Lipid Disorders

The investigational, novel, injected once-weekly “twincretin” tirzepatide met its primary efficacy endpoint of significantly cutting hemoglobin A1c as well as its secondary weight-loss endpoint in patients with type 2 diabetes when compared with control patients in top-line results from each of five discrete pivotal trials.

Courtesy Joslin Diabetes Center

The company developing tirzepatide, Lilly, announced these results in a series of four press releases issued during December 2020–May 2021. Scientific reports on the outcomes from four of these trials are scheduled during the American Diabetes Association’s Scientific Sessions being held virtually in late June 2021, with results from the fifth on track for a report during the annual meeting of the European Association for the Study of Diabetes in September 2021.

Tirzepatide is a “twincretin” because it combines in a single molecule two different gut-hormone activities. It works as both a glucagonlike peptide–1 receptor agonist (GLP-1 RA) and as an agent that mimics the glucose-dependent insulinotropic polypeptide (GIP).

While diabetologists qualified their comments on these results because of the limited scope and format of the five reports to date, they also expressed enthusiasm over what the press releases said.
 

Results give hope

“It’s quite exciting, but of course we would like to go by the data that’s presented” at upcoming meetings, commented Robert A. Gabbay, MD, PhD, chief science and medical officer of the American Diabetes Association in Arlington, Va. “The idea of GLP-1 and GIP activities working together has been out there for a while, but without any therapeutic options that leverage this,” he said in an interview.

“The preliminary results give us hope that tirzepatide will be a very effective glucose-lowering agent, perhaps the most effective among all options currently available, including insulin,” commented Ildiko Lingvay, MD, a diabetologist and professor at the University of Texas Southwestern Medical Center, Dallas. “Tirzepatide might have the added benefit of clinically meaningful weight loss,” and “the adverse event profile seems to be in line with what we are accustomed to with the GLP-1 RA class. I look forward to seeing the full results. Tirzepatide promises to be a great addition for type 2 diabetes,” Dr. Lingvay said in an interview.
 

A rare head-to-head against semaglutide

The five phase 3, randomized controlled trials described by Lilly in its four press releases all belong to the SURPASS series of studies for this agent. Perhaps the most intriguing of the five were results from SURPASS-2, announced in a release on March 4. This trial randomized 1,879 patients from the United States or any of seven other countries to 40 weeks of open-label treatment with one of three different dosages of tirzepatide administered by injection once weekly, or to the control group that received a weekly 1-mg injection of semaglutide (Ozempic), the highest dosage approved for controlling glycemia in patients with type 2 diabetes at the time the study launched.

In SURPASS-2 all three tested dosages of tirzepatide led to a significantly larger reduction, from baseline in A1c, compared with semaglutide, after 40 weeks, according to the Lilly release. Each of the three tirzepatide dosages also led to significantly greater weight loss from baseline, compared with semaglutide, and significantly greater percentages of patients who achieved an A1c of less than 7%, compared with semaglutide.

As an example, the highest tested tirzepatide dosage of 15 mg weekly led to an average A1c reduction from baseline of 2.46% and an average weight loss from baseline of 12.4 kg; 92% of patients achieved an A1c of less than 7%, and 51% had their A1c fall below 5.7% which indicates completely normalization of glycemic control. By comparison, the patients randomized to treatment with semaglutide had an average 1.86% reduction in their A1c level from baseline and a 6.2-kg average cut in body weight from baseline; 81% achieved an A1c of less than 7%, and 20% reached an A1c of less than 5.7%.
 

There are caveats

While these findings are notable as a rare example of an industry-sponsored head-to-head comparison of two new agents, the study comes with a few important asterisks.

First, it was open label, a curious limitation given that both agents are delivered by the same delivery method and schedule. “I cannot conclude based on this study that tirzepatide is superior because it was open label,” commented Anastassia Amaro, MD, medical director of Penn Metabolic Medicine at the University of Pennsylvania, Philadelphia.

“The gold standard is the double-blind study. An open-label design is a limitation,” agreed Dr. Gabbay.

A second caveat is that the Food and Drug Administration recently approved a higher dosage of semaglutide (2.4 g once/week) for treating overweight or obesity in patients with type 2 diabetes and in those without diabetes but a different weight-related condition such as hypertension of hypercholesterolemia. This means that the tested comparator dosage of 1 mg/week is no longer the maximum that most patients treated with semaglutide for glycemic control can receive.

“The inevitable question” about this comparison study is “what about a higher semaglutide dose,” and how might tirzepatide perform relative to that, said Dr. Gabbay. The recently approved higher dosage of semaglutide “adds an interesting wrinkle.”

Lilly has launched a series of studies testing tirzepatide as a treatment for overweight or obesity in people without diabetes, but the results are not expected until sometime in 2022 or 2023.

And there’s a third caveat: Semaglutide has already shown its value for cardiovascular risk reduction in patients with type 2 diabetes in the SUSTAIN 6 trial with nearly 3,300 randomized patients followed for 2 years and reported in 2016. The cardiovascular outcomes trial for tirzepatide, SURPASS-CVOT with more than 12,000 patients with type 2 diabetes, is underway but its results are not expected until 2024.

Despite these important limitations, a blinded comparison of tirzepatide and higher-dose semaglutide is unlikely, Dr. Amaro predicted. “It’s not worth the expense,” she said in an interview. A more likely scenario will be that, if tirzepatide enters the U.S. market, decisions on whether to treat patients with it or semaglutide will pivot on factors like the cost for treatment to individual patients based on their insurance coverage and tolerability, suggested both Dr. Amaro and Dr. Gabbay. “Physicians will need to develop a sense for tirzepatide: Do patients tolerate it and are they happy using it?” Dr. Amaro said.
 

Tirzepatide versus insulin, or on top of insulin

The other four trials in patients with type 2 diabetes reported by Lilly in releases included SURPASS-1, which randomized 478 patients to treatment with tirzepatide or placebo as monotherapy; SURPASS-3, which randomized 1,444 patients to tirzepatide or insulin degludec (Tresiba) on top of background treatment with metformin; SURPASS-4, which randomized 2,002 patients with high cardiovascular disease risk to treatment with tirzepatide or insulin glargine (Lantus) on top of background treatment with one to three different oral drugs; and SURPASS-5, which randomized 475 patients to treatment with tirzepatide or placebo on top of background treatment with insulin glargine and optional addition of metformin. Altogether, the five trials randomized nearly 6,300 patients.

The studies that compared tirzepatide against two different types of insulin, and the third that tested tirzepatide on top of insulin glargine, are especially notable. “It’s good to see that the combination [of tirzepatide and insulin glargine] works without causing major adverse events,” said Dr. Amaro.

“These are fair and helpful comparisons. I applaud Lilly for doing the right kind of comparisons,” said Dr. Gabbay.

In total, the five studies “provide evidence that tirzepatide will be effective at all stages of type 2 diabetes and can safely be used in combination with other glucose-lowering agents, including insulin,” said Dr. Lingvay. The studies with active comparator agents “allow us to compare tirzepatide’s efficacy against established therapies.”

The SURPASS trials were sponsored by Lilly, which is developing tirzepatide. Dr. Gabbay had no relevant disclosures. Dr. Lingvay has received research funds, consulting and advisory fees, or other support from Lilly as well as from several other companies including Novo Nordisk, which markets semaglutide (Ozempic) and insulin degludec (Tresiba), and Sanofi, which markets insulin glargine (Lantus). Dr. Amaro has received research funding from Lilly and from Fractyl, and has been a consultant to and received research funding from Novo Nordisk.

[email protected]

The investigational, novel, injected once-weekly “twincretin” tirzepatide met its primary efficacy endpoint of significantly cutting hemoglobin A1c as well as its secondary weight-loss endpoint in patients with type 2 diabetes when compared with control patients in top-line results from each of five discrete pivotal trials.

Courtesy Joslin Diabetes Center

The company developing tirzepatide, Lilly, announced these results in a series of four press releases issued during December 2020–May 2021. Scientific reports on the outcomes from four of these trials are scheduled during the American Diabetes Association’s Scientific Sessions being held virtually in late June 2021, with results from the fifth on track for a report during the annual meeting of the European Association for the Study of Diabetes in September 2021.

Tirzepatide is a “twincretin” because it combines in a single molecule two different gut-hormone activities. It works as both a glucagonlike peptide–1 receptor agonist (GLP-1 RA) and as an agent that mimics the glucose-dependent insulinotropic polypeptide (GIP).

While diabetologists qualified their comments on these results because of the limited scope and format of the five reports to date, they also expressed enthusiasm over what the press releases said.
 

Results give hope

“It’s quite exciting, but of course we would like to go by the data that’s presented” at upcoming meetings, commented Robert A. Gabbay, MD, PhD, chief science and medical officer of the American Diabetes Association in Arlington, Va. “The idea of GLP-1 and GIP activities working together has been out there for a while, but without any therapeutic options that leverage this,” he said in an interview.

“The preliminary results give us hope that tirzepatide will be a very effective glucose-lowering agent, perhaps the most effective among all options currently available, including insulin,” commented Ildiko Lingvay, MD, a diabetologist and professor at the University of Texas Southwestern Medical Center, Dallas. “Tirzepatide might have the added benefit of clinically meaningful weight loss,” and “the adverse event profile seems to be in line with what we are accustomed to with the GLP-1 RA class. I look forward to seeing the full results. Tirzepatide promises to be a great addition for type 2 diabetes,” Dr. Lingvay said in an interview.
 

A rare head-to-head against semaglutide

The five phase 3, randomized controlled trials described by Lilly in its four press releases all belong to the SURPASS series of studies for this agent. Perhaps the most intriguing of the five were results from SURPASS-2, announced in a release on March 4. This trial randomized 1,879 patients from the United States or any of seven other countries to 40 weeks of open-label treatment with one of three different dosages of tirzepatide administered by injection once weekly, or to the control group that received a weekly 1-mg injection of semaglutide (Ozempic), the highest dosage approved for controlling glycemia in patients with type 2 diabetes at the time the study launched.

In SURPASS-2 all three tested dosages of tirzepatide led to a significantly larger reduction, from baseline in A1c, compared with semaglutide, after 40 weeks, according to the Lilly release. Each of the three tirzepatide dosages also led to significantly greater weight loss from baseline, compared with semaglutide, and significantly greater percentages of patients who achieved an A1c of less than 7%, compared with semaglutide.

As an example, the highest tested tirzepatide dosage of 15 mg weekly led to an average A1c reduction from baseline of 2.46% and an average weight loss from baseline of 12.4 kg; 92% of patients achieved an A1c of less than 7%, and 51% had their A1c fall below 5.7% which indicates completely normalization of glycemic control. By comparison, the patients randomized to treatment with semaglutide had an average 1.86% reduction in their A1c level from baseline and a 6.2-kg average cut in body weight from baseline; 81% achieved an A1c of less than 7%, and 20% reached an A1c of less than 5.7%.
 

There are caveats

While these findings are notable as a rare example of an industry-sponsored head-to-head comparison of two new agents, the study comes with a few important asterisks.

First, it was open label, a curious limitation given that both agents are delivered by the same delivery method and schedule. “I cannot conclude based on this study that tirzepatide is superior because it was open label,” commented Anastassia Amaro, MD, medical director of Penn Metabolic Medicine at the University of Pennsylvania, Philadelphia.

“The gold standard is the double-blind study. An open-label design is a limitation,” agreed Dr. Gabbay.

A second caveat is that the Food and Drug Administration recently approved a higher dosage of semaglutide (2.4 g once/week) for treating overweight or obesity in patients with type 2 diabetes and in those without diabetes but a different weight-related condition such as hypertension of hypercholesterolemia. This means that the tested comparator dosage of 1 mg/week is no longer the maximum that most patients treated with semaglutide for glycemic control can receive.

“The inevitable question” about this comparison study is “what about a higher semaglutide dose,” and how might tirzepatide perform relative to that, said Dr. Gabbay. The recently approved higher dosage of semaglutide “adds an interesting wrinkle.”

Lilly has launched a series of studies testing tirzepatide as a treatment for overweight or obesity in people without diabetes, but the results are not expected until sometime in 2022 or 2023.

And there’s a third caveat: Semaglutide has already shown its value for cardiovascular risk reduction in patients with type 2 diabetes in the SUSTAIN 6 trial with nearly 3,300 randomized patients followed for 2 years and reported in 2016. The cardiovascular outcomes trial for tirzepatide, SURPASS-CVOT with more than 12,000 patients with type 2 diabetes, is underway but its results are not expected until 2024.

Despite these important limitations, a blinded comparison of tirzepatide and higher-dose semaglutide is unlikely, Dr. Amaro predicted. “It’s not worth the expense,” she said in an interview. A more likely scenario will be that, if tirzepatide enters the U.S. market, decisions on whether to treat patients with it or semaglutide will pivot on factors like the cost for treatment to individual patients based on their insurance coverage and tolerability, suggested both Dr. Amaro and Dr. Gabbay. “Physicians will need to develop a sense for tirzepatide: Do patients tolerate it and are they happy using it?” Dr. Amaro said.
 

Tirzepatide versus insulin, or on top of insulin

The other four trials in patients with type 2 diabetes reported by Lilly in releases included SURPASS-1, which randomized 478 patients to treatment with tirzepatide or placebo as monotherapy; SURPASS-3, which randomized 1,444 patients to tirzepatide or insulin degludec (Tresiba) on top of background treatment with metformin; SURPASS-4, which randomized 2,002 patients with high cardiovascular disease risk to treatment with tirzepatide or insulin glargine (Lantus) on top of background treatment with one to three different oral drugs; and SURPASS-5, which randomized 475 patients to treatment with tirzepatide or placebo on top of background treatment with insulin glargine and optional addition of metformin. Altogether, the five trials randomized nearly 6,300 patients.

The studies that compared tirzepatide against two different types of insulin, and the third that tested tirzepatide on top of insulin glargine, are especially notable. “It’s good to see that the combination [of tirzepatide and insulin glargine] works without causing major adverse events,” said Dr. Amaro.

“These are fair and helpful comparisons. I applaud Lilly for doing the right kind of comparisons,” said Dr. Gabbay.

In total, the five studies “provide evidence that tirzepatide will be effective at all stages of type 2 diabetes and can safely be used in combination with other glucose-lowering agents, including insulin,” said Dr. Lingvay. The studies with active comparator agents “allow us to compare tirzepatide’s efficacy against established therapies.”

The SURPASS trials were sponsored by Lilly, which is developing tirzepatide. Dr. Gabbay had no relevant disclosures. Dr. Lingvay has received research funds, consulting and advisory fees, or other support from Lilly as well as from several other companies including Novo Nordisk, which markets semaglutide (Ozempic) and insulin degludec (Tresiba), and Sanofi, which markets insulin glargine (Lantus). Dr. Amaro has received research funding from Lilly and from Fractyl, and has been a consultant to and received research funding from Novo Nordisk.

[email protected]

The investigational, novel, injected once-weekly “twincretin” tirzepatide met its primary efficacy endpoint of significantly cutting hemoglobin A1c as well as its secondary weight-loss endpoint in patients with type 2 diabetes when compared with control patients in top-line results from each of five discrete pivotal trials.

Courtesy Joslin Diabetes Center

The company developing tirzepatide, Lilly, announced these results in a series of four press releases issued during December 2020–May 2021. Scientific reports on the outcomes from four of these trials are scheduled during the American Diabetes Association’s Scientific Sessions being held virtually in late June 2021, with results from the fifth on track for a report during the annual meeting of the European Association for the Study of Diabetes in September 2021.

Tirzepatide is a “twincretin” because it combines in a single molecule two different gut-hormone activities. It works as both a glucagonlike peptide–1 receptor agonist (GLP-1 RA) and as an agent that mimics the glucose-dependent insulinotropic polypeptide (GIP).

While diabetologists qualified their comments on these results because of the limited scope and format of the five reports to date, they also expressed enthusiasm over what the press releases said.
 

Results give hope

“It’s quite exciting, but of course we would like to go by the data that’s presented” at upcoming meetings, commented Robert A. Gabbay, MD, PhD, chief science and medical officer of the American Diabetes Association in Arlington, Va. “The idea of GLP-1 and GIP activities working together has been out there for a while, but without any therapeutic options that leverage this,” he said in an interview.

“The preliminary results give us hope that tirzepatide will be a very effective glucose-lowering agent, perhaps the most effective among all options currently available, including insulin,” commented Ildiko Lingvay, MD, a diabetologist and professor at the University of Texas Southwestern Medical Center, Dallas. “Tirzepatide might have the added benefit of clinically meaningful weight loss,” and “the adverse event profile seems to be in line with what we are accustomed to with the GLP-1 RA class. I look forward to seeing the full results. Tirzepatide promises to be a great addition for type 2 diabetes,” Dr. Lingvay said in an interview.
 

A rare head-to-head against semaglutide

The five phase 3, randomized controlled trials described by Lilly in its four press releases all belong to the SURPASS series of studies for this agent. Perhaps the most intriguing of the five were results from SURPASS-2, announced in a release on March 4. This trial randomized 1,879 patients from the United States or any of seven other countries to 40 weeks of open-label treatment with one of three different dosages of tirzepatide administered by injection once weekly, or to the control group that received a weekly 1-mg injection of semaglutide (Ozempic), the highest dosage approved for controlling glycemia in patients with type 2 diabetes at the time the study launched.

In SURPASS-2 all three tested dosages of tirzepatide led to a significantly larger reduction, from baseline in A1c, compared with semaglutide, after 40 weeks, according to the Lilly release. Each of the three tirzepatide dosages also led to significantly greater weight loss from baseline, compared with semaglutide, and significantly greater percentages of patients who achieved an A1c of less than 7%, compared with semaglutide.

As an example, the highest tested tirzepatide dosage of 15 mg weekly led to an average A1c reduction from baseline of 2.46% and an average weight loss from baseline of 12.4 kg; 92% of patients achieved an A1c of less than 7%, and 51% had their A1c fall below 5.7% which indicates completely normalization of glycemic control. By comparison, the patients randomized to treatment with semaglutide had an average 1.86% reduction in their A1c level from baseline and a 6.2-kg average cut in body weight from baseline; 81% achieved an A1c of less than 7%, and 20% reached an A1c of less than 5.7%.
 

There are caveats

While these findings are notable as a rare example of an industry-sponsored head-to-head comparison of two new agents, the study comes with a few important asterisks.

First, it was open label, a curious limitation given that both agents are delivered by the same delivery method and schedule. “I cannot conclude based on this study that tirzepatide is superior because it was open label,” commented Anastassia Amaro, MD, medical director of Penn Metabolic Medicine at the University of Pennsylvania, Philadelphia.

“The gold standard is the double-blind study. An open-label design is a limitation,” agreed Dr. Gabbay.

A second caveat is that the Food and Drug Administration recently approved a higher dosage of semaglutide (2.4 g once/week) for treating overweight or obesity in patients with type 2 diabetes and in those without diabetes but a different weight-related condition such as hypertension of hypercholesterolemia. This means that the tested comparator dosage of 1 mg/week is no longer the maximum that most patients treated with semaglutide for glycemic control can receive.

“The inevitable question” about this comparison study is “what about a higher semaglutide dose,” and how might tirzepatide perform relative to that, said Dr. Gabbay. The recently approved higher dosage of semaglutide “adds an interesting wrinkle.”

Lilly has launched a series of studies testing tirzepatide as a treatment for overweight or obesity in people without diabetes, but the results are not expected until sometime in 2022 or 2023.

And there’s a third caveat: Semaglutide has already shown its value for cardiovascular risk reduction in patients with type 2 diabetes in the SUSTAIN 6 trial with nearly 3,300 randomized patients followed for 2 years and reported in 2016. The cardiovascular outcomes trial for tirzepatide, SURPASS-CVOT with more than 12,000 patients with type 2 diabetes, is underway but its results are not expected until 2024.

Despite these important limitations, a blinded comparison of tirzepatide and higher-dose semaglutide is unlikely, Dr. Amaro predicted. “It’s not worth the expense,” she said in an interview. A more likely scenario will be that, if tirzepatide enters the U.S. market, decisions on whether to treat patients with it or semaglutide will pivot on factors like the cost for treatment to individual patients based on their insurance coverage and tolerability, suggested both Dr. Amaro and Dr. Gabbay. “Physicians will need to develop a sense for tirzepatide: Do patients tolerate it and are they happy using it?” Dr. Amaro said.
 

Tirzepatide versus insulin, or on top of insulin

The other four trials in patients with type 2 diabetes reported by Lilly in releases included SURPASS-1, which randomized 478 patients to treatment with tirzepatide or placebo as monotherapy; SURPASS-3, which randomized 1,444 patients to tirzepatide or insulin degludec (Tresiba) on top of background treatment with metformin; SURPASS-4, which randomized 2,002 patients with high cardiovascular disease risk to treatment with tirzepatide or insulin glargine (Lantus) on top of background treatment with one to three different oral drugs; and SURPASS-5, which randomized 475 patients to treatment with tirzepatide or placebo on top of background treatment with insulin glargine and optional addition of metformin. Altogether, the five trials randomized nearly 6,300 patients.

The studies that compared tirzepatide against two different types of insulin, and the third that tested tirzepatide on top of insulin glargine, are especially notable. “It’s good to see that the combination [of tirzepatide and insulin glargine] works without causing major adverse events,” said Dr. Amaro.

“These are fair and helpful comparisons. I applaud Lilly for doing the right kind of comparisons,” said Dr. Gabbay.

In total, the five studies “provide evidence that tirzepatide will be effective at all stages of type 2 diabetes and can safely be used in combination with other glucose-lowering agents, including insulin,” said Dr. Lingvay. The studies with active comparator agents “allow us to compare tirzepatide’s efficacy against established therapies.”

The SURPASS trials were sponsored by Lilly, which is developing tirzepatide. Dr. Gabbay had no relevant disclosures. Dr. Lingvay has received research funds, consulting and advisory fees, or other support from Lilly as well as from several other companies including Novo Nordisk, which markets semaglutide (Ozempic) and insulin degludec (Tresiba), and Sanofi, which markets insulin glargine (Lantus). Dr. Amaro has received research funding from Lilly and from Fractyl, and has been a consultant to and received research funding from Novo Nordisk.

[email protected]

Further evidence that powerful magnets in some Apple iPhones can interfere with cardiac implantable electronic devices (CIEDs) comes from a small study that also suggests some devices are more susceptible than others.

The iPhone 12 Pro Max with MagSafe technology interfered with CIEDs implanted in three consecutive patients presenting to an electrophysiology lab and in 8 of 11 implantable cardioverter defibrillators (ICDs) and pacemakers (72.7%) still in their original packaging.

The results, published in the Journal of the American Heart Association, are consistent with a widely publicized single-patient report this February and evidence of electromagnetic interference with fitness wristbands and e-cigarettes.

The MagSafe technology supports wireless charging and is optimized by a ring-shaped array of magnets. Although magnet mode activation has been shown to occur in CIEDs with exposure to a magnetic field as low as 10 gauss, the field strength of the iPhone 12 Pro Max can be greater than 50 G when in direct contact, the researchers determined.

“If this becomes a standard in a lot of the new smartphones or companies start to use stronger magnets ... then we will see more and more of these consumer electronic and device interactions,” senior author Michael Wu, MD, Brown University, Providence, R.I., told this news organization.

In a May advisory on these device interactions, the U.S. Food and Drug Administration also cautioned that the number of consumer electronics with strong magnets is expected to increase over time.

That trend appears to be already underway, with Forbes reporting in February that the MagSafe batteries will be “getting stronger” as part of upgrades to the iPhone 13 and Bloomberg reporting in advance of Apple’s annual developers conference this week that an upgraded version of MagSafe is in the works to support wireless charging for its iPad. MagSafe has not been used previously in iPads.

Although Apple has acknowledged that the iPhone 12 contains more magnets than previous iPhone models, it says “they’re not expected to pose a greater risk of magnetic interference to medical devices than prior iPhone models.” The company maintains a page that specifically warns about the potential for interactions and advises that consumers keep the iPhone and MagSafe accessories more than 15 cm (6 inches) away from medical devices.

Older-generation iPhones have not shown this risk, with only one case of interference reported with the iPhone 6 and an Apple Watch in 1,352 tests among 148 patients with CIEDs and leads from four different manufacturers.

In the present study, magnet reversion mode was triggered in all three patients when the iPhone 12 Pro Max was placed on the skin over the device.

The phone inhibited tachycardia therapies in Medtronic’s Amplia MRI Quad CRT-D and Abbott’s 1231-40 Fortify VR device.

The Boston Scientific V273 Intua CRT-P device, however, “appeared to be less susceptible, as we were only able to elicit transient temporary asynchronous pacing but no sustained response by the iPhone 12 Pro Max magnet,” Dr. Wu and colleagues note.

Among the 11 ex vivo CIEDs tested, placing the iPhone 12 Pro Max directly over the packaged device inhibited tachytherapies in Medtronic’s Visia AF MRI ICD and Abbott’s Fortify Assura DR ICD and Ellipse DR ICD.

The phone also led to asynchronous pacing in Medtronic’s Azure, Advisa MRI, and Adapta pacemakers and in Abbott’s Assurity MRI pacemaker.

Boston Scientific devices again “appeared to be less susceptible, as no clear magnet interference” was noted in the Dynagen ICD, Emblem MRI S-ICD, or Accolade MRI pacemaker, Dr. Wu reported. There was temporary asynchronous pacing but no sustained response in the company’s U125 Valitude pacemaker.

Using the Medtronic Visia AF MRI ICD, the researchers found that the iPhone 12 Pro Max was able to trigger magnet reversion mode at a distance up to 1.5 cm (0.6 inch) from the anterior aspect of the device ex vivo.

The difference in magnet response to the iPhone 12 Pro Max among the different devices is likely due to different hall-sensor magnet sensitivity, as all of the devices were susceptible to a standard donut magnet, Dr. Wu noted. Boston Scientific’s Accolade MRI pacemaker, for example, requires a magnet stronger than 70 G to activate magnet mode, according to the product manual.

“Even so, sometimes with our test, we were able to trigger a brief response,” he said. “The response isn’t as lasting as some of the other companies, but with the small sample size, I can only speculate and suggest that maybe it’s possible. But we always want a formal study through the company or other agencies to really pinpoint which company has more susceptible devices.”

As to whether manufacturers should build CIEDs less susceptible to today’s stronger magnets, Dr. Wu said it’s worth exploring, but there are pros and cons.

Although magnets in consumer devices have the potential to inhibit lifesaving therapies, a magnet is also very useful in certain medical settings, such as a quick way to ensure pacing without worrying about electrocautery noise during surgery or to deactivate a defibrillator if there’s noise resulting in inappropriate shocks.

“It would require an overhaul of a lot of the devices going forward, and I think that’s something that’s worth exploring, especially now that a lot of devices are using wireless communication, Bluetooth, and other communication technology,” he said.

Even though the study is small, Dr. Wu said, it does represent many of the available devices and has clinical implications, given that people often put their smartphones in a breast pocket.

“This report highlights the importance of public awareness regarding an interaction between CIEDs and a recently released smartphone model with magnetic charging capability,” Dr. Wu and colleagues conclude.

Apple was contacted for comment but had not responded at press time.

The authors reported no study funding or relevant conflicts of interests.

A version of this article first appeared on Medscape.com.

Further evidence that powerful magnets in some Apple iPhones can interfere with cardiac implantable electronic devices (CIEDs) comes from a small study that also suggests some devices are more susceptible than others.

The iPhone 12 Pro Max with MagSafe technology interfered with CIEDs implanted in three consecutive patients presenting to an electrophysiology lab and in 8 of 11 implantable cardioverter defibrillators (ICDs) and pacemakers (72.7%) still in their original packaging.

The results, published in the Journal of the American Heart Association, are consistent with a widely publicized single-patient report this February and evidence of electromagnetic interference with fitness wristbands and e-cigarettes.

The MagSafe technology supports wireless charging and is optimized by a ring-shaped array of magnets. Although magnet mode activation has been shown to occur in CIEDs with exposure to a magnetic field as low as 10 gauss, the field strength of the iPhone 12 Pro Max can be greater than 50 G when in direct contact, the researchers determined.

“If this becomes a standard in a lot of the new smartphones or companies start to use stronger magnets ... then we will see more and more of these consumer electronic and device interactions,” senior author Michael Wu, MD, Brown University, Providence, R.I., told this news organization.

In a May advisory on these device interactions, the U.S. Food and Drug Administration also cautioned that the number of consumer electronics with strong magnets is expected to increase over time.

That trend appears to be already underway, with Forbes reporting in February that the MagSafe batteries will be “getting stronger” as part of upgrades to the iPhone 13 and Bloomberg reporting in advance of Apple’s annual developers conference this week that an upgraded version of MagSafe is in the works to support wireless charging for its iPad. MagSafe has not been used previously in iPads.

Although Apple has acknowledged that the iPhone 12 contains more magnets than previous iPhone models, it says “they’re not expected to pose a greater risk of magnetic interference to medical devices than prior iPhone models.” The company maintains a page that specifically warns about the potential for interactions and advises that consumers keep the iPhone and MagSafe accessories more than 15 cm (6 inches) away from medical devices.

Older-generation iPhones have not shown this risk, with only one case of interference reported with the iPhone 6 and an Apple Watch in 1,352 tests among 148 patients with CIEDs and leads from four different manufacturers.

In the present study, magnet reversion mode was triggered in all three patients when the iPhone 12 Pro Max was placed on the skin over the device.

The phone inhibited tachycardia therapies in Medtronic’s Amplia MRI Quad CRT-D and Abbott’s 1231-40 Fortify VR device.

The Boston Scientific V273 Intua CRT-P device, however, “appeared to be less susceptible, as we were only able to elicit transient temporary asynchronous pacing but no sustained response by the iPhone 12 Pro Max magnet,” Dr. Wu and colleagues note.

Among the 11 ex vivo CIEDs tested, placing the iPhone 12 Pro Max directly over the packaged device inhibited tachytherapies in Medtronic’s Visia AF MRI ICD and Abbott’s Fortify Assura DR ICD and Ellipse DR ICD.

The phone also led to asynchronous pacing in Medtronic’s Azure, Advisa MRI, and Adapta pacemakers and in Abbott’s Assurity MRI pacemaker.

Boston Scientific devices again “appeared to be less susceptible, as no clear magnet interference” was noted in the Dynagen ICD, Emblem MRI S-ICD, or Accolade MRI pacemaker, Dr. Wu reported. There was temporary asynchronous pacing but no sustained response in the company’s U125 Valitude pacemaker.

Using the Medtronic Visia AF MRI ICD, the researchers found that the iPhone 12 Pro Max was able to trigger magnet reversion mode at a distance up to 1.5 cm (0.6 inch) from the anterior aspect of the device ex vivo.

The difference in magnet response to the iPhone 12 Pro Max among the different devices is likely due to different hall-sensor magnet sensitivity, as all of the devices were susceptible to a standard donut magnet, Dr. Wu noted. Boston Scientific’s Accolade MRI pacemaker, for example, requires a magnet stronger than 70 G to activate magnet mode, according to the product manual.

“Even so, sometimes with our test, we were able to trigger a brief response,” he said. “The response isn’t as lasting as some of the other companies, but with the small sample size, I can only speculate and suggest that maybe it’s possible. But we always want a formal study through the company or other agencies to really pinpoint which company has more susceptible devices.”

As to whether manufacturers should build CIEDs less susceptible to today’s stronger magnets, Dr. Wu said it’s worth exploring, but there are pros and cons.

Although magnets in consumer devices have the potential to inhibit lifesaving therapies, a magnet is also very useful in certain medical settings, such as a quick way to ensure pacing without worrying about electrocautery noise during surgery or to deactivate a defibrillator if there’s noise resulting in inappropriate shocks.

“It would require an overhaul of a lot of the devices going forward, and I think that’s something that’s worth exploring, especially now that a lot of devices are using wireless communication, Bluetooth, and other communication technology,” he said.

Even though the study is small, Dr. Wu said, it does represent many of the available devices and has clinical implications, given that people often put their smartphones in a breast pocket.

“This report highlights the importance of public awareness regarding an interaction between CIEDs and a recently released smartphone model with magnetic charging capability,” Dr. Wu and colleagues conclude.

Apple was contacted for comment but had not responded at press time.

The authors reported no study funding or relevant conflicts of interests.

A version of this article first appeared on Medscape.com.

Further evidence that powerful magnets in some Apple iPhones can interfere with cardiac implantable electronic devices (CIEDs) comes from a small study that also suggests some devices are more susceptible than others.

The iPhone 12 Pro Max with MagSafe technology interfered with CIEDs implanted in three consecutive patients presenting to an electrophysiology lab and in 8 of 11 implantable cardioverter defibrillators (ICDs) and pacemakers (72.7%) still in their original packaging.

The results, published in the Journal of the American Heart Association, are consistent with a widely publicized single-patient report this February and evidence of electromagnetic interference with fitness wristbands and e-cigarettes.

The MagSafe technology supports wireless charging and is optimized by a ring-shaped array of magnets. Although magnet mode activation has been shown to occur in CIEDs with exposure to a magnetic field as low as 10 gauss, the field strength of the iPhone 12 Pro Max can be greater than 50 G when in direct contact, the researchers determined.

“If this becomes a standard in a lot of the new smartphones or companies start to use stronger magnets ... then we will see more and more of these consumer electronic and device interactions,” senior author Michael Wu, MD, Brown University, Providence, R.I., told this news organization.

In a May advisory on these device interactions, the U.S. Food and Drug Administration also cautioned that the number of consumer electronics with strong magnets is expected to increase over time.

That trend appears to be already underway, with Forbes reporting in February that the MagSafe batteries will be “getting stronger” as part of upgrades to the iPhone 13 and Bloomberg reporting in advance of Apple’s annual developers conference this week that an upgraded version of MagSafe is in the works to support wireless charging for its iPad. MagSafe has not been used previously in iPads.

Although Apple has acknowledged that the iPhone 12 contains more magnets than previous iPhone models, it says “they’re not expected to pose a greater risk of magnetic interference to medical devices than prior iPhone models.” The company maintains a page that specifically warns about the potential for interactions and advises that consumers keep the iPhone and MagSafe accessories more than 15 cm (6 inches) away from medical devices.

Older-generation iPhones have not shown this risk, with only one case of interference reported with the iPhone 6 and an Apple Watch in 1,352 tests among 148 patients with CIEDs and leads from four different manufacturers.

In the present study, magnet reversion mode was triggered in all three patients when the iPhone 12 Pro Max was placed on the skin over the device.

The phone inhibited tachycardia therapies in Medtronic’s Amplia MRI Quad CRT-D and Abbott’s 1231-40 Fortify VR device.

The Boston Scientific V273 Intua CRT-P device, however, “appeared to be less susceptible, as we were only able to elicit transient temporary asynchronous pacing but no sustained response by the iPhone 12 Pro Max magnet,” Dr. Wu and colleagues note.

Among the 11 ex vivo CIEDs tested, placing the iPhone 12 Pro Max directly over the packaged device inhibited tachytherapies in Medtronic’s Visia AF MRI ICD and Abbott’s Fortify Assura DR ICD and Ellipse DR ICD.

The phone also led to asynchronous pacing in Medtronic’s Azure, Advisa MRI, and Adapta pacemakers and in Abbott’s Assurity MRI pacemaker.

Boston Scientific devices again “appeared to be less susceptible, as no clear magnet interference” was noted in the Dynagen ICD, Emblem MRI S-ICD, or Accolade MRI pacemaker, Dr. Wu reported. There was temporary asynchronous pacing but no sustained response in the company’s U125 Valitude pacemaker.

Using the Medtronic Visia AF MRI ICD, the researchers found that the iPhone 12 Pro Max was able to trigger magnet reversion mode at a distance up to 1.5 cm (0.6 inch) from the anterior aspect of the device ex vivo.

The difference in magnet response to the iPhone 12 Pro Max among the different devices is likely due to different hall-sensor magnet sensitivity, as all of the devices were susceptible to a standard donut magnet, Dr. Wu noted. Boston Scientific’s Accolade MRI pacemaker, for example, requires a magnet stronger than 70 G to activate magnet mode, according to the product manual.

“Even so, sometimes with our test, we were able to trigger a brief response,” he said. “The response isn’t as lasting as some of the other companies, but with the small sample size, I can only speculate and suggest that maybe it’s possible. But we always want a formal study through the company or other agencies to really pinpoint which company has more susceptible devices.”

As to whether manufacturers should build CIEDs less susceptible to today’s stronger magnets, Dr. Wu said it’s worth exploring, but there are pros and cons.

Although magnets in consumer devices have the potential to inhibit lifesaving therapies, a magnet is also very useful in certain medical settings, such as a quick way to ensure pacing without worrying about electrocautery noise during surgery or to deactivate a defibrillator if there’s noise resulting in inappropriate shocks.

“It would require an overhaul of a lot of the devices going forward, and I think that’s something that’s worth exploring, especially now that a lot of devices are using wireless communication, Bluetooth, and other communication technology,” he said.

Even though the study is small, Dr. Wu said, it does represent many of the available devices and has clinical implications, given that people often put their smartphones in a breast pocket.

“This report highlights the importance of public awareness regarding an interaction between CIEDs and a recently released smartphone model with magnetic charging capability,” Dr. Wu and colleagues conclude.

Apple was contacted for comment but had not responded at press time.

The authors reported no study funding or relevant conflicts of interests.

A version of this article first appeared on Medscape.com.

Increased intake of meat was linked to the risk of coronary heart disease, and substituting plant protein for red or processed meat appeared to reduce that risk, in a study from pooled cohorts totaling more than a million persons.

Fuse/Thinkstock

“We know that red and processed meat intake has been associated with higher risks of fatal coronary heart disease,” said Laila Al-Shaar, PhD, of Penn State University, Hershey. However, very few studies have evaluated substitution of alternative protein sources for red and processed meat in relation to fatal CHD risk, she said.

In a study presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting, Dr. Al-Shaar and colleagues reviewed individual-level data from the Pooling Project of Prospective Studies of Diet and Cancer, which included 16 prospective cohorts totaling 1,364,211 participants. The average age of the participants was 57 years, and 40% were men. Individuals with a history of cancer or cardiovascular disease were excluded. The participants were followed for 7-32 years. Diet was assessed in each cohort using baselines questionnaires, and cases were identified through medical records.

Total red meat included processed meat and unprocessed red meat; animal protein sources included seafood, poultry, eggs, and low- and high-fat dairy products; and plant protein sources included nuts and beans.

The researchers identified 51,176 fatal CHD cases during the study period. After controlling for dietary and nondietary factors, they found that an increase of 100 g per day of total red meat intake was associated with a 7% increased risk of fatal coronary heart disease (relative risk, 1.07).

However, substituting 200 calories (kcal) per day from nuts, low- and high-fat dairy products, and poultry for 200 calories per day from total red meat was associated with a 6%-14% lower risk of fatal CHD, Dr. Al-Shaar added at the meeting sponsored by the American Heart Association.

These associations were stronger when substituting the alternative protein sources for processed meat, especially among women; risk was reduced by 17%-24%, on the basis of 14,888 cases.

The researchers also found that substituting 200 calories per day from eggs for 200 calories per day for total red meat and unprocessed red meat was associated with 8% and 14% higher risk of fatal CHD, respectively; but this substitution of eggs for processed meat was not significant (4%).

“When we did the association by gender, the results were even stronger in women,” said Dr. Al-Shaar. However, “these are very preliminary results” that should be interpreted with caution, and more analysis is needed, she said. “We are planning to include other cohorts with other protein sources such as soy protein,” she noted. However, the results provide additional evidence that consumption of red and processed meat contributes to an increased risk of coronary heart disease, and that substituting some red and processed meat with nuts, dairy products, or poultry may reduce this risk, she concluded.
 

Women especially benefit from red meat reduction

The study is important because of the continuing interest in various sources of dietary protein intake, Linda Van Horn, PhD, RD, of Northwestern University, Chicago, said in an interview.

“The investigators studied associations of substituting other animal and plant protein sources for total red meat, unprocessed red meat, and processed meat in relation to risk of fatal CHD,” she said.

The researchers found that swapping as little as 200 calories per day of total red meat for nuts, low- or high-fat dairy products, or poultry were associated with a 6%-14% reduced risk of fatal CHD, said Dr. Van Horn. “Alternatively, if those 200 calories per day for red meat were substituted with eggs, they saw as much as 14% higher risk of fatal CHD,” she noted.

The message for both consumers and clinicians is that the findings from this large study support recommendations for plant-based and lean animal sources of protein instead of red and processed meat or eggs, as these sources “offer significantly lower risk for CHD mortality,” Dr. Van Horn said. “This may be especially true for women, but the total population is likely to benefit from this approach,” she said.

Additional research is needed, Dr. Van Horn emphasized. “Prospective lifetime data, starting in utero and over the life course, are needed to better establish recommended dietary patterns at every age and among all ethnicities and diverse socioeconomic groups,” she said.

Dr. Al-Shaar had no financial conflicts to disclose. Dr. Van Horn had no financial conflicts to disclose.

Increased intake of meat was linked to the risk of coronary heart disease, and substituting plant protein for red or processed meat appeared to reduce that risk, in a study from pooled cohorts totaling more than a million persons.

Fuse/Thinkstock

“We know that red and processed meat intake has been associated with higher risks of fatal coronary heart disease,” said Laila Al-Shaar, PhD, of Penn State University, Hershey. However, very few studies have evaluated substitution of alternative protein sources for red and processed meat in relation to fatal CHD risk, she said.

In a study presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting, Dr. Al-Shaar and colleagues reviewed individual-level data from the Pooling Project of Prospective Studies of Diet and Cancer, which included 16 prospective cohorts totaling 1,364,211 participants. The average age of the participants was 57 years, and 40% were men. Individuals with a history of cancer or cardiovascular disease were excluded. The participants were followed for 7-32 years. Diet was assessed in each cohort using baselines questionnaires, and cases were identified through medical records.

Total red meat included processed meat and unprocessed red meat; animal protein sources included seafood, poultry, eggs, and low- and high-fat dairy products; and plant protein sources included nuts and beans.

The researchers identified 51,176 fatal CHD cases during the study period. After controlling for dietary and nondietary factors, they found that an increase of 100 g per day of total red meat intake was associated with a 7% increased risk of fatal coronary heart disease (relative risk, 1.07).

However, substituting 200 calories (kcal) per day from nuts, low- and high-fat dairy products, and poultry for 200 calories per day from total red meat was associated with a 6%-14% lower risk of fatal CHD, Dr. Al-Shaar added at the meeting sponsored by the American Heart Association.

These associations were stronger when substituting the alternative protein sources for processed meat, especially among women; risk was reduced by 17%-24%, on the basis of 14,888 cases.

The researchers also found that substituting 200 calories per day from eggs for 200 calories per day for total red meat and unprocessed red meat was associated with 8% and 14% higher risk of fatal CHD, respectively; but this substitution of eggs for processed meat was not significant (4%).

“When we did the association by gender, the results were even stronger in women,” said Dr. Al-Shaar. However, “these are very preliminary results” that should be interpreted with caution, and more analysis is needed, she said. “We are planning to include other cohorts with other protein sources such as soy protein,” she noted. However, the results provide additional evidence that consumption of red and processed meat contributes to an increased risk of coronary heart disease, and that substituting some red and processed meat with nuts, dairy products, or poultry may reduce this risk, she concluded.
 

Women especially benefit from red meat reduction

The study is important because of the continuing interest in various sources of dietary protein intake, Linda Van Horn, PhD, RD, of Northwestern University, Chicago, said in an interview.

“The investigators studied associations of substituting other animal and plant protein sources for total red meat, unprocessed red meat, and processed meat in relation to risk of fatal CHD,” she said.

The researchers found that swapping as little as 200 calories per day of total red meat for nuts, low- or high-fat dairy products, or poultry were associated with a 6%-14% reduced risk of fatal CHD, said Dr. Van Horn. “Alternatively, if those 200 calories per day for red meat were substituted with eggs, they saw as much as 14% higher risk of fatal CHD,” she noted.

The message for both consumers and clinicians is that the findings from this large study support recommendations for plant-based and lean animal sources of protein instead of red and processed meat or eggs, as these sources “offer significantly lower risk for CHD mortality,” Dr. Van Horn said. “This may be especially true for women, but the total population is likely to benefit from this approach,” she said.

Additional research is needed, Dr. Van Horn emphasized. “Prospective lifetime data, starting in utero and over the life course, are needed to better establish recommended dietary patterns at every age and among all ethnicities and diverse socioeconomic groups,” she said.

Dr. Al-Shaar had no financial conflicts to disclose. Dr. Van Horn had no financial conflicts to disclose.

Increased intake of meat was linked to the risk of coronary heart disease, and substituting plant protein for red or processed meat appeared to reduce that risk, in a study from pooled cohorts totaling more than a million persons.

Fuse/Thinkstock

“We know that red and processed meat intake has been associated with higher risks of fatal coronary heart disease,” said Laila Al-Shaar, PhD, of Penn State University, Hershey. However, very few studies have evaluated substitution of alternative protein sources for red and processed meat in relation to fatal CHD risk, she said.

In a study presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting, Dr. Al-Shaar and colleagues reviewed individual-level data from the Pooling Project of Prospective Studies of Diet and Cancer, which included 16 prospective cohorts totaling 1,364,211 participants. The average age of the participants was 57 years, and 40% were men. Individuals with a history of cancer or cardiovascular disease were excluded. The participants were followed for 7-32 years. Diet was assessed in each cohort using baselines questionnaires, and cases were identified through medical records.

Total red meat included processed meat and unprocessed red meat; animal protein sources included seafood, poultry, eggs, and low- and high-fat dairy products; and plant protein sources included nuts and beans.

The researchers identified 51,176 fatal CHD cases during the study period. After controlling for dietary and nondietary factors, they found that an increase of 100 g per day of total red meat intake was associated with a 7% increased risk of fatal coronary heart disease (relative risk, 1.07).

However, substituting 200 calories (kcal) per day from nuts, low- and high-fat dairy products, and poultry for 200 calories per day from total red meat was associated with a 6%-14% lower risk of fatal CHD, Dr. Al-Shaar added at the meeting sponsored by the American Heart Association.

These associations were stronger when substituting the alternative protein sources for processed meat, especially among women; risk was reduced by 17%-24%, on the basis of 14,888 cases.

The researchers also found that substituting 200 calories per day from eggs for 200 calories per day for total red meat and unprocessed red meat was associated with 8% and 14% higher risk of fatal CHD, respectively; but this substitution of eggs for processed meat was not significant (4%).

“When we did the association by gender, the results were even stronger in women,” said Dr. Al-Shaar. However, “these are very preliminary results” that should be interpreted with caution, and more analysis is needed, she said. “We are planning to include other cohorts with other protein sources such as soy protein,” she noted. However, the results provide additional evidence that consumption of red and processed meat contributes to an increased risk of coronary heart disease, and that substituting some red and processed meat with nuts, dairy products, or poultry may reduce this risk, she concluded.
 

Women especially benefit from red meat reduction

The study is important because of the continuing interest in various sources of dietary protein intake, Linda Van Horn, PhD, RD, of Northwestern University, Chicago, said in an interview.

“The investigators studied associations of substituting other animal and plant protein sources for total red meat, unprocessed red meat, and processed meat in relation to risk of fatal CHD,” she said.

The researchers found that swapping as little as 200 calories per day of total red meat for nuts, low- or high-fat dairy products, or poultry were associated with a 6%-14% reduced risk of fatal CHD, said Dr. Van Horn. “Alternatively, if those 200 calories per day for red meat were substituted with eggs, they saw as much as 14% higher risk of fatal CHD,” she noted.

The message for both consumers and clinicians is that the findings from this large study support recommendations for plant-based and lean animal sources of protein instead of red and processed meat or eggs, as these sources “offer significantly lower risk for CHD mortality,” Dr. Van Horn said. “This may be especially true for women, but the total population is likely to benefit from this approach,” she said.

Additional research is needed, Dr. Van Horn emphasized. “Prospective lifetime data, starting in utero and over the life course, are needed to better establish recommended dietary patterns at every age and among all ethnicities and diverse socioeconomic groups,” she said.

Dr. Al-Shaar had no financial conflicts to disclose. Dr. Van Horn had no financial conflicts to disclose.

It follows that, as the prevalence of obesity among people with type 1 diabetes mellitus (T1DM) increases, so would the incidence of nonalcoholic fatty liver (NAFL), as it does in type 2 diabetes.

However, researchers in Finland report that the incidence of NAFL in T1DM is much lower, and that the use of the waist-to-height ratio to calculate midsection girth could be a low-cost alternative to MRI and computed tomography to more precisely diagnose NAFL in T1DM.

In a cross-sectional analysis of 121 adults with T1DM in the Finnish Diabetic Nephropathy study, known as FinnDiane, researchers from the University of Helsinki report in Diabetes Care that a waist-to-height ratio of 0.5 showed a relatively high rate of accuracy for identifying NAFL that was statistically significant (P = .04).

Lead author Erika B. Parente, MD, PhD, a researcher at the Folkhälsän Research Center in Helsinki, noted that the findings do not identify any causality between what the researchers called visceral adiposity and NAFL. “As long as they have accumulation of fat in the center of body and they can develop this low-grade inflammation that also goes to insulin-load sensitivity, people with T1DM can accumulate fat in the liver as do people with T2DM and the general population,” she said in an interview.

These findings build on her group’s previous work published in Scientific Reports showing a strong relationship between waist-to-height ratio and visceral fat percentage in adults with T1DM. The most recent FinnDiane analysis found no similar relationship between NAFL and fat tissue in the hips, arms and legs, and total adipose tissue.
 

Better than BMI as a measure

“We also found that waist-to-height ratio is better than body mass index to identify those individuals at higher risk of having NAFL,” Dr. Parente said. However, it’s not possible to predict which patients referred to imaging evaluation after being screened by waist-to-height ratio of 0.5 will surely have NAFL, she added.

That answer, she said, would require a longitudinal and cost-effectiveness study with larger population.

The waist-to-height ratio cutoff of 0.5 showed an 86% sensitivity and 55% specificity for NAFL, whereas BMI of 26.6 kg/m² showed an 79% sensitivity and 57% specificity.

“The most important message from our research is that health care professionals should be aware that individuals with T1DM can have NAFL, and waist-to-height ratio may help to identify those at higher risk,” she said.

The prevalence of NAFL among the adults with T1DM in the study was 11.6%, which is lower than the prevalence other studies reported in T2DM – 76% in a U.S. study – and in the general population – ranging from 19% to 46%. This underscores, Dr. Parente noted, the importance of using waist-to-height ratio in T1DM patients to determine the status of NAFL.

She said that few studies have investigated the consequences of NAFL in T1DM, pointing to two that linked NAFL with chronic kidney disease and cardiovascular disease in T1DM (Diabetes Care. 2014;37:1729-36; J Hepatol. 2010;53:713-8). “Most of the studies about the consequences of NAFL included people with T2DM,” she said. “From our research, we cannot conclude about the impact of NAFL in cardiovascular or kidney complications in our population because this is a cross-sectional study.”

That question may be answered by a future follow-up study of the ongoing FinnDiane study, she said.

The study is a “good reminder” that people with central adiposity and metabolic syndrome can develop NAFL disease, said Jeanne Marie Clark, MD, MPH, of Johns Hopkins University, Baltimore. “Even patients we may not think of having insulin resistance, such as those with T1DM.”

However, Dr. Clark added, “I do not think we can really determine which measure of central adiposity is best.” She noted that the study was “pretty small” with only 14 patients who had NAFL disease. “Waist-to-height ratio is certainly a reasonable option,” she added. “Waist circumference alone is known to be a strong predictor. I would say some measure is better than none, and it should be more routine in clinical practice.”

Dr. Parente disclosed financial relationships with Eli Lilly, Abbott, AstraZeneca, Sanofi, and Boehringer Ingelheim. Two of eight coauthors disclosed financial relationships with AbbVie, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Elo Water, Fresenius, GE Healthcare, Medscape, Merck Sharpe and Dohme, Mundipharma, Novo Nordisk, Peer-Voice, Sanofi, and Sciarc. The remaining coauthors had no disclosures.

Dr. Clark had no disclosures.

It follows that, as the prevalence of obesity among people with type 1 diabetes mellitus (T1DM) increases, so would the incidence of nonalcoholic fatty liver (NAFL), as it does in type 2 diabetes.

However, researchers in Finland report that the incidence of NAFL in T1DM is much lower, and that the use of the waist-to-height ratio to calculate midsection girth could be a low-cost alternative to MRI and computed tomography to more precisely diagnose NAFL in T1DM.

In a cross-sectional analysis of 121 adults with T1DM in the Finnish Diabetic Nephropathy study, known as FinnDiane, researchers from the University of Helsinki report in Diabetes Care that a waist-to-height ratio of 0.5 showed a relatively high rate of accuracy for identifying NAFL that was statistically significant (P = .04).

Lead author Erika B. Parente, MD, PhD, a researcher at the Folkhälsän Research Center in Helsinki, noted that the findings do not identify any causality between what the researchers called visceral adiposity and NAFL. “As long as they have accumulation of fat in the center of body and they can develop this low-grade inflammation that also goes to insulin-load sensitivity, people with T1DM can accumulate fat in the liver as do people with T2DM and the general population,” she said in an interview.

These findings build on her group’s previous work published in Scientific Reports showing a strong relationship between waist-to-height ratio and visceral fat percentage in adults with T1DM. The most recent FinnDiane analysis found no similar relationship between NAFL and fat tissue in the hips, arms and legs, and total adipose tissue.
 

Better than BMI as a measure

“We also found that waist-to-height ratio is better than body mass index to identify those individuals at higher risk of having NAFL,” Dr. Parente said. However, it’s not possible to predict which patients referred to imaging evaluation after being screened by waist-to-height ratio of 0.5 will surely have NAFL, she added.

That answer, she said, would require a longitudinal and cost-effectiveness study with larger population.

The waist-to-height ratio cutoff of 0.5 showed an 86% sensitivity and 55% specificity for NAFL, whereas BMI of 26.6 kg/m² showed an 79% sensitivity and 57% specificity.

“The most important message from our research is that health care professionals should be aware that individuals with T1DM can have NAFL, and waist-to-height ratio may help to identify those at higher risk,” she said.

The prevalence of NAFL among the adults with T1DM in the study was 11.6%, which is lower than the prevalence other studies reported in T2DM – 76% in a U.S. study – and in the general population – ranging from 19% to 46%. This underscores, Dr. Parente noted, the importance of using waist-to-height ratio in T1DM patients to determine the status of NAFL.

She said that few studies have investigated the consequences of NAFL in T1DM, pointing to two that linked NAFL with chronic kidney disease and cardiovascular disease in T1DM (Diabetes Care. 2014;37:1729-36; J Hepatol. 2010;53:713-8). “Most of the studies about the consequences of NAFL included people with T2DM,” she said. “From our research, we cannot conclude about the impact of NAFL in cardiovascular or kidney complications in our population because this is a cross-sectional study.”

That question may be answered by a future follow-up study of the ongoing FinnDiane study, she said.

The study is a “good reminder” that people with central adiposity and metabolic syndrome can develop NAFL disease, said Jeanne Marie Clark, MD, MPH, of Johns Hopkins University, Baltimore. “Even patients we may not think of having insulin resistance, such as those with T1DM.”

However, Dr. Clark added, “I do not think we can really determine which measure of central adiposity is best.” She noted that the study was “pretty small” with only 14 patients who had NAFL disease. “Waist-to-height ratio is certainly a reasonable option,” she added. “Waist circumference alone is known to be a strong predictor. I would say some measure is better than none, and it should be more routine in clinical practice.”

Dr. Parente disclosed financial relationships with Eli Lilly, Abbott, AstraZeneca, Sanofi, and Boehringer Ingelheim. Two of eight coauthors disclosed financial relationships with AbbVie, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Elo Water, Fresenius, GE Healthcare, Medscape, Merck Sharpe and Dohme, Mundipharma, Novo Nordisk, Peer-Voice, Sanofi, and Sciarc. The remaining coauthors had no disclosures.

Dr. Clark had no disclosures.

It follows that, as the prevalence of obesity among people with type 1 diabetes mellitus (T1DM) increases, so would the incidence of nonalcoholic fatty liver (NAFL), as it does in type 2 diabetes.

However, researchers in Finland report that the incidence of NAFL in T1DM is much lower, and that the use of the waist-to-height ratio to calculate midsection girth could be a low-cost alternative to MRI and computed tomography to more precisely diagnose NAFL in T1DM.

In a cross-sectional analysis of 121 adults with T1DM in the Finnish Diabetic Nephropathy study, known as FinnDiane, researchers from the University of Helsinki report in Diabetes Care that a waist-to-height ratio of 0.5 showed a relatively high rate of accuracy for identifying NAFL that was statistically significant (P = .04).

Lead author Erika B. Parente, MD, PhD, a researcher at the Folkhälsän Research Center in Helsinki, noted that the findings do not identify any causality between what the researchers called visceral adiposity and NAFL. “As long as they have accumulation of fat in the center of body and they can develop this low-grade inflammation that also goes to insulin-load sensitivity, people with T1DM can accumulate fat in the liver as do people with T2DM and the general population,” she said in an interview.

These findings build on her group’s previous work published in Scientific Reports showing a strong relationship between waist-to-height ratio and visceral fat percentage in adults with T1DM. The most recent FinnDiane analysis found no similar relationship between NAFL and fat tissue in the hips, arms and legs, and total adipose tissue.
 

Better than BMI as a measure

“We also found that waist-to-height ratio is better than body mass index to identify those individuals at higher risk of having NAFL,” Dr. Parente said. However, it’s not possible to predict which patients referred to imaging evaluation after being screened by waist-to-height ratio of 0.5 will surely have NAFL, she added.

That answer, she said, would require a longitudinal and cost-effectiveness study with larger population.

The waist-to-height ratio cutoff of 0.5 showed an 86% sensitivity and 55% specificity for NAFL, whereas BMI of 26.6 kg/m² showed an 79% sensitivity and 57% specificity.

“The most important message from our research is that health care professionals should be aware that individuals with T1DM can have NAFL, and waist-to-height ratio may help to identify those at higher risk,” she said.

The prevalence of NAFL among the adults with T1DM in the study was 11.6%, which is lower than the prevalence other studies reported in T2DM – 76% in a U.S. study – and in the general population – ranging from 19% to 46%. This underscores, Dr. Parente noted, the importance of using waist-to-height ratio in T1DM patients to determine the status of NAFL.

She said that few studies have investigated the consequences of NAFL in T1DM, pointing to two that linked NAFL with chronic kidney disease and cardiovascular disease in T1DM (Diabetes Care. 2014;37:1729-36; J Hepatol. 2010;53:713-8). “Most of the studies about the consequences of NAFL included people with T2DM,” she said. “From our research, we cannot conclude about the impact of NAFL in cardiovascular or kidney complications in our population because this is a cross-sectional study.”

That question may be answered by a future follow-up study of the ongoing FinnDiane study, she said.

The study is a “good reminder” that people with central adiposity and metabolic syndrome can develop NAFL disease, said Jeanne Marie Clark, MD, MPH, of Johns Hopkins University, Baltimore. “Even patients we may not think of having insulin resistance, such as those with T1DM.”

However, Dr. Clark added, “I do not think we can really determine which measure of central adiposity is best.” She noted that the study was “pretty small” with only 14 patients who had NAFL disease. “Waist-to-height ratio is certainly a reasonable option,” she added. “Waist circumference alone is known to be a strong predictor. I would say some measure is better than none, and it should be more routine in clinical practice.”

Dr. Parente disclosed financial relationships with Eli Lilly, Abbott, AstraZeneca, Sanofi, and Boehringer Ingelheim. Two of eight coauthors disclosed financial relationships with AbbVie, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Elo Water, Fresenius, GE Healthcare, Medscape, Merck Sharpe and Dohme, Mundipharma, Novo Nordisk, Peer-Voice, Sanofi, and Sciarc. The remaining coauthors had no disclosures.

Dr. Clark had no disclosures.

The improved Los Angeles medical dispatch system prompted more callers with limited English proficiency to initiate telecommunicator-assisted cardiopulmonary resuscitation (T-CPR), compared with the previous system, a new study shows.

Chalabala/iStock/Getty Images Plus

The Los Angeles Tiered Dispatch System (LA-TDS), adopted in late 2014, used simplified questions aimed at identifying cardiac arrest, compared with the city’s earlier Medical Priority Dispatch System (MPDS).

The result was substantially decreased call processing times, decreased “undertriage” of out-of-hospital cardiac arrest (OHCA), and improved overall T-CPR rates (Resuscitation. 2020 Oct;155:74-81).

But now, a secondary analysis of the data shows there was a much higher jump in T-CPR rates among a small subset of callers with limited English proficiency, compared with those proficient in English (JAMA Network Open. 2021;4[6]:e216827).

“This was an unanticipated, significant, and disproportionate change, but fortunately a very good change,” lead author Stephen Sanko, MD, said in an interview.

While the T-CPR rate among English-proficient callers increased from 55% with the MPDS to 67% with the LA-TDS (odds ratio, 1.66; P = .007), it rose from 28% to 69% (OR, 5.66; P = .003) among callers with limited English proficiency. In the adjusted analysis, the new LA-TDS was associated with a 69% higher prevalence of T-CPR among English-proficient callers, compared with a 350% greater prevalence among callers with limited English proficiency.

“The emergency communication process between a caller and 911 telecommunicator is more complex than we thought, and likely constitutes a unique subsubspecialty that interacts with fields as diverse as medicine, health equity, linguistics, sociology, consumer behavior and others,” said Dr. Sanko, who is from the division of emergency medical services at the University of Southern California in Los Angeles.

“Yet in spite of this complexity, we’re starting to be able to reproducibly classify elements of the emergency conversation that we believe are tied to outcomes we all care about. ... Modulators of health disparities are present as early as the dispatch conversation, and, importantly, they can be intervened upon to promote improved outcomes,” he continued.

The retrospective cohort study was a predefined secondary analysis of a previously published study comparing telecommunicator management of out-of-hospital cardiac arrest over 3 months with the MPDS versus 3 months with the LA-TDS. The primary outcome was the number of patients who received telecommunicator-assisted chest compressions from callers with limited English proficiency.

Of the 597 emergency calls that met the inclusion criteria, 289 (48%) were in the MPDS cohort and 308 (52%) were in the LA-TDS cohort. In the MPDS cohort, 263 callers had English proficiency and 26 had limited proficiency; in the latter cohort, those figures were 273 and 35, respectively.

There were no significant differences between cohorts in the use of real-time translation services, which were employed 27%-31% of the time.

The reason for the overall T-CPR improvement is likely that the LA-TDS was tailored to the community needs, said Dr. Sanko. “Most people, including doctors, think of 911 dispatch as something simple and straightforward, like ordering a pizza or calling a ride share. [But] LA-TDS is a ‘home grown’ dispatch system whose structure, questions, and emergency instructions were all developed by EMS medical directors and telecommunicators with extensive experience in our community.”

That being said, the researchers acknowledge that the reason behind the bigger T-CPR boost in LEP callers remains unclear. Although the link between language and system was statistically significant, they noted “it was not an a priori hypothesis and appeared to be largely attributable to the low T-CPR rates for callers with limited English proficiency using MPDS.” Additionally, such callers were “remarkably under-represented” in the sample, “which included approximately 600 calls over two quarters in a large city,” said Dr Sanko.

“We hypothesize that a more direct structure, earlier commitment to treating patients with abnormal life status indicators as being suspected cardiac arrest cases, and earlier reassurance may have improved caller confidence that telecommunicators knew what they were doing. This in turn may have translated into an increased likelihood of bystander caller willingness to perform immediate life-saving maneuvers.”

Despite a number of limitations, “the study is important and highlights instructive topics for discussion that suggest potential next-step opportunities,” noted Richard Chocron, MD, PhD, Miranda Lewis, MD, and Thomas Rea, MD, MPH, in an invited commentary that accompanied the publication. Dr. Chocron is from the Paris University, Paris Research Cardiovascular Center, INSERM; Dr. Lewis is from the Georges Pompidou European Hospital in Paris; and Dr. Rea is from the Division of Emergency Medical Services, Public Health–Seattle & King County. Both Dr. Lewis and Dr. Rea are also at the University of Washington, Seattle.

“Sanko et al. found that approximately 10% of all emergency calls were classified as limited English proficiency calls in a community in which 19% of the population was considered to have limited English proficiency,” they added. “This finding suggests the possibility that populations with limited English proficiency are less likely to activate 911 for incidence of cardiac arrest. If true, this finding would compound the health disparity observed among those with limited English proficiency. This topic is important in that it transcends the role of EMS personnel and engages a broad spectrum of societal stakeholders. We must listen, learn, and ultimately deliver public safety resources to groups who have not been well served by conventional approaches.”

None of the authors or editorialists reported any conflicts of interest.

The improved Los Angeles medical dispatch system prompted more callers with limited English proficiency to initiate telecommunicator-assisted cardiopulmonary resuscitation (T-CPR), compared with the previous system, a new study shows.

Chalabala/iStock/Getty Images Plus

The Los Angeles Tiered Dispatch System (LA-TDS), adopted in late 2014, used simplified questions aimed at identifying cardiac arrest, compared with the city’s earlier Medical Priority Dispatch System (MPDS).

The result was substantially decreased call processing times, decreased “undertriage” of out-of-hospital cardiac arrest (OHCA), and improved overall T-CPR rates (Resuscitation. 2020 Oct;155:74-81).

But now, a secondary analysis of the data shows there was a much higher jump in T-CPR rates among a small subset of callers with limited English proficiency, compared with those proficient in English (JAMA Network Open. 2021;4[6]:e216827).

“This was an unanticipated, significant, and disproportionate change, but fortunately a very good change,” lead author Stephen Sanko, MD, said in an interview.

While the T-CPR rate among English-proficient callers increased from 55% with the MPDS to 67% with the LA-TDS (odds ratio, 1.66; P = .007), it rose from 28% to 69% (OR, 5.66; P = .003) among callers with limited English proficiency. In the adjusted analysis, the new LA-TDS was associated with a 69% higher prevalence of T-CPR among English-proficient callers, compared with a 350% greater prevalence among callers with limited English proficiency.

“The emergency communication process between a caller and 911 telecommunicator is more complex than we thought, and likely constitutes a unique subsubspecialty that interacts with fields as diverse as medicine, health equity, linguistics, sociology, consumer behavior and others,” said Dr. Sanko, who is from the division of emergency medical services at the University of Southern California in Los Angeles.

“Yet in spite of this complexity, we’re starting to be able to reproducibly classify elements of the emergency conversation that we believe are tied to outcomes we all care about. ... Modulators of health disparities are present as early as the dispatch conversation, and, importantly, they can be intervened upon to promote improved outcomes,” he continued.

The retrospective cohort study was a predefined secondary analysis of a previously published study comparing telecommunicator management of out-of-hospital cardiac arrest over 3 months with the MPDS versus 3 months with the LA-TDS. The primary outcome was the number of patients who received telecommunicator-assisted chest compressions from callers with limited English proficiency.

Of the 597 emergency calls that met the inclusion criteria, 289 (48%) were in the MPDS cohort and 308 (52%) were in the LA-TDS cohort. In the MPDS cohort, 263 callers had English proficiency and 26 had limited proficiency; in the latter cohort, those figures were 273 and 35, respectively.

There were no significant differences between cohorts in the use of real-time translation services, which were employed 27%-31% of the time.

The reason for the overall T-CPR improvement is likely that the LA-TDS was tailored to the community needs, said Dr. Sanko. “Most people, including doctors, think of 911 dispatch as something simple and straightforward, like ordering a pizza or calling a ride share. [But] LA-TDS is a ‘home grown’ dispatch system whose structure, questions, and emergency instructions were all developed by EMS medical directors and telecommunicators with extensive experience in our community.”

That being said, the researchers acknowledge that the reason behind the bigger T-CPR boost in LEP callers remains unclear. Although the link between language and system was statistically significant, they noted “it was not an a priori hypothesis and appeared to be largely attributable to the low T-CPR rates for callers with limited English proficiency using MPDS.” Additionally, such callers were “remarkably under-represented” in the sample, “which included approximately 600 calls over two quarters in a large city,” said Dr Sanko.

“We hypothesize that a more direct structure, earlier commitment to treating patients with abnormal life status indicators as being suspected cardiac arrest cases, and earlier reassurance may have improved caller confidence that telecommunicators knew what they were doing. This in turn may have translated into an increased likelihood of bystander caller willingness to perform immediate life-saving maneuvers.”

Despite a number of limitations, “the study is important and highlights instructive topics for discussion that suggest potential next-step opportunities,” noted Richard Chocron, MD, PhD, Miranda Lewis, MD, and Thomas Rea, MD, MPH, in an invited commentary that accompanied the publication. Dr. Chocron is from the Paris University, Paris Research Cardiovascular Center, INSERM; Dr. Lewis is from the Georges Pompidou European Hospital in Paris; and Dr. Rea is from the Division of Emergency Medical Services, Public Health–Seattle & King County. Both Dr. Lewis and Dr. Rea are also at the University of Washington, Seattle.

“Sanko et al. found that approximately 10% of all emergency calls were classified as limited English proficiency calls in a community in which 19% of the population was considered to have limited English proficiency,” they added. “This finding suggests the possibility that populations with limited English proficiency are less likely to activate 911 for incidence of cardiac arrest. If true, this finding would compound the health disparity observed among those with limited English proficiency. This topic is important in that it transcends the role of EMS personnel and engages a broad spectrum of societal stakeholders. We must listen, learn, and ultimately deliver public safety resources to groups who have not been well served by conventional approaches.”

None of the authors or editorialists reported any conflicts of interest.

The improved Los Angeles medical dispatch system prompted more callers with limited English proficiency to initiate telecommunicator-assisted cardiopulmonary resuscitation (T-CPR), compared with the previous system, a new study shows.

Chalabala/iStock/Getty Images Plus

The Los Angeles Tiered Dispatch System (LA-TDS), adopted in late 2014, used simplified questions aimed at identifying cardiac arrest, compared with the city’s earlier Medical Priority Dispatch System (MPDS).

The result was substantially decreased call processing times, decreased “undertriage” of out-of-hospital cardiac arrest (OHCA), and improved overall T-CPR rates (Resuscitation. 2020 Oct;155:74-81).

But now, a secondary analysis of the data shows there was a much higher jump in T-CPR rates among a small subset of callers with limited English proficiency, compared with those proficient in English (JAMA Network Open. 2021;4[6]:e216827).

“This was an unanticipated, significant, and disproportionate change, but fortunately a very good change,” lead author Stephen Sanko, MD, said in an interview.

While the T-CPR rate among English-proficient callers increased from 55% with the MPDS to 67% with the LA-TDS (odds ratio, 1.66; P = .007), it rose from 28% to 69% (OR, 5.66; P = .003) among callers with limited English proficiency. In the adjusted analysis, the new LA-TDS was associated with a 69% higher prevalence of T-CPR among English-proficient callers, compared with a 350% greater prevalence among callers with limited English proficiency.

“The emergency communication process between a caller and 911 telecommunicator is more complex than we thought, and likely constitutes a unique subsubspecialty that interacts with fields as diverse as medicine, health equity, linguistics, sociology, consumer behavior and others,” said Dr. Sanko, who is from the division of emergency medical services at the University of Southern California in Los Angeles.

“Yet in spite of this complexity, we’re starting to be able to reproducibly classify elements of the emergency conversation that we believe are tied to outcomes we all care about. ... Modulators of health disparities are present as early as the dispatch conversation, and, importantly, they can be intervened upon to promote improved outcomes,” he continued.

The retrospective cohort study was a predefined secondary analysis of a previously published study comparing telecommunicator management of out-of-hospital cardiac arrest over 3 months with the MPDS versus 3 months with the LA-TDS. The primary outcome was the number of patients who received telecommunicator-assisted chest compressions from callers with limited English proficiency.

Of the 597 emergency calls that met the inclusion criteria, 289 (48%) were in the MPDS cohort and 308 (52%) were in the LA-TDS cohort. In the MPDS cohort, 263 callers had English proficiency and 26 had limited proficiency; in the latter cohort, those figures were 273 and 35, respectively.

There were no significant differences between cohorts in the use of real-time translation services, which were employed 27%-31% of the time.

The reason for the overall T-CPR improvement is likely that the LA-TDS was tailored to the community needs, said Dr. Sanko. “Most people, including doctors, think of 911 dispatch as something simple and straightforward, like ordering a pizza or calling a ride share. [But] LA-TDS is a ‘home grown’ dispatch system whose structure, questions, and emergency instructions were all developed by EMS medical directors and telecommunicators with extensive experience in our community.”

That being said, the researchers acknowledge that the reason behind the bigger T-CPR boost in LEP callers remains unclear. Although the link between language and system was statistically significant, they noted “it was not an a priori hypothesis and appeared to be largely attributable to the low T-CPR rates for callers with limited English proficiency using MPDS.” Additionally, such callers were “remarkably under-represented” in the sample, “which included approximately 600 calls over two quarters in a large city,” said Dr Sanko.

“We hypothesize that a more direct structure, earlier commitment to treating patients with abnormal life status indicators as being suspected cardiac arrest cases, and earlier reassurance may have improved caller confidence that telecommunicators knew what they were doing. This in turn may have translated into an increased likelihood of bystander caller willingness to perform immediate life-saving maneuvers.”

Despite a number of limitations, “the study is important and highlights instructive topics for discussion that suggest potential next-step opportunities,” noted Richard Chocron, MD, PhD, Miranda Lewis, MD, and Thomas Rea, MD, MPH, in an invited commentary that accompanied the publication. Dr. Chocron is from the Paris University, Paris Research Cardiovascular Center, INSERM; Dr. Lewis is from the Georges Pompidou European Hospital in Paris; and Dr. Rea is from the Division of Emergency Medical Services, Public Health–Seattle & King County. Both Dr. Lewis and Dr. Rea are also at the University of Washington, Seattle.

“Sanko et al. found that approximately 10% of all emergency calls were classified as limited English proficiency calls in a community in which 19% of the population was considered to have limited English proficiency,” they added. “This finding suggests the possibility that populations with limited English proficiency are less likely to activate 911 for incidence of cardiac arrest. If true, this finding would compound the health disparity observed among those with limited English proficiency. This topic is important in that it transcends the role of EMS personnel and engages a broad spectrum of societal stakeholders. We must listen, learn, and ultimately deliver public safety resources to groups who have not been well served by conventional approaches.”

None of the authors or editorialists reported any conflicts of interest.

Researchers have discovered a new dopaminergic neural circuit leading to the hindbrain that is involved in satiety (feeling full and eating cessation) in mice, which may eventually lead to new ways to treat obesity.

Moreover, when mice were given methylphenidate (Ritalin, Concerta) – a stimulant approved to treat attention deficit hyperactivity disorder (ADHD) with a well-known side effect of decreasing appetite – signals in this dopaminergic pathway were enhanced and the mice ate less.

The study by Yong Han, PhD, a postdoctoral associate at Baylor College of Medicine, Houston, and colleagues was published online May 27 in Science Advances.

“We identified a new dopamine neural circuit from the midbrain to the hindbrain (brainstem) that regulates feeding behavior through an enhanced satiation response,” senior author Qi Wu, PhD, assistant professor in pediatrics-nutrition at Baylor College of Medicine, summarized in an interview.

The findings suggest that “people with obesity have a compromised dopaminergic neural pathway, presumably in ways that delay the satiation response, which makes them eat more, have a larger meal,” he explained.
 

Newly identified brain circuit plays a key role in satiety response

The study is about a circuit in the brain that helps precisely regulate the size of food portion consumed, Dr. Wu emphasized in a statement from the university, adding that the satiation response is as important as appetite.

Importantly, the results also provide clues about how methylphenidate can lead to weight loss.  

Regulators have deemed that methylphenidate, a controlled substance with other side effects such as anxiety and a fast heart rate, is safe and effective for ADHD, Dr. Wu noted.

He speculated that, “If researchers want to do clinical trials of methylphenidate for obesity, it ultimately could evolve to be an anti-obesity drug, alone or combined with other drugs, or possibly derivatives of methylphenidate could be tested.”

The brain circuit “we discovered is the first to be fully described to regulate portion size via dopamine signaling,” Dr. Han stressed in the statement.

“Our new study shows that a circuit connecting neurons that produce dopamine, a chemical messenger previously known for the regulation of motivation and pleasure, has a new [critical] role in the control of feeding through dynamically regulating the satiety response,” he explained.
 

Brain signals that control portion size 

Earlier studies that investigated how the dopaminergic system may regulate food intake, appetite, and body weight, have produced conflicting results, Dr. Wu said.

The researchers performed several experiments in mice that included the use of cell-specific circuitry mapping, optogenetics, and real-time recordings of brain activity.

They identified a new dopaminergic neural circuit comprised of dopaminergic neurons in the caudal ventral tegmental area (DA-VTA neurons) in the midbrain that directly innervate dopamine receptor D1-expressing neurons within the lateral parabrachial nucleus (DRD1-LPBN neurons) in the hindbrain.

There were four main findings:

• DA-VTA neurons were activated immediately before the cessation of each feeding bout.
• Actively inhibiting DA-VTA neurons before the end of each feeding bout prolonged the feeding.
• Activating DRD1-LPBN neurons inhibited feeding.
• Mice that lacked the DRD1 gene ate much more and gained weight.

“Our study illuminates a hindbrain dopaminergic circuit that controls feeding through dynamic regulation in satiety response and meal structure,” the researchers reiterate.

The study was supported by grants from the National Institutes of Health, NIH Digestive Diseases Center, Pew Charitable Trust, American Diabetes Association, Baylor Collaborative Faculty Research Investment Program, USDA/CRIS, USDA/ARS, American Heart Association, and NIH Centers of Biomedical Research Excellence, and by Pew and Kavli scholarships. The researchers have reported no relevant financial disclosures. 

A version of this article first appeared on Medscape.com.

Researchers have discovered a new dopaminergic neural circuit leading to the hindbrain that is involved in satiety (feeling full and eating cessation) in mice, which may eventually lead to new ways to treat obesity.

Moreover, when mice were given methylphenidate (Ritalin, Concerta) – a stimulant approved to treat attention deficit hyperactivity disorder (ADHD) with a well-known side effect of decreasing appetite – signals in this dopaminergic pathway were enhanced and the mice ate less.

The study by Yong Han, PhD, a postdoctoral associate at Baylor College of Medicine, Houston, and colleagues was published online May 27 in Science Advances.

“We identified a new dopamine neural circuit from the midbrain to the hindbrain (brainstem) that regulates feeding behavior through an enhanced satiation response,” senior author Qi Wu, PhD, assistant professor in pediatrics-nutrition at Baylor College of Medicine, summarized in an interview.

The findings suggest that “people with obesity have a compromised dopaminergic neural pathway, presumably in ways that delay the satiation response, which makes them eat more, have a larger meal,” he explained.
 

Newly identified brain circuit plays a key role in satiety response

The study is about a circuit in the brain that helps precisely regulate the size of food portion consumed, Dr. Wu emphasized in a statement from the university, adding that the satiation response is as important as appetite.

Importantly, the results also provide clues about how methylphenidate can lead to weight loss.  

Regulators have deemed that methylphenidate, a controlled substance with other side effects such as anxiety and a fast heart rate, is safe and effective for ADHD, Dr. Wu noted.

He speculated that, “If researchers want to do clinical trials of methylphenidate for obesity, it ultimately could evolve to be an anti-obesity drug, alone or combined with other drugs, or possibly derivatives of methylphenidate could be tested.”

The brain circuit “we discovered is the first to be fully described to regulate portion size via dopamine signaling,” Dr. Han stressed in the statement.

“Our new study shows that a circuit connecting neurons that produce dopamine, a chemical messenger previously known for the regulation of motivation and pleasure, has a new [critical] role in the control of feeding through dynamically regulating the satiety response,” he explained.
 

Brain signals that control portion size 

Earlier studies that investigated how the dopaminergic system may regulate food intake, appetite, and body weight, have produced conflicting results, Dr. Wu said.

The researchers performed several experiments in mice that included the use of cell-specific circuitry mapping, optogenetics, and real-time recordings of brain activity.

They identified a new dopaminergic neural circuit comprised of dopaminergic neurons in the caudal ventral tegmental area (DA-VTA neurons) in the midbrain that directly innervate dopamine receptor D1-expressing neurons within the lateral parabrachial nucleus (DRD1-LPBN neurons) in the hindbrain.

There were four main findings:

• DA-VTA neurons were activated immediately before the cessation of each feeding bout.
• Actively inhibiting DA-VTA neurons before the end of each feeding bout prolonged the feeding.
• Activating DRD1-LPBN neurons inhibited feeding.
• Mice that lacked the DRD1 gene ate much more and gained weight.

“Our study illuminates a hindbrain dopaminergic circuit that controls feeding through dynamic regulation in satiety response and meal structure,” the researchers reiterate.

The study was supported by grants from the National Institutes of Health, NIH Digestive Diseases Center, Pew Charitable Trust, American Diabetes Association, Baylor Collaborative Faculty Research Investment Program, USDA/CRIS, USDA/ARS, American Heart Association, and NIH Centers of Biomedical Research Excellence, and by Pew and Kavli scholarships. The researchers have reported no relevant financial disclosures. 

A version of this article first appeared on Medscape.com.

Researchers have discovered a new dopaminergic neural circuit leading to the hindbrain that is involved in satiety (feeling full and eating cessation) in mice, which may eventually lead to new ways to treat obesity.

Moreover, when mice were given methylphenidate (Ritalin, Concerta) – a stimulant approved to treat attention deficit hyperactivity disorder (ADHD) with a well-known side effect of decreasing appetite – signals in this dopaminergic pathway were enhanced and the mice ate less.

The study by Yong Han, PhD, a postdoctoral associate at Baylor College of Medicine, Houston, and colleagues was published online May 27 in Science Advances.

“We identified a new dopamine neural circuit from the midbrain to the hindbrain (brainstem) that regulates feeding behavior through an enhanced satiation response,” senior author Qi Wu, PhD, assistant professor in pediatrics-nutrition at Baylor College of Medicine, summarized in an interview.

The findings suggest that “people with obesity have a compromised dopaminergic neural pathway, presumably in ways that delay the satiation response, which makes them eat more, have a larger meal,” he explained.
 

Newly identified brain circuit plays a key role in satiety response

The study is about a circuit in the brain that helps precisely regulate the size of food portion consumed, Dr. Wu emphasized in a statement from the university, adding that the satiation response is as important as appetite.

Importantly, the results also provide clues about how methylphenidate can lead to weight loss.  

Regulators have deemed that methylphenidate, a controlled substance with other side effects such as anxiety and a fast heart rate, is safe and effective for ADHD, Dr. Wu noted.

He speculated that, “If researchers want to do clinical trials of methylphenidate for obesity, it ultimately could evolve to be an anti-obesity drug, alone or combined with other drugs, or possibly derivatives of methylphenidate could be tested.”

The brain circuit “we discovered is the first to be fully described to regulate portion size via dopamine signaling,” Dr. Han stressed in the statement.

“Our new study shows that a circuit connecting neurons that produce dopamine, a chemical messenger previously known for the regulation of motivation and pleasure, has a new [critical] role in the control of feeding through dynamically regulating the satiety response,” he explained.
 

Brain signals that control portion size 

Earlier studies that investigated how the dopaminergic system may regulate food intake, appetite, and body weight, have produced conflicting results, Dr. Wu said.

The researchers performed several experiments in mice that included the use of cell-specific circuitry mapping, optogenetics, and real-time recordings of brain activity.

They identified a new dopaminergic neural circuit comprised of dopaminergic neurons in the caudal ventral tegmental area (DA-VTA neurons) in the midbrain that directly innervate dopamine receptor D1-expressing neurons within the lateral parabrachial nucleus (DRD1-LPBN neurons) in the hindbrain.

There were four main findings:

• DA-VTA neurons were activated immediately before the cessation of each feeding bout.
• Actively inhibiting DA-VTA neurons before the end of each feeding bout prolonged the feeding.
• Activating DRD1-LPBN neurons inhibited feeding.
• Mice that lacked the DRD1 gene ate much more and gained weight.

“Our study illuminates a hindbrain dopaminergic circuit that controls feeding through dynamic regulation in satiety response and meal structure,” the researchers reiterate.

The study was supported by grants from the National Institutes of Health, NIH Digestive Diseases Center, Pew Charitable Trust, American Diabetes Association, Baylor Collaborative Faculty Research Investment Program, USDA/CRIS, USDA/ARS, American Heart Association, and NIH Centers of Biomedical Research Excellence, and by Pew and Kavli scholarships. The researchers have reported no relevant financial disclosures. 

A version of this article first appeared on Medscape.com.

Hemoglobin A1c above 5% but below the prediabetes cutoff of 5.5% is an additional potential biomarker of subclinical atherosclerosis in people with low cardiovascular disease risk, according to an analysis of data on almost 4,000 middle-aged individuals.

Mount Sinai Heart/CCA 3.0

“If one looks at the incidence of generalized subclinical atherosclerosis, we are not talking small numbers,” senior study author Valentin Fuster, MD, PhD, said in an interview. “We are talking about between 45% and 82% of this middle-age population that already has atherosclerotic disease subclinically.

“Actually,” he added, “the disease was extensive in 5%-30% of these individuals of middle age.”

The study included 3,973 participants from the Progression of Early Subclinical Atherosclerosis study who did not have diabetes. A1c showed an association with the prevalence and multiterritorial extent of subclinical atherosclerosis as measured by two-dimensional ultrasound and coronary artery calcium score (CACS; P < .001). For example, those with A1c above 6.1% (133 participants) had a 33.1% rate of generalized subclinical atherosclerosis, compared with 4.9% for those with A1c below 4.8% (243), the lowest-score group in the study.

Patients in the subprediabetes band, between 5.0% and 5.5%, had significantly higher rates of generalized subclinical atherosclerosis than did the lowest-score group: 8% in the 4.9%-5.0% group (375 participants); 9.9% in the 5.1%-5.2% range (687); 10.3% in the 5.3%-5.4% group (928); and 11.5% in the 5.5%-5.6% group (842).

Those in the 5.1%-5.2% and 5/3%-5.4% A1c groups had a 27% greater chance of having subclinical atherosclerosis, while those in the 5.5%-5.6% group had a 36% greater risk, according to an odds ratio analysis adjusted for established cardiovascular risk factors. The risks were even higher for patients with prediabetes, the researchers reported in the Journal of the American College of Cardiology.
 

A call for earlier intervention

Notably, the study found that fasting plasma glucose testing did not yield a similar association between A1c and atherosclerosis.

“The message is that we all talk about people when they are close to the development of cardiovascular events, and here we are talking about people who we should pay attention to much earlier,” said Dr. Fuster, physician-in-chief at Icahn School of Medicine at Mount Sinai in New York and director of the National Center for Cardiovascular Investigation in Madrid, where the observational study originated said. “People should be sensitized to HbA1c much more than they would’ve been in the past, and I think this study actually validates that.”

Christie Ballantyne, MD, noted in an interview that these findings support the utility of A1c for predicting CVD risk.

“I think more and more we should be ordering a HbA1c” during routine physical exams, Dr. Ballantyne said. “You don’t have to be obese to get it; there are lots of people, maybe they’re slightly overweight. It’s a reasonable test to be getting when you get to middle age and older to get an idea for assessing for both developing diabetes and also the presence of atherosclerosis and the risk for having cardiovascular events.”

Dr. Ballantyne, chief of cardiology at Baylor College of Medicine and director of cardiovascular disease prevention at Methodist DeBakey Heart Center in Houston, coauthored an editorial comment on the study.

Clinicians typically start to manage CVD and diabetes risk “late in the process,” Dr. Ballantyne said. This study suggested that earlier use of antidiabetes therapies, namely peptide-1 agonists and semisynthetic glucagon-like peptide-2 inhibitors, may be warranted in patients with intermediate risk of CVD.

“It’s just more data for the rationale that, perhaps we could end up doing trials to show we can take high-risk people and prevent them from getting both heart disease and diabetes,” Dr. Ballantyne added. “Could we start a little earlier with better precision?”

These finding don’t yet call for a change in how cardiologists and endocrinologists manage patients on the cusp of prediabetes, said Paul S. Jellinger, MD, of Hollywood, Fla., and a professor at the University of Miami. “The endpoint of subclinical atherosclerosis does not necessarily translate into the harder endpoint of CVD events, although there is certainly reason to believe it does,” he said in an interview, noting that he’s often used CACS to stratify atherosclerotic CVD risk in patients.

Hemoglobin A1c above 5% but below the prediabetes cutoff of 5.5% is an additional potential biomarker of subclinical atherosclerosis in people with low cardiovascular disease risk, according to an analysis of data on almost 4,000 middle-aged individuals.

Mount Sinai Heart/CCA 3.0

“If one looks at the incidence of generalized subclinical atherosclerosis, we are not talking small numbers,” senior study author Valentin Fuster, MD, PhD, said in an interview. “We are talking about between 45% and 82% of this middle-age population that already has atherosclerotic disease subclinically.

“Actually,” he added, “the disease was extensive in 5%-30% of these individuals of middle age.”

The study included 3,973 participants from the Progression of Early Subclinical Atherosclerosis study who did not have diabetes. A1c showed an association with the prevalence and multiterritorial extent of subclinical atherosclerosis as measured by two-dimensional ultrasound and coronary artery calcium score (CACS; P < .001). For example, those with A1c above 6.1% (133 participants) had a 33.1% rate of generalized subclinical atherosclerosis, compared with 4.9% for those with A1c below 4.8% (243), the lowest-score group in the study.

Patients in the subprediabetes band, between 5.0% and 5.5%, had significantly higher rates of generalized subclinical atherosclerosis than did the lowest-score group: 8% in the 4.9%-5.0% group (375 participants); 9.9% in the 5.1%-5.2% range (687); 10.3% in the 5.3%-5.4% group (928); and 11.5% in the 5.5%-5.6% group (842).

Those in the 5.1%-5.2% and 5/3%-5.4% A1c groups had a 27% greater chance of having subclinical atherosclerosis, while those in the 5.5%-5.6% group had a 36% greater risk, according to an odds ratio analysis adjusted for established cardiovascular risk factors. The risks were even higher for patients with prediabetes, the researchers reported in the Journal of the American College of Cardiology.
 

A call for earlier intervention

Notably, the study found that fasting plasma glucose testing did not yield a similar association between A1c and atherosclerosis.

“The message is that we all talk about people when they are close to the development of cardiovascular events, and here we are talking about people who we should pay attention to much earlier,” said Dr. Fuster, physician-in-chief at Icahn School of Medicine at Mount Sinai in New York and director of the National Center for Cardiovascular Investigation in Madrid, where the observational study originated said. “People should be sensitized to HbA1c much more than they would’ve been in the past, and I think this study actually validates that.”

Christie Ballantyne, MD, noted in an interview that these findings support the utility of A1c for predicting CVD risk.

“I think more and more we should be ordering a HbA1c” during routine physical exams, Dr. Ballantyne said. “You don’t have to be obese to get it; there are lots of people, maybe they’re slightly overweight. It’s a reasonable test to be getting when you get to middle age and older to get an idea for assessing for both developing diabetes and also the presence of atherosclerosis and the risk for having cardiovascular events.”

Dr. Ballantyne, chief of cardiology at Baylor College of Medicine and director of cardiovascular disease prevention at Methodist DeBakey Heart Center in Houston, coauthored an editorial comment on the study.

Clinicians typically start to manage CVD and diabetes risk “late in the process,” Dr. Ballantyne said. This study suggested that earlier use of antidiabetes therapies, namely peptide-1 agonists and semisynthetic glucagon-like peptide-2 inhibitors, may be warranted in patients with intermediate risk of CVD.

“It’s just more data for the rationale that, perhaps we could end up doing trials to show we can take high-risk people and prevent them from getting both heart disease and diabetes,” Dr. Ballantyne added. “Could we start a little earlier with better precision?”

These finding don’t yet call for a change in how cardiologists and endocrinologists manage patients on the cusp of prediabetes, said Paul S. Jellinger, MD, of Hollywood, Fla., and a professor at the University of Miami. “The endpoint of subclinical atherosclerosis does not necessarily translate into the harder endpoint of CVD events, although there is certainly reason to believe it does,” he said in an interview, noting that he’s often used CACS to stratify atherosclerotic CVD risk in patients.

Hemoglobin A1c above 5% but below the prediabetes cutoff of 5.5% is an additional potential biomarker of subclinical atherosclerosis in people with low cardiovascular disease risk, according to an analysis of data on almost 4,000 middle-aged individuals.

Mount Sinai Heart/CCA 3.0

“If one looks at the incidence of generalized subclinical atherosclerosis, we are not talking small numbers,” senior study author Valentin Fuster, MD, PhD, said in an interview. “We are talking about between 45% and 82% of this middle-age population that already has atherosclerotic disease subclinically.

“Actually,” he added, “the disease was extensive in 5%-30% of these individuals of middle age.”

The study included 3,973 participants from the Progression of Early Subclinical Atherosclerosis study who did not have diabetes. A1c showed an association with the prevalence and multiterritorial extent of subclinical atherosclerosis as measured by two-dimensional ultrasound and coronary artery calcium score (CACS; P < .001). For example, those with A1c above 6.1% (133 participants) had a 33.1% rate of generalized subclinical atherosclerosis, compared with 4.9% for those with A1c below 4.8% (243), the lowest-score group in the study.

Patients in the subprediabetes band, between 5.0% and 5.5%, had significantly higher rates of generalized subclinical atherosclerosis than did the lowest-score group: 8% in the 4.9%-5.0% group (375 participants); 9.9% in the 5.1%-5.2% range (687); 10.3% in the 5.3%-5.4% group (928); and 11.5% in the 5.5%-5.6% group (842).

Those in the 5.1%-5.2% and 5/3%-5.4% A1c groups had a 27% greater chance of having subclinical atherosclerosis, while those in the 5.5%-5.6% group had a 36% greater risk, according to an odds ratio analysis adjusted for established cardiovascular risk factors. The risks were even higher for patients with prediabetes, the researchers reported in the Journal of the American College of Cardiology.
 

A call for earlier intervention

Notably, the study found that fasting plasma glucose testing did not yield a similar association between A1c and atherosclerosis.

“The message is that we all talk about people when they are close to the development of cardiovascular events, and here we are talking about people who we should pay attention to much earlier,” said Dr. Fuster, physician-in-chief at Icahn School of Medicine at Mount Sinai in New York and director of the National Center for Cardiovascular Investigation in Madrid, where the observational study originated said. “People should be sensitized to HbA1c much more than they would’ve been in the past, and I think this study actually validates that.”

Christie Ballantyne, MD, noted in an interview that these findings support the utility of A1c for predicting CVD risk.

“I think more and more we should be ordering a HbA1c” during routine physical exams, Dr. Ballantyne said. “You don’t have to be obese to get it; there are lots of people, maybe they’re slightly overweight. It’s a reasonable test to be getting when you get to middle age and older to get an idea for assessing for both developing diabetes and also the presence of atherosclerosis and the risk for having cardiovascular events.”

Dr. Ballantyne, chief of cardiology at Baylor College of Medicine and director of cardiovascular disease prevention at Methodist DeBakey Heart Center in Houston, coauthored an editorial comment on the study.

Clinicians typically start to manage CVD and diabetes risk “late in the process,” Dr. Ballantyne said. This study suggested that earlier use of antidiabetes therapies, namely peptide-1 agonists and semisynthetic glucagon-like peptide-2 inhibitors, may be warranted in patients with intermediate risk of CVD.

“It’s just more data for the rationale that, perhaps we could end up doing trials to show we can take high-risk people and prevent them from getting both heart disease and diabetes,” Dr. Ballantyne added. “Could we start a little earlier with better precision?”

These finding don’t yet call for a change in how cardiologists and endocrinologists manage patients on the cusp of prediabetes, said Paul S. Jellinger, MD, of Hollywood, Fla., and a professor at the University of Miami. “The endpoint of subclinical atherosclerosis does not necessarily translate into the harder endpoint of CVD events, although there is certainly reason to believe it does,” he said in an interview, noting that he’s often used CACS to stratify atherosclerotic CVD risk in patients.

Taking more steps each day, in short spurts or longer bouts, was associated with a longer life in women older than 60 years, according to data from more than 16,000 participants in the ongoing Women’s Health Study.

The American Heart Association recommends at least 150 minutes per week of moderate physical activity, 75 minutes of vigorous physical activity, or a combination of both as fitness guidelines for adults. Walking is a safe and easy way for many adults to follow these guidelines, according to Christopher C. Moore, MS, a PhD candidate at the University of North Carolina at Chapel Hill.

The popularity of step counts reflect that they are simple and objective, and “focusing on steps can help promote an active lifestyle,” he said. Data on the impact of sporadic steps accumulated outside of longer bouts of activity on health outcomes are limited; however, technology advances in the form of fitness apps and wearable devices make it possible for researchers to track and measure the benefits of short periods of activity as well as longer periods.

In a study presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting, sponsored by the AHA, Mr. Moore and colleagues assessed data from women older than 60 years who used wearable step-counting devices to measure their daily steps and walking patterns.

The study population included 16,732 women enrolled in the Women’s Health Study, a longstanding study of heart disease, cancer, and disease prevention among women in the United States. The participants wore waist step counters 4-7 days a week during 2011-2015. The average of the women was 72 years; 96% were non-Hispanic White, and the average BMI was 26 kg/m².

The researchers divided the total number of steps for each study participant into two groups: “bouted” steps, defined as 10 minutes or longer bouts of walking with few interruptions; and “sporadic” steps, defined as short spurts of walking during regular daily activities such as housework, taking the stairs, or walking to or from a car.

A total of 804 deaths occurred during an average of 6 years of follow-up. Each initial increase of 1,000 steps including sporadic or bouted steps was associated with a 28% decrease in death, compared with no daily steps (hazard ratio, 0.72).

Each increasing quartile of sporadic steps was linked with higher total steps per day, Mr. Moore said. “Initial increase in sporadic steps corresponded to the greatest reductions in mortality,” with a HR of 0.69 per additional sporadic steps below 3,200 per day, and the impact on reduced mortality plateaued at about 4,500 sporadic steps per day.

In further analysis, the researchers also found a roughly 32% decrease in death in participants who took more than 2,000 steps daily in uninterrupted bouts (HR, 0.69).

The study findings were limited by several factors, including the relatively short follow-up period and number of events, the assessment of steps at a single time point, and the mostly homogeneous population, Mr. Moore noted. Additional research is needed to assess whether the results are generalizable to men, younger women, and diverse racial and ethnic groups.

However, the results may have implications for public health messaging, he emphasized. The message is that, to impact longevity, the total volume of steps is more important than the type of activity through which they are accumulated.

“You can accumulate your steps through longer bouts of purposeful activity or through everyday behaviors such as walking to your car, taking the stairs, and doing housework,” Mr. Moore concluded.

Find a friend, both of you benefit

On the basis of this study and other available evidence, more steps daily are recommended for everyone, Nieca Goldberg, MD, a cardiologist at New York University Langone Health, said in an interview.

“You can increase minutes of walking and frequency of walking,” she said.

Dr. Goldberg emphasized that you don’t need a fancy app or wearable device to up your steps. She offered some tips to help overcome barriers to putting one foot in front of the other. “Take the steps instead of the elevator. Park your car farther from your destination so you can walk.” Also, you can help yourself and help a friend to better health. “Get a walking buddy so you can encourage each other to walk,” Dr. Goldberg added.

Mr. Moore and Dr. Goldberg had no financial conflicts to disclose. The Women’s Health Study is funded by Brigham and Women’s Hospital; the National Heart, Lung, and Blood Institute; and the National Cancer Institute. Mr. Moore was funded by a grant from the NHLBI but had no other financial conflicts to disclose.

Taking more steps each day, in short spurts or longer bouts, was associated with a longer life in women older than 60 years, according to data from more than 16,000 participants in the ongoing Women’s Health Study.

The American Heart Association recommends at least 150 minutes per week of moderate physical activity, 75 minutes of vigorous physical activity, or a combination of both as fitness guidelines for adults. Walking is a safe and easy way for many adults to follow these guidelines, according to Christopher C. Moore, MS, a PhD candidate at the University of North Carolina at Chapel Hill.

The popularity of step counts reflect that they are simple and objective, and “focusing on steps can help promote an active lifestyle,” he said. Data on the impact of sporadic steps accumulated outside of longer bouts of activity on health outcomes are limited; however, technology advances in the form of fitness apps and wearable devices make it possible for researchers to track and measure the benefits of short periods of activity as well as longer periods.

In a study presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting, sponsored by the AHA, Mr. Moore and colleagues assessed data from women older than 60 years who used wearable step-counting devices to measure their daily steps and walking patterns.

The study population included 16,732 women enrolled in the Women’s Health Study, a longstanding study of heart disease, cancer, and disease prevention among women in the United States. The participants wore waist step counters 4-7 days a week during 2011-2015. The average of the women was 72 years; 96% were non-Hispanic White, and the average BMI was 26 kg/m².

The researchers divided the total number of steps for each study participant into two groups: “bouted” steps, defined as 10 minutes or longer bouts of walking with few interruptions; and “sporadic” steps, defined as short spurts of walking during regular daily activities such as housework, taking the stairs, or walking to or from a car.

A total of 804 deaths occurred during an average of 6 years of follow-up. Each initial increase of 1,000 steps including sporadic or bouted steps was associated with a 28% decrease in death, compared with no daily steps (hazard ratio, 0.72).

Each increasing quartile of sporadic steps was linked with higher total steps per day, Mr. Moore said. “Initial increase in sporadic steps corresponded to the greatest reductions in mortality,” with a HR of 0.69 per additional sporadic steps below 3,200 per day, and the impact on reduced mortality plateaued at about 4,500 sporadic steps per day.

In further analysis, the researchers also found a roughly 32% decrease in death in participants who took more than 2,000 steps daily in uninterrupted bouts (HR, 0.69).

The study findings were limited by several factors, including the relatively short follow-up period and number of events, the assessment of steps at a single time point, and the mostly homogeneous population, Mr. Moore noted. Additional research is needed to assess whether the results are generalizable to men, younger women, and diverse racial and ethnic groups.

However, the results may have implications for public health messaging, he emphasized. The message is that, to impact longevity, the total volume of steps is more important than the type of activity through which they are accumulated.

“You can accumulate your steps through longer bouts of purposeful activity or through everyday behaviors such as walking to your car, taking the stairs, and doing housework,” Mr. Moore concluded.

Find a friend, both of you benefit

On the basis of this study and other available evidence, more steps daily are recommended for everyone, Nieca Goldberg, MD, a cardiologist at New York University Langone Health, said in an interview.

“You can increase minutes of walking and frequency of walking,” she said.

Dr. Goldberg emphasized that you don’t need a fancy app or wearable device to up your steps. She offered some tips to help overcome barriers to putting one foot in front of the other. “Take the steps instead of the elevator. Park your car farther from your destination so you can walk.” Also, you can help yourself and help a friend to better health. “Get a walking buddy so you can encourage each other to walk,” Dr. Goldberg added.

Mr. Moore and Dr. Goldberg had no financial conflicts to disclose. The Women’s Health Study is funded by Brigham and Women’s Hospital; the National Heart, Lung, and Blood Institute; and the National Cancer Institute. Mr. Moore was funded by a grant from the NHLBI but had no other financial conflicts to disclose.

Taking more steps each day, in short spurts or longer bouts, was associated with a longer life in women older than 60 years, according to data from more than 16,000 participants in the ongoing Women’s Health Study.

The American Heart Association recommends at least 150 minutes per week of moderate physical activity, 75 minutes of vigorous physical activity, or a combination of both as fitness guidelines for adults. Walking is a safe and easy way for many adults to follow these guidelines, according to Christopher C. Moore, MS, a PhD candidate at the University of North Carolina at Chapel Hill.

The popularity of step counts reflect that they are simple and objective, and “focusing on steps can help promote an active lifestyle,” he said. Data on the impact of sporadic steps accumulated outside of longer bouts of activity on health outcomes are limited; however, technology advances in the form of fitness apps and wearable devices make it possible for researchers to track and measure the benefits of short periods of activity as well as longer periods.

In a study presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting, sponsored by the AHA, Mr. Moore and colleagues assessed data from women older than 60 years who used wearable step-counting devices to measure their daily steps and walking patterns.

The study population included 16,732 women enrolled in the Women’s Health Study, a longstanding study of heart disease, cancer, and disease prevention among women in the United States. The participants wore waist step counters 4-7 days a week during 2011-2015. The average of the women was 72 years; 96% were non-Hispanic White, and the average BMI was 26 kg/m².

The researchers divided the total number of steps for each study participant into two groups: “bouted” steps, defined as 10 minutes or longer bouts of walking with few interruptions; and “sporadic” steps, defined as short spurts of walking during regular daily activities such as housework, taking the stairs, or walking to or from a car.

A total of 804 deaths occurred during an average of 6 years of follow-up. Each initial increase of 1,000 steps including sporadic or bouted steps was associated with a 28% decrease in death, compared with no daily steps (hazard ratio, 0.72).

Each increasing quartile of sporadic steps was linked with higher total steps per day, Mr. Moore said. “Initial increase in sporadic steps corresponded to the greatest reductions in mortality,” with a HR of 0.69 per additional sporadic steps below 3,200 per day, and the impact on reduced mortality plateaued at about 4,500 sporadic steps per day.

In further analysis, the researchers also found a roughly 32% decrease in death in participants who took more than 2,000 steps daily in uninterrupted bouts (HR, 0.69).

The study findings were limited by several factors, including the relatively short follow-up period and number of events, the assessment of steps at a single time point, and the mostly homogeneous population, Mr. Moore noted. Additional research is needed to assess whether the results are generalizable to men, younger women, and diverse racial and ethnic groups.

However, the results may have implications for public health messaging, he emphasized. The message is that, to impact longevity, the total volume of steps is more important than the type of activity through which they are accumulated.

“You can accumulate your steps through longer bouts of purposeful activity or through everyday behaviors such as walking to your car, taking the stairs, and doing housework,” Mr. Moore concluded.

Find a friend, both of you benefit

On the basis of this study and other available evidence, more steps daily are recommended for everyone, Nieca Goldberg, MD, a cardiologist at New York University Langone Health, said in an interview.

“You can increase minutes of walking and frequency of walking,” she said.

Dr. Goldberg emphasized that you don’t need a fancy app or wearable device to up your steps. She offered some tips to help overcome barriers to putting one foot in front of the other. “Take the steps instead of the elevator. Park your car farther from your destination so you can walk.” Also, you can help yourself and help a friend to better health. “Get a walking buddy so you can encourage each other to walk,” Dr. Goldberg added.

Mr. Moore and Dr. Goldberg had no financial conflicts to disclose. The Women’s Health Study is funded by Brigham and Women’s Hospital; the National Heart, Lung, and Blood Institute; and the National Cancer Institute. Mr. Moore was funded by a grant from the NHLBI but had no other financial conflicts to disclose.

Anti–apolipoprotein A-I (apo A-I) antibodies are common in nonalcoholic fatty liver disease and may not only drive its development but also underlie the link between NAFLD and cardiovascular disease, suggests a novel analysis.

Conducting a clinical analysis and a series of experiments, Sabrina Pagano, PhD, diagnostic department, Geneva University Hospital, and colleagues looked for anti–apo A-I antibodies in patients with NAFLD and then examined their impact on hepatic cells and inflammatory markers.

They found that nearly half of 137 patients with NAFLD were seropositive, and that the antibodies were associated with increased lipid accumulation in the liver, altered triglyceride metabolism, and proinflammatory effects on liver cells.

“We hypothesize that anti–apo A-I IgG may be a potential driver in the development of NAFLD, and further studies are needed to support anti–apo A-I IgG as a possible link between NAFLD and cardiovascular disease,” Dr. Pagano said.

The research was presented at the European Atherosclerosis Society 2021 Virtual Congress.

Asked whether anti–apo A-I antibodies could represent a potential treatment target for NAFLD, Dr. Pagano said in an interview that they have “already developed a peptide that is recognized by the antibodies in order to try to reverse the anti–apo A-I deleterious effect.”

While this was successful in vitro, “unfortunately we didn’t observe ... the peptide reverse of these anti–apo A-I effects in mice, so ... for the moment it’s a little early,” to say whether it represents a promising target.

Approached for comment, Maciej Banach, MD, PhD, full professor of cardiology, Polish Mother’s Memorial Hospital Research Institute, Lodz, said that the results are “very interesting and encouraging.”

He said that his own global burden of disease analysis, which is set to be published soon, showed that the worldwide prevalence of NAFLD is 11%, “representing almost 900 million cases,” and a more than 33% increase in prevalence in the past 30 years.

Consequently, any “attempt to have effective, especially early, diagnosis and treatment,” is highly anticipated.

Dr. Banach said the findings from the experimental analyses are “very interesting and promising,” especially regarding the proinflammatory effects of anti–apo A-I antibodies.

However, he underlined that the clinical part, looking at antibody seropositivity in patients with NAFLD, was limited by the lack of a control group, and there was no indication as to what treatment the patients received, despite it being clear that many were obese.

Dr. Banach also believes that, taking into account the patient characteristics, it is likely that most of the patients had the more severe nonalcoholic steatohepatitis, and “it would be additionally useful to see the autoantibodies levels both in NASH and NAFLD.”

Nevertheless, the clinical utility of measuring anti–apo A-I antibodies is limited at this stage.

He said that the lack of “good, easy, and cheap diagnostic methods based on both laboratory and imaging data” for NAFLD means it would be difficult to determine whether assessing antibody seropositivity “might be indeed an added value.”
 

Independent predictors

Dr. Pagano explained that anti–apo A-I antibodies, which target the major protein fraction of HDL cholesterol, are independent predictors of cardiovascular events in high-risk populations.

They are also independently associated with cardiovascular disease in the general population, as well as atherosclerotic plaque vulnerability in both mice and humans.

She said that apo A-I antibodies have a metabolic role in vivo, and have been shown in vitro to disrupt cholesterol metabolism, promoting foam cell formation.

Studies have also indicated they play a role in hepatic fibrosis, predicting the development of cirrhosis in individuals with chronic hepatitis C infection.

The team therefore set out to determine the presence of anti–apo A-I antibodies in individuals with NAFLD, defined here as fatty acid levels greater than 5% of liver weight, as well as their effect on hepatic cells.

Working with colleagues at Magna Græcia University of Catanzaro (Italy), they obtained serum samples from 137 patients with NAFLD confirmed on ultrasound.

The patients had an average age of 49 years, and 48.9% were male. The median body mass index was 31.8 kg/m². Cholesterol levels were typically in the intermediate range.

They found that 46% of the participants had anti–apo A-I IgG antibodies, “which is quite high when compared with the 15%-20% positivity that we retrieved from the general population,” Dr. Pagano said.

To explore the link between high anti–apo A-I antibodies and NAFLD, the team studied hepatic cells, treating them with anti–apo A-I IgG antibodies or control IgG antibodies, or leaving them untreated, for 24 hours.

This revealed that anti–apo A-I IgG antibodies were associated with a significant increase in liquid droplet content in hepatic cells, compared with both cells treated with control IgG (P = .0008), and untreated cells (P = .0002).

Next, the team immunized apo E knockout mice with anti–apo A-I or control IgG antibodies. After 16 weeks, they found there was a significant increase in liver lipid content in mice given anti–apo A-I antibodies versus those treated with controls (P = .03).

They then asked whether anti–apo A-I antibodies could affect triglyceride metabolism. They examined the expression of the transcription factor sterol regulatory element binding protein (SREBP) and regulation of the triglyceride and cholesterol pathways.

Treating hepatic cells again for 24 hours with anti–apo A-I IgG antibodies or control IgG antibodies, or leaving them untreated, showed that anti–apo A-I antibodies were associated with “dramatic” increases in the active form of SREBP.

They also found that expression of two key enzymes in the triglyceride pathway, fatty acid synthetase and glycerol phosphate acyltransferase, was substantially decreased in the presence anti–apo A-I antibodies.

In both experiments, the untreated hepatic cells and those exposed to control IgG antibodies showed no significant changes.

“These results suggest that negative feedback ... turns off these enzymes, probably due to the lipid overload that is found in the cells after 24 hours of anti–apo A-I treatment,” Dr. Pagano said.

Finally, the researchers observed that anti–apo A-I, but not control antibodies, were associated with increases in inflammatory markers in liver cells.

Specifically, exposure to the antibodies was linked to an approximately 10-fold increase in interleukin-6 levels, as well as an approximate 25-fold increase in IL-8, and around a 7-fold increase in tumor necrosis factor–alpha.

Dr. Pagano suggested that the inflammatory effects are “probably mediated by binding anti–apo A-I antibodies to toll-like receptor 2, which has been previously described in macrophages.”

No funding was declared. The study authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Anti–apolipoprotein A-I (apo A-I) antibodies are common in nonalcoholic fatty liver disease and may not only drive its development but also underlie the link between NAFLD and cardiovascular disease, suggests a novel analysis.

Conducting a clinical analysis and a series of experiments, Sabrina Pagano, PhD, diagnostic department, Geneva University Hospital, and colleagues looked for anti–apo A-I antibodies in patients with NAFLD and then examined their impact on hepatic cells and inflammatory markers.

They found that nearly half of 137 patients with NAFLD were seropositive, and that the antibodies were associated with increased lipid accumulation in the liver, altered triglyceride metabolism, and proinflammatory effects on liver cells.

“We hypothesize that anti–apo A-I IgG may be a potential driver in the development of NAFLD, and further studies are needed to support anti–apo A-I IgG as a possible link between NAFLD and cardiovascular disease,” Dr. Pagano said.

The research was presented at the European Atherosclerosis Society 2021 Virtual Congress.

Asked whether anti–apo A-I antibodies could represent a potential treatment target for NAFLD, Dr. Pagano said in an interview that they have “already developed a peptide that is recognized by the antibodies in order to try to reverse the anti–apo A-I deleterious effect.”

While this was successful in vitro, “unfortunately we didn’t observe ... the peptide reverse of these anti–apo A-I effects in mice, so ... for the moment it’s a little early,” to say whether it represents a promising target.

Approached for comment, Maciej Banach, MD, PhD, full professor of cardiology, Polish Mother’s Memorial Hospital Research Institute, Lodz, said that the results are “very interesting and encouraging.”

He said that his own global burden of disease analysis, which is set to be published soon, showed that the worldwide prevalence of NAFLD is 11%, “representing almost 900 million cases,” and a more than 33% increase in prevalence in the past 30 years.

Consequently, any “attempt to have effective, especially early, diagnosis and treatment,” is highly anticipated.

Dr. Banach said the findings from the experimental analyses are “very interesting and promising,” especially regarding the proinflammatory effects of anti–apo A-I antibodies.

However, he underlined that the clinical part, looking at antibody seropositivity in patients with NAFLD, was limited by the lack of a control group, and there was no indication as to what treatment the patients received, despite it being clear that many were obese.

Dr. Banach also believes that, taking into account the patient characteristics, it is likely that most of the patients had the more severe nonalcoholic steatohepatitis, and “it would be additionally useful to see the autoantibodies levels both in NASH and NAFLD.”

Nevertheless, the clinical utility of measuring anti–apo A-I antibodies is limited at this stage.

He said that the lack of “good, easy, and cheap diagnostic methods based on both laboratory and imaging data” for NAFLD means it would be difficult to determine whether assessing antibody seropositivity “might be indeed an added value.”
 

Independent predictors

Dr. Pagano explained that anti–apo A-I antibodies, which target the major protein fraction of HDL cholesterol, are independent predictors of cardiovascular events in high-risk populations.

They are also independently associated with cardiovascular disease in the general population, as well as atherosclerotic plaque vulnerability in both mice and humans.

She said that apo A-I antibodies have a metabolic role in vivo, and have been shown in vitro to disrupt cholesterol metabolism, promoting foam cell formation.

Studies have also indicated they play a role in hepatic fibrosis, predicting the development of cirrhosis in individuals with chronic hepatitis C infection.

The team therefore set out to determine the presence of anti–apo A-I antibodies in individuals with NAFLD, defined here as fatty acid levels greater than 5% of liver weight, as well as their effect on hepatic cells.

Working with colleagues at Magna Græcia University of Catanzaro (Italy), they obtained serum samples from 137 patients with NAFLD confirmed on ultrasound.

The patients had an average age of 49 years, and 48.9% were male. The median body mass index was 31.8 kg/m². Cholesterol levels were typically in the intermediate range.

They found that 46% of the participants had anti–apo A-I IgG antibodies, “which is quite high when compared with the 15%-20% positivity that we retrieved from the general population,” Dr. Pagano said.

To explore the link between high anti–apo A-I antibodies and NAFLD, the team studied hepatic cells, treating them with anti–apo A-I IgG antibodies or control IgG antibodies, or leaving them untreated, for 24 hours.

This revealed that anti–apo A-I IgG antibodies were associated with a significant increase in liquid droplet content in hepatic cells, compared with both cells treated with control IgG (P = .0008), and untreated cells (P = .0002).

Next, the team immunized apo E knockout mice with anti–apo A-I or control IgG antibodies. After 16 weeks, they found there was a significant increase in liver lipid content in mice given anti–apo A-I antibodies versus those treated with controls (P = .03).

They then asked whether anti–apo A-I antibodies could affect triglyceride metabolism. They examined the expression of the transcription factor sterol regulatory element binding protein (SREBP) and regulation of the triglyceride and cholesterol pathways.

Treating hepatic cells again for 24 hours with anti–apo A-I IgG antibodies or control IgG antibodies, or leaving them untreated, showed that anti–apo A-I antibodies were associated with “dramatic” increases in the active form of SREBP.

They also found that expression of two key enzymes in the triglyceride pathway, fatty acid synthetase and glycerol phosphate acyltransferase, was substantially decreased in the presence anti–apo A-I antibodies.

In both experiments, the untreated hepatic cells and those exposed to control IgG antibodies showed no significant changes.

“These results suggest that negative feedback ... turns off these enzymes, probably due to the lipid overload that is found in the cells after 24 hours of anti–apo A-I treatment,” Dr. Pagano said.

Finally, the researchers observed that anti–apo A-I, but not control antibodies, were associated with increases in inflammatory markers in liver cells.

Specifically, exposure to the antibodies was linked to an approximately 10-fold increase in interleukin-6 levels, as well as an approximate 25-fold increase in IL-8, and around a 7-fold increase in tumor necrosis factor–alpha.

Dr. Pagano suggested that the inflammatory effects are “probably mediated by binding anti–apo A-I antibodies to toll-like receptor 2, which has been previously described in macrophages.”

No funding was declared. The study authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Anti–apolipoprotein A-I (apo A-I) antibodies are common in nonalcoholic fatty liver disease and may not only drive its development but also underlie the link between NAFLD and cardiovascular disease, suggests a novel analysis.

Conducting a clinical analysis and a series of experiments, Sabrina Pagano, PhD, diagnostic department, Geneva University Hospital, and colleagues looked for anti–apo A-I antibodies in patients with NAFLD and then examined their impact on hepatic cells and inflammatory markers.

They found that nearly half of 137 patients with NAFLD were seropositive, and that the antibodies were associated with increased lipid accumulation in the liver, altered triglyceride metabolism, and proinflammatory effects on liver cells.

“We hypothesize that anti–apo A-I IgG may be a potential driver in the development of NAFLD, and further studies are needed to support anti–apo A-I IgG as a possible link between NAFLD and cardiovascular disease,” Dr. Pagano said.

The research was presented at the European Atherosclerosis Society 2021 Virtual Congress.

Asked whether anti–apo A-I antibodies could represent a potential treatment target for NAFLD, Dr. Pagano said in an interview that they have “already developed a peptide that is recognized by the antibodies in order to try to reverse the anti–apo A-I deleterious effect.”

While this was successful in vitro, “unfortunately we didn’t observe ... the peptide reverse of these anti–apo A-I effects in mice, so ... for the moment it’s a little early,” to say whether it represents a promising target.

Approached for comment, Maciej Banach, MD, PhD, full professor of cardiology, Polish Mother’s Memorial Hospital Research Institute, Lodz, said that the results are “very interesting and encouraging.”

He said that his own global burden of disease analysis, which is set to be published soon, showed that the worldwide prevalence of NAFLD is 11%, “representing almost 900 million cases,” and a more than 33% increase in prevalence in the past 30 years.

Consequently, any “attempt to have effective, especially early, diagnosis and treatment,” is highly anticipated.

Dr. Banach said the findings from the experimental analyses are “very interesting and promising,” especially regarding the proinflammatory effects of anti–apo A-I antibodies.

However, he underlined that the clinical part, looking at antibody seropositivity in patients with NAFLD, was limited by the lack of a control group, and there was no indication as to what treatment the patients received, despite it being clear that many were obese.

Dr. Banach also believes that, taking into account the patient characteristics, it is likely that most of the patients had the more severe nonalcoholic steatohepatitis, and “it would be additionally useful to see the autoantibodies levels both in NASH and NAFLD.”

Nevertheless, the clinical utility of measuring anti–apo A-I antibodies is limited at this stage.

He said that the lack of “good, easy, and cheap diagnostic methods based on both laboratory and imaging data” for NAFLD means it would be difficult to determine whether assessing antibody seropositivity “might be indeed an added value.”
 

Independent predictors

Dr. Pagano explained that anti–apo A-I antibodies, which target the major protein fraction of HDL cholesterol, are independent predictors of cardiovascular events in high-risk populations.

They are also independently associated with cardiovascular disease in the general population, as well as atherosclerotic plaque vulnerability in both mice and humans.

She said that apo A-I antibodies have a metabolic role in vivo, and have been shown in vitro to disrupt cholesterol metabolism, promoting foam cell formation.

Studies have also indicated they play a role in hepatic fibrosis, predicting the development of cirrhosis in individuals with chronic hepatitis C infection.

The team therefore set out to determine the presence of anti–apo A-I antibodies in individuals with NAFLD, defined here as fatty acid levels greater than 5% of liver weight, as well as their effect on hepatic cells.

Working with colleagues at Magna Græcia University of Catanzaro (Italy), they obtained serum samples from 137 patients with NAFLD confirmed on ultrasound.

The patients had an average age of 49 years, and 48.9% were male. The median body mass index was 31.8 kg/m². Cholesterol levels were typically in the intermediate range.

They found that 46% of the participants had anti–apo A-I IgG antibodies, “which is quite high when compared with the 15%-20% positivity that we retrieved from the general population,” Dr. Pagano said.

To explore the link between high anti–apo A-I antibodies and NAFLD, the team studied hepatic cells, treating them with anti–apo A-I IgG antibodies or control IgG antibodies, or leaving them untreated, for 24 hours.

This revealed that anti–apo A-I IgG antibodies were associated with a significant increase in liquid droplet content in hepatic cells, compared with both cells treated with control IgG (P = .0008), and untreated cells (P = .0002).

Next, the team immunized apo E knockout mice with anti–apo A-I or control IgG antibodies. After 16 weeks, they found there was a significant increase in liver lipid content in mice given anti–apo A-I antibodies versus those treated with controls (P = .03).

They then asked whether anti–apo A-I antibodies could affect triglyceride metabolism. They examined the expression of the transcription factor sterol regulatory element binding protein (SREBP) and regulation of the triglyceride and cholesterol pathways.

Treating hepatic cells again for 24 hours with anti–apo A-I IgG antibodies or control IgG antibodies, or leaving them untreated, showed that anti–apo A-I antibodies were associated with “dramatic” increases in the active form of SREBP.

They also found that expression of two key enzymes in the triglyceride pathway, fatty acid synthetase and glycerol phosphate acyltransferase, was substantially decreased in the presence anti–apo A-I antibodies.

In both experiments, the untreated hepatic cells and those exposed to control IgG antibodies showed no significant changes.

“These results suggest that negative feedback ... turns off these enzymes, probably due to the lipid overload that is found in the cells after 24 hours of anti–apo A-I treatment,” Dr. Pagano said.

Finally, the researchers observed that anti–apo A-I, but not control antibodies, were associated with increases in inflammatory markers in liver cells.

Specifically, exposure to the antibodies was linked to an approximately 10-fold increase in interleukin-6 levels, as well as an approximate 25-fold increase in IL-8, and around a 7-fold increase in tumor necrosis factor–alpha.

Dr. Pagano suggested that the inflammatory effects are “probably mediated by binding anti–apo A-I antibodies to toll-like receptor 2, which has been previously described in macrophages.”

No funding was declared. The study authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Although recent trial results have established the sodium glucose cotransporter 2 inhibitors dapagliflozin and empagliflozin as a key new part of the recommended multidrug treatment regimen for patients with heart failure with reduced ejection fraction, the current U.S. cost for dapagliflozin means it has merely “intermediate” value when it comes to cost-effectiveness.

adventtr/iStock/Getty Images Plus

A typical regimen with dapagliflozin to treat patients with heart failure with reduced ejection fraction (HFrEF) costs about $474/month or roughly $5,700/year based on Medicare pricing. After factoring in the incremental clinical benefits producing by dapagliflozin seen in the DAPA-HF pivotal trial that helped establish its role, this price produces a cost per quality-adjusted life-year (QALY) gain of about $84,000, which puts dapagliflozin squarely in the intermediate range for value set in 2014 by a task force of the American College of Cardiology and the American Heart Association.

This cost-effectiveness value depends largely on the proven efficacy of dapagliflozin (Farxiga) for decreasing the incidence of cardiovascular death among treated patients with HFrEF, and puts the drug’s value roughly on par with another agent recently approved to treat such patients, sacubitril/valsartan (Entresto), which carries a cost-effectiveness value of about $45,000/QALY.

The U.S. cost per QALY for dapagliflozin treatment of patients with HFrEF dwarfed the value numbers calculated for several other countries that were generally one-tenth this size. This disparity stemmed from both the relatively high price for dapagliflozin in the U.S. compared with other countries – nearly tenfold higher – and relatively higher costs for all types of U.S. medical care, Justin T. Parizo, MD, and coauthors said in a recent report. But the cost, and hence the cost per QALY, of dapagliflozin may soon drop because certain patents on the drug expired in October 2020, added Dr. Parizo, a cardiologist at Stanford (Calif.) University, and associates. Despite the expired patents, as of June 2021 no generic form of dapagliflozin appeared available for U.S. sale.
 

Medicare patients pay about $1,630/year out-of-pocket

“A key caveat” to this finding for dapagliflozin is that being cost-effective “is not by itself a mandate for routine clinical use,” Derek S. Chew, MD, and Daniel B. Mark, MD, said in an editorial that accompanied the report.

A major stumbling block for widespread U.S. prescribing of dapagliflozin to patients with HFrEF is its overall price tag for U.S. patients, estimated at $12 billion/year, as well as an out-of-pocket annual cost for individual Medicare patients of roughly $1,630/year. Adding this out-of-pocket cost to the copay for sacubitril/valsartan and two other much less expensive drug classes that together form the current mainstay, quadruple-drug regimen for HFrEF treatment means a potential annual cost paid by each Medicare patient of about $3,000, wrote Dr. Chew, a cardiologist, and Dr. Mark, a cardiologist and professor, both at Duke University, Durham, N.C.

They cited the precedent of the “unexpectedly slow” and “anemic” uptake of sacubitril/valsartan since its U.S. approval in 2015, a cost-effective agent with “comparable clinical effectiveness” to dapagliflozin. “Even with full inclusion [of sacubitril/valsartan] on formularies and elimination of preapproval requirements, use remains very low, and patient-borne out-of-pocket costs may be a key factor,” wrote Dr. Chew and Dr. Mark. They cited a results from a study that showed abandonment of new prescriptions at retail U.S. pharmacies spiked to a 60% rate when out-of-pocket cost exceeded $500.
 

More than what patients ‘can afford or are willing to spend’

The estimated $3,000-plus total out-of-pocket cost currently borne by some Medicare beneficiaries with HFrEF who have to shell out for both sacubitril/valsartan and dapagliflozin “appears to substantially exceed what many patients with heart failure can afford or are willing to spend,” wrote Dr. Chew and Dr. Mark.

Dr. Parizo and coauthors developed their cost-effectiveness model for dapagliflozin in treating HFrEF using primarily data collected in the DAPA-HF trial, which proved the efficacy of the drug for reducing cardiovascular deaths or acute heart failure events that led to hospitalization or intravenous outpatient treatment in more than 4,700 randomized patients with HFrEF. The trial enrolled roughly similar numbers of patients with or without type 2 diabetes.

The model showed an overall incremental cost-effectiveness ratio of $83,650/QALY, which was about the same regardless of whether patients also had type 2 diabetes. On a more granular level, the cost-effectiveness value estimate was $78,483/QALY in patients with mild health-status impairment due to their heart failure, and $97,608/QALY in patients with moderate impairment, a finding that underscores the importance of starting dapagliflozin treatment early in the course of HFrEF when disease effects are less severe. The analysis could not address value in patients with more advanced heart failure and in New York Heart Association functional class IV because fewer than 1% of patients in DAPA-HF were in this category.

Drug cost was a major determinant of cost-effectiveness. A 50% drop in cost from the Medicare benchmark of $473.64/month resulted in an incremental cost-effectiveness ratio of about $45,000/QALY (putting it into the high-value category based on the 2014 ACC/AHA formula), while a 50% rise in price yielded a value of nearly $123,000/QALY (still in the intermediate range, which spans from $50,000/QALY to $150,000/QALY). No other cost parameters had a meaningful effect on the cost-effectiveness calculation. The analyses also showed that using the basic cost assumptions, treatment with dapagliflozin needs to persist and remain effective for at least 44 months to produce a cost per QALY that’s less than $150,000. The authors stressed that their analysis considered heart failure effects and did not account for added benefit from treatment with dapagliflozin on preservation of renal function.

While it’s indisputable that treatment with dapagliflozin decreases health care costs by, for example, reducing hospitalizations for heart failure, each hospitalization costs just over $12,000, according to the assumptions made by Dr. Parizo and coauthors. But given dapagliflozin’s impact on this outcome, this cost saving translates into about $500/patient during 18 months on treatment (the median duration of treatment in DAPA-HF), which means the savings barely counterbalances the current cost of dapagliflozin treatment for 1 month, noted Dr. Chew and Dr. Mark.

The DAPA-HF trial was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Parizo had no disclosures and none of his coauthors had a relationship with AstraZeneca. Dr. Chew had no disclosures. Dr. Mark has received research grants from HeartFlow, Mayo Clinic, and Merck.

[email protected]

Although recent trial results have established the sodium glucose cotransporter 2 inhibitors dapagliflozin and empagliflozin as a key new part of the recommended multidrug treatment regimen for patients with heart failure with reduced ejection fraction, the current U.S. cost for dapagliflozin means it has merely “intermediate” value when it comes to cost-effectiveness.

adventtr/iStock/Getty Images Plus

A typical regimen with dapagliflozin to treat patients with heart failure with reduced ejection fraction (HFrEF) costs about $474/month or roughly $5,700/year based on Medicare pricing. After factoring in the incremental clinical benefits producing by dapagliflozin seen in the DAPA-HF pivotal trial that helped establish its role, this price produces a cost per quality-adjusted life-year (QALY) gain of about $84,000, which puts dapagliflozin squarely in the intermediate range for value set in 2014 by a task force of the American College of Cardiology and the American Heart Association.

This cost-effectiveness value depends largely on the proven efficacy of dapagliflozin (Farxiga) for decreasing the incidence of cardiovascular death among treated patients with HFrEF, and puts the drug’s value roughly on par with another agent recently approved to treat such patients, sacubitril/valsartan (Entresto), which carries a cost-effectiveness value of about $45,000/QALY.

The U.S. cost per QALY for dapagliflozin treatment of patients with HFrEF dwarfed the value numbers calculated for several other countries that were generally one-tenth this size. This disparity stemmed from both the relatively high price for dapagliflozin in the U.S. compared with other countries – nearly tenfold higher – and relatively higher costs for all types of U.S. medical care, Justin T. Parizo, MD, and coauthors said in a recent report. But the cost, and hence the cost per QALY, of dapagliflozin may soon drop because certain patents on the drug expired in October 2020, added Dr. Parizo, a cardiologist at Stanford (Calif.) University, and associates. Despite the expired patents, as of June 2021 no generic form of dapagliflozin appeared available for U.S. sale.
 

Medicare patients pay about $1,630/year out-of-pocket

“A key caveat” to this finding for dapagliflozin is that being cost-effective “is not by itself a mandate for routine clinical use,” Derek S. Chew, MD, and Daniel B. Mark, MD, said in an editorial that accompanied the report.

A major stumbling block for widespread U.S. prescribing of dapagliflozin to patients with HFrEF is its overall price tag for U.S. patients, estimated at $12 billion/year, as well as an out-of-pocket annual cost for individual Medicare patients of roughly $1,630/year. Adding this out-of-pocket cost to the copay for sacubitril/valsartan and two other much less expensive drug classes that together form the current mainstay, quadruple-drug regimen for HFrEF treatment means a potential annual cost paid by each Medicare patient of about $3,000, wrote Dr. Chew, a cardiologist, and Dr. Mark, a cardiologist and professor, both at Duke University, Durham, N.C.

They cited the precedent of the “unexpectedly slow” and “anemic” uptake of sacubitril/valsartan since its U.S. approval in 2015, a cost-effective agent with “comparable clinical effectiveness” to dapagliflozin. “Even with full inclusion [of sacubitril/valsartan] on formularies and elimination of preapproval requirements, use remains very low, and patient-borne out-of-pocket costs may be a key factor,” wrote Dr. Chew and Dr. Mark. They cited a results from a study that showed abandonment of new prescriptions at retail U.S. pharmacies spiked to a 60% rate when out-of-pocket cost exceeded $500.
 

More than what patients ‘can afford or are willing to spend’

The estimated $3,000-plus total out-of-pocket cost currently borne by some Medicare beneficiaries with HFrEF who have to shell out for both sacubitril/valsartan and dapagliflozin “appears to substantially exceed what many patients with heart failure can afford or are willing to spend,” wrote Dr. Chew and Dr. Mark.

Dr. Parizo and coauthors developed their cost-effectiveness model for dapagliflozin in treating HFrEF using primarily data collected in the DAPA-HF trial, which proved the efficacy of the drug for reducing cardiovascular deaths or acute heart failure events that led to hospitalization or intravenous outpatient treatment in more than 4,700 randomized patients with HFrEF. The trial enrolled roughly similar numbers of patients with or without type 2 diabetes.

The model showed an overall incremental cost-effectiveness ratio of $83,650/QALY, which was about the same regardless of whether patients also had type 2 diabetes. On a more granular level, the cost-effectiveness value estimate was $78,483/QALY in patients with mild health-status impairment due to their heart failure, and $97,608/QALY in patients with moderate impairment, a finding that underscores the importance of starting dapagliflozin treatment early in the course of HFrEF when disease effects are less severe. The analysis could not address value in patients with more advanced heart failure and in New York Heart Association functional class IV because fewer than 1% of patients in DAPA-HF were in this category.

Drug cost was a major determinant of cost-effectiveness. A 50% drop in cost from the Medicare benchmark of $473.64/month resulted in an incremental cost-effectiveness ratio of about $45,000/QALY (putting it into the high-value category based on the 2014 ACC/AHA formula), while a 50% rise in price yielded a value of nearly $123,000/QALY (still in the intermediate range, which spans from $50,000/QALY to $150,000/QALY). No other cost parameters had a meaningful effect on the cost-effectiveness calculation. The analyses also showed that using the basic cost assumptions, treatment with dapagliflozin needs to persist and remain effective for at least 44 months to produce a cost per QALY that’s less than $150,000. The authors stressed that their analysis considered heart failure effects and did not account for added benefit from treatment with dapagliflozin on preservation of renal function.

While it’s indisputable that treatment with dapagliflozin decreases health care costs by, for example, reducing hospitalizations for heart failure, each hospitalization costs just over $12,000, according to the assumptions made by Dr. Parizo and coauthors. But given dapagliflozin’s impact on this outcome, this cost saving translates into about $500/patient during 18 months on treatment (the median duration of treatment in DAPA-HF), which means the savings barely counterbalances the current cost of dapagliflozin treatment for 1 month, noted Dr. Chew and Dr. Mark.

The DAPA-HF trial was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Parizo had no disclosures and none of his coauthors had a relationship with AstraZeneca. Dr. Chew had no disclosures. Dr. Mark has received research grants from HeartFlow, Mayo Clinic, and Merck.

[email protected]

Although recent trial results have established the sodium glucose cotransporter 2 inhibitors dapagliflozin and empagliflozin as a key new part of the recommended multidrug treatment regimen for patients with heart failure with reduced ejection fraction, the current U.S. cost for dapagliflozin means it has merely “intermediate” value when it comes to cost-effectiveness.

adventtr/iStock/Getty Images Plus

A typical regimen with dapagliflozin to treat patients with heart failure with reduced ejection fraction (HFrEF) costs about $474/month or roughly $5,700/year based on Medicare pricing. After factoring in the incremental clinical benefits producing by dapagliflozin seen in the DAPA-HF pivotal trial that helped establish its role, this price produces a cost per quality-adjusted life-year (QALY) gain of about $84,000, which puts dapagliflozin squarely in the intermediate range for value set in 2014 by a task force of the American College of Cardiology and the American Heart Association.

This cost-effectiveness value depends largely on the proven efficacy of dapagliflozin (Farxiga) for decreasing the incidence of cardiovascular death among treated patients with HFrEF, and puts the drug’s value roughly on par with another agent recently approved to treat such patients, sacubitril/valsartan (Entresto), which carries a cost-effectiveness value of about $45,000/QALY.

The U.S. cost per QALY for dapagliflozin treatment of patients with HFrEF dwarfed the value numbers calculated for several other countries that were generally one-tenth this size. This disparity stemmed from both the relatively high price for dapagliflozin in the U.S. compared with other countries – nearly tenfold higher – and relatively higher costs for all types of U.S. medical care, Justin T. Parizo, MD, and coauthors said in a recent report. But the cost, and hence the cost per QALY, of dapagliflozin may soon drop because certain patents on the drug expired in October 2020, added Dr. Parizo, a cardiologist at Stanford (Calif.) University, and associates. Despite the expired patents, as of June 2021 no generic form of dapagliflozin appeared available for U.S. sale.
 

Medicare patients pay about $1,630/year out-of-pocket

“A key caveat” to this finding for dapagliflozin is that being cost-effective “is not by itself a mandate for routine clinical use,” Derek S. Chew, MD, and Daniel B. Mark, MD, said in an editorial that accompanied the report.

A major stumbling block for widespread U.S. prescribing of dapagliflozin to patients with HFrEF is its overall price tag for U.S. patients, estimated at $12 billion/year, as well as an out-of-pocket annual cost for individual Medicare patients of roughly $1,630/year. Adding this out-of-pocket cost to the copay for sacubitril/valsartan and two other much less expensive drug classes that together form the current mainstay, quadruple-drug regimen for HFrEF treatment means a potential annual cost paid by each Medicare patient of about $3,000, wrote Dr. Chew, a cardiologist, and Dr. Mark, a cardiologist and professor, both at Duke University, Durham, N.C.

They cited the precedent of the “unexpectedly slow” and “anemic” uptake of sacubitril/valsartan since its U.S. approval in 2015, a cost-effective agent with “comparable clinical effectiveness” to dapagliflozin. “Even with full inclusion [of sacubitril/valsartan] on formularies and elimination of preapproval requirements, use remains very low, and patient-borne out-of-pocket costs may be a key factor,” wrote Dr. Chew and Dr. Mark. They cited a results from a study that showed abandonment of new prescriptions at retail U.S. pharmacies spiked to a 60% rate when out-of-pocket cost exceeded $500.
 

More than what patients ‘can afford or are willing to spend’

The estimated $3,000-plus total out-of-pocket cost currently borne by some Medicare beneficiaries with HFrEF who have to shell out for both sacubitril/valsartan and dapagliflozin “appears to substantially exceed what many patients with heart failure can afford or are willing to spend,” wrote Dr. Chew and Dr. Mark.

Dr. Parizo and coauthors developed their cost-effectiveness model for dapagliflozin in treating HFrEF using primarily data collected in the DAPA-HF trial, which proved the efficacy of the drug for reducing cardiovascular deaths or acute heart failure events that led to hospitalization or intravenous outpatient treatment in more than 4,700 randomized patients with HFrEF. The trial enrolled roughly similar numbers of patients with or without type 2 diabetes.

The model showed an overall incremental cost-effectiveness ratio of $83,650/QALY, which was about the same regardless of whether patients also had type 2 diabetes. On a more granular level, the cost-effectiveness value estimate was $78,483/QALY in patients with mild health-status impairment due to their heart failure, and $97,608/QALY in patients with moderate impairment, a finding that underscores the importance of starting dapagliflozin treatment early in the course of HFrEF when disease effects are less severe. The analysis could not address value in patients with more advanced heart failure and in New York Heart Association functional class IV because fewer than 1% of patients in DAPA-HF were in this category.

Drug cost was a major determinant of cost-effectiveness. A 50% drop in cost from the Medicare benchmark of $473.64/month resulted in an incremental cost-effectiveness ratio of about $45,000/QALY (putting it into the high-value category based on the 2014 ACC/AHA formula), while a 50% rise in price yielded a value of nearly $123,000/QALY (still in the intermediate range, which spans from $50,000/QALY to $150,000/QALY). No other cost parameters had a meaningful effect on the cost-effectiveness calculation. The analyses also showed that using the basic cost assumptions, treatment with dapagliflozin needs to persist and remain effective for at least 44 months to produce a cost per QALY that’s less than $150,000. The authors stressed that their analysis considered heart failure effects and did not account for added benefit from treatment with dapagliflozin on preservation of renal function.

While it’s indisputable that treatment with dapagliflozin decreases health care costs by, for example, reducing hospitalizations for heart failure, each hospitalization costs just over $12,000, according to the assumptions made by Dr. Parizo and coauthors. But given dapagliflozin’s impact on this outcome, this cost saving translates into about $500/patient during 18 months on treatment (the median duration of treatment in DAPA-HF), which means the savings barely counterbalances the current cost of dapagliflozin treatment for 1 month, noted Dr. Chew and Dr. Mark.

The DAPA-HF trial was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Parizo had no disclosures and none of his coauthors had a relationship with AstraZeneca. Dr. Chew had no disclosures. Dr. Mark has received research grants from HeartFlow, Mayo Clinic, and Merck.

[email protected]