D.C. Week: HHS Seeks to End Discrimination for Transgender People

The ACP protests plans to deport undocumented immigrants

• by Shannon Firth
  Contributing Writer

WASHINGTON -- The nation's capital fell relatively quiet this week with Congress still on recess. But the Department of Health and Human Services (HHS) was busy. It proposed a new rule that would prevent insurers from discriminating against transgender beneficiaries as well as women, non-English speakers, and the disabled. The agency also announced long-awaited revisions to the Common Rule, a policy meant to safeguard human research subjects. The American College of Physicians (ACP) pushed back against Republican presidential candidates for promoting deportation of undocumented immigrants, and the Centers for Medicare & Medicaid Services (CMS) announced plans to test a value-based Medicare Advantage model.
HHS Issues Anti-Discrimination Rules for Transgender People
Health insurers can no longer exclude coverage for care related to gender transition under a proposed rule issued Thursday by HHS.
The proposed rule, entitled "Nondiscrimination in Health Programs and Activities," also includes requirements for communicating with disabled patients and beefs up language assistance requirements for those with limited English proficiency.
"This proposed rule is an important step to strengthen protections for people who have often been subject to discrimination in our health care system," Health and Human Services Secretary Sylvia Burwell said in a press release. "This is another example of this administration's commitment to giving every American access to the healthcare they deserve."
ACP Opposes 'Mass Deportation' Proposals on Health Grounds
The internal medicine society kicked another political hornets' nest Tuesday, urging physicians to make public statements opposing the deportation of all undocumented immigrants, which has been advocated by a number of Republican presidential candidates.
It's the latest salvo from an increasingly activist ACP leadership, which earlier this year waded into controversies over gun violence and gay marriage.
In a statement posted on the ACP website, the group "called on physicians, individually and collectively, to speak out against proposals to deport the 12 million U.S. residents who lack documentation of legal residency status."
'Common Rule' Revision Arrives
The department released a long-awaited proposed rule intended to strengthen protections for human research subjects on Thursday. Changes to the Common Rule -- a law governing human research at 17 federal agencies and offices -- were first initiated 4 years ago.
HHS said the goal of the proposed rule is to "enhance and streamline the review process, reduce inefficiencies, and hold unaffiliated IRBs [institutional review boards] directly accountable for regulatory compliance, without compromising ethical principles and protections."
Michael Carome, MD, director of Public Citizen's Health Research group, called the revisions a "mixed bag." A benefit of the rule is that it will expand federal oversight to any clinical trial performed at an institution if any branch of that institution receives federal funding for human research, irrespective of how individual trials are funded. A drawback of the rule, according to the advocacy group, is that it will grant oversight to only one institutional review board for collaborative trials occurring at multiples sites.
"[T]he proposed rule is premised on the dubious assumption that reducing the time and effort IRBs spend reviewing low-risk research will allow them to spend more time and effort reviewing higher risk research, but HHS offers no evidence to back this up," according to Carome.
Comments on the new rule may be submitted for 90 days beginning Sept. 8.
CMS to Launch new Medicare Advantage Model
A new program for Medicare Advantage beneficiaries aimed at reducing high-cost care and improving health outcomes was announced. The Medicare Advantage Value-Based Insurance Design Model, enables health plans to additional benefits or lower cost-sharing for beneficiaries with chronic conditions such as diabetes, chronic obstructive pulmonary disorder (COPD), congestive heart failure, and mood disorders.
"The Medicare Advantage Value-Based Insurance Design Model fills an immediate need for testing ways to improve care and reduce cost in Medicare Advantage Plans and offers the prospect of lower out-of-pocket costs and premiums along with better benefits for enrollees in Medicare Advantage," said Patrick Conway, MD, MSc, deputy administrator and chief medical officer for CMS.
The model will launch in January 2017 and continue for 5 years in 7 states: Arizona, Indiana, Iowa, Massachusetts, Oregon, Pennsylvania, and Tennessee.
Next Week
On Wednesday, Health Affairs will hold a briefing on non-communicable diseases.
Also on Wednesday the House will explore Planned Parenthood's abortion practices.
On Thursday and Friday, the Medicare Payment Advisory Committee will meet to discuss issues of policy, and two FDA advisory committees will review a pair of new oxycodone painkillers.
Also on Thursday, Research!America will host National Health Research Forum to examine issues related to medical innovation and public health.

Patients With Renal Disease: One of the Remaining Challenges in HCV Therapy

Nancy Reau, MD - 8/25/2015  More from this author

Patients and clinicians demanded highly effective, safe, all-oral therapy for HCV infection, and this challenge was met. As a consequence, the conversation with our patients has shifted from how to manage adverse events to how and when to deliver a cure. In response to the rapid evolution of therapy, the AASLD/IDSA provides real-time guidance to facilitate clinicians with treatment nuances. Although we now have highly effective therapies for nearly all patients, subsets of patients still exist where treatment options remain less than optimal.
For example, last week I evaluated a 57-year-old patient who was considering renal transplantation. Dialysis, although not yet required, appeared to be inevitable. During his kidney transplant evaluation, he was found to have HCV infection and was referred to my practice for pretransplant clearance. However, the ensuing discussion elucidated the lack of straightforward treatment options and complex goals for viral eradiation in this patient and others like him.
Hepatitis C and Renal Disease: A Complicated RelationshipInfections, including HCV, can cause renal disease, and HCV infection is seen frequently in patients with chronic kidney disease. It would stand to reason that we should treat HCV infection in all patients with HCV and chronic kidney disease: HCV can initiate cryoglobulinemia-related mesangiocapillary glomerulonephritis, and a growing body of evidence suggests that the interaction extends well beyond these traditional extrahepatic manifestations. Dialysis is a potential source for HCV transmission, and HCV has a negative impact on survival in individuals on chronic dialysis and in kidney graft recipients.
Traditionally, HCV treatment options for patients with renal disease were limited both by adverse events and efficacy. Peginterferon and ribavirin were poorly tolerated and rarely effective—requiring dose modifications and even treatment disruption. In addition, many patients with chronic kidney disease are anemic, creating an even greater challenge to the use of ribavirin. All-oral options have eliminated the treatment gap for many special populations, yet renal patients continue to present challenges.
Today’s DilemmaMost individuals with HCV infection in the United States are infected with genotype 1 HCV. We currently have 3 FDA-approved all-oral treatment options for this genotype (all of which may have ribavirin added in certain situations to either decrease the interval of therapy or to improve efficacy): sofosbuvir/ledipasvir, ombitasvir/paritaprevir/ritonavir plus dasabuvir, and simeprevir in combination with sofosbuvir.
Notably, while the combination of daclatasvir and sofosbuvir was recently approved by the FDA for the treatment of genotype 3 HCV infection only, this regimen has also been evaluated for the treatment of genotype 1 HCV infection and is recommended by the AASLD/IDSA guidance in this population as well.
Although all 4 regimens are equally advocated for genotype 1 patients in the HCV guidance, patients with renal impairment are highlighted as a unique patient population requiring dose modifications. For example, no sofosbuvir-containing regimen is approved for those with creatinine clearance < 30 mL/min because it is renally metabolized. In these patients, reduced creatinine clearance leads to an increased area under the curve of sofosbuvir and its inactive metabolite GS-331007. Despite this, the observational cohort study HCV-TARGET included a small number of patients with severe renal impairment who received sofosbuvir-containing regimens. High SVR rates were reported in this group, but the small numbers and observational nature make it difficult to interpret safety data, and the AASLD/IDSA guidance recommends that sofosbuvir can be considered in the subgroup of these patients who are ribavirin intolerant or ineligible, but only in consultation with an expert.
Although daclatasvir requires no dose adjustment with any degree of renal impairment, it is subject to the same restrictions as other sofosbuvir-containing regimens in patients with severe renal impairment.
For patients with creatinine clearance < 30 mL/min (without cirrhosis) who require therapy and are not candidates for renal transplant, the AASLD/IDSA guidance recommends ombitasvir/paritaprevir/ritonavir plus dasabuvir based on limited data, although care must be taken to avoid anemia if ribavirin is added, such as in patients with genotype 1a HCV infection. Preliminary data from RUBY-1 supports this as a safe and effective alternative even in those on hemodialysis, although this combination has not been investigated in patients with concomitant cirrhosis and severe renal disease.
We also recognize that there are other options under investigation. Results of the C-SURFER trial showed high efficacy and safety in genotype 1 HCV–infected individuals with end-stage renal disease who were treated with grazoprevir/elbasvir, including a subset with cirrhosis. 
Yet the story doesn’t stop there. Even if the therapeutic choices are straightforward, the timing of treatment remains controversial. Our patient was considering the option to receive an HCV-positive organ in order to decrease the wait time on the transplant list. With that goal, viral eradication should be deferred until after transplant to allow him a larger organ pool. In fact, the AASLD/IDSA guidance recommends treating HCV in patients with severe renal impairment only if treatment is urgent and renal transplant is not an option. However, this patient’s nephrologist was hoping that with viral eradication, his renal function might stabilize, thereby delaying—and possibly avoiding—the need for renal transplantation altogether.
Upcoming Discussions on Harder-to-Treat PopulationsDespite recent advances, managing HCV infection remains a challenge in selected populations such as those with renal disease. Next month, I and other colleagues, including Mark S. Sulkowski, MD, and Ira M. Jacobson, MD, will host a series of live case-based discussions on treatment decisions for challenging patients, including those with cirrhosis, genotype 3 HCV infection, reduced renal function, and HIV/HCV coinfection. I hope that you will join us for one of these exciting events, which you can prepare for by participating in my online CME-certified activity on these key patient populations.
We are interested in hearing what questions you might want addressed during upcoming meetings on harder-to-treat populations. Please leave a comment below.

Stroke Rounds: HbA1C Has Modest Impact on CVD Risk

Study is important step in assessing utility of abnormal blood glucose testing in ASCVD primary prevention

• by Salynn Boyles
  

  Contributing Writer

• This article is a collaboration between MedPage Today® and:
  

Action Points

• Note that this analysis of NHANES data suggests that adding hemoglobin A1C level to the atherosclerotic cardiovascular disease risk score may modestly improve CVD risk stratification.
• Be aware that the authors did not have data on patient outcomes. Rather, they were imputed based on rates seen in prior studies.

Adding hemoglobin A1C (HbA1c) to conventional cardiovascular risk assessment had only a modest effect on post-test, 10-year atherosclerotic cardiovascular disease (ASCVD) risk, researchers reported.
Using data from the 2010-2011 National Health and Nutrition Examination Surveys (NHANES), Mark J. Pletcher, MD, MPH, of the University of California San Francisco, and colleagues devised a risk regression model that allowed them to incorporate HbA1C into the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) 10-year ASCVD risk calculator.
They found that having an HbA1C of less than 5.7% (normal level) was found to reduce post ASCVD-test risk by 0.4% to 2.0% points, while having an HbA1C of 6.5% (the threshold for diabetes mellitus) or greater increased post-test risk by 1.0% to 2.5% points, they wrote in Circulation: Cardiovascular Quality and Outcomes.
"Hemoglobin A1C testing is inexpensive and has few direct adverse effects, so it is possible that even small changes in risk prediction may be valuable enough to warrant measurement," they stated.
But in an accompanying editorial, Khurram Nasir, MD, expressed doubt that adding HbA1C to conventional cardiovascular (CVD) risk assessment would meaningfully inform patient management or improve outcomes. Nasir is the director of the Center for Healthcare Advancement & Outcomes for the healthcare network Baptist Health South Florida in Miami.
He noted that among patients with a pretest ASCVD risk of 7.5%, which indicates elevated 10-year risk warranting statin treatment, a normal HbA1C would lower the estimated post-test 10-year risk by just over 1%.
"Whether this difference is meaningful and would affect the decision to avoid statins is debatable, as the risk still remains above threshold suggested by guidelines for considering moderate intensity statins," he wrote.
In another accompanying editorial, Harlan M. Krumholz, MD, of Yale University School of Medicine, pointed out that the Institute of Medicine "defines biomarkers as indicators of normal biological processes, pathogenic processes, or pharmacological responses to an intervention, but even as biomarkers can reflect the influence of an intervention, changes in their levels may not be indicative of changes in risk."
The 2013 AHA/ACC ASCVD model incorporates a clinical diagnosis of type 2 diabetes, but not specific glycemic level, in the risk calculator.
Although HbA1C is associated with increased risk of cardiovascular events, its use for prediction of CVD events in combination with conventional risk factors remains controversial, the researchers noted.
In an effort to better understand the impact of HBA1C on CVD risk prediction, the authors devised regression models that incorporated the diabetes biomarker into the ASCVD model. They identified 2,000 individuals, ages 40-79, from NHANES who did not have pre-existing diabetes or CVD.
The regression model was used to predict HbA1C distribution based on individual patient characteristics, and the researchers calculated post-test 10-year ASCVD risk by incorporating actual versus predicted HbA1C.
Age, sex, race/ethnicity, and traditional cardiovascular risk factors were significant predictors of HbA1C in the model, with the expected HbA1C distribution being significantly higher in non-Hispanic black, non-Hispanic Asian, and Hispanic individuals versus non-Hispanic whites and others.
"Our analysis is an intermediate step toward the larger goal of evaluating the clinical utility of HbA1C ," the researchers wrote, adding that adequately designed, cost-effectiveness studies will be needed to determine if HbA1C has clinical value in CVD risk assessment.
The cross-sectional nature of the NHANES data used in the analysis was cited by the researchers as a potential study limitation.
"Although the costs of HbA1C testing are low and potential consequences of testing seem benign, the net comparative effectiveness and efficiency (cost-effectiveness) of this approach for guiding HbA1C testing has not been proven," the researchers wrote. "Future randomized, controlled trials of an integrated screening and targeted prevention strategy or careful modeling of expected benefits, harms, and costs are necessary to fully assess the potential implications of this strategy."
In his editorial, Nasir suggested that the focus on biomarkers to improve CVD risk prediction may be misplaced.
"Given the plethora of biomarkers that have been associated with cardiovascular outcomes, why did the current risk prediction model still end up with 6 basic risk factors first established almost a half a century ago?," he asked, adding that none of the candidate biomarkers have been proven to have a meaningful impact on patient risk assessment.
"If we truly wish to accelerate our efforts in personalizing patient-centric risk prediction models, our persistent resolve with biomarkers in this pursuit is perplexing, especially when historically this approach has consistently not yielded high dividends in CVD risk reclassification," he wrote.
Nasir noted that directly identifying disease progression, such as using noncontrast CT to identify coronary artery calcium (CAC), may better inform clinicians about patient risk.
"Strikingly, within primary prevention settings, no other test offers better prognostication, discrimination and reclassification for CVD risk," he wrote. "Compared with limited performance with surrogate biomarkers, CAC testing provides net reclassification improvements in nearly two-thirds of individuals with intermediate risk level to significantly influence treatment decisions."

The study was funded by the NIH and the National Cancer Institute.
Pletcher and co-authors disclosed no relevant relationships with industry. One co-author disclosed serving as a member of the U.S. Preventive Services Task Force.
Nasir disclosed relevant relationships with Quest Diagnostic and Regeneron.
Krumholz disclosed support from the National Heart, Lung, and Blood Institute through his institution. He disclosed relevant relationships with Medtronic, Johnson & Johnson, and United Healthcare.

• Reviewed by F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine

last updated 09.08.2015

• Primary Source

  Circulation: Cardiovascular Quality and Outcomes

  Source Reference: Jarmul JA, et al "Interpreting hemoglobin A1C in combination with conventional risk factors for prediction of cardiovascular risk" Circ: Cardio Qual Outcomes 2015; DOI: 10.1161/CIRCOUTCOMES.115.001639.

• Secondary Source

  Circulation: Cardiovascular Quality and Outcomes

  Source Reference: Nasir K "Overhauling cardiovascular risk prediction in primary prevention difficult journey worth the destination" Circ: Cardio Qual Outcomes 2015; DOI: 10.1161/CIRCOUTCOMES.115.002207.

• Additional Source

  Circulation: Cardiovascular Quality and Outcomes

  Source Reference: Krumholz HM "Biomarkers, Risk Factors, and risk clarifying the controversy about surrogate end points and clinical outcomes" Circ: Cardio Qual Outcomes 2015; DOI: 10.1161/CIRCOUTCOMES.115.002245.

CardioBreak: Discount PCSK9 Drugs, Expanded Brilinta Use

Recent developments of interest in cardiovascular medicine

• 
• by Crystal Phend
  

  Senior Staff Writer, MedPage Today

Whereas evolocumab (Repatha) will cost $14,100 per year on the U.S. market, the annual price will be only $6,870 in the U.K. and $8,220 in Austria.
And the U.K. approved early access to LCZ-696 (Entresto) while awaiting the European Commission approval for heart failure, despite the $12.50 per pill ($25 per day) price-tag.
The FDA approved a new 60-mg dose of ticagrelor (Brilinta) for use with aspirin in an expanded indication for long-term use in acute coronary syndrome patients, and patients who have previously had a myocardial infarction (MI). Additional data released from the PEGASUS trial, upon which the indication was based, showed that stopping ticagrelor too soon can increase the risk of stroke or cardiovascular death.
An NBC News investigation suggests Bard downplayed the 300 non-fatal problems and 27 deaths related to its Recovery inferior vena cava filter, hiring a public relations firm instead of recalling the device. A regulatory specialist who refused to sign the FDA application over safety concerns indicated her signature might have been forged.
In other industry news, Abbott finished acquiring the mitral valve replacement company Tendyne and Medtronic bought Medina Medical, which makes a transcatheter embolization device for cerebral aneurysms.
The FDA extended the PDUFA response date for sebelipase alfa (Kanuma), an investigational enzyme replacement therapy for lysosomal acid lipase deficiency. The agency gave itself until Dec. 8 to review Alexion's response to its question on manufacturing. Meanwhile, the drug was approved by the European Commission to treat the "ultra-rare" metabolic disease.
Mitralign got clearance from the FDA to start phase I feasibility studies with its percutaneous tricuspid valve.
The factor VIIIa-mimetic bispecific antibody ACE-910 got breakthrough therapy status from the FDA for prophylactic treatment of hemophilia A.
Injections of abobotulinumtoxinA eased upper limb spasticity in stroke patients and those with traumatic brain injury in a pivotal phase III trial, with effects lasting up to 20 weeks.
Total knee replacement was associated with elevated 30-day risk of MI and risk of venous thromboembolism that persisted for years after the procedure, a large study showed.
Most cardiac resynchronization therapy (CRT) pacemaker patients don't need a defibrillator, the CeRtiTuDe cohort study showed.
European cardiomyopathy patients are getting more defibrillators than expected, and more genetic testing too, a registry found.
Heart age, reflecting cardiovascular risk profile, averages 7.8 and 5.4 years older than chronological age for men and women, respectively, the CDC reported from national data.
The FDA cleared a wireless digital stethoscope, Eko Core, for use as a Class II device, although cardiologists' auscultation skills with even a traditional stethoscope got a failing grade overall.
The agency warned Cardiac Designs that the plant making its ECG Check Wireless Lead Cardiac Monitor doesn't meet good manufacturing practice requirements, particularly in design validation and in handling complaints about the device.
The BioMonitor 2 device for remote monitoring of heart rhythms got clearance from European regulators. Device maker Biotronik released results of a pilot study showing 90% success in sending transmissions from the device.
CardioBreak is a guide to what's new and interesting on the Web for cardiologists and other healthcare professionals with an interest in cardiovascular disease, powered by the MedPage Today community. Got a tip? Send it to us: c.phend@medpagetoday.com.

CardioBrief: Genes and CAD -- It's Complicated

Large genetic study of coronary artery disease shows how much we don't know

• by Larry Husten
  

  CardioBrief

• This article is a collaboration between MedPage Today® and:
  

We still have a very long way to go before we understand the genetic underpinnings of coronary artery disease (CAD), according to the largest and most comprehensive study in the field performed to date.
In a series of tweets, Sekar Kathiresan, MD, director of preventive cardiology at Massachusetts General Hospital in Boston and co-leader of the study, summarized the meta-analysis of genome-wide association studies, which was published in Nature Genetics:
"Our latest analysis of coronary artery disease genetics is out. 58 DNA variants confer risk. Takeaways from latest CAD genetics study:

• Of 58 variants, <20% relate to known risk factors.
• Lots of common variants with weak effects, few low-frequency variants of larger effect.
• Biggest yield = biology @ 80% CAD loci not related to known risk factors -- difficult but nothing worth doing is easy.
• Which risk factors matter most for CAD? Unbiased genetic survey finds only LDL, Lp(a), TG, & SBP."

Responding to questions by email, Kathiresan said that "the holy grail for therapeutics is non-lipid mechanisms. We really need to understand the causal genes and mechanism at the 80% of CAD gene regions that are non-lipid. ... identifying non-lipid causal factors could open the door to a new series of treatments."
The study lends support to the view that further progress in understanding and treating CAD will depend less on lipid research and more on vessel wall biology.
In their paper, the researchers write "a number of preventative strategies target the vessel wall (control of blood pressure and smoking cessation), but the large majority of existing drug treatments for lowering CAD risk operate through manipulation of circulating lipid levels and few directly target vessel wall processes. Detailed investigation of new aspects of vessel wall biology that are implicated by genetic association but have not previously been explored in atherosclerosis may provide new insights into the complex etiology of disease and, hence, identify new targets."
From the American Heart Association:

• Basic Concepts and Potential Applications of Genetics and Genomics for Cardiovascular and Stroke Clinicians: A Scientific Statement From the American Heart Association
• Genetics and Genomics for the Prevention and Treatment of Cardiovascular Disease

last updated 09.08.2015

• Primary Source

  Nature Genetics

  Source Reference: Nickpay M, et al "A comprehensive 1000 Genomes–based genome-wide association meta-analysis of coronary artery disease" Nature Genet online, September 7, 2015; DOI: 10.1038/ng.3396.

Body Fat, Not BMI, Tied to Foot Pain

Study suggests adipose tissue is associated with the presence and development of foot pain

• by Pam Harrison
  

  Contributing Writer

Action Points

• Note that this large, observational study found that increase in body fat was associated with an increase in foot pain.
• Be aware that causality can not be inferred given this study design.

An increase in fat mass index (FMI), but not body mass index (BMI), was associated with both prevalent and future foot pain, a large community-based study showed.
Among a subset of participants, ages 50 and up, from the North West Adelaide Health Study (NWAHS), foot pain was present in 20.2% of the cohort between 2004 and 2006 (stage 2) while 36.4% of the same group had foot pain between 2008 and 2010 (stage 3) of the study. Following multivariable modeling, the odds of having foot pain at stage 2 increased by 8% for each FMI unit at an odds ratio (OR) of 1.08 (95% CI 1.04-1.12), reported Tom Walsh, MHlthSci, of Flinders University in Bedford Park, Australia and colleagues.
The odds of having foot pain at stage 3 of the study increased by 6% for each FMI unit at stage 2 (OR 1.06, 95% CI 1.02-1.11), they wrote in Arthritis Care & Research.
The results suggest that body fat may contribute more to foot pain than body weight, they said.
However, the authors noted that physical activity was protective of foot pain. Also, serum adipokines, tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) were not associated with foot pain at any stage of the study.
"To our knowledge, this is the largest investigation of the association of foot pain, fat mass and adipokines," Walsh's group wrote. "This study ... adds further to the concept of metabolically, rather than mechanically, derived foot pain."
The NWAHS is a representative cohort study of randomly selected adults from the north-west region of Adelaide.
The study was started in 1999 to 2003 and stage 2 was conducted from 2004-2006. Stage 3 was done from 2008-2010.
During all three stages, data were collected using a Computer Assisted Telephone Interview (CATI), a self-completed questionnaire, and a clinical assessment.
Data collected as part of Stage 2 were used to examined the factors associated with prevalent foot pain. These covariates from Stage 2 were then used to determine predictors of future foot pain in Stage 3, the authors explained.
Some 1,462 participants were the focus of the current analysis.
The mean BMI for the cohort was 28.37 kg/m² while the mean FMI was 10.18 kg/m².
"Both FMI and BMI were significantly different between those with and without foot pain," the investigators observed.
For example, the mean rank for those with prevalent foot pain was 913.56 based on FMI as a continuous variable versus 750.23 for those who reported no foot pain (P<0.001).
For BMI as a continuous variable, the mean rank for those with prevalent foot pain was 1,082.03 versus 930.36 among those who had reported no foot pain (P<0.001).
In stage 3, the mean rank for foot pain was 523.67 based on FMI as a continuous variable compared with 469.81 for those without future foot pain (P=0.008). Also, the mean rank for future foot pain based on BMI as a continuous variable was 602.58 versus 559.01 (P=0.046).
However, when fat mass was added to the multivariable model, BMI lost its significance.
After multivariable analysis, FMI, depression, poor general health, diabetes, osteoarthritis, arthritis of unknown type, and rheumatoid arthritis remained significantly associated with prevalent foot pain.
Only FMI (P<0.005), arthritis of unknown type (P<0.001) and depression (P<0.035) were significantly associated with future foot pain on multivariable analysis.
The authors did find that physical activity was found to be protective of foot pain (OR of 0.76, 95% CI 0.58-0.99, P=0.048).
Study limitations include the question investigators used to define foot pain, which could have excluded people with nondisabling foot pain and led to an underestimate of the prevalence of foot pain in the study sample.
The authors also did not examine the feet either clinically or radiographically so they could not report on foot structure or function.
Finally, socioeconomic status was not included in the model and that could mediate the effect of foot pain, the said.
And the authors were only able to report on a limited number of adipokines, TNF-α and IL-6, excluding other cytokines which may have been relevant to the findings.
"The clinical implications of our findings are that FMI but not BMI is associated with both prevalent and the development of foot pain after multivariable analysis in adults age ≥50 years," they stated. "Given the association of FMI with future foot pain, patients with increased fat are at risk of developing foot pain and should be counselled as such, particularly given increased fat mass is modifiable and should not be considered as a chronic condition."

The North West Adelaide Health Study was funded by the University of Adelaide, the South Australian Department of Health, and the Premier's Science and Research fund.
Walsh disclosed funding from a Nursing and Allied Health Scholarship and Support Scheme. One co-author disclosed funding from the National Health and Medical Research Council.
Walsh and co-authors disclosed no relevant relationships with industry.

• Reviewed by F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine

• Primary Source

  Arthritis Care and Research

  Source Reference: Walsh T, et al "The association of fat mass and adipokines with foot pain in a community cohort" Arthritis Care Res 2015; DOI: 10.1002/acr.22719.

An excellent way to circumcise

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