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Tag: Heart

  • Non-invasive imaging test identifies patients needing heart procedures

    Non-invasive imaging test identifies patients needing heart procedures

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    A new study showed that a non-invasive imaging test can help identify patients with coronary artery blockage or narrowing who need a revascularization procedure. The findings were published as a Special Report in Radiology: Cardiothoracic Imaging, a journal of the Radiological Society of North America (RSNA).

    Doctors use coronary CT angiography (CTA) to diagnose narrowed or blocked arteries in the heart. A CTA exam receives a score from mild (0-1) to moderate (2-3) to severe (4-5). Patients with scores above 3 typically require medical treatments and can potentially benefit from stents or surgeries (revascularization) to restore blood flow to the heart.

    CTA tells you the degree to which a vessel is blocked. But the degree of blockage doesn’t always reliably predict the amount of blood flow in the vessel.”


    Mangun Kaur Randhawa, M.D., post-doctoral research fellow, Department of Radiology at Massachusetts General Hospital (MGH), Boston

    Doctors have traditionally relied on an invasive procedure known as invasive coronary angiography to image vessels and more recently have added other invasive tests like fractional flow reserve (FFR) to identify and assess significant blockages in the vessels. CT-FFR is a relatively new alternative that non-invasively models a patient’s coronary blood flow using CTA images of the heart, AI algorithms and/or computational fluid dynamics.

    To assess the impact of the selective use of CT-FFR on clinical outcomes, Dr. Randhawa’s research team conducted a retrospective study of patients who underwent coronary CTA at MGH between August 2020 and August 2021.

    During the study period, 3,098 patients underwent coronary CTA. Of these, 113 coronary bypass grafting patients were excluded. Of the remaining 2,985 patients, 292 (9.7%) were referred for CT-FFR analysis, and eight of these exams were excluded, leaving a final study group of 284.

    As expected, most referrals to CT-FFR were patients with scores of 3 or above. CT-FFR was requested in the majority (73.5 %) of patients with a score of 3 (moderate narrowing/blockage).

    “In patients with moderate narrowing or blockage of the arteries, there can be ambiguity about who would benefit from invasive testing and revascularization procedures,” Dr. Randhawa said. “CT-FFR helps us identify and select those patients who are most likely to benefit.”

    Out of the 284 patients, 160 (56.3%) had a negative CT-FFR result of > 0.80, 88 patients (30.9%) had a clearly positive (abnormal) result of ≤ 0.75, and the remaining 36 patients (12.6%) had a borderline result between 0.76-0.80.

    Patients with significant narrowing/blockages on coronary CTA who underwent CT-FFR had lower rates of invasive coronary angiography (25.5% vs. 74.5%) and subsequent percutaneous coronary intervention (21.1% vs. 78.9%) than patients who were not referred for a CT-FFR.

    “CT-FFR helps us identify patients who would most benefit from undergoing invasive procedures and to defer stenting or surgical treatment in patients who likely won’t,” said senior author Brian B. Ghoshhajra, M.D., M.B.A., associate chair for operations and academic chief of cardiovascular imaging at MGH. “CT-FFR makes the CT ‘better’, but we found that the benefits were highest when used selectively.”

    Dr. Ghoshhajra added that their CT-FFR analysis was successful in the large majority of patients, regardless of challenging factors such as elevated or irregular heart rates and obesity.

    “When you objectively measure coronary artery flow with CT-FFR, you induce fewer patients to be further investigated and treated, because you tend to treat not just what the eyeball sees, but what the physiology supports,” he said.

    The researchers said the study results demonstrate the utility of CT-FFR in clinical practice, when used selectively, highlighting its potential to reduce the frequency of invasive procedures in patients with significant coronary artery narrowing or blockages without compromising safety.

    Source:

    Radiological Society of North America

    Journal reference:

    Randhawa, M. K., et al. (2024). Selective Use of CT Fractional Flow at a Large Academic Medical Center: Insights from Clinical Implementation after 1 Year of Practice. Radiology. Cardiothoracic Imaging. doi.org/10.1148/ryct.230073.

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  • Integrating social determinants of health to enhance heart failure risk prediction

    Integrating social determinants of health to enhance heart failure risk prediction

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    A recent study by Case Western Reserve University used national data from U.S. military veterans with diabetes to validate and modify a widely accepted model used to predict the risk of heart failure in diabetic patients.

    The model, called the WATCH-DM score, is used to predict the likelihood of heart failure in diabetes patients within five years.

    But because it overlooks the influence of social determinants of health‚ such as housing, food and a patient’s neighborhood, the researchers used a social deprivation index (SDI), a multi-component summary score, to adjust the WATCH-DM score. 

    The SDI, introduced by the Robert Graham Center, a group of clinical researchers, can quantify the level of disadvantage in particular areas using food, housing, transportation and community conditions. Prior research demonstrated this score is directly proportional to the level of health disparities observed in communities.

    The study identified about 1 million U.S. veterans with type 2 diabetes without heart failure treated as outpatients at Veterans Affairs medical sites nationally in 2010.

    Researchers used patient zip codes to obtain their SDI, which was then entered into the risk calculator to determine how likely they would be hospitalized for heart failure within five years. 

    While the hospitalization rate for heart failure for the whole cohort of more than 1 million patients was 5.39%, this incidence varied from 3% (in the least socially deprived) to 11% (in the most deprived). 

    Researchers found that, depending on the patients’ other clinical information, adding the SDI into the risk-prediction model could even double the probability of that patient developing heart failure in the next five years.

    The team of investigators then optimized the WATCH-DM score for each SDI group using a statistical correction factor and improved its predictive accuracy across the whole range of the social determinants of health. 

    “We found that adding the SDI enhanced the WATCH-DM score’s ability to forecast risk,” said Salil Deo, an associate professor in the Department of Surgery at the Case Western Reserve School of Medicine, who led the study. “These results highlight the necessity of including social determinants of health in any future clinical risk prediction algorithms. This will increase their accuracy, which will benefit patients by improving their health outcomes.”

    This calculator is available to the public from their device for free here. 

    We hope our study encourages healthcare providers to adopt a wholistic approach when treating patients in the future. Understanding and quantifying social inequity is likely the first step we can take toward trying to ensure that it does not affect the health of our patients.” 


    Salil Deo, Associate Professor, Department of Surgery, Case Western Reserve School of Medicine

    Source:

    Case Western Reserve University

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  • Heart transplant recipient’s journey: From patient to advocate

    Heart transplant recipient’s journey: From patient to advocate

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    Glen Kelley’s journey as a heart transplant recipient came full circle today in Prague, as he addressed attendees of the Annual Meeting and Scientific Sessions of the International Society for Heart and Lung Transplantation (ISHLT), including members of his own care teams.

    As a high school senior outside of Peoria, Illinois, Kelley was diagnosed with stage-4 Hodgkin’s lymphoma and underwent eight months of chemotherapy and radiation. After 10 months in remission, the cancer returned, and he received a bone marrow transplant. With his cancer once again in remission, he finished college and went on to enjoy an extremely active life for the next 17 years, skiing, cycling, climbing mountains, and even running marathons.

    Then out of nowhere, Kelley suffered a heart attack at 36. Doctors found his right coronary artery nearly completely blocked and placed three stents to prop it open. Over the next decade, his ailing heart would require more stents, valve replacements, and not one but two coronary artery bypasses at the University of Minnesota Medical Center in Minneapolis. By 2015, Kelley was in heart failure -; most likely the result of the radiation he received in his teens.

    He was placed on the transplant list and eventually transferred to Baylor University Medical Center in Dallas, where he received a new heart in 2016. An unusually long and rough recovery period followed, during which he suffered kidney failure, a fungal infection, and two bouts of organ rejection. In 2019, he received his second organ transplant, a kidney indirectly donated from his youngest son.

    I had support along the way from my physicians and healthcare providers to volunteers at the support group Second Chance for Life. I don’t think my outcomes would have been nearly as successful without the support I received throughout my journey.”


    Glen Kelley, heart transplant recipient

    Despite all his health problems, Kelley led a successful career in IT and marketing, including 17 years at IBM. But it was through his experiences as a patient that he realized his true calling.

    “My metrics changed from how well I did at my day job to how many patients I could help,” he said. “Patients became my currency.”

    Kelley dedicated himself to supporting patients dealing with advanced heart disease through in-person and phone visitation and support groups, ultimately serving as president of Second Chance for Life for four years. During his tenure, the group created an alliance with the international group Mending Hearts, the world’s the largest peer-to-peer heart patient support organization with 115,000+ members.

    With Mended Hearts, Kelley had an opportunity to continue working in patient education and support -; and to become more involved in advocacy and legislation at the state and federal levels. Today, he serves as the group’s Patient Voice and Advocacy Leader.

    “Working in advocacy allowed me to help not one but thousands of patients at a time,” he said.

    Today, Kelley fills his days with phone calls to patients, in-person visits, and advising. In his new role as Patient Advocate Trustee on ISHLT Foundation Board of Trustees, Kelley will help to ensure the Foundation agenda addresses issues that matter most to patients with advanced heart and lung disease.

    His highest calling yet may be serving the United States’ new Organ Procurement and Transplantation Network (OPTN). Created last fall by a bipartisan law, OPTN is charged with revamping the country’s organ transplant system. Kelley was elected thoracic patient representative to OPTN’s Board of Directors.

    “Patients always need support, whether they know it or not, at some point in their journey,” said Kelley. “This motivates me to do the work I do. I want to empower patients through support and education and teach them how to self-advocate.”

    Source:

    International Society for Heart and Lung Transplantation

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  • Patient-centered cardiovascular care enhances outcomes

    Patient-centered cardiovascular care enhances outcomes

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    Adult cardiovascular care centered on the patient can improve individuals’ experiences and their medical outcomes, according to a new American Heart Association Scientific Statement published today in Circulation.

    Patient-centered care means seeing the patient as a person and being respectful of their beliefs, preferences and values. Patient-centered care combines the health care professional’s expertise with consideration of the patient’s health priorities. It involves empowering patients to make informed decisions by providing information and developing an active partnership among the patient, family and the health care team. Patient-centered care does not mean that patients can choose what they want, when they want.”


    Michael J. Goldfarb, M.D., M.Sc., chair of the scientific statement writing committee and associate professor of cardiology at the Jewish General Hospital and McGill University in Montreal, Quebec, Canada

    “There is a need for health care professionals managing adults with heart disease to receive guidance and practical tools on how to incorporate a person-centered care approach into routine clinical practice,” said Goldfarb.

     The new scientific statement describes several elements that are essential to patient-centered care, including shared decision-making, medication management and patient-oriented outcomes.

    Shared decision-making is a collaborative partnership among patients, family and health care professionals based on trust, mutual respect and open and honest communication. Health professionals need to consider their patient’s level of health literacy and provide clear, jargon-free and relevant information about risk factors, current health conditions and the realities, risks and benefits of possible screening and treatment options. Patients must have the opportunity to ask questions, express their values, preferences and goals, and work together with the medical team to agree on a plan for managing their heart disease.

    Although the benefits of using medication to prevent and treat heart disease are well known, for a myriad of reasons, more than half of patients with cardiovascular disease do not always take their medications as prescribed. Conditions such as high blood pressure and high cholesterol raise the risk of heart attack and stroke, but undertreatment of these silent conditions is common.

    Patient-centered discussions of current and proposed medications may also help to improve adherence to needed medications and minimize drug costs and side effects. In some cases, a combination pill may reduce the number of tablets that must be taken each day, or a less expensive but equally effective medication may be substituted for a more expensive option. An open, honest discussion about medication may also lead to the decision to eliminate a longstanding medication that may no longer be needed.

    “Prior to starting, adjusting or stopping cardiovascular medications, there is a need to establish and take into account patient preferences and goals,” said Goldfarb.

    While physical examinations and lab tests provide important data about how a patient with heart disease is doing, patient-centered care incorporates people’s own reports of their physical functioning, symptom burden, emotional well-being, social functioning and quality of life. Collecting this information gives health care professionals a more complete picture of how a patient is doing so they may detect subtle changes in the progression of heart disease and assess the impact (negative or positive) of current or proposed treatments.

    “While some care outcomes are important for health care professionals and health systems, these may not always reflect what is important to the patient. For example, while the length of a hospital stay is often recorded as a marker of care quality, the patient may prioritize their physical functioning and quality of life after a heart attack,” said Goldfarb.

    Ensuring patient-centered care for all

    The statement gives special consideration to overcoming barriers to patient-centered care and in applying patient-centered care to the people who carry an outsized burden of cardiovascular disease. For example:

    • People from underrepresented and historically underserved races and ethnicities have the highest rates of cardiovascular disease and death and are often affected by adverse social determinants of health (SDOH, including measures such as economic stability, education, neighborhood safety and access to quality health care ). Effective patient-centered care may involve the use of tools to assess SDOH, followed by care provided by culturally and linguistically competent multidisciplinary teams that include social workers, interpreters and patient navigators.

    • Older adults often face other complex aging-related health issues in addition to heart disease. Patient-centered care needs to consider age-associated risks (such as multiple medications, frailty, dementia, falls, social isolation) when evaluating the pros and cons of various medications and interventions.

    • Women can benefit from patient-centered cardiovascular care throughout adulthood, including care to prevent and treat pregnancy-related heart issues, and care at time of menopause.

    • Individuals with behavioral and mental health disorders may face psychological challenges that often impact heart health. Patient-centered care for these individuals should include behavioral health services in addition to specialized cardiovascular care.

    • Adults with congenital heart disease are an increasing group of patients who, throughout their lifetimes, benefit from a patient-centered approach as they transition from pediatric into adult care and face decisions about high-level medical and surgical treatment.

    • People with physical disabilities often have reduced access to health services and report worse overall health than adults without disabilities. According to the statement, the health care system should address inadequate access to preventive care and the treatment of heart disease and other chronic conditions for individuals with disabilities.

    Barriers to patient-centered care

    There are many barriers to incorporating patient-centered care, including those arising from patients, clinicians and health systems.

    • Patients, who may distrust or lack access to the health system, have limited health literacy, limited English proficiency or cultural barriers to communicating with health care professionals, be more concerned about their caregivers and family than themselves, or hold medical beliefs and preferences that conflict with best health practices.

    • Clinicians, who operate under time pressures and increasing demands for documentation, may have different incentives than patients and may also work in settings where the workforce lacks the diversity of the patients served.

    • Health systems may be fragmented, provide limited access to specialty care, have limited space or inadequate systems to share information and/or lack team-based care.

    “Patient-centered care is possible-;and already occurs to a certain extent-;in today’s care delivery systems. Further development and inclusion of patient-centered outcomes measures will be important for optimizing care for patients, their families and caregivers,” said Goldfarb.

    This scientific statement was prepared by the volunteer writing group on behalf of the American Heart Association’s Council of Clinical Cardiology; the Council on Cardiovascular and Stroke Nursing; the Council on Hypertension; the Council on Lifestyle and Cardiometabolic Health; the Council on Peripheral Vascular Disease; and the Council on Quality of Care and Outcomes Research. American Heart Association scientific statements promote greater awareness about cardiovascular diseases and stroke issues and help facilitate informed health care decisions. Scientific statements outline what is currently known about a topic and what areas need additional research. While scientific statements inform the development of guidelines, they do not make treatment recommendations. American Heart Association guidelines provide the Association’s official clinical practice recommendations.

    Source:

    American Heart Association

    Journal reference:

    Goldfarb, M. J., et al. (2024) Patient-Centered Adult Cardiovascular Care: A Scientific Statement From the American Heart Association. Circulation. doi.org/10.1161/CIR.0000000000001233.

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  • Advances in mechanical circulatory support devices

    Advances in mechanical circulatory support devices

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    The same technology that enables a bullet train to travel at speeds up to 200 mph without touching its rails now keeps a failing heart pumping-;and in the near future, it will do so via a wireless power connection. Mandeep R. Mehra, MD, FRCP described the cutting-edge heart pump and other advances in mechanical circulatory support (MCS) today at the Annual Meeting and Scientific Sessions of the International Society for Heart and Lung Transplantation (ISHLT) in Prague.

    It’s been very difficult to realize gains over the last 30 years in the field of mechanical circulatory support. But we’re now at a point where surgically implanted devices have moved from rescuing patients on the brink of death to providing long-term therapy, prolonged survival, and functional capacity.”


    Dr. Mandeep R. Mehra, executive director of the Center for Advanced Heart Disease at Brigham Health, Boston

    MCS devices are temporarily or permanently implanted in patients with advanced heart failure to keep the heart pumping enough blood. Dr. Mehra likened the generational shifts in MCS devices to the evolution of automobile technology.

    “I think we’ve come from the Model T Ford to a Mercedes Benz or BMW,” he said. “Now we need to move to the Porsche and Ferrari.”

    Early MCS devices mimicked human heart function. Large, bulky, and heavy, they had multiple moving parts that could fail. The next generation of devices, small non-pulsatile continuous-flow pumps, are smaller but come with a risk of bleeding from mucosal sites such as the intestines.

    “These devices need a power line that exits through the patient’s abdomen and connects to external batteries,” he said. “So while patients with this pump live longer and have greater functional capacity, they are tethered to a battery.”

    The latest development in MCS devices, the magnetically levitated centrifugal-flow pump, prevents clotting and reduces bleeding and other complications inherent in earlier devices. It features a motor and a rotating disk that is completely suspended in a magnetic field, operating under the same ‘maglev’ principle used in high-speed trains. With no mechanical bearings and wider passages for blood flow, the frictionless pump creates an artificial pulse by rapidly changing rotor speed.

    Dr. Mehra said patients with left ventricular assisted devices (LVADs) engineered with the technology now live beyond five years, a survival rate which rivals that of many heart transplant patients.

    “At this point in time, MCS devices are much more forgiving,” he said. “But we need to move to an era where they become forgettable.”

    The cutting-edge maglev heart pump has been implanted in well over 10,000 patients, but Dr. Mehra said that number could increase ten-fold with additional advancements, including further miniaturization and fewer peripheral components.

    “In the next five years, new pumps will have a fully internalized power line and be wirelessly powered from outside the body, just like our iPhones,” he said. “We’ll implant these devices, and the patient will be able to forget about them.”

    In his presentation, Dr. Mehra also reported on other advances revolutionizing the field, including xenotransplants and bacteriostatic, biocompatible surfaces that minimize infections.

    “We have the potential to serve many more heart failure patients, adding years to their lives and, importantly, life to their years,” he said. “The scalable impact is huge, and we’re just scratching the surface now. In the next five to seven years, unnecessary patient deaths will be a thing of the past.”

    Source:

     International Society for Heart and Lung Transplantation

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  • Xenotransplantation poised to become a clinical reality soon

    Xenotransplantation poised to become a clinical reality soon

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    Speaking today at the Annual Meeting and Scientific Sessions of the International Society for Heart and Lung Transplantation (ISHLT) in Prague, Muhammad Mohiuddin, MBBS, said xenotransplantation, hailed as the future of organ transplantation, is poised to become a clinical reality within the next several years.

    In January 2022, the University of Maryland School of Medicine (UMSOM) became the first institution in the world to implant a genetically modified pig heart into a human patient. A second patient underwent heart xenotransplantation at UMSOM in 2023.

    Every 80 minutes, a person on the waiting list for a new heart dies worldwide. Not everyone is going to get a heart transplant.”


    Dr. Muhammad Mohiuddin, professor of surgery and program director of UMSOM’s Cardiac Xenotransplantation Program

    Dr. Mohiuddin has implanted several hundred genetically modified pig hearts in animals throughout his three-decade career, helping to prepare for the first genetically modified xenotransplant in a living patient. Advances in cloning, gene editing, and infection control paved the way for the breakthrough in human xenotransplantation, which was performed under the US FDA’s expanded access program.

    “Using this option, we hope to eventually save millions of lives,” Dr. Mohiuddin said. “Genetically modified pig hearts could expand the pool of donor organs available for transplantation.”

    Pig organs are anatomically similar to humans, and pig heart valves have been used for decades to replace diseased human heart valves. A one-year-old genetically modified pig can support a human weighing up to 200 pounds. The pig’s lifespan is 20 years.

    The two human patients who received modified pig hearts at UMSOM lived approximately 40-60 days following their procedures.

    “We had the opportunity to learn a lot from our human patients,” Mohiuddin told attendees. “We found additional obstacles that we are hopeful we can overcome.”

    During his presentation, Mohiuddin shared a roadmap for the future of xenotransplantation and meeting the growing need for organs.

    “We want to get to the point that the same immunosuppression used in human heart transplants can also prolong the pig heart,” he said. “The advantage of using genetic modification is that we can modify the donor, which, of course, can’t be done with a human donor heart.”

    Source:

    International Society for Heart and Lung Transplantation

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  • How diet and hypertension sway risks for heart disease and cancer

    How diet and hypertension sway risks for heart disease and cancer

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    In a recent research review published in Nature Reviews Cardiology, researchers reviewed epidemiological studies on shared mechanisms and modifiable risk factors for cardiovascular disease (CVD) and cancer.

    CVD and cancer are leading causes of morbidity and death worldwide, and both illnesses are increasingly understood to be fundamentally linked. Understanding the risk factors and processes that link CVD and cancers allows for the prediction, prevention, and treatment of both, which is critical for advancing the area of cardio-oncology and improving the standard of care.

    In the present review, researchers reviewed existing data on the association between CVD and cancer.

    Cardiovascular disease and cancer: shared risk factors and mechanisms. Image Credit: ESB Professional / ShutterstockCardiovascular disease and cancer: shared risk factors and mechanisms. Image Credit: ESB Professional / Shutterstock

    Shared modifiable factors contributing to cardiovascular disease and cancer risk

    Hypertension contributes to CVD and several cancer types, including colorectal, breast, and renal cell cancers. Cancer patients and survivors have higher hypertension rates than healthy individuals. Hyperlipidemia is also associated with atherosclerotic CVD and low-density cholesterol (LDL)–lowering treatment can decrease CVD-related and any-cause deaths. Studies indicate that hyperlipidemia increases breast and colorectal cancer risk.

    Obesity, an independent CVD risk factor, exacerbates other risk factors such as diabetes, hypertension, and hyperlipidemia. Diabetes, an established contributory factor for cardiovascular disease, increases colorectal, breast, endometrial, and gallbladder cancer risk. Smoking elevates CVD risk and cancer incidence, increasing cardiovascular morbidities and deaths and malignancies in the upper respiratory organs.

    The link between alcohol intake and CVD risk is ambiguous; however, excessive drinking can increase CVD risk. The Mediterranean diet and increased exercise are dose-dependent and significantly related to a lower risk of cardiovascular disease, tumors, and related deaths. Socioeconomic determinants of health (SDOH) measures are strongly related to worsened cardiovascular health and poorer cancer outcomes.

    The dysregulation of systems regulating cellular aging, proliferation, metabolism, and damage connect cardiovascular disease and cancer. Oxidative stress in CVD raises noncommunicable disease risk, whereas clonal hematopoiesis causes chronic inflammation, which leads to atherosclerosis and inflammation. Microbial dysbiosis in cancer is associated with increased cell turnover, genotoxic metabolite production, inadequate immune surveillance, and chronic inflammation. Metabolic instability in cancer cells can result in circulating oncometabolites and cardiovascular remodeling. Environmental factors such as diet and medication use can influence dysbiosis. Circulating soluble chemicals are potential mediators of accelerated tumor growth and increased cancer risk in CVD patients.  

    Epidemiological evidence concerning shared factors increasing CVD and cancer risk

    Each 5.0 mmHg decrease in systolic blood pressure (SBP) lowers major adverse cardiovascular events [MACE, hazard ratio (HR) 0.9 without prior CVD; HR 0.9 with prior CVD] risk. A 10-mm Hg drop in SBP lowers CVD [relative risk (RR) 0.8] and any-cause mortality (RR 0.9) risks. Hypertension raises the chance of developing kidney, colorectal, and breast cancers.

    Elevated serum triglyceride raises colorectal cancer risk (HR 1.2), but increased high-density cholesterol (HDL) lowers colorectal (adjusted HR 0.8) and breast cancer incidences (RR 0.9). A 5.0 kg/m2 rise in body mass index (BMI) increases CVD risk factor risk, including hypertension, heart failure, ischemic stroke, atrial fibrillation, rectal cancer, and biliary tract cancers with RR values of 1.5, 1.4, 1.4, 1.2, 1.1, and 1.6, respectively. Elevated BMI is also associated with coronary artery diseases (HR, 1.2) and CVD-related deaths (HR, 1.5).

    Diabetes mellitus is associated with increased cardiovascular and any-cause deaths (HR 1.2). Smoking raises significant CVD risk (RR 1.6) and related deaths (HR 2.8). Quitting cigarette smoking within five years lowers the incidence of new-onset CVD (HR 0.6). Low-level drinking (1.3–5.0 g of alcohol daily) reduces coronary heart disease-related death risk compared to non-drinkers (RR 0.8); however, drinking >50 g of alcohol daily increases the risk of oropharyngeal, oesophageal, colorectal, laryngeal, and breast cancers.

    The Mediterranean diet, which includes olive oil and mixed nuts, lowers the incidence of CVD (HR 0.7). Mediterranean diets reduce the risk of nonfatal MI (RR 0.5), CVD mortality [odds ratio (OR) 0.6], all-cause mortality (OR 0.7), colorectal and breast cancers, and cancer death (RR 0.9). Low cardiorespiratory fitness raises all-cause mortality and CVD events (HR 1.7). High leisure-time physical activity lowers the incidence of 13 malignancies, with the most robust relationships seen in esophageal, lung, and kidney cancers (HR 0.6). The presence of at least one SDOH increases 90-day mortality after heart failure hospitalization (HR 2.8). Three or more SDOHs raise the likelihood of fatal events (CVD HR 1.5) and cancer-related mortality (HR 1.3 for those over 65 years).

    Based on the findings, CVD and cancer have a bidirectional link, with shared processes and risk factors producing both conditions. CVD raises the risk of certain types of cancer and cancer-related mortality, whereas cancer raises the risk of certain types of CVD and CVD-related death. Common risk factors include hypertension, high cholesterol, diabetes, obesity, smoking, nutrition, physical activity, and SDOH. Addressing shared risk factors for CVD and cancer has far-reaching public health consequences, as technological discoveries have made cancer a chronic illness, and an increasing population of aging adult survivors may acquire comorbid CVD.

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  • The global quest for the right balance of sodium and potassium in the diet

    The global quest for the right balance of sodium and potassium in the diet

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    In a recent review published in the journal Hypertension Research, a group of authors compared global dietary sodium and potassium intake guidelines with Japan’s, highlighting the importance of customized recommendations to cultural dietary practices to address non-communicable diseases (NCDs).

    Mini Review: Global guidelines recommendations for dietary sodium and potassium intake. Image Credit: Degimages / ShutterstockMini Review: Global guidelines recommendations for dietary sodium and potassium intake. Image Credit: Degimages / Shutterstock

    Background 

    Due to unhealthy eating habits, NCDs have been identified as a global health concern that causes high mortality rates. The intake of sodium and potassium must be regulated in order to avoid any possible adverse effects on the human body, such as hypertension and heart diseases, among others. Further research is needed to customize dietary guidelines to cultural and regional eating habits, ensuring they are both effective and culturally sensitive in reducing NCDs globally.

    Global sodium intake recommendations

    Sodium intake guidelines are different globally and tend to be suited to regional dietary habits as well as health objectives, as stated by major health organizations.

    The World Health Organization’s (WHO’s) approach

    In 2012, the WHO set sodium intake guidelines for adults and children in order to achieve better health outcomes. It suggests that adults should consume a maximum of 2.0 grams of sodium per day, while children’s sodium levels should be adjusted on the basis of relative energy requirements. This guidance, backed by strong epidemiological and clinical research, seeks to reduce cardiovascular diseases by advocating for a global lower sodium intake.

    American Heart Association (AHA) and American College of Cardiology (ACC) ‘s guidelines 

    In 2011, the AHA recommended reducing daily sodium intake to 1.5 grams to manage blood pressure, especially among adults at risk of hypertension. Subsequent studies affirm the importance of limiting salt intake in preventing heart disease. Despite some debate over the rigor of this limit, the AHA and ACC maintain a recommended limit of 1.5 grams, aiming for even lower intakes in certain populations.

    Insights from the Dietary Guidelines for Americans (DGA)

    The 2020-2025 DGA advocates for a varied, nutrient-dense diet and specifies sodium intake limits based on age and risk factors. With a general recommendation of 2.3 grams daily, it advises further reduction to 1.5 grams for those at heightened risk of hypertension, emphasizing personalization in dietary choices.

    The European Food Safety Authority (EFSA)’s Recommendations

    In 2019, the EFSA updated its sodium intake guidelines to 2.0 grams per day for adults, aligning with the need to maintain sodium balance and support overall health. These guidelines, intended to inform policy and health advice within the European Union, also specify intake levels for children and special populations.

    Japan’s unique dietary guidelines

    Japan’s dietary guidelines reflect its specific nutritional context and historical dietary patterns. With a higher sodium intake goal compared to many countries, influenced by traditional food preferences, Japan aims to reconcile its guidelines with global recommendations while considering cultural and dietary practices. The guidelines suggest a gradual reduction in sodium intake, advocating for a balanced approach to align more closely with international standards.

    Potassium intake guidelines: Bridging global recommendations

    WHO’s perspective on potassium

    The WHO emphasizes potassium’s role in countering the adverse effects of high sodium intake, recommending a daily intake of at least 3.51 grams for adults. This guideline, supported by a comprehensive review of scientific evidence, underscores potassium’s importance in cardiovascular health.

    ACC/AHA and Potassium

    The ACC/AHA guidelines suggest enhancing potassium intake within a balanced diet to prevent cardiovascular diseases. While specific targets are not strongly emphasized, the recommendation is to consume 3.5 to 5.0 grams from potassium-rich foods daily, underscoring the nutrient’s role in heart health.

    DGA on potassium

    Echoing the importance of potassium, the 2020-2025 DGA recommends adult intake levels of 2.6 grams for women and 3.4 grams for men, promoting potassium-rich foods to support blood pressure management and reduce disease risk.

    EFSA’s potassium intake recommendations

    The EFSA, updating its guidelines based on recent evidence, sets the adult potassium intake at 3.5 grams daily. This guidance aims to inform health policies and advice, highlighting the ongoing need for research to further understand potassium’s health impacts.

    Japan’s approach to potassium intake

    In line with efforts to address high sodium consumption, Japan’s guidelines also advocate for increased potassium intake, especially from fruits and vegetables. This reflects an awareness of the balance between sodium and potassium intake in promoting health and preventing lifestyle-related diseases.

    Comparative analysis and the path forward

    The review of sodium and potassium intake guidelines reveals a global consensus on limiting sodium and enhancing potassium intake for health benefits. However, regional differences in dietary patterns necessitate tailored approaches to guideline implementation. Japan’s guidelines, for instance, illustrate the challenges and opportunities in aligning national recommendations with global standards. Countries like Japan are committed to public health by continuously revising dietary guidelines and adapting global recommendations to local contexts. This ongoing dialogue between global and national health recommendations underscores the complexity of dietary guideline formulation and the importance of culturally sensitive, evidence-based approaches to dietary policy.

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  • High blood levels of TMAO predicts chronic kidney disease risk in future

    High blood levels of TMAO predicts chronic kidney disease risk in future

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    New findings from Cleveland Clinic and Tufts University researchers show high blood levels of TMAO (trimethylamine N-oxide) predicts future risk of developing chronic kidney disease over time.

    The findings build on more than a decade of research spearheaded by Stanley Hazen, M.D., Ph.D., and a team related to the gut microbiome’s role in cardiovascular health and disease, including the adverse effects of TMAO, a byproduct formed by the gut bacteria from nutrients abundant in red meat, eggs and other animal source foods.

    The study, published in the Journal of the American Society of Nephrology, was a collaboration between a Cleveland Clinic research team led by Dr. Hazen and investigators from the Food is Medicine Institute at the Friedman School of Nutrition Science and Policy at Tufts University, including first author Meng Wang, Ph.D., and co-senior author Dariush Mozaffarian, M.D., Dr.PH.

    The large-scale study measured blood levels of TMAO over time in two large National Institutes of Health populations and followed the kidney function of more than 10,000 U.S. adults with normal kidney function at baseline over an average follow-up period of 10 years. The investigators found that participants with elevated TMAO blood levels were at increased risk for future development of chronic kidney disease.

    Higher TMAO levels were also associated with a faster rate of declining kidney function in people with normal or impaired kidney function at baseline. These associations were independent of sociodemographic characteristics, lifestyle habits, diet and other known risk factors for kidney disease. The findings also are consistent with earlier reported preclinical model studies showing TMAO directly fosters both kidney functional decline and tissue fibrosis.

    The findings indicate a remarkably strong clinical link between elevated TMAO and increased risk for developing chronic kidney disease. The results are from individuals of diverse ethnic and sociodemographic backgrounds who had normal kidney function at the start. The diversity of the participants helps ensure the results are generalizable.”


    Dr. Stanley Hazen, chair of the Department of Cardiovascular and Metabolic Sciences and at Cleveland Clinic’s Lerner Research Institute and co-section head of Preventive Cardiology in the Heart, Vascular & Thoracic Institute

    Chronic kidney disease is a major and growing public health challenge in both the U.S. and globally, affecting about 10-15% of the population worldwide. It also is a strong risk factor for cardiovascular disease. The study showed that TMAO levels were as strong or even stronger an indicator of chronic kidney disease risk than the well-known risk factors such as diabetes, hypertension, advancing age and race.

    The study results reinforce the growing body of evidence indicating that lowering TMAO with prescribed drugs could be an effective treatment in patients at risk for, or with early signs of, kidney disease.

    “Our study is a crucial complement to studies in preclinical models supporting TMAO as a novel biological risk factor for chronic kidney disease,” said Dr. Wang, research assistant professor at the Friedman School. “TMAO levels are highly modifiable by both lifestyle-like diet and pharmacologic interventions. Besides using novel drugs to lower TMAO in patients, using dietary interventions to lower TMAO in the general population could be a cost-efficient and low-risk preventive strategy for chronic kidney disease development.”

    Plans for future studies include examining genetic data to help assess the potential cause-and-effect relationship between TMAO and chronic kidney disease, as well as studying more definitively whether lifestyle changes may prevent chronic kidney disease development and progression.

    Dr. Hazen also directs Cleveland Clinic’s Center for Microbiome and Human Health and holds the Jan Bleeksma Chair in Vascular Cell Biology and Atherosclerosis.

    This research was supported by grants from the National Institutes of Health, as well as the American Heart Association Postdoctoral Fellowship.

    Source:

    Journal reference:

    Wang, M., et al. (2024). The Gut Microbial Metabolite Trimethylamine N-oxide, Incident CKD, and Kidney Function Decline. Journal of the American Society of Nephrology. doi.org/10.1681/ASN.0000000000000344.

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  • Research identifies how leukemia develops resistance to first line treatments

    Research identifies how leukemia develops resistance to first line treatments

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    Relapses in a common form of leukemia may be preventable following new research which has identified how the cancer develops resistance to first line treatments.

    New research published in iScience by researchers from the University of Birmingham, the Institute of Cancer Research (ICR), Newcastle University, the Princess Maxima Centre of Pediatric oncology and the University of Virginia identified changes in a mutated form of acute myeloid leukemia (AML) samples from patients who relapsed after receiving FLT3 inhibitor treatment.

    The team found that the resistant cancer had up-regulated multiple other signalling pathways to overcome the drug’s action, and that the genetic change was able to be replicated in lab tests.

    These experiments revealed that by targeting RAS family proteins, using a small molecule inhibitor developed from a chemical library screen using the paratope of an inhibitory intracellular antibody by Terry Rabbitts’ team at the Weatherall Institute of Molecular Medicine University of Oxford and the ICR, increased signalling no longer rescued the cells from cell death.

    The team identified that the transcription factors AP-1 and RUNX1 were at the heart of mediating drug resistance. The two factors cooperate and bind to their target genes together, but only in the presence of growth factor signalling. The drugs targeting FLT3 rewire the cell, resulting in the upregulation of other signalling pathway associated genes, which then restored AP-1 and RUNX1 binding. Drugging RAS, which is a key component in multiple signalling pathways, prevented this restoration of RUNX1 binding, and therefore signalling from growth factors no longer rescued the cancer cells from death.

    Professor Constanze Bonifer from the Institute of Cancer and Genomic Sciences at the University of Birmingham, who has just taken up a position at the University of Melbourne, and is one of the senior authors of the paper said:

    “The pharmaceutical industry had high hopes that drugs targeting aberrant growth factor receptors such as the FLT3-ITD would prevent people from relapse. However, cancer cells are smart, and rewire their growth control machinery to use other growth factors present in the body. Targeting RAS family members prevents the cancer from rewiring and using different signalling pathways to escape cell death.”

    Targeting RAS blocks rewiring

    The small molecule inhibitors used to target RAS in this study were developed using intracellular antibody technology. This technology involves screening a large number of antibody fragments to identify those which bind to the target protein in cells and prevent their protein-protein interactions. Small molecule inhibitors are can be screened from chemical libraries that interact with the parts of the target protein where these antibody fragments bind (the paratope). Due to the unparalleled natural specificity of these antibody fragments, this technology (called Antibody derived or Abd technology) can be used to target difficult to drug proteins and identify new parts of the protein which can be targeted to prevent protein-protein interactions.

    Professor Terry Rabbitts from the Institute of Cancer Research who developed these drugs said:

    “The strength of the Antibody-derived technology approach is that intracellular antibodies can selected to essentially any protein. In turn, their specific binding sites can be employed to select chemical compounds for drug discovery against hard to drug proteins. Mutant RAS was considered undruggable, but the Abd technology facilitated the development of the RAS-binding compounds used in the current study of cancer cell re-wiring. Abd technology will allow development of a new generation of drugs to hard-to-drug and intrinsically disordered proteins.“

    AML with a FLT3-ITD mutation occurs in nearly 30% of all patients and is a highly aggressive disease with a poor prognosis. This genetic change causes the expression of a mutant growth factor receptor which is always active and therefore cancer cells expressing it grow uncontrollably. While inhibitors which specifically target the FLT3 protein are now in use in the clinic, patients treated with these inhibitors frequently relapse.

    This work was funded by Leukaemia Research UK, the Medical Research Council, Blood Cancer Research UK, the Royal Society, the Wellcome and Cancer Research UK. The first author, Daniel Coleman is a John Goldman Fellow of Leukaemia UK.

    Source:

    Journal reference:

    Daniel J.L., et al. (2024). Pharmacological inhibition of RAS overcomes FLT3 inhibitor resistance in FLT3-ITD+ AML through AP-1 and RUNX1. iScience. doi.org/10.1016/j.isci.2024.109576.

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