RESUMO
Essentials The association of venous thromboembolism (VTE) with subsequent physical function remains unclear. We prospectively evaluated this relationship among women from the Nurses' Health Studies. We found a decline in physical function over four years in women with incident VTE. This decline was somewhat greater among women specifically reporting a pulmonary embolism. SUMMARY: Background Physical function is integral to healthy aging; however, limited research has examined the association of venous thromboembolism(VTE) with subsequent physical function. Objectives To prospectively evaluate the relationship between VTE and decline in physical function among 80 836 women from the Nurses' Health Study(NHS), ages 46-72 in 1992, and 84 304 women from the Nurses' Health Study II(NHS II), ages 29-48 in 1993. Methods Physical function was measured by the Medical Outcomes Short Form-36 physical function scale, administered every 4 years. We compared change in physical function for women with vs. without an incident VTE in each 4-year follow-up period using multivariable linear regression. Results We observed a decline in physical function over 4 years when comparing women with vs. those without incident VTE in both older (NHS) and younger (NHS II) women (multivariable-adjusted mean difference NHS, -6.5 points [95% CI -7.4, -5.6] per 4 years; NHS II, -3.8 [95% CI -5.6, -2.0]). This difference appeared greater among women specifically reporting a pulmonary embolism (NHS, -7.4 [95% CI -8.7, -6.1]; NHS II, -4.8 [95% CI -6.8, -2.8]), and was equivalent to 6.2 years of aging. Whereas longer-term slopes of physical function decline following a VTE were not different from the slopes of decline in women without a VTE, the absolute level of physical function of women with VTE was worse at the end of follow-up compared to women without VTE. Conclusions In this prospective cohort, incident VTE was strongly associated with an acute decline in physical function. These results suggest it may be clinically important to consider approaches to ameliorating functional deficits shortly after VTE diagnosis.
RESUMO
Essentials Risk-stratification often fails to predict clinical deterioration in pulmonary embolism (PE). First-ever high-throughput metabolomics analysis of risk-stratified PE patients. Changes in circulating metabolites reflect a compromised energy metabolism in PE. Metabolites play a key role in the pathophysiology and risk stratification of PE. SUMMARY: Background Patients with acute pulmonary embolism (PE) exhibit wide variation in clinical presentation and outcomes. Our understanding of the pathophysiologic mechanisms differentiating low-risk and high-risk PE is limited, so current risk-stratification efforts often fail to predict clinical deterioration and are insufficient to guide management. Objectives To improve our understanding of the physiology differentiating low-risk from high-risk PE, we conducted the first-ever high-throughput metabolomics analysis (843 named metabolites) comparing PE patients across risk strata within a nested case-control study. Patients/methods We enrolled 92 patients diagnosed with acute PE and collected plasma within 24 h of PE diagnosis. We used linear regression and pathway analysis to identify metabolites and pathways associated with PE risk-strata. Results When we compared 46 low-risk with 46 intermediate/high-risk PEs, 50 metabolites were significantly different after multiple testing correction. These metabolites were enriched in the following pathways: tricarboxylic acid (TCA) cycle, fatty acid metabolism (acyl carnitine) and purine metabolism, (hypo)xanthine/inosine containing. Additionally, energy, nucleotide and amino acid pathways were downregulated in intermediate/high-risk PE patients. When we compared 28 intermediate-risk with 18 high-risk PE patients, 41 metabolites differed at a nominal P-value level. These metabolites were enriched in fatty acid metabolism (acyl cholines), and hemoglobin and porphyrin metabolism. Conclusion Our results suggest that high-throughput metabolomics can provide insight into the pathophysiology of PE. Specifically, changes in circulating metabolites reflect compromised energy metabolism in intermediate/high-risk PE patients. These findings demonstrate the important role metabolites play in the pathophysiology of PE and highlight metabolomics as a potential tool for risk stratification of PE.