Coronary Disease Morbidity and Mortality in a Population

在奥姆斯特德县，RO1 HL59205初始周期期间获得的数据显示，冠心病的长期趋势随性别和年龄的变化而不同，老年人的冠心病死亡率、心肌梗死发生率、心肌梗死后死亡率和发病率的变化不太有利。这些数据与所有测量指标一致，强调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相当大，尽管治疗取得进展，心肌梗死的发病率仍然很高。这些不良趋势对人口老龄化具有深远的影响，对其持续监测对于了解冠心病的负担至关重要。为此，作为冠心病重要指标的心肌梗死的临床诊断标准最近改变为依赖肌钙蛋白，这是一种新的生物标志物，具有更高的诊断率。这将增加病例数量并改变疾病范围，从而对临床和公共卫生产生深远影响。监测研究在测量冠心病趋势和解释这些变化的流行病学和临床意义方面发挥着核心作用，迄今尚未对这些变化进行研究。然而，对于非并发项目，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。基于我们资助初期开发的方法，目前的竞争性更新提出了一种新的主动监测方法，需要对肌钙蛋白和CK/CKMB的每个病例进行双重确定。获取精确定时血液样本的新方法将使我们能够直接测量肌钙蛋白引起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，同时还可以评估治疗的伴随趋势。此外，我们建议利用这种活性系统来检验定量肌钙蛋白峰值（在24-36小时测量）和高灵敏度（hs） CRP（在症状出现后早期测量）在我们的心肌梗死队列中的预后价值。这些标志物被建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患者的风险进行分层，这些患者被新标准归类为MIs，因此预后研究应联合检查这两种标志物的价值。为此，我们提出四个具体目标。1)检验肌钙蛋白的使用对住院心肌梗死发病率的影响，并检验肌钙蛋白与发病率增加有暂时相关性的假设，当用CK/CKMB测量时，这一假设没有改变。2)测量心肌梗死的临床表现和严重程度的趋势，并检验仅用肌钙蛋白识别的心肌梗死比用CK/CKMB识别的心肌梗死更严重的假设。3)：研究心肌梗死的结果，并验证仅由肌钙蛋白识别的心肌梗死与由CK/CKMB识别的心肌梗死存在差异的假设。4)检验肌钙蛋白峰值和hsCRP的预后价值，以检验它们提供预后信息的假设，增量于传统的风险指标。本研究的意义在于，通过我们的方法，我们将量化肌钙蛋白引起的心肌梗死发生率的任何增加，直接测量病例组合的变化，并分析后续结果，同时确保心肌梗死监测的连续性。这对于理解心肌梗死诊断作为新定义和不断变化的冠心病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.