Amyloid-Beta (1-40) and the Risk of Death From Cardiovascular Causes in Patients With Coronary Heart Disease

Stamatelopoulos, Kimon; Sibbing, Dirk; Rallidis, Lοukianos S.; Georgiopoulos, Georgios; Stakos, Dimitrios; Braun, Siegmund; Gatsiou, Aikaterini; Sopova, Kateryna; Kotakos, Christos; Varounis, Christos; Tellis, Constantinos C.; Kastritis, Efstathios; Alevizaki, Maria; Tselepis, Alexandros D.; Alexopoulos, Panagiotis; Laske, Christoph; Keller, Till; Kastrati, Adnan; Dimmeler, Stefanie; Zeiher, Andreas M.; Stellos, Konstantinos

doi:10.1016/j.jacc.2014.12.035

Cited by 101 publications

(71 citation statements)

References 28 publications

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“…121 Established markers of inflammation (Table 2), such as hsCRP, are associated with adverse cardiovascular events in patients with stable coronary artery disease. 122 In addition, emerging novel inflammatory risk markers include heat shock protein 70, 122 amyloid β-peptide, 123 and levels of circulating progenitor cells. 124 miRNA are small noncoding RNA with many regulatory roles in the pathophysiology of cardiovascular disease (Table 4).…”

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confidence: 99%

Novel Risk Markers and Risk Assessments for Cardiovascular Disease

Thomas

Lip

2017

Circulation Research

117

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Abstract:The use of risk markers has transformed cardiovascular medicine, exemplified by the routine assessment of troponin, for both diagnosis and assessment of prognosis in patients with chest pain. Clinical risk factors form the basis for risk assessment of cardiovascular disease and the addition of biochemical, cellular, and imaging parameters offers further refinement. Identifying novel risk factors may allow greater risk stratification and a steady, but gradual progression toward precision medicine. Indeed, the generation of data in this area of research is explosive and when combined with new technologies and techniques provides the potential for more refined, targeted approaches to cardiovascular medicine. Although discussing the most recent developments in this field, this review article aims to strike a balance between novelty and validity by focusing on recent large samplesize studies that have been validated in a separate cohort in most cases. Risk markers related to atherosclerosis, thrombosis, inflammation, cardiac injury, and fibrosis are introduced in the context of their pathophysiology. Rapidly developing new areas, such as assessment of micro-RNA, are also explored. Subsequently the prognostic ability of these risk markers in coronary artery disease, heart failure, and atrial fibrillation is discussed in detail. ( addition to these roles in the pathogenesis of coronary artery disease, lipid-related molecules have been identified to be markers of inflammation and oxidative stress (Table 1). Thrombosis-Related Risk MarkersAfter atherosclerotic plaque rupture, platelets adhere to exposed subendothelial components, such as collagen and von Willebrand factor, which promotes platelet activation and aggregation. 10 In addition, platelet activation is potentiated by exposure to released soluble agonists, such as thrombin and ADP.10 Activated platelets then further release ADP, which acts on platelet P2Y 12 ADP receptors and has a central role in amplifying the response of platelets to the initial stimulus. 10 Platelet reactivity to various agonists, including ADP, has been studied extensively in the context of acute coronary syndrome (ACS; Table 2). 11 The VerifyNow and Multiplate pointof-care tests allow for the measurement of platelet aggregation in response to stimulation, and it has been shown that high platelet reactivity is associated with adverse cardiovascular events. 26 Platelet microparticles are released on platelet activation, and their role in cardiovascular disease is an area of active investigation (Table 2). 15 Circulating microparticles are released from cells undergoing activation or apoptosis and are a type of small plasma membrane vesicle that retain defined properties from their original cell lineage. 15 Platelet activation and aggregation lead to the activation of the coagulation cascade and the formation of a stable crosslinked fibrin clot. The balance between prothrombotic factors and endogenous fibrinolysis determines whether the thrombus propagates or instead proceeds to dis...

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confidence: 99%

Novel Risk Markers and Risk Assessments for Cardiovascular Disease

Thomas

Lip

2017

Circulation Research

117

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“…The latter is also regarded as the reverse link between myocardial functional decline in AD and aging (38,41). Furthermore circulating Aβ 40 was shown to worsen vascular atherosclerosis, and to predict disease progression and cardiovascular mortality in patients with established CAD (42,43). Here, we tested whether other mechanisms link cardiac dysfunction to the brain disorder in the absence of any known causes of compromised cardiovascular function.…”

Section: Discussionmentioning

confidence: 99%

Aβ Amyloid Pathology Affects the Hearts of Patients With Alzheimer’s Disease

Troncone

Luciani

Coggins

et al. 2016

Journal of the American College of Cardiology

149

117

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Background Individually, heart failure (HF) and Alzheimer Disease (AD) are severe threats to population health, and their potential coexistence is an alarming prospect. In addition to sharing analogous epidemiological and genetic profiles, biochemical characteristics, and common triggers, we recently recognized common molecular and pathological features between the 2 conditions. Whereas cognitive impairment has been linked to HF through perfusion defects, angiopathy, and inflammation, whether patients with AD present with myocardial dysfunction, and if the 2 conditions bear a common pathogenesis as neglected siblings is unknown. Objectives Here we investigated if amyloid beta (Aβ) protein aggregates are present in the hearts of patients with a primary diagnosis of AD, affecting myocardial function. Methods We examined myocardial function in a retrospective cross-sectional study from a cohort of AD patients and age-matched controls. Imaging and proteomics approaches were used to identify and quantify Aβ deposits in AD heart and brain specimens compared to controls. Cell shortening and calcium transients were measured on isolated adult cardiomyocytes. Results Echocardiographic measurements of myocardial function suggest that patients with AD present with an anticipated diastolic dysfunction. As in the brain, Aβ40 and Aβ42 are present in the heart, and their expression is increased in AD. Conclusions Here we provide the first report of the presence of compromised myocardial function and intramyocardial deposits of Aβ in AD patients. Our findings depict a novel biological framework in which AD may be viewed either as a systemic disease or as a metastatic disorder leading to heart, and possibly multiorgan failure. AD and HF are both debilitating and life-threatening conditions, affecting enormous patient populations. Our findings underline a previously dismissed problem of a magnitude that will require new diagnostic approaches and treatments for brain and heart disease, and their combination.

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“…The increased risk for acute myocardial infarction has become of concern with NAFLD associated with poor hepatic xenobiotic and LPS [63]- [66] that may now be the factors involved in the induction of toxic amyloid beta (Aβ) associated with NAFLD and cardiovascular disease in global populations. Sirt1 down regulation promotes abnormal hepatic cholesterol homeostasis that exist as the primary cellular mechanism involved in the inactivation of the peripheral sink (Aβ) clearance pathway with generation of toxic Aβ involved in cardiovascular disease and the risk for death [59]- [62]. Aβ [67] is a proteolytic product of a larger protein, the amyloid precursor protein (APP).…”

Section: Magnesium Therapy Regulates Amyloid Beta Metabolism With Impmentioning

confidence: 99%

“…Stress, diet and lifestyles are closely linked to imbalances [53] in magnesium therapy that may accelerate aging with disturbances in eating [54], growth and nutrient metabolism that may involve dietary fat/carbohydrate [55]- [58] (Figure 1). Diets that contain xenobiotics [39]/bacterial lipopolysaccharides (LPS) are involved in post-transcriptional modifications with magnesium/Sirt1 dysregulation in diabetes and Alzheimer's disease that may involve toxic amyloidogenic pathways and myocardial infarction in global populations [59]- [63].…”

Section: Introductionmentioning

confidence: 99%

Magnesium Therapy Prevents Senescence with the Reversal of Diabetes and Alzheimer’s Disease

Martins¹

2016

Health

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In the current global epidemic for Non Alcoholic Fatty Liver Disease (NAFLD), diabetes and neurodegenerative diseases such as Alzheimer's disease there has been a major interest in magnesium therapy to delay the severity of NAFLD, Type 3 diabetes and neurodegeneration in the developing and developed world. The objective of magnesium therapy is to activate the anti-aging gene Sirtuin 1 (Sirt1) to prevent cardiovascular disease, NAFLD and diabetes. Reduced consumption of nutrients such as fatty acids, glucose, cholesterol and increased magnesium consumption is closely linked to reduced bacterial lipopolysaccharides (LPS) and activation of Sirt1 relevant to active nuclear and mitochondria interactions with the prevention of myocardial infarction and Type 3 diabetes. Magnesium deficiency and its effects on Sirt1 regulation have become important with magnesium deficiency associated with appetite dysregulation, senescence, glucose/nitric oxide dyshomeostasis, increased ceramide and toxic amyloid beta formation. Magnesium therapy activates the peripheral sink amyloid beta clearance pathway with the reversal of cell senescence associated with various chronic diseases such as cardiovascular disease, Type 3 diabetes and Alzheimer's disease.

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Amyloid-Beta (1-40) and the Risk of Death From Cardiovascular Causes in Patients With Coronary Heart Disease

Abstract: Measuring blood levels of Abeta40 identified patients at high risk for CV death.

Cited by 101 publications

References 28 publications

Novel Risk Markers and Risk Assessments for Cardiovascular Disease

Novel Risk Markers and Risk Assessments for Cardiovascular Disease

Aβ Amyloid Pathology Affects the Hearts of Patients With Alzheimer’s Disease

Magnesium Therapy Prevents Senescence with the Reversal of Diabetes and Alzheimer’s Disease

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