Reduced calf pump function (CPF) appears to be a risk factor for venous thromboembolism (VTE), according to a study published in Blood. In addition, reduced CPF was found to be an independent predictor of all-cause mortality.
Lead study author Damon Houghton, MD, from Mayo Clinic in Rochester, Minnesota, told ASH Clinical News that reduced CPF “may be very common in certain populations, particularly older individuals and those with multiple comorbidities. Therefore, it might be a significant contributor to VTE development in the population more broadly.”
To understand the association between CPF and VTE, Dr. Houghton and colleagues analyzed CPF measurements from venous plethysmography studies conducted at Mayo Clinic from 1998 to 2015 in 1,532 patients with no prior VTE history. The researchers identified nursing-validated VTE outcomes from the Rochester Epidemiology Project that occurred after the index study date.
Investigators compared outcomes in the following groups:
- 591 patients with normal CPF
- 941 patients with reduced CPF (rCPF), including 353 with unilateral rCPF and 588 with bilateral rCPF
Overall, the median age of patients was 63.9 years, and the median body mass index (BMI) was 28.8 kg/m2. The authors noted that patients with rCPF were significantly older than those with normal CPF (68.3 years for bilateral rCPF and 64.3 years for unilateral rCPF vs. 60.3 years for normal CPF; p<0.001). Comorbidities such as diabetes, renal disease, and metastatic solid tumors were reported more frequently in patients with bilateral rCPF. There was a statistically significant lower frequency of liver disease in patients with bilateral rCPF versus those with normal CPF (2.0% vs. 0.2%, p=0.006).
After a median follow-up period of 11.7 years, the primary outcome (a composite of any incident VTE, including proximal and distal deep vein thrombosis [DVT] and pulmonary embolism) occurred in 5.7% of patients (n=87). In an analysis adjusted for age, BMI, and Charlson Comorbidity Index, patients with bilateral rCPF were 68% more likely to develop incident VTE, compared with those with bilateral normal CPF (hazard ratio [HR] = 1.68; 95% CI 0.98-2.89).
A total of 352 patients (23%) died during the study period. The cumulative incidence of death was 11.0% in the normal CPF group, 22.4% in patients with unilateral rCPF, and 35.4% in those with bilateral rCPF. Compared with the normal CPF group, mortality was significantly greater in patients with bilateral rCPF (p<0.001) and unilateral rCPF (p<0.001). The adjusted HR for death was 1.34 (95% CI 1.00-1.79) in patients with bilateral rCPF compared to those with bilateral normal CPF.
“As calf pump function is a quantifiable physiologic measurement, it may enhance VTE prediction models that are typically based on comorbidities,” Dr. Houghton said. Numerous clinical scenarios could benefit from improved risk stratification, he added, including making decisions about whether to provide anticoagulant prophylaxis in the post-surgical or post-hospital settings; in patients with cancer who are eligible for prophylaxis while receiving chemotherapy; or to determine benefit of long-term preventative anticoagulation in patients with an initial DVT.
Dr. Houghton and his colleagues are currently developing a study to identify an optimal cut-off value for CPF that is predictive for thrombosis. “Ultimately, CPF needs to be studied prospectively and in higher-risk populations to determine if CPF measurements can enhance or replace existing risk stratification tools for clinical use,” he explained.
This study is limited by its retrospective nature, which increased the potential for missing data. Additionally, some patients were lost to follow up after moving out of Olmsted County, Minnesota, where the study was conducted.
Study authors report no relevant conflicts of interest.
Houghton DE, Ashrani AA, Liedl D, et al. Reduced calf muscle pump function is a risk factor for venous thromboembolism: a population-based cohort study. [published online ahead of print, 2021 Mar 3]. Blood. doi: 10.1182/blood.2020010231.
The robust association of poor CPF with VTE risk shown in this paper makes sense, since poor muscle pump function leads to venous stasis, one of the elements of Virchow’s triad. These findings are physiologically plausible, with similar risk of VTE in patients with unilateral or bilateral poor CPF.
However, I’m not sure that these results are immediately impactful for clinical care. While risk scores for VTE recurrence are widely used, risk scores for incident VTE are far less commonly used outside of surgical or medically hospitalized patients. Risk scores are not used for the general population due to relatively low baseline risk of VTE.
It would be interesting to see how combining CPF with other clinical predictors may improve VTE risk assessment for post-operative and hospitalized patients. The latter could help to identify a subgroup at higher risk for hospital-associated VTE who would benefit from extended VTE prophylaxis. This study lays the foundational work for future studies to explore these questions.
Geoffrey Barnes, MD
University of Michigan