Is Hyperuricemia, an Early-Onset Metabolic Disorder, Causally Associated with Cardiovascular Disease Events in Han Chinese?

Abstract

Background: Serum uric acid (SUA) has gradually been recognized as a potential risk factor for cardiovascular disease (CVD). However, whether the relationship is causal remains controversial. Methods: We employed two methods to demonstrate the importance of SUA in CVD development. First, we examined the onset sequence of hyperuricemia in relation to five cardiometabolic (CM) diseases. Second, we conducted a Mendelian randomization (MR) study to causally infer the relationship between SUA and CVD. The information collected from the Cardiovascular Disease Risk Factors Two-Township Study (CVDFACTS) and Taiwan Biobank was used, respectively. Results: The onset sequence study showed that hyperuricemia and hypo-alpha-lipoproteinemia (low HDL-C) have earlier ages of onset than other CM diseases. For the MR analysis, the high weighted genetic risk score (WGRS) group had a significantly increased cumulative lifetime risk of CVD compared with the low WGRS group (OR = 1.62, (1.17−2.23), P = 0.003). Sensitivity analysis using the WGRS derived from other populations’ SUA-influential SNPs revealed similar results. Conclusions: We showed that hyperuricemia is an earlier-onset metabolic disorder than hypertension, hypertriglyceridemia, and diabetes mellitus, indicating that high SUA plays an upstream role in CM development. Moreover, our MR study results support the idea that hyperuricemia may play a causal role in CVD development. Further validation studies in more populations are needed.

Associations between Health-Related Physical Fitness and Cardiovascular Disease Risk Factors in Overweight and Obese University Staff

“…UA is the final product of purine metabolism. An excessive accumulation of UA in the body may cause not only gout but also heart failure [6,7]. In recent years, UA has been observed to slow age-related muscle decline [33,34].…”

“…The risk factors of CVD include dyslipidemia, diabetes, and obesity [5]. In recent years, hyperuricemia has also been recognized as a potential risk factor for CVD, following the discovery of a causal relationship between uric acid and the adverse outcomes of CVD [6,7]. Among the many risk factors, obesity affects cardiovascular disease in several ways; for instance, obesity affects the morbidity of CVD, and early obesity may increase the risk of future CVD events [8].…”

Construction and expression of recombinant uricase‑expressing genetically engineered bacteria and its application in rat model of hyperuricemia

“…The clinical diagnostic criteria for hyperuricemia are SUA >420 µmol/l in males and SUA >360 µmol/l in females (5). Recent studies have shown that following changes to the structure of the human diet, the incidence of hyperuricemia in the world is increasing (6)(7)(8), and the age of onset of hyperuricemia is decreasing (9,10).…”

Impact of monocyte to high-density lipoprotein ratio on prevalent hyperuricemia: findings from a rural Chinese population

“…In recent decades, hyperuricemia is becoming a major public health issue due to its close association with critical diseases such as gout, hypertension, diabetes mellitus, chronic kidney disease and other cardiovascular diseases (CVD) [1][2][3][4][5][6]. For example, the Mendelian randomization study supported that hyperuricemia may play a causal role in the development of CVD, suggesting its great significance for early screening and prevention of CVD [5]. Accordingly, there is a clear need for a simple approach to improve the risk stratification and prevention of hyperuricemia.…”