We comprehensively examined the association of comorbidities and co-occurring comorbidities and VTE in a unique population of older adults undergoing primary total hip and knee replacement, high risk surgeries for VTE. We found that the rates of VTE captured in administrative data of older adults for the period immediately following THR and TKR to be low at 0.8-1.2%. Having CHF substantially increased the odds of VTE after THR or TKR and having COPD somewhat increased the odds of VTE after TKR. Co-occurring comorbidities did not increase the risk of VTE beyond their individual effects.
Comparison of our results with previous studies is limited by differences in outcomes measured and populations studied. Gangireddy et al.  conducted one of the largest studies to date using data from the Veterans Affairs National Surgical Quality Improvement Program (NSQIP), which included veterans undergoing nine different surgeries, including THR, between 1996 and 2001. After controlling for multiple preoperative and postoperative clinical variables, a multivariate analysis with 76,771 individuals showed that CHF and COPD were not associated with increased rates of VTE. This study supported our findings of the association between diabetes and a slightly lower rate of VTE (OR = 0.75).
We also detected a 29% reduction in the risk of VTE in patients undergoing THR with CVD. This result was not statistically significant nor did we detect an association in the knee population. There has been little evidence, however, regarding the relationship between CVD and postoperative VTE. Prior work  has suggested a common inflammatory pathway but this has not been evaluated extensively in the postoperative setting. In our study the association was not present for both knee and hip cohorts and was not statistically significant. We plan to re-assess this relationship in our future work.
Kikura et al.  examined 21,903 Japanese patients of multiple ages and multiple surgery types and found that history of acute myocardial infarction (AMI) was significantly related (OR = 7.7 95% CI 1.7-34.7) to the development of postoperative thrombotic events (including repeat AMI). Although we did collect information about the history of AMI in particular, we did not find an association with CAD in general in our analysis. In a cohort of 269 post-menopausal women undergoing THR and TKR, Jaffer et al.  found a trend towards CHF predicting more postoperative VTE events (OR = 5.50 95% CI 0.94-43.3) but a trend towards COPD predicting fewer VTE events (OR = 0.42 95% CI 0.07-1.98).
The association of CHF and VTE may relate to blood flow stasis as discussed earlier. Alternatively, CHF may indicate a degree of immobility that was not measured in the data we analyzed. Other comorbidities may also contribute to the development of postoperative VTE but their effects may have been attenuated by a selection bias. Surgeons may select only the healthiest subset of older adults with comorbidities for surgery. The absence of positive interactions between frequently co-occurring comorbidities (especially CAD and CHF) also suggests a potential source of a selection bias. Older adults with co-occurring comorbidities deemed to be suitable surgical candidates are presumably healthier in other ways than other older adults with the same comorbidities.
In the case of COPD, we only detected an increase in risk for older adults undergoing knee surgery. This could be explained by the generally weak predictor effect of COPD on VTE or it could be related to the inherent differences between hip and knee surgery. Postoperative mobility may be significantly less for hip surgery and the effect of immobility in this group may dwarf other predictors such as COPD. Future work should examine the interaction between mobility and surgery type in data where this information is available.
The association of CHF and COPD with postoperative VTE has important implications. Although the American College of Chest Physicians currently recommends high potency prophylaxis such as fondaparinux or LMWH for all individuals undergoing THR and TKR , surgeons are reluctant to prescribe these regimens, fearing bleeding complications. Identification of a high risk subset among a group of older adults already at increased risk for VTE based on the surgery planned would be an important improvement in the way we currently perform preoperative assessment. In addition to the use of high potency prophylaxis, surgeons may also use the risk information to incorporate other practices, such as regional anesthesia, mechanical prophylaxis devices, or stockings, aimed at lowering VTE rates.
There are limitations to the work we presented. Due to the nature of the NIS administrative data we have limited ability to capture VTE. A recent study , suggests that administrative data capture only 58% of VTE events. There is no evidence, however, to suggest that the events indentified are differentially being diagnosed in individuals with CHF or other comorbidities. In addition, we did not have access to medication information including prophylaxis agent. A recent study by Cohen et al. in 2008  indicated that in the United States, only 48% of medical patients are receiving the recommended ACCP prophylaxis and only 71% of surgical patients are receiving prophylaxis . If comorbidities prompted physicians to prescribe more potent prophylaxis in older adults with CHF or other comorbidities, however, the effects we observed would represent an underestimate of the true effect. A recent survey  suggests that orthopedic surgeons vary their prescribing patterns less than 10% of the time when evaluating a patient with cardiopulmonary disease. Future work should examine the relationship between comorbidities and VTE while controlling for prophylaxis agents in data where medication information is available.
We did not have information about events which took place after hospitalization. Given that the median time for development of DVT is 17 days for THR and 7 days for TKR  and the median length of stay was 3 or 4 days for each surgery in our analysis, the associations we present may not reflect the experience of older adults who develop injury in the post discharge period. Controlling for length of stay would not disentangle the relation between these comorbidities and VTE and we, therefore, did not control for it in our analysis. Length of stay may very well be a surrogate for immobility and stasis which are on the causal pathway of VTE development. Alternatively, increased length of stay may also be associated with VTE because of added time needed to achieve therapeutic levels of warfarin. Even though NIS data does not allow for measurement of the 30 or 90 day incidence of VTE, we believe that post discharge rates of VTE events will be similarly disparate in individuals with compared to those without comorbidities. In the future we plan to confirm these associations in data where this information is available.
Administrative data are susceptible to upcoding where medical coders assign a diagnosis that may have only been considered but not proven. We did not have information about those VTE events that were present on admission compared to those that occurred during hospitalization. We plan to conduct further validation studies in other databases where pre-existing diagnosis modifiers are available. We cannot firmly establish causality between comorbidities and VTE using the data available to us. Comorbidities may be linked to other processes such as increased operative time or difficulty weaning from a ventilator after surgery. Future research with datasets containing these clinical variables may clarify the exact causal pathway. Lastly, although in our analysis we controlled for the presence of several factors that might increase the risk of VTE, we did not have data on the smoking status of individuals, which might be related to both the exposure and outcome.