Risk Factors for Incident Hyperuricemia During Mid-adulthood
Risk Factors for Incident Hyperuricemia During Mid-adulthood
There were 8,342 participants included in our study; 63% were female and 19% were African-American. The 9-year cumulative incidence of hyperuricemia was 4% and subgroup cumulative incidence rates were: 5% for men; 3% for women; 6% for African Americans and 3% for whites.
Cohort demographic and clinical risk factors differed by incident hyperuricemia status (Table 1). Overall, participants who developed hyperuricemia were more likely to be male (49% vs. 37%, p-value < 0.001), and African American (33% vs. 18%, p-value < 0.001), and were less likely to have a high school education or higher (73% vs. 83%, p-value < 0.001). Furthermore, participants who developed hyperuricemia were more likely to have chronic conditions at baseline: hypertension (44% vs. 24%, p-value < 0.001), obesity (BMI ≥ 30 kg/m; 37% vs. 21%, p-value < 0.001), diabetes (11% vs. 8%, p-value < 0.05), and CHD (6% vs. 3%, p-value < 0.05). Participants with incident hyperuricemia were more likely to have an eGFR <60 ml/min/1.73 m (4% vs. 1%) or 60–90 ml/min/1.73 m (40% vs. 39%; p-value for trend < 0.001) than those without hyperuricemia. Among female participants, who were free of hyperuricemia by design, there was no difference in menopausal status at baseline and incidence of hyperuricemia, which may be the result of the exclusion of those with hyperuricemia at baseline (Table 1).
Participants who developed hyperuricemia were more likely to have a higher serum urate at baseline, even though the level did not cross the threshold of hyperuricemia by design (6.1 vs. 5.3 mg/dL, p-value < 0.001). This trend persisted during follow-up (3 years after baseline) (7.0 vs. 5.5 mg/dL, p-value < 0.001). Furthermore, there was a greater change in serum urate levels over 3 years (0.87 vs. 0.19, p-value < 0.001) for those who developed hyperuricemia.
The final adjusted model included 9 demographic and clinical risk factors for incident hyperuricemia over 9 years (Table 2). Men were at 1.73-fold (95% CI: 1.36–2.21) increased risk of developing hyperuricemia and African-American participants were at 1.79-fold (95% CI: 1.37–2.33) increased risk. Additional participant demographics such as current smoker (RR = 1.27, 95% CI: 0.97–1.67) and less than a high school education (RR = 1.27, 95% CI: 0.99–1.63) were associated with an increased risk of developing hyperuricemia. Participants with hypertension were at 1.65-fold (95% CI: 1.30–2.09) increased risk of developing hyperuricemia and CHD was associated with an increased but not significant risk of hyperuricemia (RR = 1.57, 95% CI: 0.99–2.50). Additionally, BMI was a strong predictor of incident hyperuricemia; there was an increased risk of developing hyperuricemia for participants who were overweight (RR = 2.01, 95% CI: 1.46–2.78), or had 30 ≤ BMI < 35 kg/m (RR = 2.37, 95% CI: 1.65–3.41) and BMI ≥ 35 kg/m (RR = 3.47, 95% CI: 2.33–5.18). eGFR < 60 (RR = 2.85, 95% CI: 1.62–5.01) at baseline was associated with incident hyperuricemia. Finally, high triglyceride levels were a predictor of incident hyperuricemia (quartile 4 vs. quartile 1: RR = 2.00, 95% CI: 1.38–2.89). There were no differences in the association of smoking status, education, hypertension, BMI, or kidney function between men and women as well as between African Americans and white participants (all p-values for these interactions >0.05).
Serum urate levels at baseline (RR for a 1 mg/dL increase =2.33, 95% CI: 1.94–2.80) and at visit 2 (RR for a 1 mg/dL increase =1.92, 95% CI: 1.78–2.07) were associated with the development of hyperuricemia after accounting for demographic and clinical risk factors (Table 2). Adjusting for baseline and follow-up (3 years after baseline) serum urate levels attenuated the associations of the demographic and clinical risk factors for hyperuricemia. Additionally, the 3-year change in serum urate level was associated with an increased risk of hyperuricemia, such that for every 1 mg/dL increase in serum urate, participants were 1.60-times (95% CI: 1.47–1.74) more likely to develop hyperuricemia after accounting for demographic and clinical risk factors. The association of serum urate level did not differ by sex (women RR = 2.49, 95% CI: 1.96–3.17; men RR = 2.41, 95% CI: 1.77–3.27; p-value for interaction = 0.98).
The results did not materially change when we defined incident hyperuricemia as a serum urate level >6.8 mg/dL. Additionally, the results were similar when the analysis was restricted to post-menopausal women (urate level at visit 1: RR = 2.36, 95% CI: 1.65–3.37; urate level at visit 2: RR = 1.96, 95% CI: 1.74–2.20; change in urate level RR = 1.73, 95% CI: 1.50–2.01).
Results
Study Cohort Characteristics
There were 8,342 participants included in our study; 63% were female and 19% were African-American. The 9-year cumulative incidence of hyperuricemia was 4% and subgroup cumulative incidence rates were: 5% for men; 3% for women; 6% for African Americans and 3% for whites.
Cohort demographic and clinical risk factors differed by incident hyperuricemia status (Table 1). Overall, participants who developed hyperuricemia were more likely to be male (49% vs. 37%, p-value < 0.001), and African American (33% vs. 18%, p-value < 0.001), and were less likely to have a high school education or higher (73% vs. 83%, p-value < 0.001). Furthermore, participants who developed hyperuricemia were more likely to have chronic conditions at baseline: hypertension (44% vs. 24%, p-value < 0.001), obesity (BMI ≥ 30 kg/m; 37% vs. 21%, p-value < 0.001), diabetes (11% vs. 8%, p-value < 0.05), and CHD (6% vs. 3%, p-value < 0.05). Participants with incident hyperuricemia were more likely to have an eGFR <60 ml/min/1.73 m (4% vs. 1%) or 60–90 ml/min/1.73 m (40% vs. 39%; p-value for trend < 0.001) than those without hyperuricemia. Among female participants, who were free of hyperuricemia by design, there was no difference in menopausal status at baseline and incidence of hyperuricemia, which may be the result of the exclusion of those with hyperuricemia at baseline (Table 1).
Participants who developed hyperuricemia were more likely to have a higher serum urate at baseline, even though the level did not cross the threshold of hyperuricemia by design (6.1 vs. 5.3 mg/dL, p-value < 0.001). This trend persisted during follow-up (3 years after baseline) (7.0 vs. 5.5 mg/dL, p-value < 0.001). Furthermore, there was a greater change in serum urate levels over 3 years (0.87 vs. 0.19, p-value < 0.001) for those who developed hyperuricemia.
Demographic and Clinical Risk Factors for Incident Hyperuricemia
The final adjusted model included 9 demographic and clinical risk factors for incident hyperuricemia over 9 years (Table 2). Men were at 1.73-fold (95% CI: 1.36–2.21) increased risk of developing hyperuricemia and African-American participants were at 1.79-fold (95% CI: 1.37–2.33) increased risk. Additional participant demographics such as current smoker (RR = 1.27, 95% CI: 0.97–1.67) and less than a high school education (RR = 1.27, 95% CI: 0.99–1.63) were associated with an increased risk of developing hyperuricemia. Participants with hypertension were at 1.65-fold (95% CI: 1.30–2.09) increased risk of developing hyperuricemia and CHD was associated with an increased but not significant risk of hyperuricemia (RR = 1.57, 95% CI: 0.99–2.50). Additionally, BMI was a strong predictor of incident hyperuricemia; there was an increased risk of developing hyperuricemia for participants who were overweight (RR = 2.01, 95% CI: 1.46–2.78), or had 30 ≤ BMI < 35 kg/m (RR = 2.37, 95% CI: 1.65–3.41) and BMI ≥ 35 kg/m (RR = 3.47, 95% CI: 2.33–5.18). eGFR < 60 (RR = 2.85, 95% CI: 1.62–5.01) at baseline was associated with incident hyperuricemia. Finally, high triglyceride levels were a predictor of incident hyperuricemia (quartile 4 vs. quartile 1: RR = 2.00, 95% CI: 1.38–2.89). There were no differences in the association of smoking status, education, hypertension, BMI, or kidney function between men and women as well as between African Americans and white participants (all p-values for these interactions >0.05).
Serum Urate Level and Incident Hyperuricemia
Serum urate levels at baseline (RR for a 1 mg/dL increase =2.33, 95% CI: 1.94–2.80) and at visit 2 (RR for a 1 mg/dL increase =1.92, 95% CI: 1.78–2.07) were associated with the development of hyperuricemia after accounting for demographic and clinical risk factors (Table 2). Adjusting for baseline and follow-up (3 years after baseline) serum urate levels attenuated the associations of the demographic and clinical risk factors for hyperuricemia. Additionally, the 3-year change in serum urate level was associated with an increased risk of hyperuricemia, such that for every 1 mg/dL increase in serum urate, participants were 1.60-times (95% CI: 1.47–1.74) more likely to develop hyperuricemia after accounting for demographic and clinical risk factors. The association of serum urate level did not differ by sex (women RR = 2.49, 95% CI: 1.96–3.17; men RR = 2.41, 95% CI: 1.77–3.27; p-value for interaction = 0.98).
The results did not materially change when we defined incident hyperuricemia as a serum urate level >6.8 mg/dL. Additionally, the results were similar when the analysis was restricted to post-menopausal women (urate level at visit 1: RR = 2.36, 95% CI: 1.65–3.37; urate level at visit 2: RR = 1.96, 95% CI: 1.74–2.20; change in urate level RR = 1.73, 95% CI: 1.50–2.01).
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