Physicians' Academy for Cardiovascular Education

Large heterogeneity in relationships between risk factors and various CVD manifestations

Stoekenbroek RM et al., Eur Heart J 2016


Heterogeneous impact of classic atherosclerotic risk factors on different arterial territories: the EPIC-Norfolk prospective population study

Stoekenbroek RM, Boekholdt SM, Luben R, et al.
Eur Heart J 2016;37:880-889


Various clinical manifestations of atherosclerosis, such as coronary artery disease (CAD), peripheral artery disease (PAD), and abdominal aortic aneurysms (AAA) share risk factors. Varying strengths of associations between particular risk factors and different clinical CVD manifestations have been reported, with the variation possibly partly being explained by  the chosen study population and characteristics. For instance, large differences in the strength of associations between high blood pressure and various CVD outcomes have been reported [1].
Also, limited data are available about the relationships between multiple risk factors and various CVD manifestations considered simultaneously within one population [2,3]. As a result, the relative strength of the associations of conventional risk factors with CVD remains unclear.
From a pathophysiology perspective, certain risk factors may differentially impact various vascular beds. Furthermore, understanding the relative contribution of certain risk factors to CVD can help to estimate the benefit that can be obtained when improving a particular risk factor [4].  
In this study the associations between LDL-C, systolic blood pressure (SBP), and smoking, and the incidence of CAD, stroke (ischaemic and haemorrhagic), PAD, and AAA were evaluated in the general population. For this purpose, data of 21,798 participants without previous CVD of the EPIC-Norfolk population study were analysed.

Main results

  • The overall crude incidence rates per 1000 person-years were: CAD: 9.2 (95%CI: 8.8–9.5), ischaemic stroke: 1.1 (95%CI: 0.9–1.2), haemorrhagic stroke: 0.5 (95%CI: 0.4–0.6), AAA: 0.6  (95%CI: 0.5–0.7) and PAD: 0.9 (95%CI: 0.8–1.0).
  • LDL-C (highest vs lowest quartile) was strongly associated with CAD (adjusted HR: 1.63; 95%CI: 1.44–1.86). HRs for all other CVD types did not reach statistical significance.
  • SBP (highest vs lowest quartile) was a strong risk factor for all of the studied outcomes except for AAA. Strong associations were observed for PAD (adjusted HR: 2.95; 95%CI: 1.78–4.89) and ischaemic stroke (adjusted HR: 2.48; 95%CI: 1.55–3.97)
  • Smoking (current vs. never-smoker) was significantly associated with all event types except haemorrhagic stroke. Particularly strong associations were observed for incident AAA (adjusted HR: 7.66; 95%CI: 4.50–13.04) and PAD (adjusted HR: 4.66; 95% CI 3.29– 6.61).


In this large cohort study, substantial heterogeneity was seen in the strength of associations between LDL-C, SBP, smoking and various CVD manifestations. These findings support the hypothesis of different pathophysiologic mechanisms underlying the development of atherosclerotic diseases in different vascular beds, and therefore the differential importance of risk factors for different disease manifestations. Based on these data, risk factor modification management for high-risk patients could be adjusted and improved.
Find this article online at Eur Heart J


1. Rapsomaniki E, Timmis A, George J, et al. Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age–specific associations in 1.25 million people. Lancet 2014;383:1899–1911
2. D’Agostino RB Sr, Vasan RS, Pencina MJ, et al. General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation 2008;117:743–753
3.  Fowkes FG, Housley E, Riemersma RA. Smoking, lipids, glucose intolerance, and blood pressure as risk factors for peripheral atherosclerosis compared with ischaemic heart disease in the Edinburgh Artery Study. Am J Epidemiol 1992;135:331–340
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