儿茶酚胺-β-肾上腺素能受体-cAMP系统与高血压心血管事件的预测

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

作者信息

Peng Ying-Xin, Shan Jiang, Qi Xiao-Yong, Zhang Su-Jun, Ma Shu-Ping, Wang Na, Li Jun-Ping, Xue Hao, Wu Min

机构信息

Department of Cardiology, College of Medicine, Zhejiang University and Cardiac Center, Hebei Provincial People's Hospital, Shijiazhuang, China.

出版信息

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

DOI:10.1111/j.1440-1681.2006.04350.x

PMID:16487266

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.

摘要

虽然循环血浆儿茶酚胺水平升高对高血压患者心脏结构和功能重塑的重要性已有充分记载，但尚不清楚儿茶酚胺-β-肾上腺素能受体（βAR）-环磷酸腺苷（cAMP）系统能否预测不同的心血管事件。2. 共有601例确诊的高血压患者，其基线和随访时的血浆去甲肾上腺素（NA）和肾上腺素（Adr）水平、淋巴细胞βAR密度（B(max)）以及外周血淋巴细胞内cAMP水平（最后一次检查相隔60±26个月），随后又随访了24±12个月。3. 最后一次随访后，139例患者（23.1%）发生了心血管死亡、非致命性心肌梗死（MI）和中风的复合终点事件。在Cox分析中，在调整了其他标准因素以及治疗效果后，NA（风险比1.22；95%置信区间（CI）1.17 - 1.28；P = 0.0008）、Adr（风险比1.53；95% CI 1.18 - 2.00；P = 0.002）、βAR（风险比1.12；95% CI 1.06 - 1.17；P = 0.007）和cAMP（风险比1.15；95% CI 1.09 - 1.21；P = 0.005）分别预测心血管死亡率。去甲肾上腺素、肾上腺素、βAR和淋巴细胞内cAMP分别预测致命性/非致命性心肌梗死；NA和Adr预测致命性/非致命性中风，而B(max)和淋巴细胞内cAMP水平不是致命性/非致命性中风的显著预测指标。当根据NA或Adr（中位数4 nmol/L）、B(max)（中位数600 fmol/10(7)个细胞）和cAMP（中位数5.0 pmol/mg蛋白）将研究人群分为高于和低于中位数两组时，高于中位数的患者有复合心血管终点事件（所有P < 0.001）和较高的心血管死亡率（所有P < 0.01，对数秩检验）。4. 这些结果表明，血浆NA和Adr是心血管死亡率、心肌梗死和中风的重要预测指标。B(max)和淋巴细胞内cAMP水平是心血管死亡率和心肌梗死的重要预测指标，但不是中风的预测指标。