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Beware of metabolic syndrome: Predisposition to periprosthetic joint infection
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Metabolic syndrome is a compilation of diseases related to insulin resistance. Typical definitions of metabolic syndrome (MetS) include the presence of increased waist circumference, hypertension, diabetes and dyslipidemia.
Metabolic syndrome has become prevalent in the United States with greater than 40% of adults older than 60 years of age with the disease. It is likely that the incidence of MetS in the joint replacement population is greater as it is a risk factor for development of osteoarthritis.
Multiple health organizations, including the World Health Organization, American Heart Association, and International Diabetes Foundation, provide independent definitions of MetS. The presence of these multiple definitions is similar to the recent state of periprosthetic joint infection (PJI) definition in the orthopedic community. These conflicting definitions lead to confusion in clinical practice and limits any direct comparison of studies using alternative definitions, muddling the literature with observations of dissimilar groups with the “same” disease. Unfortunately, this is not the end of the relationship between MetS and PJI.
Main components
Some of the main components of MetS – diabetes, dyslipidemia and obesity – have been investigated thoroughly for their association with immunosuppression, specifically development of PJI. Pulido and colleagues and Peersman and colleagues found that obesity was an independent predictor of PJI. This finding was supported by Dowsey and colleagues, who found that infection rates in obese and morbidly obese patients were 2.6% and 9.1%, respectively, compared to 1% in the non-obese population.
Javad Parvizi
Benjamin Zmistowski
Pulido and colleagues also found an association between hypercholesteremia and PJI, which was not maintained in multivariate analysis. In their analysis for risk factors of PJI, Peersman and colleagues also reported diabetes as a significant predictor of PJI development. This is not unexpected, as diabetes has long been associated with severe infection. Furthermore, an innovative analysis by Marchant and colleagues investigated the discrepancy in postoperative complication rates following joint replacement between controlled and uncontrolled diabetics.
With relation to infection, they found patients with uncontrolled diabetes had a risk of infection two-fold greater than patients without diabetes. Interestingly, patients in whom diabetes was controlled were at no greater risk of infection than those patients without diabetes. Also, patients with uncontrolled type 2 diabetes (as insulin resistance is at the heart of MetS) were found to be more likely to develop an infection than patients with uncontrolled type 1 diabetes.
Increased risk
There is no shortage of evidence that the components of MetS raise the risk of PJI. However, the direct relationship between MetS and PJI is less studied. In many analyses, it was found that the risk of postoperative complications presented by MetS was greater than the sum of risks from each component, suggesting a synergistic effect of their concomitant presentation. It is unknown if this synergistic effect exists for risk of infection as well, however it is hypothesized.
This hypothesis is supported by the following potential mechanisms for predisposition to PJI. Metabolic syndrome is most well known for its associated cardiovascular effects. Gandhi and colleagues demonstrated an increased risk of cardiovascular complications (pulmonary embolism, atrial fibrillation and cardiac arrest, among others) following total joint arthroplasty. In a separate study, Gandhi and colleagues also reported a significant risk for deep vein thrombosis following total knee arthroplasty in MetS patients. These results are indicative of the prothrombotic state characteristic of MetS. Of concern is the relationship Pulido and colleagues noted (although not surviving rigorous multivariate analysis) between history of venous thromboembolism and PJI. This provides the first direct link between MetS and PJI.
Pickup and colleagues showed that patients with MetS possess increased systemic levels of acute phase response cytokines and cortisol. These elevations compared to patients without MetS are suggestive of a misregulated immune response unable to form an effective attack against an invading pathogen. While yet unproven, this has the potential to predispose patients to infection.
Due to these recent findings, a study was undertaken by these authors to investigate the effects of uncontrolled vs. controlled MetS on postoperative complications following joint arthroplasty. In this yet-to-be published research, patients with all four components of MetS were identified (136 patients) and placed into controlled (101 patients) and uncontrolled (35 patients) cohorts. Controlled MetS was defined as sustained control of diabetes, hypertension and lipid levels. It was found that nearly half (48.5%) of those patients presenting with uncontrolled MetS developed a postoperative complication.
Pertaining to this current discussion, five patients (14.3%) in the uncontrolled group developed PJI compared to zero patients in the controlled group. These five patients were deemed uncontrolled due to elevated blood pressure in four patients and increased glucose level in one. To further assess the effect of MetS on postoperative complications, a “healthy” control group was formed from the remaining joint replacement population by matching for standard demographic criteria. The rate of postoperative complications between the “healthy” group and controlled MetS were similar. Furthermore, the rate of PJI in the “healthy” group was 0.8% ( one patient). These results reiterate the findings of Marcant and colleagues. The effect of uncontrolled disease is profound. In this setting, it appears that appropriately controlled disease places the patient at no greater risk than the general population.
Risk factor for PJI
While this study is the first of its kind and has yet to undergo peer review, it provides evidence that MetS is a risk factor for PJI. More importantly, this research specifies that control of MetS is essential in preventing PJI and other postoperative complications. It is essential to understand the current status of treatment for PJI.
Even when using the most aggressive surgery, two-stage prosthetic exchange with a temporary antibiotic-loaded cement spacer, success is achieved in 70% to 90% of cases. Furthermore, with successful outcomes, treatment is prolonged and difficult for the patient. In failure, the patient may require repeat surgery, with minimized joint function and reduced quality of life. It must be noted that these findings make no distinction between causation and association for MetS and PJI. Regardless, with the current knowledge it would be difficult to suggest that the risk of PJI in the uncontrolled MetS cohort is outweighed by the benefit of joint replacement.
References:
- Dowsey MM, Choong PFM. Obesity is a major risk factor for prosthetic infection after primary hip arthroplasty. Clin Orthop Relat Res. 2008;466(1):153-158.
- Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: Findings from the third National Health and Nutrition Examination Survey. JAMA. 2002;287(3):356-359.
- Gandhi R, Razak F, Tso P, Davey JR, Mahomed NN. Metabolic syndrome and the incidence of symptomatic deep vein thrombosis following total knee arthroplasty. J Rheumatol. 2009;36(10):2298-2301.
- Gandhi K, Viscusi ER, Schwenk ES, Pulido L, et al. Quantifying cardiovascular risks in patients with metabolic syndrome undergoing total joint arthroplasty. J Arthroplasty. 2012;27(4):514-519.
- Marchant MH, Viens NA, Cook C, Vail TP, et al. The impact of glycemic control and diabetes mellitus on perioperative outcomes after total joint arthroplasty. J Bone Joint Surg Am. 2009;91(7):1621-1629. doi:10.2106/JBJS.H.00116.
- Pulido L, Ghanem E, Joshi A, Purtill JJ, et al. Periprosthetic joint infection: The incidence, timing, and predisposing factors. Clin Orthop Relat Res. 2008;466(7):1710-1715. doi:10.1007/s11999-008-0209-4.
- Peersman G, Laskin R, Davis J, Peterson M. Infection in total knee replacement: a retrospective review of 6489 total knee replacements. Clin Orthop Relat Res. 2001; (392):15-23.
- Pickup JC, Mattock MB, Chusney GD, Burt D. NIDDM as a disease of the innate immune system: Association of acute-phase reactants and interleukin-6 with metabolic syndrome X. Diabetologia. 1997;40(11):1286-1292.
- Gandhi R, Razak F, Tso P, Davey JR, et al. Metabolic syndrome and the incidence of symptomatic deep vein thrombosis following total knee arthroplasty. J Rheumatol. 2009;36(10):2298-2301.
- Gandhi K, Viscusi ER, Schwenk ES, Pulido L, et al. Quantifying cardiovascular risks in patients with metabolic syndrome undergoing total joint arthroplasty. J Arthroplasty. 2012;27(4):514-519.
For more information:
- Javad Parvizi, MD, FRCS, editor of Infection Watch, can be reached at the Rothman Institute, 925 Chestnut St., 5th Floor, Philadelphia, PA 19107; email: parvj@aol.com.
Disclosures:
- Parvizi is a consultant to Zimmer, Smith & Nephew, 3M and Convatec; Schwarz is a paid consultant of MedImmune Inc. and his lab has osteomyelitis research funding from the National Institutes of Health, the AOTrauma Foundation and Codevax LLC. Zmistowski has no relevant financial disclosures.