Platelet reactivity in overweight and obese patients undergoing cardiac surgery

Ranucci, Marco; Aloisio, Tommaso; Dedda, Umberto Di; Rovere, Maria Teresa La; Arroyabe, Blanca Martinez Lopez De; Baryshnikova, Ekaterina

doi:10.1080/09537104.2018.1492108

Cited by 18 publications

(15 citation statements)

References 31 publications

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“…BMI and specifically overweight and obesity have been associated with increased platelet reactivity [ 23 ]. SGLT2i treatment is associated with an average 2-kg to 4-kg reduction of body weight [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

The Effect of Empagliflozin on Platelet Function Profiles in Patients with Stable Coronary Artery Disease in Trinidad: The EFFECT Pilot Study

Seecheran

Ramdeen²,

Debideen³

et al. 2020

Cardiol Ther

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Introduction This prospective pharmacodynamic (PD) study aimed to assess the effect of the sodium–glucose cotransporter 2 inhibitor (SGLT2i) empagliflozin on platelet reactivity. Methods Patients with stable coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) ( n = 20) who were actively treated with dual antiplatelet therapy (DAPT) of aspirin 81 mg daily and clopidogrel 75 mg daily were recruited. Platelet function was measured with the VerifyNow™ P2Y 12 assay (Instrumentation Laboratory, Massachusetts, USA) and assessed before the initiation of and after 10 days of treatment with empagliflozin 25 mg once daily maintenance dose regimen. Results were compared with a paired t test. Results The mean P2Y 12 reaction units (PRU) on empagliflozin was significantly less than without empagliflozin at baseline (187.35, 95% confidence interval (CI) 155.38–219.32 vs. 217.25, CI 180.60–253.90; p < 0.030). The mean difference in PRU was 29.90 (95% CI 3.17–56.63). No patients experienced any serious adverse events (SAEs). Conclusions Significantly attenuated platelet reactivity was observed on empagliflozin as compared to without empagliflozin. This dedicated pharmacodynamic study could be clinically pertinent for Trinidadian patients with stable CAD and T2DM on DAPT. Further studies are required to confirm these exploratory findings. (Funded by the University of the West Indies, St. Augustine; EFFECT). Clinical Trial Registration ClinicalTrials.gov number NCT04342819.

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Section: Discussionmentioning

confidence: 99%

The Effect of Empagliflozin on Platelet Function Profiles in Patients with Stable Coronary Artery Disease in Trinidad: The EFFECT Pilot Study

Seecheran

Ramdeen²,

Debideen³

et al. 2020

Cardiol Ther

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“…In this context, our methodology allowed a high degree of reproducibility between groups allowing more than 99% of pure washed platelets. In terms of platelet-related parameters, platelet counts, and platelet size are both commonly associated with platelet dysfunction [23][24][25][26] . Indeed, both parameters are directly related with cardiovascular risk; indeed there is a positive correlation between platelet counts and other anthropometric parameters such abdominal circumference, and fat distribution 27 .…”

Section: Discussionmentioning

confidence: 99%

Analysis of platelets from a diet-induced obesity rat model: elucidating platelet dysfunction in obesity

Barrachina

Morán

Izquierdo

et al. 2020

Sci Rep

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Obesity is one of the main health problems in industrialized countries. The contribution of multiple factors developed in obesity can hardly be modeled in vitro. In this context, the development of animal models mimicking human obesity could be essential. the aim of the present study was to compare platelets from a diet-induced obesity (Dio) rat model with their lean control group in order to elucidate platelet dysfunction mechanisms in obesity and correlate the results with previous data from morbid obese patients. In parallel, we also established a blood collection and platelet isolation methodology to study the DIO rat model at biochemical and functional level. Optimal blood collection was obtained from vena cava and platelet isolation was based on a serial of centrifugations avoiding platelet activation. Our results show that the DIO rat model simulate obesity pathologically since weight gain, fasting glucose and platelet counts are increased in obese rats. Interestingly, platelet levels of the active form of Src (pTyr 419) showed a tendency to increase in Dio rats pointing towards a potential dysfunction in Src family kinases-related signalling pathways in obesity. Moreover, platelets from DIO rats adhere more to collagen compared with the control group, pointing towards Glycoprotein VI (GPVI) as one of the dysregulated receptors in obesity, in agreement with our recent studies in humans. These results confirm that obesity, in line with human studies, present a platelet dysregulation, and highlight the relevance of considering novel antithrombotic drug targets in these patients, such as GPVI. The global obesity epidemic represents one of the biggest health problems in industrialized countries. It is well known that obesity-associated alterations constitute relevant risk factors for several diseases, including diabetes, cancer, arthritis, high blood pressure, and cardiovascular diseases (CVD). In fact, the link between obesity and CVD has been repeatedly reported with the chronic exposure to a pro-inflammatory and pro-thrombotic state in obese individuals in which platelets have a pivotal role 1. Moreover, recent studies described the pathogenetic role of platelet hyperactivation and reduced sensitivity to antiaggregating therapy in obesity 1. Nonetheless, the exact mechanisms by which adiposity induces platelet dysfunction remain poorly investigated 2. The contribution of multiple factors developed in obesity can hardly be modeled in vitro and that is why using animal models could be critical for this purpose. Whilst animal models cannot thoroughly replicate human obesity, they are a powerful tool to develop new therapeutic approaches for preventing and treating the pathology. Over the last 2 decades, many groups have employed a established animal model, diet-induced obesity (DIO) model, to understand the development and persistence of obesity, as well as the metabolic complications that accompany the excess weight 3. To perform this model, rats are into a regimen of a high-fat diet (more than 40% of

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“…Overweight and particularly obesity have been related with increased platelet reactivity assessed by different laboratory platelet function tests in different series of patients. Increased MPV, platelet microparticles, thromboxane B2 metabolites and thrombin receptor activated peptide-6 induced aggregation are among the platelet function features described in subjects with obesity 23 . Increased oxidative stress with higher reactive oxygen species production, frequently observed in subjects with central obesity, has been attributed as a relevant factor causing platelet dysfunction and nitric oxide (NO) availability 24 .…”

Section: Discussionmentioning

confidence: 99%

Relation between platelet coagulant and vascular function, sex-specific analysis in adult survivors of childhood cancer compared to a population-based sample

Panova‐Noeva

Wagner

Nagler

et al. 2019

Sci Rep

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Female sex is a risk factor for long-term adverse outcome in cancer survivors, however very little is known for the underlying pathophysiological mechanisms rendering the increased risk. This study investigated sex-specifically the relation between thrombin generation (TG) with and without presence of platelets and vascular function in 200 adult survivors of a childhood cancer compared to 335 population-based control individuals. TG lag time, peak height and endogenous thrombin potential (ETP) measured in presence and absence of platelets were correlated to reflection index (RI) and stiffness index (SI). A sex-specific correlation analysis showed a negative relation in female survivors for platelet-dependent peak height and/or ETP and RI only. An age adjusted linear regression model confirmed the negative association between RI and platelet-dependent ETP (beta estimate: −6.85, 95% confidence interval: −12.19,−1.51) in females. Adjustment for cardiovascular risk factors resulted in loss of the association, whereby arterial hypertension and obesity showed the largest effects on the observed association. No other relevant associations were found in male and female cancer survivors and all population-based controls. This study demonstrates a link between platelet coagulant and vascular function of resistance vessels, found in female cancer survivors, potentially mediated by the presence of arterial hypertension and obesity.

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Platelet reactivity in overweight and obese patients undergoing cardiac surgery

Cited by 18 publications

References 31 publications

The Effect of Empagliflozin on Platelet Function Profiles in Patients with Stable Coronary Artery Disease in Trinidad: The EFFECT Pilot Study

The Effect of Empagliflozin on Platelet Function Profiles in Patients with Stable Coronary Artery Disease in Trinidad: The EFFECT Pilot Study

Analysis of platelets from a diet-induced obesity rat model: elucidating platelet dysfunction in obesity

Relation between platelet coagulant and vascular function, sex-specific analysis in adult survivors of childhood cancer compared to a population-based sample

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