Background/Purpose:

When serum is hyperuricemic, so too are all interstitial fluids other than CSF and sweat.  Anecdotally, urate crystals deposit as grossly visible tophi in many non-articular organs, including cardiac valves, but no microscopic studies of crystal prevalence have been done at those sites.  Are the tophi unique, or are they the tip of a crystalline iceberg?  Evidence from new imaging modalities including dual energy CT and ultrasound suggest that they may be surprisingly common.

Just as urate crystals drive gouty arthritis, such deposits may be a factor in extraarticular inflammation.  Higher urate levels within prostatic secretions have correlated with symptoms of chronic prostatitis, and a single placebo-controlled study found that allopurinol decreased prostatic urate secretion and improved subjective pain.  In addition, gout and hyperuricemia are now accepted as independent risk factors for coronary artery disease and all-cause mortality, and allopurinol use may lead to decreased mortality.  The cardiac risk has been attributed to hyperuricemia, but the possibility of arterial urate crystals has not been considered.  If present, such crystals could cause intimal inflammation leading to coronary thrombosis.  To investigate this possibility, we used polarizing microscopy to examine tissues from 3 sites of enigmatic inflammation: coronary arteries, cardiac valves, and prostates.

Methods:

Tissues were:  1.  Alcohol-fixed and H&E stained coronary arteries (left anterior descending, right coronary, and circumflex) from 50 explanted hearts collected from 2000-2003.  2.  Twenty-three alcohol-fixed, unstained aortic valves from replacement surgery done in 2011-2013.  3.  Frozen, unstained, non-malignant regions of 40 consecutive prostatectomies for cancer in 2012-2013.  Clinical data regarding gout and hyperuricemia were unavailable or incomplete for all subjects.

Results:

Conclusion:

We have observed birefringent crystals, primarily negatively so, in 12% of coronary arteries, 48% of prostates, and 4% aortic valves examined thus far.  Alcohol fixation, rather than formalin which is known to dissolve urate crystals, and polarizing microscopy are necessary in order to recognize urate crystals in pathologic tissues. 

“Gouty arteritis” should be considered as a possible factor in ischemic heart disease.  We hope these tools will be applied by pathologists conducting autopsies on patients who have suffered fatal myocardial infarctions.  In addition, if our preliminary findings are confirmed within the prostate, further studies will be indicated with urate lowering agents and anti-inflammatory drugs known to be effective in gouty arthritis.