Validation of New Identified Cardiovascular Biomarkers in the Japanese General Population

社区研究的受试者从普通人群中招募（n= 26，469;女性65.4%，平均年龄=62岁）。在基线时测定血浆BNP水平、血清CRP和心血管危险因素。从区域卒中登记数据中确定了队列中的几个心血管终点（CVE），包括卒中（缺血性和出血性卒中）和心力衰竭（CHF）。结果（1）在男性中，经经典心血管危险因素和房颤校正后，血浆BNP水平最高四分位数发生缺血性脑卒中的危险比（HR）显著高于血浆BNP水平最低四分位数（HR=2.40; 95% CI=1.08 - 5.35; P=0.032）。血浆BNP水平升高（每增加1个标准差BNP值）与缺血性卒中风险升高相关（HR=1.45; 95%CI =1.01 - 2.08; P-0.0 关于我们 45）。血浆BNP水平高于第80百分位数者，缺血性脑卒中的危险性增加（HR=2.88，95% CI=1.63 ~ 5.09，P<0.001）。结果（2）在男性中，校正心血管危险因素后，高血压前期（preHT）组发生缺血性脑卒中的危险比（HR=2.65，95%CI，1.12-6.26）显著高于正常血压组（HR=2.65，95%CI，1.12-6.26），且高CRP水平（> 0.5mg/L）的PreHT组发生缺血性脑卒中的HR显著高于正常血压组（FIR = 2.65，95%CI，1.12-6.26）。HR = 4.04，95%CI，1.66-9.86）与高血压组（HR=3.98，95%CI，1.78-8.92）相当。而CRP水平低于0.5mg/L的PreHT患者HR（HR =1.10，95% CI，0.32-3.77）与正常对照组无显著性差异。在女性中，即使按hsCRP水平中位数分层，PreHT组也与缺血性卒中的HR增加无关。I结果（3）在校正包括房颤在内的传统心血管危险因素后，BNP水平高于第75百分位数时，CHF发生的危险比男性为13.4（p<0.001），女性为8.5（p<0.001）。同样，BNP对数水平每增加1 SD，男性风险比增加8.8（p<0.001），女性风险比增加6.7（p<0.001）。受试者工作特征曲线下面积对预测CHF的发生有显著意义（男性：0.853，女性：0.838）。此外，血浆BNP水平升高意味着男性任何原因死亡的高风险（高于第75百分位数;风险比=1.8，p=0.005：增加1 SD;风险比=1.4，p=0.024），但这种关系在女性中是次优的。少

Subjects of community-based study were recruited from the general population (n=26,469; women 65.4%, mean age=62 years). Plasma BNP levels, serum CRP and cardiovascular risk factors were determined at baseline. Several cardiovascular endpoints (CVEs) including stroke (ischemic and hemorrhagic stroke), and heart failure (CHF) in the cohort were identified from regional stroke registry data. A multivariate Cox regression analysis was performed to analyze the relationship between plasma BNP level, serum CRP, blood pressure and the risk of the onset of CVES.Results (1) In men, after adjustment for classical cardiovascular risk factors and atrial fibrillation, hazard ratio (HR) for ischemic stroke of the highest quartile of plasma BNP was significantly higher than that for the lowest quartile (HR=2.40; 95% CI=1.08 to 5.35; P=0.032). Increasing plasma BNP levels (1 SD increment per in log BNP values)were associated with an elevated risk of ischemic stroke (HR=1.45; 95% CI=1.01 to 2.08; P-0.0 … More 45). Values above the 80th percentile of plasma BNP were also associated with an increase in the risk of ischemic stroke (HR=2.88; 95% CI=1.63 to 5 09; P<0.001). Results (2) In men, after adjustment for cardiovascular risk factors, a significantly increased hazard ratio (BR) of ischemic stroke was found in the prehypertension (preHT) group (HR=2.65, 95% CI, 1.12-6.26) compared with the normotensive group, and further the HR for the onset of ischemic stroke for the PreHT with higher CRP level (> 0.5 mg/L) (FIR.=4.04, 95% CI, 1.66-9.86) was comparable to that for the hypertensive group (HR=3.98, 95% CI, 1.78-8.92). In contrast, the HR for the PreHT with lower CRP level (<0.5mg/L) (HR =1.10, 95% CI, 0.32-3.77) did not differ from that for the normotesive group. In women the PreHT group, even stratified by hsCRP level of median level was not associated with increased HR of ischemic stroke. I Results (3)After adjustment for traditional cardiovascular risk factors including atrial fibrillation, hazard ratios for CHF development for values above the 75th percentile of BNP were 13.4 (p<0.001)in men and 8.5 (p<0.001)m women. Similarly, each increment of 1SD in log BNP levels increased the hazard ratio by 8.8 (p<0.001)in men, and 6.7 (p<0.001)in women. The area under the receiver operating characteristic curve was significant for prediction of the onset of CHF (men; 0 853, women; 0.838). In addition, increased plasma BNP levels implied high risk of any-cause mortality m men (above the 75th percentile; hazard ratio=1.8, p=0.005: increment of 1SD; hazard ratio=1.4, p=0.024), but this relationship was suboptimal in women. Less