Sample characteristics
Among the 29,742 participants included in the analysis, 4,505 (15.15%) reported a history of CVD. Their mean age was 57.21 ± 11.89 years, and 47.38% were male. The average UHR was 11.27 ± 5.18 mg/dL. The weighted sample characteristics across UHR quartiles are shown in Table 2. The higher UHR quartile group tends to be older, have more males, and have a higher body mass index (BMI). Furthermore, the higher UHR quartile group has more CVD cases, including coronary heart disease, heart attack, heart failure, angina pectoris, and stroke, and higher all-cause and CVD-specific mortality. These findings suggest positive associations between UHR and CVD risk and mortality.
Relationship between UHR and CVDs
Table 3 presents the relationships between UHR and various CVDs using multiple logistic regression models, both with and without adjustments for covariates. The results indicate that UHR is significantly and positively correlated with total CVD, including coronary heart disease, heart attack, heart failure, angina pectoris, and stroke (P all< 0.05).
A positive association between UHR and the total CVD risk was consistently observed in Model 1 (OR = 1.07, 95% CI: 1.06–1.08, P < 0.001), Model 2 (OR = 1.07, 95% CI: 1.06–1.08, P < 0.001), and Model 3 (OR = 1.04, 95% CI: 1.03–1.05, P < 0.001). Model 3 revealed that each unit increase in UHR was associated with a 4% increase in the total CVD risk. Quartile analysis further showed that the highest UHR quartile group had significantly higher total CVD risk than the lowest quartile group (OR = 1.60, 95% CI: 1.38–1.81, P < 0.001) after full adjustment.
The association between UHR and heart failure was similarly robust, with every unit increase in UHR corresponding to a 7% increased risk in Model 3 (OR = 1.07, 95% CI: 1.05–1.08, P < 0.001). Quartile comparisons showed that the highest UHR quartile group had over twice the risk of heart failure than the lowest quartile group (OR = 2.23, 95% CI: 1.69–2.95, P < 0.001).
For coronary heart disease, angina pectoris, and heart attack, UHR remained significantly associated with increased risk in all models, with risk increments of approximately 4% per unit increase in UHR. Participants in the highest quartile consistently exhibited significantly higher risks for these conditions compared to the lowest quartile. Finally, stroke risk was also positively associated with UHR, with a 3% increase in risk per unit of UHR in Model 3 (OR = 1.03, 95% CI: 1.01–1.04, P < 0.001). The highest UHR quartile group had a higher risk of stroke than the lowest quartile group (OR = 1.32, 95% CI: 1.04–1.67, P = 0.024).
RCS analysis investigating the relationship between UHR and CVDs
Figure 3 illustrates the flexible modeling of the relationship between UHR and various CVD types, including coronary heart disease, heart attack, heart failure, angina pectoris, stroke, and total CVD, using restricted cubic splines (RCS). In Model 3, UHR showed linear associations with heart attack, heart failure, angina pectoris, stroke, and total CVD (P overall < 0.001, P nonlinear > 0.05) and a nonlinear association with coronary heart disease (P overall < 0.001, P nonlinear = 0.018).
Restricted cubic spline curve for the association between UHR and CVDs risk in model 3 (adjusted for age, sex, race, education levels, marital status, BMI, smoking, hypertension, diabetes, total cholesterol, and cancer). (a) Restricted cubic spline curve for the association between UHR and Total CVD. (b) Restricted cubic spline curve for the association between UHR and Heart Failure. (c) Restricted cubic spline curve for the association between UHR and Coronary Heart Disease. (d) Restricted cubic spline curve for the association between UHR and Angina Pectoris. (e) Restricted cubic spline curve for the association between UHR and Heart Attack. (f) Restricted cubic spline curve for the association between UHR and Stroke. Lines represent odds ratios (OR), and colored areas represent 95% confidence intervals (CI). UHR, Uric acid to High-density lipoprotein cholesterol ratio.
Associations between UHR and All-Cause and CVD-specific mortality
Over 9.14 years of follow-up, 6,298 participants (15.58%) died, of which 1,618 deaths (3.90%) were attributed to cardiovascular disease. Table 4 shows the associations between UHR and all-cause and CVD-specific mortality based on weighted Cox regression models, both unadjusted and adjusted for covariates. The analyses revealed a significant positive relationship between UHR and the two outcomes (P < 0.05).
For all-cause mortality, higher UHR consistently correlated with increased risk in all models, including Model 1 (HR = 1.03, 95% CI: 1.02–1.04), Model 2 (HR = 1.03, 95% CI: 1.02–1.04), and Model 3 (HR = 1.02, 95% CI: 1.02–1.03, P < 0.001). In Modell 3, every one-unit increase in UHR corresponded to a 2% rise in mortality risk. Quartile analysis further revealed that the highest UHR quartile group had significantly higher all-cause mortality risk than the lowest quartile group (HR = 1.36, 95% CI: 1.15–1.61, P < 0.001).
Regarding cardiovascular disease mortality, a similar positive association was observed in all models. In Model 3, if UHR increased by one unit, CVD-specific mortality would increase by 3% (HR = 1.03, 95% CI: 1.02–1.05, P < 0.001). Quartile comparisons also highlighted that the highest UHR quartile group had a higher CVD-specific mortality risk than the lowest quartile group (HR = 1.37, 95% CI: 1.00–1.89, P = 0.049).
RCS analyses
RCS was applied within the Cox proportional hazards model further to test the linear association between UHR and mortality (Fig. 4). In Model 3, UHR presented a significant nonlinear relationship with all-cause mortality (P overall < 0.001, P nonlinear < 0.001) and a linear association with CVD-specific mortality (P overall < 0.001, P nonlinear = 0.408).
Restricted cubic spline curve for the association between UHR and and mortality in model 3 (adjusted for age, sex, race, education levels, marital status, BMI, smoking, hypertension, diabetes, total cholesterol, and cancer). (a) Restricted cubic spline curve for the association between UHR and All-cause mortality. (b) Restricted cubic spline curve for the association between UHR and Cardiovascular disease mortality. Lines represent hazard ratios (HR), and colored areas represent 95% confidence intervals (CI). UHR, Uric acid to High-density lipoprotein cholesterol ratio.
Subgroup analyses
Subgroup analyses were conducted to test whether the relationship between UHR and all-cause and CVD-specific mortality varied across various subgroups stratified by sociodemographics (e.g., race, sex, age, education, marital status) and medical history (e.g., diabetes, hypertension, and cancer). As shown in Table 5, the associations between UHR and both mortality outcomes remained stable across all subgroups (P interaction > 0.00625), indicating no significant interactions with these stratification variables.
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