Hyperuricemia is associated with metabolic syndrome in the community very elderly in Chengdu

Hyperuricemia is a risk factor for cardiovascular metabolic diseases. However, in the very elderly, the relationship between hyperuricemia and the metabolic syndrome (MetS) is not yet clear. This study was aimed to investigate the potential association between hyperuricemia and MetS in community very elderly in Chengdu. In this cross-sectional study, 1056 very elderly in the community were enrolled. Serum uric acid (SUA), fast plasma glucose, triglycerides and high–density lipoprotein cholesterol were measured, and then MetS components were calculated. Logistic regression models were used to explore risk factors for MetS in the very elderly. Finally, 1035 participants were included in analysis whose ages ranged between 80 and 100 with a mean age of 83.6 ± 3.4 years. The mean SUA level was 356.2 ± 95.0 µmol/L. The estimated prevalence of MetS in the very elderly was 25.0% vs. 21.6% (international diabetes federation (IDF) criteria vs. Chinese guideline), which was significantly higher for women (IDF criteria:17.3% in men vs 33.6% in women, p < 0.001). Logistic regression has found that participants with hyperuricemia (SUA level > 416 µmol/L in men and > 357 µmol/L in women) had a higher risk (IDF criteria: odds ratio (OR): 2.136, 95% confidence interval(CI): 1.525–2.993, p < 0.001. Chinese guideline: OR: 1.769, 95%CI: 1.249–2.503, p = 0.001) of MetS in very elderly Chinese. MetS is common in the community of very elderly Chinese in Chengdu. Hyperuricemia is associated with MetS in general very elderly and lifestyle changing should also be considered in the very elderly.

Data collection and measurement. Previously well-trained physicians and nurses collected data from the participants with a questionnaire-based face to face interview during clinical visits, which was described elsewhere 16 . Basic demographic characteristics, past medical history and lifestyle risk factors of participants were obtained from a standardized questionnaire during the interview with participating investigators. The body mass index (BMI) was defined as weight in kilograms divided by the square of the height in meters. The blood pressure (BP) was measured three times in a sitting position by using a standardized automatic electronic sphygmomanometer (HEM-7300, Omron, Kyoto, Japan) and average values were calculated and used in the analysis. Fasting blood samples were collected in the morning after at least 8 hours of fasting for all participants. SUA and other biochemical parameters, such as fast plasma glucose(FPG), total cholesterol(TC), triglycerides(TG), and lowdensity lipoprotein cholesterol(LDL-C) were analyzed enzymatically on an auto-analyzer (AU5421 Chemistry Analyzer, Beckman, Brea, California, United States) in the central laboratory.
Finally, the estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease study equation modified for the Chinese population: eGFR = 186 × serum creatinine −1.154 × Age −0.203 × 0.742 (if female).
MetS, according to the Consensus Worldwide Definition from the international diabetes federation (IDF) 18 and the Chinese guideline for dyslipidemia management 19 , was defined as follows, respectively: MetS defined by IDF: abdominal obesity with ethnic-specific waist circumference (WC) cut-points (for Chinese: ≥ 90 cm in men and ≥ 80 cm in women) and fulfills two items of the following: TG ≥ 150 mg/dL (1.7 mmol/L) or treatment for hypertriglycerides, HDL cholesterol <40 mg/dL (1.03 mmol/L) in men or <50 mg/ dL (1.29 mmol/L) in women or treatment for low HDL, FPG ≥ 100 mg/dL (5.6 mmol/L) or previously diagnosed type 2 diabetes, and BP ≥ 130/85 mmHg or treatment for hypertension.
Statistical analysis. SPSS software (Version 22.0, SPSS Inc, Chicago, IL) were used to performed the statistical analyses. Continuous variables with normal distribution are expressed as mean ± standard deviation and skewed continuous variables expressed as median (interquartile range). Frequencies are presented as percentages with 95% confidence interval (95%CI). ANOVA or Kruskal-Wallis test was used to compare the continuous variables between groups, whereas x 2 test was applied to compare frequencies. Logistic regression models were used to evaluate the potential association between hyperuricemia and MetS. The receiver operating characteristic (ROC) curve analysis was employed to evaluate the efficiency of SUA level in predicting MetS. A two-sided p value < 0.05 was considered statistically significant.

Results
Baseline characteristics. A total of 1035 participants with a mean age of 83.6 ± 3.4 years were enrolled in the final statistical analysis, of which 52.6% were men with a mean age of 83.6 ± 3.3 years. The overall mean SUA level was 356.2 ± 95.0 µmol/L with a mean level of 374.2 ± 94.5 µmol/L in men and 335.2 ± 89.3 µmol/L in women (p < 0.001). According to both sets of criteria explained above, participants with MetS had a significantly higher mean SUA level (IDF criteria: 375.8 ± 90.8 vs. 349.5 ± 95.6 µmol/L, p < 0.001; Chinese guideline: 375.2 ± 88.8 vs. 350.7 ± 96.0 µmol/L, p < 0.001). The overall mean level of eGFR was 58.4 ± 13.9 ml/(min•1.73m 2 ) (men vs. women: 61.8 ± 14.1 vs. 54.6 ± 12.6 ml/(min•1.73m 2 ), p < 0.001). As shown in Table 1, participants with more MetS components were more likely to be abdominal obese with higher levels of WC, BMI, SBP, DBP, FBG, TC, TG, LDL and SUA, but a lower level of HDL. estimated prevalence of MetS and its components. The overall estimated prevalence of MetS in the very elderly was 25.0% (17.3% in men vs. 33.6% in women, p < 0.001) according to the IDF criteria, which was significantly higher (p < 0.001) than that of the Chinese guideline (21.6%, 17.8% in men vs. 25.8% in women, p = 0.002). Table 2 describes the prevalence of its components. estimated prevalence of MetS in the very elderly with hyperuricemia. The estimated prevalence of MetS in participants with hyperuricemia was 39.4% vs. 32.9% (p < 0.001) according to the IDF and Chinese guideline, respectively. The estimated prevalence of MetS in very elderly women with hyperuricemia was significantly higher than it was in men according to both the IDF criteria (66.9% vs. 33.1%, p < 0.001) and the Chinese guideline (39.3% vs. 26.6%, p = 0.016).

Discussion
The main findings of this study are as follows: 1) MetS is common in the very elderly in Chengdu, especially in very elderly women. 2) hyperuricemia was generally associated with MetS in the very elderly in Southwest China.

MetS in the very elderly.
Because of the dramatic changes in the environment and rapid westernization of lifestyles such as more saturated fat and sugar consumption and less physical activity, the prevalence of MetS and ASCVD has been increasing rapidly during the past decades in China 2,3 . In addition, it has been shown that the prevalence of MetS is age-dependent. As per other studies in middle-aged and elderly Chinese 14,20 , Korean 21 , and Japanese 22 , our findings show that the prevalence of MetS is remarkably high in the general community very elderly as well as in very elderly with hyperuricemia. The potential causes could be the clustering of more MetS components with aging in the very elderly (such as hypertension and abdominal obesity), decreased physical activities, and chilly and oil-rich local food style, which result in obesity and considerably dyslipidemia 23 .
Furthermore, following other studies 20,24 , this study also demonstrates that MetS is more common in very elderly women and those with hyperuricemia. Previous analysis has already showed a significantly higher prevalence of abdominal obesity and hypertriglyceridemia in very elderly women than it is in men 23 and increased WC and extreme obesity increase more risk of MetS in women than in men 25 . Although the difference in the definition of MetS between the IDF criteria and the Chinese guideline results in the variation of the estimated prevalence of MetS without surprising, we could not ignore the fact that the prevalence of MetS is unexpectedly high in the very elderly residents in Chengdu, especially in very elderly women.
Association between hyperuricemia and MetS. Elevated SUA level and hyperuricemia have already been reported to be associated with MetS and its components in middle-aged or elderly populations in other areas of China 14,15 . For the first time, this study describes the association between hyperuricemia and MetS in the community very elderly in Southwest China. The potential mechanisms for this association between hyperuricemia and MetS include inflammation and oxidative stress induced by SUA in adipocytes, which cause abnormal adipocytokine secretion and resulting in insulin resistance and the development of MetS 26,27 .
Previous studies 14,15,22,28 establish that there is a gender difference in the prevalence of MetS. Furthermore, some studies 14,15,22,29 show that the association between hyperuricemia and MetS is more evident in the middle-aged and elderly women. Following these findings, sub-analyses of our study find that there is a greater OR value of hyperuricemia for MetS in very elderly women than in men but without significant sex interaction. Therefore, whether hyperuricemia could differently contribute to the development of MetS in very elderly women and men, it still needs further prospective studies to clarify that.
In this very elderly population, hyperuricemia is found to be associated with abdominal obesity and dyslipidemia while not with hyperglycemia, which supports the results of some other studies 15  www.nature.com/scientificreports www.nature.com/scientificreports/ explanation may be that glucose can competitively inhibit SUA reabsorption and enhance its excretion at the same anatomical position in the gut and that SUA reduces after the onset of diabetes 30,31 .
It is well known that kidneys play a key role in SUA elimination, including glomerular filtration, tubular reabsorption, secretion and resorption 32 . However, renal function decreases with ageing even in apparently healthy individuals, but yet less in individuals with different chronic cardiovascular diseases 33 . Therefore, renal function can influence on the SUA level. Similar to the eGFR level in very elderly Chinese in CKD-EPI study 34 , the mean eGFR value in this study was around 60 ml/(min•1.73m 2 ), which might decrease SUA elimination and increase the SUA level. Taking this into consideration, it would not be surprising that the SUA level in this study is a little higher than that in the previous study with about 2000 Chinese elderly residents 35 .
The ability of SUA level for predicting a four year MetS incidence in general elderly Italian with an AUC value of 0.647 has been verified previously 29 . Similar to the results of that study, the AUC value in our research also indicates that the predictive ability of SUA for MetS is reasonable in the very elderly population in Chengdu.
In conclusion, the prevalence of MetS in the very elderly in Chengdu is relatively high and hyperuricemia is associated with the risk of MetS. On the other hand, it implicates that more efficient prevention strategies for cardiovascular and metabolic disease, including all MetS components and hyperuricemia, are urgently needed for middle-aged and elderly residents, especially for women 36 .