulates sodium

transport; and

the G protein beta 3 subunit, a protein involved in intracellular signal

transduction. Advances in knowledge and technology associated with

the Human

Genome Project, combined with continuing basic research on the

physiologic and

biochemical causes of hypertension, offer promise for improved

diagnosis and

therapy of this prevalent disease.

Publication Types:

Review

PMID: 10386272 [PubMed - indexed for MEDLINE]

17: Lancet. 1999 Apr 17;353(9161):1341-7.

Mineralocorticoid hypertension.

PM.

Department of Medicine, Queen Hospital, Edgbaston,

Birmingham, UK.

p.m.stewart@...

Hypertension with hypokalaemia and suppression of plasma renin

activity is known

as mineralocorticoid hypertension. Although mineralocorticoid

hypertension

accounts for a small number of patients labelled as having " essential "

hypertension, it is a potentially reversible cause of high blood

pressure. The

most common cause of mineralocorticoid hypertension is probably primary

aldosteronism; controlled posture studies to measure plasma renin

activity and

aldosterone concentrations, followed by adrenal imaging, will ensure the

differential diagnosis between an aldosterone-producing adenoma and

idiopathic

adrenal hyperplasia in most cases. Three monogenic forms of

mineralocorticoid

hypertension have been described: glucocorticoid-suppressible

hyperaldosteronism,

Liddle's syndrome, and apparent mineralocorticoid excess, which have

provided new

insights into mineralocorticoid hormone action. Many patients with

mineralocorticoid-based hypertension are now known to have normal

serum potassium

concentrations. Until the true prevalence of primary aldosteronism

and monogenic

forms of mineralocorticoid hypertension are defined, a high index of

suspicion is

needed in every hypertensive patient. Hypertensive patients with

hypokalaemia,

together with those with severe hypertension or a family history of

hypertension

or stroke, should be screened for mineralocorticoid excess.

Publication Types:

Review

PMID: 10218547 [PubMed - indexed for MEDLINE]

May your pressure be low!



CE Grim BS, MS, MD

High Blood Pressure Consulting

Senior Consultant to Shared Care Research and Education Consulting

Inc.(sharedcareinc.com)

Clinical Professor of Internal Medicine Medical and Cardiology

Medical College of Wisconsin

Board certified in Internal Med, Geriatrics and Hypertension.

Interests:

1. Difficult to control high blood pressure.

2. The effect of recent evolutionary forces on high blood pressure

in human populations.

3. Improving blood pressure measurement in the office and out.