While high saturated fat levels in red meat have long been known to contribute to heart disease for people in general, the new finding suggests that a subgroup of the population may be at heightened risk for a different reason — a food allergen.

The study, which is supported by the US National Heart, Lung, and Blood Institute, part of the National Institutes of Health, appears in Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB), a peer-reviewed journal of the American Heart Association, the Science Daily reported.

“This novel finding from a small group of subjects from Virginia raises the intriguing possibility that allergy to red meat may be an underrecognized factor in heart disease,” said study leader Coleen McNamara, M.D., a professor of medicine in the Cardiovascular Research Center of the University of Virginia Health System, Charlottesville. “These preliminary findings underscore the need for further clinical studies in larger populations from diverse geographic regions and additional laboratory work.”

The number of people with red meat allergies in the United States is unclear, but researchers estimate that it may be 1 percent of the population in some areas. The number of people who develop blood antibodies to the red meat allergen without having full-blown symptoms is much higher — as much as 20 percent of the population in some areas, the researchers say.

Only in recent years did scientists identify the main allergen in red meat, called galactose-α-1,3-galactose, or alpha-Gal, a type of complex sugar. They also found that a tick — the Lone Star tick — sensitizes people to this allergen when it bites them. That is why red meat allergies tend to be more common where these ticks are more prevalent, such as the Southeastern United States, but also extending to other areas, including Long Island, New York.

Researchers have suspected for some time that allergens can trigger certain immunological changes that might be associated with plaque buildup and artery blockages, but no one had identified a specific substance that is responsible for this effect. In the current study, researchers showed for the first time that a specific blood marker for red meat allergy was associated with higher levels of arterial plaque, or fatty deposits on the inner lining of the arteries. The blood marker they identified is a type of antibody (immunoglobulin or IgE) that is specific to the alpha-Gal allergen.

To identify this blood marker, the researchers analyzed blood samples from 118 adults and detected antibodies to alpha-Gal, indicating sensitivity to red meat, in 26 percent of them. Using an imaging procedure, the researchers found that the quantity of plaque was 30 percent higher in the alpha-Gal sensitized patients than in the non-sensitized patients. These plaques, a hallmark of atherosclerosis (hardening of the arteries), also tended to be more structurally unstable, which means that they have an increased likelihood of causing heart attack and stroke.

The evidence for a link between red meat allergens and coronary artery disease is still preliminary, the researchers noted, so they plan to conduct detailed animal and human studies to confirm their initial findings. Currently, the only treatment for red meat allergy once it is diagnosed is strict avoidance of red meat.

“While more studies are needed, the current work provides a potential new approach or target for preventing or treating heart disease in a subgroup of people who are sensitized to red meat,” said Ahmed Hasan, M.D., Ph.D., a medical officer and program director in NHLBI’s Atherothrombosis & Coronary Artery Disease Branch.

For now, consumers are encouraged to follow current recommendations for a heart-healthy lifestyle. This includes adapting a healthy diet, such as eating plenty of vegetables, fruits, whole grains, and other heart-healthy foods. Lean red meats can be part of a heart-healthy diet for those who are not allergic. Other heart-healthy lifestyle changes also include aiming for a healthy weight, managing stress, getting more exercise, and quitting smoking.

The diminutive size of our aortic valve — just shy of a quarter — belies its essential role in pushing oxygen-rich blood from the heart into the aorta, our body’s largest vessel, and from there to all other organs. Yet for decades, researchers have focused less on damaged valves than on atherosclerosis, the gradual hardening of the blood vessels themselves.

Thanks, in part, to pigs at the University of Wisconsin-Madison’s Arlington Agricultural Research Station, scientists now are catching up on understanding the roots of calcific aortic valve disease.

“For a long time, people thought CAVD was just the valvular equivalent of atherosclerosis,” says Kristyn Masters, a professor of biomedical engineering at UW-Madison. “Today, we know that valve cells are quite unique and distinct from the smooth muscle cells in our blood vessels, which explains why some treatments for atherosclerosis, such as statins, don’t work for CAVD, and why the search for drugs has to start from scratch.”

A team led by Masters has jumped a longstanding hurdle in that search with a study published Monday in the journal Proceedings of the National Academy of Sciences. The researchers teased apart, for the first time, the early cascade of events that may eventually cause stenosis, a severe narrowing of the aortic valve that reduces blood flow to body tissues and weakens the heart.

The only current treatment for stenosis is valve replacement, which typically requires risky and expensive open-heart surgery, Science Daily reported.

“Our study sheds new light on the differences between atherosclerosis and CAVD, especially in terms of bottleneck events that we can target with drugs,” says Masters, whose work is supported by the National Institutes of Health and the American Heart Association. “With a better understanding of how the disease progresses from early to later stages, we may eventually be able to stop CAVD in its tracks and avoid valve replacement surgery.”

Since the hearts of mice and other small animals are vastly different from the human organ, CAVD research has long been hampered by a lack of good animal models. That’s why the pigs — specifically those bred to have an overdose of fatty molecules in their arteries — were an important starting point for the current study.

Their valves provided a snapshot of early CAVD that is challenging to capture in humans, showing that it typically begins with the accumulation of certain sugar molecules called glycosaminoglycans (GAGs) in valve tissue. But to examine exactly how this tissue responds to increasing levels of GAGs, the researchers needed a greater amount of valve tissue than living pigs could provide.

That prompted them to create a first-of-its-kind platform mimicking hallmarks of early porcine CAVD in a lab dish. Key for this model was the ability to grow valve cells in their native healthy form, an important distinction from many previous studies that had focused on already diseased cells.

When the researchers changed only the amount of GAGs these native valve cells were exposed to, while keeping all other conditions the same, they observed surprising results that challenged previous assumptions.

“We thought the GAGs would play a major role in driving the disease process, but the more we added, the fewer inflammatory factors the cells produced and the happier they were,” says Masters. “When we examined this unexpected finding more closely, we noticed two distinct effects: GAGs directly increased a chemical needed to grow new blood vessels, and also trapped low-density lipoprotein (LDL) molecules.”

Neither of these effects was immediately detrimental for valve cells, but the trapping made it more likely for oxygen to react with LDL molecules, and the accumulation of oxidized LDL appeared to be a bottleneck event for a multi-stage process toward valve cell damage, Masters says. This multi-stage process may explain why 25 percent of adults over the age of 65 have CAVD with partially blocked aortic valves, but only one percent goes on to develop stenosis due to a valve that can no longer open and close properly. The fact that native valve cells cannot oxidize LDL themselves, while smooth muscle cells in blood vessels can, also highlights a key distinction between CAVD and atherosclerosis. The study, which included first author Ana Porras, a postdoctoral in Masters’ lab, has important implications for the development of new drugs that may prevent early CAVD from progressing to stenosis by making GAGs less likely to bind LDL.

“The take-home message of our study is that CAVD is a multi-stage process and that healthy valve cells respond differently to LDL than blood vessel cells,” Masters says. “The ability to examine multiple steps in this novel in vitro model for early CAVD opens up several promising avenues for developing drugs that are distinct from those for atherosclerosis.”

The study published Wednesday in the Journal of the American College of Cardiology is the largest to date looking at frequency of nut consumption in relation to incident cardiovascular disease.

Recently, dietary recommendations have shifted toward diets including higher quantities of plant-based foods over animal-based foods, with most dietary patterns including nuts because of their association with reduced cardiovascular risk factors and unique nutritional composition.

While many past studies focused on nut consumption as a whole, researchers in this study also looked at the association between specific types of nuts — peanut butter, peanuts, walnuts and tree nuts — with major cardiovascular events. Peanuts were included even though they are actually a legume because they have a similar fatty acid and nutrient profile as other nuts.

The study looked at over 210,000 people, including women from the Nurses’ Health Study and Nurses’ Health Study II and men from the Health Professionals Follow-up Study, with up to 32 years of follow up. In all three groups, information about medical history, lifestyle and health conditions were collected via self-administered questionnaires every two years, Science Daily reported.

The primary endpoint of the study was major cardiovascular disease, defined as a combined endpoint of myocardial infarction, stroke or fatal cardiovascular disease. Secondary endpoints were total coronary heart disease, defined as fatal or non-fatal myocardial infarction, and total stroke, which included all fatal and non-fatal strokes. Researchers documented 14,136 cardiovascular disease cases, including 8,390 coronary heart disease cases and 5,910 stroke cases.

The study found a consistent inverse association between total nut consumption and total cardiovascular disease and coronary heart disease. Also, after looking at individual nut consumption, eating walnuts one or more times per week was associated with a 19 percent lower risk of cardiovascular disease and 21 percent lower risk of coronary heart disease. Participants who ate peanuts or tree nuts two or more times per week had a 13 percent and 15 percent lower risk of cardiovascular disease, respectively, and a 15 percent and 23 percent, lower risk of coronary heart disease, respectively, compared to those who never consumed nuts.

Participants who consumed five or more servings of nuts a week had a 14 percent lower risk of cardiovascular disease and a 20 percent lower risk of coronary heart disease than participants who never or almost never consumed nuts. The results were similar when accounting for consumption of tree nuts, peanuts and walnuts individually. Researchers found no evidence of an association between total nut consumption and risk of stroke, but eating peanuts and walnuts was inversely associated with the risk of stroke. Peanut butter and tree nuts were not associated with stroke risk.

“Our findings support recommendations of increasing the intake of a variety of nuts, as part of healthy dietary patterns, to reduce the risk of chronic disease in the general populations,” said Marta Guasch-Ferre, PhD, lead author of the study and research fellow at the department of nutrition at Harvard T.H. Chan School of Public Health.

Several limitations were noted in the study, including that the sample size was limited to white health professionals. However, the researchers note that the results can be generalized to men and women of different ethnicities because there is no reason to expect the underlying mechanisms to be different. Also, because the nut intake was self-reported, errors are inevitable, and there was not data on how the nuts were prepared, so the influence of preparation methods was not able to be tested.

In an accompanying editorial comment, Emilio Ros, MD, PHD, of the Endocrinology and Nutrition service at the Hospital Clínic in Barcelona and investigator of CIBEROBN, a research network of Instituto de Salud Carlos III, Spain, confirmed that the consistency of the findings strongly suggests an association between nut consumption and heart disease protection, but there is more to research.

“Ideally, further investigations should test the effects of long-term consumption of nuts supplemented into the usual diet on hard cardiometabolic events,” Ros said. “In the meantime, raw nuts, if possible unpeeled and otherwise unprocessed, may be considered as natural health capsules that can be easily incorporated into any heart-protective diet to further cardiovascular well-being and promote healthy aging.”