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The catecholamine-beta-adrenoreceptor-cAMP system and prediction of cardiovascular events in hypertension
Ying-Xin Peng1, Jiang Shan, Xiao-Yong Qi
1Department of Cardiology, College of Medicine, Zhejiang University and Cardiac Center, Hebei Provincial People's Hospital, Shijiazhuang, China. upls@hotmail.com
Insights
Elevated plasma catecholamines, including noradrenaline and adrenaline, predict cardiovascular events in hypertensive patients. Beta-adrenoreceptor density and cAMP levels also predict mortality and myocardial infarction, but not stroke.
Area of Science:
- Cardiology
- Hypertension Research
- Biomarkers
Background:
- Elevated plasma catecholamines are linked to hypertension-related cardiac remodeling.
- The predictive value of the catecholamine-beta-adrenoreceptor (beta AR)-cAMP system for cardiovascular events remains unclear.
Purpose of the Study:
- To investigate whether plasma catecholamine levels, beta AR density, and intra-lymphocyte cAMP levels can predict cardiovascular events in hypertensive patients.
Main Methods:
- A cohort of 601 hypertensive patients had baseline and follow-up measurements of plasma noradrenaline (NA), adrenaline (Adr), lymphocyte beta AR density (Bmax), and intra-lymphocyte cAMP.
- Patients were followed for a composite endpoint of cardiovascular death, non-fatal myocardial infarction (MI), and stroke.
Main Results:
- Plasma NA and Adr, lymphocyte beta AR density, and cAMP levels independently predicted cardiovascular mortality.
- NA, Adr, beta AR, and cAMP predicted fatal/non-fatal MI. NA and Adr predicted stroke, but Bmax and cAMP did not.
- Patients with levels above median for NA, Adr, Bmax, and cAMP had significantly higher composite cardiovascular endpoints and cardiovascular death.
Conclusions:
- Plasma noradrenaline and adrenaline are significant predictors of cardiovascular mortality, MI, and stroke in hypertensive individuals.
- Lymphocyte beta AR density and cAMP levels predict cardiovascular mortality and MI, but not stroke.
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.
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