Coronary Artery Disease: Ethnicity, Sex and Risk Prediction

Despite major advances in prevention and treatment, cardiovascular disease is still the leading cause of death around the globe. In particular, coronary artery disease (CAD) has become a disease of men and women of all ethnicities. In the first part of this thesis we examined ethnic differences in CAD risk factors, CAD biomarkers and CAD severity. From a systematic literature review we found profound differences in CAD biomarkers between Asians and Whites in the general population (mainly inflammatory markers and markers of glucose metabolism) with a most hazardous profile among South Asians and more benign profiles in Japanese and Chinese. Then, in a general population cohort we found inter-ethnic differences in the relation of the Framingham risk factors with carotid intima-media thickness and the occurrence of cardiovascular events. These small, but significant differences might prove to be important when implementing global prevention strategies. In the multi-ethnic United Coronary Biobank (UNICORN) we found that severity of CAD differed by ethnicity and that CAD risk factors related with CAD severity in an ethnicity-specific manner. Also our data suggested that different biomarker cut-offs might be indicated for certain ethnic groups. The SYNTAX score, which quantifies CAD severity, differed significantly among Asian and White patients undergoing percutaneous coronary intervention for stable CAD or myocardial infarction. SYNTAX scores were particularly high in Malays, who might also have poorer survival after myocardial infarction. By combining Swedish and Singporean heart failure cohorts we found that electrocardiographic QRS-prolongation occured in heart failure in both Asians and Whites. But with deterioration of the ejection fraction QRS-prolongation was more extreme in Asians than Whites. QRS-prolongation was associated with poorer outcome in both Asians and Whites, but different cut-offs might need to be considered. In the second part of this thesis we addressed sex differences in CAD. Women with stable complaints had less severe CAD than men upon angiography. However, women who presented with myocardial infarction or who happened to have multi-vessel disease upon angiography were found to have a poorer prognosis than men. Women, regardless of the indication for angiography or the severity of CAD, reported worse health-related quality of life (HRQOL) than men. Paradoxically, the lower HRQOL in women conferred less risk of future adverse events than for men. Importantly, people who did not respond to the HRQOL questionnaire had the poorest survival, indicating an important non-response bias. In the final part of this thesis we discuss the predictive potential of hematological parameters. Hematological parameters are measured on a very regular basis for many purposes. But these parameters are overlooked as CAD biomarkers. Among leukocyte parameters we found that the monocyte-to-lymphocyte ratio (MLR) is capable of improving prediction of mortality in addition to clinical characteristics. And when considering all hematological parameters the red cell distribution width (RDW) showed to improve prediction of mortality and adverse events after coronary angiography, superiorly to high-sensitivity troponin and NT-pro brain natriuretic peptide. Measuring MLR and RDW is inexpensive and in many cases these parameters are readily available.