Hopkins Med News Update

Study Suggests ‘Remnant Cholesterol’ As Stand-alone Risk for Heart Attack and Stroke

Media Contact: Caslon Hatch, [email protected]

An analysis of data gathered from more than 17,000 adults by Johns Hopkins Medicine researchers supports the belief that so-called “remnant cholesterol” (RC) provides an accurate stand-alone metric — just as doctors currently use measures of low-density lipoprotein (LDL) — for predicting risk of clogged arteries, heart attacks and strokes. In fact, the researchers say, an RC measure may detect the potential for disease when LDL levels do not.

Remnant cholesterol represents the amount of cholesterol in remnant lipoproteins, a form of very low-density lipoproteins (VLDL) from which sugary fatty acids — called triglycerides — have been removed. Along with traditional measurements of blood LDL cholesterol (frequently called “bad cholesterol”) levels, the cholesterol within remnant lipoproteins has been studied as an additional means of assessing a person’s risk for developing cardiovascular disease and stroke.

Remnant cholesterol levels are basically calculated as the total cholesterol amount minus the LDL and high-density lipoprotein cholesterol (HDL, the so-called “good cholesterol”) counts.

In their study, first published July 19, 2021, in the European Heart Journal, the researchers suggest that for people with relatively low levels of LDL cholesterol, a measured RC level greater than 24 micrograms per deciliter (24 millionths of a gram in a little more than a quart) of blood have a 40–50% higher risk for major heart disease or stroke.

“For decades, the thought was that people with low LDL cholesterol levels and relatively high levels of HDL cholesterol [the so-called “good cholesterol”] were at low risk for major heart disease,” says study lead author Renato Quispe, M.D., M.H.S., a cardiovascular disease clinical and research fellow at the Johns Hopkins University School of Medicine. “But over time, studies kept suggesting that remnant cholesterol was a predictor of heart disease, independent of LDL cholesterol levels.”

To better assess the purported link between remnant cholesterol and disease risk, the Johns Hopkins Medicine team pooled information on 17,532 adults, obtained from three U.S. research databases. The data were from men and women between the ages of 30 and 68, who had no history of atherosclerotic cardiovascular disease (buildup of fatty plaque inside arteries) when they were originally studied. Data included cholesterol levels and other important cardiovascular risk factors, as well as which people developed major heart disease or stroke after recruitment to one of the databases. 

The new study found that almost one of five individuals with levels of RC at or greater than 24 micrograms per deciliter experienced major heart disease or stroke within the following 18 years. Interestingly, say the researchers, this proportion was similar to those who had relatively low LDL cholesterol.

After accounting for non-cholesterol-related heart disease risk factors — such as tobacco use, high blood pressure, diabetes, advanced age and race (Blacks are at higher risk) — the researchers found a steady link between higher than normal RC and major heart disease.

Another important finding, the researchers claim, is that individuals with higher levels of RC also had more obesity and diabetes, and almost everyone had high triglyceride levels.

“We’re not saying LDL cholesterol is a poor measure of cardiovascular disease risk,” Quispe notes. “Instead, our analysis suggests that LDL should remain an important assessment tool; however, clinicians also should look at remnant cholesterol because it indicates a significant amount of risk on its own.”

Quispe emphasizes that calculating remnant cholesterol can be done easily with data available from a standard lipid panel — a test commonly given to patients by their doctors.

The U.S. Centers for Disease Control and Prevention estimates that 38 percent of the American adult population has high levels of total cholesterol, and one in four shows high levels of triglycerides. One-third of all deaths in this country are attributed to heart disease, stroke and other cardiovascular disease.

Quispe says future studies are likely to increase attention to remnant cholesterol measures and encourage clinical trials of drugs and lifestyle changes designed to reduce the risk of the diseases for which they provide warning.

Quispe is available for interviews.


Johns Hopkins Medicine Team Proposes Ways to Regulate and Better Manage E-Cigarette Use

Media Contact: Michel Morris, [email protected]

Despite short-term harms and emerging negative long-term effects, the use of electronic nicotine delivery systems — better known as e-cigarettes — among both American adolescents and adults has accelerated and presents public health concerns for tobacco control efforts.

Now, a Johns Hopkins Medicine researcher and his colleagues have proposed e-cigarette regulatory recommendations based upon tiered nicotine exposure standards and associated distribution controls. Currently, the U.S. Food and Drug Administration (FDA) does not have a clear regulatory structure for e-cigarette products, and for the first time, they are reviewing over 6.4 million applications for the entry of such products into the market.

“Tobacco companies already know that e-cigarettes are their future,” says former regulator Brian Miller, M.D., M.B.A., M.P.H., a hospitalist and assistant professor of medicine at the Johns Hopkins University School of Medicine. “This is an opportunity to help shape the marketplace. If you don’t create regulations early, the opportunity may slip away.”

Developed in China in 2003, e-cigarettes are devices of varying shapes and sizes that electronically aerosolize a nicotine-containing solution delivered to users via inhalation, a practice also known as “vaping.” The rapid delivery of vaporized nicotine, absence of tobacco aroma and use behaviors that mimic conventional smoking often make vaping a more attractive alternative to smoking than nicotine-replacement therapies, such as patches or gum.

In a paper published Aug. 13, 2021, in the journal Tobacco Control, Miller and his colleagues discuss the ways e-cigarettes challenge regulators worldwide and address their rising use by adolescents, as well as their potential for being a tool to reduce the dangerous risks from traditional combustible cigarettes.

Rather than leave nicotine content to manufacturers, Miller and his colleagues recommend that the FDA modify its existing regulatory approach and adopt a “tiered” nicotine exposure framework that differentiates products based on the level of exposure to the chemical a user receives from a specific e-cigarette.

Miller says that products meeting an adult nicotine exposure standard would be available as a consumer-driven means of reducing nicotine harm — however, only in state-licensed alcohol beverage control (ABC) stores, “behind the counter” in pharmacies and adult-only tobacco shops. Products with very high nicotine levels exceeding the adult exposure standard would need to be prescribed as a physician-supervised form of harm reduction.

“We explored how a pragmatic, risk-based approach based on tiered nicotine exposure standards and risk-based point-of-sale restrictions would provide a mechanism through which regulators worldwide might unlock the potential of e-cigarettes as harm reduction tools, while ensuring these products meet a standard that is appropriate for the protection of public health,” Miller says.

Because e-cigarettes do not currently have a regulatory framework, Miller says it’s hard for users to know what dose of nicotine they are getting. He hopes that the new recommendations will help primary care doctors and tobacco users work together to find ways to use e-cigarettes for harm reduction.

“We want both groups to continue together on the journey that will eventually cease nicotine use and reduce the burdens of tobacco-related disease,” Miller says. “Patients deserve a choice of consumer-driven and clinician-supervised forms of harm reduction. It’s the first principle of people health: Meet people where they are.” 

Miller is available for interviews.


Gene Self-Correction in ‘Chromosome Caps’ Can Beat Mutations, Help Prevent Blood Cancers

Media Contact: Vanessa Wasta, [email protected] 

People with rare disorders that cause shortened telomeres — protective caps that sit at the end of chromosomes — may be more likely to have blood cancers such as leukemia or myelodyplastic syndrome. Now, Johns Hopkins Medicine scientists have discovered several “self-correcting” genetic mutations in bone marrow that may protect such patients from these cancers.

In a study published online August 3, 2021, in the Journal of Clinical Investigation, the researchers also suggest these mutations can serve as biomarkers that may indicate if patients with short telomere syndromes are likely to develop blood cancers.

“These are the most common cancers we see in patients with short telomere syndromes,” says Mary Armanios, M.D., director of the Telomere Center and professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. “We know that at a certain point, the cells of patients with shortened telomeres either become cancerous or stay healthy.”

Armanios and her team suspected that a self-correcting mechanism in areas of the body with high cell turnover, such as bone marrow, was allowing normal cells to turn malignant. It turns out that the self-correcting mechanism they discovered instead protects cells from becoming cancerous.

With more than 300 billion blood cells produced in the bone marrow each day, the researchers suspected they could find evidence of cellular self-correction in this area of the body, especially amid the spongey interior of bones, where quick adaptation is crucial for high-volume cell production.

The researchers tested the bone marrow and blood cells of 84 study participants divided into three groups: those with short telomere syndromes and myelodyplastic syndromes or leukemia; those with short telomere syndromes and no myelodyplastic syndromes or leukemia; and those in the control group without short telomere syndromes or any cancers.

Using ultra-deep genetic sequencing (where parts of the genome are sequenced repeatedly to locate hard-to-find mutations), Armanios and her team observed genetic mutations and self-correction in several genes associated with telomeres. Nearly a quarter of patients with short telomere syndromes had these mutations, with some even showing multiple mutations.

One such mutation in a gene called TERT enables the production of crucial parts of an enzyme called telomerase, which in its complete form, stabilizes telomeres, the end-caps that protect the DNA in chromosomes.

By enhancing telomerase production and overwriting copies of the TERT gene that don’t work properly, the researchers found that bone marrow cells seemed to correct themselves to avoid becoming cancerous.

“Our findings speak to the versatility of the bone marrow and other areas with high cell turnover in the body,” says Armanios. “Such advantageous mutations provide the body with a better chance to protect itself. These findings may be important in the screening process of shortened telomere patients so that we can predict who may be protected from cancer.”

Armanios is available for interviews.

This news tip was researched and written by science writing intern Haley Wasserman.


Young Johns Hopkins Children’s Center Patient Shows Superhero Powers in Fight with Cancer

Media Contact: Kim Polyniak, [email protected]

 “What the heck is happening?” recalls Melissa Southward, the mother of now-three-year-old Sam, when he started having nose bleeds and developed a yellowish skin color in August 2020. Southward took Sam to his primary care physician, near their home in Frederick, Maryland, where bloodwork was done. The results showed that Sam had B-cell acute lymphoblastic leukemia.

 “Your mind goes to the worst place immediately,” Southward says. “Standing in my backyard when they told me, I fell on my knees and started bawling.”

 The family was immediately directed to go to the hospital. “I told [Sam] that he was going to a special doctor,” Southward says. “Hearing that, he assured us that ‘I am going to be OK, because I’m going to see a special doctor’.”

 Acute lymphoblastic leukemia (ALL), the most common type of cancer in children, affects the blood and bone marrow. The leukemic cells grow rapidly, making it difficult for the bone marrow to make normal cells. It’s unclear what causes ALL; however, certain factors — such as previous cancer treatment, exposure to radiation and genetic disorders — can increase the risk.

 From his local hospital, Sam was transferred to the oncology unit at Johns Hopkins Children’s Center (JHCC), where he was started on a regimen of medication and chemotherapy to try and get the leukemia quickly into remission. He also received multiple blood transfusions.

 “The doctors said, ‘Leukemia is one of the more treatable cancers’,” Southward recalls.

 After eight days at JHCC, Sam’s bone marrow was retested and there was no sign of cancer. He was released from the hospital. Twenty days later, he was considered in remission.

 Since then, Sam has continued medication and chemotherapy to ensure that the cancer doesn’t return, which is typical in cases like his. This treatment will continue for another 18 months.

 Sam also has regular visits with his oncologist, Patrick Brown, M.D., professor of oncology in the Johns Hopkins University School of Medicine, and director of the Pediatric Leukemia Program at JHCC and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.

 Sam has been readmitted to JHCC a few times because of fevers, and once, suffered a 30-minute seizure. The seizure resulted in Todd’s palsy, a neurological condition that causes a temporary paralysis of his left side — a day that Southward says was the scariest of her life. The Todd’s palsy disappeared within 24 hours, but Sam is now followed by a neurology team, along with his oncology team.

 Overall, Sam’s doctors believe his prognosis is good.

 During his time at JHCC, Sam acquired the nickname “Batman Sam” after he was asked by a nurse what would be his superhero name.

 “Without hesitation, he told her ‘Batman Sam’,” Southward says. “The nickname has become a symbol of courage and support for Sam and our family.”

 “Sam’s cancer was thankfully caught at an early stage, which is beneficial, as we try to get him into remission as quickly as possible,” Brown says. “He is doing well, and is truly a superhero, considering everything he has been through.”

 “He’s been incredible,” says Southward of her son. “You would think it would be mania with a three-year old, but he’s had such incredible patience and perseverance.”

 Southward and Brown are available for interviews.

 September is Childhood Cancer Awareness Month to increase knowledge about childhood cancers and emphasize the need for research to help cure them.


To Prevent Suicides, Johns Hopkins Medicine Says, Know Warning Signs; Follow Tips

Media Contacts: Marisol Martinez, [email protected]Kim Polyniak, [email protected]

According to the National Institute of Mental Health, suicide is the 10th leading overall cause of death in the United States and the second leading cause of death in children and young adults between 10 and 34 years old. Research has shown that the majority of suicides are a consequence of mental illness — most commonly depression. Depression can cause someone to feel worthless, hopeless and a burden on others. The illness may prevent people from recognizing that these feelings are temporary, making suicide falsely appear to be a solution. 

 “Suicide risk is very hard to predict,” says Paul Nestadt, M.D., assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine.  “Even seasoned experts are hard pressed to accurately determine the risk.”

 Nestadt says the general warning signs of suicide risk may include the symptoms of major depressive disorder — a change in usual activities; isolation; losing interest in people and activities that previously brought joy; new or increased use of drugs or alcohol; unintentional weight loss or low energy; negative self-talk; and suicidal thoughts.

 According to the U.S. Centers for Disease Control and Prevention, more than 15,000 people under the age of 34 in the United States died from suicide in 2019, the most recent year with statistics. Sadly, say experts at Johns Hopkins Children’s Center (JHCC), this shows that children and young adults are especially vulnerable to suicide.

 “Pandemic or no pandemic, suicide kills way more kids than infectious diseases every year, including during the COVID-19 pandemic,” says John Campo, M.D., director of the Division of Child and Adolescent Psychiatry at JHCC and professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. “Even if we take the pandemic off the table, we’ve been asleep to the risk of suicide to kids.”

Nestadt and Campo admit that suicide is a difficult topic to discuss, but they say it’s vitally important because talking openly and honestly about it can help save a life.

 “If you are concerned about someone having suicidal thoughts, it is appropriate to ask ‘Are you having thoughts that life is not worth living?’ or ‘Are you thinking about suicide?’” says Nestadt. “These questions will not ‘plant the idea’ or otherwise increase the risk of suicide, but they are good ways to tell if someone may be at risk.”

 In recognition of September being National Suicide Prevention Awareness Month, here are some tips from Johns Hopkins Medicine on interventions:

 Offer help and support. If a loved one is struggling, encourage them to seek care.

  • Restrict access to weapons as much as possible. Any firearms should be locked away securely or temporarily transferred out of the house. Even small barriers to lethal means can be dramatically lifesaving.
  • Look out for each other. Reach out when struggling; be honest with your feelings; and trust your support system.
  • For parents who think their child might be at risk for suicide, consult with the child’s pediatrician or a mental health professional without delay.

 If you or a loved one is in crisis, call the toll-free National Suicide Prevention Lifeline at 1-800-273-TALK (8255). The service is available 24 hours a day, 7 days a week, and all calls are confidential.

Nestadt and Campo are available for interviews.