Definition of Metabolic Syndrome

CONCLUSION: In these 2310 Chinese study participants aged 40 years and older, metabolic syndrome was associated with CKD.

Mayo Clin Proc. 2007;82(7):822-827

BP = blood pressure; CKD ■ chronic kidney disease; Cl - confidence interval; eGFR ■ estimated glomerular filtration rate; FBG ■ fasting blood glucose; HDL = high-density lipoprotein; IDF ■ International Diabetes Federation; NHANES III " Third National Health and Nutrition Examination Survey; OR * odds ratio; SCr = serum creatinine: TG - trigtyceride

Metabolic syndrome, a cluster of risk factors for car­diovascular disease, is a common disorder in devel­oped countries. Data from the Third National Health and Nutrition Examination Survey (NHANES III) indicated that 47 million US residents (23.7%) aged 20 years and older have metabolic syndrome.¹ With its dramatic economic development and the consequent changes in lifestyle and diet, China too has seen the metabolic syndrome become an important health care problem. Using the recommendations for Asian populations detailed in the modified standards of the National Cholesterol Education Program Adult Treat­ment Panel III, Gu et al² recently reported that 71 million adults (15.1%) aged 35 to 74 years living in China have metabolic syndrome.

Chronic kidney disease (CKD) has also become an im­portant public health challenge in China. In 2002, the annual incidence of hemodialysis in Beijing and Shanghai was 146.4and 148.1 per million population, respectively,- almost double the rates reported in 1999.⁴ Studies from NHANES 11! and the Atherosclerosis Risk in Communities Study show that metabolic syndrome is independently associated with CKD, both in the general population and in nondiabetic adults.¹⁵ However, to our knowledge, the relationship be­tween metabolic syndrome and CKD has never been tested in a developing country such as China, where genetic and envi­ronmental backgrounds differ from those in Western coun­tries. To fill this gap in the research, we initiated this cross-sectional study of a Beijing population (a40 years) to examine the relationship between metabolic syndrome and CKD.

PARTICIPANTS AND METHODS

The study population was described previously.'¹ All resi­dents served by a community hospital (Gucheng Hospital) in an urban district of Beijing who were 40 years or older were invited to participate in the study. Between May 12 and June 30, 2004, a local general practitioner contacted residents by telephone to inform them of study details. Of the 5593 residents 40 years and older who were contacted, 2353 (42.1%) volunteered to participate, 2310 (98.2%) of whom were ultimately included in the study because complete information on them was available. The inves­tigation began on May 12 and ended on December 7, 2004. All participants gave their informed consent.

Study Measurements

Sociodemographic characteristics, personal health history (eg, coronary artery disease, stroke, hypertension, and diabetes), and details about lifestyle (eg, smoking status) were obtained by questionnaire. Waist circumference, height, and weight were measured according to the standard protocol. Central obesity was defined on the basis of ethnic-specific values for waist circumference. Blood pressures were measured according to the guidelines presented in the Seventh Report of the Joint National Committee on Pre­vention, Detection, Evaluation, and Treatment of High

From the Institute of Nephroiogy and Division of Nephroiogy, Peking University First Hospital, Beijing, China (L.X.Z., L.Z., F.W., M.W., H.Y.W.); and Beijing Hypertension League Institute, Beijing, China (S.Y.W.. L.S.L.).

Individual reprints of this article are not available. Address correspondence to HaiYan Wang. MD, Institute of Nephrology and Division of Nephrology. Peking University First Hospital, No. 8 Xishiku St, Xicheng District, Beijing, 100034. PR China (e-mail: why@bjmu.edu.cn).

Blood Pressure.⁷ Three readings were taken at 5-minute intervals, and a mean was calculated. However, if the difference between any 2 readings was greater than 10 mm Hg, the 2 closest of the 3 measurements were used. Blood was collected by venipuncture after an overnight fast of at least 10 hours. Plasma glucose level was measured using a hexokinase enzyme reference method and serum creatinine (SCr) using an enzymatic method on an autoanalyzer (Hitachi 7170, Hitachi, Tokyo, Japan). Serum high-density lipoprotein (HDL) cholesterol and triglyceride (TG) levels were determined enzymatically with commercially available reagents. Furthermore, all participants, except those with a known diagnosis of diabetes, underwent a standard 75-g oral glucose tolerance test to determine plasma glucose levels. Participants were asked to fast for at least 10 hours over­night, and then 2 blood specimens were collected, 1 just before and 1 two hours after drinking a 75-g oral glucose solution. In addition, a spot urine sample was obtained, and levels of albumin were determined by immunoturbidimetric methods (Audit Diagnostics, Cork, Ireland) and urinary creatinine levels by the same methods as for SCr.

Definition of Metabolic Syndrome

According to the new definition by the International Diabe­tes Federation (IDF),^S metabolic syndrome can be diagnosed if central obesity (waist measurement >90 cm for men or >80 cm for women) is accompanied by any 2 of the following 4 factors: (1) TG levels of 1.7 mmol/L or greater, (2) an HDL cholesterol lower than 1.03 mmol/L for men or lower than 1.29 mmol/L for women, (3) a blood pressure (BP) of 130/85 mm Hg or greater or treatment of previously diagnosed hypertension, and (4) a fasting blood glucose (FBG) of 5.6 mmol/L or greater or previously diagnosed type 2 diabetes.

Definition of CKD

In a previous study, our group analyzed the SCr of 52 fresh-frozen serum samples using both the enzymatic method and Jaffe kinetic method on an autoanalyzer (Hitachi 7170). A calibration equation was generated from the results (/?²=0.999): Jaffe Kinetic Method SCr (mg/dL) = 0.795 x [Enzymatic Method SCr (mg/dL)] + 0.29.

The estimated glomerular filtration rate (eGFR) was calculated using a new equation developed by tailoring the Modification of Diet in Renal Disease equation to data from Chinese patients with CKD.⁰ Reduced renal function was defined as an eGFR of less than 60 mL/min per 1.73 nr: eGFR (mL/min/1.73 m²) = 175 x SCr (mg/dL)-'^:i4x Age (y)^¹⁷⁰ [Female x 0.79],

For practical purposes, albuminuria was defined as a spot urinary albumin-to-creatinine ratio higher than 30 mg/g. Chronic kidney disease was defined by the presence of reduced renal function and/or albuminuria.

Other Definitions

Hypertension was defined as systolie BP of 140 mm Hg or greater or a diastolic BP of 90 mm Hg or greater or as use of antihypertensive medications irrespective of the BP. Stan­dard World Health Organization criteria¹⁰ for the diagnosis of diabetes mellitus were used, ie, an FBG of 7.0 mmol/L or greater or a 2-hour plasma glucose of 11.1 mmol/L or greater.

Statistical Analyses

Data entry and management were performed on Epidata software, version 3.1 (Epidata Association, Odense, Den­mark). All analyses and calculations were performed using an SPSS statistical package, version 10.0 (SPSS, Inc, Chicago, 111). Data are presented as the mean ± SD for continuous variables and as proportions for categorical variables. Due to an extremely skewed distribution, vari­ables such as TGs were reported as the median, 25th, and 75th percentile. Descriptive analyses were used to charac­terize the participant population by sociodemographic data (age, sex) and health status (eg, body mass index, traits of metabolic syndrome). Prevalence and mean values of selected conditions (such as components of metabolic syndrome and indicators of kidney damage) were compared between participants with and without metabolic syndrome, by using %² statistics for categorical variables and the Student / test for continuous values. Furthermore, the %^: test was used to determine the prevalence of components of metabolic syndrome in regard to CKD status. The unadjusted odds ratio (OR) between traits of metabolic syndrome and CKD was determined by univariate logistic regression analysis and then adjustments were made for age and sex, as well as other factors including regular physical activity, a high school education or higher, active smoking, myocardial infarction, and stroke. In addition, the associations between the different traits of metabolic syndrome and CKD were analyzed by univariate logistic regression analysis and multivariate logistic regression analysis (adjusted for age and sex). Variables were selected on the basis of previous reports.⁵""" Finally, the association between metabolic syn­drome and CKD was also analyzed in regard to hypertension and diabetes status, by both univariate logistic regression analysis and multivariate logistic regression analysis (ad­justed for age and sex). All statistical tests were 2 sided. P<.05 was considered statistically significant.

RESULTS

General Participant Characteristics

Of the 2310 study participants, all were Chinese, and 49.5% were men. The mean age of participants was 60.7±9.9 years. General participant characteristics are given in Table 1.

TABLE 1. General Characteristics of Study Participants From Beijing, China*

glomerular nurauon rate; nuL *= nign-uensiiy lipoprotein,

f Reported as the median (the 25th percentile-the 75th percentile) due to skewed distribution. ^Defined as a urinary albumin-to-creatinine ratio greater than 30 mg/g. §Defined as an eGFR calculated using an equation developed by tailoring the Modification of Diet in

Renal Disease equation to data from Chinese patients with CKD.^ IIDefined as an eGFR of less than 60 mL/min per 1.73 m² and/or albuminuria.

Prevalence of Metabolic Syndrome

The frequency of metabolic syndrome traits differed significantly by sex (Figure 1). Women were more likely to have central obesity and dyslipidemia, whereas men had a higher frequency of elevated BP and elevated FBG levels. The overall prevalence of metabolic syndrome was 34.1% (95% confidence interval [CI], 31.7%-36.5%): metabolic syndrome was more prevalent in women than in men (41.3% vs 26.7%; P<.001).

Prevalence of CKD

The overall prevalence of albuminuria was 6.2% (n=142; 95% CI, 5.3%-7.3%). A total of 119 participants (5.2%: 95% CI, 4.3%-7.3%) had an eGFR of less than 60 mL/min

participants (5.2%: 95% CI, 4.3%-7.3%) had an eGFR

FIGURE 1. Frequency of metabolic syndrome traits by sex. BP = blood pressure; FBG = fasting blood glucose; HDL-C = high-density lipoprotein cholesterol; MS = metabolic syn­drome; TGs = triglycerides.

TABLE 2. Prevalence of Chronic Kidney Disease (CKD) by Individual Metabolic Syndrome Trait in 2310 Study Participants From Beijing, China*

'Values adjusted lor age, sex, and other metabolic syndrome traits. BP = blood pressure; eGFR = estimated glomerular filtration rate; FBG = fasting blood glucose; HDL-C = high-density lipoprotein cholesterol; TGs = triglycerides.

per 1.73 m². with the mean eGFR being 52.9±7.l mL/min per 1.73 nr. The overall prevalence of CKD was 10.7% (95% CI, 9.4%-] 2.1%) and did not differ significantly between men and women (P=.19).

Associations Between Metabolic Syndrome and CKD The prevalence of albuminuria and of an eGFR less than 60 mL/min per 1.73 m² was higher in study participants with than in those without metabolic syndrome (9.0% vs 4.8%; P<.001; 7.4% vs 4.0%; /*=.001). The overall prevalence of CKD was also higher in participants with than in those without metabolic syndrome (15.4% vs 8.3%; P<.001). Unadjusted associations between CKD and metabolic syn­drome (OR. 2.01; 95% CI, 1.54-2.63) were observed. After adjustments for age and sex, the OR (1.83; 95% CI, 1.39- 2.42) decreased. Further adjustments for other variables (regular physical activity, a high school education or be­yond, active smoking, myocardial infarction, and stroke) had little effect on the OR (1.74; 95% CI, 1.32- 2.30).

The association between each trait of the metabolic syndrome and CKD was also examined (Table 2). The prevalence of CKD was higher in participants who had a trait of the metabolic syndrome than in those who did not. After adjustments were made for age and sex, CKD was found to be associated with central obesity, elevated TG levels, elevated BP, and increased FBG levels (Table 3). However, after further adjustments were made for other metabolic syndrome traits, only elevated TG levels (OR, 1.45; 95% CI, 1.07-1.95), elevated BP (OR, 1.78; 95% CI, 1.29-2.44), and increased FBG levels (OR, 2.05; 95% CI, 1.55-2.72) were independently associated with CKD. We also analyzed the association between metabolic syndrome and CKD based on hypertension and diabetes status. In participants without hypertension and diabetes, CKD was more prevalent in those with than in those without meta­bolic syndrome (9.5% vs 4.6%; P=.O3). After adjustments were made for age and sex, a significant association be­tween metabolic syndrome and CKD was noted in partici­pants without hypertension and diabetes (OR, 2.03; 95% CI, 1.05-3.94; P<.001).

DISCUSSION

In our study of a Chinese population aged 40 years and older, metabolic syndrome, as newly defined by the IDF, was found to be associated with CKD. This association was independent of age, sex, and other possible risk factors for CKD.

Several cross-sectional studies have revealed an asso­ciation between microalbuminuria and the metabolic syn­drome, as defined by recent guidelines, or proxy measures of insulin resistance, in patients with and without diabe­tes.¹⁴ "^, Chen et al" extracted data from NHANES III, which contained detailed clinical information from more

TABLE 3. Odds Ratios (ORs) of Chronic Kidney Disease (CKD) by Individual Metabolic Syndrome Trait*