Pilot Untargeted Metabolomics for Primary Aldosteronism in Plasma (PUMPAP)
Primary aldosteronism (PA) is a common and likely under-diagnosed cause of secondary hypertension with associated cardiovascular morbidity and mortality. Current diagnosis comprises screening, confirmatory testing and sub-type classification (lateralisation) to distinguish unilateral disease (requiring surgery) from bilateral disease (requiring medical management). This multi-step process is complex and variable with a lack of uniformity in diagnostic protocols, standardised/reference assay methodologies, and diagnostic thresholds. There is evidence in the literature that targeted serum steroid panels may have a role in diagnosis of PA, and both targeted steroid panels and untargeted metabolomics in serum and urine are a promising area of research. This study aims to identify and recruit participants (n=40; 20 with confirmed PA and 20 with other causes of hypertension) willing to donate lithium heparin plasma for a metabolomics pilot study. This plasma will be interrogated through untargeted metabolomics using gas/liquid chromatography-mass-spectrometric methods and computational data processing to allow power calculations and inform experimental design for future studies. The utility of metabolites from the metabolomics dataset will be evaluated by comparison against current biomarkers for screening, diagnosis and lateralisation as well as radiology and histology acquired through routine diagnostic work-up. The long-term aim for larger studies is to identify suitable candidate analytes in plasma for future development into targeted, clinically-useful analyte panels.
⁃ Screening for PA to be performed in people with:
• sustained blood pressure (BP) above 150/100 mm Hg on each of three measurements obtained on different days, with hypertension (BP \>140/90 mm Hg) resistant to three conventional antihypertensive drugs (including a diuretic), or controlled BP (\<140/90 mm Hg) on four or more antihypertensive drugs.
• hypertension and spontaneous or diuretic-induced hypokalaemia.
• hypertension and adrenal incidentaloma.
• hypertension and sleep apnoea.
• hypertension and a family history of early onset hypertension or cerebrovascular accident at a young age (\<40 years).
• all hypertensive first-degree relatives of people with PA.
⁃ Subset of people being screened for PA who are eligible for inclusion in this study:
• 18 years of age or older.
• People under the care of LUHFT.
• Able to give informed consent.
• Having lithium heparin plasma samples collected as part of their routine care.