Glycation Product Linked to Hip Fracture Risk


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Published: Nov 1, 2013

By Cole Petrochko, Staff Writer, MedPage Today
Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania

Action Points

  • A characteristic of biological aging is the non-enzymatic glycation of long-lasting proteins, such as collagen, which weakens collagen’s biomechanical properties and leads to increased bone matrix stiffening and fragility.
  • This study shows that increasing levels of carboxy-methyl-lysine, an advanced glycation end product, are associated with hip fracture risk in older adults, independent of hip bone mineral density.

Patients with the highest level of serum carboxy-methyl-lysine were at the greatest risk for hip fracture, researchers found.

A higher quartile of carboxy-methyl-lysine in blood was significantly associated with increased risk of hip fracture, at 27% for each increase in quartile (95% CI 1.16-1.40, P<0.001), according to Joshua Barzilay, MD, of Kaiser Permanente of Georgia in Duluth, and colleagues.

This association remained significant after adjustment for age, sex, race, body mass index, smoking, alcohol consumption, prevalence coronary heart disease, energy expenditure, and estimated glomerular filtration rate (HR 1.17, 95% CI 1.05-1.31, P=0.006), they wrote in the Journal of Bone and Mineral Research.

Past research has shown vitamin D levels are predictive of hip fracture in older patients, and that aggressive osteoporosis care can lower rates of hip fracture. Additionally, bone strength has been associated with insulin resistance.

Carboxy-methyl-lysine is an advanced glycation end product, which can occur in the body in diabetes and with age. These end products can accumulate in bones and “leads to increased bone matrix stiffening and fragility,” they wrote.

They added that little past research has looked at bone fracture risk with presence of advanced glycation end products.

The authors analyzed serum carboxy-methyl-lysine levels in a cohort of 3,373 older patients enrolled in the Cardiovascular Health Study for associations with hip fracture risks.

All participants were Medicare-eligible U.S. citizens who received a baseline evaluation and annual follow-up from 1998 to 1999 and from 2005 to 2006. Researchers contacted participants by phone each year between the exam periods, and twice a year from 2000 to 2004 and again in 2007.

Participants’ renal function was measured through cystatin C levels, as was an estimation of glomerular filtration rate. They reported smoking history, medication use, history of falls in the year prior, kcal expenditure per week, and alcohol use through questionnaire and in-person interview.

In addition, measures of bone mineral density, weight, blood pressure, body mass index, grip strength, and time needed to walk 15 feet — in seconds — were recorded. Bone mineral density was recorded 1 to 2 years before the study.

Frailty was defined as having three or more of the following:

  • Unintended weight loss of more than 10 pounds in the year prior
  • Self-reported exhaustion “most of the time”
  • Physical activity in the lowest 20% of the cohort (less than 383 kcal/week in men and less than 270 kcal/week in women)
  • Grip strength in the lowest 20% of the cohort (less than 23 kg/m2 in men and less than 17 kg/m2 in women)
  • Pace of walking in the lowest 20% of the cohort

Those with only one or two criteria were considered “pre-frail,” which meant the patient was at risk for frailty.

Hip fracture was recorded through patient report and confirmed through hospital records.

Carboxy-methyl-lysine was measured through assay blood analysis. Levels were divided into quartiles.

Median measure of carboxy-methyl-lysine was 584 ng/mL. Median follow-up was 9.22 years. There were 348 hip fractures over the follow-up period.

Participants with the lowest carboxy-methyl-lysine levels had the greatest survival free of hip fracture rates, with similar rates of fracture among the middle quartiles, and the highest rates of fracture among those in the highest quartile (log-rank P<0.001).

There was no significant differences between sexes or patients with or without diabetes for risks of hip fracture. There was also no significant association between carboxy-methyl-lysine levels and bone mineral density.

The authors said their study was limited by the limited characterization of bone health, such as absence of markers for bone turnover and resorption. Bone mineral density and carboxy-methyl-lysine were also only measured at a single point, and hemoglobin A1c and pentosidine were not measured.

The authors declared no conflicts of interest.

Primary source: Journal of Bone and Mineral Research
Source reference: Barzilay J, et al “Circulating levels of carboxy-methyl-lysine are associated with hip fracture risk: the cardiovascular health study” J Bone Miner Res 2013; DOI: 10.1002/jbmr.2123.

Cole Petrochko started his journalism career at MedPage Today in 2009, after graduating from New York University with B.A.s in Journalism and Psychology. When not writing for MedPage Today, he blogs about nerd culture, designs websites, and buys and sells collectible card game cards. He is based out of MedPage Today‘s Little Falls, N.J. Headquarters.

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TCT: New Methods ID Significant Coronary Lesions


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Meeting Coverage

Published: Oct 31, 2013

By Todd Neale, Senior Staff Writer, MedPage Today
Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania

Action Points

  • Note that these studies were published as abstracts and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
  • In one study, non-invasive fractional flow reserve (FFR) derived from coronary CT angiography demonstrated high diagnostic accuracy for detection of ischemia in suspected coronary artery disease.
  • In another study, a combination of a technique called instantaneous wave-free ratio and invasive FFR correctly classified the hemodynamic significance of the vast majority of lesions, and would have prevented the use of adenosine in two-thirds.

SAN FRANCISCO — Newer methods may help in the assessment of which coronary lesions are hemodynamically significant enough to justify a revascularization procedure, two studies showed.

In the first, a non-invasive, CT-derived measure of fractional flow reserve (FFR) had good diagnostic performance compared with the gold-standard invasive FFR, indicated by an area under the receiver operating characteristics curve (AUC) of 0.82 in a per-patient analysis, according to Bjarne Norgaard, MD, PhD, of Aarhus University Hospital in Denmark.

Using invasive FFR as the reference, CT-derived FFR had significantly better specificity (79%) — at a P-value of less than 0.0001 — than assessments of stenosis with either invasive coronary angiography (64%) or coronary CT angiography (53%).

And in a second study reported by Javier Escaned, MD, PhD, of the Hospital Clinico San Carlos in Madrid, a combination of a technique called instantaneous wave-free ratio (iFR) — which measures intracoronary resistance at rest — and invasive FFR correctly classified the hemodynamic significance of 94.2% of lesions and would have prevented the use of adenosine in 65.1% of patients.

Both studies were presented at the Transcatheter Cardiovascular Therapeutics meeting here.

Referring to the second study, James Hermiller, MD, of St. Vincent Heart Center of Indiana, said, “I think for someone in the cath lab it’s great. It’s less time, it’s less money because you don’t have to give adenosine, and it’s easy. So that’s a good equation.”

Non-invasive, CT-Derived FFR

Current non-invasive methods for determining which patients should or should not be sent to the cath lab are not very accurate at identifying which patients actually require catheterization.

In the HeartFlowNXT trial, Norgaard and colleagues evaluated a non-invasive, CT-derived method of determining FFR — which has been shown to predict which lesions are hemodynamically significant enough to require revascularization with either CABG or percutaneous coronary intervention, usually at a cutoff of 0.80 or less — that doesn’t require any additional imaging or medication administration beyond standard CT exams.

The trial included 254 patients (mean age 64) who were undergoing non-emergent, clinically indicated invasive angiography for suspected coronary artery disease at 10 sites in Europe, Asia, and Australia. About a third (32%) had a lesion with an FFR of 0.80 or less.

Using an invasive FFR cutoff of 0.80 or less as the reference, CT-derived FFR had better discrimination for identifying hemodynamically significant lesions compared with coronary CT angiography in both a per-vessel analysis (AUC 0.93 versus 0.79) and a per-patient analysis (0.82 versus 0.63) — P-value less than 0.001 for both.

CT-derived FFR had 81% accuracy, 79% specificity, 86% sensitivity, 65% positive predictive value, and 92% negative predictive value in terms of per-patient diagnostic performance, with similar results for the per-vessel analysis.

Although the CT-derived measure performed well compared with invasive FFR, cost-effectiveness still needs to be studied in future trials, Norgaard said.

“We know that our stress testing that we do to try and figure out if somebody with chest pain or symptoms has a significant lesion [has] poor specificity, poor sensitivity. We cath a lot of patients that don’t have any disease and we often don’t cath patients that we should,” Hermiller commented.

“And I think what we heard today was CT-derived FFR gives us much more fidelity compared to just doing a [CT angiography] and anatomy,” he said, noting that specificity is improved without losing sensitivity.

Instantaneous Wave-Free Ratio

In the ADVISE II trial, Escaned and colleagues evaluated the utility of iFR, which does not require the use of drugs like adenosine to measure the pressure within an artery. The prospective, nonrandomized trial was conducted at 40 centers in the U.S., Europe, and Asia and included 797 patients (mean age 64).

With iFR, values of 0.94 or greater indicated a high likelihood that a lesion would be deemed insignificant by FFR with adenosine, and values of 0.85 or less indicated a high likelihood that a lesion would be deemed significant and in need of intervention by FFR with adenosine.

Using those thresholds, iFR correctly classified 91.6% of stenoses, using a standard FFR value of 0.80 or less as the reference.

A hybrid approach that used iFR for values of 0.94 or greater and 0.85 or less and standard FFR for values in between correctly classified 94.2% of stenoses. Only 31% of stenoses had an iFR that indicated a need for FFR with adenosine.

Hermiller noted that CT-derived FFR and iFR are not competitive approaches; CT-derived FFR can be used for non-invasive outpatient evaluation and iFR can be used when a patient is brought into the cath lab to help decide on the need for intervention.

The HeartFlowNXT trial was funded by HeartFlow. None of the study authors had a financial interest related to the company.

ADVISE II was sponsored by Volcano Corporation. Escaned reported relationships with Boston Scientific, St. Jude Medical, and Volcano Corporation.

Primary source: Transcatheter Cardiovascular Therapeutics
Source reference: Norgaard B, et al “HeartFlowNXT: a prospective registry evaluation of non-invasive FFRCT versus invasive FFR” TCT 2013.

Additional source: Transcatheter Cardiovascular Therapeutics
Source reference:Escaned J, et al “ADVISE II: a prospective registry evaluation of iFR versus FFR” TCT 2013.

Todd Neale, MedPage Today Staff Writer, got his start in journalism at Audubon Magazine and made a stop in directory publishing before landing at MedPage Today. He received a B.S. in biology from the University of Massachusetts Amherst and an M.A. in journalism from the Science, Health, and Environmental Reporting program at New York University.

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Diabetes screenings, supplies, and training – Medicare has you covered

Diabetes affects millions of people – are you one of them? November is American Diabetes Month and a perfect time to find out about the supplies and self-management training that Medicare covers to help you manage your diabetes. Many people with diabetes don’t know that they have it – and Medicare covers screening tests so you can find out if you do.

If you’re at high risk for developing diabetes, Medicare covers up to two fasting blood glucose (blood sugar) tests each year. If your doctor accepts assignment, you pay nothing for these tests. You may be at high risk for diabetes if you’re obese, have high blood pressure, high cholesterol, or a family history of diabetes. Talk to your doctor to find out when you should get your free screening test.

If you have diabetes, Medicare covers many of your supplies, including test strips, monitors, and control solutions. In some cases, Medicare also covers therapeutic shoes if you have diabetic foot problems. You pay 20% of the Medicare-approved amount for these supplies.

Medicare also covers diabetes self-management training to help you learn how to better manage your diabetes. You can learn how to monitor your blood sugar, control your diet, exercise, and manage your prescriptions. Talk to your doctor about how this training can help you stay healthy and avoid serious complications.

Take control of your health – talk to your doctor today about screening tests and what supplies and training you may need for your health.

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