Heterogeneous associations of traditional atherosclerotic risk factors and long-term events in different arterial territories: the EPIC Norfolk prospective population cohort

Abstract Background Atherosclerotic risk factors have been associated with cardiovascular disease (CVD) events in specific arterial territories. However, these observations are limited by relatively short-term follow-up (i.e. ten years) and a focus on a limited number of outcome events. We therefore investigated associations between atherosclerotic risk factors and territory-specific cardiovascular events in a large cohort with ≥20 years follow-up. Methods We included participants without baseline CVD from the European Prospective Investigation of Cancer (EPIC) Norfolk prospective population cohort. The strengths of associations between CVD risk factors (smoking, low-density lipoprotein cholesterol (LDL-c), and systolic blood pressure (SBP)) and the first occurrence of a CVD event were evaluated using a competing risk-adjusted regression model. CVD events were defined as hospitalisations or death due to ischemic heart disease (IHD), ischemic stroke, haemorrhagic stroke, peripheral arterial disease (PAD) or aortic aneurysm (AA). Patients were followed-up until the first event, non-CVD death (competing risk) or end of study (15-03-2018). The model was adjusted for sex, age, diabetes, HDL-c, kidney function and body mass index. LDL-c and SBP were analysed by comparing highest versus lowest quartiles. Smoking (at baseline) was compared to never smoking. Results We included 23,581 participants (56% women) with a median baseline age of 58 years [interquartile range (IQR) 51-66]. During median follow up of 21.3 years (IQR 19.0-22.8), 26.4% of individuals experienced ≥1 CVD event. The first event of occurrence was IHD in 17.3%, ischemic stroke in 3.6%, haemorrhagic stroke in 1.4%, PAD in 3.1% and AA in 1.4%. LDL-c was strongest associated with IHD [adjusted hazard rate (aHR) 1.7, 95% confidence interval (CI) 1.5-1.9], SBP with ischemic stroke (aHR 1.9, 95%CI 1.5-2.5) and smoking with AA (aHR 4.8, 95%CI 3.5-6.5) (Figure 1). Conclusions There is considerable heterogeneity in the associations between atherosclerotic risk factors and long-term, first, territory-specific cardiovascular events. Knowledge of these differences may assist in personalised treatment decisions and risk communication.