Cardiac troponins are released into the circulation following myocardial injury with measurement of serum troponin concentration integral to the diagnosis of myocardial infarction. The next generation of high-sensitivity cardiac troponin assays have enhanced precision at very low concentrations and for the first time permit troponin concentrations to be reliably quantified outwith acute coronary syndromes. My aim was to evaluate the impact of more sensitive troponin assays on the diagnosis of myocardial infarction and to determine the potential for novel applications in stable cardiovascular diseases. In 2,929 consecutive hospitalised patients with myocardial injury I assessed the impact of implementing a contemporary sensitive troponin assay and a lower diagnostic threshold, on the incidence, management and outcome of patients with primary (type 1) and secondary (type 2) causes of myocardial infarction. Lowering the threshold improved outcomes in patients with type 1 myocardial infarction, but disproportionately increased the diagnosis of type 2 myocardial infarction, and identified a group of patients who remained at high-risk of death over the next 12 months. In 1,126 consecutive patients with suspected acute coronary syndrome I evaluated the impact of a high-sensitivity cardiac troponin I assay and sex-specific diagnostic thresholds on the diagnosis of myocardial infarction. Whilst having little effect in men, the use of sex-specific diagnostic thresholds would double the diagnosis of myocardial infarction in women, identifying those at increased risk of recurrent events. In a second cohort of 4,870 patients, I evaluated the optimal threshold to rule out myocardial infarction. The negative predictive value for myocardial infarction or cardiac death at 30 days was evaluated for a range of troponin concentrations. Troponin concentrations < 5 ng/L on presentation identified half of all patients with suspected acute myocardial infarction as low risk. Implementation of this assay and approach would markedly reduce hospital admissions and improve the diagnosis of myocardial infarction, particularly in women. High-sensitivity cardiac troponin assays may help us to manage patients with chronic cardiovascular diseases, such as aortic stenosis or stable angina pectoris. In patients with aortic stenosis, cardiac troponin was associated with an advanced hypertrophic response on electrocardiography and the presence of myocardial fibrosis on cardiac magnetic resonance imaging. Furthermore, cardiac troponin concentrations were a strong independent predictor of cardiovascular death or aortic valve replacement. In patients with stable angina, cardiac troponin was associated with transient ST-segment depression on ambulatory monitoring, suggesting that troponin concentrations may be modified by silent myocardial ischaemia. My findings suggest that high-sensitivity troponin assays have major potential to improve the assessment, treatment and outcome of patients with suspected acute coronary syndrome. The potential for cardiac troponins to improve risk stratification and monitoring of disease progression in patients with chronic cardiovascular disease now needs to be evaluated in prospective cohort studies.

Thesis (M.S.)--Boston University

Thesis (M.S. in chemical engineering)--Washington State University, December 2009. / Title from PDF title page (viewed on Feb. 12, 2010). "School of Chemical Engineering and Bioengineering." Includes bibliographical references.

Thesis (M. Phil.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 175-192).

published_or_final_version / Medicine / Master / Doctor of Medicine

published_or_final_version / abstract / toc / Clinical Psychology / Master / Master of Social Sciences

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Objective Increases in the number of CD34+ stem cells and progenitor cells in blood and infarcted areas after acute myocardial infarction (AMI) are a documented phenomenon. However, no study has yet reported on the dynamic changes in specific populations of adult stem cells, such as c-kit +Lin- cells or ckit + Lin - Sca1 + (KLS cells), following AMI. This study investigated the dynamic changes in these cells in multiple systems/organs following MI in mice. Methods The C57BU6J mice received either no surgery (normal control, n=6) or surgical ligation of the left anterior descending coronary artery to create AMI (n=24). On day-1 (n=7), -3 (n=5), -6 (n=6), and -12 (n=6) after AMI, mononuclear cells were isolated from theblood, spleen, and bone marrow, and stained with Lineage-PEcy7, c-kit-PE, and Sca1-APC antibodies. The c-kit +Lin - cell and KLS cell populations in the mononuclear cells were analyzed by FACS flowcytometry. Results The pattern of changes in the c-kit + Lin - cells was very similar to that in the KLS cells in the bone marrow, circulating blood, and spleen following AMI. There was a significant increase in these cells on day-3 in the bone marrow (c-kit +Lin- cells: 1.470 ± 0.094% vs control 1.127 ± 0.019%, and KLS cells: 0.365 ± 0.012 % vs control 0.1848 ± 0.019%, p<0.05), which then slowly declined from day-6 to -12. In the blood, these cells, particularly the KLS cells, decreased slightly from day-1 to -12. On day-3, -6, and -12 the cells increased continuously and significantly in the spleen, (on day 3, c-kit +Lin-cells: 0.253 ± 0.0107 % vs control 0.1305 ± 0.014 %; it was 0.3212 ± 0.028 % on day-6). (on day-6 KLS cells: 0.1078 ± 0.076 % vs control 0.0425 ± 0.0064 % while on day 12 it was 0.1174 ± 0.035 % p<0.05). Conclusion This study provides for the first time the longest observation of the dynamic changes of specific sub-groups of adult stem cells (c-kit +Lin- cells and KLS cells) in multiple systems following AMI. The study demonstrates that AMI results in significant changes, or mobilization, of these cells in the bone marrow, spleen, and blood. Significant and continuous accumulation of the cells in the spleen occurs following AMI, despite the decreased level of the cells in the blood. The role of the spleen in stem cell mobilization after AMI is unclear and requires further investigation.