Shuai Yuan, from the Karolinska Institutet in Stockholm, and colleagues used a Mendelian randomization approach to examine the causality of the associations of RA with CAD and stroke. Seventy independent single nucleotide polymorphisms strongly associated with RA were selected as instrumental variables from a genome-wide association meta-analysis involving 14,361 RA cases and 43,923 controls. From meta-analyses of genetic studies, international genetic consortia, the U.K. Biobank, and the FinnGen consortium, summary-level data for CAD, all stroke, any ischemic stroke and its subtypes, intracerebral hemorrhage, and subarachnoid hemorrhage were obtained.
The researchers found that genetic liability to RA was associated with an elevated risk for CAD and intracerebral hemorrhage, with combined odds ratios of 1.02 and 1.05, respectively, for a 1-unit increase in log odds of RA. Increased levels of tumor necrosis factor and C-reactive protein (CRP) were seen in association with genetic liability to RA. After adjustment for genetically predicted CRP levels, the association for CAD was attenuated. No associations of genetic liability to RA were seen with other studied outcomes.
“These findings highlight the importance of active monitoring and prevention of cardiovascular risk to combat CAD and intracerebral hemorrhage in RA patients,” the authors write. “We further suggest that dampening inflammation might be a preventive strategy for CAD in RA patients and well-designed clinical trials are required to assess this.”