Effect of Biologics on Cardiovascular Inflammation: Mechanistic Insights and Risk Reduction

Abstract

It is increasingly recognized that atherosclerosis and consequently cardiovascular disease (CVD) are closely linked with inflammatory processes. The latter is in the center of the pathogenic mechanism underlying autoimmune rheumatic diseases (ARD). It follows then, that optimal control of inflammation in ARDs may lead to a decrease of the accompanied CVD risk. Major trials (eg, CANTOS, CIRT), aimed at examining the possible benefits of immunomodulatory treatments in CVD, demonstrated conflicting results. On the other hand, substantial evidence is accumulating about the possible beneficial effects of biologic disease modifying antirheumatic drugs (bDMARDs) in patients with ARDs, particularly those with rheumatoid arthritis (RA). It seems that bDMARDs (some more than others) alter the lipid profile in RA patients but do not adversely affect, in most cases, the TC/HDL ratio. Favorable effects are noted for arterial stiffness and endothelial function. This is reflected in the lower risk for CVD events, seen in observational studies of RA patients treated with bDMARDs. It should be stressed that more data exist for the TNF-inhibitors than for other bDMARDs, such as tocilizumab, abatacept and rituximab. As regards the spondyloarthropathies (SpA), data are less robust. For TNF-inhibitors, effects appear to be on par with those seen in RA but no conclusions can be drawn for newer biologic drugs used in SpA (eg, IL-17 blockers). Finally, there is accumulating evidence for a beneficial effect of immunosuppressive treatment in cardiac inflammation and function in several ARDs. Introduction of newer therapeutic options in clinical practice seem to have a positive impact on CVD in the setting of ARD. This is probably due to better control of inflammation, but direct improvement in vascular pathology is also a valid hypothesis. Most data are derived from observational studies and, therefore, randomized controlled trials are needed to assess the possible favorable effect of bDMARDs on CVD outcomes.

Hyperalphalipoproteinemia and Beyond: The Role of HDL in Cardiovascular Diseases

“…Several classes of commonly used drugs in clinical practice exert effects both on HDL levels and functions through various mechanisms. Among them are anti-inflammatory medication (NSAIDs, corticosteroids, methotrexate, sulfasalazine, hydroxychloroquine or biologics) [ 36 , 37 , 38 ] and lipid-lowering drugs (statins, fibrates, and niacin) [ 39 ].…”

“…Several classes of commonly used drugs in clinical practice exert effects both on HDL levels and functions through various mechanisms. Among them are anti-inflammatory medication (NSAIDs, corticosteroids, methotrexate, sulfasalazine, hydroxychloroquine or biologics) [36][37][38] and lipid-lowering drugs (statins, fibrates, and niacin) [39]. Although in this review we will mainly focus on the primary familial causes of HALP, it is worth mentioning that several conditions are known to be associated with Although in this review we will mainly focus on the primary familial causes of HALP, it is worth mentioning that several conditions are known to be associated with In the RCT process, the ApoA-I receives the cholesterol from the foam cells (macrophages) through the ATPbinding cassette transporter member 1 (ABCA1) (1), leading HDL to become mature in a mechanism mediated by the transporter ABCG1 (2).…”

Cardiotoxicity in Biological Agent-Targeted Therapy for Rheumatoid Arthritis: ADR Signal Mining and Analysis of Food and Drug Administration Adverse Event Reporting System Database

“…Moreover, biologic therapies have experienced a marked expansion as a therapeutic option for cardiovascular disease (CVD) (16). Furthermore, other studies have shown TNF-a to confer cardiomyocyte resistance to ischemic injury through a mechanism similar to preconditioning (17). When given before myocardial ischemia, low doses of TNF-a seem to improve myocyte survival, whereas higher doses of TNF-a increase the size of infarction.…”

Monitoring and Managing Cardiovascular Risk in Immune Mediated Inflammatory Diseases

“…Accumulating evidence suggests a possible reduction in CVD risk mediated by biologic agents, attributable to the improvement of endothelial function, the decrease in inflammation and the reduction of insulin resistance associated with their use. 19 In particular, treatment with anti-TNF-α agents in patients with RA, psoriasis and PsA has been associated in relevant meta-analyses with significant reductions in the risk of all CVD events, including myocardial infarction, stroke, and major adverse cardiac events, 111 , 112 although blood-pressure lowering properties have not been consistently reported and relevant information on newest biological treatments is not definite. 113 , 114 Furthermore, biologic DMARDs may promote atherogenic lipid profile of patients with RA by increasing the levels of high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and triglycerides.…”

“… 17 The main domains of such preventive strategies include effective control of systemic inflammation, management of classic CVD risk factors and lifestyle changes, 18 taking also into account that a number of antirheumatic drugs may affect CVD risk positively or negatively. 19 , 20 The aim of the current paper is to provide an overview of current and emerging strategies for mitigating CVD risk in IMIDs, with a special focus on assessment of comprehensive individual risk via risk algorithms and relevant recommendations, non-pharmacological interventions and disease modifying drugs (DMARDs) modifications according to cardiovascular comorbidities and disease-related risk profile of the patients. Aspects of applications of new technologies in the assessment and management of cardiovascular comorbidities will also be discussed.…”