US Pharm. 2024;49(2):11-47.


Research on Twins Indicates Vegan Diet Improves Cardiovascular Health

In a study of identical twins, Stanford Medicine researchers and their colleagues have found that a vegan diet improves cardiovascular health in as few  as 8 weeks.

Although it is well-known that eating less meat improves cardiovascular health, diet studies are often hampered by factors such as genetic differences, upbringing, and lifestyle choices. By studying identical twins, however, the researchers were able to control for genetics and limit the other factors, as the twins grew up in the same households and reported similar lifestyles.

“Not only did this study provide a groundbreaking way to assert that a vegan diet is healthier than the conventional omnivore diet, but the twins were also a riot to work with,” said Christopher Gardner, PhD, the Rehnborg Farquhar Professor and a professor of medicine. “They dressed the same, they talked the same and they had a banter between them that you could have only if you spent an inordinate amount of time together.”

The study was published in JAMA Network Open, and Dr. Gardner was the senior author. The study was cofirst–authored by Matthew Landry, PhD, a former Stanford Prevention Research Center postdoctoral scholar, now at the University of California, Irvine, and Catherine Ward, PhD, a postdoctoral scholar at the center.

The trial, conducted from May 2022 to July 2022, consisted of 22 pairs of identical twins for a total of 44 participants. The study authors selected healthy participants without cardiovascular disease from the Stanford Twin Registry—a database of fraternal and identical twins who have agreed to participate in research studies—and matched one twin from each pair with either a vegan or omnivore diet.

Both diets were healthy, replete with vegetables, legumes, fruits, and whole grains and void of sugars and refined starches. The vegan diet was entirely plant-based and included no meat or animal products, such as eggs or milk. The omnivore diet included chicken, fish, eggs, cheese, dairy, and other animal-sourced foods.

During the first 4 weeks, a meal service delivered 21 meals per week: seven breakfasts, lunches, and dinners. For the remaining 4 weeks, the participants prepared their own meals.

A registered dietitian was on call to offer suggestions and answer questions regarding the diets during the duration of the study. The participants were interviewed about their dietary intake and kept a log of the food they ate.

Forty-three participants completed the study, which, Dr. Gardner said, demonstrates how feasible it is to learn how to a prepare a healthy diet in 4 weeks.

“Our study used a generalizable diet that is accessible to anyone, because 21 out of the 22 vegans followed through with the diet,” said Dr. Gardner, who is a professor in the Stanford Prevention Research Center. “This suggests that anyone who chooses a vegan diet can improve their long-term health in 2 months, with the most change seen in the first month.”

The authors found the most improvement over the first 4 weeks of the diet change. The participants with a vegan diet had significantly lower low-density lipoprotein cholesterol (LDL-C) levels, insulin, and body weight, all of which are associated with improved cardiovascular health, than the omnivore participants.

At the beginning of the trial, at 4 weeks, and at 8 weeks, the researchers weighed the participants and drew their blood. The average baseline LDL-C level for the vegans was 110.7 mg/dL and 118.5 mg/dL for the omnivore participants; it dropped to 95.5 mg/dL for vegans and 116.1 mg/dL for omnivores at the end of the study. The optimal healthy LDL-C level is less than 100 mg/dL.

Because the participants already had healthy LDL-C levels, there was less room for improvement, Dr. Gardner said, speculating that participants who had higher baseline levels would show greater change.

The vegan participants also showed about a 20% drop in fasting insulin (higher insulin level is a risk factor for developing diabetes). The vegans also lost an average of 4.2 more pounds than the omnivores. “Based on these results and thinking about longevity, most of us would benefit from going to a more plant-based diet,” Dr. Gardner said.

The vegan participants (and the omnivores to some extent) did the three most important things to improve cardiovascular health, he added: They cut back on saturated fats, increased dietary fiber, and lost weight.


Discovery Could Lead to CVD- and Stroke-Prevention Therapies

Researchers at the University of Leicester in the United Kingdom have discovered the mechanism by which cholesterol in our diet is absorbed into our cells. This discovery, which was published in Science, may open up new opportunities for interventions to control cholesterol uptake that could complement other therapies and potentially save lives.

The research, conducted with colleagues from the United States, China, and Australia, has shown that two proteins (called Aster B and Aster C) play a key role in transporting cholesterol from the membrane of the cells lining our intestine to the internal compartment, where it is modified prior to circulation.

University of Leicester researchers from the Institute of Structural and Chemical Biology used their expertise to reveal how ezetimibe, a cholesterol-lowering drug, blocks the ability of Aster B and C to transport cholesterol.

John Schwabe, director of the Institute for Structural and Chemical Biology, said, “This breakthrough is the result of a long-lasting collaboration and forms part of an international effort to identify ways in which we can combat cardiovascular disease and stroke. A better understanding of important areas of cholesterol absorption and metabolism and, particularly, how cholesterol moves within cells and tissues, is essential. This knowledge will allow us to design new drugs and therapies that target specific proteins involved in these pathways to combat most pressing public health problems, such as heart attacks and stroke.”

Dr. Schwabe said, “If we can prevent some cholesterol from being absorbed into our cells, we may ultimately be able to prevent individuals from having high cholesterol and cut down their risks of heart attack and stroke and therefore potentially save lives.

“In addition to target cholesterol absorption, we are trying to identify how cholesterol metabolism and transport affect cholesterol levels and atherosclerotic disease. Cholesterol transporters are essential to regulate blood cholesterol levels; therefore, we are testing small molecules that influence the function of these transporters in order to develop drugs that ultimately lower the risk for heart attack and stroke,” he added.


Increasing Workplace Flexibility Linked With Lower CVD Risk

Increasing workplace flexibility may lower employees’ risk of cardiovascular disease (CVD), according to a study led by Harvard T.H. Chan School of Public Health and Penn State University. In workplaces that implemented interventions designed to reduce conflict between employees’ work and their personal/family lives, researchers observed that employees at higher baseline cardiometabolic risk, particularly older employees, experienced a reduction in their risk for CVD equivalent to between 5 and 10 years of age-related cardiometabolic changes.

The study, among the first to assess whether changes to the work environment can affect cardiometabolic risk, was published in The American Journal of Public Health.

“The study illustrates how working conditions are important social determinants of health,” said colead author Lisa Berkman, Thomas D. Cabot Professor of Public Policy and of Epidemiology at Harvard Chan School and director of the Harvard Center for Population and Development Studies.

“When stressful workplace conditions and work-family conflict were mitigated, we saw a reduction in the risk of cardiovascular disease among more vulnerable employees, without any negative impact on their productivity. These findings could be particularly consequential for low- and middle-wage workers who traditionally have less control over their schedules and job demands and are subject to greater health inequities.”

As part of the Work, Family and Health Network, the researchers designed a workplace intervention meant to increase work-life balance: Supervisors were trained on strategies to show support for employees’ personal and family lives alongside their job performances, and teams (supervisors and employees) attended hands-on trainings to identify new ways to increase employees’ control over their schedules and tasks.

The researchers randomly assigned the intervention to work units/sites within two companies: an IT company comprised of 555 participating employees and a long-term care company with 973 participating employees. The IT employees consisted of male and female high- and moderate-salaried technical workers; the long-term care employees mostly consisted of female, low-wage direct caregivers. Other units/sites were not assigned the intervention and, therefore, conducted their business as usual.

These 1,528 employees across the experimental and control groups had their systolic blood pressure, BMI, glycated hemoglobin, smoking status, high-density lipoprotein (HDL) cholesterol, and total cholesterol recorded at the beginning of the study and again 12 months later. The researchers used this health information to calculate a cardiometabolic risk score (CRS) for each employee, with a higher score indicating a higher estimated risk of developing CVD within the decade.

The study found that the workplace intervention did not have any significant overall effects on employees’ CRS. However, the researchers observed reductions in CRS, specifically among those with a higher baseline CRS: Those employees of the IT company and of the long-term care company saw a reduction in their CRS equivalent to 5.5 and 10.3 years of age-related changes, respectively. Age also played a role: Employees aged older than 45 years with a higher baseline CRS were likelier to see a reduction than their younger counterparts.

“The intervention was designed to change the culture of the workplace over time with the intention of reducing conflict between employees’ work and personal lives and ultimately improving their health,” said colead author Orfeu Buxton, professor of biobehavioral health and director of the Sleep, Health & Society Collaboratory at Penn State University. “Now we know such changes can improve employee health and should be more broadly implemented.”


Heart Valve Infections Deaths Drop Overall but Surge Among Young Adults

Death rates related to infective endocarditis declined in most adults across the United States within the past 2 decades yet accelerated among young adults aged 25 to 44 years, according to research published in the Journal of the American Heart Association.

Infective endocarditis, also called bacterial endocarditis, is an infection caused by bacteria that enter the bloodstream and settle in the heart lining, a heart valve, or a blood vessel. The disease is rare, however, and people with previous valve surgeries, heart valve abnormalities, artificial valves, congenital heart defects, or previous infective endocarditis have a greater risk of developing it. It can also be a complication of injecting illicit drugs.

“Our study findings raise a public health concern, especially since the deaths in younger age groups are on the rise,” said study lead author Sudarshan Balla, MD, an associate professor of medicine at the West Virginia University Heart and Vascular Institute at J.W. Ruby Memorial Hospital in Morgantown. “We speculate that this acceleration was likely, in the most part, due to the opioid crisis that has engulfed several states and involved principally younger adults.”

Researchers examined death certificate data from the CDC Multiple Cause of Death dataset, which contains death rates and population counts for all U.S. counties. They looked for national trends in deaths caused by infective endocarditis plus differences in deaths related to age, sex, race, and geography among states from 1999 to 2020.

Researchers also analyzed the association with substance use disorder, considering the emergence of the opioid epidemic during the study’s time frame.

The analysis found the following:  In the 21-year period analyzed, infective endocarditis death rates declined overall in the U.S.; death rates increased significantly for young adults, at an average annual change of more than 5% for the 25-to-34 years age group and more than 2% for the 35-to-44 years age group; in the 45-to-54 years age category, death rates remained stagnant at 0.5%, and there was a significant decline among those aged 55 years and older.

The scientists also found that substance use disorder associated with multiple causes of death increased drastically—between twofold and sevenfold among the 25-to-44 years age group, and that Kentucky, Tennessee, and West Virginia showed an acceleration in deaths caused by infective endocarditis in contrast to other states, with either a predominant decline or no change.

“We found that substance use was listed as a contributing cause that could explain the higher death rates in the younger age groups and also in the states in those who died due to endocarditis,” Dr. Balla said.

The study researchers called the rise of infective endocarditis as the underlying cause of death in adults aged 25 to 44 years “alarming” and recommended more investigation to identify the reasons for these trends among young adults and in the three states noted.

The researchers speculated that the increase is connected to the opioid crisis that has engulfed several states and involves primarily younger adults. “Comprehensive care plans for those treated for infective endocarditis should also include screening and treatment for substance use disorder,” Dr. Balla said.

To address IV drug use, some states have started harm-reduction programs, which are public health efforts to reduce the harm from substance use and drug abuse, such as increased risk of infectious diseases like HIV, viral hepatitis, and bacterial and fungal infections.

“Whether these programs make an impact is yet to be determined,” Dr. Balla said.

The researchers were limited in the medical details that they could collect because of the use of death certificate data, which may contain inaccuracies, such as errors in diagnosis, data entry, and cause of death. For similar reasons, researchers could not determine a direct cause-and-effect relationship between the rise in deaths caused by infective endocarditis in younger adults and substance use disorder.


Increased Risk of Heart Rhythm Disruption After COVID-19

Individuals infected with COVID-19 are also at an increased risk of suffering from heart rhythm disturbances, such as atrial fibrillation. This is shown in a new study at Umeå University, Sweden.

“The results underline the importance of both being vaccinated against COVID-19 and that the healthcare system identifies people at increased risk of this type of complications, so that the correct diagnosis is made and appropriate treatment is started in time,” said Ioannis Katsoularis, first author of the study and cardiologist at University Hospital of Northern Sweden in Umeå.

The researchers were able to show that those who had been ill with COVID-19 could also suffer from heart rhythm disturbances, both in the form of so-called tachycardias, when the heart rate is high, and bradyarrhythmias, when the heart is slow and for which a pacemaker is sometimes needed.

The study shows that the risk of atrial fibrillation and flutter was increased up to 2 months after infection. In the first month, the risk was 12 times greater than for people who did not suffer from COVID-19 infection. Even the risk of a specific subset of tachycardias, paroxysmal supraventricular tachycardias, was elevated up to 6 months after the infection and was five times greater in the first month.

Bradyarrhythmia risk was increased up to 14 days after the infection and was three times greater in the first month compared with subjects without COVID-19. Previous research in this area had not focused as much on which individuals are most at risk.

“We found that the risks were higher in older individuals, individuals with severe COVID-19, and during the first wave of the pandemic. We could also see that unvaccinated people were at higher risk than vaccinated people. Overall, the severity of the infection was the strongest risk factor,” said Anne-Marie Fors Connolly, who leads the research group at Umeå University that is behind the study.

In the study, information from large national registers was cross-checked. All people who tested positive for the virus in Sweden from the start of the pandemic until May 2021 were included, as well as a comparison group of individuals without a positive test for the virus. Over 1 million individuals with COVID-19 and over 4 million control individuals were included in this nationwide study, which is one of the largest of its kind in the world. Researchers at Umeå University have previously shown that COVID-19 leads to an increased risk of blood clots, myocardial infarction, and stroke.

Artery Calcification More Common in Night Owls

Artery calcification is almost twice as common in night owls compared with early birds, according to a study from the University of Gothenburg, Sweden. Circadian function appears to be particularly important during the early stages of cardiovascular disease.

Atherosclerosis involves fatty deposits accumulating on the inside of the arteries, making it harder for blood to pass through. The disease develops over a very long period of time and is not evident until it leads to blood clots causing angina, heart attack, or stroke.

Previous research has shown that people with late-night habits have an increased risk of cardiovascular disease, but this is the first study to show how circadian rhythms specifically affect calcification of the arteries. The study, published in the journal Sleep Medicine, involved 771 men and women aged 50 to 64 years, all of whom are part of the SCAPIS larger population study.

The degree of artery calcification in the heart’s coronary arteries was examined using computer tomography. Participants indicated their so-called chronotype on a five-point scale: extreme morning, moderate morning, intermediate, moderate evening, or extreme evening.

Of the 771 participants, 144 identified as extreme-morning types and 128 as extreme-evening types. Among the group who were most alert in the morning, 22.2% had pronounced artery calcification—the lowest proportion of all five chronotypes. The extreme evening–type group had the highest prevalence of severe coronary artery calcification, at 40.6%.

The first author of the study, Mio Kobayashi Frisk, a doctoral student at Sahlgrenska Academy, University of Gothenburg, said, “Our results indicate that extreme evening chronotype may be linked not only to poorer cardiovascular health in general, but also more specifically to calcification in the coronary arteries calcification and atherosclerosis.”

The statistical analysis considered a range of other factors that can affect the risk of atherosclerosis, including blood pressure, blood lipids, weight, physical activity, stress level, sleep, and smoking.

The last author of the study, Ding Zou, a researcher at Sahlgrenska Academy, University of Gothenburg, said, “As well as the previously known factors, the individual circadian rhythm also appears to be an important risk factor for atherosclerosis. We interpret our results as indicating that circadian rhythms are more significant early in the disease process. It should therefore particularly be considered in the preventive treatment of cardiovascular diseases.”

Those who had experienced a heart attack were excluded from the study, meaning that the study participants were healthier than the general population. Another weakness identified by the researchers is that participants themselves provided their chronotype. Each chronotype can be said to have an average time when half of the night’s sleep has passed.

In a previous study on the same population, though not necessarily the same individuals, this time occurred at 2:55 AM for the extreme morning-type group and at 4:25 AM for the extreme evening-type group. The remaining chronotype groups’ mid-sleep times were somewhere in between these extremes.

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