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

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.

Cardiac risk stratification in patients with congestive heart failure: a catecholamines-beta-adrenoceptor-cAMP pathway.

OBJECTIVE: To investigate the stratification risk of catecholamines-beta-adrenoceptor (beta-AR)-cAMP pathway for cardiogenic death events in patients with congestive heart failure (CHF). METHODS: A total of 83 identified CHF patients with a baseline and follow-up plasma levels of norepinephrine (NE) and epinephrine (E), lymphocytes beta-AR density (Bmax), and intralymphocyte cAMP content in peripheral blood were followed up. Major cardiogenic death events were registered. RESULTS: The period between the initial entry and the last follow-up measurement were 51 +/- 16 months, the total duration of clinical follow-up after the last measurement were 14 +/- 8 months. During follow-up, 39 patients died of cardiogenic (sudden death 17 patients, worsening heart failure 22 patients). Persistence of high NE, E, and cAMP from baseline to follow-up were confirmed as risk predicting factors of cardiovascular events. Persistence NE above 4.0 nmol/L, E above 3.5 nmol/L, and the intralymphocyte cAMP content above 3.5 pmd x mg(-1) x pro(-1) from baseline to follow-up were significant adverse prognostic predictors. The major cardiogenic death events rates per 100 patients-years were 1.33 and 4.82 in patients with NE below and above 4.0 nmol/L (HR: 2.91; 95% CI: 1.08-7.33; P = 0.015); were 1.42 and 4.36 in the patients with E levels below and above 3.5 nmol/L (HR: 2.64; 95% CI: 1.02-6.41; P = 0.019); were 1.81 and 4.67 in the patients with the intralymphocyte cAMP content below and above 3.5 pmd x mg(-1) x pro(-1) (HR: 2.79; 95% CI: 1.04-6.83; P = 0.017), but difference was not significant between the beta-AR density below and above median. CONCLUSIONS: Persistent increase in circulating catecholamines and intralymphocyte cAMP content may increase the long-term mortality in CHF patients.