ABSTRACT
BACKGROUND: Patients with primary aldosteronism (PA) experience more cardiovascular events compared to patients with essential hypertension (EHT), independent from blood pressure levels. In animals, mineralocorticoid receptor antagonists limit ischaemia-reperfusion (IR) injury by increasing extracellular adenosine formation and adenosine receptor stimulation. Adenosine is an endogenous compound with profound cardiovascular protective effects. Firstly, we hypothesized that patients with PA have lower circulating adenosine levels which might contribute to the observed increased cardiovascular risk. Secondly, we hypothesized that by this mechanism, patients with PA are more susceptible to IR compared to patients with EHT. DESIGN: In our prospective study in 20 patients with PA and 20 patients with EHT, circulating adenosine was measured using a pharmacological blocker solution that halts adenosine metabolism after blood drawing. Brachial artery flow-mediated dilation (FMD) before and after forearm IR was used as a well-established method to study IR injury. RESULTS: Patients with PA had a 33% lower adenosine level compared to patients with EHT (15.3 [13.3-20.4] vs 22.7 [19.4-36.8] nmol/L, respectively, P < .01). The reduction in FMD after IR, however, did not differ between patients with PA and patients with EHT (-1.0 ± 2.9% vs -1.6 ± 1.6%, respectively, P = .52). CONCLUSIONS: As adenosine receptor stimulation induces various powerful protective cardiovascular effects, its lower concentration in patients with PA might be an important novel mechanism that contributes to their increased cardiovascular risk. We suggest that modulation of the adenosine metabolism is an exciting novel pharmacological opportunity to limit cardiovascular risk in patients with PA that needs further exploration.
Subject(s)
Adenosine/blood , Brachial Artery/physiopathology , Essential Hypertension/blood , Hyperaldosteronism/blood , Reperfusion Injury/physiopathology , Vasodilation/physiology , Adult , Case-Control Studies , Essential Hypertension/physiopathology , Female , Forearm , Humans , Hyperaldosteronism/physiopathology , Male , Middle Aged , Prospective StudiesABSTRACT
BACKGROUND: The incidence of cardiovascular events is higher in patients with primary aldosteronism than in patients with essential hypertension (EHT), despite similar blood pressure levels. This suggests detrimental cardiovascular effects of aldosterone. Amongst others, it has been suggested that galectin-3 (Gal-3) is a key mediator in aldosterone-induced myocardial fibrosis. OBJECTIVE: We studied whether patients with primary aldosteronism have higher plasma Gal-3 concentrations than patients with EHT and evaluated its reversibility after adrenalectomy. METHODS: In a retrospective cohort from our tertiary referral centre, we measured plasma Gal-3 concentrations in 78 patients with primary aldosteronism, 39 cured primary aldosteronism patients after adrenalectomy and 56 patients with EHT. Paired samples were available in 11 patients (preadrenalectomy and postadrenalectomy). We compared plasma Gal-3 levels by univariate analysis of covariance with correction for cardiovascular risk factors, plasma creatinine concentration, plasma potassium levels and alcohol intake. RESULTS: Adjusted plasma Gal-3 concentrations in patients with primary aldosteronism, patients after adrenalectomy and patients with EHT were 11.39â±â0.60, 11.64â±â0.81 and 11.41â±â0.73âng/ml, respectively (meanâ±âSD; Pâ=â0.95). In 11 patients of whom paired samples were available, mean Gal-3 concentrations increased from 10.03â±â1.67âng/ml preadrenalectomy to 14.36â±â2.07âng/ml postadrenalectomy (Pâ<â0.01). CONCLUSION: In patients with primary aldosteronism, plasma Gal-3 concentrations are not elevated when compared with patients with EHT, and levels do not decrease after adrenalectomy. These results are in contrast to previous studies and do not support a pathophysiological role of plasma Gal-3 in the increased cardiovascular risk in patients with primary aldosteronism.
