The Clinical Course of Chronic Venous Disease

The clinical manifestations of chronic venous disease (CVD) range from varicose veins (VV) to, ultimately, venous ulceration, representing a spectrum of disease states. This study aimed to evaluate the clinical course of CVD using electronic healthcare records (EHRs).

A retrospective, longitudinal study evaluating data from EHRs gathered from national databases, with a nested case control study, was performed to evaluate factors associated with CVD development. Analytics were performed using machine learning methods.

The study population comprised 890 982 cases. VV were associated with being overweight (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.04 - 1.20), a previous pregnancy (OR 5.83, 95% CI 4.37 - 7.79), and hormonal therapies (OR 2.13, 95% CI 1.75 - 2.58). Venous ulceration (VLU) was associated with White ethnicity (OR 21.54, 95% CI 3.80 - 122.17), men (p < .001), obesity (OR 1.46, 95% CI 1.20 - 1.79), frailty (OR 1.77, 95% CI 1.51 - 2.09), and previous venous thromboembolism (OR 3.07, 95% CI 2.49 - 3.78). An increased OR of CVD was found with cardiovascular conditions such as coronary artery disease (OR 20.05, 95% CI 14.09 - 28.55) and hypercholesterolaemia (OR 3.76, 95% CI 3.18 - 4.45). Biochemical markers, such as vitamin D deficiency (OR 1.52, 95% CI 1.31 - 1.76), were associated with VLU. Regarding disease progression, 1 - 2% of patients presenting with VV went on to develop VLU (median 7 years); 23% of patients with VLU developed ulcer recurrence; median time to recurrence was 207 days. Compared with a matched control group, VLU led to an increased risk in mortality (hazard ratio 1.39, 95% CI 1.23 - 1.58). At median follow up (11.5 years), mortality was significantly higher in VLU participants (28%) compared with control participants (7.3%; p < .001).

There are common factors associated with the different clinical manifestations of CVD. However, participants with VV and VLU appear to be phenotypically distinct, with only a small proportion of patients with VV developing VLU. Other aetiological factors should be considered when understanding why superficial venous reflux can manifest in clinically heterogenous ways.