Abstract
Objective
Asymptomatic hyperuricemia is a precursor of gout and is also associated with cardiovascular disease and chronic kidney disease. The aim of this study was to understand perceptions about asymptomatic hyperuricemia and views about urate‐lowering therapy in people with asymptomatic hyperuricemia.
Methods
Participants in a multinational study of asymptomatic hyperuricemia completed questionnaires about their perceptions of hyperuricemia, concern about hyperuricemia‐associated health conditions, and willingness to take urate‐lowering medication. All had a screening serum urate of ≥0.48 mmol/L (8 mg/dL) and no current or previous symptoms of gout.
Results
Overall, participants perceived that hyperuricemia had no or very few consequences on their life. Dietary factors were the most reported cause, whereas 37% did not know the cause. Participants reported a wide range in concern about hyperuricemia and the risk of developing gout. Concern about the risk of developing kidney disease or cardiovascular disease was also highly variable but was higher than concern about elevated serum urate (P < 0.001). Most did not think a urate‐lowering medication was necessary, and there was moderate concern about the long‐term use of urate‐lowering medication. Medication necessity beliefs were most strongly associated with whether participants were willing to take urate‐lowering medication (partial R2 = 0.27, P < 0.001).
Conclusion
Most participants perceived minimal consequences of asymptomatic hyperuricemia. Hyperuricemia was not well understood by participants, and biologic causes were generally underrecognized. Despite a range of concerns about hyperuricemia‐associated conditions, particularly kidney disease and cardiovascular disease, a urate‐lowering medication for asymptomatic hyperuricemia was not considered necessary, which aligns with most current management guidelines.
INTRODUCTION
Hyperuricemia (elevated serum urate level) is the necessary precursor for the development of gout 1 , 2 and is also associated with cardiovascular disease and chronic kidney disease. 3 , 4 Many factors contribute to serum urate concentrations, including genetic factors, kidney function, body mass index, dietary factors, and medications. 5 , 6 There is a strong concentration‐dependent relationship between serum urate and development of gout, with a hazard ratio of >60 for the highest concentrations of serum urate. 2 Currently, urate‐lowering therapy is not recommended for asymptomatic hyperuricemia, 7 and most people with hyperuricemia have no symptoms and do not develop gout. 2
SIGNIFICANCE & INNOVATIONS.
Illness perceptions are key determinants of patients’ behavior for managing health conditions.
Asymptomatic hyperuricemia is common and is a precursor to gout.
This study provides new insights into perceptions about hyperuricemia and views about urate‐lowering therapy in people with asymptomatic hyperuricemia.
Illness perceptions are key determinants of patients’ behavior for managing health conditions and have been associated with important outcomes in chronic diseases. 8 When faced with a new health threat, individuals will actively construct a mental representation of the illness and this guides their behavior to manage the condition, such as engagement with treatment. 9 Research suggests that it is difficult for individuals to conceive of illnesses without symptoms and consider such symptom‐less illnesses to be a serious threat to health. 10 , 11
Perceptions of the benefits and concerns about medication are also important factors in patients’ acceptance and adherence to new treatment regimens. Perceptions of the necessity of the medicine, as well as concerns about potential adverse effects, strongly influence a person's willingness to initiate and maintain a prescribed therapy. 12 Studies suggest that individuals who view medications as essential for managing their condition are more likely to adhere, whereas those with concerns about dependency or side effects exhibit lower adherence and persistence with the treatment. 13
Although many studies have examined patient perceptions about gout, perceptions of asymptomatic hyperuricemia have not been reported. This is a relevant question because asymptomatic hyperuricemia is common 14 and can progress to gout. The aim of this study was to understand perceptions about asymptomatic hyperuricemia and views about urate‐lowering therapy in people with asymptomatic hyperuricemia.
METHODS
This was a prespecified analysis of baseline data from the Transitions in Gout Research (TIGER) study. The TIGER study is a five‐year international multicenter prospective cohort study designed to understand risk factors for development of gout in people with asymptomatic hyperuricemia. The study has been registered (ACTRN12619000915156), and the full study protocol has been published. 15
In brief, TIGER study participants were recruited from June 2019 to August 2024 at study sites in New Zealand (three sites), France, Spain, Lithuania, United States, China, and Mexico. Participants were recruited from primary and secondary care settings, by public advertising, and through community pathology collection centers. All participants had a screening serum urate of ≥0.48 mmol/L (8 mg/dL), had no current or previous clinical symptoms of gout, and were aged between 18 and 80 years. The key exclusion criteria were as follows: CKD4 or worse; other forms of inflammatory arthritis; serious illness with poor prognosis less than five years; previous synovial fluid analysis showing monosodium urate crystals; clinically evident tophi; taking urate‐lowering therapy, canakinumab, or colchicine. This study was approved by the New Zealand Ministry of Health Southern Health and Disability Ethics Committee (MEC/05/10/130AM16) and by the local institutional review board for each participating center. All participants provided written informed consent.
All participants completed a baseline visit at the study site. The baseline visit included recording of demographic data, clinical risk factor assessment, and physical examination including body mass index and waist circumference. Current medications and health conditions were recorded, including those documented in the modified Rheumatic Disease Comorbidity Index (mRDCI). 16 Participants also completed 100 mm pain visual analog scales for pain over the last week and global assessment of health. Laboratory tests were taken for measurement of serum creatinine, and estimated glomerular filtration rate (eGFR) was calculated according to the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) equation. 17
At the baseline visit, participants also completed a hyperuricemia‐specific Brief Illness Perceptions Questionnaire (BIPQ) 18 ; because urate‐lowering therapy use was an exclusion, the treatment control item in the BIPQ was not included. Participants also were asked about their concern about hyperuricemia‐associated health conditions (gout, kidney disease, and cardiovascular disease; 0–10 Likert scale) and completed the Beliefs About Medicines Questionnaire 19 subscales, which assessed their views about medicines in general, and two questions about their specific views about taking medications to reduce serum urate (0–10 Likert scale): “How much do you feel you need medication to reduce your urate level?” and “How concerned are you about the long‐term use of a medicine to reduce your urate level?” To assess how willing the person would be to take a medication to reduce their serum urate we asked, “How agreeable would you be to taking a medication to reduce your urate level?” (0–10 Likert scale, with 0 being not at all agreeable and 10 being extremely agreeable). All questionnaires were translated and completed in the local language.
The current analysis was a descriptive and exploratory (hypothesis generating) cross‐sectional study because a specific hypothesis was not tested and inferential analysis was not the main objective. Given the low missing data rate, complete case analysis/listwise deletion was used throughout. Data from all participating sites were entered into a central database at the coordinating site at the University of Auckland, Auckland, New Zealand. Means with SDs and percentages were used to describe the demographic and clinical characteristics of participants. Medians with interquartile ranges (IQRs) and percentages were used to describe the results of the questionnaires. “Agreeable to take a medication to reduce serum urate” scores were modeled. Variables were selected for inclusion in the model using external clinical judgment based upon previous experience with each of the instruments to reduce the risk of overfitting and to avoid a completely P value–driven model selection process. A further screening process to determine those variables with significant Spearman correlation with the prespecified dependent variable was performed to reduce the number of variables in the model, and iterative stepwise regression was then performed to optimize the order of inclusion of variables in the model because some collinearity was anticipated. Diagnostic plots, including plots of residual, normal probability plots and leverage plots were produced using the REG procedure of SAS and inspected to establish the goodness of fit of the model and that the residuals were normally distributed. Multicollinearity was assessed using the variance inflation factor. A variance inflation factor >5 indicated multicollinearity. 20 The final model was reviewed for clinical and scientific relevance to determine whether post hoc inclusion of additional variables in the model was required, and the final model was selected on the basis of clinical relevance, parsimony, and goodness of fit. Standardized beta coefficients were tabulated to enable comparison between variables. General linear modeling was used to compare concern between hyperuricemia‐associated disease conditions. A significant main effect was reduced to pairwise comparisons with P adjusted using the method of Tukey to preserve an overall 5% significance level. The procedures of SAS (version 9.04; SAS Institute Inc) were used for these analyses.
RESULTS
Participant characteristics
The cohort included 268 people with asymptomatic hyperuricemia who completed the BIPQ. None of the participants had a history of arthritis or clinical evidence of synovitis or subcutaneous tophi at the time of the baseline study visit. The clinical features of these individuals are shown in Table 1. Participants were predominantly men, with mean age 48 years and mean body mass index 30.5 kg/m2. Pain scores were low, and global assessment of health was high. Mean serum urate concentration was 0.52 mmol/L (8.7 mg/dL).
Table 1.
Clinical features of participants*
| Clinical feature (n = 268) | Mean (±SD) or n (%) |
|---|---|
| Age, y | 48 (±18) |
| Male | 218 (81) |
| Ethnicity | |
| African/Black | 5 (1.9) |
| East Asian | 65 (24.3) |
| Hispanic | 10 (3.7) |
| Māori | 11 (4.1) |
| Pacific Islander | 19 (7.1) |
| South Asian | 36 (13.4) |
| White | 112 (41.8) |
| Other Indigenous | 1 (0.4) |
| Other/unknown | 9 (3.4) |
| Country of residence | |
| New Zealand | 144 (53.7) |
| China | 64 (23.9) |
| France | 21 (7.8) |
| Spain | 21 (7.8) |
| Mexico | 10 (3.7) |
| Lithuania | 8 (3.0) |
| Hypertension | 109 (40.7) |
| Cardiovascular disease a | 58 (22) |
| Type 2 diabetes | 34 (12.7) |
| eGFR < 60 mL/minute/1.73 m2 | 38 (15) |
| eGFR, mL/minute/1.73 m2 | 90.4 (±25.2) |
| Modified Rheumatic Disease Comorbidity Index score | 2.38 (±2.20) |
| Units of alcohol/day | 4.2 (±7.6) |
| Units of beer/day | 1.9 (±5.2) |
| Aspirin use | 23 (8.6) |
| Diuretic use | 44 (16.4) |
| Body mass index, kg/m2 | 30.5 (±6.5) |
| Waist circumference, cm | 103.3 (±15.6) |
| Pain score, 100‐mm VAS | 12.0 (±21.4) |
| Patient global assessment of health, 100‐mm VAS | 81.1 (±16.3) |
| Serum urate, mmol/L | 0.52 (±0.04) |
| Serum creatinine, μmol/L | 91.4 (±26.3) |
eGFR, estimated glomerular filatration rate; VAS, visual analog scale.
Included are chronic heart failure, peripheral vascular disease, myocardial revascularization, peripheral artery surgery revascularization (including aortic aneurysm), cardiac arrhythmia (atrial fibrillation/flutter), angina, myocardial infarction, and stroke.
Perceptions about hyperuricemia
Overall, participants perceived that hyperuricemia had no or very little consequences on their life, and the presence of hyperuricemia had little emotional impact (Table 2). There was wide variation in participants’ perceptions of chronicity and personal control and concern about elevated serum urate levels. Participants tended to report low understanding about hyperuricemia. Dietary factors were the most reported factor believed to cause elevated serum urate levels, whereas 37% described that the cause of their hyperuricemia as unknown. Genetic factors were believed to be the most important cause in 8.9% of participants.
Table 2.
Perceptions about hyperuricemia, beliefs about medicines in general, and views about medications to reduce serum urate*
| Characteristic | Median (25th–75th percentile range) |
|---|---|
| Brief Hyperuricemia Perception Questionnaire | |
| Consequences (10 = severely affects life) | 0 (0–2) |
| Timeline (10 = will continue forever) | 4 (2–7) |
| Personal control (10 = extreme amount) | 5 (2–6) |
| Symptoms (10 = severe symptoms) | 0 (0–1) |
| Concern (10 = extremely concerned) | 5 (2–7) |
| Understanding (10 = very clearly) | 4 (1–7) |
| Emotional response (10 = extremely affected) | 1 (0–3) |
| Most important factor believed to cause hyperuricemia | |
| Dietary factors, n (%) | 102 (38) |
| Unknown, n (%) | 100 (37) |
| Genetic factors, n (%) | 24 (8.9) |
| Overweight, n (%) | 18 (6.7) |
| Medications, n (%) | 7 (2.6) |
| Kidney disease, n (%) | 7 (2.6) |
| Other health condition, n (%) | 7 (2.6) |
| Lack of exercise, n (%) | 3 (1.1) |
| Other, n (%) | 2 (0.7) |
| Concern about hyperuricemia‐associated health conditions | |
| Concern about risk of developing gout (10 = extremely concerned) | 5 (3–8) |
| Concern about risk of developing kidney disease (10 = extremely concerned) | 6 (3–9) |
| Concern about risk of developing cardiovascular disease (10 = extremely concerned) | 6 (3–9) |
| Beliefs About Medicines Questionnaire—general subscales | |
| Harm subscale (maximum score 20) | 9.5 (9–12) |
| Overuse subscale (maximum score 20) | 12 (10–14) |
| Benefit subscale (maximum score 20) a | 16 (15–18) |
| Views about using medication to reduce serum urate | |
| Need to take medication to reduce serum urate (10 = essential) | 2 (0–5) |
| Agreeable to take a medication to reduce serum urate (10 = extremely agreeable) b | 5 (2–8) |
| Concern about the long‐term use of a medication to reduce serum urate (10 = extremely concerned) | 6 (2–8) |
a The benefit subscale is missing beliefs about medicines benefit questions from one site (n = 247 for this variable).
Responses were available from 258 participants.
Consistent with concern about elevated serum urate levels, participants reported a wide range in concern about the risk of developing gout (Table 2). There was similar concern about hyperuricemia and the risk of developing gout (post hoc Tukey P = 0.11). Concern about the risk of developing kidney disease or cardiovascular disease was also highly variable but was higher than concern about hyperuricemia (post hoc Tukey P < 0.001 for both kidney disease and cardiovascular disease).
Views about medications to reduce serum urate levels
Generally, participants viewed medications positively (Table 2). Most did not think they needed medication to reduce their serum urate, and there was moderate concern about long‐term medication use. There was a highly variable response about whether they were agreeable to take a medication to reduce the serum urate with median (IQR) score 5 (2–8; Figure 1).
Figure 1.
Distribution of agreeable to taking a medication to reduce serum urate scores (0 being not at all agreeable and 10 being extremely agreeable).
In bivariable analysis, willingness to take a medication to reduce the serum urate associated with concern about hyperuricemia and risk of developing hyperuricemia‐associated health conditions (gout, kidney disease, and cardiovascular disease), perceived need to take a medication to reduce the serum urate, beliefs about medicines, and comorbidities (Table 3). In multivariable analysis, the perceived need for medication to reduce serum urate was most strongly associated with whether participants were agreeable to take urate‐lowering medication (R2 = 0.27, P < 0.001; Table 4). In addition, beliefs about the harms and benefits of medicines, the mRDCI, and concern about hyperuricemia were significantly associated (model cumulative R2 = 0.38, P < 0.001). Sex or geographic region was not associated with willingness to take urate‐lowering medications.
Table 3.
Correlations between being agreeable to take a medication to reduce serum urate scores and other variables*
| Variables | Spearman r (95% CI) | P value |
|---|---|---|
| Age, y | 0.08 (−0.04 to 0.20) | 0.18 |
| Male sex | 0.04 (−0.09 to 0.16) | 0.56 |
| Serum urate level | 0.03 (−0.15 to 0.10) | 0.68 |
| Modified Rheumatic Disease Comorbidity Index | 0.24 (0.12 to 0.35) | <0.0001 |
| Brief Hyperuricemia Perception Questionnaire | ||
| Consequences (10 = severely affects life) | 0.02 (−0.10 to 0.14) | 0.74 |
| Timeline (10 = will continue forever) | 0.06 (−0.07 to 0.18) | 0.37 |
| Personal control (10 = extreme amount) | −0.002 (−0.13 to 0.12) | 0.98 |
| Symptoms (10 = severe symptoms) | 0.05 (−0.07 to 0.18) | 0.37 |
| Concern (10 = extremely concerned) | 0.17 (0.05 to 0.29) | 0.0061 |
| Understanding (10 = very clearly) | 0.08 (−0.04 to 0.20) | 0.21 |
| Emotional response (10 = extremely affected) | 0.04 (−0.08 to 0.16) | 0.51 |
| Concern about hyperuricemia‐associated health conditions | ||
| Concern about risk of developing gout (10 = extremely concerned) | 0.22 (0.09 to 0.33) | 0.0006 |
| Concern about risk of developing kidney disease (10 = extremely concerned) | 0.22 (0.11 to 0.34) | 0.0003 |
| Concern about risk of developing cardiovascular disease (10 = extremely concerned) | 0.24 (0.12 to 0.35) | 0.0001 |
| Beliefs About Medicines Questionnaire—general subscales | ||
| Harm subscale (maximum score 20) | −0.28 (−0.39 to −0.16) | <0.0001 |
| Overuse subscale (maximum score 20) | −0.15 (−0.28 to −0.03) | 0.015 |
| Benefit subscale (maximum score 20) | 0.30 (0.18 to 0.41) | <0.0001 |
| Views about medications to reduce serum urate | ||
| Need to take medication to reduce serum urate (10 = essential) | 0.45 (0.34 to 0.54) | <0.0001 |
| Concern about the long‐term use of a medication to reduce serum urate (10 = extremely concerned) | 0.02 (−0.11 to 0.14) | 0.80 |
CI, confidence interval.
Table 4.
Stepwise linear regression model to determine variables associated with being agreeable to taking a medication to reduce serum urate scores*
| Variable | ß coefficient | SE | Standardized ß coefficient | 95% confidence intervals | t value | P value | Partial R2 | Cumulative R2 | VIF |
|---|---|---|---|---|---|---|---|---|---|
| Perceived need for medication to reduce urate | 0.497 | 0.066 | 0.419 | 0.366 to 0.627 | 7.50 | <0.0001 | 0.270 | 0.270 | 1.152 |
| BMQ‐harm | −0.227 | 0.064 | −0.202 | −0.353 to −0.101 | −3.55 | 0.0005 | 0.059 | 0.329 | 1.193 |
| Modified Rheumatic Disease Comorbidity Index | 0.205 | 0.084 | 0.132 | 0.043 to 0.370 | 2.45 | 0.015 | 0.017 | 0.346 | 1.069 |
| BMQ‐benefit | 0.190 | 0.081 | 0.137 | 0.030 to 0.350 | 2.35 | 0.020 | 0.012 | 0.358 | 1.250 |
| Brief Hyperuricemia Perception Questionnaire‐concern | 0.157 | 0.058 | 0.149 | 0.041 to 0.272 | 2.68 | 0.008 | 0.019 | 0.377 | 1.145 |
All variables with P < 0.05 in the bivariate correlation analysis shown in Table 3 were included in the model. The following variables were included in this model: modified Rheumatic Disease Comorbidity Index, Brief Hyperuricemia Perception Questionnaire‐concern, concern about gout risk, concern about kidney disease risk, concern about heart disease risk, BMQ‐harm, BMQ‐overuse, BMQ‐benefit, and perceived need for medication to reduce urate. BMQ, Beliefs About Medicines Questionnaire. VIF, variance inflation factor.
DISCUSSION
This study provides novel insights into the views and experience of people with asymptomatic hyperuricemia. Consistent with an asymptomatic condition, participants reported low scores for the consequences, symptoms, and emotional response domains of the hyperuricemia‐specific BIPQ. There was a broad range of concern about hyperuricemia and hyperuricemia‐associated conditions including gout, kidney disease, and cardiovascular disease. Participants did not consider that a urate‐lowering medication was needed, which is consistent with most current international management guidelines.
As reported in our prior studies of gout, dietary factors were considered the most important factor causing asymptomatic hyperuricemia. 21 , 22 , 23 , 24 More than one‐third of participants did not know the cause, and fewer than 10% of participants reported that genetic factors were the most important factor. Biologic causes such as genetic variants, kidney function, and body composition were generally underrecognized in contrast to the scientific literature, which shows that these factors play a central role in serum urate regulation. 5 , 6 , 25 , 26 These findings highlight the ongoing gap of translating scientific discoveries to community understanding about hyperuricemia and gout.
The study provides insights into personal decisions about taking medications, particularly for an asymptomatic laboratory finding. Our findings indicate the importance of patient perceptions about the need for medication. In the context of asymptomatic hyperuricemia, there is some evidence that incident gout can be prevented with urate‐lowering therapy, 27 but there is no compelling evidence for prevention of kidney disease progression 28 , 29 , 30 or cardiovascular disease. 27 Study participants reported low necessity beliefs about urate‐lowering medication, which is consistent with current evidence and management guidelines. Collectively, these data indicate that much more compelling evidence would be needed for people with asymptomatic hyperuricemia to adopt urate‐lowering medication.
Our findings about willingness to take urate‐lowering therapy for asymptomatic hyperuricemia align with numerous studies that reported that beliefs about the necessity of treatment is a strong predictor of medication adherence in long‐term symptomatic health conditions. 13 The results suggest that it would be difficult for individuals to take long‐term medication for asymptomatic hyperuricemia because the condition elicits a low level of concern and perceived consequences. Moreover, the treatment is seen as not essential, and people with asymptomatic hyperuricemia have moderate concern for taking medication for the condition long term.
Study strengths include the well‐characterized multinational cohort, with consistent phenotyping and data collection. It should be noted that the study findings may not be generalizable to all people with asymptomatic hyperuricemia because the study participants were volunteers in a cohort study of asymptomatic hyperuricemia and may have had different perceptions and health concerns to those not volunteering for the study. Additionally, this was a cross‐sectional study, and hypothetical views about taking a medication in the context of a research questionnaire may not translate to medication adherence in real life.
In summary, most people with asymptomatic hyperuricemia report no or very few self‐identified consequences of this laboratory finding. Asymptomatic hyperuricemia is not well understood, and biologic causes are generally underrecognized by people with asymptomatic hyperuricemia. Despite a range of concerns about hyperuricemia‐associated conditions, particularly kidney disease and cardiovascular disease, a urate‐lowering medication was not considered necessary by individuals with asymptomatic hyperuricemia, which is in line with most of the current management guidelines regarding asymptomatic hyperuricemia.
AUTHOR CONTRIBUTIONS
All authors contributed to at least one of the following manuscript preparation roles: conceptualization AND/OR methodology, software, investigation, formal analysis, data curation, visualization, and validation AND drafting or reviewing/editing the final draft. As corresponding author, Dr Dalbeth confirms that all authors have provided the final approval of the version to be published, and takes responsibility for the affirmations regarding article submission (eg, not under consideration by another journal), the integrity of the data presented, and the statements regarding compliance with institutional review board/Declaration of Helsinki requirements.
ROLE OF THE STUDY SPONSOR
The Health Research Council of New Zealand had no role in the study design or in the collection, analysis, or interpretation of the data or the decision to submit the manuscript for publication. Publication of this article was not contingent upon approval by Health Research Council of New Zealand.
Supporting information
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ACKNOWLEDGMENTS
Open access publishing facilitated by The University of Auckland, as part of the Wiley ‐ The University of Auckland agreement via the Council of Australian University Librarians.
Supported by the Health Research Council of New Zealand (grant 19/232). Dr Stewarts's work was supported by the Auckland Medical Research Foundation Postdoctoral Fellowship (grant 1318001). Dr Neogi's work was supported by National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH (grants K24‐AR‐070892 and P30‐AR‐072571). Dr Pascart's work was supported by funding from Horizon Pharmaceuticals (Amgen) for the French site. Dr Sun's work was supported by an Excellent Physician Scholarship from Simcere Pharma, Nanjing, China. Dr Li's work was supported by the National Key Research and Development Program of China (2022YFC2503300).
Author disclosures are available at https://onlinelibrary.wiley.com/doi/10.1002/acr.25639.
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