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Recent studies have demonstrated an association of gout with an increased risk of cardiovascular (CV) mortality. The association proven is indirect, through the relation of gout with CV-related comorbidity and risk factors. The objective was to test whether the relation of mortality and gout may be direct, that is, whether the severity of gout may be associated to CV mortality.
Method:
Prospective longitudinal study of all gout patients ever attended at a single Gout clinic. Baseline variables included sociodemographics, use of urate lowering drugs (ULD), number of joints affected, presence of tophi, number of flares in the previous year, prevalent CV disease, alcohol intake, and CV risk factors. Vital status was investigated in any patient who did not attend a follow-up visit. Kaplan-Meier estimates and log-rank test were used to identify variables associated with mortality. Variables found to have a statistical association with mortality in the bivariate analysis were selected for a multivariate Cox proportional hazard regression analysis using a stepwise model. The Standardized Mortality Rate (SMR) was calculated comparing the mortality observed in the sample to the expected rate in the general population of similar age and sex (2005 National Statistics).
Results:
From 1992 to November 2008, 706 patients were included, 662 (94%) of whom were men. At baseline, 436 (72%) had never received ULDs, 358 (51%) had 2 to 4 joints involved and 244 (35%) >4, and 215 (31%) had tophi. A CV disease was present in 178 (26%) cases, 153 (22%) used diuretics regularly, 142 (20%) had diabetes mellitus, 291 (41%) had arterial hypertension, and 298 (42%) had hyperlipidemia. During follow-up (range: 1 month to 14 years), 64 (9%) patients died (55 men and 9 women), with 38 (70%) attributed to CV cause. The SMR (any cause) in patients with gout was 2.37 (95% CI: 1.82 to 3.03)[men 1.57 (95% CI: 1.18 to 2.05); women 4.50 (95% CI: 2.06 to 8.54)]. The SMR (CV cause) was 3.88 (95% CI: 2.70 to 5.40). The following baseline variables were significantly associated to mortality in the bivariate analysis: age, gender, number of flares, presence of tophi, number of joints involved, secondary gout, ethanol intake, hypertension, diabetes, renal insufficiency, diuretic use, and previous cardiovascular disease. Only four of these variables were found to be independently and statistically significantly associated with mortality:
Table 1. Variables independently associated with mortality in gout patients.
| Hazard ratio | 95% CI | p | |
| Age (by year) | 1.07 | 1.04 – 1.10 | <.001 |
| Serum urate (per mg/dl) | 1.20 | 1.06 – 1.36 | .004 |
| Secondary gout | 2.45 | 1.33 – 4.54 | .004 |
| Presence of tophi | 1.84 | 1.12 – 3.02 | .016 |
| Prevalent CV disease | 2.01 | 1.06 – 3.81 | .033 |
Conclusions:
Patients with gout may have an excess mortality and an excess CV mortality. Severity of gout at baseline is associated to increased mortality as much as prevalent CV disease. These results emphasize the importance of not delaying intense treatment in gout patients.
Disclosure: F. Perez-Ruiz, Ipsen, 5, Savient, 5, Pfizer Inc, 5, Ardea Biosciences, 5 ; L. Martinez-Indart, None; L. Carmona, None; A. M. Herrero-Beites, Ipsen, 5, Savient, 5, Pfizer Inc, 5, Ardea Biosciences, 5 ; J. I. Pijoan, None.