Quantitative Assessment of Baseline Serum HDL-C to Predict Gout Flares During Urate-Lowering Therapy Initiation: A Prospective Cohort Study

Abstract

Purpose: Previous studies have linked high-density lipoprotein cholesterol (HDL-C) to gout, but little is known about the dose-effect relationship between serum HDL-C levels and gout flares. This study aimed to quantify the association between the two during urate-lowering therapy initiation and develop a regression equation to predict gout flares.

Patients and methods: We conducted a prospective, observational, single-center cohort study of men with gout. Patients were identified and grouped according to the level of serum HDL-C (1.16 mmol/L) at baseline and followed-up every four weeks until 12 weeks.

Results: A total of 394 participants completed the study (203 in the low HDL-C group; 191 in the high HDL-C group). The proportion of participants with gout flares in the low HDL-C group was significantly higher than in the high HDL-C group after 12 weeks follow-up (52.2% versus 35.6%, P=0.001). Patients with lower serum HDL-C level had higher risk of gout flares analyzed by restricted cubic spline and when serum HDL-C level = 1.15mmol/L, flare_HR = 1. When combined with well-known risk factors, serum HDL-C predicted gout flares with an area under curve (AUC) of 0.75 (95% CI=0.70-0.80). Based on the logistic regression coefficients, we derived the following regression equation: Logit (P)= -2.282+0.05× [disease duration]+1.015× [recurrent flares in the last year]+0.698× [palpable tophus]+0.345× [serum urate]-1.349×[serum HDL-C].

Conclusion: Patients with gout presented a negative linear relationship between serum HDL-C and gout flares. Together with common clinical indicators, the AUC for gout flare prediction increased to 0.75. For patients with gout, remaining serum HDL-C level above 1.15 mmol/L may reduce the risk of gout flares.

Keywords: AUC; inflammation; life style intervention; prediction.

Figure 1

Flow chart.

Figure 2

Gout flares in the low and high HDL-C group over the 12 weeks follow-up. (A) Comparison of percentage of patients with gout flares between the low and high HDL-C group over 12 weeks. (B) Comparison of percentage of patients with gout flares between the low and high HDL-C group every 4 weeks. (C) Comparison of percentage of patients without gout flare between the low and high HDL-C group during the follow-up. (D) Comparison of percentage of patients without recurrent gout flares between the low and high HDL-C group during the follow-up. HDL-C, high-density lipoprotein cholesterol.

Figure 3

Restricted cubic spline of the association between serum HDL-C and gout flares. Spline plot of serum HDL-C level and gout flares. (A) Original model to explore relationship between serum HDL-C and gout flares without adjustment. (B) Adjusted for disease duration, palpable tophus, BMI, eGFR, serum urate, ALT, AST, blood glucose, triglyceride, LDL-C. The hazard ratios and 95% confidence intervals (CIs) were calculated with cox regression model. The dashed lines were x–value when HR was 1. BMI, body mass index; eGFR, estimated glomerular filtration rate; ALT, alanine aminotransferase; AST, aspartate aminotransferase; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol. P for overall < 0.05 means serum HDL-C and gout flares had correlation. P for nonlinear > 0.05 means correlation between serum HDL-C and gout flares was linear.

Figure 4

ROC curve of HDL-C for gout flare over 12 weeks. ROC: receiver operating characteristic. AUC: area under the curve. Five variables including serum HDL-C, serum urate, disease duration, palpable tophus and recurrent flares in the last year (≥ 2).