Coronary Disease Morbidity and Mortality in a Population

在奥姆斯特县，在RO1 HL59205的初始周期中获得的数据表明，冠心病的长期趋势与性别和年龄的函数不同，而老年人的冠心病死亡率、心肌梗死发病率和心肌梗死后死亡率和发病率的变化不太有利。这些数据在衡量的所有指标中都是一致的，强调了尽管年龄调整后的冠心病死亡人数有所下降，但冠心病的负担仍然很大，尽管治疗取得了进展，心肌梗死的发病率仍然很高。这些不利的趋势对人口老龄化具有深远的影响，持续监测这些趋势对于了解冠心病的负担至关重要。为此，诊断心肌梗死的临床标准最近改变为依赖肌钙蛋白，这是一种新的生物标记物，具有更高的诊断效率。这将增加病例数量并改变疾病谱，这将对临床和公共卫生产生深远影响。监测研究在衡量冠心病趋势和解释此类变化的流行病学和临床影响方面发挥着核心作用，但迄今尚未对此进行研究。然而，对于非并发程序，这一重要任务构成了NHLBI社区监测工作组认识到的相当大的挑战，该工作组建议研究同时收集肌钙蛋白和CK/CKMB。在我们资助最初周期开发的方法的基础上，本次竞争性更新提出了一种新的主动监测方法，用于同时确定每个病例的肌钙蛋白和CK/CKMB。采购精心安排时间的血样的新方法将使我们能够直接测量肌钙蛋白导致的心肌梗死病例数量的增加，直接确定病例组合的后续变化并解释结果，同时还可以评估伴随的治疗趋势。此外，我们建议利用这个活跃的系统来检验定量峰值肌钙蛋白(在24-36小时内测量)和高敏感性(Hs)C反应蛋白(在症状出现后早期测量)在我们的MI队列中的预后价值。这些标记物被建议用来对肌钙蛋白升高但CK/CKMB阴性的急性冠脉综合征患者的风险进行分层，根据新的标准将其归类为心肌梗死，因此预后研究应联合检查这两个标记物的价值。为此，我们提出了四个具体目标。1)研究肌钙蛋白的使用对住院心肌梗死发生率的影响，并检验肌钙蛋白与发病率增加之间存在时间相关性的假说，这一假说在用CK/CKMB测量时没有改变。2)测量心肌梗塞的临床表现和严重程度的趋势，并检验仅由肌钙蛋白误诊的假说没有CK/CKMB所确定的假说严重。3)：研究心肌梗死的转归，检验肌钙蛋白鉴定的心肌梗死与CK/CKMB鉴定的心肌梗死不同的假说。4)研究峰值肌钙蛋白和hsCRP对预后的预测价值，以检验它们提供预后信息的假说，增加传统的危险指标。这项研究的意义在于，通过我们的方法，我们将量化肌钙蛋白导致的心肌梗死发病率的任何增加，直接测量由此导致的病例组合变化，并分析后续结果，同时确保心肌梗死监测的连续性。这对于理解MI诊断作为新定义和变化的CHD趋势的含义至关重要，这两个方面对于临床护理和流行病学研究都是至关重要的。

In Olmsted County, data acquired during the initial cycle of RO1 HL59205 document diverging CHD secular trends as a function of sex and age with less favorable changes in CHD mortality, MI incidence and post-MI mortality and morbidity among the elderly. These data, consistent across all indicators measured, underscore that, notwithstanding the decline in age- adjusted CHD deaths, the burden of CHD remains considerable and the morbidity of MI is substantial despite therapeutic progress. These adverse trends have profound implications in an aging population and their continued monitoring is of paramount importance to understand the burden of CHD. To this end, the clinical criteria to diagnose MI, an essential indicator of CHD, recently changed to rely on troponin, a new biomarker with enhanced diagnostic yield. This will increase the number of cases and shift the spectrum of disease, which has profound clinical as well as public health consequences. Surveillance studies play a central role in the measurement of CHD trends and the interpretation of the epidemiological and clinical implications of such changes, which to date have not been studied. For non-concurrent programs, however this important task poses considerable challenges recognized by the NHLBI Working Group on Community Surveillance, which recommended studies collecting simultaneously troponin and CK/CKMB. Building on methods developed during the initial cycle of our grant, the present competitive renewal proposes a novel active surveillance approach required for the dual ascertainment of each case with both troponin and CK/CKMB. Novel approaches to the procurement of carefully timed blood samples will allow us to directly measure the increase in the number of cases of MI due to troponin, directly ascertain the subsequent change in case mix and interpret outcomes, while also assessing concomitant trends in therapies. Further, we propose to capitalize on this active system to examine the prognostic value of quantitative peak troponin (measured at 24-36 hours) and high sensitivity (hs) CRP (measured early after symptom onset) in our MI cohort. These markers were proposed to stratify risk among cases of acute coronary syndromes with elevated troponin but negative CK/CKMB, classified as MIs by the new criteria, such that prognostic studies should examine jointly the value of both markers. To these ends, we propose four specific aims. 1) To examine the impact of the use of troponin on the incidence of hospitalized MI and test the hypothesis that troponin is temporally associated with an increase in incidence, which has not changed when measured with CK/CKMB 2) To measure the trends in the clinical presentation and severity of MI and test the hypotheses that MIs identified only by troponin are less severe than those identified by CK/CKMB. 3): To study the outcomes of MI and test the hypotheses that, they differ in MIs identified only by troponin as compared to MIs identified by CK/CKMB. 4) To examine the prognostic value of peak troponin and hsCRP to test the hypotheses that they provide prognostic information, incremental to conventional risk indicators. The significance of this study resides in the fact that, through our approach, we will quantify any increase in MI incidence due to troponin, measure directly the resulting change in case mix and analyze subsequent outcomes while simultaneously ensuring continuity for MI surveillance. This is crucial to understand the implications of MI diagnoses as newly defined and changing CHD trends, both aspects critically needed for clinical care as well as for epidemiological studies.