Gout has long been recognized not merely as a localized joint disease but as a systemic metabolic disorder associated with a significant burden of comorbidities. These range from conditions affecting the quality of life, such as erectile dysfunction 1, to life-threatening complications, most notably cardiovascular disease (CVD) 2. Furthermore, gout significantly augments the risk of CVD in patients with concurrent inflammatory conditions, such as psoriasis 3. While the direct link between gout flares and acute cardiovascular events is well-established, recent evidence highlights that this danger begins precisely at the onset of the disease. In a critical 2025 study, Cipolletta and colleagues demonstrated a significant, transient spike in cardiovascular events—including myocardial infarction and stroke—within the first 30 days following a new gout diagnosis 4. This early risk is likely driven by intense systemic and vascular inflammation during initial gout flares, underscoring the urgent need for proactive cardiovascular risk management from the very first consultation. Recognizing this immediate cardiovascular threat naturally leads to the question of whether “treating to target” (T2T) with urate-lowering therapy (ULT) can effectively reduce this long-term cardiovascular burden. Previous observational cohort studies have provided encouraging signals, suggesting that continuous ULT may prevent the development of coronary artery disease 5 and mitigate the risks of hospitalized stroke and overall mortality in patients with gout 6. Building upon this foundation, a landmark study published in JAMA Internal Medicine by Cipolletta et al. recently provided compelling evidence that helps resolve the remaining uncertainty 7. Using a robust “emulated target trial” design involving over 109 000 patients with newly diagnosed gout, they demonstrated that achieving a serum urate (SU) target of < 6 mg/dL within 12 months significantly lowers the risk of major adverse cardiovascular events (MACE) 7. Although the emulated target trial design strengthens causal inference, it remains a quasi-experimental approach where residual confounding cannot be entirely eliminated. Consequently, while the suppression of systemic inflammation through strict urate control provides a biologically plausible mechanism for cardiovascular protection, it is not definitively proven. Nevertheless, achieving this target was associated with a potentially meaningful reduction in cardiovascular risk, as patients in the T2T arm had a lower 5-year risk of MACE compared to those who did not achieve the target 7. Furthermore, a dose–response relationship was observed, where patients achieving a stricter target of < 5 mg/dL experienced an even greater reduction in cardiovascular risk 7. This observation supports the “lower is better” hypothesis for high-risk populations. However, this endorsement of a < 5 mg/dL target should be interpreted cautiously. Randomized cardiovascular outcome trials specifically powered to evaluate MACE in gout remain limited, and there is notable global heterogeneity among clinical guidelines (e.g., EULAR vs. ACR positioning) regarding the optimal strictness of urate targets. Despite these variations, regional documents such as the 2021 Asia-Pacific League of Associations for Rheumatology (APLAR) clinical practice guideline 8, the multidisciplinary consensus in Taiwan 9, and the 2024 update of the Chinese guidelines 10 all strongly advocate for strict SU targets to manage comorbidities effectively. However, a potential paradox remains in the clinical application of these findings: the fear of the “J-shaped curve.” Uric acid is a potent antioxidant, and concerns persist that lowering levels too aggressively might increase the risk of neurodegenerative conditions. Fortunately, recent nationwide population-based studies have offered reassurance, indicating that the use of anti-gout preparations does not inherently increase the risk of dementia and requires nuanced clinical interpretation 11. While the recent literature clearly demonstrates the cardiovascular benefits of targets < 5 mg/dL, the safety of extremely low urate levels still necessitates a balanced approach. This is particularly highlighted in recent consensus statements for specific populations, such as adolescents, where long-term safety is paramount 12. The evolving landscape of gout management, supported by advanced diagnostic tools like dual-energy CT (DECT) which can detect subclinical crystal burden 13, suggests that the future of therapy lies in precision medicine. We must now learn to tailor our urate targets. For patients with high cardiovascular risk, the evidence now strongly supports a target of < 5 mg/dL. For others, a standard target of < 6 mg/dL remains appropriate. In conclusion, recent studies serve as a pivotal reminder that ULT is not just for joint protection but is a critical component of cardiovascular prevention across the entire disease timeline. By integrating these robust clinical findings with established guidelines 8-10, clinicians can confidently adopt a comprehensive T2T strategy, ensuring that we protect the heart with the same vigor as we protect the joints. Robert T. Keenan: conceptualization, writing – review and editing. Tang-Kai Cheng: conceptualization, writing – original draft. James Cheng-Chung Wei: conceptualization, supervision, writing – review and editing. The authors declare no conflicts of interest. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
Keenan et al. (Fri,) studied this question.