scholarly journals Cyclo-Oxygenase (COX) Inhibitors and Cardiovascular Risk: Are Non-Steroidal Anti-Inflammatory Drugs Really Anti-Inflammatory?

2019 ◽  
Vol 20 (17) ◽  
pp. 4262 ◽  
Author(s):  
Shanzana Khan ◽  
Karen L. Andrews ◽  
Jaye P. F. Chin-Dusting

Cyclo-oxygenase (COX) inhibitors are among the most commonly used drugs in the western world for their anti-inflammatory and analgesic effects. However, they are also well-known to increase the risk of coronary events. This area is of renewed significance given alarming new evidence suggesting this effect can occur even with acute usage. This contrasts with the well-established usage of aspirin as a mainstay for cardiovascular prophylaxis, as well as overwhelming evidence that COX inhibition induces vasodilation and is protective for vascular function. Here, we present an updated review of the preclinical and clinical literature regarding the cardiotoxicity of COX inhibitors. While studies to date have focussed on the role of COX in influencing renal and vascular function, we suggest an interaction between prostanoids and T cells may be a novel factor, mediating elevated cardiovascular disease risk with NSAID use.

1970 ◽  
Vol 2 (2) ◽  
pp. 245-251
Author(s):  
AEM M Islam ◽  
AAS Mazumder

Increasing burden of cardiovascular disease risk factors has led to increase in the incidence in the coronary artery disease (CAD). Advancements in medical and surgical care of patients with heart disease have led to a large number of people surviving acute coronary events. Patients with acute coronary syndrome (ACS) are at high risk for recurrent coronary events, sudden death, and all cause mortality. Conventional revascularization therapies reduce the risk of further ischaemia but do not affect the underlying atherosclerotic disease. Statins have a proven record in the secondary prevention of coronary heart disease. Furthermore, statins have been shown to exert various pleotropic effects, which may stabilize vulnerable atherosclerotic plaques. Therefore, initiating, statin therapy in patients with established CAD is both beneficial and more cost effective. Trials conducted in recent times have addressed the issue of whether higher dose statin therapy provides further reductions in the risks of cardiovascular events following an acute coronary syndrome diagnosis, over and above that provided by a conventional dose statin regimen. However, recent trials of high dose statin therapy in patients with acute coronary syndromes have yielded conflicting results. The aim of this article is to provide a critical and up-to-date summary of the findings of clinical trials of intensive statin therapy, including a brief overview of safety and efficacy of such treatments. Keywords: Statin; Acute coronary syndrome. DOI: 10.3329/cardio.v2i2.6648Cardiovasc. j. 2010; 2(2) : 245-251


2021 ◽  
Vol 320 (1) ◽  
pp. H29-H35
Author(s):  
Joshua M. Cherubini ◽  
Jem L. Cheng ◽  
Jennifer S. Williams ◽  
Maureen J. MacDonald

Sleep is critical for the maintenance of physiological homeostasis and, as such, inadequate sleep beckons a myriad of pathologies. Sleep deprivation is a growing health concern in contemporary society since short sleep durations are associated with increased cardiovascular disease risk and atherosclerotic plaque development. Vascular endothelial dysfunction is an antecedent to atherosclerosis and cardiovascular disease. Herein, we review seminal literature indicating that short sleep durations attenuate endothelial function and explore more recent evidence indicating that sleep deprivation perturbs autonomic balance and the circadian rhythmicity of peripheral vascular clock components. We further examine literature that indicates a mechanistic link between short sleep duration and endothelial dysfunction and subsequent morbidity. Understanding the mechanisms that regulate endothelial function in the context of sleep deprivation facilitates the development and optimization of interventions, such as exercise, that mitigate the ramifications of inadequate sleep on vascular function and cardiovascular health. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/sleep-deprivation-and-endothelial-function/


2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Amy C. Keller ◽  
Leslie A. Knaub ◽  
P. Mason McClatchey ◽  
Chelsea A. Connon ◽  
Ron Bouchard ◽  
...  

Diabetes affects more than 330 million people worldwide and causes elevated cardiovascular disease risk. Mitochondria are critical for vascular function, generate cellular reactive oxygen species (ROS), and are perturbed by diabetes, representing a novel target for therapeutics. We hypothesized that adaptive mitochondrial plasticity in response to nutrient stress would be impaired in diabetes cellular physiology via a nitric oxide synthase- (NOS-) mediated decrease in mitochondrial function. Primary smooth muscle cells (SMCs) from aorta of the nonobese, insulin resistant rat diabetes model Goto-Kakizaki (GK) and the Wistar control rat were exposed to high glucose (25 mM). At baseline, significantly greater nitric oxide evolution, ROS production, and respiratory control ratio (RCR) were observed in GK SMCs. Upon exposure to high glucose, expression of phosphorylated eNOS, uncoupled respiration, and expression of mitochondrial complexes I, II, III, and V were significantly decreased in GK SMCs (p<0.05). Mitochondrial superoxide increased with high glucose in Wistar SMCs (p<0.05) with no change in the GK beyond elevated baseline concentrations. Baseline comparisons show persistent metabolic perturbations in a diabetes phenotype. Overall, nutrient stress in GK SMCs caused a persistent decline in eNOS and mitochondrial function and disrupted mitochondrial plasticity, illustrating eNOS and mitochondria as potential therapeutic targets.


BMJ Open ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. e026913 ◽  
Author(s):  
Yon Ho Jee ◽  
Hyoungyoon Chang ◽  
Keum Ji Jung ◽  
Sun Ha Jee

ObjectivesDepression has been reported to be a risk factor of cardiovascular disease in the western world, but the association has not yet been studied among Asian populations. The aim of this study was to investigate whether depression increases the risk of developing atherosclerotic cardiovascular disease (ASCVD) in a large Korean cohort study.DesignPopulation based cohort study.SettingDatabase of National Health Insurance System, Republic of Korea.Participants481 355 Koreans (260 695 men and 220 660 women) aged 40–80 years who had a biennial health check-up between 2002 and 2005.Main outcome measureThe main outcome in this study was the first ASCVD event (hospital admission or death).ResultsDepression increased the risk of developing ASCVD by 41% for men and 48% for women. In men, 3–4 outpatient visits for depression increased the risk of angina pectoris by 2.12 times (95% CI 1.55 to 2.90) and acute myocardial infarction by 2.29 times (95% CI 1.33 to 3.95). Depression was also associated with stroke in men (HR 1.29, 95% CI 1.19 to 1.39) and in women (HR 1.37, 95% CI 1.29 to 1.46). However, no increased risk of ASCVD was found for men who received 10 or more depressive treatments, compared with those without any outpatient visit for depression.ConclusionsIn this cohort, depressed people were at increased risk of ASCVD incidence. Therefore, individuals with depression may need routine monitoring of heart health that may prevent their future CVD risk.


2013 ◽  
Vol 218 (2) ◽  
pp. 205-213 ◽  
Author(s):  
Sieneke Labruijere ◽  
E Leonie A F van Houten ◽  
René de Vries ◽  
Usha M Musterd-Bagghoe ◽  
Ingrid M Garrelds ◽  
...  

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of the reproductive age, but the exact pathophysiological mechanisms involved remain unclear. Cardiovascular disease risk is increased in PCOS patients and endothelial damage has been observed. We recently developed a mouse model of PCOS with reproductive and metabolic characteristics resembling those observed in women with PCOS. In this model we studied vascular function with particular emphasis on markers of vascular endothelial function. Animals were treated for 90 days with dihydrotestosterone (DHT; 27.5 μg/day) or placebo using subcutaneous continuous-release pellets. Aortas were isolated for isometric force recordings in organ baths to investigate endothelial and vascular smooth muscle characteristics. Lungs were used to analyze endothelial nitric oxide synthase (eNOS) expression and phosphorylation. Asymmetric dimethylarginine (ADMA) levels were investigated in serum to assess endothelial damage. Expression of androgen receptor (Ar) mRNA was studied in aortas. DHT treatment (compared with placebo) induced i) a significant decrease in acetylcholine-induced aortic relaxations, with no change in calcitonin gene-related peptide- or sodium nitroprusside-induced relaxations, as well as 5-hydroxytryptamine-induced contractions; ii) no change in eNOS expression/phosphorylation in lungs or in plasma ADMA levels; and iii) a twofold increase in aortic AR expression. Our results suggest that, in DHT-exposed mice, hyperandrogenemia specifically decreases endothelium-dependent vasorelaxation without deterioration of smooth muscle function. This study may initiate further investigations to elucidate underlying mechanism for the phenotype that is present in these animals, as well as in PCOS patients.


2018 ◽  
Vol 132 (1) ◽  
pp. 131-143 ◽  
Author(s):  
Shanzana I. Khan ◽  
Karen L. Andrews ◽  
Ann-Maree Jefferis ◽  
Garry L. Jennings ◽  
Amanda K. Sampson ◽  
...  

Vascular dysfunction is a hallmark of hypertension and the strongest risk factor to date for coronary artery disease. As Y chromosome lineage has emerged as one of the strongest genetic predictors of cardiovascular disease risk to date, we investigated if Y chromosome lineage modulated this important facet in the stroke-prone spontaneously hypertensive rat (SHRSP) using consomic strains. Here, we show that vascular dysfunction in the SHRSP is attributable to differential cyclooxygenase (COX) activity with nitric oxide (NO) levels playing a less significant role. Measurement of prostacyclin, the most abundant product of COX in the vasculature, confirmed the augmented COX activity in the SHRSP aorta. This was accompanied by functional impairment of the vasodilatory prostacyclin (IP) receptor, while inhibition of the thromboxane (TP) receptor significantly ameliorated vascular dysfunction in the SHRSP, suggesting this is the downstream target responsible for constrictor prostanoid activity. Importantly, Y chromosome lineage was shown to modulate vascular function in the SHRSP through influencing COX activity, prostacyclin levels and IP dysfunction. Vascular dysfunction in the renal and intrarenal arteries was also found to be prostanoid and Y chromosome dependent. Interestingly, despite no apparent differences in agonist-stimulated NO levels, basal NO levels were compromised in the SHRSP aorta, which was also Y chromosome dependent. Thus, in contrast with the widely held view that COX inhibition is deleterious for the vasculature due to inhibition of the vasodilator prostacyclin, we show that COX inhibition abolishes vascular dysfunction in three distinct vascular beds, with IP dysfunction likely being a key mechanism underlying this effect. We also delineate a novel role for Y chromosome lineage in regulating vascular function through modulation of COX and basal NO levels.


Author(s):  
Stephen M. Ratchford ◽  
Jonathon Lee Stickford ◽  
Valesha M Province ◽  
Nina Stute ◽  
Marc Andrew Augenreich ◽  
...  

Background: While SARS-CoV-2 primarily affects the lungs, the virus may be inflicting detriments to the cardiovascular system, both directly through angiotensin converting enzyme 2 receptor as well as initiating systemic inflammation. Persistent systemic inflammation may be provoking vascular dysfunction, an early indication of cardiovascular disease risk. Methods: In order to establish the potential effects of SARS-CoV-2 on the systemic vasculature in the arms and legs, we performed a cross-sectional analysis of young healthy adults (Control: 5M/15F, 23.0±1.3y, 167±9cm, 63.0±7.4kg) and young adults who, 3-4 weeks prior to testing, had tested positive for SARS-CoV-2 (SARS-CoV-2: 4M/7F, 20.2±1.1y, 172±12cm, 69.5±12.4kg) (mean±SD). Using Doppler ultrasound, brachial artery flow-mediated dilation (FMD) in the arm and single passive limb movement (sPLM) in the leg were assessed as markers of vascular function. Pulse wave velocity (PWVcf) was assessed as a marker of arterial stiffness. Results: FMD was lower in the SARS-CoV-2 group (2.71±1.21%) compared to the Control group (8.81±2.96%) (P<0.01) and when made relative to the shear stimulus (SARS-CoV-2: 0.04±0.02AU, Control: 0.13±0.06AU, P<0.01). The femoral artery blood flow response, as evidenced by the area under the curve, from the sPLM was lower in the SARS-CoV-2 group (-3±91ml) compared with the Control group (118±114ml) (P<0.01). PWVcf was higher in the SARS-CoV-2 group (5.83±0.62m/s) compared with the Control group (5.17±0.66m/s) (P<0.01). Conclusions: Significantly lower systemic vascular function and higher arterial stiffness are evident weeks after testing positive for SARS-CoV-2 among young adults compared to controls.


2020 ◽  
Author(s):  
Prinya Wongsa

Rice (Oryza sativa L.) is one of the most important staple plant foods for global population especially in Asian countries. Pigmented rice including red rice, black, and purple contains a range of bioactive compounds including phenolics acids and flavonoids. Anthocyanins and proanthocyanidins are recognized as a major functional component in pigmented rice. Recently, pigmented rice varieties have received increasing attention from consumers due to its high nutritional values and bioactive compounds, providing its potential health benefits including antioxidant, anti-inflammatory, anticancer, and antidiabetic. Therefore, the objective of this chapter is to provide an up-to-date coverage of a systematic and advanced isolation, extraction and analytical methods, and potential health benefit studies related to antioxidant, anti-inflammatory, antidiabetic cardiovascular disease risk inhibition potential and anti-neurodegenerative potential of pigmented rice.


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