Hydroxychloroquine, a promising choice for coronary artery disease?

doi:10.1016/j.mehy.2016.04.045

Medical Hypotheses

Volume 93, August 2016, Pages 5-7

https://doi.org/10.1016/j.mehy.2016.04.045 Get rights and content

Abstract

Coronary artery disease is a common disease that seriously threaten the health of more than 150 million people per year. Atherosclerosis is considered to be the main cause of coronary artery disease which begins with damage or injury to the inner layer of a coronary artery, sometimes as early as childhood. The damage may be caused by various factors, including: smoking, high blood pressure, hypercholesterolemia, sedentary lifestyle, diabetes and insulin resistance. Once a coronary artery disease has developed, all patients need to be treated with long term standard treatment, including heart-healthy lifestyle changes, medicines, and medical procedures or surgery. Hydroxychloroquine, an original antimalarial drug, prevents inflammation caused by lupus erythematosus and rheumatoid arthritis. It is relatively safe and well-tolerated during the treatment. Since atherosclerosis and rheumatoid arthritis have resemble mechanism and increasing clinical researches confirm that hydroxychloroquine has an important role in both anti-rheumatoid arthritis and cardiovascular protection (such as anti-platelet, anti-thrombotic, lipid-regulating, anti-hypertension, hypoglycemia, and so on), we hypothesize that hydroxychloroquine might be a promising choice to coronary artery disease patients for its multiple benefits.

Section snippets

Introduction to coronary artery disease and its current treatment

Coronary artery disease (CAD) is the most common cause of death (and premature death) in the China, 1 in 5 men and 1 in 7 women die from CAD [1]. CAD is characterized as a chronic inflammatory disease, and our previous research suggested that Th17/Th1 cell and its cytokines may be key factors in CAD development [2]. There are several well-established risk factors, including age, sex, CAD family history, smoking, hypertension, diabetes mellitus, dyslipidemia, etc. To reduce the morbidity,

The effect of hydroxychloroquine

Hydroxychloroquine (HCQ) was originally developed as an antimalarial drug, and it has been used in the management of rheumatoid arthritis (RA) for its various immunomodulatory and immunosuppressive effects. It inhibits antigen presentation in dendritic cells, cytokine production in macrophages, and calcium and Toll-like receptor (TLR) signaling in B, T and other immune cells. Besides, its effectiveness has been increasingly recognized in nearly all major branches of medicine, including

The similarity of pathophysiological mechanism between atherosclerosis and rheumatoid arthritis

The main cause of CAD is thought to be atherosclerosis (AS), and the initiating process in atherogenesis is the endothelial dysfunction. The endothelial cells, lining the inner arterial surface stimulated by the modified lipoproteins, express adhesion molecules that capture leukocytes on their surface. After then, the bound leukocytes were directed migrated into the intima and the monocyte (the most numerous of the leukocytes recruited) mature into macrophage. Finally, macrophages engulf

Hypothesis

We proposed that HCQ might be a beneficial choice in the treatment of CAD. To our best knowledge, once diagnosed with CAD, one was bound to a recommended standard medical therapy lifelong approximately, a combination of several drugs, including anti-platelet drugs, anti-hypertensive drugs, hypoglycemic drugs, hypolipidemic drugs, endothelial function improving and/or anti-inflammatory drugs, etc. Abundant pills do not always match satisfactory therapeutic effects. Except the limited

Conflicts of interest

The authors declare that there is no conflict of interest.

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Cited by (16)

Use of hydroxychloroquine and risk of major adverse cardiovascular events in patients with lupus erythematosus: A Danish nationwide cohort study
2021, Journal of the American Academy of Dermatology
Citation Excerpt :
Chronic inflammation has been suggested to be the common pathogenetic background between LE and atherosclerosis.29,30 Increasing evidence indicates that HCQ has a cardiovascular protective role, working in multiple ways with a positive effect on the lipid profile, and reduces the risk of diabetes and CVD, shown in patients with different rheumatic diseases.1,2,5,9,26,31-37 A meta-analysis from 2018 found statistically significant associations between HCQ/chloroquine use and reduced risk of CVD in patients with different rheumatic diseases.
Limited data suggest that hydroxychloroquine may affect risk of cardiovascular disease in patients with lupus erythematosus (LE).
To investigate whether hydroxychloroquine treatment is associated with major adverse cardiovascular events (MACE) (myocardial infarction, ischemic stroke, or cardiovascular-associated death) in patients with cutaneous LE (CLE) or systemic LE (SLE).
Based on the Danish nationwide registers, an observational cohort study was conducted including patients with first-time diagnosis of CLE or SLE (between 1997 and 2017). Cox regression models calculating the hazard ratio (HR) analyzing the risk of MACE were performed comparing time on and off hydroxychloroquine (including never users). The models were adjusted for age, sex, socioeconomic status, concomitant treatment, and cardiovascular risk factors.
Among 4587 patients with LE, 51% (n = 2343) were treated with hydroxychloroquine during the study period. An inverse association between use of hydroxychloroquine and MACE risk was observed among patients with SLE (adjusted HR, 0.65; 95% confidence interval, 0.46-0.90) and patients with CLE (adjusted HR, 0.71; 95% confidence interval, 0.42-1.19). Consistent results were found in sensitivity analyses including a case-time control design.
No information on disease activity/severity was available.
Our findings indicate an opportunity to reduce the risk of cardiovascular events in patients with LE through use of hydroxychloroquine.
Cardiovascular disease in systemic lupus erythematosus: A comprehensive update
2017, Journal of Autoimmunity
Citation Excerpt :
Thus, lower incidence of the use of cyclophosphamide has been identified as independent determinant of carotid plaque [80] and cyclosporine use was shown to display protective properties regarding carotid arterial thickening (IMT) [113]; these data point towards the benefits of aggressive treatment. Antimalarials are commonly used in lupus treatment and are reported to be beneficial against CVD through cholesterol lowering [112,114], reduction of thrombotic risk [115,116] and possibly through dampening of type I interferon (IFN) production [117], which is viewed as a major pathogenetic determinant in lupus related atherosclerosis [118] (see below). Additionally, antimalarial use has been inversely associated with plaque [80] and carotid/femoral arterial stiffness [119] and was shown to be protective against MetS [55].
Heightened rates of both cardiovascular (CV) events and subclinical atherosclerosis, documented by imaging and vascular function techniques are well established in systemic lupus erythematosus (SLE). While traditional CV factors such as smoking, dyslipidemia, diabetes mellitus (DM), hypertension, central obesity and hyperhomocysteinemia have been reported to be prevalent in lupus patients, they do not fully explain the high rates of ischemic events so far reported, implying that other factors inherent to disease itself could account for the enhanced risk, including disease duration, activity and chronicity, psychosocial factors, medications, genetic variants and altered immunological mechanisms. Though the exact pathogenesis of atherosclerosis in the setting of lupus remains ill defined, an imbalance between endothelial damage and atheroprotection seems to be a central event. Insults leading to endothelial damage in the setting of lupus include oxidized low density lipoprotein (oxLDL), autoantibodies against endothelial cells and phospholipids, type I interferons (IFN) and neutrophil extracellular traps (NETs) directly or through activation of type I IFN pathway. Increased oxidative stress, reduced levels of the normally antioxidant high density lipoprotein (HDL), increased levels of proinflammatory HDL (piHDL) and reduced paraoxonase activity have been related to increased oxLDL levels. On the other hand, impaired atheroprotective mechanisms in lupus include decreased capacity of endothelial repair-partly mediated by type I IFN- and dampened production of atheroprotective autoantibodies. In the present review, traditional and disease related risk factors for CV disease (CVD) in the setting of chronic autoimmune disorders with special focus on SLE will be discussed.
Cardiovascular disease risk and pathogenesis in systemic lupus erythematosus
2022, Seminars in Immunopathology
Understanding Accelerated Atherosclerosis in Systemic Lupus Erythematosus: Toward Better Treatment and Prevention
2021, Inflammation
Safety and Utility of Chloroquine/ Hydroxychloroquine in Palliative Care Patients
2021, American Journal of Hospice and Palliative Medicine
Effects of Chloroquine and Hydroxychloroquine on the Cardiovascular System - Limitations for Use in the Treatment of COVID-19
2021, International Journal of Cardiovascular Sciences

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Hydroxychloroquine, a promising choice for coronary artery disease?

Abstract

Section snippets

Introduction to coronary artery disease and its current treatment

The effect of hydroxychloroquine

The similarity of pathophysiological mechanism between atherosclerosis and rheumatoid arthritis

Hypothesis

Conflicts of interest

Atherosclerosis

Thromb Res

Heart Rhythm

Am J Med

Semin Arthritis Rheum

Report for Chinese cardiovascular disease in 2014

Chin Circul J

AHA/ACC/ASH release guideline on the treatment of hypertension and CAD

Am Fam Physician

Chloroquine analogues in drug discovery: new directions of uses, mechanisms of actions and toxic manifestations from malaria to multifarious diseases

J Antimicrob Chemother

Recent developments in the understanding of the pharmacokinetics and mechanism of action of chloroquine

Ther Drug Monit

Mechanisms of cell association of chloroquine to leucocytes

J Pharmacol Exp Ther

Hydroxychloroquine’s efficacy as an antiplatelet agent study in healthy volunteers: a proof of concept study

J Cardiovasc Pharmacol Ther