One of the positive aspects about the PREVENT Risk Calculator is its incorporation of Urinary Albumin to Creatinine Ratio (UACR), a marker of protein in the urine.  And if you’re leaking protein in your urine, your Home Security System (endothelial integrity) is NOT as good as you think it is!  Pea protein is disgusting, and pee in your protein is similarly horrifying, particularly when elevated UACR carries an 148% risk of all-cause mortality and a 203% risk of cardiovascular mortality EVEN IN PEOPLE WITHOUT DIABETES OR HYPERTENSION.

But there is another urinary marker of endothelial function that could potentially complement UACR called Urinary Orosomucoid to Creatinine Ratio (UOCR), and THIS STUDY showed that elevated UOCR was independently associated with heart attacks, strokes, and all-cause mortality in a Norwegian cohort followed over 13.2 years.  Adjustments were made for eGFR (a measure of kidney function), UACR, and traditional risk factors (such as diabetes and hypertension), and UOCR still remained significantly associated with the aforementioned Terrible Trifecta.  The highest UOCR levels were associated with a 45% greater risk of myocardial infarction, 234% greater risk of ischemic stroke, and 72% greater risk of death from any cause.

So what is orosomucoid?  Well, it’s produced primarily by the liver and is also known as alpha-1-acid glycoprotein (which probably does absolutely nothing for you unless you are familiar with GlycA and the Metabolic Vulnerability Index, or MVX.  I discuss these topics in my books, but since only a few people read those I’ll post about them sometime on here).  But GlycA is a composite of various proteins related to inflammation, including orosomucoid, and may capture inflammatory risk that traditional markers such as hs-CRP fail to identify.

Orosomucoid has several isoforms and many potential binding partners, and there are still many things about it that we still need to learn.  But interestingly, orosomucoid seems to have PROTECTIVE effects against Metabolic Miscreants such as hyperinsulinemia, elevated blood sugars, TNF-alpha, lysophosphatidylcholine, and free fatty acids.  Although orosomucoid levels rise in response to these factors, it seems to actually alleviate the insulin resistance and inflammation. 

Since “oso” is the Spanish word for bear, I think of orosomucoid as an Angry Momma Bear that is trying to protect her cubs from endothelial invaders.  The Momma Bear isn’t bad herself, but she is a sign of a SCARY Physiologic Neighborhood.  It’s probably best if we don’t continually poke her…it would seem that folks with the most Angry Momma Bears in their body are dying more often.

I would love to see another study in which UOCR levels are adjusted for other factors such as fasting insulin or c-peptide, but for now, I think if we don’t observe many Angry Momma Bears in your Metabolic Milieu, you’re probably prioritizing the Pillars of your Metabolic Home Security System.  But maybe in the future, UOCR and UACR will represent a Dynamic Duo that can help us in the ongoing quest to refine our approach to Cardiovascular Risk Stratification.