Ischaemic Heart Disease: Early Recognition and Risk Disparities

Abstract

Ischaemic heart disease (IHD) comprises the principal clinical manifestations of coronary artery disease - myocardial infarction, stable and unstable angina pectoris, heart failure and sudden death - and is the leading cause of morbidity and mortality worldwide. The relentlessly growing burden of IHD poses an enormous health economical challenge. We aimed to improve diagnostic strategies for patients suspected of IHD, because early recognition and treatment of IHD reduces the risk of irreversible cardiac injury and improves prognosis. We adopted a twin-track approach. Firstly, we studied whether novel blood-based biomarkers were able to expedite the recognition of IHD among patients presenting with either acute or non-acute chest pain. In a diagnostic accuracy study among patients presenting to the emergency department with suspected acute coronary syndrome, we show that heart-type fatty acid binding protein assays cannot overcome the sensitivity deficit of high-sensitivity troponin measurements for the detection of unstable angina and for the detection of myocardial infarction in the first hours after chest pain onset. Furthermore, we report that in a two-phase biomarker study in a large cohort of stable outpatients undergoing Rubidium-82 PET/CT, no circulating microRNA’s could be identified that have the potential to be used as diagnostic blood-based biomarkers for myocardial ischaemia. The ultimate goal in the field of biomarkers for IHD remains to develop a sensitive and reliable biomarker to detect ischaemic myocardium, irrespective of the presence of myocardial necrosis. Secondly, we investigated whether ethnicity- and sex-based disparities in the prevalence of IHD and associated conditions are present among patients suspected of IHD, and whether these risk disparities should be considered in the diagnostic approach to IHD. In a multi-ethnic cohort study conducted in Singapore and The Netherlands, we observed significant ethnicity-based differences in cardiovascular risk profile, the prevalence of myocardial infarction and unstable angina, revascularisation rates and the severity of coronary heart disease among patients presenting to the emergency department with chest pain. Ethnicity-based differences were also observed in the levels of biomarkers related to coronary artery disease, and in the strength of de association between the biomarkers and severity of coronary artery disease. Despite aforementioned disparities, we demonstrate that the HEART score performs equally well in the risk stratification of Asian compared with Caucasian patients with suspected acute coronary syndrome. Contrastingly, regarding sex-based disparities, men assigned to the low-, intermediate-, or high-risk HEART score had markedly higher 6-week risk of major adverse cardiac events compared to women assigned to the same HEART risk category. Lastly, we provided valuable insight into the disparities in prevalence of diabetes and its impact on Asian and Caucasian patients with heart failure: despite younger age and lower prevalence of obesity, diabetes was 3-fold more common in Asian compared with Caucasian patients with heart failure. All of the above-mentioned results underscore the importance of an ethnicity- and sex-tailored diagnostic approach to IHD, subgroups that are currently not adequately represented in the evidence-based clinical practice guidelines.