scholarly journals Inflammation and Cardiovascular Disease: The Future

2021 ◽  
Vol 16 ◽  
Author(s):  
Natalie Arnold ◽  
Katharina Lechner ◽  
Christoph Waldeyer ◽  
Michael D Shapiro ◽  
Wolfgang Koenig
Keyword(s):  
Cardiovascular Disease ◽  
Risk Stratification ◽  
Systemic Circulation ◽  
Low Grade ◽  
Atherosclerotic Cardiovascular Disease ◽  
Improve Risk Stratification ◽  
Clinical Complications ◽  
Modified Lipoproteins ◽  
Inflammatory Processes ◽  
Low Grade Inflammation

Despite considerable advances in reducing the global burden of atherosclerotic cardiovascular disease by targeting conventional risk factors, significant residual risk remains, with low-grade inflammation being one of the strongest risk modifiers. Inflammatory processes within the arterial wall or systemic circulation, which are driven in a large part by modified lipoproteins but subsequently trigger a hypercoagulable state, are a hallmark of atherosclerotic cardiovascular disease and, in particular, its clinical complications. Extending conventional guideline-based clinical risk stratification algorithms by adding biomarkers of inflammation may refine phenotypic screening, improve risk stratification and guide treatment eligibility in cardiovascular disease prevention. The integration of interventions aimed at lowering the inflammatory burden, alone or in combination with aggressive lipid-modifying or even antithrombotic agents, for those at high cardiovascular risk may hold the potential to reduce the still substantial burden of cardiometabolic disease. This review provides perspectives on future clinical research in atherosclerosis addressing the tight interplay between inflammation, lipid metabolism and thrombosis, and its translation into clinical practice.

scholarly journals Multifactorial Activation of NLRP3 Inflammasome: Relevance for a Precision Approach to Atherosclerotic Cardiovascular Risk and Disease

2020 ◽  
Vol 21 (12) ◽  
pp. 4459 ◽  
Author(s):  
Andrea Baragetti ◽  
Alberico Luigi Catapano ◽  
Paolo Magni
Keyword(s):  
Cardiovascular Disease ◽  
Oral Microbiota ◽  
Low Grade ◽  
Atherosclerotic Cardiovascular Disease ◽  
Nucleotide Polymorphisms ◽  
Cvd Risk ◽  
Number Of Factors ◽  
Elevated Cholesterol ◽  
Inflammatory Pattern ◽  
Low Grade Inflammation

Chronic low-grade inflammation, through the specific activation of the NACHT leucine-rich repeat- and PYD-containing (NLRP)3 inflammasome-interleukin (IL)-1β pathway, is an important contributor to the development of atherosclerotic cardiovascular disease (ASCVD), being triggered by intracellular cholesterol accumulation within cells. Within this pathological context, this complex pathway is activated by a number of factors, such as unhealthy nutrition, altered gut and oral microbiota, and elevated cholesterol itself. Moreover, evidence from autoinflammatory diseases, like psoriasis and others, which are also associated with higher cardiovascular disease (CVD) risk, suggests that variants of NLRP3 pathway-related genes (like NLRP3 itself, caspase recruitment domain-containing protein (CARD)8, caspase-1 and IL-1β) may carry gain-of-function mutations leading, in some individuals, to a constitutive pro-inflammatory pattern. Indeed, some reports have recently associated the presence of specific single nucleotide polymorphisms (SNPs) on such genes with greater ASCVD prevalence. Based on these observations, a potential effective strategy in this context may be the identification of carriers of these NLRP3-related SNPs, to generate a genomic score, potentially useful for a better CVD risk prediction, and, possibly, for personalized therapeutic approaches targeted to the NLRP3-IL-1β pathway.

scholarly journals Asthma and obesity: endotoxin another insult to add to injury?

2021 ◽  
Vol 135 (24) ◽  
pp. 2729-2748
Author(s):  
Nikita Lad ◽  
Alice M. Murphy ◽  
Cristina Parenti ◽  
Carl P. Nelson ◽  
Neil C. Williams ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Inflammatory Response ◽  
Gut Microbiota ◽  
Inflammatory Diseases ◽  
Systemic Circulation ◽  
Current Evidence ◽  
Low Grade ◽  
Direct Role ◽  
Low Grade Inflammation

Abstract Low-grade inflammation is often an underlying cause of several chronic diseases such as asthma, obesity, cardiovascular disease, and type 2 diabetes mellitus (T2DM). Defining the mediators of such chronic low-grade inflammation often appears dependent on which disease is being investigated. However, downstream systemic inflammatory cytokine responses in these diseases often overlap, noting there is no doubt more than one factor at play to heighten the inflammatory response. Furthermore, it is increasingly believed that diet and an altered gut microbiota may play an important role in the pathology of such diverse diseases. More specifically, the inflammatory mediator endotoxin, which is a complex lipopolysaccharide (LPS) derived from the outer membrane cell wall of Gram-negative bacteria and is abundant within the gut microbiota, and may play a direct role alongside inhaled allergens in eliciting an inflammatory response in asthma. Endotoxin has immunogenic effects and is sufficiently microscopic to traverse the gut mucosa and enter the systemic circulation to act as a mediator of chronic low-grade inflammation in disease. Whilst the role of endotoxin has been considered in conditions of obesity, cardiovascular disease and T2DM, endotoxin as an inflammatory trigger in asthma is less well understood. This review has sought to examine the current evidence for the role of endotoxin in asthma, and whether the gut microbiota could be a dietary target to improve disease management. This may expand our understanding of endotoxin as a mediator of further low-grade inflammatory diseases, and how endotoxin may represent yet another insult to add to injury.

scholarly journals Role of gut microbiota in chronic low-grade inflammation as potential driver for atherosclerotic cardiovascular disease: a systematic review of human studies

2018 ◽  
Vol 19 (12) ◽  
pp. 1719-1734 ◽  
Author(s):  
I. C. L. van den Munckhof ◽  
A. Kurilshikov ◽  
R. ter Horst ◽  
N. P. Riksen ◽  
L. A. B. Joosten ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cardiovascular Disease ◽  
Gut Microbiota ◽  
Human Studies ◽  
Low Grade ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Grade Inflammation

Abstract P019: A Single Model For Predicting Major Adverse Cardiovascular Events In Individuals With And Without History Of Atherosclerotic Cardiovascular Disease: The Atherosclerosis Risk In Communities (aric) Study

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Yejin Mok ◽  
Lena Mathews ◽  
Ron C Hoogeveen ◽  
Michael J Blaha ◽  
Christie M Ballantyne ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
High Risk ◽  
Risk Stratification ◽  
Cardiovascular Events ◽  
Major Adverse Cardiovascular Events ◽  
Atherosclerotic Cardiovascular Disease ◽  
Single Model ◽  
History Of ◽  
Very High

Background: In the 2018 AHA/ACC Cholesterol guideline, risk stratification is an essential element. The use of a Pooled Cohort Equation (PCE) is recommended for individuals without atherosclerotic cardiovascular disease (ASCVD), and the new dichotomous classification of very high-risk vs. high-risk has been introduced for patients with ASCVD. These distinct risk stratification systems mainly rely on traditional risk factors, raising the possibility that a single model can predict major adverse cardiovascular events (MACEs) in persons with and without ASCVD. Methods: We studied 11,335 ARIC participants with (n=885) and without (n=10,450) a history of ASCVD (myocardial infarction, ischemic stroke, and symptomatic peripheral artery disease) at baseline (1996-98). We modeled factors in the PCE and the new classification for ASCVD patients (Figure legend) in a single CVD prediction model. We examined their associations with MACEs (myocardial infarction, stroke, and heart failure) using Cox models and evaluated the discrimination and calibration for a single model including those factors. Results: During a median follow-up of 18.4 years, there were 3,658 MACEs (3,105 in participants without ASCVD). In general, the factors in the PCE and the risk classification system for ASCVD patients were associated similarly with MACEs regardless of baseline ASCVD status, although age and systolic blood pressure showed significant interactions. A single model with these predictors and the relevant interaction terms showed good calibration and discrimination for those with and without ASCVD (c-statistic=0.729 and 0.704, respectively) (Figure). Conclusion: A single CVD prediction model performed well in persons with and without ASCVD. This approach will provide a specific predicted risk to ASCVD patients (instead of dichotomy of very high vs. high risk) and eliminate a practice gap between primary vs. secondary prevention due to different risk prediction tools.

Abstract 11600: Long Sleep Duration and Low-Grade Inflammation: New Indicators of Arterial Stiffness in the Japanese at High-risk of Cardiovascular Disease

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Satoshi Niijima ◽  
Michiaki Nagai ◽  
Satoshi Hoshide ◽  
Mami Takahashi ◽  
Masahisa Shimpo ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
High Risk ◽  
Sleep Duration ◽  
Aortic Stiffness ◽  
The Other ◽  
Low Grade ◽  
Long Sleep ◽  
Hs Crp ◽  
Low Grade Inflammation

Background: Recently, several studies have reported that long sleep duration was independently associated with increased aortic stiffness. On the other hand, high-sensitive C-reactive protein (hs-CRP) was associated with increased aortic stiffness. In this study, the relationships among self-reported sleep duration, hs-CRP and pulse wave velocity (PWV) were investigated in the Japanese at high-risk of cardiovascular disease. In addition, we investigated whether antihypertensive treatment moderated these relationships or not. Methods: Among 4310 patients with one or more cardiovascular risks recruited for the Japan Morning Surge-Home Blood Pressure Study, brachial-ankle PWV and hs-CRP measurement were performed in the 2304 patients (64.7 years old, male 49.6%). A self-administered questionnaire included items on daily sleep duration was used. Results: According to the sleep duration (6h or less,6h to 8h,8h or more per night), significant associations of sleep duration were observed with PWV (1594 vs 1644 vs 1763 cm/s, p<0.0001).In the multiple regression analysis adjustment for confounders including age body mass index, total cholesterol, HbA1c and clinic systolic blood pressure (SBP), long sleep duration (8h or more per night) (B: 29, 95%CI: 1.0-56, p<0.05) and log hs-CRP (B: 25, 95%CI: 3.1-48, p<0.05) were significantly positively associated with PWV. A significant interaction was found between long sleep duration and antihypertensive agent non-use for PWV (p<0.05). Especially, in the group without calcium channel blockers (CCBs), long sleep duration was significantly associated with PWV (p<0.01), while a marginal significant synergetic relationship was observed between long sleep duration and log hs-CRP for PWV (p=0.07). On the other hand, there were no significant interactions between long sleep duration and angiotensin receptor blockers non-use. Conclusions: Long sleep duration and hs-CRP were significant indicators of increased PVW in the high-risk Japanese population. In those without CCBs, long sleep duration served as a strong determinant for arterial stiffness, marginally interacted by low-grade inflammation. CCBs use might be important not to aggravate artery remodeling caused by long sleep duration.

scholarly journals Osteopontin Expression in Human and Murine Obesity: Extensive Local Up-Regulation in Adipose Tissue but Minimal Systemic Alterations

Endocrinology ◽  
2007 ◽  
Vol 149 (3) ◽  
pp. 1350-1357 ◽  
Author(s):  
Florian W. Kiefer ◽  
Maximilian Zeyda ◽  
Jelena Todoric ◽  
Joakim Huber ◽  
René Geyeregger ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Plasma Concentrations ◽  
Morbidly Obese ◽  
Low Grade ◽  
Obese Patients ◽  
Multifunctional Protein ◽  
Inflammatory Processes ◽  
Low Grade Inflammation

Obesity is associated with a chronic low-grade inflammation characterized by macrophage infiltration of adipose tissue (AT) that may underlie the development of insulin resistance and type 2 diabetes. Osteopontin (OPN) is a multifunctional protein involved in various inflammatory processes, cell migration, and tissue remodeling. Because these processes occur in the AT of obese patients, we studied in detail the regulation of OPN expression in human and murine obesity. The study included 20 morbidly obese patients and 20 age- and sex-matched control subjects, as well as two models (diet-induced and genetic) of murine obesity. In high-fat diet-induced and genetically obese mice, OPN expression was drastically up-regulated in AT (40 and 80-fold, respectively) but remained largely unaltered in liver (&lt;2-fold). Moreover, OPN plasma concentrations remained unchanged in both murine models of obesity, suggesting a particular local but not systemic importance for OPN. OPN expression was strongly elevated also in the AT of obese patients compared with lean subjects in both omental and sc AT. In addition, we detected three OPN isoforms to be expressed in human AT and, strikingly, an obesity induced alteration of the OPN isoform expression pattern. Analysis of AT cellular fractions revealed that OPN is exceptionally highly expressed in AT macrophages in humans and mice. Moreover, OPN expression in AT macrophages was strongly up-regulated by obesity. In conclusion, our data point toward a specific local role of OPN in obese AT. Therefore, OPN could be a critical regulator in obesity induced AT inflammation and insulin resistance.

scholarly journals Non-alcoholic fatty liver disease and cardiovascular disease: assessing the evidence for causality

Diabetologia ◽  
2019 ◽  
Vol 63 (2) ◽  
pp. 253-260 ◽  
Author(s):  
Martijn C. G. J. Brouwers ◽  
Nynke Simons ◽  
Coen D. A. Stehouwer ◽  
Aaron Isaacs
Keyword(s):  
Cardiovascular Disease ◽  
Liver Disease ◽  
Fatty Liver Disease ◽  
Plasma Lipids ◽  
Low Grade ◽  
Alcoholic Fatty Liver ◽  
Important Mediator ◽  
Low Grade Inflammation ◽  
The Relationship ◽  
Alcoholic Fatty Liver Disease

Abstract Non-alcoholic fatty liver disease (NAFLD) is highly prevalent among individuals with type 2 diabetes. Although epidemiological studies have shown that NAFLD is associated with cardiovascular disease (CVD), it remains unknown whether NAFLD is an active contributor or an innocent bystander. Plasma lipids, low-grade inflammation, impaired fibrinolysis and hepatokines are potential mediators of the relationship between NAFLD and CVD. The Mendelian randomisation approach can help to make causal inferences. Studies that used common variants in PNPLA3, TM6SF2 and GCKR as instruments to investigate the relationship between NAFLD and coronary artery disease (CAD) have reported contrasting results. Variants in PNPLA3 and TM6SF2 were found to protect against CAD, whereas variants in GCKR were positively associated with CAD. Since all three genes have been associated with non-alcoholic steatohepatitis, the second stage of NAFLD, the question of whether low-grade inflammation is an important mediator of the relationship between NAFLD and CAD arises. In contrast, the differential effects of these genes on plasma lipids (i.e. lipid-lowering for PNPLA3 and TM6SF2, and lipid-raising for GCKR) strongly suggest that plasma lipids account for their differential effects on CAD risk. This concept has recently been confirmed in an extended set of 12 NAFLD susceptibility genes. From these studies it appears that plasma lipids are an important mediator between NAFLD and CVD risk. These findings have important clinical implications, particularly for the design of anti-NAFLD drugs that also affect lipid metabolism.

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