The participation of vasopressin in the mechanisms of resistant hypertension is unclear. We compared plasma copeptin concentration, a surrogate marker for vasopressin secretion, between patients with resistant hypertension and those with controlled blood pressure (CBP), in a post hoc analysis of the Prise en charge de l’Hypertension Artérielle RESistante au traitement trial.
After 4-week treatment with irbesartan 300 mg/day, hydrochlorothiazide 12.5 mg/day, and amlodipine 5 mg/day (baseline), 166 patients were classified as having resistant hypertension (n = 140) or CBP (n = 26) by ambulatory BP monitoring. Patients with resistant hypertension were then randomized for 12 weeks of sequential nephron blockade (n = 74) or sequential renin–angiotensin system blockade (n = 66). Plasma copeptin concentration was measured at baseline and week 12 by immunoassay.
Baseline plasma copeptin concentration was positively associated with male sex, plasma osmolality, BP, and negatively with glomerular filtration rate. It was higher in the resistant hypertension than in the CBP group [geometric mean 5.7 (confidence interval 95% 5.1–6.4) vs. 2.9 (2.3–3.9) fmol/ml, adjusted P
< 0.0001). The relationship between plasma copeptin concentration and urinary osmolality was similar in the two groups. At 12 weeks, plasma copeptin concentration in patients whose BP was controlled by sequential nephron blockade or sequential renin–angiotensin system blockade [6.8 (5.6–8.2) and 4.3 (3.0–5.9) fmol/ml, respectively) remained significantly higher than in patients with CBP at baseline (P
< 0.0001 vs. both).
In patients with resistant hypertension, plasma copeptin concentrations were approximately two-fold higher than those of patients with CBP, after adjustment for plasma osmolality. This difference was not accounted for by renal resistance to vasopressin, suggesting a primary reset of osmostat.
aServiço de Saúde da Região Autónoma da Madeira, Dr Rui Adriano de Freitas Health Centre, Funchal, Madeira, Portugal
bAssistance Publique Hôpitaux de Paris, Centre d’Investigation Clinique, Hôpital Européen Georges Pompidou
cUniversité Paris Descartes, Faculté de Médecine, Sorbonne Paris Cité
dINSERM, CIC 1418
eAssistance Publique Hôpitaux de Paris, département de génétique
fAssistance Publique Hôpitaux de Paris, Unité d’Hypertension Artérielle, Hôpital Européen Georges Pompidou, Paris, France
Correspondence to Anne Blanchard, Assistance Publique Hôpitaux de Paris, Centre d’investigation Clinique, Hôpital Européen Georges Pompidou, 20–40 rue Leblanc 75015 Paris, France. Tel: +00 33 1 56 09 29 13; fax: +00 33 1 56 09 29 29; e-mail: email@example.com
Abbreviations: 95% CI, 95% confidence interval; ANCOVA, analysis of covariance; AVP, arginine vasopressin; BP, blood pressure; CBP, controlled blood pressure; dASBP, daytime ambulatory SBP; eGFR, estimated glomerular filtration rate; EOsm, effective plasma osmolality; POsm, plasma osmolality; RAS, renin–angiotensin system; SNB, sequential nephron blockade; SRASB, sequential renin–angiotensin system blockade; UOsm, urine osmolality
Received 11 May, 2016
Revised 21 July, 2016
Accepted 5 August, 2016
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