Gout increases risk of vascular disease, especially for women

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Is gout a cardiovascular risk factor?

The significant strengths of Dr. Clarson and colleagues’ study of the association between gout and vascular disease are its large sample size, its accounting for many potentially confounding risk factors, and its exclusion of those with known antecedent heart disease. It is limited by its lack of validation of gout and cardiac diagnoses and the self-selection bias inherent in using primary care registries, rather than a true population-based cohort.

For individuals without gout, women’s overall vascular risk is lower, but the lack of a difference in cardiovascular disease risk in men and women with gout means that we do not yet understand why women’s risk rises more with the disease. It is possible that systemic inflammation induced by gout in women is more atherogenic than that in men, which necessitates studies to determine whether there are sex-based differences in the pathogenesis of gout-associated heart disease.

Dr. Jasvinder Singh

Patients older than 35 or 40 with gout should be screened and followed with lipid profiles, hemoglobin A1c levels, blood pressure levels, and smoking status, and should undergo an assessment of other lifestyle factors that may impact cardiovascular risk.

Recognizing gout’s contribution to cardiac risk, and managing both the disease and associated risk factors, will be a key task for primary care doctors, rheumatologists, and cardiologists going forward.

Dr. Jasvinder Singh is a professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama, Birmingham. These comments are summarized from his editorial accompanying Dr. Clarson’s report (Ann. Rheum. Dis. 2015;74:631-4). He reported receiving research and travel grants from Takeda and Savient, and consultant fees from Takeda, Savient, Regeneron, and Allergan.




Gout’s association with a host of vascular events was confirmed in a new study that explored the links between the inflammatory condition and coronary artery disease, peripheral vascular disease, and cerebrovascular events.

Though both men and women with gout were at increased risk for vascular events overall, the association appeared strongest for women. Dr. Lorna Clarson of Keele (England) University and her associates drew these conclusions from a retrospective cohort study of men and women with an incident diagnosis of gout (Ann. Rheum. Dis. 2015;74:642-7).

Gout, caused by the deposition of uric acid crystals in joints, is characterized by acute flares of intensely painful and inflamed joints. However, the state of hyperuricemia that predisposes patients to acute attacks of gout may precede the first attack by years, and may persist between flares. The proinflammatory course of the natural history of gout has increasingly been recognized as a potential contributor to vascular disease.

The precise mechanism by which gout may increase vascular risk has not been identified. Dr. Clarson and associates noted that in addition to the acute and chronic inflammation associated with gout and hyperuricemia, serum uric acid may have a more direct effect on vascular health, as urate crystal deposition on vessel walls may promote vascular damage.

To clarify gout’s impact on vascular risk, Dr. Clarson and her associates used the Clinical Practice Datalink, a large United Kingdom health database, to compare 8,366 patients with gout to 39,766 age- and sex-matched controls. None of those studied had a baseline history of vascular disease, and all were aged 50 or older.

Careful accounting for covariates was accomplished by multivariate analysis that took into account sex, age, body mass index, tobacco and alcohol consumption, statin or aspirin use, and any history of hypertension, dyslipidemia, or chronic kidney disease. In addition, the study employed the composite Charlson Comorbidity Index, which weights 19 comorbid conditions – including diabetes – to arrive at a single score that captures many risk factors. Patients in the cohort were tracked until their first vascular event, or until death or loss to follow-up. Patient data collection was censored at 10 years from baseline or at the end of study data collection, whichever came first.

To assess the incidence of vascular events, the study noted the first recording in the medical record of any events signaling vascular disease. These included angina or myocardial infarction, transient ischemic attack and stroke, and a range of diagnoses associated with peripheral vascular disease.

Final analysis after accounting for the many covariates tracked in the study showed increased risk for vascular events for those with gout, with a definite difference between the sexes. For men, gout predicted an increased risk of any vascular event (hazard ratio, 1.06; 95% confidence interval, 1.01–1.12) and of coronary heart disease and peripheral vascular disease. For women, gout predicted an increased risk of all vascular events (HR, 1.25; 95% CI, 1.15-1.35) except myocardial infarction and cerebrovascular disease overall. Further, the degree of increased risk of vascular events was greater for women than for men with gout (P< .001 for intersex difference).

Dr. Clarson and her associates proposed that the higher risk for vascular events among women with gout may arise from the longer exposure to elevated serum uric acid, since women have a longer prodrome before first gout attack, though they recommend further study to elucidate the mechanism.

Noting that “clinical management of gout in primary care is suboptimal,” Dr. Clarson and her colleagues urged greater attention to screening for vascular risk in those diagnosed with gout; these individuals comprise a significant population of over 8 million people in the United States. International guidelines recommend screening for cardiovascular risk when gout is diagnosed, but only one in four gout patients are so evaluated.

Regarding the sex differences unearthed in their study, Dr. Clarson and her associates observed that “both gout and vascular disease have historically been considered diseases of men ... [M]ore attention should be paid to prompt and reliable diagnosis of gout, followed by optimal management in female patients, including serious consideration of vascular risk reduction.”

The United Kingdom’s National School for Primary Research funded the study. The authors reported no relevant disclosures.

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