Coronary Disease Morbidity and Mortality in a Population

描述（由申请人提供）：冠心病（CHD）是导致死亡的主要原因，年龄调整死亡率的下降反映了死亡发生向老年人转移。此外，心血管疾病的惊人发病率可能会随着肥胖和糖尿病的流行而增加。美国心脏协会和健康人2010年确定了改善心血管健康的目标，这需要对人口进行监测以评估进展。我们的研究回应了这一需求，通过测量冠心病事件，评估其预后和在地理上定义的人群中的管理。我们证明心肌梗死（MI）的发生率随着时间的推移保持稳定，而趋势因年龄和性别而异，女性和老年人增加。冠心病死亡率趋势还表明，冠心病负担向妇女和老年人转移。心肌梗死发病率趋势与冠心病发病率趋势平行，支持依靠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改变为推荐肌钙蛋白作为首选生物标志物。由于肌钙蛋白比以前的生物标志物（肌酸激酶及其MB分数）更敏感，我们假设新的定义将改变心肌梗死的数量和病例组合。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。在同一人群的所有病例中测量了新的和以前的生物标志物，并确定新标准显着增加了MIs的数量，但增量根据新标准的临床接受程度而变化。重要的是，新的定义模糊了不稳定心绞痛（UA）和心肌梗死之间的界限，因此冠心病监测现在必须适用于包括UA在内的急性冠脉综合征（ACS）。生物标志物的改变也改变了病例组合和结果。最后，虽然肌钙蛋白可以预测ACS的风险，但其他标志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）和死亡相关，而脂蛋白相关磷脂酶A2 （Lp-PLA2）与死亡相关，但与心力衰竭或心肌梗死后缺血无关。这强调了“多标志物策略”在风险预测方面的挑战，因为风险随时间或事件类型的不同而不同。此外，应评估新标记物相对于已知指标的附加价值。我们在Aim 1中提出，研究ACS （MI和UA）的发病率和生存率，以检验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的生存率提高而MIs的生存率低于UA的假设。在目标2中，前瞻性地描述病例组合并检验假设，即仅符合肌钙蛋白标准的病例比符合CKMB-标准的病例有更好的结果。在目标3中：检验新的生物标志物预测ACS后风险的假设，但其相关性根据生物标志物和事件的类型而变化。我们将评估生物标志物在已知预测因子上的附加价值。我们的研究在这种情况下具有独特的可能性，因为它建立在以前的资助周期的成熟方法和发现的基础上，将被动监测和社区的前瞻性研究结合起来。公共卫生相关性：本研究将通过急性冠状动脉综合征（包括不稳定型心绞痛和心肌梗死）来衡量社区心脏病负担，提供重要信息。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.