The Journal of Arthroplasty Vol. 25 No. 3 2010

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city and thePrevalence of Metabolic Syndrome in the

Osteoarthritic Total Knee Arthroplasty Population

Rajiv Gandhi, MD, SM, FRCSC,* Fahad Razak, MSc,*y Peggy Tso, BHSc,*J. Roderick Davey, MD, FRCSC,* and Nizar N. Mahomed, MD, ScD, FRCSC*

Abstract: Metabolic syndrome (MS) is a known risk factor for the development of osteoarthritis(OA). We asked whether the prevalence of MS varies across ethnicity among patients who undergototal knee arthroplasty for end-stage OA. In our population of 1460 patients undergoing primaryknee arthroplasty, MS was defined as body mass index greater than 30 kg/m2, diabetes,hypertension, and hypercholesterolemia. Among the 1334 white patients, 114 (8.5%) had MS ascompared with 3 of 36 (8.3%) blacks and 18 of 90 (20%) Asians (P = .006) Adjusted analysis showedthat those of Asian ethnicity had a 2.0 (95% confidence interval, 1.1-3.8; P = .03) times greater oddsof MS as compared with those of other ethnicity. Metabolic syndrome is a risk factor for OA, andAsians demonstrate a greater prevalence of MS as compared with whites and blacks in thispopulation. Keywords: metabolic syndrome, ethnicity, knee osteoarthritis, Asians.© 2010 Elsevier Inc. All rights reserved.

The metabolic syndrome (MS) is defined by the findings ofcentral adiposity, elevated fasting glucose, hypertension,and dyslipidemia defined by high serum triglycerides andlow high-density lipoprotein (HDL) cholesterol [1,2].Patients with at least 3 of these 5 criteria have a 1.5 to2 times increased risk of cardiovascular disease [2].Moreover, MS is associated with a systemic proinflam-matory and prothrombotic state [1,3-5].Many authors have documented the impact of these

shared risk factors of obesity, cardiovascular disease,hypertension, and dysglycemia on the risk of osteoar-thritis (OA) [6-8]. Adipose tissue is now regarded as anactive endocrine organ that produces tumor necrosisfactor α, interleukin-6, and C-reactive protein, whichtogether induce a systemic proinflammatory state andmediate insulin resistance [9-11]. Insulin resistancefurther induces a chronic inflammatory state throughincreased lipolysis and elevated systemic levels of freefatty acids. Moreover, visceral adipocytes release thepeptide hormone leptin that also promotes systemicinflammation [12-15]. This overall elevated inflamma-tory state has been linked to chondrocyte death and

the *Division of Orthopedic Surgery, Toronto Western Hospital,y of Toronto, Toronto, Ontario, Canada; and yPopulation HealthInstitute, McMaster University, Hamilton, Ontario, Canada.itted July 7, 2008; accepted February 4, 2009.nefits or funds were received in support of the study.t requests: Rajiv Gandhi, MD, SM, FRCSC, Toronto WesternEast Wing 1-439, 399 Bathurst St, Toronto, ON, CanadaM5T 2S8.0 Elsevier Inc. All rights reserved.5403/09/2503-0014$36.00/0.1016/j.arth.2009.02.005

416

matrix degeneration [16,17]. Moreover, a recent hypoth-esis has been put forward suggesting a link betweenobesity-induced atherosclerosis and OA [8]. Microvascu-lar disease, particularly in the subchondral bone, maylead to cartilage degeneration through poor cartilagenutrition and a direct ischemic insult.In the medical literature, Asians have been shown to be

at a greater risk for MS as compared with any other ethnicgroups [18-20]. The prevalence of MS in Asians rangesbetween 15% and 50% depending on the populationstudied [18-20]. However, it has been suggested that,because Asians develop MS at a lower body mass index(BMI) and waist circumference than others, the pre-valence may be underestimated by as much as 25%[19,21]. In large population-based studies of whitepatients in the United States, the prevalence of MS rangesbetween 10% and 22% [22,23]. The possibility of anethnic difference in the prevalence of MS has not beenexplored in an OA population.We asked whether the prevalence of MS varies

across ethnicity among patients who undergo totalknee arthroplasty (TKA) for end-stage OA. Wehypothesized a priori that the prevalence would begreatest in Asian patients.

Patients and MethodsPatients were recruited to participate in a total joint

arthroplasty registry from a single Canadian academicinstitution, the Toronto Western Hospital, while on awaiting list for primary knee arthroplasty. All patientsgave informed consent to participate in the registry. Ourinclusion criteria for this retrospective study were being at

Table 1. Unadjusted Analysis Comparing Demographic andBaseline Functional Outcome Scores Between Patients Withand Without MS

MS (n = 135) Without MS (n = 1325) P Value

Mean age (SD) 66.1 (9.2) 66.6 (9.9) .85% Male 33.0 36.5 .57Mean BMI,

kg/m2 (SD)32.8 (2.1) 30.4 (6.8) .02

Preop WOMAC scoresWOMAC total(SD)

55.8 (15.2) 53.4 (17.9) .16

WOMAC pain(SD)

15.3 (15.4) 10.5 (3.8) .63

Ethnicity and Metabolic Syndrome � Gandhi et al 417

least 18 years old and having a diagnosis of primary OA.The study protocol was approved by the Human SubjectReview Committee.All surgeries were performed by 1 of 3 fellowship-

trained arthroplasty surgeons between the years of 1998and 2006. All patients were included only once in theanalysis even if they underwent contralateral surgery at alater date. All data were collected by an independentassessor not involved in the medical care of the patients.

Collection of DataBaseline demographic data of age, sex, BMI, and

medical comorbidity were collected by patient self-report.Education was recorded as either high education level(university or above) or low education level (high schoolor below).Ethnicity was recorded by patient self-report under the

categories of white, black, European, Asian, or Aborigi-nal. Patients could choose as many as were appropriate.We had no patients under the category of Aboriginal.Those patients selecting white or European were col-lapsed into a white category. Asian refers to individualswho classified themselves as South Asian (India, Pakistan,Bangladesh, and Sri Lanka) or East Asian (China, Japan,Taiwan, Korea).

Metabolic SyndromeThere is a lack of complete consensus on the definition

of MS, as many debate the significance of insulinresistance. The World Health Organization (WHO) [24]defines MS as follows:Insulin resistance (type 2 diabetes, impaired fasting

glucose, impaired glucose tolerance)Plus any 2 of the following:

Elevated blood pressurePlasma triglyceride of at least 150 mg/dLHDL not exceeding 35 mg/dL (men) or not exceeding40 mg/dL (women)BMI of at least 30 and/or waist/hip circumference of atleast 0.9 (men) or at least 0.85 (women)Urinary albumin of at least 20 mg/min; albumin/creatinine of at least 30 mg/g

The American Heart Association (AHA) defines MSas patients having 3 or more of the following riskfactors [25]:

Increased waist circumference: men, at least 102 cm;women, at least 88 cmElevated triglycerides of at least 150 mg/dLReduced HDL cholesterol: men, less than 40 mg/dL;women, less than 50 mg/dLElevated blood pressure of at least 130/85 mm HgElevated fasting glucose of at least 100 mg/dL

Laboratory values of cholesterol, fasting glucose, bloodpressure, or waist circumference were not routinelycollected as part of our registry. We classified MS in our

study based on a BMI of at least 30 kg/m2 and patient self-report of the diagnosis of diabetes, hypertension, andhypercholesterolemia.Functional status and pain level were assessed

preoperatively with the Western Ontario McMasterUniversity Osteoarthritis Index (WOMAC) functionand pain scores, respectively [26]. A greater score onthe WOMAC scale represents poorer function orgreater pain.

Statistical AnalysisContinuous data such as age, BMI, and WOMAC scores

were compared between groups using t tests. Means andstandard deviations are reported for all continuousvariables. Categorical data such as sex, education, andethnicity are reported with frequencies; and groups werecompared with the Fisher exact test.Multivariable logistic regression modeling was per-

formed to determine the impact of ethnicity on theprevalence of MS. For this model, we collapsed theethnicity variable into a binary term of Asian vs non-Asian. The variables entered into the model were age,sex, education, and ethnicity.All statistical analyses were performed with SPSS

version 13.0 (Chicago, IL). Odds ratios (ORs) forregression modeling and their 95% confidence intervals(CIs) are reported. All reported P values are 2-tailed withan α of .05.

ResultsIn our registry, we had complete demographic and

comorbidity data on 1460 of 1625 (89.8%) patients whocomprised our study cohort. Responders were notsignificantly different from nonresponders in age, BMI,sex, or comorbidity. The overall prevalence of MS in ourcohort was 135 of 1460 (9.2%).At the time of surgery, there were no differences

between those patients with and without MS in age,sex, or baseline functional status (P N .05). The patientswith MS had a significantly greater BMI at 32.8 kg/m2

as compared with 30.4 kg/m2 in those without MS.(Table 1).Among the 1334 white patients, 114 (8.5%) had MS as

compared with 3 of 36 (8.3%) blacks and 18 of 90 (20%)

Table 3. Logistic RegressionModel Predicting Prevalence of MSby Age, Sex, Education, and Asian Ethnicity

OR (95% CI) P Value

Age 1.0 (0.99) .81Sex 1.1 (0.7) .69Education 1.2 (0.8) .38Asian Ethnicity 2.0 (1.1) .03

418 The Journal of Arthroplasty Vol. 25 No. 3 April 2010

Asians (Table 2, P = .006). Asian ethnicity was asignificant predictor for MS, independent of age, sex,and education (adjusted OR = 2.0; 95% CI, 1.1-3.8; P =.03; Table 3). The model demonstrated significantpredictive value by the likelihood ratio test (P b .001).

DiscussionOur study shows that, in this population with end-

stage OA undergoing elective primary TKA, MS, asdefined by self-reported BMI of at least 30, hyperten-sion, hypercholesterolemia, and diabetes, was moreprevalent among those of Asian ancestry than amongnon-Asians. The prevalence of MS in our Asian patientswas 20%. This is consistent with what others havereported in the general population, with the prevalencevarying between 15% and 50% for Asians dependingon the definitions used [18-20]. The criteria we used toclassify MS almost certainly overestimate the prevalenceof MS as defined by the WHO and/or the AHA becausewe did not confirm elevation of triglyceride levels or adecreased serum HDL and also because not all obesepatients by BMI criteria would necessarily have met thecut point for central obesity. On the other hand, all ofthese various criteria (WHO, AHA, and our criteria)may differentially underrepresent the true prevalence ofMS among Asians, as some authors have suggested thatAsians develop metabolic abnormalities at a lower BMIand waist circumference than other ethnic groups[19,21]. Our overall prevalence of MS was 9.2%. Theprevalence of the condition is known to increase withage, ranging from 5% in those aged 20 to 29 years toup to 30% in those aged 60 to 69 years [27]. Theprevalence numbers we report are on the low end ofthe presented ranges and could be explained by the factthat we are studying a selected population consideredmedically fit for elective surgery.The MS has been linked to elevated rates of cardiovas-

cular disease [2,19] and ischemic strokes [2]. Theconstellation of risk factors that make up the MS hasalso been demonstrated to have independent relation-ships to degenerative joint disease [6-8,28]. This effect islikely mediated through both mechanical and biochem-ical implications of the truncal obesity. The biochemicallink involves an elevated level of systemic inflammationand atherosclerotic, microvascular disease that negativelyimpacts on the subchondral blood supply of the joint andsubsequent cartilage nutrition [8-15,28]. Moreover,patients with MS have been shown to be in a chronicallyelevated prothrombotic state [3-5]. Parvizi et al [29]showed that patients with MS were at a 1.5 times greater

Table 2. Unadjusted Analysis Comparing Prevalence of MSAmong the Various Ethnicities

White(n = 1334)

Blacks(n = 36)

Asians(n = 90) P Value

Prevalence of MS 114 (8.5%) 3 (8.3%) 18 (20%) .006

risk for pulmonary embolism after hip and kneearthroplasty. In the general medical literature, patientswithMS have been shown to be at a 2 times increased riskof venous thromboembolism compared with those with-out MS [30-32].A potential limitation of our study is that our classifica-

tion did not distinguish between Asians of South Asian orEast Asian descent. However, both ethnic groups havebeen shown to have similar systemic metabolic effects oftruncal obesity [33-35]; and therefore, we feel ourconclusions remain valid. Second, we studied a NorthAmerican population who had surgery in Toronto; andthe risks of obesity, hyperlipidemia, diabetes, andhypertension have potential geographic and environ-mental associations. As such, the results may only begeneralizable to a similar population. Third, we did notask patients their country of birth; and such future workshould be directed toward understanding generationaleffects of ethnicity on MS.In conclusion, Asians demonstrate a greater pre-

valence of MS than whites or blacks in a knee OApopulation undergoing TKA. Recognizing MS as a riskfactor for OA, future work should involve evaluatingif MS is a modifiable risk factor for incident OA inthese patients.

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