Venous thromboembolism: Lifetime risk and novel risk factors

Abstract

Deep vein thrombosis and pulmonary embolism are viewed as different manifestations of the same disease process, termed venous thromboembolism (VTE). VTE represents a significant source of mortality and morbidity. The first two manuscripts of this dissertation use data from two large, prospective cohort studies: the Cardiovascular Health Study (CHS) and the Atherosclerosis Risk in Communities (ARIC) study. We followed participants, aged 45-64 years in ARIC and >=65 in CHS at baseline (1987-89 in ARIC, 1989-90 and 1992-C93 in CHS), for incident VTE (through 2011 and 2001 in ARIC and CHS, respectively). In manuscript 1, we estimated the lifetime risk and 95% confidence interval of incident VTE, using data from CHS and ARIC. We used a modified Kaplan-Meier method, accounting for the competing risk of death. We calculated that 1 in 12 middle-aged adults develop VTE in their lifetime. This estimate of lifetime risk may be useful to promote awareness of VTE and guide decisions at both clinical and policy levels. Manuscripts 2 and 3 aimed to identify and clarify novel risk factors for VTE. The etiology of VTE is not fully understood, especially in contrast to atherothrombosis. Further identification of VTE risk factors may yield pathophysiological insights into the disease that could eventually provide new prevention or treatment options. In manuscript 2, we quantified the association between orthostatic hypotension (OH) at baseline and VTE, using data from ARIC and CHS. In CHS, there was a positive association between incident VTE and OH (Hazard ratio for total VTE = 1.74 (95% confidence interval: 1.20-2.51)). In contrast, there was no association between OH and VTE in ARIC. In conclusion, community-dwelling older adults with OH have a moderately increased risk of VTE. These results were not replicated in a population-based middle-aged cohort. In manuscript 3, we conducted a systematic review and meta-analysis to quantify the association between diabetes and VTE. We identified 19 eligible studies. The pooled relative risk for the association of diabetes with VTE was 1.10 (95% confidence interval: 0.94-1.29). This literature-based systematic review and meta-analysis supports either no association or a very modest positive one between diabetes and VTE in the general population. Diabetes is unlikely to play a major role in VTE development.