— Results support need for interventions to reduce the excess risk in this population, researchers say

by Nancy Walsh, Senior Staff Writer, MedPage Today April 21, 2020

Older individuals with gout were at increased risk for incident heart failure, a large population-based cohort study found.

Among participants enrolled in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study, the multivariate-adjusted hazard ratio for heart failure hospitalization for those with gout was 1.97 (95% CI 1.22-3.19) compared with patients without gout, according to Lisandro D. Colantonio, MD, PhD, of the University of Alabama at Birmingham, and colleagues.

And gout also was associated with an elevated risk for heart failure hospitalization with both reduced (HR 1.77, 95% CI 0.83-3.79) and preserved left ventricular ejection fraction (LVEF; HR 2.32, 95% CI 1.12-4.79), the researchers reported online in Arthritis Research & Therapy.

Previous research has demonstrated that gout is associated with coronary heart disease and stroke, and the conditions also share many risk factors such as obesity, hypertension, and diabetes — which also have been linked with heart failure.

“If gout is associated with an increased risk for heart failure, this would support the need for interventions to prevent its occurrence in this population,” Colantonio and colleagues wrote.

To explore this, they analyzed data from individuals enrolled in REGARDS from 2003 to 2007 who were 65.5 years of age or older, excluding those with a history of coronary heart disease, heart failure, or stroke.

At baseline, participants underwent a physical examination and reported detailed sociodemographic information, dietary patterns, and medication use. Participants then were contacted by phone every 6 months for updates on hospitalizations and mortality.

The researchers also obtained claims data for a 5% random sample of Medicare beneficiaries from 2008 to 2015 for an additional analysis of rates of heart failure, myocardial infarction, stroke, and all-cause mortality in gout patients.

Of the 5,713 REGARDS participants, 3.3% (187) had gout. Compared with individuals in REGARDS without gout, those with gout were older, more likely to be black and male, more likely to have higher body mass index, and more often had diabetes, high systolic blood pressure, and chronic kidney disease.

The cumulative incidence of heart failure hospitalization, coronary heart disease, and all-cause mortality was higher among those with gout. After multivariate adjustment, the risk for hospitalization for heart failure was significantly higher, but the risks for coronary heart disease, stroke, and all-cause mortality did not show significant differences among those with and without gout.

Further analysis found that the risk for all-cause mortality among individuals with gout was increased among blacks (HR 1.46, 95% CI 1.05-2.02) but not whites (HR 0.85, 95% CI 0.61-1.17). Gout also was associated with higher risks for heart failure hospitalization among both men and women.

In the additional analysis of the Medicare cohort (n=29,753), those with gout were older, more often were black and male, and more likely to have various comorbidities including diabetes, hypertension, or atrial fibrillation, and to be taking diuretics, statins, or nonsteroidal anti-inflammatory drugs. They also had a higher incidence of heart failure, myocardial infarction, stroke, and all-cause mortality.

After multivariate adjustment, the hazard ratios for those with gout in the Medicare cohort were 1.32 (95% CI 1.25-1.39) for heart failure hospitalization, 1.06 (95% CI 1-1.11) for myocardial infarction, 1.06 (95% CI 1-1.12) for stroke, and 0.95 (95% CI 0.93-0.98) for all-cause mortality. These hazard ratios for this cohort were not significantly different from those reported in the REGARDS cohort.

The observation in this study that the risk for incident heart failure was elevated among patients with gout even after adjustment for risk factors such as high blood pressure, obesity, smoking, and diabetes “support that the association of gout with incident heart failure is independent of a prior history of atherosclerosis disease or other well known risk factors,” the researchers wrote.

They also noted that, while risks for heart failure were increased with both reduced and preserved LVEF, the underlying pathophysiology differs in those conditions: “Patients with heart failure who have reduced LVEF are more likely to show upregulation of pathways related to cellular growth and metabolism, while those who have preserved LVEF are more likely to show upregulation of pathways related to inflammation and extracellular matrix reorganization,” the team explained.

Accordingly, gout may influence the development of heart failure via multiple pathways, and greater understanding of these mechanisms may help in the development of interventions to prevent heart failure in patients with gout.

The risk also may relate to factors such as inflammation, serum urate elevations, and insulin resistance, the researchers noted, adding that the inflammatory marker interleukin-1 has been implicated both in gout flares and heart failure with preserved LVEF in preclinical studies, and insulin resistance has been linked with preserved and reduced LVEF heart failure.

“Future studies should determine whether interleukin-1 blockade, pharmacologic insulin sensitization, or uric acid-lowering therapy is effective to reduce the risk for heart failure among adults with gout,” Colantonio and co-authors concluded.

A limitation of the study, they said, was its reliance on claims data.