Category: Cardiovascular Disease

Categories : Cardiovascular Disease NeurologyTags :

The Heart has a ‘Brain’ of its Own

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Human heart. Credit: Scientific Animations CC4.0

New research from Karolinska Institutet and Columbia University shows that the heart has a mini-brain – its own nervous system that controls the heartbeat. A better understanding of this system, which is much more diverse and complex than previously thought, could lead to new treatments for heart diseases. The study, conducted on zebrafish, is published in Nature Communications.

The heart has long been thought to be controlled solely by the autonomic nervous system, which transmits signals from the brain. The heart’s neural network, which is embedded in the superficial layers of the heart wall, has been considered a simple structure that relays the signals from the brain. However, recent research suggests that it has a more advanced function than that.

Controlling the heartbeat

Scientists have now discovered that the heart has its own complex nervous system that is crucial to controlling its rhythm.

“This ‘little brain’ has a key role in maintaining and controlling the heartbeat, similar to how the brain regulates rhythmic functions such as locomotion and breathing,” explains Konstantinos Ampatzis, principal researcher and docent at the Department of Neuroscience, Karolinska Institutet, Sweden, who led the study.

The researchers identified several types of neurons in the heart that have different functions, including a small group of neurons with pacemaker properties. The finding challenges the current view on how the heartbeat is controlled, which may have clinical implications.

Surprising complexity revealed

“We were surprised to see how complex the nervous system within the heart is,” says Konstantinos Ampatzis. “Understanding this system better could lead to new insights into heart diseases and help develop new treatments for diseases such as arrhythmias.” 

The study was conducted on zebrafish, an animal model that exhibits strong similarities to human heart rate and overall cardiac function. The researchers were able to map out the composition, organisation and function of neurons within the heart using a combination of methods such as single-cell RNA sequencing, anatomical studies and electrophysiological techniques.

New therapeutic targets

“We will now continue to investigate how the heart’s brain interacts with the actual brain to regulate heart functions under different conditions such as exercise, stress, or disease,” says Konstantinos Ampatzis. “We aim to identify new therapeutic targets by examining how disruptions in the heart’s neuronal network contribute to different heart disorders.”

Source: Karolinska Institutet

Categories : Cardiovascular Disease New Compounds and TreatmentsTags :

Deep Depletion of Blood Lipoprotein(a) Levels with New Drug

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Image by Scientific Animations, CC4.0

In a new study, researchers found that a new drug under development, zerlasiran, depleted levels of lipoprotein(a) by more than 80% in participants with increased cardiovascular risk. The drug was well tolerated and the findings, published in JAMA Network, suggest that this could be the first viable treatment for elevated levels of lipoprotein(a).

Elevated levels of lipoprotein(a) (LPa) – a type of cholesterol – is a genetic risk factor for cardiovascular disease. Present in 20% of the population, it increases the risk of atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis. Currently, there are no interventions which can bring down high LPa levels: it is unresponsive to diet, exercise, and other lifestyle changes and there is no available drug.

Zerlasiran, a small-interfering RNA that targets synthesis of LPa serum concentration, was developed to fill this gap. It is effectively a gene silencer that shuts down LPA, a gene which produces a protein found only in LPa. This in turn is expected to reduce cardiovascular risk.

A phase I clinical trial had shown that zerlasiran was safe and effective.

For the study, researchers enrolled 178 patients (average age 63.7 years, 46 female) with ASCVD and LPa concentrations greater than or equal to 125nmol/L. They were randomised to subcutaneously receive zerlasiran 300mg or 450mg, or a placebo, every 16 or every 24 weeks. The least-squares mean placebo-adjusted time-averaged percent change in LPa serum concentrations was −85.6%, −82.8%, and −81.3% for the 450mg every 24 weeks, 300mg every 16 weeks, and 300 mg every 24 weeks groups, respectively. The most common adverse events were injection site reactions, with mild pain occurring in 2.3% to 7.1% of participants in the first day following drug administration. There were 20 serious adverse events in 17 patients, none considered related to the study drug. For the group receiving a 300mcg dose every 16 weeks, it was found that even at the 60 week follow-up, 28 weeks after the last administration, that lipoprotein(a) serum concentrations were still 60% lower than baseline.

Categories : Cardiovascular Disease Obstetrics & GynaecologyTags :

The Risks of Various Menopausal Hormone Treatments Vary

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Researchers have analysed the effects of seven different hormone treatments for menopausal symptoms, and the risk of blood clots, stroke and heart attack. The risks differ depending on the active substance and how the medicine is taken, according to the study findings which appear in the BMJ. In this world’s largest and most comprehensive study of currently prescribed hormonal substances, researchers analysed the risks for one million women aged 50–58.

“There is concern among women that menopausal hormone therapy increases the risk of cardiovascular disease. This concern is based on older studies conducted more than 20 years ago that only looked at one type of treatment. Since then, many new preparations have been introduced and our study shows that the previous conclusions do not apply to all types of treatments,” says Therese Johansson, postdoctoral researcher and lead author of the study, which was part of her thesis at Uppsala University.

To counteract the health effects of menopause, such as hot flashes and osteoporosis, women may be prescribed hormone replacement therapy which consists of hormones or hormone-like substances.

Treatment available since the 1970s

In Sweden alone, hundreds of thousands of women currently use hormone replacement therapy and this type of treatment has been available since the 1970s. At that time, there was only one type of hormone replacement therapy and when a major study in the 1990s showed that it increased the risk of cardiovascular disease, its use rapidly declined. Since then, new preparations have entered the market, and following this, the use of hormone replacement therapy in connection with menopause has increased significantly in recent years.

In the new study, the researchers looked at seven different types of currently used hormone replacement treatments, administered via tablets, hormone patches or hormone-releasing IUDs. The study is based on all prescriptions for hormone replacement therapy in Sweden from 2007 to 2020 and covers nearly one million women aged 50 to 58. The women were monitored for two years after starting hormone replacement therapy. The risk of blood clots and cardiovascular disease was compared between women who had and had not collected a prescription medicine for hormone replacement therapy.

Different therapies, different risks

The results show clearly that the risks of hormone replacement therapy vary depending on the type of treatment.

For example, the synthetic hormone tibolone, which mimics the effects of the body’s natural hormones, was linked to an increased risk of both heart attack and stroke, but not to an increased risk of blood clots. The risk of heart attack or stroke due to tibolone is estimated at one in a thousand women.

Combined preparations containing both oestrogen and progesterone instead increase the risk of blood clots, including deep vein thrombosis and pulmonary embolism. The researchers estimate that the risk of deep vein thrombosis resulting from this combined preparation is about 7000 women per year.

“It is important that both doctors and women are aware of the risks of menopausal hormone therapy and, in particular, that the existing drugs carry different risks of blood clots and cardiovascular disease. Tibolone in particular was associated with an increased risk of stroke and heart attack. Tibolone is used in Europe but is not approved in countries such as the United States. We hope that our study will lead to the drug being withdrawn from use here as well,” says Åsa Johansson, research group leader at Uppsala University and SciLifeLab, and the study’s senior author.

During the period of the study, 2007–2020, a roughly 50% increase hormone patch use was observed, and these preparations were not linked to the same higher risk. The increased use of safer alternatives, such as patches, is an important step forward in reducing the risk of cardiovascular disease among menopausal women.

Identify individual increased risk

“The next step in our research will be to develop strategies to identify which women are at increased risk of certain diseases in connection with using hormonal drugs. In this way, we can guide patients to the most appropriate medicine for each individual and drastically reduce the number of side effects,” Åsa Johansson says.

Source: Uppsala University

Categories : Cardiovascular Disease New Compounds and TreatmentsTags :

An Experimental Drug to Prevent Post-heart Attack Heart Failure

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Scientists at UCLA have developed a first-of-its-kind experimental therapy that has the potential to enhance heart repair following a heart attack, preventing the onset of heart failure. After a heart attack, the heart’s innate ability to regenerate is limited, causing the muscle to develop scars to maintain its structural integrity. This inflexible scar tissue, however, interferes with the heart’s ability to pump blood, leading to heart failure in many patients – 50% of whom do not survive beyond five years.

The new therapeutic approach aims to improve heart function after a heart attack by blocking a protein called ENPP1, which is responsible for increasing the inflammation and scar tissue formation that exacerbate heart damage. The findings, published in Cell Reports Medicine, could represent a major advance in post-heart attack treatment.

The research was led by senior author Dr Arjun Deb, a professor of medicine and molecular, cell and developmental biology at UCLA.

“Despite the prevalence of heart attacks, therapeutic options have stagnated over the last few decades,” said Deb, who is also a member of the UCLA Broad Stem Cell Research Center. “There are currently no medications specifically designed to make the heart heal or repair better after a heart attack.”

The experimental therapy uses a therapeutic monoclonal antibody engineered by Deb and his team. This targeted drug therapy is designed to mimic human antibodies and inhibit the activity of ENPP1, which Deb had previously established increases in the aftermath of a heart attack.

The researchers found that a single dose of the antibody significantly enhanced heart repair in mice, preventing extensive tissue damage, reducing scar tissue formation and improving cardiac function. Four weeks after a simulated heart attack, only 5% of animals that received the antibody developed severe heart failure, compared with 52% of animals in the control group.

This therapeutic approach could become the first to directly enhance tissue repair in the heart following a heart attack; an advantage over current therapies that focus on preventing further damage but not actively promoting healing. This can be attributed to the way the antibody is designed to target cellular cross-talk, benefitting multiple cell types in the heart, including heart muscle cells, the endothelial cells that form blood vessels, and fibroblasts, which contribute to scar formation. 

Initial findings from preclinical studies also show that the antibody therapy safely decreased scar tissue formation without increasing the risk of heart rupture – a common concern after a heart attack. However, Deb acknowledges that more work is needed to understand potential long-term effects of inhibiting ENPP1, including potential adverse effects on bone mass or bone calcification. 

Deb’s team is now preparing to move this therapy into clinical trials. The team plans to submit an Investigational New Drug, or IND, application to the U.S. Food and Drug Administration this winter with the goal of beginning first-in-human studies in early 2025. These studies will be designed to administer a single dose of the drug in eligible individuals soon after a heart attack, helping the heart repair itself in the critical initial days after the cardiac event.

While the current focus is on heart repair after heart attacks, Deb’s team is also exploring the potential for this therapy to aid in the repair of other vital organs.

“The mechanisms of tissue repair are broadly conserved across organs, so we are examining how this therapeutic might help in other instances of tissue injury,” said Deb, who is also the director of the UCLA Cardiovascular Research Theme at the David Geffen School of Medicine. “Based on its effect on heart repair, this could represent a new class of tissue repair-enhancing drugs.”

Categories : Cardiovascular DiseaseTags :

Standing Time at Work can be Detrimental to Blood Pressure

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A Finnish study found that prolonged standing at work had a negative impact on the research participants’ 24-hour blood pressure. In contrast, spending more time sitting at work was associated with better blood pressure. The study suggests that the type of activity during working hours may be more relevant to 24-hour blood pressure than recreational physical activity.

Regular exercise is important for controlling blood pressure. In particular, more vigorous, aerobic exercise is effective for lowering blood pressure, but also everyday physical activity can have a beneficial impact. Previous studies have shown that exercise in leisure time is more beneficial for the cardiovascular system than physical activity at work, which can even be detrimental to health.

24-hour blood pressure important for cardiovascular health

In the Finnish Retirement and Aging study (FIREA) conducted at the University of Turku, the physical activity of municipal employees approaching retirement age was measured using thigh-worn accelerometers during working hours, leisure time, and days off.

In addition, the research participants used a portable blood pressure monitor that automatically measured their blood pressure every 30 minutes for 24 hours.

“Rather than any single measurement, 24-hour blood pressure is a better indication of how blood pressure stresses the heart and blood vessels throughout the day and night. If blood pressure is slightly high throughout the day and does not fall sufficiently even at night, blood vessels start to stiffen and the heart has to work harder to cope with the increased pressure. Over the years, this can lead to the development of cardiovascular disease,” says Doctoral Researcher Jooa Norha.

Take a break from standing during the workday

The latest results confirm previous findings that physical activity at work can be harmful to the heart and circulatory system.

In particular, prolonged standing can raise blood pressure as the body boosts circulation to the lower limbs by constricting blood vessels and increasing the pumping power of the heart.

“A standing desk can provide a nice change from sitting at the office, but too much standing can be harmful. It’s a good idea to take a break from standing during the work day, either by walking every half an hour or sitting for some parts of the day,” Norha recommends.

Recreational physical activity is also needed

In addition, the results of the study suggest that sedentary work in itself is not necessarily harmful to blood pressure.

Instead, researchers stress the importance of recreational physical activity for both office and construction workers.

“It is good to remember that being physically active at work is not enough on its own. Engaging in diverse physical exercise during leisure time helps to maintain fitness, making work-related strain more manageable. Similarly, employees with predominantly sedentary jobs should ensure that they get enough exercise during their leisure time,” Norha highlights.

Source: University of TYurku

Categories : Cardiovascular DiseaseTags :

The Factors Behind the Shifting Trends of Ischaemic Heart Disease and Stroke

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Incidence of stroke and ischaemic heart disease are declining around the world, except for in a handful of regions, according to research in the open access journal PLOS Global Public Health. Wanghong Xu of Fudan University and colleagues find that in East and West Sub-Saharan Africa, East and Central Asia and Oceania, ischaemic heart disease is increasing, which may be attributed to eight factors that include diet, high BMI, household air pollution and more.

Cardiovascular disease is a leading cause of death and disability worldwide, and ischemic heart disease and stroke accounted for 16% and 11% of total deaths in 2019 respectively. Over time both have decreased in incidence, but the distribution of this decline varies and in some regions there is an upward trend.

The team analysed global data from 1990-2019 for incidence of ischaemic heart disease and stroke and for exposure to 87 potential attributable factors. The authors describe the incidences and trends at a global, regional and national level, and find higher rates of ischaemic heart disease than stroke. Over three decades ischaemic heart disease reduced from 316 to 262 per 100 000 people and stroke declined from 181 to 151 per 100 000. The increases of ischaemic heart disease seen in some regions may be associated with the shifting distribution of eight factors: a diet high in trans-fatty acids; diet low in calcium; high BMI; household air pollution from solid fuels; non-exclusive breastfeeding; occupational ergonomic factors; vitamin A deficiency; and, occupational exposure to particulate matter, gases and fumes, which were determined by the World Bank income levels.

The results indicate how the potential socioeconomic development of some countries is affecting rates of cardiovascular disease and stroke, and that places experiencing rapid economic transitions – and rapidly changing lifestyle changes – may also be experiencing higher rates of disease. This study and provides insight into mechanisms involved and the potential for targeted interventions.

The authors add: “This study profiles the significantly different incidence trends of ischemic heart disease and stroke across countries, identifies eight potential contributors to the disparities, and reveals the pivotal role of socioeconomic development in shaping the country-level associations of the risk factors with the incidences of the two cardiovascular diseases.”

Provided by PLOS

Categories : Cardiovascular Disease Regenerative MedicineTags :

Human Hearts may Possess a Latent Ability to Regenerate Cardiomyocytes

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Right side heart failure. Credit: Scientific Animations CC4.0

After severe heart failure, the ability of the heart to heal by forming new cells is very low. But now Karolinska Institutet researchers found that, after use of a supportive heart pump, the capacity of a damaged heart to repair itself with new cardiomyocytes becomes significantly higher – even greater than that of a healthy heart. This study is published in the journal Circulation.

The ability of the human heart to renew itself by regenerating its muscle cells, myocytes, is very limited. But what happens to this capability when the heart is damaged by severe heart failure has been unknown.

Researchers at Karolinska Institutet have now discovered that after an injury, the rate of cell renewal is even lower than in a healthy heart. Standard-of-care for patients with advanced heart failure is a surgically implanted pump that helps propel blood, a so-called left ventricular assist device (LVAD).

Kick-starting repair

Surprisingly, the researchers found that patients with such a heart pump, who have shown significant improvement in their heart function, can regenerate heart muscle cells at a rate more than six times higher than in healthy hearts.

“The results suggest that there might be a hidden key to kick-start the heart’s own repair mechanism”, says Olaf Bergmann, senior researcher at the Department of Cell and Molecular Biology at Karolinska Institutet and last author of the paper.

The mechanism behind the effect is still unknown and there is not yet any hypothesis to explain it.

“It is difficult to say. In the existing data we cannot find an explanation for the effect, but we will now continue to study this process at a cellular and molecular level,” says Olaf Bergmann.

The findings open the possibility of developing new therapies for patients with serious heart conditions that stimulate the heart’s ability to repair itself after damage. This way, patients wouldn’t have to rely only on heart transplants or other kinds of long-term mechanical support.

“This offers some hope that the recovery after a heart incident can somehow be boosted,” says Olaf Bergmann.

Atomic bombs enable cell age estimation

It is generally difficult to determine the age of cells in the human body and to decide which cells are new and which are old. However, by using a method earlier devised by Jonas Frisén, professor of stem cell research at Karolinska Institutet, the group has been able to count the rate of renewal of myocytes in the heart. The method is based upon the fact that the percentage of radioactive carbon in the atmosphere, and subsequently in our cells, has steadily decreased since the nuclear test ban in 1963. For every following year, there is a little less radioactivity in newly formed cells, which means that they can be ‘dated’. 

Source: Karolinska Institute

Categories : Cardiovascular DiseaseTags :

Tirzepatide Found to Protect against Worsening Heart Failure

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Right side heart failure. Credit: Scientific Animations CC4.0

The diabetes drug tirzepatide can reduce the risk of death or worsening heart failure for patients with heart failure, preserved heart pump function and obesity, new research from UVA Health reveals.

Researchers tested the GLP-1 receptor agonist in the SUMMIT clinical trial, where a total of 731 patients with diastolic heart failure and a body mass index (BMI) of 30 or above were randomised to receive injections of either tirzepatide or a harmless placebo. The researchers then followed the patients for a median period of two years. Tirzepatide is also prescribed as a weight loss drug in certain countries.

During that time, 56 placebo recipients died or suffered worsening heart failure, compared with only 36 of those receiving tirzepatide. Participants taking tirzepatide also lost 11.6% of their body weight.

“This class of drugs continue to show benefits far beyond weight loss,” said researcher Christopher Kramer, MD, chief of UVA Health’s Division of Cardiovascular Medicine. “This drug will become an important part of the armamentarium for patients with obesity-related heart failure and preserved heart function.”

Obesity and heart failure

Obesity is a major contributing factor to heart failure, so Kramer and his collaborators in the SUMMIT trial wanted to see if tirzepatide, a weight-loss drug already approved by the federal Food and Drug Administration, could help. 

The trial found that tirzepatide offered substantial benefits for managing diastolic heart failure, reducing deaths, preventing hospitalizations and generally benefiting recipients’ health and quality of life. For example, recipients saw improvements in how far they could walk in six minutes, as well as substantial decreases in a biological indictor used to measure inflammation and predict risk of serious cardiovascular events.

Side effects seen in the tirzepatide group consisted of gastrointestinal issues such as nausea and diarrhea, and these were mostly mild or moderate, the researchers reported Saturday at a meeting of the American Heart Association in Chicago.

Tirzepatide Findings

Kramer, a cardiovascular imager, also led a magnetic resonance imaging substudy looking at how tirzepatide affected recipients’ heart structure and function. The researchers found beneficial reductions in both left ventricular mass (weight of the heart) and in the amount of surrounding fat tissue. The reduction in LV mass correlated with the reduction in body weight, as well as with decreases in left ventricular volumes.

“This drug is reversing the abnormal properties of the heart brought on by obesity,” Kramer said. “There is much more to these drugs than weight loss alone.”

The findings from these studies by Kramer and his fellow researchers from SUMMIT are being published simultaneous with the American Heart meeting in Chicago in four separate manuscripts, including the New England Journal of Medicine, Nature Medicine, Circulation and the Journal of the American College of Cardiology.

Source: University of Virginia Health System

Categories : Cardiovascular DiseaseTags :

A Link between Heart Shape and Cardiovascular Disease Risk

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Researchers from Queen Mary University of London and other universities have for the first time examined the genetic basis of the heart’s left and right ventricles using advanced 3D imaging and machine learning.

Prior research primarily focused on the heart’s size and volume and specific chambers. By studying both ventricles together, the team was able to capture the more intricate, multi-dimensional aspects of the heart shape.

This new approach of exploring shape has led to the discovery of new heart-associated genes and provided a better understanding of the biological pathways linking heart shape to cardiovascular disease.

Cardiovascular disease is among the leading causes of death in the UK and globally. The findings of this study could change how cardiac disease risk is evaluated. Genetic information related to heart shape can provide a risk score for heart disease, offering potentially early and more tailored assessment in clinical settings.

“This study provides new information on how we think about heart disease risk,” said Patricia B. Munroe, Professor of Molecular Medicine at Queen Mary and co-author of the study. “We’ve long known that size and volume of the heart matter, but by examining shape, we’re uncovering new insights into genetic risks. This discovery could provide valuable additional tools for clinicians to predict disease earlier and with more precision.”

The team used cardiovascular MRI images from over 40 000 individuals from the UK Biobank to create 3D models of the ventricles. Through statistical analysis, they identified 11 shape dimensions that describe the primary variations in heart shape.

Subsequent genetic analysis found 45 specific areas in the human genome linked to different heart shapes. Fourteen of these areas had not been previously known to influence heart traits.

“This study sets an important foundation for the exploration of genetics in both ventricles”, said Dr Richard Burns, Statistical Geneticist at Queen Mary. “The study confirms that combined cardiac shape is influenced by genetics, and demonstrates the usefulness of cardiac shape analysis in both ventricles for predicting individual risk of cardiometabolic diseases alongside established clinical measures.”

This research marks an exciting new chapter in understanding how genetics influence the heart and opens the doors to further studies on how these findings could be integrated into clinical practice, ultimately benefiting millions at risk of heart disease.

Source: Queen Mary University of London

Categories : Cardiovascular Disease PaediatricsTags :

Breaking up Sedentary Time with Light Exercise Lowers BP

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More than six sedentary hours per day from childhood through young adulthood may cause an excess increase of 4mmHg in systolic blood pressure, a new study shows. Continuously engaging in light physical activity (LPA) significantly mitigated the rise in blood pressure – while longer bouts of more vigorous exercise . The results were published in the prestigious Journal of Cachexia, Sarcopenia and Muscle.

In the present study, a collaboration between the Universities of Bristol and Exeter, and the University of Eastern Finland, 2513 children drawn from the Children of the 90s cohort were followed up from age 11 until 24 years. At baseline, the children spent six hours per day sedentary, six hours per day engaging in LPA, and approximately 55 minutes per day in moderate-to-vigorous physical activity (MVPA). At follow-up in young adulthood, nine hours per day were spent sedentary, three hours per day in LPA, and approximately 50 minutes per day in MVPA. 

The average blood pressure in childhood was 106/56mmHg which increased to 117/67mmHg in young adulthood, partly due to normal physiological development. Persistent increase in sedentary time from age 11 through 24 years was associated with an average of 4mmHg excess increase in systolic blood pressure. Participating in LPA from childhood lowered the final level by 3mmHg, but engaging in MVPA had no blood pressure-lowering effect. 

“Furthermore, when 10 minutes out of every hour spent sedentary was  replaced with an equal amount of LPA from childhood through young adulthood in a simulation model, systolic blood pressure decreased by 3mmHg and diastolic blood pressure by 2mmHg. This is significant, as it has been reported in adults that a systolic blood pressure reduction of 5mmHg decreases the risk of heart attack and stroke by ten percent,” says Andrew Agbaje, an award-winning physician and associate professor (docent) of Clinical Epidemiology and Child Health at the University of Eastern Finland.

The current study is the largest and the longest follow-up of accelerometer-measured movement behaviour and blood pressure progression in youth in the world. Measurements of blood pressure, sedentary time, LPA and, MVPA were taken at ages 11, 15, and 24 years. The children’s fasting blood samples were also repeatedly measured for low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, glucose, insulin, and high-sensitivity C-reactive protein. Heart rate, socio-economic status, family history of cardiovascular disease, smoking status as well as dual-energy X-ray absorptiometry measured fat mass and lean mass were accounted for in the analyses. 

“We have earlier shown that elevated blood pressure and hypertension in adolescence increase the risk of premature cardiac damage in young adulthood. The identification of childhood sedentariness as a potential cause of elevated blood pressure and hypertension with LPA as an effective antidote is of clinical and public health significance. Several MVPA-based randomised controlled trials in the young population have been unsuccessful in lowering blood pressure. We noted an MVPA-induced increase in muscle mass enhanced a physiologic increase in blood pressure explaining why earlier MVPA-based randomised clinical trials were unsuccessful,” says Agbaje.

Source: University of Eastern Finland