HUMAN IGM-ANTIBODIES TO MALONDIALDEHYDE CONJUGATED WITH ALBUMIN ARE PROTECTIVE AGAINST CARDIOVASCULAR DISEASE AMONG 60-YEAR OLDS: ANTI-INFLAMMATORY PROPERTIES AND POSSIBLE MECHANISMS

Background: Chronic inflammation and immune system activation underlie a variety of seemingly unrelated cardiac conditions including not only atherosclerosis and the subsequent coronary artery disease but also peripheral artery disease, hypertension with target organ damage and heart failure. The beneficial effects of HMG-CoA reductase inhibitors or statins are mainly attributed to their ability to inhibit hepatic cholesterol biosynthesis. Beyond their lipid lowering activity, ample evidence exists in support of their potent anti-inflammatory properties which initiate from the inhibition of GTPase isoprenylation, activating a cataract of secondary pathways and extend to the inhibition and blocking of immune cell activation and interaction. Objective: To summarize the anti-inflammatory mechanisms of statins in clinical and experimental settings in cardiovascular disease. Methods: A systematic search of PubMed and the Cochrane Database was conducted in order to identify the majority of trials, studies, current guidelines and novel articles related to the subject. Results: In vitro, statins have immuno-modulatory and anti-inflammatory effects, and they can exert antiatherosclerotic effects independently of their hypolipidemic actions. In addition, positive results have emerged from mechanistic and experimental studies on the active role of HMG-CoA reductase inhibitors in HF. By extrapolating those data in clinical setting, we further understand how HMG-CoA reductase inhibitors can beneficially affect not only systolic but also diastolic HF. Conclusion: In this review article, we present the basic pathophysiologic data supporting the anti-inflammatory actions of statins in clinical and experimental settings and we link these mechanisms with confirmatory clinical data on the potent non lipid lowering effects of HMG-CoA reductase inhibitors.

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The 3-Year Effect of the Mediterranean Diet Intervention on Inflammatory Biomarkers Related to Cardiovascular Disease

Biomedicines ◽

10.3390/biomedicines9080862 ◽

2021 ◽

Vol 9 (8) ◽

pp. 862

Author(s):

Mireia Urpi-Sarda ◽

Rosa Casas ◽

Emilio Sacanella ◽

Dolores Corella ◽

Cristina Andrés-Lacueva ◽

...

Keyword(s):

Cardiovascular Disease ◽

Mediterranean Diet ◽

Virgin Olive Oil ◽

Extra Virgin Olive Oil ◽

Inflammatory Biomarkers ◽

Year Effect ◽

Tnf Α ◽

The Mediterranean ◽

Anti Inflammatory

The intervention with the Mediterranean diet (MD) pattern has evidenced short-term anti-inflammatory effects, but little is known about its long-term anti-inflammatory properties at molecular level. This study aims to investigate the 3-year effect of MD interventions compared to low-fat diet (LFD) on changes on inflammatory biomarkers related to atherosclerosis in a free-living population with a high-risk of cardiovascular disease (CD). Participants (n = 285) in the PREDIMED trial were randomly assigned into three intervention groups: MD with extra-virgin olive oil (EVOO) or MD-Nuts, and a LFD. Fourteen plasma inflammatory biomarkers were determined by Luminex assays. An additional pilot study of gene expression (GE) was determined by RT-PCR in 35 participants. After 3 years, both MDs showed a significant reduction in the plasma levels of IL-1β, IL-6, IL-8, TNF-α, IFN-γ, hs-CRP, MCP-1, MIP-1β, RANTES, and ENA78 (p < 0.05; all). The decreased levels of IL-1β, IL-6, IL-8, and TNF-α after MD significantly differed from those in the LFD (p < 0.05). No significant changes were observed at the gene level after MD interventions, however, the GE of CXCR2 and CXCR3 tended to increase in the control LFD group (p = 0.09). This study supports the implementation of MD as a healthy long-term dietary pattern in the prevention of CD in populations at high cardiovascular risk.

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Mediational g-formula for time-varying treatment and repeated-measured multiple mediators: Application to atorvastatin’s effect on cardiovascular disease via cholesterol lowering and anti-inflammatory actions in elderly type 2 diabetics

Statistical Methods in Medical Research ◽

10.1177/09622802211025988 ◽

2021 ◽

pp. 096228022110259

Author(s):

Shintaro Yamamuro ◽

Tomohiro Shinozaki ◽

Satoshi Iimuro ◽

Yutaka Matsuyama

Keyword(s):

Cardiovascular Disease ◽

Blood Cell ◽

Indirect Effects ◽

Time Varying ◽

Cell Counts ◽

Blood Cell Counts ◽

Anti Inflammatory ◽

White Blood Cell Counts ◽

Inflammatory Action

Modern causal mediation theory has formalized several types of indirect and direct effects of treatment on outcomes regarding specific mediator variables. We reviewed and unified distinct approaches to estimate the “interventional” direct and indirect effects for multiple mediators and time-varying variables. This study was motivated by a clinical trial of elderly type-2 diabetic patients in which atorvastatin was widely prescribed to control patients’ cholesterol levels to reduce diabetic complications, including cardiovascular disease. Among atorvastatin’s preventive side-effects (pleiotropic effects), we focus on its anti-inflammatory action as measured by white blood cell counts. Hence, we estimate atorvastatin’s interventional indirect effects through cholesterol lowering and through anti-inflammatory action, and interventional direct effect bypassing these two actions. In our analysis, total effect (six-year cardiovascular disease risk difference) estimated by standard plug-in g-formula of −3.65% (95% confidence interval: −10.29%, 4.38%) is decomposed into indirect effect via low-density lipoprotein cholesterol (−0.90% [−1.91%, −0.07%]), via white blood cell counts (−0.03% [−0.22%, 0.11%]), and direct effect (−2.84% [−9.71%, 5.41%]) by the proposed parametric mediational g-formula. The SAS program and its evaluation via simulated datasets are provided in the Supplemental materials.

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Risks of Cardiovascular Disease and Beyond in Prescription of Nonsteroidal Anti-Inflammatory Drugs

Journal of Cardiovascular Pharmacology and Therapeutics ◽

10.1177/1074248419871902 ◽

2019 ◽

Vol 25 (1) ◽

pp. 3-6 ◽

Cited By ~ 4

Author(s):

Manas A. Rane ◽

Alexander Gitin ◽

Benjamin Fiedler ◽

Lawrence Fiedler ◽

Charles H. Hennekens

Keyword(s):

Cardiovascular Disease ◽

Side Effects ◽

Health Care Providers ◽

Clinical Decision Making ◽

Clinical Decision ◽

Care Providers ◽

Relieve Pain ◽

Gastrointestinal Side Effects ◽

Inflammatory Drugs ◽

Anti Inflammatory

Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) include aspirin, naproxen, diclofenac, and ibuprofen, as well as selective cyclooxygenase 2 inhibitors such as celecoxib. Their use is common, as well as their side effects which cause 100 000 hospitalizations and 17 000 deaths annually. Recently, the US Food and Drug Administration strengthened its warning about the risks of cardiovascular disease (CVD) attributed to nonaspirin NSAIDs. Methods: When the sample size is large, randomization provides control of confounding not possible to achieve with any observational study. Further, observational studies and, especially, claims data have inherent confounding by indication larger than the small to moderate effects being sought. Results: While trials are necessary, they must be of sufficient size and duration and achieve high compliance and follow-up. Until then, clinicians should remain uncertain about benefits and risks of these drugs. Conclusions: Since the totality of evidence remains incomplete, health-care providers should consider all these aforementioned benefits and risks, both CVD and beyond, in deciding whether and, if so, which, NSAID to prescribe. The factors in the decision of whether and, if so, which NSAID to prescribe for relief of pain from inflammatory arthritis should not be limited to risks of CVD or gastrointestinal side effects but should also include potential benefits including improvements in overall quality of life resulting from decreases in pain or impairment from musculoskeletal pain syndromes. The judicious individual clinical decision-making about the prescription of NSAIDs to relieve pain based on all these considerations has the potential to do much more good than harm.

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Trends in prescribing of non-steroidal anti-inflammatory drugs in patients with cardiovascular disease: influence of national guidelines in UK primary care

Family Practice ◽

10.1093/fampra/cmx142 ◽

2018 ◽

Vol 35 (4) ◽

pp. 426-432 ◽

Cited By ~ 7

Author(s):

Ying Chen ◽

John Bedson ◽

Richard A Hayward ◽

Kelvin P Jordan

Keyword(s):

Cardiovascular Disease ◽

Primary Care ◽

National Guidelines ◽

Inflammatory Drugs ◽

Anti Inflammatory

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Hydrogen sulfide-mediated cardioprotection: mechanisms and therapeutic potential

Clinical Science ◽

10.1042/cs20100462 ◽

2010 ◽

Vol 120 (6) ◽

pp. 219-229 ◽

Cited By ~ 104

Author(s):

Madhav Lavu ◽

Shashi Bhushan ◽

David J. Lefer

Keyword(s):

Blood Pressure ◽

Cardiovascular Disease ◽

Hydrogen Sulfide ◽

Therapeutic Potential ◽

Blood Pressure Regulation ◽

Pressure Regulation ◽

Signalling Molecule ◽

Anti Inflammatory ◽

Antioxidant Effects

H2S (hydrogen sulfide), viewed with dread for more than 300 years, is rapidly becoming a ubiquitously present and physiologically relevant signalling molecule. Knowledge of the production and metabolism of H2S has spurred interest in delineating its functions both in physiology and pathophysiology of disease. Although its role in blood pressure regulation and interaction with NO is controversial, H2S, through its anti-apoptotic, anti-inflammatory and antioxidant effects, has demonstrated significant cardioprotection. As a result, a number of sulfide-donor drugs, including garlic-derived polysulfides, are currently being designed and investigated for the treatment of cardiovascular conditions, specifically myocardial ischaemic disease. However, huge gaps remain in our knowledge about this gasotransmitter. Only by additional studies will we understand more about the role of this intriguing molecule in the treatment of cardiovascular disease.

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Potential Impact of Statins on Neuronal Stress Responses in Patients at Risk for Cardiovascular Disease

Journal of Personalized Medicine ◽

10.3390/jpm11040261 ◽

2021 ◽

Vol 11 (4) ◽

pp. 261

Author(s):

Flavia Diggelmann ◽

Susan Bengs ◽

Ahmed Haider ◽

Gioia Epprecht ◽

Anna Luisa Beeler ◽

...

Keyword(s):

Cardiovascular Disease ◽

At Risk ◽

Bone Marrow ◽

Metabolic Activity ◽

Stress Responses ◽

Cardiovascular Outcomes ◽

Inflammatory Activity ◽

18F Fdg ◽

Anti Inflammatory ◽

Neuronal Stress

Background: Recent studies indicate that enhanced neuronal stress responses are associated with adverse cardiovascular outcomes. A chronic inflammatory state seems to mediate this detrimental neuro-cardiac communication. Statins are among the most widely prescribed medications in primary and secondary cardiovascular disease (CVD) prevention and not only lower lipid levels but also exhibit strong anti-inflammatory and neuroprotective effects. We therefore sought to investigate the influence of statins on neuronal stress responses in a patient cohort at risk for CVD. Methods: 563 patients (61.5 ± 14.0 years) who underwent echocardiography and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) were retrospectively identified. Metabolic activity of the amygdala, a part of the brain’s salience network, was quantified by 18F-FDG uptake, while normal cardiac morphology and function were assured by echocardiography. Vertebral bone marrow metabolism, a marker of inflammatory activity, was measured by 18F-FDG PET. Results: Increased neuronal stress responses were associated with an increased inflammatory activity in the bone marrow (r = 0.152, p = 0.015) as well as with a subclinical reduction in left ventricular ejection fraction (LVEF, r = −0.138, p = 0.025). In a fully-adjusted linear regression model, statin treatment was identified as an independent, negative predictor of amygdalar metabolic activity (B-coefficient −0.171, p = 0.043). Conclusions: Our hypothesis-generating investigation suggests a potential link between the anti-inflammatory actions of statins and reduced neuronal stress responses which could lead to improved cardiovascular outcomes. The latter warrants further studies in a larger and prospective population.

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Anti-Inflammatory Properties of Diet: Role in Healthy Aging

Biomedicines ◽

10.3390/biomedicines9080922 ◽

2021 ◽

Vol 9 (8) ◽

pp. 922

Author(s):

Kristine Stromsnes ◽

Angela G. Correas ◽

Jenny Lehmann ◽

Juan Gambini ◽

Gloria Olaso-Gonzalez

Keyword(s):

Cardiovascular Disease ◽

Autoimmune Disease ◽

Neurological Disease ◽

Healthy Aging ◽

Dietary Guidelines ◽

The Body ◽

Inflammatory Activity ◽

Allergic Reactions ◽

Inflammatory Processes ◽

Anti Inflammatory

Inflammation is a physiological process involved in the defenses of the body and the repair of tissues. It is acutely activated by infections, trauma, toxins, or allergic reactions. However, if it becomes chronic, inflammation can end up stimulating the development of diseases such as cardiovascular disease, autoimmune disease, neurological disease, or cancer. Additionally, during aging, inflammation becomes increasingly more chronic. Furthermore, we found that certain foods, such as saturated fats, have pro-inflammatory activity. Taking this into account, in this review we have discussed different diets with possible anti-inflammatory activity, the commonly ingested components of each diet and their active compounds. In addition, we have proposed some dietary guidelines, as well as a list of compounds present in foods with anti-inflammatory activity, outlining how to combine them to achieve optimal anti-inflammatory effects. Therefore, we can conclude that the compounds in our diet with anti-inflammatory activity could help alleviate the inflammatory processes derived from diseases and unhealthy diets, and thereby promote healthy aging.

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