Coronary Disease Morbidity and Mortality in a Population

在Olmsted县，在RO 1 HL 59205初始周期期间获得的数据记录了不同性别和年龄的CHD长期趋势，老年人CHD死亡率、MI发病率和MI后死亡率和发病率的变化不太有利。 这些数据在所有测量的指标中一致，强调尽管年龄调整的CHD死亡率下降，但CHD的负担仍然相当大，尽管治疗取得了进展，但MI的发病率仍然很高。这些不利趋势对老龄化人口具有深远的影响，对其进行持续监测对于了解CHD的负担至关重要。 为此，诊断心肌梗塞（CHD的一个重要指标）的临床标准最近改为依赖肌钙蛋白（一种诊断率更高的新生物标志物）。 这将增加病例数量，改变疾病谱，从而产生深远的临床和公共卫生后果。 监测研究在衡量冠心病趋势和解释这种变化的流行病学和临床意义方面发挥着核心作用，迄今为止尚未进行研究。 然而，对于非同步项目，NHLBI社区监测工作组认识到这一重要任务带来了相当大的挑战，该工作组建议同时收集肌钙蛋白和CK/CKMB。 在我们赠款的初始周期开发的方法的基础上，目前的竞争性更新提出了一种新的主动监测方法，需要对每个病例进行肌钙蛋白和CK/CKMB的双重确认。 新的方法来采购仔细定时的血液样本将使我们能够直接测量由于肌钙蛋白引起的MI病例数量的增加，直接确定病例组合的后续变化并解释结局，同时还评估治疗的伴随趋势。 此外，我们建议利用这一主动系统来检查定量峰值肌钙蛋白（在24-36小时测量）和高灵敏度（hs）CRP（在症状发作后早期测量）在我们的MI队列中的预后价值。 这些标志物被提议用于对肌钙蛋白升高但CK/CKMB阴性的急性冠状动脉综合征病例进行风险分层，根据新标准归类为MI，因此预后研究应联合检查两种标志物的价值。 为此，我们提出了四个具体目标。 1)检查使用肌钙蛋白对住院MI发生率的影响，并检验肌钙蛋白与发生率增加存在时间相关性的假设，当使用CK/CKMB测量时，发生率没有变化2）测量MI的临床表现和严重程度的趋势，并检验仅通过肌钙蛋白识别的MI比通过CK/CKMB识别的MI严重程度低的假设。 3）：研究MI的结局，并检验仅通过肌钙蛋白识别的MI与通过CK/CKMB识别的MI不同的假设。 4)研究肌钙蛋白峰值和hsCRP的预后价值，以检验它们提供预后信息的假设，增加传统的风险指标。 本研究的意义在于，通过我们的方法，我们将量化由于肌钙蛋白引起的MI发病率的任何增加，直接测量病例组合的变化并分析后续结局，同时确保MI监测的连续性。这对于理解MI诊断作为新定义和不断变化的CHD趋势的意义至关重要，这两个方面对于临床护理以及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.