Prevalence of metabolic syndrome risk factors and their relationships with renal function in Chinese centenarians

As the first time, this study was to investigate the prevalence of metabolic syndrome (MetS) risk factors and explore their relationships with renal function in Chinese centenarians. China Hainan Centenarian Cohort Study was performed in 18 cities and counties of Hainan Province. Home interview, physical examination and blood analysis were performed in 874 centenarians following standard procedures. Prevalence of MetS was 15.6% (136 centenarians). There were 229 centenarians with abdominal obesity (26.2%), 645 centenarians (73.8%) with hypertension, 349 centenarians with dyslipidemia (39.9%) and 92 centenarians with diabetes mellitus (10.5%). In multivariate linear regression, age, smoking, waist circumstance (WC), systolic blood pressure (SBP) and triglyceride levels were inversely and diastolic blood pressure (DBP) levels were positively associated with glomerular filtration rate levels (P < 0.05 for all). This study reported low prevalence of MetS risk factors and demonstrated that age, smoking, abdominal obesity (WC), hypertension (SBP and DBP) and triglyceride levels were independently associated with renal function in Chinese centenarians. This study provided reliable data about Chinese centenarians, analyzed significant relationships between Mets risk factors and renal function, and explained possible reason (low prevalence of MetS and its risk factors) and mechanism (interrelationship of age, Mets risk factors with renal function) of longevity.

model, whether the interaction between MetS and RFD exists in the aging process of centenarians is still unclear and needs further studies.
Prevalence of MetS increases with age, reaching 42.0% in U.S. adults 70 years or older 15 . However, prevalence of MetS and its risk factors are still unclear in Chinese centenarians 16 . Moreover, its relationship with renal function still has significant debate in the elderly, not to say the centenarians 17 . Considering the specificity of centenarians, previous studies in the general population can not accurately represent the centenarians 18 . Meanwhile, in order to understand the reasons and mechanisms of longevity, it is very valuable to perform the studies in Chinese centenarians. Hainan is a longevity area with the highest population density of centenarians in China, and China Hainan Centenarian Cohort Study (CHCCS) with a considerable sample size provides a significantly population-based sample of Chinese centenarians. As the first time all over the world, this study was designed to investigate the prevalence of MetS risk factors and explore their relationships with renal function in a representative sample of Chinese centenarians.

Discussion
Studies about the centenarians can help us understand the reasons and mechanisms of longevity. In previous studies, Mets has a prevalence more than 20% in the general population and a higher prevalence in the elderly [19][20][21] . In U.S. adults, prevalence of MetS increases with age, reaching 42.0% in those 70 years or older 15 . This study reported that there was obviously low prevalence of Mets (15.6%) and its risk factors in Chinese centenarians. Georgia Centenarian Study has concluded that major barriers to reaching centenarians come from several incident chronic age-related disorders, especially cardiovascular disorders 20 Table 4. Relationships between metabolic syndrome risk factors and GFR in multivariate logistic regression analysis. Abbreviations: GFR: glomerular filtration rate; DM: diabetes mellitus.
Both MetS and RFD have been underlined to be independently associated with cardiovascular incidence, events and mortality [2][3][4][5][6][7][8] . Previous studies have shown significant relationship between MetS and renal function, but drawn controversial conclusions 8,9,17 . Meanwhile, most of these studies about the centenarians are performed in the general population of developed countries, with little information available on the centenarians in China 9,18 . Additionally, the data on ethnic Chinese are limited, and the relationship between MetS and renal function is still unknown in ethnic Chinese 9,10 . This study realized a possible mechanism of longevity in Chinese centenarians that not only age, but also Mets and its risk factors had significant relationships with renal function. On the one hand, Mets and its risk factors may impair the renal function, aggravate the cardiovascular disorders and reduce the life expectancy. The hypothesized mechanism is that as age increases, the clustering of MetS risk factors may result in oxidative stress and endothelial dysfunction, which consequently cause the atherosclerosis-related RFD 23 . In turn, RFD may gradually affect the blood pressure, glucose and lipids, and also aggravate the metabolic disturbance and promote the development of MetS 24 . On the other hand, the relationships between age, Mets and renal function also remind us that Mets and RFD may result from a common cause linked to the aging phenomenon. Either one of MetS and RFD may enforce the effects of other one on cardiovascular disorders and their incidence, and the interrelationship between MetS and RFD may worsen further cardiovascular events and mortality 7,8 .
Abdominal obesity is a fundamental pathology of MetS, and contributes to the development of other MetS risk factors, such as hypertension, dyslipidemia and DM. Abdominal obesity is significantly associated with high mortality risk, and there is an obviously increased prevalence of abdominal obesity in many developed and developing countries 25,26 . There have been inconsistent study results on the relationship between abdominal obesity and renal function. Several studies have realized that abdominal obesity is significantly associated with renal function in the general population. But other study has not verified significant association between abdominal obesity and renal function in the elderly 16 . This study observed that with a prevalence of 26.2%, abdominal obesity was independently associated with renal function in Chinese centenarians.
As prevalence of hypertension is rapidly increasing all over the world, the relationship between blood pressure and renal function has drawn considerable attention. Previous studies have shown that hypertension was significantly associated with renal function 27,28 . However, other study has also found that blood pressure has no significant association with renal function 16 . This study showed that with a prevalence of 73.8%, hypertension was inversely associated with renal function. More interestingly, SBP was inversely associated with renal function, but DBP was positively associated with renal function in this study. One the one hand, elevated SBP may induce the glomerulosclerosis and lower GFR, while reduced DBP may cause the renal hypoperfusion and lower GFR. On the other hand, RFD may affect the sodium and water retention, activate the renin-angiotensin-aldosterone system and induce the abnormality of SBP and DBP 29 .
It is a significant issue to analyze the relationships between different types of dyslipidemia and renal function, especially in the elderly, and there has been a controversial relationship between TG levels and renal function. Previous studies have proved that TG levels were significantly associated with renal function 28 . Triglyceride-rich apolipoprotein B-containing lipoproteins may promote the progression of RFD 30 . However, Helsinki Heart Study has provided an evidence that there is no significant association between TG levels and renal function 31 . This study confirmed that TG levels were significantly associated with renal function in Chinese centenarians, and lowering TG therapy may play a role in preserving renal function in addition to preventing cardiovascular disorders.
Smoking is a significant public health problem all over the world, and has been considered to be harmful to renal function in previous studies 32 . Meanwhile, there has been a concern for many countries about the relationship between DM and renal function, and previous large-scale survey in the US general population has concluded that DM was not associated with renal function 33 . Consistent with previous studies, this study demonstrated that with a prevalence of 3.3%, smoking exerted harmful effects on renal function. And with a prevalence of 10.5%, DM had no significant association with renal function in Chinese centenarians.
The current study had one limitation. Smoking was assessed by asking each centenarian whether he or she was a current smoker. Although ex-smoker does not seem to be counted as smoker, it should be considered to be one limitation.

Conclusion
As the first time all over the world, this study reported low prevalence of MetS and its risk factors, and demonstrated that age, smoking, abdominal obesity (or WC), hypertension (or SBP and DBP) and TG levels were independently associated with renal function in Chinese centenarians. Low prevalence of MetS and its risk factors was a possible reason of longevity, and the interrelationship of age, Mets and its risk factors with renal function was a possible mechanism of longevity in Chinese centenarians. Based on CHCCS, this study not only provided reliable data about Chinese centenarians and analyzed significant relationships between Mets risk factors and renal function, but also explained possible reason and mechanism of longevity.

Methods
Study population. CHCCS was performed in population-based individuals aged 100 or above from July 2014 to December 2016 in 18 cities and counties of Hainan Province, China. Its cohort profile has been described previously 34 . Based on National Civil Registry, a total of 1,002 centenarians were identified by Hainan Civil Affairs Bureau and enrolled in this study. Age was ascertained from national identification cards. The following inclusion criteria were used to recruit study participants: (1) was 100 years or older; (2) volunteered to participate in the study and provided written informed consent; and (3) was conscious and could cooperate to complete the home interview, physical examination and blood analysis. The following were participant exclusion criteria: (1) personal identity information was not complete or identification cards showed an age of less than 100 years; (2) refused to comply with the requirements of the study, including the collection of physical or blood samples. There were 874 centenarians included in the final analysis. This study followed the approval from Ethics Committee of Hainan branch of Chinese People's Liberation Army General Hospital (Sanya, Hainan; Number: 301hn11201601). Written informed consent was obtained from all centenarians in this study. All methods were performed in accordance with the relevant guidelines and regulations.
Standard procedures. Home interview, physical examination and blood analysis were performed following standard procedures 35 . The research team included internists, geriatricians, cardiologists, endocrinologists, nephrologists and nurses. Smoking was assessed by asking each centenarian whether he or she was a current smoker 36 . Waist circumstance (WC) was measured with a soft tape midway between the lowest rib and the iliac crest. Consistent with current recommendations, systolic and diastolic blood pressures (SBP and DBP) were measured with the right arm of centenarians two times consecutively, with at least 1 minute between measurements, and the reported blood pressures were the average of these two measurements. Samples of venous blood were obtained from the centenarians and transported in chilled bio-transport container (4 °C) to our Central Laboratory within 4 hours. Serum concentrations of fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoproteincholesterol (HDL-C) and creatinine were measured using the enzymatic assays (Roche Products Ltd, Basel, Switzerland) on a fully automatic biochemical autoanalyzer (Cobas c702; Roche Products Ltd, Basel, Switzerland). All assays were performed by qualified technicians without knowledge of clinical data.

Variable definitions. Based on the worldwide consensus on the definition of MetS recommended by
International Diabetes Federation, MetS was defined as abdominal obesity plus any two of four additional factors: SBP ≥130 mmHg or DBP ≥85 mmHg (or previously diagnosed hypertension); FBG ≥5.6 mmol/L (or previously diagnosed DM); and TG ≥1.7 mmol/L, HDL-C <1.0 mmol/L in males and <1.3 mmol/L in females (or previously diagnosed dyslipidemia) 37 . Based on Chinese guidelines on prevention and control of obesity, abdominal obesity was defined as WC ≥85 cm for men and ≥80 cm for women 38 . Hypertension was defined as SBP ≥140 mmHg, DBP ≥90 mmHg or taking anti-hypertensive drugs 39 . DM was defined as FBG ≥7.0 mmol/L or taking hypoglycemic drugs/insulin 40  Statistical analyses. Continuous variables were described as the mean and standard deviation for variables with normal distribution and the median and interquartile range for variables with skewed distribution. Categorical variables were described as the number and percentage. Continuous variables were compared with Student's t-test (normal distribution) and Mann-Whitney U test (skewed distribution). Categorical variables were compared with Chi-square test. Pearson's (continuous variables with normal distribution) and Spearman's (continuous variables with skewed distribution and categorical variables) correlations were used to assess the simple relationships between MetS risk factors and renal function. In order to assess the independent relationships between MetS risk factors and renal function, multivariate linear regression analyses were adjusted by age, sex, smoking, WC, SBP, DBP, TC, TG, HDL-C, LDL-C and FBG, and multivariate logistic regression analyses were adjusted by age, sex, smoking, abdominal obesity, hypertension, dyslipidemia and DM. Statistical significance was accepted at the two-sided 0.05 level, and confidence interval (CI) was computed at the 95% level. Statistical analyses were performed with Statistic Package for Social Science (SPSS) version 17 (SPSS Inc., Chicago, IL, U.S.).
Availability of data and materials. In attempt to preserve privacy of patients, clinical data of patients will not be shared; data can be available from authors upon request.