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Older adults frequently experience venous ulceration and strive to prevent future ulceration.
To determine the risk factors for future venous ulceration and develop a model for venous ulcer development.
All patients over 60 years in a primary care panel in Olmsted County, MN, on January 1, 2005 were enrolled (N=12,650.).
This was a retrospective cohort study of clinical outpatients. The primary outcome was a new diagnosis of venous ulceration within two years. The predictor risk variables included demographic and co-morbid health risk factors. Data analysis involved univariate and multivariate logistic regression. A final model to predict venous ulceration was created based on multivariate risk factors.
215 (1.7%) subjects developed new venous ulcers in 2 years. Previous venous ulceration was the most significant risk factor (OR 19.4; 95% CI 14.5-25.9); thus, a 19 fold increased risk of future venous ulceration. In the final model, prior venous ulceration, renal insufficiency, blindness, and cataracts were the significant risk factors identified. The final model had an area under the curve of 0.797 and a cutoff score of 3.
Prior venous ulceration remains the most important factor for future venous ulceration and itself predicts a high risk of future ulceration.
Venous ulcers are a common health concern for many older adults. The estimates of the prevalence of venous ulcers vary; however, venous ulcers may be present in 1% of the US population.1 The point prevalence in a Swedish cohort was lower at 2.4 cases/ 1000 persons in 2008.2 In a retrospective cohort study from 300,000 inpatients in China, the prevalence of venous ulcers in a hospitalized population was higher at above 6%.3 Venous ulcers can be painful and often require considerable work and effort on the part of the patient and the family.4 The cornerstone of venous ulcer therapy is edema control through external compression of the edematous legs.5 For direct wound management, clinicians focus on controlling the exudate to prevent maceration around the ulcer.6 Thus, the patient undergoes considerable effort, time, pain and expense when he suffers a venous wound. The cost of an individual venous wound is estimated at 814 to 1994 euros (1100-2800 U.S. dollars) in a recent Cochrane review of venous ulcer compression.7 The development of a model or risk scoring system to predict venous ulceration would be helpful for targeting preventive care toward higher-risk patients.
Several predictors of venous ulceration have been identified which would guide the creation of a new model or risk scoring system. However, many of the risk factors were developed in a younger population and may not be relevant to patients over sixty years of age. In a retrospective study of 62 patients undergoing venous surgery a previous history of venous ulceration was a significant predictor of future venous ulceration.8 In a prospective study of 229 patients, patients with venous insufficiency also developed venous ulceration much more frequently with venous refill time a good indicator for venous ulceration.9 These studies provide a good basis for future work; however, many questions remain about potential venous ulcer risks in an outpatient, older population. The objective of this study was to determine the association between demographic, venous, vascular, and co-morbid health factors and the development of venous ulceration in an older population in order to create a model aimed at the prevention of this significant disease. We undertook a retrospective cohort study of all community dwelling elderly subjects in one outpatient community practice to answer this question as well as to develop a model to help predict venous ulceration in this cohort.
This was a retrospective cohort study of adult outpatients within the division of Primary Care Internal Medicine (PCIM) at Mayo Clinic, Rochester. The subjects included all patients over 60 years of age impanelled on January 1, 2005. The Mayo Clinic, Rochester is an academic medical center with both faculty physician and training healthcare providers. The Mayo Clinic Institutional Review Board (IRB) reviewed and approved the protocol. The authors conducted all aspects of the research on this project in accordance with the principles of the Declaration of Helsinki.10 The authors performed the study in adherence to Minnesota state statue with regard to medical record use and privacy.11 All adults age 60 and older, who were assigned to a PCIM primary care provider on January 1, 2005, were included in the analysis. All subjects were community dwelling or lived in an assisted living facility within Olmsted County. The exclusion criteria included residents living within a skilled nursing facility on January 1, 2005. Patients who did not give consent were also excluded. Patients sign forms that request their medical records not be used for medical research.
Health science research personnel extracted data from the electronic medical record (EMR) of the patients enrolled in the study. The abstractors were blinded to the study hypothesis and were not involved with the analysis or interpretation of the data. The EMR contains all medical diagnosis and surgical interventions for each patient as well as demographic information. Mayo Clinic Rochester maintains EMR information within one electronic system for clinical use, billing, and for medical archives through the Rochester Epidemiology Project.12 Using this administrative electronic information, the authors collected predictor variables of demographics, venous disease, arterial vascular risk factors, and other co-morbid risk factors. The investigators collected all predictor variables from the EMR in dates prior to 1/1/2005 and prior to any subsequent event. The final diagnosis within the EMR was made clinically by the medical provider. The accuracy of medical diagnosis for all conditions varies; however, for some venous deep venous thrombosis, the specificity of the medical record was as high as 99%.13
The primary outcome was the development of a new venous ulcer within 2 years of 1/1/2005. The diagnosis of venous ulceration was made clinically by medical providers and was documented in the medical record and/or subsequently billed as a venous ulcer.
The demographic variables collected included the following: age, gender, and marital status as of 1/1/2005. The venous disease risk factors included both a previous history of venous ulceration and a history of venous insufficiency. Arterial vascular co-morbid health conditions included coronary artery disease (CAD), stroke, peripheral vascular disease (PAD), renal insufficiency, congestive heart failure (CHF), previous history of myocardial infarction (MI), hypertension, hyperlipidemia, stroke, and combined cardiac outcomes of a history of CAD/CHF/MI. The other co-morbid medical illnesses included a history of cancer, diabetes, depression, dementia, rheumatoid arthritis, degenerative arthritis, peripheral neuropathy, hypothyroidism, decubitus ulcer, fall, hip fracture, chronic obstructive pulmonary disease (COPD), and cataracts. All comorbid health conditions were present and recognized prior to 1/1/2005.
Health Research Services directly entered all information via electronic abstraction into a Microsoft Excel version 2003 spreadsheet (Microsoft, Redmond, WA) for data entry, retrieval, and analysis. The investigators analyzed the final information using SAS 9.13 software (SAS Institute Inc., Cary, NC). The initial analysis included unadjusted analysis of individual predictor variables (demographics, venous disease, arterial vascular co-morbid health disease, and other co-morbid health illness) and the development of venous ulceration by either Pearson Chi-Square tests or 2-sample t-tests. The age-adjusted odds ratios and the 95% CI and p-values for individual variables were obtained using a logistic regression model. All significant variables from the unadjusted risk variables were placed in a multivariate model. The multivariate logistic model was constructed using all factors with a p value of <0.10 and the authors used a stepwise elimination approach. Those factors in the final model with a p<0.05 were considered significant. Following the completion of the multivariate model, the authors constructed a venous ulcer instrument with all the significant predictors. The final model was validated using a Bayesian approach rerunning the final model 1,000 times to confirm that the final variables were still significant. The final model included a scoring system based upon the odds ratios from the final risk factors in the multivariate model. Using this instrument, the authors created a receiver operator curve (ROC) to demonstrate the optimum cutpoint to reach the maximum of both sensitivity and specificity. The ROC curve allows for a method to determine the accuracy of the model using both sensitivity and specificity. The area under the curve (AUC) and its standard error (SE) were also obtained.14
The demographic and the epidemiological factors revealed important findings in our study. A total of 12, 650 patients over 60 years old gave consent for medical record review for this retrospective cohort study. All records of patients giving consent were used for the study starting on date 1/1/2005. Of the 12,650 patients, 215 patients (1.7%) developed a new venous ulcer over the subsequent 2 years. The incidence of venous ulceration was 8.6 cases/ 1000 patient-years. In the group without venous ulceration, 701 patients of the 12,435 patients died (6%) compared to 15 of 215 (7%) who had developed venous ulceration. This was not a significant difference. The demographic differences between the groups who did and did not develop a venous ulcer are noted in Table One. The univariate odds ratios estimates for individual predictor variables are noted with 95% confidence intervals in Table Two and both table one and two reveal some important findings. Patients with a history of previous venous ulceration or venous insufficiency had the highest risk of future venous ulceration with odds ratios of 19.4 [95% CI 14.5-25.9] and 19.4 [14.5-25.9] respective. Thus the presence of either previous venous ulceration or venous insufficiency had a 19 fold increased risk of future venous ulceration. Of the vascular and other co-morbid risk factors, decubitus ulceration had the highest risk with an odds ratio of 3.68 [95% CI 2.07-6.54]. Other significant factors included age, diabetes, rheumatoid arthritis, degenerative arthritis, peripheral neuropathy, falls and cataracts.
The multivariate model is noted in Table Three. Of the initially significant factors found with univariate analysis, the remaining predictor variables in the multiple variable model were prior venous ulceration, renal insufficiency, cataracts, blindness and decubitus ulceration. Having a previous venous ulcer had an odds ratio of 18.7 [95% CI 14.0-25.0] after adjustment. The validation of the model using a Bayesian modeling system found prior venous ulceration remained significant with an odds ratio of 19.0 (SD 2.9) and was significant in all models. Renal insufficiency was also significant in 98% of models. Decubitus ulceration, cataracts and blindness all had odds ratios over 1.7, and the significance only changed with blindness with significance in 49% of the models. After the Bayesian validation, we used the scoring system for the 12,650 patients and found the optimal cutoff total score was 3. This score resulted in a sensitivity of 0.63 and a specificity of 0.88. The receiver operating curve based upon this system is noted in figure one below. The area under the curve was 0.797 with a standard error of 0.018.
This study presents novel findings regarding risk factors for venous ulceration in a cohort of older community-dwelling patients. We found an incidence of 8.6 cases/ 1000 patient years in our population. Our number is higher than the Swedish cohort; however, our cohort had an older population over 60.2 Previous venous ulceration remains the strongest predictor of future venous ulceration in both the univariate and multivariate model. Presence of prior venous ulceration with a score of 19 on the instrument automatically places a patient at high risk and should be treated as such. In other cohort studies of patients of all ages without an emphasis on older adults, up to 70% of patient with an initial venous ulcer developed a subsequent venous ulcer.15 Venous insufficiency is the primary physiological reason for venous ulceration, and we found an odds ratio of 19.4 [95% CI 14.5-25.9] for future ulceration in patients with venous insufficiency on univariate analysis. This indicates that there is a 19 fold increased risk of venous ulceration in patients with venous insufficiency compared to patients without venous insufficiency. This factor was not significant after multivariate analysis and was not included in the final model. Ulceration of the leg often involves venous incompetence. In a cross-sectional study of 463 lower extremity ulcers, 72% of subjects had venous insufficiency as documented by ultrasound.16 In our study, decubitus ulcers also had a strong association with future venous ulceration with an odds ratio of 3.68 [95% CI 2.07-6.54]. Decubitus ulcers have not previously been described in association with venous ulceration. The final model of significant risk factors of prior venous ulcers, decubitus ulceration, blindness, cataracts and venous insufficiency performed well when placed in a receiver operating curve with a cutoff score of three. The area under the curve was 0.797 with a SE of 0.018 and an optimal sensitivity of 0.63 and a specificity of 0.88. These parameters indicate a good model and the well defined curve in figure one shows a good instrument as indicated by the high area under the curve. The high specificity of 0.88 indicates that if a patient has a low score, the risk of development of a venous ulcer is low. If a patient scores high, it does not necessarily mean that the patient will develop a venous ulcer.
Demographic risk factors were not related to venous ulceration in the final model of our study. In the initial univariate model, age was a risk factor for venous ulcer development with an odds ratio of 1.05 [95% CI 1.04-1.06]. However, after adjustment, age was not included in the final model. Previous cohort studies have shown advancing age is associated with venous ulceration in a broad community cohort study area17. Our study used an older population; thus, within this narrow range, age did not influence venous ulcer development. Gender was not associated with venous ulcer development in our study. In previous retrospective cohort studies in general practice, more females than males had venous insufficiency.17-19 In one cohort study, the incidence of venous ulcers is higher in younger women; however, in men ages 60-70, the incidence of venous ulcers may be higher in men.19 This difference with age may explain the lack of gender difference in our study. Marital status also was not associated with venous ulceration.
Of the vascular risk factors, only renal insufficiency and hypertension were included in the final multivariate model. The presence of renal disease impacts healing in both venous ulcers and ischemic ulcers.20 The remaining vascular illnesses of combined heart disease (coronary disease, myocardial infarction and congestive heart failure (CHF)), stroke, peripheral vascular disease and hyperlipidemia were not risk factors for venous ulceration on unadjusted analysis. Hypertension was borderline significant in univariate analysis and was not significant after adjustment with other variables. In one study of long term care residents, CHF was associated with venous ulceration.21 The concurrence of arterial and venous disease in lower extremity ulceration is common in many patients; thus, the potential expectation of an association between vascular disease and venous insufficiency. 2, 22 One explanation may be that underlying vascular disease may not have been recognized in our cohort or was not reported. These findings reinforce the importance of venous disease and edema as the primary risk factors of venous ulceration and not underlying ischemic disease.
Other co-morbid health conditions, specifically cataracts and blindness, were significantly related to the development of venous ulceration in both unadjusted analysis and in the final model. Diabetes, degenerative arthritis, falls, peripheral neuropathy and inflammatory arthritis were all significant on univariate evaluation but were not significant after multivariate analysis. Previous studies in patients with rheumatoid arthritis often show an association between rheumatoid arthritis and venous ulceration in large epidemiological studies which confirms our findings on univariate analysis but differs after adjustment.23 Cataracts were important with an initial odds ratio of 1.94 [95% CI 1.36-2.77]. After the stepwise multivariate model, the odds ratio was 1.64 [95% CI 1.16-2.34]. This association has not been previously reported. There have been some initial genetic linkages between cataracts and congential heart disease. Blindness had the lowest concurrence of significance using the Bayesian validation. The possible reasons for cataracts and blindness as risk factors are unclear; however, it may relate to the challenges of skin care with decreased vision or potential leg trauma. Cancer, depression, dementia, hypothyroidism and chronic obstructive pulmonary disease were not associated with venous ulceration. These findings differ from previous studies evaluating the relationship between depression and venous ulceration. Depression and anxiety have previously been reported as significant factors in patients with venous ulceration.24, 25 Ultimately, cataracts as a risk factor for venous ulceration should be considered by providers.
This study possesses numerous strengths which enhance the validity of the multivariate model and the findings. The retrospective cohort design and the method of data collection do create inherent limitations. Mayo Clinic maintains a robust data system and comprehensive electronic medical record which collects demographic, medical utilization and co-morbid health data. Administrative data systems suffer inherent weaknesses including potential missing information or miscoded information. It is possible that events like mortality or significant comorbid illnesses could be missed. Previous studies evaluating the accuracy of the medical record at Mayo Clinic, Rochester estimate accuracy at 97% for specific conditions.12, 13 Generally, the medical record may be more accurate than survey or self report.26 A second concern involves the incident diagnosis of venous ulceration. It is potentially possible that some patients developed a venous ulcer and did not seek medical attention; thus, this model represents the more serious cases of venous ulceration that come to medical attention. The diagnosis of venous ulceration was made clinically by the provider without verification of venous insufficiency with diagnostic testing; thus, there is potential for misclassification and non-specific billing codes. However, in clinical practice, most venous ulcers are diagnosed clinically without benefit of diagnostic tests. The ability to generalize this study outside of Olmsted County, Minnesota remains challenging in populations with vastly different outpatient populations. The population of Olmsted County is primarily Northern European with over 90% being white.27 Despite this potential weakness, many of the risk factors in this older population confirm previous risk factors in different age and ethnic populations.
In the 1.7% of patients who developed a new venous ulcer in our older outpatient cohort, there were clear risk factors that predicted future venous ulcers. A history of previous venous ulcers was the strongest predictor of future ulceration in our cohort. Patients with prior venous ulceration should be considered high risk for future venous ulceration and should have aggressive edema control. Renal insufficiency, blindness, cataracts and a history of decubitus ulceration also were important factors for the development of venous ulcers. Placing these risk factors in a model with a cutoff total score of 3 yielded a sensitivity of 0.63 and a specificity of 0.88. Practically, the presence of previous venous disease should guide the provider to aggressive prevention. The risk factors in the final model can guide aggressive treatment in particular those patients with edema. Using these findings can help providers target preventive measures through edema management in high risk older adults. Further studies on using this index prospectively with an aggressive intervention might help with clinical care for patients at risk for venous ulceration.