Why is Uric Acid level important enough that I should read this? How does Uric Acid Cause Heart Disease & Heart Attack?
In short, modest elevations in uric acid level put you, your family, and your friends at increased risk of developing preventable heart disease, heart attack and sudden death.
Have you ever wondered why some of your acquaintances have suddenly had heart attacks or dropped dead without much notice that they had heart disease?
Have you ever wondered why heart disease occurs without having particularly high cholesterol levels?
If this gets your attention, please read on........
Uric acid, a byproduct of purine metabolism, has been increasingly recognized as a potential contributor to cardiovascular diseases, including heart attacks. Elevated serum uric acid (SUA) levels, also known as hyperuricemia, have long been associated with gout, but emerging evidence suggests a significant link between hyperuricemia and adverse cardiovascular outcomes. This relationship is particularly concerning given the increasing prevalence of hyperuricemia worldwide.
Hyperuricemia has been implicated in the development of endothelial dysfunction, which plays a critical role in the initiation and progression of atherosclerosis—a major precursor to myocardial infarction. At relatively modest concentrations, Uric Acid crystalizes and these small crystals can damage the inner lining of the arteries, destroying the lining called the Glycocalyx.
Elevated uric acid levels can induce oxidative stress and inflammation in endothelial cells, impairing nitric oxide bioavailability and promoting vascular stiffness. These mechanisms establish a direct pathophysiological link between uric acid and cardiovascular risk (Becker & Jolly, 2006).
What Uric Acid level seems to be the threshold for causing heart disease? This is where the fun begins.
Numerous epidemiological studies have shown a correlation between elevated SUA levels and an increased risk of coronary artery disease and heart attacks. A meta-analysis of over 16 studies involving more than 200,000 participants found that individuals with hyperuricemia had a 20-40% higher risk of coronary heart disease compared to those with normal SUA levels (Li et al., 2014).
The risk of heart disease increases and the risk of serious damage begins at the level of 5.5 mg/dl. This is well below the level seen as 'high' or consistent with Gout. (please see my other Blog on Uric Acid for the data & reference)
This association remained significant even after adjusting for traditional cardiovascular risk factors such as hypertension, diabetes, and hyperlipidemia.
The role of uric acid as an independent risk factor for heart attacks has been debated, partly because hyperuricemia often coexists with other metabolic disorders. For instance, hyperuricemia is frequently associated with hypertension, insulin resistance, and obesity, all of which are established cardiovascular risk factors (Feig et al., 2008). While these conditions may confound the relationship, experimental evidence supports a direct role for uric acid in cardiovascular pathophysiology.
Uric acid has also been linked to the activation of the renin-angiotensin-aldosterone system (RAAS) and increased production of inflammatory cytokines, further exacerbating cardiovascular risk. Elevated SUA levels can lead to renal microvascular damage, promoting hypertension—a well-known risk factor for myocardial infarction (Mazzali et al., 2001). This interaction highlights the systemic impact of hyperuricemia on cardiovascular health.
Clinical studies have suggested that reducing uric acid levels through pharmacological interventions, such as allopurinol or febuxostat, may mitigate cardiovascular risk. For instance, a randomized controlled trial found that allopurinol improved endothelial function and reduced arterial stiffness in patients with hyperuricemia (Kanbay et al., 2011). While these findings are promising, further research is needed to confirm the cardiovascular benefits of uric acid-lowering therapy.
Gender differences in the relationship between uric acid and cardiovascular risk have also been observed. Women, particularly premenopausal women, appear to have a weaker association between hyperuricemia and heart attacks compared to men, possibly due to the uricosuric effects of estrogen. However, postmenopausal women show a similar risk profile to men, underscoring the complex interplay between sex hormones and uric acid metabolism (Chen et al., 2015).
Hyperuricemia has also been associated with the formation of microvascular thrombi, which can contribute to acute coronary syndromes. Uric acid crystals can activate the NLRP3 inflammasome, leading to the release of interleukin-1β and subsequent inflammatory cascades that destabilize atherosclerotic plaques (Martinon et al., 2006). These processes further elucidate the mechanistic link between uric acid and myocardial infarction.
Despite the growing evidence, some experts argue that uric acid may serve more as a marker of cardiovascular risk rather than a causative factor. This perspective emphasizes the need for well-designed longitudinal studies and clinical trials to disentangle the complex relationship between SUA levels and heart attacks (Kuwabara et al., 2018).
In conclusion, elevated uric acid levels are strongly associated with an increased risk of heart attack through multiple mechanisms, including endothelial dysfunction, oxidative stress, and inflammation. While hyperuricemia is often intertwined with other cardiovascular risk factors, it may also independently contribute to myocardial infarction.
Addressing hyperuricemia through lifestyle modifications and pharmacological interventions could potentially reduce cardiovascular risk, but further research is essential to validate these strategies.
What can I realistically do to address this potential problem?
Get your uric acid level checked regularly. At my practice, Stages of Life Medical Institute, we check our patients every 3 to 6 months.
Maintain your level below 5.4
My preferred medication is Allopurinol. Starting dosage is 100 mg tablet, 2 in the morning. Titrate the dosage upward after subsequent blood work confirms the level and suggests a change, usually an increase in dosage.
Eat sensibly. Go to your favorite search engine and read about what foods are good for patients with gout, and you are well on your way to getting this under control.
In my practice, I have found that the CRP levels, used to look for inflammation decrease substantially when the uric acid levels are lowered below 4.2 mg/dl.
References
1. Becker, M. A., & Jolly, M. (2006). Hyperuricemia and associated diseases. Rheumatic Disease Clinics of North America, 32(2), 275-293.
2. Li, M., Hou, W., Zhang, X., Hu, L., Tang, Z., & Wang, C. (2014). Hyperuricemia and risk of stroke: a systematic review and meta-analysis of prospective studies. Atherosclerosis, 232(2), 265-270.
3. Feig, D. I., Kang, D. H., & Johnson, R. J. (2008). Uric acid and cardiovascular risk. New England Journal of Medicine, 359(17), 1811-1821.
4. Mazzali, M., Hughes, J., Kim, Y. G., et al. (2001). Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. Hypertension, 38(5), 1101-1106.
5. Kanbay, M., Ozkara, A., Selcoki, Y., et al. (2011). Effect of treatment of hyperuricemia with allopurinol on blood pressure, creatinine clearance, and proteinuria in patients with normal renal functions. International Urology and Nephrology, 39(4), 1227-1233.
6. Chen, L., Zhu, W., & Chen, Z. (2015). Gender and age specific prevalence of hyperuricemia and its associated risk factors in Chinese adults: A longitudinal study. BMC Public Health, 15(1), 537.
7. Martinon, F., Pétrilli, V., Mayor, A., Tardivel, A., & Tschopp, J. (2006). Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature, 440(7081), 237-241.
8. Kuwabara, M., Niwa, K., Nishi, Y., et al. (2018). Relationship between serum uric acid levels and cardiovascular disease risk factors in a Japanese cohort. Journal of Cardiology, 71(3), 283-288.
9. Borghi, C., & Cicero, A. F. G. (2016). Serum uric acid and cardiovascular risk: state of the art and future perspectives. Current Cardiology Reports, 18(2), 118.
10. Gagliardi, A. C., Miname, M. H., & Santos, R. D. (2009). Uric acid: A marker of increased cardiovascular risk. Atherosclerosis, 202(1), 11-17.
David S. Klein, MD, FACA, FACPM
1917 Boothe Circle
Longwood, Florida 32750
Tel: 407-679-3337
Fax: 407-678-7246