Does increased plasma urate cause heart diseases? A recent research study published in the Lancet Diabetes and Endocrinology journal in April 2016 addresses the widely believed myth of correlation between high levels of plasma urate and the elevated risk of coronary heart disease. Annually, 370,000 people die in USA because of coronary heart disease (CHD).

Researchers have long tried to determine the relationship between the two because usually patients diagnosed with coronary heart disease are known to have elevated plasma urate concentrations as compared to the people who do not have this disease.

The study finds that even if there is any potential causal effect of plasma urate concentration in the development of coronary heart disease, it is but modest. The study was not gauging the efficacy of plasma urate concentration reduction by addressing the therapeutic goals.

Dr. Jon White, PhD, UCL Genetics Institute, University College, London, was of the view that his team carried out that study to surface the causal role of urate on coronary heart disease by using a superior analytical model Mendelian randomization analysis.

But the results could not pinpoint the crystal clear answer to the question under scrutiny. However, Dr. Jon said, ‘the findings might help investigators to judge the relative priority of plasma urate, as against other risk factors, as a therapeutic target for the prevention of coronary heart disease’.

Increased Plasma Urate Cause Heart Diseases

It is a common belief that increased plasma urate concentrations in human body causes coronary heart diseases, but how much of this belief is true is not clear. Abnormally elevated concentration of uric acid in the blood is known as hyperuricaemia, which is defined as ≥7 mg/dL for men and ≥6.0 mg/dL for women.

It has also been found to be related to coronary heart disease risk factors such as high blood pressure, type 2 diabetes, increased BMI, reduction in HDL cholesterol, and an increase in triglycerides and LDL cholesterol in body.

Even though the presence of high levels of plasma urate have been associated with coronary diseases, there has been a constant debate for the past many years as to if hyperuricaemia causes coronary heart disease or not with different previous studies presenting discrepant results.

The findings from this latest study have brought new aspects of this association to light and might help other investigators in judging plasma urate against other potential risk factors such as blood pressure, triglycerides, and HDL cholesterol. The result is achieved by using 31 SNPs identified from GWAS while utilizing many Mendelian randomization models to form a powerful genetic instrument rather than forming isolated single variant.

The Analytical Model’s Superiority Over Conventional Model

This research preferred the Egger Mendelian randomization analysis over the conventional Mendelian randomization, which has been used in several previous studies that suggest plasma urate might have a causal role in coronary heart diseases due to the fact that the latter gives biased results.

This method of analysis adopted by the researchers takes into account pleiotropy which simply refers to the influence of a single gene on multiple traits. While the conventional method does account for measured pleiotropy, it does not neutralize the effects of unmeasured or unknown interventional factors; however, Egger Mendelian randomization analysis has the ability of reducing inflation in estimation of causal effect as a result of both measured and unmeasured pleiotropy.

The results of this research add to those of a previous study that had 70,000 participants with 7,000 coronary heart disease cases which also found the absence of any causal association between plasma urate and coronary heart diseases.

However, the data in this latest study was collected from a larger number of individuals, around 145,000 individuals (68 studies) with information about genotype and urate concentration and 198,598 individuals (51 studies) with information about genotype and coronary heart disease (60,785 coronary heart disease events) and were included in the Mendelian randomization analysis.

Allopurinol — A Trouble Creator For The Research

A drug known as allopurinol which is useful in preventing buildup of uric acid and keeping it at correct levels in the blood has been observed to be beneficial in cardiovascular issues, including endothelial function, angina symptoms, blood pressure, left ventricular mass, and exercise capacity. However, because of the fact that this drug reduces the production of free-radical i.e., reactive oxygen species, it is still not clear if the positive effects seen after allopurinol usage are due to this reason or actually the lowering of plasma urate concentration.

A good news is that a study is already currently in progress where clinical trial of consortium between standard care availability and Allopurinol of dosage 600mg per day is compared against the standard care alone in coronary heart disease patients. This would help in determining the Allopurinol’s effect on CHR and stroke.

What Is Plasma Urate?

Plama urate, which is commonly known as uric acid is the product of purine nucleotides metabolism in humans. It has not yet been proven to have any physiological function but acts as an antioxidant in human body. It can create crystals which can be deposited in joints causing gout and in kidney causing nephrolithiasis. It is also associated with other medical conditions such as diabetes and the formation of kidney stones.

The results of this study have shown that relation between increased plasma urate concentrations and coronary heart diseases is modest, and is most likely affected by other confounding risk factors.

This groundbreaking research will prove to be extremely beneficial for future research in this field because it not only establishes that plasma urate does not directly cause coronary heart diseases but also presents them in relation to a urate lowering drug which has beneficial effects on cardiovascular endpoints. Egger Mendelian randomization analysis that was used in this study to analyze the data also reduces the bias which was present in many previous studies, making this study more reliable and advanced.

Overall, this is a comprehensive study and caters all important aspects of the problem in question and will help in answering the long asked question: Does increased concentration of uric acid cause coronary heart diseases?