— Odds ratios doubled for coronary artery calcification among men, but not women, with high serum urate levels

by Nancy Walsh, Senior Staff Writer, MedPage Today February 25, 2020

High levels of serum urate were associated with the presence of coronary artery calcification in men, though not in women, Swedish researchers found.

In a multivariate analysis, the odds ratio for coronary artery calcification being detected in men whose serum urate levels were in the highest quartile was 2.3 (95% CI 1.2-4.4, P=0.01), according to Panagiota Drivelegka, MD, of the University of Gothenburg, and colleagues.

Odds ratios also were increased in men for the second quartile (OR 2.2, 95% CI 1.2-4, P=0.008) and third quartile (OR 1.9, 95% CI 1-3.6, P=0.04).

But for women, odds ratios for all quartiles were nonsignificant, being 1 (95% CI 0.5-2, P=0.96) in the highest quartile, the researchers reported online in Arthritis Research & Therapy.

“Hyperuricemia is closely associated with cardiovascular disease, although it has not been definitively established whether this is due to covariation with the traditional cardiovascular risk factors or a causative role of its own,” the team wrote.

Higher levels of serum urate also have been linked with hypertension, dyslipidemia, metabolic syndrome, and higher body mass index (BMI). These levels also are higher in men than women.

Evaluation of subclinical atherosclerosis is important for early intervention and prevention of cardiovascular disease. Computed tomography detection of coronary artery calcification has been recommended as an aid in risk assessment for patients who are at risk for myocardial infarction. Other potential predictors of early atherosclerotic changes include ultrasound measurement of carotid intima-media thickness and plaque volumes.

Previous studies looking at potential relationships between serum urate and subclinical atherosclerosis using these tools have had conflicting results, however, with heterogeneous populations and varying study sizes.

Therefore, to further explore potential links between these related conditions, researchers conducted a population-based cross-sectional analysis of individuals enrolled in the Swedish Cardiopulmonary Bioimage Study, which is intended to improve risk predictions for cardiovascular disease and obtain insight into disease mechanisms.

The analysis included 1,040 participants whose mean age was 57.6. Slightly more than half were women.

A coronary artery calcification score or plaque score greater than zero was considered positive, as was a carotid intima-media category above the 75th percentile.

Serum urate quartiles in µmol/L among men were defined as: first quartile, 31-307; second, 308-346; third, 347-391; and fourth, 392-584, while among women, the corresponding ranges were 143-229, 230-262, 263-304, and 305-702.

For both men and women, higher serum urate quartiles were associated with BMI. In men, the mean BMI for the first quartile was 26.1 compared with 29.2 in the top quartile, and for women, BMIs were 24.5 and 30.4 in the first and fourth quartiles, respectively (P<0.0001 for both).

For C-reactive protein levels, the mean level in the first and fourth serum urate quartiles were 1.7 mg/L versus 3.1 among men (P=0.007) and 1.4 versus 3.9 among women (P<0.0001). For hypertension, the percentages were 21% versus 40% in men (P=0.003) and 23% versus 50% in women (P<0.0001).

Higher serum urate levels also were associated with dyslipidemia and lower socioeconomic status in women.

Coronary artery calcification was considered positive in 58% of men compared with only 26% of women.

In contrast with coronary artery calcification, there was no significant association with serum urate levels and carotid intima media thickness after multivariate adjustments for factors including age, BMI, hypertension, dyslipidemia, diabetes, and education level.

A total of 61% of men had evidence of carotid plaque, as did 51% of women. No significant association with serum urate level was observed after multivariate adjustments.

As to why the association between serum urate and coronary artery calcification should be limited to men, researchers suggested that atherosclerotic processes begin earlier in men, and men also have higher serum urate levels throughout life. In women, only after menopause do serum urate levels begin to rise considerably.

“These results imply different biological effects of serum urate in men and women or reflect different vascular beds or stages of the atherosclerotic process,” Drivelegka and colleagues concluded.

A limitation of the study, they said, was the relatively young age of the participants.