Genetically Determined Uric Acid and the Risk of Cardiovascular and Neurovascular Diseases: A Mendelian Randomization Study of Outcomes Investigated in Randomized Trials

Efstathiadou, Anthoula; Gill, Dipender; McGrane, Frances; Quinn, Terence J; Dawson, Jesse

doi:10.1161/jaha.119.012738

Cited by 51 publications

(41 citation statements)

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“…16,17 Genetic causes of hyperuricemia have been linked with derangement of nitric oxide synthesis, and thus, endothelial dysfunction acts as a harbinger for inflammation and cardiovascular compromise. 18 The results of this study reveal that serum uric acid levels significantly rises with the severity of the disease, from a single vessel to triple vessel involvement. High sensitivity troponins levels were elevated in all the patients and based on that the diagnosis of MI was made.…”

Section: Discussionmentioning

confidence: 64%

Hyperuricemia as a risk factor for increase severity of coronary vessel occlusion disease: a cross-sectional study in North Indian population

et al. 2020

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Background: Cardiovascular disease (CVD) is the most common cause of death worldwide. The present study was conducted to study uric acid as a potential biomarker in predicting the severity of CVD in terms of vessel involvement.Methods: A cross-sectional study, conducted at Rajiv Gandhi Super Speciality Hospital, Tahirpur, Delhi. A total of 52 consecutive male and female patients age between 30 to 70 years was included in this study. Written informed consent was obtained from all the enrolled patients. Automated analysers were used for the analysis of blood glucose, lipid profile and serum uric acid level. IBM SPSS Statistics (Version 20.0, IBM SPSS, IL, USA) was used for the statistical analyses.Results: In this study, a total of 52 consecutive patients were divided into three groups; single-vessel disease (n=19), double vessel disease (n=19) and triple vessel disease (n=14). Biochemical profile of all the groups was calculated. A group of triple vessel disease patients showing higher amount (164±42 mg/dl) of cholesterol level as compared to the other two groups (157±34 mg/dl). The mean level of serum uric acid levels significantly differed and its mean levels increases as the severity of vessel diseases increases. The receiver operating characteristic curve shows the uric level has 71% sensitivity and 52.5% specificity for detecting the severity of coronary vessel disease.Conclusions: This study demonstrated an increased serum uric acid levels were associated with increased severity of vessel disease, and serum uric acid is an independent risk factor for coronary artery disease.

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Section: Discussionmentioning

confidence: 64%

Hyperuricemia as a risk factor for increase severity of coronary vessel occlusion disease: a cross-sectional study in North Indian population

et al. 2020

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“…The Mendelian randomization can be thought of as a naturally randomized controlled trial, based on the random allocation of alleles when passed from parents to offspring during the meiotic process, known as Mendel’s second law 31 . Recently, Efstathiadou et al 9 conducted a Mendelian randomization study to determine the clinically relevant causal effect between serum urate and the cardiovascular outcome. However, they failed to show any clinical causal relationship between uric acid and coronary heart disease, myocardial infarctions, the systolic blood pressure, or any type of ischaemic stroke 9 .…”

Section: Discussionmentioning

confidence: 99%

“…Recently, Efstathiadou et al 9 conducted a Mendelian randomization study to determine the clinically relevant causal effect between serum urate and the cardiovascular outcome. However, they failed to show any clinical causal relationship between uric acid and coronary heart disease, myocardial infarctions, the systolic blood pressure, or any type of ischaemic stroke 9 . On the strength of that study, we selected nine genes from the 30 uric acid genes found in European populations.…”

Section: Discussionmentioning

confidence: 99%

“…The Mendelian randomization analysis has previously demonstrated the genetic causal association between a high uric acid level and adverse cardiovascular outcomes, especially sudden cardiac death, using UK biobank data 8 . However, other Mendelian randomization studies did not show a causality between uric acid and coronary heart disease, myocardial infarctions, the systolic blood pressure, or any type of ischaemic stroke 9 . The aims of this study were to explore the relationship between the serum uric acid level and AF prevalence in a relatively high number of patients (over 4000), and to determine their clinical and genetic causal relationships by utilizing the Mendelian randomization method.…”

Section: Introductionmentioning

confidence: 99%

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A mendelian randomization analysis: The causal association between serum uric acid and atrial fibrillation

Hong

Park

Yang

et al. 2020

Eur J Clin Investigation

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Background: Observational studies have shown that high levels of serum uric acid (UA) were associated with atrial fibrillation (AF). However, the causal effect of urate on the risk of AF is still unknown. To clarify the potential causal association between UA and AF, we performed a Mendelian randomization (MR) analysis using genetic instrumental variables (IVs). Materials and methods: From the Korean GWAS dataset of 633 patients with AF (mean age 50.6 ± 7.8 years, 80.9% male, Yonsei AF Ablation cohort) who underwent radiofrequency catheter ablation and the data from 3533 controls (from the Korea Genome Epidemiology Study), we selected 9 SNPs, with a P value less than .05, associated with an increased UA serum level. Additionally, we calculated the weighted genetic risk score (wGRS) using the selected 9 SNPs, to use it as an instrumental variable. A Mendelian randomization analysis was calculated by a 2-stage estimator method. Results: The conventional association between the serum UA and AF was significant (P = .001) after adjusting for potential confounding factors. The SNP rs1165196 on SLC17A1 (F-statistics = 208.34, 0.18 mg/mL per allele change, P < .001) and wGRS (F-statistics = 222.26, 0.20 mg/mL per 1SD change, P < .001) were significantly associated with an increase in the UA level. The MR analysis was causally associated with rs1165196 (estimated odds ratio (OR), 0.21, 95% confidence interval (CI), 0.06-0.75, P = .017), but not wGRS (estimated OR, 1.07, 95% CI, 0.57-2.01, P = .832). Conclusion: The serum UA level was independently associated with the AF risk.

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“…Furthermore, HU and gout may also be potential risk factors for hypertension, CVD, CKD, and the metabolic syndrome [ 8 , 10 ]. In studies using Mendelian randomization (MR) analyses, there is some support for obesity as a causal risk factor for HU and gout [ 11 ], whereas such studies have so far failed to support causality between HU and/or gout and other risk factors including CVD, CKD, and diabetes [ 12 – 14 ].…”

Section: Introductionmentioning

confidence: 99%

The absolute risk of gout by clusters of gout-associated comorbidities and lifestyle factors—30 years follow-up of the Malmö Preventive Project

et al. 2020

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Background Gout is predicted by a number of comorbidities and lifestyle factors. We aimed to identify discrete phenotype clusters of these factors in a Swedish population-based health survey. In these clusters, we calculated and compared the incidence and relative risk of gout. Methods Cluster analyses were performed to group variables with close proximity and to obtain homogenous clusters of individuals (n = 22,057) in the Malmö Preventive Project (MPP) cohort. Variables clustered included obesity, kidney dysfunction, diabetes mellitus (DM), hypertension, cardiovascular disease (CVD), dyslipidemia, pulmonary dysfunction (PD), smoking, and the use of diuretics. Incidence rates and hazard ratios (HRs) for gout, adjusted for age and sex, were computed for each cluster. Results Five clusters (C1–C5) were identified. Cluster C1 (n = 16,063) was characterized by few comorbidities. All participants in C2 (n = 750) had kidney dysfunction (100%), and none had CVD. In C3 (n = 528), 100% had CVD and most participants were smokers (74%). C4 (n = 3673) had the greatest fractions of obesity (34%) and dyslipidemia (74%). In C5 (n = 1043), proportions with DM (51%), hypertension (54%), and diuretics (52%) were highest. C1 was by far the most common in the population (73%), followed by C4 (17%). These two pathways included 86% of incident gout cases. The four smaller clusters (C2–C5) had higher incidence rates and a 2- to 3-fold increased risk for incident gout. Conclusions Five distinct clusters based on gout-related comorbidities and lifestyle factors were identified. Most incident gout cases occurred in the cluster of few comorbidities, and the four comorbidity pathways had overall a modest influence on the incidence of gout.

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Genetically Determined Uric Acid and the Risk of Cardiovascular and Neurovascular Diseases: A Mendelian Randomization Study of Outcomes Investigated in Randomized Trials

Cited by 51 publications

References 50 publications

Hyperuricemia as a risk factor for increase severity of coronary vessel occlusion disease: a cross-sectional study in North Indian population

Hyperuricemia as a risk factor for increase severity of coronary vessel occlusion disease: a cross-sectional study in North Indian population

A mendelian randomization analysis: The causal association between serum uric acid and atrial fibrillation

The absolute risk of gout by clusters of gout-associated comorbidities and lifestyle factors—30 years follow-up of the Malmö Preventive Project

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