2022 Southern Medical Research Conference
Study Shows Strong Association Between Atherosclerosis And Accelerated Aging
Atherosclerosis—the much-feared 'hardening' of our arteries—impacts our health long before the appearance of symptomatic cardiovascular disease. A new study by a team at the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) demonstrates a strong association between atherosclerosis at subclinical stages and an accelerated aging process.
The study is published in the European Heart Journal. Lead author and CNIC General Director Dr. Valentín Fuster emphasized that the results underline the benefits of reducing inflammation by adopting a healthy lifestyle (healthy diet, regular physical activity, etc.) or taking specific medication, such as cholesterol-lowering statins "that can block, or at least slow, the transition from the subclinical phase of atherosclerosis to the appearance of severe cerebrovascular events, like myocardial infarction or stroke."
The study shows that there is a strong association between the presence, extent, and progression of atherosclerosis at the subclinical level and accelerated epigenetic aging in otherwise healthy young individuals, said Dr. Enrique Lara Pezzi, an author on the study.
Epigenetic age is a measure of a person's biological age (the functional age of their cells and tissues) based on the idea of the epigenetic clock. Epigenetic clocks use machine learning algorithms to predict a person's biological age and life expectancy based on their level of DNA methylation, explained study first author Fátima Sánchez Cabo.
But sometimes, said Sánchez Cabo, this prediction does not correspond to a person's chronological age (the time elapsed since birth), "so that someone's epigenetic age can be older than their chronological age, whereas someone else might have an epigenetic age younger than their chronological age."
Fortunately, unlike the germinal mutations we carry in our genome, "changes in DNA methylation are reversible, opening up the possibility of 'slowing down' our epigenetic aging," assured Lara Pezzi.
The identification of an association between subclinical atherosclerosis and reduced life expectancy based on epigenetic clocks was possible thanks to a massive analysis of data from the PESA-CNIC-SANTANDER study, which is led Dr. Valentín Fuster. Since 2010, the PESA-CNIC-SANTANDER study has analyzed the progression of subclinical atherosclerosis in more than 4000 Banco Santander employees aged 40 to 54 years at the start of the study and with no prior history of cardiovascular disease.
"The follow-up of this cohort constitutes one of the most important cardiovascular prevention studies in the world," said Dr. Fuster.
The European Heart Journal study combines data on the progression of atherosclerosis obtained with advanced imaging techniques with detailed information on participants' lifestyle and data from molecular omics studies.
"These molecular data allowed us to advance our knowledge of the causal mechanisms of subclinical atherosclerosis, as well as its clinical consequences, providing key information for a more personalized treatment of the disease in its early stages," said Lara Pezzi.
Using transcriptomic and proteomic data, the study demonstrates that systemic inflammation triggered in individuals with a high burden of atherosclerotic plaques may be a key factor in accelerating their epigenetic aging.
The authors conclude that the study identifies a solid association between the presence, extent, and progression of subclinical atherosclerosis and accelerated epigenetic aging, mediated in part by low-grade chronic inflammation induced by inflammatory cytokines.
The authors nevertheless recognize that further longitudinal studies are needed over a longer follow-up period and supported by more experimental data, in order to provide a more thorough characterization of the effect of atherosclerosis on health and life expectancy and to identify underlying mechanisms.
More information: Fátima Sánchez-Cabo et al, Subclinical atherosclerosis and accelerated epigenetic age mediated by inflammation: a multi-omics study, European Heart Journal (2023). DOI: 10.1093/eurheartj/ehad361
Provided by Centro Nacional de Investigaciones Cardiovasculares Carlos III (F.S.P.)
Citation: Study shows strong association between atherosclerosis and accelerated aging (2023, June 21) retrieved 22 June 2023 from https://medicalxpress.Com/news/2023-06-strong-association-atherosclerosis-aging.Html
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U.S. FDA Approves First Anti-Inflammatory Drug For Cardiovascular Disease
LODOCO® (colchicine, 0.5 mg tablet) Reduces Cardiac Event Risk in Adult Patients with Established Atherosclerotic Cardiovascular Disease (ASCVD) by an Additional 31% on Top of Standard of Care.
LODOCO Targets Residual Inflammation as an Underlying Cause of ASCVD and Can be Used Alone or in Combination with Cholesterol-Lowering Medications
PARSIPPANY, N.J., June 20, 2023--(BUSINESS WIRE)--AGEPHA Pharma USA, LLC, today announced that, following a Priority Review, the U.S. Food and Drug Administration (FDA) has approved LODOCO® as the first anti-inflammatory atheroprotective cardiovascular treatment demonstrated to reduce the risk of myocardial infarction (MI), stroke, coronary revascularization, and cardiovascular death in adult patients with established atherosclerotic disease or with multiple risk factors for cardiovascular disease.1
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LODOCO can reduce the risk of cardiac events in patients with established cardiovascular diseases by 31% on top of standard of care, will be available for prescription in the second half of 2023. (Photo: Business Wire)
AGEPHA Pharma anticipates that LODOCO, which can reduce the risk of cardiac events in patients with established cardiovascular diseases by 31%2 on top of standard of care, will be available for prescription in the second half of 2023.
Clinical Evidence of LODOCO for Heart Attack and Stroke Prevention
The effectiveness and safety of LODOCO in preventing heart attack and stroke is supported by randomized trial data reported in the New England Journal of Medicine, Circulation, Journal of the American College of Cardiology, and European Heart Journal, while data emphasizing the critical need to address inflammation as much as cholesterol in heart disease patients has been recently described in The Lancet.
The multi-national, randomized, double-blind, placebo-controlled clinical trial was conducted among 5,522 patients with chronic coronary disease all of whom were taking guideline-directed medical care including high-intensity statins. In the trial, 0.5 mg colchicine was found to significantly reduce the overall risk of cardiovascular death, spontaneous myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization by 31% in comparison with the placebo group when added to high-intensity statins and other cardiology prevention therapies (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.57 to 0.83; P<0.001).2
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Entering a New Era of Patient Care
It has been long understood that inflammation as well as high cholesterol increases cardiovascular risks.
"Approval by the FDA of the first drug to target cardiovascular inflammation is an important step forward for the care of our patients," said Paul Ridker, MD, MPH, professor of medicine, Harvard Medical School and director of the Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, who has been instrumental in elucidating the role of inflammation in cardiovascular disease. Dr. Ridker added, "To treat coronary disease effectively, cardiologists must aggressively reduce inflammation and cholesterol. For appropriate patients already taking a statin, adding the anti-inflammatory drug colchicine at a dose of 0.5 mg daily has been proven to significantly lower risks of recurrent heart attack and stroke."
A recent study in The Lancet, on which Dr. Ridker served as lead author, demonstrated that among contemporary statin-treated patients, vascular inflammation strongly predicts future cardiovascular events – perhaps even more than high cholesterol.
Reduce Inflammation, Reduce Plaque Formation
Inflammation plays a critical role in Atherosclerotic Cardiovascular Disease (ASCVD). ASCVD is a condition where the arteries become narrowed and hardened due to the buildup of plaque, which can lead to heart attacks and strokes3 and refers to conditions including coronary artery disease, acute coronary syndrome, peripheral artery disease, and cerebrovascular disease. Patients with ASCVD, the leading cause of morbidity and mortality in the United States4, are at high risk for acute cardiovascular events.5
The formation of atherosclerotic plaque, in which inflammation plays a substantial role, contributes to the development and progression of ASCVD.6LODOCO inhibits microtubule assembly and has multiple anti-inflammatory mechanisms.7,8 High-sensitivity C-reactive protein (hs-CRP) is the inflammatory biomarker most widely used to predict residual inflammatory risk and ASCVD outcomes.9
Michael Blaha, MD, MPH, director of clinical research and professor of medicine at the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease said, "For the first time, patients with residual inflammatory risk, as measured by hs-CRP, will have an FDA-approved treatment option demonstrated to reduce the risk of cardiovascular disease by targeting the inflammatory pathways that influence major cardiac events."
Dr. Blaha added, "The cardiovascular research community has demonstrated that focusing on unmet patient medical needs and addressing the long-standing challenge of reducing cardiac inflammation can translate into meaningful risk reduction in the incidence of cardiac events."
Disease burden in the United States
ASCVD patients in USA
26 million10
ASCVD hospitalizations/ year
2 million11
ASCVD Deaths/ year
400,00011
No. 1 cause of death
Heart Disease12
Heart attacks / year
800,00013
Rate of recurrence
20% (equivalent of 200,000)13
No. 5 cause of death
Stroke12
Stroke / year
795,00013
Rate of recurrence
25% (equivalent to 185,000)13
LODOCO's Place in Therapy
LODOCO tablets are formulated as a once-daily, continuous-use oral treatment for adults and can be used safely alone or in combination with standard-of-care lipid-lowering medications and other therapies, to effectively reduce the risk of heart attack and stroke.
Patients with kidney failure or severe liver disease should not take LODOCO. Patients should temporarily stop taking LODOCO if prescribed certain drugs like azithromycin or ketoconazole as these medications should not be taken simultaneously.
Groundbreaking Therapy Championed by EU-Founded, Family-Led Pharma Company
Antonia Riel-Köllmann, managing director of AGEPHA Pharma, the family owned and operated company stated, "As the third generation of my family dedicated to developing high-quality European pharmaceuticals, it's a privilege to bring this life-sustaining therapy, which represents the company's first product launch in the United States, to the global market. We are dedicated to addressing heart disease, the leading cause of death, by ensuring all patients have access to LODOCO."
About AGEPHA Pharma
AGEPHA Pharma is a family-owned, leading multinational pharmaceutical company focused on bringing treatments to patients who need them most. Since 1947, they have invested in proven therapies, including a wide range of pharmaceuticals, medical devices, and nutritional supplements, supported by a highly qualified team of clinical scientists and regulatory experts.
For more information, please visit AGEPHA Pharma's U.S. Corporate website or follow AGEPHA Pharma on Twitter (@AGEPHAPharmaUS) and LinkedIn.
IMPORTANT SAFETY INFORMATION
Indication
LODOCO is indicated to reduce the risk of myocardial infarction (MI), stroke, coronary revascularization, and cardiovascular death in adult patients with established atherosclerotic disease or with multiple risk factors for cardiovascular disease.
IMPORTANT SAFETY INFORMATION LODOCO® (COLCHICINE) 0.5 MG TABLETS
Do not take LODOCO if you:
take certain medicines called strong CYP3A4 inhibitors or P-glycoprotein inhibitors. Ask your healthcare provider if you are not sure. Taking certain medicines with LODOCO may cause your level of LODOCO to be too high in your body and cause life-threatening side effects or death.
have severe kidney or liver problems.
have blood problems.
are allergic to colchicine or any of the ingredients in LODOCO.
What are the possible side effects of LODOCO?
LODOCO may cause serious side effects, including:
Blood problems. LODOCO can cause low red blood cell counts, low white blood cell counts, and low platelet counts, which can be life-threatening or may lead to death.
Muscle weakness (neuromuscular toxicity). LODOCO can cause muscle weakness and muscle problems.
The most common side effects of LODOCO include:
Fatal overdoses have been reported with colchicine in adults and children. Keep LODOCO out of the reach of children.
References:
1 LODOCO. Prescribing information. AGEPHA Pharma FZ, LLC; 2023.2 Nidorf SM, Fiolet ATL, Mosterd A, et al. Colchicine in Patients with Chronic Coronary Disease. N Engl J Med. 2020;383(19):1838-1847. Doi:10.1056/NEJMoa20213723 What is atherosclerosis? American Heart Association. Published April 3, 2023. Accessed April 12, 2023. Https://www.Heart.Org/en/health-topics/cholesterol/about-cholesterol/atherosclerosis4 Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines [published correction appears in Circulation. 2019 Sep 10;140(11):e649-e650] [published correction appears in Circulation. 2020 Jan 28;141(4):e60] [published correction appears in Circulation. 2020 Apr 21;141(16):e774]. Circulation. 2019;140(11):e596-e646. Doi:10.1161/CIR.00000000000006785 van Trier TJ, Snaterse M, Hageman SHJ, et al. Unexploited potential of risk factor treatment in patients with atherosclerotic cardiovascular disease. Eur J Prev Cardiol. 2023;30(7):601-610. Doi:10.1093/eurjpc/zwad0386 Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature. 2011 May 19;473(7347):317-25. Doi: 10.1038/nature10146. PMID: 21593864.7 Leung YY, Yao Hui LL, Kraus VB. Colchicine--Update on mechanisms of action and therapeutic uses. Semin Arthritis Rheum. 2015;45(3):341-350. Doi:10.1016/j.Semarthrit.2015.06.0138 Zhang FS, He QZ, Qin CH, Little PJ, Weng JP, Xu SW. Therapeutic potential of colchicine in cardiovascular medicine: a pharmacological review. Acta Pharmacol Sin. 2022;43(9):2173-2190. Doi:10.1038/s41401-021-00835-w9 Rossello X, et al. Lifetime Risk Estimation in Atherosclerotic Cardiovascular Disease. J Am Coll Cardiol. 2021 Sep, 78 (11) 1095–1096. Https://doi.Org/10.1016/j.Jacc.2021.07.03510 Virani SS, Alonso A, Aparicio HJ, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, Chamberlain AM, Cheng S, Delling FNet al. Heart disease and stroke statistics-2021 update: a report from the American Heart Association. Circulation. 2021; 143:e254–e743. Doi: 10.1161/CIR.000000000000095011 Ritchey MD, Wall HK, Owens PL, Wright JS. Vital Signs: State-Level Variation in Nonfatal and Fatal Cardiovascular Events Targeted for Prevention by Million Hearts 2022. MMWR Morb Mortal Wkly Rep. 2018;67(35):974-982. Published 2018 Sep 7. Doi:10.15585/mmwr.Mm6735a312 Heart disease and stroke. Centers for Disease Control and Prevention. Published September 8, 2022. Accessed April 25, 2023. Https://www.Cdc.Gov/chronicdisease/resources/publications/factsheets/heart-disease-stroke.Htm13 Tsao CW, Aday AW, Almarzooq ZI, et al. Heart Disease and Stroke Statistics-2022 Update: A Report From the American Heart Association [published correction appears in Circulation. 2022 Sep 6;146(10):e141]. Circulation. 2022;145(8):e153-e639. Doi:10.1161/CIR.000000000000105
Disclosure: Dr. Paul Ridker and Dr. Michael Blaha are AGEPHA Pharma consultants. AGEPHA Pharma does not guide or comment on their data and peer-review submissions.
View source version on businesswire.Com: https://www.Businesswire.Com/news/home/20230620113838/en/
Contacts
AGEPHA PharmaMedia Inquiries
Laura O'Neill for AGEPHA PharmaFINN Partnerslaura.Oneill@finnpartners.Com402-499-8203
The Lesser-known Risk Factors For Heart Disease
Most people know that the risk factors for heart disease are high blood pressure, smoking, raised cholesterol and being overweight. However, many people who have a heart attack do not have any of these traditional risk factors.
Research has suggested that conditions such as gout, psoriasis, inflammatory bowel disease and rheumatoid arthritis are also risk factors for heart disease. What they have in common is chronic inflammation.
In fact, some researchers have begun to re-frame cardiovascular disease as a chronic inflammatory disease of the arteries. Scientists sometimes refer to this as the inflammatory hypothesis of atherosclerotic cardiovascular disease (ASCVD).
Atherosclerosis is where fatty plaques develop in the walls of our arteries, making them stiff. When this happens in the arteries that supply oxygenated blood to the heart, it is referred to as coronary artery disease.
ASCVD can cause heart attacks, where not enough blood is being supplied to the heart, and ischemic strokes, where not enough blood is being supplied to the brain. To understand why ASCVD is an inflammatory condition, we need to consider how this process starts.
The first stage of developing atherosclerosis is thought to be some form of injury to the endothelium, the single layer of cells that line the arteries. This can be caused by high levels of low-density lipoprotein (LDL) cholesterol, sometimes referred to as "bad cholesterol".
The toxins contained in cigarettes can also irritate the lining of the arteries and cause this initial injury. When the endothelial cells are injured, they release chemical messages that attract white blood cells, an important component of the immune system, to the site.
These white blood cells enter the artery wall and cause inflammation in the artery. The white blood cells also consume the cholesterol in the walls of the artery, leading to the formation of "fatty streaks"—one of the earliest visible signs of atherosclerosis.
Fatty streaks begin to form at a young age. By the time we are in our twenties, most of us will have some evidence of fatty streaks in our arteries.
This process of endothelial cell damage, white blood cell infiltration and chronic inflammation can continue silently over the years, eventually leading to the build up of plaque in the arteries. This may also explain why people who suffer from chronic inflammatory conditions are at an increased risk of cardiovascular disease.
Long-term inflammation of the arteries supplying the heart and brain can eventually lead to heart attacks and strokes.
A heart attack occurs when a plaque in the artery supplying the heart becomes unstable. This can lead to rupture (bursting) of the plaque, leading to a clot forming in the artery and the blood supply to the muscle of the heart being interrupted.
People who experience a heart attack often have increased levels of inflammation and plaque instability in the days and weeks before the event. The eventual "heart attack" and resultant damage to the heart muscle can be seen as this unstable inflammatory process reaching its zenith.
Because this chronic inflammatory process happens silently, many patients without traditional risk factors for heart disease will not be aware that they are at an increased risk of heart disease.
Measuring inflammationThankfully, there is a way to measure inflammation in the body. One way of doing this is with a blood test called high-sensitivity c-reactive protein (hs-CRP). People with raised levels of hs-CRP have an increased risk of heart attacks and strokes. Raised levels of LDL-cholesterol are also a risk factor for ASCVD.
Several studies have reported that people who have high levels of both LDL cholesterol and hs-CRP seem to have the highest risk of cardiovascular disease.
A large clinical trial called Cantos tested the inflammatory hypothesis of cardiovascular disease by treating patients who had had a heart attack and had high levels of hs-CRP with an anti-inflammatory drug called canakinumab.
The use of this anti-inflammatory drug reduced the levels of hs-CRP and resulted in a small but statistically significant reduction in the number of heart attacks experienced by these patients. Unfortunately, there also appeared to be an increased risk of infections in the group receiving the drug.
This risk, alongside the high cost of the drug, means it is not likely we are going to start using canakinumab to treat ASCVD any time soon.
However, the study was considered groundbreaking in that it supported the hypothesis that inflammation plays an important role in ASCVD, and that targeting inflammation may be useful to reduce the risk of repeat cardiovascular events.
Embracing this change in how we think about the risk factors for ASCVD may allow us to better identify patients who are at risk of heart attacks and strokes.
Also, this may enable us to focus on treating inflammation in order to reduce cardiovascular risk. Already, several studies are looking at using cheaper anti-inflammatory drugs, such as colchicine and methotrexate, to reduce inflammation and prevent the progression of cardiovascular disease.
Lifestyle changes to reduce inflammationFortunately, it is possible to reduce inflammation in our bodies without resorting to drugs. We can think of everything we do in our lives as being either pro-inflammatory or anti-inflammatory.
Smoking is pro-inflammatory as the toxins in cigarettes irritate the body. High levels of cholesterol in the blood and a diet rich in ultra-processed foods can also lead to chronic inflammation in our arteries. Conversely, a diet rich in fruit, vegetables, whole grains and fatty fish is thought to be anti-inflammatory.
Exercise also reduces the levels of inflammation in the body. Obesity, in particular carrying excess weight around your midsection, appears to cause chronic inflammation. Losing weight around your midsection will help to reduce this inflammation.
Stress can also induce a chronic low-grade inflammatory response in the body, and it is important to try to manage our stress levels. It is also important to maintain healthy blood pressure, cholesterol and body mass index—the traditional markers of heart disease risk.
By making anti-inflammatory choices and leading a healthy lifestyle we can all reduce our chances of developing heart disease and improve our quality of life.
This article is republished from The Conversation under a Creative Commons license. Read the original article.
Citation: The lesser-known risk factors for heart disease (2023, June 16) retrieved 22 June 2023 from https://medicalxpress.Com/news/2023-06-lesser-known-factors-heart-disease.Html
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.
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