Background
Methods
Results
# | Paper, year of publication Study design (prospective or retrospective) Country | Study population (hypertension, resistant hypertension, others) | Inclusion criteria (IC) and exclusion criteria (EC) | Population characteristics Number of patients screened for PA Sex (%M, %F) Age (years) mean (SD or range) | Handling of BP medications | Serum K (mmol/L) (SD or range) | Assays Assay, unit of measurement | % fulfilled screening criteria, % proceeded to confirmatory testing, % tested positive on confirmatory test | ARR threshold | Confirmatory testing (threshold) (if SIT, seated or supine) | Final diagnoses, PA prevalence |
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1 | Galati (2016) [10] Prospective USA | All hypertension | IC: ≥ 18 years, 2x BP > 140/90 or treatment with antihypertensive agents EC: Current use of MRA, systemic steroid, serum creatinine >1.5 mg/dL (>133 µmol/L), previously screened for PA by physicians or already enrolled in another clinical trial | N = 296 32%M, 68%F PA cases: 59 (14.1) Controls:59 (14) | Did not discontinue antihypertensive treatment except MRA | PA cases: 3.96 (0.5) Controls: 4.16 (0.4) | Aldosterone: assay not specified, ng/dL Renin: assay not specified, ng/mL/h | 14/296 (4.7%) screened positive 6/14 (42.9%) proceeded to confirmatory OSLT 2/6 (33.3%) tested positive on confirmatory test | ARR ≥ 20 ng/dL per ng/mL/h with PAC ≥ 10 ng/dL and suppressed PRA ( < 1 ng/mL/h) | OSLT. PA if post-OSLT U NA > 200 mmol/day and U aldosterone >12 µg/day (or > 33 nmol/day) | PA prevalence, 0.7% |
2 | Volpe (2013) [11] Prospective Sweden | Newly diagnosed hypertension or had already been treated for SBP > 140 mmHg and/or DBP > 90 mmHg | IC: 18–70 years EC: Secondary hypertension, heart failure, myocardial infarction, transient ischaemic attack/stroke within last 6 months, creatinine >130 µmol/L, malignancy, severe illness, unable to consent to study Excluded 9 patients because of severe illness, cardiovascular disease or renal failure that preclude confirmatory testing | N = 178 41%M, 59%F 62 (25–70) | Stopped amiloride and MRA > 4 weeks. If ARR elevated and on beta blocker or non-steroidal anti-inflammatory drug, withdraw for 2 weeks. Given hydralazine, doxazosin, raised dose of calcium antagonista | Majority (93%) had normal K levels Potassium supplement if hypoK | Aldosterone: Siemens Coat-A-Count RIA kit, pmol/L Renin: Electrabox CISBIO immunoradiometric assay, ng/L | 6/178 (3.4%) screened positive All 6/6 (100%) proceeded to confirmatory testing 2/6 (33.3%) tested positive on confirmatory test 1/6 had PA confirmed before investigation was started | ARR > 50 pmol/ng (chosen to reduce risk of false negative ARR due to suppressive effects of medications) and PAC > 350 pmol/L.b If ARR elevated, repeated ARR and collect 24 h U aldosterone/NA/K. If U aldosterone elevated (reference interval for urine aldosterone 5.5–35 nmol/24 h), refer for confirmation PA highly unlikely if PRC > 33 ng/L | OSLT (24 h U aldosterone during increased oral salt intake (U NA > 200 mmol/24 h)), or FST. Post-OSLT 24 h U aldosterone threshold and post-FST PAC threshold for PA were not stated | PA prevalence, 1.6% If including 3 more patients with ‘pathological ARR’ but who declined further investigation, PA prevalence, 3.3% |
3 | Xu (2020) [14] Prospective China | All newly diagnosed hypertension | IC: 18–75 years; new diagnosis (within 12 months) of hypertension, not taking antihypertensives EC: Other causes of secondary hypertension, eGFR <30, severe heart failure New York Heart Association class III | N = 1020 65%M, 35%F All: 51 Non-PA: 50 (43–60) Probable PA: 54 (49–66) PA: 47 (35–55) | Severe hypertension: commenced on non-dihydropyridine CCB, terazosin or doxazosin | PA: 3.9 (3.6–4.2) | Aldosterone: DiaSorin LIAISON chemiluminescent immunoassay, ng/dL Renin: DiaSorin LIAISON chemiluminescent immunoassay, mU/L | 93/1020 (9.1%) screened positive 61/93 (65.6%) proceeded to confirmatory testing 40/61 (65.6%) tested positive on confirmatory test | ARR > 20 ng/mU (>55 pmol/mU) with PAC >10 ng/dL (>277 pmol/L) | CCT as first test. If post-CCT PAC indeterminate (8–11 ng/dL) then SIT PA if post-CCT PAC > 11 ng/dL or post-SIT PAC > 6 ng/dL | Prevalence, 4% (40/988) PA, 3% probable PA 8 APA, 21 BAH, 11 indeterminate |
4 | Kayser (2018) [15] Retrospective The Netherlands | Untreated hypertension | IC: Newly diagnosed, untreated hypertension ≥18 years EC: Prior use of antihypertensives, hypertensive crisis, heart failure New York Heart Association class II-IV, eGFR <45, pregnancy, breast feeding, diabetes mellitus, presence of severe comorbidity (seriously interfering with diagnostics or possible therapy) | N = 361 52%M, 48%F 53.4 (11.1) | Subjects with prior use of antihypertensives were excluded | PA negative: 4.43 (0.33) PA positive: 4.11 (0.26) | Aldosterone: Siemens Coat-A-Count RIA (Aug 2013 – Dec 2014), pmol/L Beckman Coulter Active ALD RIA (Dec 2014 – Dec 2015), pmol/L Renin: Diagnostic Systems Laboratories DSL-2100 active REN immunoradiometric assay, mU/L | 92/361 (35.5%) screened positive 72/92 (78.3%) proceeded to confirmatory testing 9/72 (12.5%) tested positive on confirmatory test | ARR > 40 pmol/mU and PAC >400 pmol/L | Semi-recumbent SIT. PA if post-SIT PAC > 280 pmol/L; PA excluded if post-SIT PAC < 140 pmol/L If post-SIT PAC indeterminate (140–280 pmol/L), SIT repeated; if still indeterminate, PA diagnosis by consensus | Prevalence, 2.6% (9/343) |
5 | Monticone (2017) [18] Prospective Italy | Newly or previously diagnosed hypertension 19 general practices | IC: 18–60 years, newly or previously diagnosed hypertension EC: Not stated | N = 1672 57%M, 43%F Mean age not stated | All interfering medications withdrawn for >4 weeks (6 weeks for diuretics and MRAs) CCB and/or doxazosin used to control BP | HypoK corrected with K supplement | Aldosterone: ng/dL Solid-phase RIA ALDOCTK-2 (DiaSorin) Renin: ng/mL/h RENCTK RIA kit (DiaSorin) | 232/1672 (13.9%) screened positive All 232/232 (100%) proceeded to confirmatory testing 99/232 (42.7%) tested positive on confirmatory test | ARR ≥ 30 ng/dL per ng/mL/h) (≥830 pmol/L per ng/mL/h) and PAC >10 ng/dL (>277 pmol/L) | SIT. PA if post-SIT PAC > 5 ng/dL (>139 pmol/L) If contraindication to acute volume expansion, CCT; PA if post-CCT ARR > 30 ng/dL per ng/mL/h | Prevalence, 5.9% (99/1672) Adrenal vein sampling was performed in all patients: 65% BAH, 27% APA, 8% Undetermined |
6 | Westerdahl (2011) [12] Prospective Sweden | Newly diagnosed, medical untreated hypertension 6 primary health care | IC: Newly diagnosed, medically untreated hypertension EC: Not stated | N = 200 43%M, 57%F Female: range, 24–75 years Male: range, 21–75 years | Doxazosin or amlodipine for BP management | PA: 3.7 (IQR 0.5) | Aldosterone: Aldosterone Coat-A-Count, pmol/L Renin: Cis-Bio Renin III (International France) direct method, mU/L | 36/200 (18.0%) screened positive 27/36 (75.0%) proceeded to confirmatory testing 11/27 (40.7%) tested positive on confirmatory test | One or two ARR > 65 pmol/mU | FST. Post-FST PAC threshold 225 pmol/L based on a previous study31 | Prevalence, 5.5% (11/200) with incomplete PAC suppression post-FST |
7 | Schmiemann (2012) [16] Prospective Germany | BP > 140/90 mmHg while on ≥3 antihypertensives 2 urban group practices in Northern Germany | IC: BP > 140/90 mmHg while on ≥3 antihypertensives EC: Pregnancy, known secondary hypertension, necessity of spironolactone | N = 63 30%M, 70%F Mean 69 (SD 10.4) | ARR after cessation of beta-blockers for 2 weeks (4 weeks for spironolactone) | Pre-existing hypoK corrected | Aldosterone: RIA, pg/mL Renin: RIA, pg/mL | 15/63 (23.8%) screened positive 3/15 (20.0%) proceeded to confirmatory testing 3/3 (100%) tested positive on confirmatory test | ARR > 45 pg/mL:pg/mL and PAC > 310 pg/mL | “Sodium chloride loading test” and/or diagnostic imaging It is unclear if the “sodium chloride loading test” is SIT or OSLT | Prevalence, 4.8% (3/63) 2 APA, 1 IHA |
8 | Westerdahl (2006) [13] Prospective Sweden | Hypertension | IC: 75 years of age or younger EC: insulin-dependent diabetes mellitus, dementia, stroke, mental health disorder, malignant tumours | N = 200 Sex breakdown not stated Mean age not stated | Beta blockers, ACE-I, alpha-1 receptor blocking, angiotensin II-antagonists withdrawn 2 weeks before CCBs continued | ARR > 100 pmol/L per ng/L: 3.9 (0.3) ARR < 100 pmol/L per ng/L: 4.0 (0.2) | Aldosterone: RIA DPC Skafte AB, pmol/L Renin: Pasteur method (Elektrabox), ng/L | 50/200 (25.0%) screened positive 26/50 (52.0%) proceeded to confirmatory testing 16/26 (61.5%) tested positive on confirmatory test | ARR > 100 pmol/L per ng/L Confirmed by in-house ARR (age 21–57 years, 11 men, 17 women) and derived upper limit by mean + 2 SD | FST. Post-FST PAC > 160 pmol/L on day 5, in sitting position after 15-min rest | Prevalence, 8.5% (17/200) FST: 16/26 had incomplete PAC suppression; 1 had previously diagnosed PA |
9 | Loh (2000) [17] Prospective Singapore | Hypertension 2 large primary care clinics | IC: Not stated EC: Renal impairment (serum creatinine >140 µmol/L), treatment with spironolactone or glucocorticoids | N = 350 All: 39%M, 61%F PA: 56%M, 44%F EH: 38%M, 62%F All: 55.2 years (SD 8.6) PA: 50.6 years (11.3) EH: 55.4 years (8.6) | No description of withholding or adjusting medications | PA: 3.7 (0.1) EH: 4.2 (0.0) | Aldosterone: Coat-A-Count ALD RIA (Diagnostic Products) Renin: PRA GammaCoat PRA RIA (INCSTAR Corp) | 63/350 (18.0%) screened positive 56/63 (88.9%) proceeded to confirmatory testing 16/56 (28.6%) tested positive on confirmatory test | ARR > 20 ng/dL:ng/ml/h and PAC > 15 ng/dL (>416 pmol/L) based on 95th percentile ARR and 75th percentile PAC derived from healthy normotensive volunteers | Potassium supplementation if hypokalaemia SIT (seated). PA if post-SIT PAC failed to suppress to <10 ng/dL (<277 pmol/L) | Estimated prevalence, 5.1% Computed tomography and adrenal vein sampling: 8 potentially curable by unilateral adrenalectomy |
Study | True Positive ARR | False Positive ARR | Population | ARR Threshold (pmol/mU) | ARR Threshold (pmol/ng) | ARR Threshold (ng/mU) | ARR Threshold (ng/dL:ng/ml/h) |
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Galati (2016) [10] | 2/6 (33.3%) | 4/6 (66.7%) | Hypertension | ARR ≥ 67 pmol/mU with PAC ≥ 277 pmol/L and suppressed PRC (<8.2 mU/L) | ARR > 108 pmol/ng with PAC ≥ 277 pmol/L and suppressed PRC (<8.2 mU/L) | ARR > 24 ng/mU | *ARR ≥ 20 ng/dL per ng/ml/h with PAC ≥ 10 ng/dL and suppressed PRA (<1 ng/mL/h) |
Volpe (2013) [11] | 2/6 (33.3%) | 4/6 (66.7%) | Hypertension | ARR > 31 pmol/mU and PAC > 350 pmol/L | *ARR > 50 pmol/ng and PAC > 350 pmol/L | ARR > 11 ng/mU and PAC >13 ng/dL | ARR > 9 ng/dL:ng/ml/h and PAC > 13 ng/dL |
Xu (2020) [14] | 40/93 (43.0%) | 53/93 (57.0%) | Hypertension | *ARR > 55 pmol/mU and PAC > 277 pmol/L | ARR > 89 pmol/ng and PAC > 277 pmol/L | *ARR > 20 ng/mU and PAC > 10 ng/dL | ARR > 16 ng/dL:ng/ml/h and PAC > 10 ng/dL |
Kayser (2018) [15] | 9/74 (12.2%) | 65/74 (87.8%) | Hypertension | *ARR > 40 pmol/mU and PAC > 400 pmol/L | ARR > 65 pmol/ng and PAC > 400 pmol/L | ARR > 14 ng/mU and PAC > 15 ng/dL | ARR > 12 ng/dL:ng/ml/h and PAC > 15 ng/dL |
Monticone (2017) [18] | 99/232 (42.7%) | 133/232 (57.3%) | Hypertension | ARR ≥ 100 pmol/mU and PAC > 277 pmol/L | ARR ≥ 161 pmol/ng and PAC > 277 pmol/L | ARR ≥ 35 ng/mU and PAC > 10 ng/dL | *ARR > 30 ng/dL per ng/ml/h (>830 pmol/L per ng/mL/h) and PAC > 10 ng/dL (>277 pmol/L) |
Westerdahl (2011) [12] | 11/32 (34.4%)a | 21/32 (65.6%)a | Hypertension | *ARR > 65 pmol/mU | ARR > 105 pmol/ng | ARR > 23 ng/mU | ARR > 19 ng/dL:ng/ml/h |
Schmiemann (2012) [16] | 3/15 (20.0%) | 12/15 (80.0%) | Resistant hypertension | ARR > 78 pmol/mU and PAC > 859 pmol/L | ARR > 126 pmol/ng and PAC > 859 pmol/L | ARR > 28 ng/mU and PAC > 310 pg/mL (note: unit for PAC is pg/mL) | *ARR > 45 pg/mL per pg/mL and PAC > 310 pg/mL (note: unit for ARR is pg/mL per pg/mL) |
Westerdahl (2006) [13] | 17/26 (65.4%) | 9/26 (34.6%) | Hypertension | ARR > 63 pmol/mU | *ARR > 100 pmol/ng | ARR > 20 ng/mU | ARR > 18 ng/dL:ng/ml/h |
Loh (2000) [17] | 16/56 (28.6%) | 40/56 (71.4%) | Hypertension | ARR > 67 pmol/mU and PAC > 416 pmol/L | ARR > 108 pmol/ng and PAC > 416 pmol/L | ARR > 20 ng/mU and PAC > 15 ng/dL | *ARR > 20 ng/dL per ng/ml/h and PAC > 15 ng/dL |