In the JournalsPerspective

Obesity, hypertension, diuretic use each double risk for gout

Obesity, hypertension and the use of diuretics each represent independent risk factors for incident gout, individually associated with a twofold increase in risk, according to findings published in Arthritis Research & Therapy.

BMI and hypertension have been identified as risk factors for incident gout in a number of large epidemiological studies, yet the magnitude of risk varies between studies,” James A. Prior, PhD, MSc, of Keele University, Staffordshire, U.K., and colleagues wrote. “Diuretics are perhaps the most well-known medications to be associated with gout; they raise serum uric acid levels by increasing uric acid reabsorption and decreasing uric acid secretion in the kidneys. However, it has also been proposed that diuretic use alone does not increase the risk of gout and that the observed associated risk is due to the presence of comorbidities which they are used to treat; commonly hypertension, heart failure and renal failure.”

To determine the risk for incident gout linked with obesity, hypertension and diuretics, the researchers conducted a systematic review and meta-analysis of prospective and retrospective cohort studies. The researchers focused on studies of adults aged 18 years and older, from primary care or general populations, who had obesity or hypertension, or had used diuretics. In addition, the studies all had to include incident gout as an outcome.

Obesity, hypertension and the use of diuretics each represent independent risk factors for incident gout, according to findings.
Source: Shutterstock

Prior and colleagues narrowed their search to 14 articles for their systematic review, and 11 for their meta-analysis. All included articles had sample sizes that ranged from 923 to 60,181. The number of incident gout cases in each study ranged from 43 to 1,341.

According to the researchers, gout was 2.24 times more likely to occur in patients with a BMI of 30 kg/m2 or greater (adjusted RR = 2.24; 95% CI, 1.76-2.86). In addition, patients with hypertension were more than twice as likely to experience incident gout (aRR = 2.11; 95% CI, 1.34-2.01) than those without hypertension. Individuals who had used diuretics had almost 2.5 times the risk for developing gout (aRR = 2.39; 95% CI, 1.57-3.65).

“Obesity, hypertension and diuretic use are all risk factors for incident gout, independent of one another and each more than doubling the risk of developing gout compared with those without these conditions,” Prior and colleagues wrote. “Such patients should be recognized by clinicians as being at greater risk of developing gout and provided with appropriate management and treatment options.” – by Jason Laday

Disclosure: Evans reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

Obesity, hypertension and the use of diuretics each represent independent risk factors for incident gout, individually associated with a twofold increase in risk, according to findings published in Arthritis Research & Therapy.

BMI and hypertension have been identified as risk factors for incident gout in a number of large epidemiological studies, yet the magnitude of risk varies between studies,” James A. Prior, PhD, MSc, of Keele University, Staffordshire, U.K., and colleagues wrote. “Diuretics are perhaps the most well-known medications to be associated with gout; they raise serum uric acid levels by increasing uric acid reabsorption and decreasing uric acid secretion in the kidneys. However, it has also been proposed that diuretic use alone does not increase the risk of gout and that the observed associated risk is due to the presence of comorbidities which they are used to treat; commonly hypertension, heart failure and renal failure.”

To determine the risk for incident gout linked with obesity, hypertension and diuretics, the researchers conducted a systematic review and meta-analysis of prospective and retrospective cohort studies. The researchers focused on studies of adults aged 18 years and older, from primary care or general populations, who had obesity or hypertension, or had used diuretics. In addition, the studies all had to include incident gout as an outcome.

Obesity, hypertension and the use of diuretics each represent independent risk factors for incident gout, according to findings.
Source: Shutterstock

Prior and colleagues narrowed their search to 14 articles for their systematic review, and 11 for their meta-analysis. All included articles had sample sizes that ranged from 923 to 60,181. The number of incident gout cases in each study ranged from 43 to 1,341.

According to the researchers, gout was 2.24 times more likely to occur in patients with a BMI of 30 kg/m2 or greater (adjusted RR = 2.24; 95% CI, 1.76-2.86). In addition, patients with hypertension were more than twice as likely to experience incident gout (aRR = 2.11; 95% CI, 1.34-2.01) than those without hypertension. Individuals who had used diuretics had almost 2.5 times the risk for developing gout (aRR = 2.39; 95% CI, 1.57-3.65).

“Obesity, hypertension and diuretic use are all risk factors for incident gout, independent of one another and each more than doubling the risk of developing gout compared with those without these conditions,” Prior and colleagues wrote. “Such patients should be recognized by clinicians as being at greater risk of developing gout and provided with appropriate management and treatment options.” – by Jason Laday

Disclosure: Evans reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

    Perspective
    Brian F. Mandell

    Brian F. Mandell

    Recognizing epidemiologic associations between external or biological factors and disease behavior, in this case newly diagnosed gout, poses the possibility of influencing the disease course by reducing associated risk factors. But (and it is a big but) this is likely true only if the recognized associated risk factor is causative.

    There is no question in my mind that the management of gout is suboptimal, despite the fact that we have a solid understanding of its pathophysiology, as well as the tools to control hyperuricemia, the root cause, to a degree above the saturation of serum urate of approximately 6.8 mg/dL. The presence of hyperuricemia, and hence of gout, is linked to all components of the metabolic syndrome, as well as to chronic kidney disease.

    As yet, there are minimal data that reducing these associated risk factors will reduce hyperuricemia and gout, although I suspect that patients undergoing successful bariatric surgery may experience benefit. At present, we have stronger suggestive data — mostly observational in nature — that treating hyperuricemia may reduce progression of CKD and affect other comorbidities.

    Associated risk factors like obesity and hypertension may increase the risk for incident gout by several fold. However, for perspective, across the spectrum of serum urate levels from < 6 mg/dL to > 10 mg/dL, the incident gout rate over 10 years ranges from 0.8% to 40%; yet, for studied patients with a serum urate > 10 mg/dL, only 50% develop incident gout at 15 years. While we can identify risk factors associated with the development of gout, it is not clear to me that their identification warrants any clinical interdiction for the sole goal of preventing an initial gout attack — this would be very inefficient. That said, there are obviously many other health reasons to treat identified gout comorbidities including hypertension, obesity, sleep apnea and insulin resistance/diabetes.

    We need to be mindful of the many inter-relationships between the comorbidities that associate with gout. Hypertension may be initiated or influenced in some patients by hyperuricemia, and once established, the hypertension can reduce kidney function and is often treated with a thiazide class antihypertensive — both of which can increase the serum urate. However, this should not drive clinicians to stop using thiazides in patients who are successfully responding to their use with lowered blood pressure simply for the sake of lowering the serum urate by likely 1 mg/dL or less. More to the point — and this goes back to my belief that gout is suboptimally managed — is that clinicians need to make the decision as to who with gout needs to receive urate-lowering therapy, which may be influenced by the presence of comorbidities.

    Once the decision to treat with urate-lowering therapy is made, the serum urate level must be monitored to assure that urate level is reached and maintained; this should be performed in the same way that the blood pressure is monitored after initiating antihypertensive therapy: Intensely at first, then at longer intervals unless there are clinical changes that warrant the return to more intense monitoring. We know that tophi will dissolve at a rate that is inverse to the serum urate level. If the therapy is stopped and the urate is allowed to rise again to > 6.8 mg/dL, deposits and tophi will begin to form and grow again. We do not understand to the same degree the relationship between serum urate and the metabolic comorbidities.

    As our understanding of the comorbidities associated with gout continues to grow, hopefully we will learn more about the nature of the associations: Which comorbidities are causative for hyperuricemia and/or gout attacks and what are the reciprocal effects of manipulating the serum urate and the comorbidities?

    In the meantime, for patients with hyperuricemia who need to have their gout treated, let’s be attentive to lowering their serum urate to a level which will dissolve the uric acid deposits and ultimately cease attacks completely, even without prophylactic anti-inflammatory medication. As for those patients without gout who have comorbidities associated with incident gout and hyperuricemia, let’s hope that clinical investigation will provide us with the tools to identify which patients — if any — should leave our offices with a prescription for urate-lowering therapy as well as the hackneyed admonition to lose weight and exercise more.

    • Brian F. Mandell, MD, PhD
    • Professor and chairman of academic medicine
      Cleveland Clinic Lerner College of Medicine
      Department of rheumatic and immunologic disease
      Center for Vasculitis Care and Research
      Cleveland Clinic

    Disclosures: Mandell reports consulting for Horizon and Ironwood pharmaceuticals; being a clinical investigator for Horizon; and being the editor of rheumatology and immunology for The Merck Manual (no product association).