Coronary Disease Morbidity and Mortality in a Population

描述(申请人提供)：冠心病(CHD)是主要的死亡原因，年龄调整死亡率的下降反映了死亡发生向老年人的转变。此外，随着肥胖和糖尿病的流行，心血管疾病的惊人发病率可能会增加。美国心脏协会和2010年健康人定义了改善心血管健康的目标，这需要人口监测来评估进展情况。我们的研究通过测量CHD事件、评估其预后和在地理上定义的人群中的管理来响应这一需求。我们证明心肌梗死(MI)的发病率随着时间的推移保持稳定，而随着女性和老年人的增加，年龄和性别的趋势有所不同。冠心病死亡率的趋势也表明，冠心病的负担正在向妇女和老年人转移。心肌梗死发病率的趋势与冠心病发病率平行，支持依赖心肌梗死评估冠心病趋势的传统方法。心肌梗死的定义随后被修改为推荐肌钙蛋白作为首选生物标记物。由于肌钙蛋白比以前的生物标志物(肌酸激酶及其MB部分)更敏感，因此假设新的定义将改变MI的数量和病例组合。为了验证这一假设，我们用一种新的前瞻性方法扩大了我们的被动监测，测量了同一人群中所有病例的新的和以前的生物标记物，并确定新的标准显著增加了误诊的数量，但增加的幅度根据临床对新标准的接受程度而不同。重要的是，新的定义模糊了不稳定型心绞痛(UA)和心肌梗死(MI)之间的界限，因此CHD监测现在必须与包括UA在内的急性冠状动脉综合征(ACS)有关。生物标记物的变化也改变了病例组合和结果。最后，虽然肌钙蛋白可以预测急性冠脉综合征的风险，但其他标记物也可以提供预后信息。我们发现C反应蛋白(CRP)与心力衰竭(HF)和死亡有关，而脂蛋白相关磷脂酶A2(LP-PLA2)与死亡有关，但与心力衰竭或心肌梗死后缺血无关。这突显了风险预测的“多标记策略”的挑战，因为风险因时间或事件类型而异。此外，应评估新标记相对于已知指标的附加值。在目标1中，我们建议检查急性冠脉综合征(MI和UA)的发病率和存活率，以检验以下假设：ACS的发病率保持稳定，但MI的发病率增加，而UA的发病率下降，ACS的存活率提高，而MIS的存活率比UA差。在目标2中，前瞻性地描述病例组合并检验假设，即只满足肌钙蛋白标准的患者比符合CKMB标准的患者有更好的结果。目标3：检验新的生物标记物预测急性冠脉综合征后风险的假设，但相关性因生物标记物的类型和事件而异。我们将评估生物标志物的附加值，而不是已知预测指标的附加值。我们的研究在这种情况下是唯一可能的，因为它建立在先前赠款周期的成熟方法和结果的基础上，以整合社区中的被动监测和前瞻性研究。公共卫生相关性：这项研究将提供以急性冠脉综合征(包括不稳定心绞痛和心肌梗死)衡量的社区心脏病负担的重要信息。这将决定新的生物标志物在临床实践中预测不良事件风险的重要性。

DESCRIPTION (provided by applicant): Coronary heart disease (CHD) is the leading cause of death and the decline in age-adjusted mortality reflects a shift in the occurrence of death towards older persons. Further, the staggering morbidity of cardiovascular disease will likely increase with the obesity and diabetes epidemics. The American Heart Association and Healthy People 2010 defined goals to improve cardiovascular health, which require population surveillance to assess progress. Our study responds to this need by measuring CHD events, evaluating their prognosis and management in a geographically-defined population. We demonstrated that the incidence of myocardial infarction (MI) remained stable over time while trends diverged by age and sex with an increase in women and the elderly. CHD mortality trends also showed a shift in the burden of CHD towards women and the elderly. Trends in MI incidence paralleled CHD incidence, supporting the conventional approach of relying on MI to assess CHD trends. The definition of MI was then changed to recommend troponin as the preferred biomarker. As troponin is more sensitive than previous biomarkers (creatine kinase and its MB fraction), it was hypothesized that the new definition would change the number and case mix of MI. To test this hypothesis, we amplified our passive surveillance with a novel prospective approach, measured both new and previous biomarkers in all cases in the same population and determined that the new criteria markedly increased the number of MIs but the increment varied according to the clinical acceptance of the new criteria. Importantly, the new definition obscured the boundaries between unstable angina (UA) and MI such that CHD surveillance must now pertain to acute coronary syndromes (ACS) including UA. The biomarker change also altered case mix and outcome. Finally, while troponin predicts risk in ACS, other markers also offer prognostic information. We showed that C-Reactive Protein (CRP) was associated with heart failure (HF) and death while lipoprotein- associated phospholipase A2 (Lp-PLA2), was associated with death but not HF or ischemia post MI. This underscores the challenges of a "multimarker strategy" for risk prediction as risk differs by time or type of event. Further, the added value of novel markers over known indicators should be evaluated. We propose in Aim 1, to examine the incidence and survival of ACS (MI and UA) to test the hypotheses that incidence of ACS remained stable, but the incidence of MI increased while that of UA decreased and that the survival of ACS improved while MIs had worse survival than UA cases. In Aim 2, to prospectively characterize case mix and test the hypothesis that cases meeting only troponin criteria have better outcomes than those meeting CKMB- criteria. In Aim 3: to test the hypothesis that novel biomarkers predict risk after ACS but that the associations vary according to the type of biomarker and event. We will assess the added value of biomarkers over that of known predictors. Our research is uniquely possible in this setting as it builds on the proven method and findings of previous grant cycles to integrate passive surveillance and prospective studies in the community. PUBLIC HEALTH RELEVANCE: This research will provide important information on the burden of heart disease in the community as measured by acute coronary syndromes, including unstable angina and myocardial infarction. It will determine the importance of novel biomarkers to predict the risk of adverse events in clinical practice.