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.
Department of Cardiology, College of Medicine, Zhejiang University and Cardiac Center, Hebei Provincial People's Hospital, Shijiazhuang, China. upls@hotmail.com
Ying-Xin
YX
Peng
Jiang
J
Shan
Xiao-Yong
XY
Qi
Su-Jun
SJ
Zhang
Shu-Ping
SP
Ma
Na
N
Wang
Jun-Ping
JP
Li
Hao
H
Xue
Min
M
Wu
D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000209:etiology / Q000401:mortality / Q000503:physiopathology*; D002395:Catecholamines / Q000097:blood / Q000502:physiology*; D000242:Cyclic AMP / Q000097:blood / Q000502:physiology*; D004837:Epinephrine / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000401:mortality / Q000503:physiopathology*; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000401:mortality; D009638:Norepinephrine / Q000097:blood; D011943:Receptors, Adrenergic, beta / Q000378:metabolism / Q000502:physiology*; D012307:Risk Factors; D020521:Stroke / Q000209:etiology / Q000401:mortality; D016019:Survival Analysis
D002395:Catecholamines; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D009638:Norepinephrine; D004837:Epinephrine