The catecholamine-beta-adrenoreceptor-cAMP system and prediction of cardiovascular events in hypertension

Clin Exp Pharmacol Physiol. 2006 Mar;33(3):227-31. doi: 10.1111/j.1440-1681.2006.04350.x.

Abstract

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-beta-adrenoreceptor (beta AR)-cAMP system can predict different cardiovascular events. 2. A total of 601 identified hypertensive patients with baseline and follow-up plasma levels of noradrenaline (NA) and adrenaline (Adr), lymphocyte beta AR density (B(max)) and intra-lymphocyte cAMP levels in peripheral blood (last examination 60+/-26 months apart) were followed up for an additional 24+/-12 months. 3. 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), beta AR (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, beta AR and intra-lymphocyte cAMP separately predicted fatal/non-fatal MI; NA and Adr predicted fatal/non-fatal stroke, whereas B(max) and intra-lymphocyte 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), B(max) (median 600 fmol/10(7) 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). 4. These results suggest that plasma NA and Adr are significant predictors of cardiovascular mortality, MI and stroke. The B(max) and intra-lymphocyte cAMP levels are significant predictors of cardiovascular mortality and MI, but not stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / physiopathology*
  • Catecholamines / blood
  • Catecholamines / physiology*
  • Cyclic AMP / blood
  • Cyclic AMP / physiology*
  • Epinephrine / blood
  • Female
  • Follow-Up Studies
  • Humans
  • Hypertension / complications
  • Hypertension / mortality
  • Hypertension / physiopathology*
  • Lymphocytes / metabolism
  • Male
  • Middle Aged
  • Myocardial Infarction / etiology
  • Myocardial Infarction / mortality
  • Norepinephrine / blood
  • Receptors, Adrenergic, beta / metabolism
  • Receptors, Adrenergic, beta / physiology*
  • Risk Factors
  • Stroke / etiology
  • Stroke / mortality
  • Survival Analysis

Substances

  • Catecholamines
  • Receptors, Adrenergic, beta
  • Cyclic AMP
  • Norepinephrine
  • Epinephrine