Tag: cholesterol

Eggs are Sunny-side up for Cholesterol Levels

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From poached to panfried, when it comes to eggs, it’s all sunny side up, as new research from the University of South Australia confirms that this breakfast favourite won’t crack your cholesterol.

Long blamed for high cholesterol, eggs have been beaten up for their assumed role in cardiovascular disease (CVD). Now, UniSA researchers have shown definitively that it’s not dietary cholesterol in eggs but the saturated fat in our diets that’s the real heart health concern.

In a world-first study, researchers examined the independent effects of dietary cholesterol and saturated fat on LDL cholesterol (the ‘bad’ kind), finding that eating two eggs a day – as part of a high cholesterol but low saturated fat diet – can actually reduce LDL levels and lower the risk of heart disease.

CVD is the leading cause of death worldwide, responsible for nearly 18 million deaths each year. In Australia, one person dies from CVD every 12 minutes, accounting for one in four of deaths nationwide.

Lead researcher, UniSA’s Professor Jon Buckley, says it’s time to rethink the reputation of eggs.

“Eggs have long been unfairly cracked by outdated dietary advice,” Prof Buckley says.

“They’re unique – high in cholesterol, yes, but low in saturated fat. Yet it’s their cholesterol level that has often caused people to question their place in a healthy diet,” Prof Buckley says.

“In this study, we separated the effects of cholesterol and saturated fat, finding that high dietary cholesterol from eggs, when eaten as part of a low saturated fat diet, does not raise bad cholesterol levels.

“Instead, it was the saturated fat that was the real driver of cholesterol elevation.

“You could say we’ve delivered hard-boiled evidence in defence of the humble egg.”

“So, when it comes to a cooked breakfast, it’s not the eggs you need to worry about – it’s the extra serve of bacon or the side of sausage that’s more likely to impact your heart health.”

Source: University of South Australia

Boosting Apolipoprotein-M May Block Age-related Macular Degeneration

Retina showing reticular pseudodrusen. Although they can infrequently appear in individuals with no other apparent pathology, their highest rates of occurrence are in association with age-related macular degeneration (AMD), for which they hold clinical significance by being highly correlated with end-stage disease sub-types, choroidal neovascularisation and geographic atrophy. Credit: National Eye Institute

A new study from Washington University School of Medicine in St. Louis identifies a possible way to slow or block progression of age-related macular degeneration, a leading cause of blindness in people over age 50. The WashU Medicine researchers and their international collaborators implicated problems with cholesterol metabolism in this type of vision loss, perhaps helping to explain the links between macular degeneration and cardiovascular disease, which both worsen with age.

The new findings, using human plasma samples and mouse models of macular degeneration, suggest that increasing the amount of a molecule called apolipoprotein M (ApoM) in the blood fixes problems in cholesterol processing that lead to cellular damage in the eyes and other organs. Various methods of dialing up ApoM could serve as new treatment strategies for age-related macular degeneration and perhaps some forms of heart failure triggered by similar dysfunctional cholesterol processing.

The study appears June 24 in the journal Nature Communications.

“Our study points to a possible way to address a major unmet clinical need,” said senior author Rajendra S. Apte, MD, PhD, professor of ophthalmology and visual sciences at WashU Medicine. “Current therapies that reduce the chance of further vision loss are limited to only the most advanced stages of macular degeneration and do not reverse the disease. Our findings suggest that developing treatments that increase ApoM levels could treat or even prevent the disease and therefore preserve people’s vision as they age.”

In macular degeneration, doctors can see cholesterol-rich deposits under the retina during an eye exam, according to Apte. In early stages, vision might still be normal, but the deposits increase inflammation and other damaging processes the lead to the gradual loss of central vision. In the most common type, “dry” macular degeneration, the cells in the central part of the retina can be damaged, causing a type of neurodegeneration called geographic atrophy, which is similar to what happens in the brain in conditions such as Alzheimer’s disease. Dry macular degeneration can turn into “wet” macular degeneration, in which abnormal blood vessel growth damages vision.

Geographic atrophy and wet macular degeneration are advanced forms of the disease that are accompanied by vision loss. Although some approved therapies for advanced disease are available, the disease process itself is not reversible at that stage.

A common culprit in eye disease and heart failure

In recent years, evidence has emerged that ApoM can serve as a protective molecule with known anti-inflammatory effects and roles in maintaining healthy cholesterol metabolism. With that in mind, Apte and co-senior author Ali Javaheri, MD, PhD, an assistant professor of medicine, were interested in assessing whether reduced ApoM levels, which fall with age, could be involved in the dysfunctional cholesterol metabolism that is at the root of multiple diseases of aging, including macular degeneration and heart disease. They showed that patients with macular degeneration have reduced levels of ApoM circulating in the blood compared with healthy controls. And past work by Javaheri, a WashU Medicine cardiologist, showed that patients with various forms of heart failure also had reduced levels of ApoM in the blood.

This study revealed that ApoM is a key component in the “good cholesterol” pathways that mop up excess “bad” LDL cholesterol and excrete it via the liver.

Apte and Javaheri’s research suggests that when ApoM is low, cells in the retina and heart muscle can’t correctly metabolise cholesterol deposits and struggle to clear these accumulating lipids. When these lipids build up, it leads to inflammation and cellular damage.

To see if they could reverse the harmful effects of low ApoM, the researchers increased ApoM levels in mouse models of macular degeneration, using genetic modification or plasma transfer from other mice. The mice showed evidence of improved retinal health, improved function of light-sensing cells in the retina and reduced accumulation of cholesterol deposits. The researchers further found evidence that ApoM triggers a signalling pathway that breaks down the cholesterol in cellular compartments called lysosomes, which are known for playing important roles in disposing of cellular waste.

The researchers also found that ApoM must be bound to a molecule called sphingosine-1-phosphate (S1P) to get the beneficial effects of ApoM treatment in the mice.

The findings also could have implications for future interventions that raise ApoM in patients with heart failure.

“One of the exciting things about this collaboration is realising the links between retinal pigment epithelial cells and heart muscle cell, which are both vulnerable to low ApoM,” Javeheri said. “It is possible that the interaction between ApoM and S1P is regulating cholesterol metabolism in both cell types. We look forward to exploring strategies to increase ApoM in ways that could help the eye and the heart maintain healthy cholesterol metabolism over time and stave off two major diseases of aging.”

Source: WashU Medicine

Metabolic Syndrome Linked to Increased Risk of Young-onset Dementia

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Having a larger waistline, high blood pressure and other risk factors that make up metabolic syndrome is associated with an increased risk of young-onset dementia, according to a study published on April 23, 2025, online in Neurology®, the medical journal of the American Academy of Neurology. Young-onset dementia is diagnosed before the age of 65. The study does not prove that metabolic syndrome causes young-onset dementia, it only shows an association.

Metabolic syndrome is defined as having excess belly fat plus two or more of the following risk factors: high blood pressure, high blood sugar, higher than normal triglycerides, which are a type of fat found in the blood, and low high-density lipoprotein (HDL) cholesterol, or “good” cholesterol.

“While most dementia is diagnosed in older age, young-onset dementia occurs while a person is still working and perhaps raising a family,” said study author Minwoo Lee, MD, PhD, of Hallym University Sacred Heart Hospital in Anyang, South Korea. “Our study found having metabolic syndrome in middle age is a risk factor for young-onset dementia.”

For the study, researchers reviewed national health insurance data in South Korea to identify nearly two million people between the ages of 40 and 60 who had a health check-up. The check-up included measurements of waist circumference, blood pressure, blood sugar, triglyceride and cholesterol levels. Of all participants, 25% had metabolic syndrome.

Over an average follow-up period of eight years, 8921 people, or 0.45% of all participants, developed dementia. For those with metabolic syndrome, the incidence rate was 0.86 cases per 1000 person-years, compared to 0.49 cases for those without metabolic syndrome. Person-years represent both the number of people in the study and the amount of time each person spends in the study.

After adjusting for age, education and health factors such as level of physical activity, depression and stroke, researchers found metabolic syndrome was associated with a 24% higher risk of dementia. When looking at specific types of dementia, it was associated with a 12% increased risk of Alzheimer’s disease and a 21% increased risk of vascular dementia.

Researchers found female participants with metabolic syndrome had a 34% increased risk of dementia compared to male participants who had a 15% increased risk. People in their 40s had a greater risk than people in their 50s.

Researchers found each component of metabolic syndrome was associated with an increased risk of dementia, which was cumulative. People with all five components had a 70% increased risk of dementia.

“Our findings suggest that lifestyle changes to reduce the risk of metabolic syndrome, such as eating a healthy diet, exercising regularly, maintaining a healthy weight, quitting smoking and reducing stress, may help reduce the risk of young-onset dementia,” said Lee. “Future research that follows people over longer periods of time and uses brain scans to look for biomarkers of dementia is needed to confirm and expand upon our findings.”

A limitation of the study was that researchers did not review genetic risk factors for Alzheimer’s disease.

The study was supported by the Korean National Research Foundation.

Source: American Academy of Neurology

Add-on for Statins Greatly Reduces Recurrence of Heart Attacks

Photo by Mikhail Nilov: https://www.pexels.com/photo/paramedics-using-a-defibrillator-on-a-patient-8942635/

Patients who receive an add-on medication soon after a heart attack have a significantly better prognosis than those who receive it later, or not at all. These are the findings of a new study from researchers at Lund University in Sweden and Imperial College London.

Their analysis suggests that treating patients earlier with a combination of statins and the cholesterol-lowering drug ezetimibe could prevent thousands of new heart attacks in the UK over a decade.

Cardiovascular disease is by far the most common cause of death worldwide, with heart attack (‘myocardial infarction’) being the most common acute event.

For those who survive a heart attack, the risk of a new heart attack is greatest in the first year after the initial event because the blood vessels are more sensitive, making it easier for blood clots to develop.

Our findings suggest that a simple change in treatment guidelines could have a huge impact on patients and reduce the demand on the NHS.

Professor Kausik Ray, School of Public Health

Reducing LDL or “bad” cholesterol in the blood can stabilise changes in the vessels, decreasing the risk for new events.

The current treatment guidelines for patients are high-potency statins immediately after a heart attack, to lower their cholesterol levels.

However, the majority of patients do not reach recommended cholesterol levels using only statins, and so need an add-on treatment, such as ezetimibe.

“Today’s guidelines recommend stepwise addition of lipid-lowering treatment. But it’s often the case that this escalation takes too long, it’s ineffective and patients are lost to follow-up,” says Margrét Leósdóttir, Associate Professor at Lund University and senior cardiology consultant at Skåne University Hospital in Malmö, Sweden. “By giving patients a combination treatment earlier, we could help to prevent many more heart attacks.”

Co-investigator Professor Kausik Ray, from Imperial College London’s School of Public Health, said: “This study shows that we could save lives and reduce further heart attacks by giving patients a combination of two low-cost drugs.

“But at the moment patients across the world aren’t receiving these drugs together. That’s causing unnecessary and avoidable heart attacks and deaths – and also places unnecessary costs on healthcare systems.

“Our study shows the way forward; care pathways must now change for patients after this type of heart event.”

Reducing heart attacks

In the latest study, the international team examined outcomes for heart attack patients if they received a combination of statins with the add-on therapy ezetimibe (within 12 weeks after a heart attack), statins with ezetimibe added later (between 13 weeks and 16 months), or just statins with no ezetimibe at all.

Based on Swedish registry data from 36 000 patients who had a heart attack between 2015 and 2022, the researchers used advanced statistical models to emulate a clinical trial.

The results show that patients who received a combination treatment of statins and ezetimibe within 12 weeks of a heart attack and were able to lower cholesterol to the target level early, had a better prognosis and less risk of new cardiovascular events and death than those who received the add-on treatment later, or not at all.

From the analysis, the researchers believe many new heart attacks, strokes and deaths could be prevented every year internationally if the treatment strategy were to be changed.

Under a scenario in which 100% of patients would receive ezetimibe early, they estimate 133 heart attacks could be avoided in a population of 10 000 patients in 3 years.

The researchers suggest that in the UK, which records an estimated 100 000 hospital admissions from heart attacks a year,[1] this would equate to an estimated 5000 heart attacks being prevented over a ten year period.[2]

Improving guidance

Dr Leósdóttir said: “Combination therapy is not applied up-front for two main reasons. General recommendations are not included in today’s guidelines and a precautionary principle is applied to avoid side effects and overmedication.

However, there are positive effects from applying both medicines as soon after the infarction as possible. Not doing this entails an increased risk. In addition, the drug we have examined in the study causes few side effects and is readily available and inexpensive in many countries.”

Margrét Leósdóttir hopes that the research results will in time provide support for changes in the recommendations. A treatment algorithm has already been introduced at her hospital in Sweden to help doctors to prescribe appropriate lipid-lowering treatment for patients who have had a myocardial infarction.

It has been noted that patients achieve their treatment goals earlier and two months after the infarction twice as many patients have reduced their bad cholesterol to the target level, compared with previously.

“Several other hospitals in Sweden have also adopted the algorithm and there are similar examples from other countries that have produced as good results. My hope is that even more will review their procedures, so that more patients will get the right treatment in time, and we can thereby prevent unnecessary suffering and save lives.”

Source: Imperial College London

Eggs are not the Cholesterol Menace They were Thought to be

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Many people hesitate to eat eggs amid concerns that they may raise cholesterol levels, with negative cardiovascular consequences. However, results from a prospective, controlled trial presented at the American College of Cardiology’s Annual Scientific Session show that over a four-month period cholesterol levels and other cardiovascular markers were similar among people who ate fortified eggs most days of the week compared with a non-egg eating control group.

A total of 140 patients with or at high risk for cardiovascular disease were enrolled in the PROSPERITY trial, which aimed to assess the effects of eating 12 or more fortified eggs a week versus a non-egg diet (consuming less than two eggs a week) on HDL- and LDL-cholesterol, as well as other key markers of cardiovascular health over a four-month study period.

“We know that cardiovascular disease is, to some extent, mediated through risk factors like high blood pressure, high cholesterol and increased BMI and diabetes. Dietary patterns and habits can have a notable influence on these and there’s been a lot of conflicting information about whether or not eggs are safe to eat, especially for people who have or are at risk for heart disease,” said Nina Nouhravesh, MD, a research fellow at the Duke Clinical Research Institute in Durham, North Carolina, and the study’s lead author. “This is a small study, but it gives us reassurance that eating fortified eggs is OK with regard to lipid effects over four months, even among a more high-risk population.”

Eggs are a common and relatively inexpensive source of protein and dietary cholesterol. Nouhravesh and her team wanted to look specifically at fortified eggs as they contain less saturated fat and additional vitamins and minerals, such as iodine, vitamin D, selenium, vitamin B2, 5 and 12, and omega-3 fatty acids.

For this study, patients were randomly assigned to eat 12 fortified eggs a week (cooked in whatever manner they chose) or to eat fewer than two eggs of any kind (fortified or not) per week.  All patients were 50 years of age or older (the average age was 66 years), half were female and 27% were Black. All patients had experienced one prior cardiovascular event or had two cardiovascular risk factors, such as high blood pressure, high cholesterol, increased BMI or diabetes. The co-primary endpoint was LDL and HDL cholesterol at four months. Secondary endpoints included lipid, cardiometabolic and inflammatory biomarkers and levels of vitamin and minerals. 

Patients had in-person clinic visits at the start of the study and visits at one and four months to take vital signs and have bloodwork done. Phone check-ins occurred at two and three months and patients in the fortified egg group were asked about their weekly egg consumption. Those with low adherence were provided additional education materials.

Results showed a -0.64mg/dL and a -3.14mg/dL reduction in HDL-cholesterol and LDL cholesterol, respectively, in the fortified egg group. While these differences weren’t statistically significant, the researchers said the differences suggest that eating 12 fortified eggs each week had no adverse effect on blood cholesterol. In terms of secondary endpoints, researchers observed a numerical reduction in total cholesterol, LDL particle number, another lipid biomarker called apoB, high-sensitivity troponin (a marker of heart damage), and insulin resistance scores in the fortified egg group, while vitamin B increased.

“While this is a neutral study, we did not observe adverse effects on biomarkers of cardiovascular health and there were signals of potential benefits of eating fortified eggs that warrant further investigation in larger studies as they are more hypothesis generating here,” Nouhravesh said, explaining that subgroup analyses revealed numerical increases in HDL cholesterol and reductions in LDL cholesterol in patients 65 years or older and those with diabetes in the fortified egg group compared with those eating fewer than two eggs.

So why have eggs gotten a bad rap? Some of the confusion stems from the fact that egg yolks contain cholesterol. Experts said a more important consideration, especially in the context of these findings, might be what people are eating alongside their eggs, such as buttered toast, bacon and other processed meats, which are not heart healthy choices. As always, Nouhravesh said it’s a good idea for people with heart disease to talk with their doctor about a heart healthy diet.

This single-centre study is limited by its small size and reliance on patients’ self-reporting of their egg consumption and other dietary patterns. It was also an unblinded study, which means patients knew what study group they were in, which can influence their health behaviours.

The study was funded by Eggland’s Best.

Source: American College of Cardiology

Cholesterol Discovery could Lead to New Therapies to Prevent Cardiovascular Disease

Source: CC0

Researchers at the University of Leicester have discovered the mechanism by which cholesterol in the diet is absorbed into cells. This discovery, which has just been published in the journal Science opens up new opportunities for therapeutic intervention to control cholesterol uptake that could complement other therapies and potentially save lives.

The research, conducted with colleagues from the USA, 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.

Funding came from the Leducq Foundation which awarded $6 million to eight laboratories across the USA and Europe for collaborative research into how cholesterol is transported in our bodies.

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.

Professor 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.

Professor Schwabe added: “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.

“The Leducq team of experts have different expertise that is used to target the problem at different levels and following different approaches. 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.”

Postdoctoral Researcher, Dr Beatriz Romartinez-Alonso, added: “This has been a great project to work on – discovering new science highly relevant to human health.”

Source: University of Leicester

Fluctuating Cholesterol and Triglyceride Levels Linked to Developing Dementia

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Older people who have fluctuating levels of total cholesterol and triglycerides may have a higher risk of Alzheimer’s disease and related dementias compared to people who have steady levels, according to new research published online in Neurology. Since the study is observational, it cannot establish a causative link.

“Prevention strategies for Alzheimer’s and related dementias are urgently needed,” said study author Suzette J. Bielinski, PhD, of the Mayo Clinic in Rochester, Minnesota. “Routine screenings for cholesterol and triglyceride levels are commonly done as part of standard medical care. Fluctuations in these results over time could potentially help us identify who is at greater risk for dementia, help us understand mechanisms for the development of dementia and ultimately determine whether levelling out these fluctuations could play a role in reducing dementia risk.”

Researchers used health care data to identify 11 571 people age 60 or older without a prior diagnosis of Alzheimer’s disease or dementia. They assessed total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) for the participants on at least three different days in the five years before the start of the study. Then participants were assigned into five equal groups based on the degree of measurement fluctuation, from lowest to highest.

Participants were followed for an average of 13 years. During that time, 2473 of them developed Alzheimer’s disease or another form of dementia. After adjusting for confounding variables, researchers found for total cholesterol, participants in the highest fluctuation group had a 19% increased risk of dementia compared to those in the lowest group. Of the 2311 people in the highest group, 515 developed dementia compared to 483 of the 2311 people in the lowest group. For triglycerides, those in highest group had a 23% increased risk.

No link was found between dementia and variations in LDL and HDL, however.

“It remains unclear why and how fluctuating levels of cholesterol and triglycerides are related to the risk of Alzheimer’s disease,” said Bielinski. “Further studies looking at the changes over time for this relationship are needed in order to confirm our results and potentially consider preventative strategies.”

One study limitation was that researchers looked at Alzheimer’s disease and related dementias as a whole and did not differentiate between the types of dementia.

Source: American Academy of Neurology

Atherosclerosis is a Greater Heart Attack Risk for Women

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Postmenopausal women with atherosclerosis are at higher risk of heart attacks than men of similar age, according to research presented at EACVI 2023, a scientific congress of the European Society of Cardiology (ESC), and published in European Heart Journal – Cardiovascular Imaging. Researchers used imaging techniques to examine the arteries of nearly 25 000 patients and followed them for heart attacks and death.

“The study suggests that a given burden of atherosclerosis is riskier in postmenopausal women than it is in men of that age,” said study author Dr Sophie van Rosendael of Leiden University Medical Centre. “Since atherosclerotic plaque burden is emerging as a target to decide the intensity of therapy to prevent heart attacks, the findings may impact treatment. Our results indicate that after menopause, women may need a higher dose of statins or the addition of another lipid-lowering drug. More studies are needed to confirm these findings.”

While young women do have heart attacks, in general, women develop atherosclerosis (narrowing of arteries due to plaque buildup) later in life than men and have heart attacks at an older age than men, in part because of the protective effect of oestrogen. This study examined whether the prognostic importance of atherosclerotic plaques are the same for women and men at different ages as this could be important for selecting treatments to prevent heart attacks.

The study included 24 950 patients referred for coronary computed tomography angiography (CCTA) and enrolled in the CONFIRM registry, which was conducted in six countries in North America, Europe, and Asia. CCTA is used to obtain 3D images of the arteries in the heart.

Total atherosclerotic burden was rated using the Leiden CCTA score, which incorporates the following items for each coronary segment: plaque presence (yes/no), composition (calcified, noncalcified or mixed), location, and severity of narrowing, for a final value of 0 to 42. Patients were divided into three categories previously found to predict the risk myocardial infarction: low atherosclerotic burden (0 to 5), medium (6 to 20) and high (over 20). In addition, obstructive coronary artery disease was defined as 50% narrowing or more.

The primary outcome was the difference in Leiden CCTA score between women and men of similar age. The investigators also analysed sex differences in the rates of major adverse cardiovascular events (MACE), which included all-cause death and myocardial infarction, after adjusting for age and cardiovascular risk factors (hypertension, high cholesterol, diabetes, current smoking and family history of coronary artery disease).

A total of 11 678 women (average age 58.5 years) and 13 272 men (average age 55.6 years) were followed for 3.7 years. Regarding the primary outcome, the study showed an approximately 12 year delay in the onset of coronary atherosclerosis in women: the median Leiden CCTA risk score was above zero at age 64 to 68 years in women versus 52 to 56 years in men (p<0.001). In addition, the overall plaque burden as quantified by the Leiden CCTA score was significantly lower in women, who had more non-obstructive disease.

Dr. van Rosendael said: “The results confirm the previously reported delay in the start of atherosclerosis in women. We also found that women are more likely to have non-obstructive disease. It was formerly thought that only obstructive atherosclerosis caused myocardial infarction but we now know that non-obstructive disease is also risky.”
 
The burden of atherosclerosis was equally predictive of MACE in premenopausal women (aged under 55 years) and men of the same age group. However, in postmenopausal women (age 55 years and older), the risk of MACE was higher than men for a given score. In postmenopausal women, compared to those with a low burden, those with a medium and high burden had 2.21-fold and 6.11-fold higher risks of MACE. While in men aged 55 years and older, compared to those with a low burden, those with a medium and high burden had 1.57-fold and 2.25-fold greater risks of MACE.

Dr van Rosendael said: “In this study, the elevated risk for women versus men was especially observed in postmenopausal women with the highest Leiden CCTA score. This could be partly because the inner diameter of coronary arteries is smaller in women, meaning that the same amount of plaque could have a larger impact on blood flow. Our findings link the known acceleration of atherosclerosis development after menopause with a significant increase in relative risk for women compared to men, despite a similar burden of atherosclerotic disease. This may have implications for the intensity of medical treatment.”

Source: European Society of Cardiology

A New Drug Class Lowers Cholesterol by 70%

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A new study using mouse models describes an orally administered small-molecule drug that reduces lowers cholesterol by 70% by preventing the degradation of low-density lipoprotein (LDL) receptors. Published in Cell Reports, the findings point to a previously unrecognised strategy for managing cholesterol – one which may also impact cancer treatments.

“Cholesterol lowering is one of the most important therapies we have to prolong life and protect people from heart disease, which is still the number one cause of morbidity and mortality in the Western world,” said senior author Jonathan S. Stamler, MD, professor at Case Western Reserve School of Medicine.

“Statins only lower cholesterol so far. This is a drug class that we think would represent a new way to lower cholesterol, a new way to hit PCSK9.”

Study Findings

Central to cholesterol regulation are LDL receptors, which sit at the surface of liver cells and remove cholesterol from the blood, thereby lowering serum levels. PCSK9 in the bloodstream controls the number of LDL receptors by marking them for degradation. Therefore, agents that inhibit PCSK9 increase the number of LDL receptors that remove cholesterol.

Nitric oxide is a molecule that is known to prevent heart attacks by dilating blood vessels. In the new study, Stamler and colleagues show that nitric oxide can also target and inhibit PCSK9, thus lowering cholesterol. They identify a small molecule drug that functions to increase nitric oxide inactivation of PCSK9. Mice treated with the drug display a 70% reduction in LDL cholesterol.

Beyond Cholesterol to Cancer

In addition to impacting the field of cholesterol metabolism, the findings may impact patients with cancer, as emerging evidence suggests targeting PCSK9 can improve the efficacy of cancer immunotherapies.

“PCSK9 not only targets LDL receptors for degradation, it also mediates the degradation of MHC 1 on lymphocytes, which is used for recognition of cancer cells” said Stamler. “PCSK9 is effectively preventing your lymphocytes from recognising cancer cells. So, if you inhibit PCSK9, you can boost the body’s cancer surveillance. There may be an opportunity one day to apply these new drugs to that need.”

An Egg a Day Keeps the Cardiologist Away

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Research published in eLife has shown how moderate egg consumption can increase the amount of heart-healthy metabolites in the blood. The findings suggest that eating up to one egg per day may help lower the risk of developing cardiovascular disease.

A rich source of dietary cholesterol, eggs also contain a variety of essential nutrients. Eggs have long had a bad rap when it comes to cardiovascular health, with conflicting evidence as to whether egg consumption is beneficial or harmful to heart health. A large study in China showed that those who ate one egg a day had a lower cardiovascular disease risk than those who ate eggs occasionally. To explore this, researchers carried out a population-based study exploring how egg consumption affects markers of cardiovascular health in the blood.

“Few studies have looked at the role that plasma cholesterol metabolism plays in the association between egg consumption and the risk of cardiovascular diseases, so we wanted to help address this gap,” explained first author Lang Pan, MSc at the Department of Epidemiology and Biostatistics, Peking University, Beijing, China.

Pan and the team selected 4778 participants from the China Kadoorie Biobank, 3401 of whom had a cardiovascular disease and 1377 did not. Measuring 225 metabolites in plasma samples taken from the participants’ blood, they identified 24 that were associated with self-reported levels of egg consumption.

Their analyses showed that individuals who ate a moderate amount of eggs had higher levels of a protein in their blood called apolipoprotein A1- a building-block of high-density lipoprotein (HDL). These individuals especially had more large, protective HDL molecules in their blood.

The researchers further identified 14 metabolites linked to heart disease, and participants who ate fewer eggs had lower levels of beneficial metabolites and higher levels of harmful ones in their blood, compared to regular egg eaters.

“Together, our results provide a potential explanation for how eating a moderate amount of eggs can help protect against heart disease,” says author Canqing Yu, Associate Professor at the Department of Epidemiology and Biostatistics, Peking University. “More studies are needed to verify the causal roles that lipid metabolites play in the association between egg consumption and the risk of cardiovascular disease.”

“This study may also have implications for Chinese national dietary guidelines,” adds senior author Liming Li, Boya Distinguished Professor at the Department of Epidemiology and Biostatistics, Peking University. “Current health guidelines in China suggest eating one egg a day, but data indicate that the average consumption is lower than this. Our work highlights the need for more strategies to encourage moderate egg consumption among the population, to help lower the overall risk of cardiovascular disease.”

Source: eLife