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THE CATECHOLAMINE–β-ADRENORECEPTOR–cAMP SYSTEM AND PREDICTION OF CARDIOVASCULAR EVENTS IN HYPERTENSION

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SUMMARY



Although the importance of elevated circulating plasma catecholamines on cardiac structural and functional remodelling of hypertension is well documented, it is unclear whether the catecholamine–b-adrenoreceptor (bAR)–cAMP system can predict different cardiovascular events.



A total of 601 identified hypertensive patients with baseline and follow-up plasma levels of noradrenaline (NA) and adrenaline (Adr), lymphocyte bAR density (Bmax) and intralymphocyte cAMP levels in peripheral blood (last examination 60 ± 26 months apart) were followed up for an additional 24 ± 12 months.



After the last follow up, a composite end-point of cardiovascular death, non-fatal myocardial infarction (MI) and stroke occurred in 139 patients (23.1%). In Cox analyses, adjusting for other standard factors as well as treatment effect, NA (hazard ratio 1.22; 95% confidence interval (CI) 1.17–1.28; P = 0.0008), Adr (hazard ratio 1.53; 95% CI 1.18–2.00; P = 0.002), bAR (hazard ratio 1.12; 95% CI 1.06–1.17; P = 0.007) and cAMP (hazard ratio 1.15; 95% CI 1.09–1.21; P = 0.005) separately predicted cardiovascular mortality. Noradrenaline, Adr, bAR and intralymphocyte cAMP separately predicted fatal/non-fatal MI; NA and Adr predicted fatal/non-fatal stroke, whereas Bmax and intralymphocyte cAMP levels were not a significant predictor of fatal/non-fatal stroke. When stratifying the study population by NA or Adr (median 4 nmol/L), Bmax (median 600 fmol/107 cells) and cAMP (median 5.0 pmol/mg protein) above and below the median values in both parameters categories, patients above the median had composite cardiovascular end-point (all P < 0.001) and high cardiovascular death (all P < 0.01, log-rank test).



These results suggest that plasma NA and Adr are significant predictors of cardiovascular mortality, MI and stroke. The Bmax and intralymphocyte cAMP levels are significant predictors of cardiovascular mortality and MI, but not stroke.
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Keywords: adrenaline; myocardial infarction; noradrenaline; stroke; survival

Document Type: Research Article

Publication date: March 1, 2006

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