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Incidence of acute coronary syndrome (ACS) was significantly higher among gout patients than in the general Swedish population, researchers found, even when data were adjusted for common comorbidities.

First-time ACS was diagnosed at a rate of 9.1 per 1,000 person-years in a cohort of about 20,000 gout patients followed through registry data, compared with 6.3 per 1,000 person-years among matched controls drawn from the general public (HR 1.44, 95% CI 1.33-1.56), according to Panagiota Drivelegka, MD, PhD, of Sahlgrenska University Hospital in Gothenburg, and colleagues.

In a multivariate analysis that adjusted for comorbidities that commonly accompany gout, however, such as obesity, hypertension, and alcoholism, the difference in ACS risk between patients and controls shrank substantially, though it remained statistically significant (HR 1.15, 95% CI 1.06-1.25), the researchers .

Thus, the ACS risk "is largely explained by the underlying comorbidities, but there is still a modestly increased risk, that may be due to gout-related factors," Drivelegka and colleagues wrote.

Clinically, they added, the results "underline the importance of regular cardiovascular risk assessment for the patients with gout, and [emphasize] the need of appropriate management of gout, as well as of the underlying cardiovascular risk factors."

It was already understood that gout patients face higher risk of cardiovascular mortality, though that was based primarily on data now approaching 10 years old. It was also unclear to what extent gout itself (i.e., accumulation of urate crystals and the resultant inflammatory response) was responsible versus the comorbidities commonly seen with gout, many of which also contribute to cardiovascular event risk.

Drivelegka and colleagues observed that these correlates of gout have made "distinguishing the isolated influence of gout very difficult," and they called the literature on this subject "conflicting and debatable." Two previous studies -- with data now more than 20 years old -- had found that gout itself had no influence on heart risk when the contributions of comorbidities were removed.

To get what Drivelegka and colleagues called a "more contemporary" view, they analyzed Sweden's relatively comprehensive health registry data to track outcomes in 20,146 individuals residing in the western part of the country who were diagnosed with gout from 2007 onward. Each of these patients was matched with five people by age, sex, and county of residence. All were followed through 2017. Controls who developed gout during follow-up were treated as controls up to the date of diagnosis, after which they joined the gout cohort.

About two-thirds of each group were men; mean age was about 63 for men and 70 for women. As expected, comorbidities known to promote cardiovascular events were more common in the gout group versus controls:

• Hypertension: 53.6% vs 30.7%

• Hyperlipidemia: 28.7% vs 18.1%

• Obesity: 11.8% vs 4.5%

• Kidney disease: 10.0% vs 3.8%

• Alcoholism: 4.0% vs 2.2%

• Heart failure: 11.1% vs 3.2%

Most of these were more common in female vs male gout patients (alcoholism was an exception), related to which of the patients' risk of ACS was elevated more in women than men (HR 1.64 vs 1.36, both highly significant relative to controls).

But once the contribution from comorbidities was removed via statistical adjustment, there was little difference in gout-associated ACS risk between the sexes (HR 1.12 for men, 1.21 for women, with heavily overlapping 95% confidence intervals).

It's worth noting, however, that most gout patients managed to avoid ACS episodes. Through 10 years of follow-up, event-free survival rates stood at about 90% for male and 92% for female patients, and these rates differed from those among controls by only 1-2 percentage points.

Overall, the findings seem to confirm that gout per se does increase cardiovascular disease risk, if less strongly than its common comorbidities.

Drivelegka and colleagues cited some limitations to the study: Gout patients were identified through ICD codes, which are not totally reliable. Certain comorbidities including obesity and alcoholism may have been undercounted for the same reason. Also, the data could not account for use of over-the-counter medications, which could have influenced ACS risks unevenly. And perhaps most importantly, with the study's conduct in one part of Sweden, the results may not be generalizable to other countries or populations.

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