ATLANTA – Renal dysfunction is independently associated with incident cardiovascular disease in patients with rheumatoid arthritis, according to findings from a prospective Dutch cohort study.
Of 353 RA patients who were part of the Cardiovascular Research and Rheumatoid Arthritis (CARRE) study and who were followed for at least 3 years, 23 developed a cardiovascular event. Serum creatinine levels and glomerular filtration rate (GFR) findings were unfavorable in the patients who had a cardiovascular event, compared with those who did not, Dr. Alper M. van Sijl reported at the annual meeting of the American College of Rheumatology.
Patients with a cardiovascular event had a mean serum creatinine level of 101, compared with 88 micromol/L in the unaffected group; GFR as measured using the Cockcroft-Gault (CG) formula was 63 vs. 80 mL/min, and GFR as measured using the Modification of Diet in Renal Disease (MDRD) formula was 59 vs. 78 mL/min, in the groups, respectively, said Dr. van Sijl of the Jan van Breemen Institute and VU Medical Center, Amsterdam.
Dr. van Sijl and his colleagues used logistic regression analysis to calculate whether incremental increases of 5 micromol/L in serum creatinine level, and incremental decreases of 5 mL/min in glomerular filtration rate as measured using both the CG and MDRD formulas were associated with incident cardiovascular disease. Indeed, all were significantly positively associated with incident cardiovascular disease (odds ratios of 1.13, 1.12, and 1.21, respectively).
"When adjusted for age, gender, body mass index, and prior cardiovascular disease, the association remains. And when adjusted additionally for traditional cardiovascular risk factors, the association becomes even stronger," he said, explaining that a decrease in GFR of 5 mL/min was associated with a 30%-35% increased risk of cardiovascular disease, independent of traditional cardiovascular risk factors.
By comparison, a prior cohort study showed that diabetes patients have about a 20% cardiovascular disease risk increase for every 5-mL/min decrease in GFR, he noted.
The findings of the current study suggest that renal dysfunction might be a "missing link" in the established, but only partially defined, connection between RA and cardiovascular disease, he said.
RA patients are known to have an increased risk of mortality, compared with the general population, and much of that risk has been shown to be attributable to cardiovascular disease. However, standard cardiovascular risk factors – particularly hypercholesterolemia, hypertension, and insulin resistance – explain only part of this association.
Furthermore, renal dysfunction has been shown to be associated with cardiovascular disease in the general population, although findings from landmark studies have shown that risk depends on coexisting hypertension, prior cardiovascular disease, and diabetes, Dr. van Sijl said.
Study findings have shown an association between renal dysfunction and RA. Renal dysfunction in the RA population has been attributed to extra-articular manifestations, NSAID use, and chronic inflammation. At least one study showed an association between renal function and prevalent cardiovascular disease in RA, he said.
Although the current findings do support the idea that decreased renal function can help identify RA patients at increased risk for future cardiovascular disease, further study is needed to determine whether chronic inflammation causes the decreases in GFR, and whether GFR can accurately predict cardiovascular disease occurrence in RA, he said.
"Also still unknown to us is whether possible residual confounding is still present in the form of newly discovered markers of both renal dysfunction and cardiovascular disease such as uric acid, endothelial dysfunction, and cumulative inflammatory burden," he said.
Dr. van Sijl said he had no disclosures to report.