Aldosterone excretion among subjects with resistant hypertension and symptoms of sleep apnea

OBJECTIVE: The severity of obstructive sleep apnea (OSA) correlates with the difficulty of controlling BP. The mechanism, however, by which sleep apnea contributes to the development of resistant hypertension remains obscure. Having observed a high prevalence of OSA among hypertensive subjects with primary hyperaldosteronism, we hypothesized a possible association between sleep apnea and aldosterone excretion. DESIGN: In consecutive subjects referred to a university clinic for resistant hypertension, we prospectively determined plasma renin activity (PRA), plasma aldosterone concentration (PAC), and 24-h urinary aldosterone excretion during high dietary salt ingestion. In addition, all subjects completed the Berlin Questionnaire, a survey designed to identify subjects at risk of having sleep apnea. Primary hyperaldosteronism (PA) was defined as a PRA < 1.0 ng/mL/h and 24-h urinary aldosterone excretion > 12 micro g during high urinary sodium excretion (> 200 mEq/24 h). RESULTS: Of the 114 subjects evaluated, 72 subjects had a high probability and 42 subjects had a low probability of having sleep apnea based on their responses to the Berlin Questionnaire. Subjects at high risk for sleep apnea were almost two times more likely to have PA diagnosed (36 vs 19%, p < 0.05), tended to have lower PRA (1.2 +/- 1.8 ng/mL/h vs 1.9 +/- 4.1 ng/mL/h), and had significantly greater 24-h urinary aldosterone excretion (13.6 +/- 9.6 micro g vs 9.8 +/- 7.6 micro g, p < 0.05) compared to subjects at low risk of sleep apnea. CONCLUSION: These data provide evidence of increased aldosterone excretion in subjects with resistant hypertension and symptoms of sleep apnea. While the causality of this association is unknown, it is hypothesized that sleep apnea contributes to the development of resistant hypertension by stimulating aldosterone excretion.     

Unadjusted Plasma Renin Activity as a “First‐Look” Test to Decide Upon Further Investigations for Primary Aldosteronism

The authors sought to define the 95th percentile of plasma renin activity (PRA) in a sample of patients with confirmed primary aldosteronism (PA) prior to adjustment of medications as a practical “first‐look” test to identify those with very low ultimate likelihood of having PA. The aldosterone to renin ratio (ARR) was measured without adjustment of antihypertensive medications, with further workup as appropriate. Two groups were defined: patients with surgically “confirmed PA” (n=58) and patients with “high‐probability PA” (n=59), defined as having any of the following: computed tomography–confirmed adrenal adenoma plus lateralizing adrenal vein sampling (AVS) without surgery, high ARR and hypokalemia but nonlateralizing AVS, or ARR more than four times the upper limit of normal. The PRA 95th percentile was 1.0 ng/mL/h. All outliers had hypokalemia and two had adrenal adenomas. There was no difference between the confirmed and high probability groups. In the absence of highly suspicious clinical features, patients with unadjusted PRA >1.0 ng/mL/h do not warrant further investigation for PA.     

Primary aldosteronism

In 1955 Dr Jerome Conn first documented primary aldosteronism (PA). Since then, screening, diagnosis and treatment have developed, in the process both refining and complicating management. Currently, screening requires 4–6 weeks of lead-up, including major changes in antihypertensive therapy, followed by a blood draw for plasma aldosterone concentration (PAC) and plasma renin activity (PRA) or concentration (PRC). Screening is considered indicative of PA on the basis of the PAC and the aldosterone to renin ratio (ARR). This is then followed by one or more of 6 confirmatory/exclusion tests. Three things have changed. First is now incontrovertible evidence that a single spot PAC is a deeply flawed index of true aldosterone status, so that many referred patients with PA fall at the first hurdle. A valid index of aldosterone status is an integrated value, measured as urinary aldosterone excretion (UEA) over 24 h. On the basis of the UEA, the prevalence of PA appears to be 3–5 times higher than the currently accepted figure of 5–10% of hypertensives. The second is the recognition that inadequately treated PA has a cardiovascular risk profile ~threefold that of matched essential hypertensives. Third is the realization that <1% of hypertensives are ever screened for PA, who are thus in double jeopardy for the risks of untreated PA on top of those for hypertension per se. Taken together, this a major if occult public health issue; if it is to be addressed, radical changes in management are needed. Some are in screening, which needs to be simply done on all newly-presenting hypertensives; others are major simplifications of screening in established hypertension. The front-line actors need to be Internists/Primary Care Providers; the costs will be significant, but much less than those of increased morbidity/premature mortality in unrecognized PA. Possible suggestions as to how best to address this constitute the final chapter of this article.     

尿醛固酮在原发性醛固酮增多症筛查中的价值及钠摄入对其筛查效率的影响

目的探讨尿醛固酮在原发性醛固酮增多症(PA)筛查中的作用并评估钠盐摄入对其筛查效率的影响。方法收集2006-09-2009-07中山大学附属第二医院内分泌科门诊和住院的高血压患者269例,其中包括原发性高血压患者237例(女119例,男118例,平均年龄47.4岁)和PA患者32例(女20例,男12例,平均年龄41.9岁)。所有入组的研究对象均测定立位1h血清醛固酮(SAC)和血浆肾素活性(PRA),并留取24h尿检测尿醛固酮、尿钠和尿钾。通过构建受试者工作特征曲线(ROC),评估尿醛固酮在PA筛查中的效率并确定最佳切点。以尿钠/尿钾作为钠盐摄入的评估方法,以尿钠/尿钾中位数作为切点将原发性高血压组分为高尿钠/尿钾组(n=119)和低尿钠/尿钾组(n=118),分别以这两组高血压人群作为阴性人群,以PA组作为阳性人群进行ROC分析,比较不同钠盐摄入情况对尿醛固酮水平及其PA筛查效率的影响。结果通过构建ROC曲线评估尿醛固酮在PA筛查中的作用,其曲线下面积为0.824(95%CI0.773～0.867,P<0.01),应用Youden’s指数确定尿醛固酮诊断PA的最佳切点值为11.6μg/24h,其敏感性和特异性分别为81.2%(95%CI63.3%～92.7%)和74.3%(95%CI68.2%～79.7%);在原发性高血压患者中,尿醛固酮与尿钠/尿钾呈负相关(r=-0.174,P<0.01)。高尿钠/尿钾组尿醛固酮、SAC和PRA水平明显低于低尿钠/尿钾组。结论尿醛固酮在PA筛查有一定意义,采用11.6μg/24h作为切点可取得较高的筛查效率。钠摄入可影响尿醛固酮水平,但不影响其筛查效率。     

Hyperaldosteronism among black and white subjects with resistant hypertension

Recent reports suggesting that the prevalence of primary hyperaldosteronism may be higher than historically thought have relied on an elevated plasma aldosterone concentration/plasma renin activity ratio to either diagnose or identify subjects at high risk of having primary hyperaldosteronism and have not included suppression testing of all evaluated subjects. In this prospective study of 88 consecutive patients referred to a university clinic for resistant hypertension, we determined the 24-hour urinary aldosterone excretion during high dietary salt ingestion, baseline plasma renin activity, and plasma aldosterone in all subjects. Primary hyperaldosteronism was confirmed if plasma renin activity was <1.0 ng/mL per hour and urinary aldosterone was >12 microg/24-hour during high urinary sodium excretion (>200 mEq/24-hour). Eighteen subjects (20%) were confirmed to have primary hyperaldosteronism. The prevalence of hyperaldosteronism was similar in black and white subjects. Of the 14 subjects with confirmed hyperaldosteronism who have been treated with spironolactone, all have manifested a significant reduction in blood pressure. In this population, an elevated plasma aldosterone/plasma renin activity ratio (>20) had a sensitivity of 89% and a specificity of 71% with a corresponding positive predictive value of 44% and a negative predictive value of 96%. These data provide strong evidence that hyperaldosteronism is a common cause of resistant hypertension in black and white subjects. The accuracy of these results is strengthened by having done suppression testing of all evaluated subjects.     

Effect of age on aldosterone/renin ratio (ARR) and comparison of screening accuracy of ARR plus elevated serum aldosterone concentration for primary aldosteronism screening in different age groups

The serum aldosterone concentration (SAC)/plasma renin activity (PRA) ratio (ARR) is considered a useful screening test in the differential diagnosis of essential hypertension (EH) and primary aldosteronism (PA). The purpose of this study is to investigate the effect of age on ARR and compare the screening accuracy of ARR plus elevated SAC for PA screening in different age groups. Thirty-nine patients with PA, 274 patients with EH, and 153 healthy volunteers were recruited. Blood was sampled for SAC and PRA measuring under keeping upright posture for 1 h. Levels of SAC, PRA, and ARR were compared at different ages range for the respective three groups of subjects. The screening accuracy of ARR plus elevated SAC was compared in different age groups and PA patients served as the same positive subjects. In the EH group, logarithmically transformed ARR (Log-ARR) increased with advancing age and reached its peak in the ≥ 60 years group; in the normotensives group, Log-ARR reached its peak in the 40-49 years group and slightly declined with advancing age. In the PA group, Log-ARR was not age dependent. Screening accuracy increased when combined index of ARR and SAC was used in the ≥ 40 years group but not in the <40 years group. Although the number of EH patients with elevated ARR increased with advancing age, but the screening accuracy and cutoff values of ARR were not affected by age. Using the combined index of ARR and SAC increased the screening accuracy for the patients older than 40 years, but not necessary for the patients younger than 40 years.     

Efficacy of low-dose spironolactone in subjects with resistant hypertension

BackgroundPrevious reports have demonstrated the antihypertensive efficacy of high doses of spironolactone in subjects with primary aldosteronism and, to a lesser degree, subjects with resistant hypertension.MethodsIn current analysis, we examined the antihypertensive benefit of adding low-dose spironolactone to multidrug regimens that included a diuretic and an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) in subjects with resistant hypertension with and without primary aldosteronism. Subjects referred for resistant hypertension were evaluated with an early morning plasma renin activity, 24-h urinary aldosterone and sodium during a high dietary salt ingestion. The diagnosis of primary aldosteronism was confirmed with a renin activity <1.0 ng/mL/h, urinary aldosterone >12 μg/24 h and urinary sodium >200 mEq/24 h. After biochemical evaluation, spironolactone (12.5 to 25 mg/d) was added to each subject's antihypertensive regimen. If blood pressure (BP) remained uncontrolled, the dose of spironolactone was titrated up to 50 mg/d. Follow-up BP was determined at 6 weeks, 3 months, and 6 months.ResultsA total number of 76 subjects were included in the analysis, 34 of whom had biochemical primary aldosteronism. Low-dose spironolactone was associated with an additional mean decrease in BP of 21 ± 21/10 ± 14 mm Hg at 6 weeks and 25 ± 20/12 ± 12 mm Hg at 6-month follow-up. The BP reduction was similar in subjects with and without primary aldosteronism and was additive to the use of ACE inhibitors, ARBs, and diuretics.ConclusionsWe conclude that low-dose spironolactone provides significant additive BP reduction in African American and white subjects with resistant hypertension with and without primary aldosteronism.     

Establishment of reference values for endocrine tests. III: Primary aldosteronism

BACKGROUND: In our laboratory well-defined reference values for the screening test and confirmation test used in the diagnosis of primary aldosteronism were lacking. In this study we established the reference-values of the plasma aldosterone concentration (PA), plasma renin activity (PRA) and PA/PRA ratio after a two-hour upright period, and of the urinary aldosterone excretion after oral sodium loading. METHODS: Fifty healthy volunteers, equally distributed according to sex and aged between 20 and 70 years, went through the screening and confirmation test of primary aldosteronism. PA, PRA and the PA/PRA ratios were measured after a two-hour upright period (screening test). Urinary aldosterone excretion was determined in two 24-hour urine samples after an oral suppletion of 6 g NaCl a day for five days (confirmation test). RESULTS: The following reference values were established: PA (after two-hour upright position) <0.03-1.05 nmol/l (mean: 0.47), PA/PRA ratio 0.05-0.47 (mean: 0.15) and urinary aldosterone excretion after sodium loading <3.0-47.0 nmol/24h (mean: 10.5). PRA showed a significant decrease with advancing age: median values in the 3rd to 7th decade are 3.9, 3.5, 2.5, 1.6 and 2.1 ng A1/ml/h respectively (p=0.04). PA was lower in subjects > or = 50 years old. Age did not affect the PA/PRA ratio or the urinary aldosterone excretion. There were no significant differences between the sexes in any of the above-mentioned parameters. CONCLUSION: In this study we established reference values for the screening and confirmation test used in the diagnosis of primary aldosteronism.     

SFE/SFHTA/AFCE Consensus on Primary Aldosteronism,part 2: First diagnostic steps

In patients with suspected primary aldosteronism (PA), the first diagnostic step, screening, must have high sensitivity and negative predictive value. The aldosterone-to-renin ratio (ARR) is used because it has higher sensitivity and lower variability than other measures (serum potassium, plasma aldosterone, urinary aldosterone). ARR is calculated from the plasma aldosterone (PA) and plasma renin activity (PRA) or direct plasma renin (DR) values. These measurements must be taken under standard conditions: in the morning, more than 2 hours after awakening, in sitting position after 5 to 15 minutes, with normal dietary salt intake, normal serum potassium level and without antihypertensive drugs significantly interfering with the renin-angiotensin-aldosterone system. To rule out ARR elevation due to very low renin values, ARR screening is applied only if aldosterone is > 240 pmol/l (90 pg/ml); DR values < 5 mIU/l are assimilated to 5 mIU/l and PRA values < 0.2 ng/ml/h to 0.2 ng/ml/h. We propose threshold ARR values depending on the units used and a conversion factor (pg to mIU) for DR. If ARR exceeds threshold, PA should be suspected and exploration continued. If ARR is below threshold or if plasma aldosterone is < 240 pmol/l (90 pg/ml) on two measurements, diagnosis of PA is excluded.     

Active renin versus plasma renin activity to define aldosterone-to-renin ratio for primary aldosteronism

BACKGROUND: In recent years, the assessment of the plasma aldosterone-to-renin ratio (ARR) has become an established screening method for the diagnosis of primary aldosteronism. Plasma renin activity (PRA) is usually measured to define ARR although, increasingly, renin concentration alone is often measured in clinical routine. OBJECTIVE: To determine the threshold of ARR using active renin concentration to screen for primary aldosteronism. DESIGN AND PARTICIPANTS: To determine the ARR threshold based on plasma immunoreactive renin concentration (irR), we measured plasma aldosterone concentration (PAC), irR and PRA in 36 hypertensive patients, nine thereof with adrenal adenoma, and compared ARRs calculated from irR and PRA, respectively. SETTING: Single-centre, hypertension clinic in a tertiary care hospital. RESULTS: PRA ranged from 0.41-14.9 ng/ml per h and irR from 1.1-72 ng/l. There was an excellent correlation between PRA and irR (r = 0.98, P < 0.0001) and between ARRPRA and ARRirR (r = 0.96, P < 0.0001). An ARRPRA > 750 pmol/l per ng/ml per h was previously found to be highly predictive of primary aldosteronism because 90% of the corresponding patients failed to suppress PAC upon saline infusion or fludrocortisone. The corresponding threshold value for ARRirR was 150 pmol/ng in our patients. Using these cut-offs, nine subjects had both increased ARRPRA and ARRirR while, in three patients, either ARRPRA or ARRirR were increased. The nine patients with increased ARRPRA and ARRirR also had PAC > 650 pmol/l. Only these patients had adrenal adenomas. CONCLUSIONS: The ARR threshold to screen for primary aldosteronism may be based on measurement of irR. An ARRirR > 150 pmol/ng may indicate primary aldosteronism.     

The use of aldosterone-renin ratio as a diagnostic test for primary hyperaldosteronism and its test characteristics under different conditions of blood sampling

Recent reviews recommended the use of the aldosterone/renin ratio (ARR) to screen for primary hyperaldosteronism. However, widely different cutoff levels have been proposed, and test characteristics of ARR under different conditions of sampling are not known. We conducted a retrospective review among 45 subjects with carefully validated diagnoses of primary hyperaldosteronism and 17 subjects with essential hypertension to study the utility of ARR. Sixty-two patients with 75 sets of plasma renin activity (PRA), aldosterone, and ARR values from a postural study and 48 sets of values from a saline suppression test were analyzed. Ninety-four percent of these subjects underwent investigations because of hypokalemic hypertension.ARR yielded larger areas under the curve in the receiver-operating-characteristics curve than PRA or aldosterone under all conditions of testing. Our results confirmed the superiority of ARR to either aldosterone or PRA alone as a diagnostic test for primary hyperaldosteronism.ARR cutoff levels were significantly affected by the condition of testing. Depending on posture and time of day, it varied from 13.1-35.0 ng/dl per ng/ml.h in our study population. When using ARR for screening primary hyperaldosteronism, posture and time of sampling should be standardized both within and between centers to minimize variability in cutoff levels.     

High prevalence of primary aldosteronism in the Tayside hypertension clinic population

Primary aldosteronism (PA) was thought to be rare but recent evidence from Australia suggests that it may be more common. As this has important implications in terms of hypertension management, we undertook to screen for this treatable condition in our hypertension clinic. We obtained blood samples in sequential patients referred for assessment in our hypertension clinic in Tayside for plasma renin activity (PRA) and aldosterone. The aldosterone to PRA ratio (ARR) was used as an initial screening test to identify potential patients with PA. Those patients with an elevated ratio (> or =750) were admitted for the salt loading and fludrocortisone suppression test. These patients also underwent adrenal CT scanning, and in selected patients, adrenal scintigraphy. Between May 1995 and January 1997 (21 months), we screened a total of 495 patients. ARR was available in 465 (93.9%) patients. Out of that number, 77 (16. 6%) had an elevated ratio of > or =750, five of whom had an adrenal adenoma (one had previous adrenalectomy). Forty-five of these patients were admitted for the salt loading and fludrocortisone suppression test with 41 positive test results suggesting PA. One patient with a negative salt loading test result however had an adenoma proven on histology. A total of 43 cases of PA were identified, giving a minimum prevalence of 9.2% (43/465). Potentially the prevalence may be up to 15% assuming that the ARR has a sensitivity of 93% (42/45) in predicting PA. In conclusion, about one in 10 patients attending a hypertension clinic may have PA. This suggests that the prevalence of PA in Tayside is as high as that in the Australian hypertensive population, and this is likely to be true elsewhere, with obvious important implications for hypertension management.     

Aldosterone to renin ratio as a determinant of exercise blood pressure response in hypertensive patients

Aldosterone to renin ratio (ARR) is a marker of inappropriate aldosterone activity in hypertension. Since aldosterone may adversely affect vascular compliance, we hypothesised that the ARR would relate to exercise blood pressure (BP) responses in hypertension. Blood sampling was done in untreated hypertensives for plasma renin activity (PRA, ng/mL/hr) and plasma aldosterone (PA, pmol/L). ARR was derived by dividing the PA value by the PRA value, and this index was normalised by natural logarithm (lnARR) for further analyses. Each patient underwent 24-h ambulatory BP (ABP), and a 3-min submaximal exercise test using the Dundee Step Test. The Spearman rank correlation coefficients between lnARR and office BP (OBP), ABP and exercise BPs and BP changes estimated during exercise were assessed. A total of 119 (66 males) hypertensive subjects aged 48 (s.d. 12) years were studied. The respective OBP, ABP, exercise BP and the change in exercise BP were 167(23)/105(11), 140(15)/87(10), 189(26)/107(12) and 25(15)/2(9) mmHg. lnARR was significantly correlated with exercise systolic BP (r = 0.24, P < 0.001), exercise diastolic bp (r = 0.23, P < 0.05), systolic abp (r = 0.22, P < 0.05) and systolic obp (r = 0.19, P < 0.05). in a multiple regressional analysis controlling for age and sex and all other bp measurements to assess the relative strengths of correlation between all the bp indices with lnarr, only exercise systolic bp (P = 0.012) and the change in systolic BP during exercise (negatively, P = 0.013) emerged as significant independent predictors of lnARR. In conclusion, there was an independent and significant correlation between ARR and exercise systolic BP.     

Prevalence of primary aldosteronism among unselected hypertensive patients: a prospective study based on the use of an aldosterone/renin ratio above 25 as a screening test.

Primary aldosteronism (PA) has been considered a rare cause of hypertension. The introduction of the aldosterone/renin ratio (ARR) as a screening test has led to an increase in the detection rate. The aim of this study was to evaluate the prevalence of PA among unselected hypertensive patients by using an ARR >25 as a screening test. We studied 3,000 consecutive unselected hypertensive patients. Blood samples for the determination of plasma renin activity (PRA), aldosterone (ALD) and electrolytes were drawn in the morning, and patients with an ARR >25 underwent intravenous saline infusion as a confirmatory test. Adrenal CT and a dexamethasone suppression test were performed in patients with confirmed PA. Patients with a positive dexamethasone test underwent genetic testing for glucocorticoid-remediable aldosteronism (GRA). Out of 3,000 hypertensives, 684 (22.8%) showed an ARR >25 and 177 of them (5.9% of the whole population) had a positive saline loading test. Only 44 of them (24.8%) were hypokalemic. CT was performed in all the patients with confirmed PA and 53 of them (29.9%) had a solitary adrenal macroadenoma, 112 (63.3%) had bilateral adrenal enlargement and 12 (6.8%) had normal appearing adrenal glands. Of 177 patients given dexamethasone to identify GRA, 8 (4.5%) showed aldosterone suppression but only one (0.1%) tested positive for the chimeric gene. In conclusion, our findings indicate that standardized application of an ARR >25 to unselected hypertensive patients, followed by i.v. saline loading as a confirmatory test, can result in the detection of a large number of patients with PA (5.9% of the studied population), most of whom are normokalemic. Bilateral adrenal hypertrophy represents the more common form of PA.     

The Cutoff Value of Aldosterone-to-Renin Ratio for the Diagnosis of Primary Aldosteronism in Patients Taking Antihypertensive Medicine

Background. Primary aldosteronism (PA) may account for as much as 6–20% of cases of refractory hypertension referred to hypertension clinics. Because antihypertensive agents affect the physiologic renin-angiotensin-aldosterone system, screening diagnostic tests for PA are generally performed after antihypertensive agents are discontinued. However, such tests can be dangerous for patients with severe hypertension or other cardiovascular complications. However, a reliable cutoff value for the aldosterone-to-renin ratio (ARR) has not been established, especially for Asians, including the Japanese. Method. Fifty-five consecutive patients with clinically suspected PA were evaluated from July 10, 2001, to March 1, 2005, at the National Cardiovascular Center in Japan. Every referred patient was screened prospectively for PA with the ARR at the outpatient clinic. The patients tested continued to be treated with a variety of antihypertensive agents. We reviewed the sensitivity, specificity, and accuracy of the ARR without modifying the antihypertensive agents. The diagnosis of PA was established with the results of both abdominal computed tomography and adrenal scintigraphy. Results. Of the 55 patients, 27 were found to have PA, including adrenal adenoma (n = 18) and bilateral adrenal hyperplasia (n = 9). The mean ARR of patients with PA was significantly higher than that of patients without PA. By assuming a cutoff value of the ARR ≥ 69 calculated from the receiver operating characteristics curve, the highest sensitivity (81%), specificity (82%), positive-predictive value (81%), and negative-predictive value (81%) were obtained. Conclusion. The data suggest that an ARR ≥ 69 strongly indicates PA in Japanese patients with hypertension being treated with antihypertensive agents.     

Association of adrenal steroids with hypertension and the metabolic syndrome in blacks

Blacks have a high prevalence of hypertension and adrenal cortical adenomas/hyperplasia. We evaluated the hypothesis that adrenal steroids are associated with hypertension and the metabolic syndrome in blacks. Ambulatory blood pressures, anthropometric measurements, and measurements of plasma renin activity (PRA), aldosterone, fasting lipids, glucose, and insulin were obtained in 397 subjects (46% hypertensive and 50% female) after discontinuing antihypertensive and lipid-lowering medications. Hypertension was defined as average ambulatory blood pressure >130/85 mm Hg. Late-night and early morning salivary cortisol, 24-hour urine-free cortisol, and cortisone excretion were measured in a consecutive subsample of 97 subjects (40% hypertensive and 52% female). Compared with normotensive subjects, hypertensive subjects had greater waist circumference and unfavorable lipid profiles, were more insulin resistant, and had lower PRA and higher plasma aldosterone and both late-night and early morning salivary cortisol concentrations. Twenty-four-hour urine-free cortisol and cortisone did not differ. Overall, ambulatory blood pressure was positively correlated with plasma aldosterone (r=0.22; P<0.0001) and late-night salivary cortisol (r=0.23; P=0.03) and inversely correlated with PRA (r=-0.21; P<0.001). Plasma aldosterone correlated significantly with waist circumference, total cholesterol, triglycerides, insulin, and the insulin-resistance index. Based on Adult Treatment Panel III criteria, 17% of all of the subjects were classified as having the metabolic syndrome. Plasma aldosterone levels, but not PRA, were elevated in subjects with the metabolic syndrome (P=0.0002). The association of aldosterone with blood pressure, waist circumference, and insulin resistance suggests that aldosterone may contribute to obesity-related hypertension in blacks. In addition, we speculate that relatively high aldosterone and low PRA in these hypertensive individuals may reflect a mild variant of primary aldosteronism.     

Prevalence of primary hyperaldosteronism in mild to moderate hypertension without hypokalaemia

Screening for primary hyperaldosteronism (PHA) is often indicated in individuals with resistant hypertension or hypokalaemia. However, in the far larger subset of the hypertensive population who do not fit into these criteria, the evidence for screening is conflicting and dependent on the disease prevalence. The purpose of this study was to examine the prevalence of PHA in a large population with mild to moderate hypertension and without hypokalaemia using a carefully controlled study protocol including a normotensive control population. Hypertensive subjects underwent medication washout and both hypertensive and normotensive subjects placed on a high-sodium diet prior to biochemical and haemodynamic testing. Study specific cutoff values were based on results from the normotensive population studied under identical conditions. A screening test (serum aldosterone/PRA ratio [ARR]>25 with a serum aldosterone level >8 ng/dl) was followed by a confirmatory test (urine aldosterone excretion rate [AER] >17 microg/24 h) to demonstrate evidence of PHA. An elevated ARR with a concomitant elevated serum aldosterone was present in 26 (7.5%) individuals. Of these, 11 (3.2%) had an elevated AER, consistent with evidence of PHA. Individuals with PHA had higher blood pressure and lower serum potassium levels while on a high-sodium diet. Sodium restriction neutralized these differences between PHA and essential hypertensives. The prevalence of PHA in this mild to moderate hypertensive population without hypokalaemia is at most 3.2%, a rate that might lead to excessive false positives with random screening in comparable populations. Hyperaldosteronism, when present, is responsive to sodium restriction.     

Diagnosis of primary aldosteronism: value of different screening parameters and influence of antihypertensive medication

OBJECTIVE: The aim of this study was to investigate the utility of different screening techniques for primary aldosteronism (PA), including serum aldosterone (SA), plasma renin activity (PRA) and the SA/PRA ratio in hypertensive patients of a tertiary-care centre. Furthermore, the influence of antihypertensive medication on SA and the SA/PRA ratio were studied. DESIGN: Clinical records of 425 hypertensive patients who had SA and PRA measurements over a 27-month period were analysed retrospectively. Eighty patients were excluded from further analysis because of incomplete data. The remaining 345 patients were classified into the following groups: patients with essential hypertension (EH) (n=260, 75.4%), patients with PA (n=49, 14.2%) and patients with secondary hypertension other than PA (n=36, 10.4%). Diagnosis of PA was made in accordance with established laboratory criteria (including measurements of SA, PRA, urinary excretion of aldosterone and metabolites, imaging techniques and response to treatment). RESULTS: Although mean serum potassium values were significantly lower (P<0.001) in the PA group compared with the EH group, 61% of PA subjects were normokalaemic (3.4-5.2 mmol/l). The SA/PRA ratio alone identified 94% of the patients with PA, but was false positive in 30% of the patients with EH. The SA/PRA ratio together with SA>150 g/ml increased the diagnostic accuracy, led to the correct identification of 84% of the patients with PA, and decreased the false-positive rate to 3%. A multivariate binary logistic regression analysis based on SA and PRA was performed, which identified PA with 90% sensitivity and 91% accuracy. The SA(2)/PRA or the SA(3)/PRA ratio was found useful for simplification of the regression analysis. Antihypertensive medication influenced SA, PRA and the SA/PRA ratio only in EH patients. In EH patients taking beta-adrenoceptor antagonists PRA tended to be lower, leading to a significantly higher SA/PRA ratio and therefore increasing the false-negative rate. CONCLUSION: To reduce false-positive results in screening for PA, and thereby avoid unnecessary and cost-intensive diagnostic procedures, SA should be taken into account in addition to the SA/PRA ratio as a second screening criterion. Alternatively, the SA(2)/PRA or the SA(3)/PRA ratio is more accurate screening tests than the SA/PRA ratio. Beta-blockers should be avoided whilst screening for PA.     

Primary aldosteronism: Diagnostic and therapeutic considerations

Recent evaluations indicate that primary aldosteronism (PA) is common in patients with hypertension. In patients with mild to moderate hypertension the prevalence of PA is 5% to 10%, whereas in subjects with resistant hypertension the prevalence is approximately 20%. As such, PA has become the most common secondary cause of hypertension. Such high prevalence rates are distinctly different from earlier assessments in which PA was found to be rare, with a prevalence of generally less than 1% of hypertensive patients. Why PA is seemingly so much more common now than when first described remains unknown. Accurate identification of PA allows for specific therapy with aldosterone antagonists or with surgical resection of aldosteroneproducing adenomas. Determination of the plasma aldosterone to plasma renin activity ratio is an effective screen for PA in that it has a high negative predictive value even in the setting of ongoing antihypertensive therapy. Its specificity, however, is low such that a high ratio is suggestive of PA but must be confirmed by demonstration of high and autonomous secretion of aldosterone.     

新疆乌鲁木齐地区原发性醛固酮增多症105例临床分析

目的分析原发性醛固酮增多症(PA)的临床表现、辅助检查及治疗情况。方法对1999年7月至2005年3月间连续确诊的105例患者的临床资料进行回顾性分析。结果89例患者中有低血钾者占85%,血浆立、卧位肾素活性处于正常低值,立、卧位醛固酮水平均增高。醛固酮和肾素活性比值(ARR)>25者占71%,ARR>50者占8%。81例行B超检查,99例行CT检查,20例行MRI检查,其阳性率分别为:51.9%,80.8%,85%。58例原发性醛固酮增多症患者行手术治疗,其中43例血压均恢复正常,15例仍需要药物继续控制血压。结论血浆肾素活性,血浆醛固酮水平,以及血浆醛固酮和肾素活性比值(ARR)是原发性醛固酮增多症的主要定性诊断方法。CT是原发性醛固酮增多症的主要定位诊断依据。外科手术是治疗原发性醛固酮增多症的重要方法。