Reticulated Platelets: Changing Focus from Basics to Outcomes

2018 ◽  
Vol 118 (09) ◽  
pp. 1517-1527 ◽  
Author(s):  
Bashar Hannawi ◽  
Yousef Hannawi ◽  
Neal Kleiman

AbstractPlatelets play an essential role in the pathophysiology of atherothrombosis. Reticulated platelets (RPs) are the youngest platelet population in the circulation; their presence is an indicator of platelet turnover. Circulating levels of RPs are increased in patients with coronary artery disease and stroke. Preliminary indications are that the proportion of circulating RP is associated with the likelihood of ischaemic events such as acute coronary syndrome and stroke. Plausible mechanisms include: (1) increased participation of these platelets in thrombosis due to messenger ribonucleic acid that may be translated to active proteins, (2) lack of exposure to anti-platelet drugs since they are newly released from the bone marrow or (3) their presence is a non-specific marker of inflammation. In this state-of-the-art review, we discuss the implication of RP in coronary artery disease and in hypo-responsiveness to the most commonly used anti-platelet drugs.

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Gorre Manjula ◽  
Rayabarapu Pranavchand ◽  
Irgam Kumuda ◽  
B. Sriteja Reddy ◽  
Battini Mohan Reddy

AbstractDevelopment of coronary artery disease (CAD) is primarily due to the process of atherosclerosis, however the prognosis of CAD depends on pleiotropic effects of the genes located at 9p21.3 region. Genome wide association studies revealed association of variants in this region with CAD pathology. However, specific marker in predicting CAD development or progression is not yet identified. In the present study, 35 SNPs at 9p21.3 region, located in the cyclin dependent kinase inhibitor (CDKN2A/CDKN2B) genes, were genotyped among 350 CAD cases and 480 controls from the southern Indian population of Hyderabad using fluidigm nanofluidic SNP genotyping system and the data were analyzed using PLINK and R softwares. Of the 35 SNPs analysed, only one SNP, rs7865618, was found to be highly significantly associated with CAD, even after correction for multiple testing (p = 0.008). The AG and GG genotypes of this SNP conferred 3.08 and 1.93 folds increased risk for CAD respectively. In particular, this SNP was significantly associated with severe anatomic (triple vessel disease p = 0.023) and phenotypic (acute coronary syndrome p = 0.007) categories of CAD. Pair wise SNP interaction analysis between the SNPs of 9p21.3 and 11q23.3 regions revealed significantly increased risk of three SNPs of 11q23.3 region that were not associated individually, in conjunction with rs7865618 of 9p21.3.


2020 ◽  
Vol 11 (5) ◽  
pp. 49-53
Author(s):  
Archana Bhat ◽  
Arunachalam Ramachandran ◽  
Pradeep Periera ◽  
Akshatha Rao Aroor

Background: Vitamin D, a fat-soluble vitamin has its receptor present in myriad of tissues and it modulates multiple cellular processes. Vitamin D deficiency is reported to be associated with coronary artery disease. Cardiovascular disease is the leading cause of mortality worldwide. Aims and Objective: The primary outcome was to investigate if there is a correlation of 25-OH levels with the percentage of luminal stenosis, as measured with coronary angiogram. The secondary outcome was to determine the differences in angiographically proven luminal stenosis across categories of 25-OH vitamin D levels. Materials and Methods: Thirty patients with acute coronary syndrome with diabetes mellitus were included in this cross-sectional descriptive study. All patients were tested for fasting vitamin D levels, fasting blood sugar, HbA1C and serum creatinine. Detailed history of the patients was recorded. Data was analyzed by the statistical software SPSS version 19 and p value <0.05 was considered significant. Statistical tests like Chi- square, independent t test and log regression was used. Results: In this study 30 patients undergoing coronary angiography for acute coronary syndrome, Vitamin D levels showed severe deficiency in 6.7% (2) cases while mild deficiency was seen in 50% of the cases. Patients with single vessel disease on the coronary angiogram had lower mean HbA1C (9.18) levels in our study. Patients with triple vessel disease had poorly controlled mean HbA1C levels (10.42). Conclusion: In this study we did not find any significant difference between the serum Vitamin D deficiency levels with patients with angiographic severity of the coronary artery disease. Patients with poorly controlled diabetes mellitus had more severe angiographic proven coronary artery disease.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J.P Dias Ferreira Reis ◽  
R Ramos ◽  
P Modas Daniel ◽  
S Aguiar Rosa ◽  
L Almeida Morais ◽  
...  

Abstract Aim In patients (pts) with suspected coronary artery disease (CAD), computed tomographic angiography (CTA) may improve pt selection for invasive coronary angiography (ICA) as alternative to functional testing. However. the role of CTA in symptomatic pts after abnormal functional test (FT) is incompletely defined. Methods and results This randomized clinical trial conducted in single academic tertiary center selected 218 symptomatic pts with mild to moderately abnormal FT referred to ICA to receive either the originally intended ICA (n=103) or CTA (n=115). CTA interpretation and subsequent care decisions were made by the clinical team. Pts with high risk features on FT, previous acute coronary syndrome, previously documented CAD, chronic kidney disease (GFR&lt;60ml/min/1.73m2) or persistent atrial fibrillation were excluded. The primary endpoint was the percentage of ICA with no significant obstructive CAD (no stenosis ≥50%) in each group. Diagnostic (DY) and revascularization (RY) yields of ICA in either group were also assessed. Pts were followed up for at least 1 year for the primary safety endpoint of all cause death/ nonfatal myocardial infarction/ stroke. Unplanned revascularization (UP) and symptomatic status (SS) were also evaluated. Pts averaged 68±9 years of age, 60% were male, 29% were diabetic. Nuclear perfusion stress test was used in 33.9% in CTA group and 31.1% in control group (p=0.655). Mean post (functional) test probability of obstructive CAD was 34%. Overall prevalence of obstructive CAD was 32.1%. In the CTA group, ICA was cancelled by referring physicians in 83 of the pts (72.2%) after receiving CTA results. For those undergoing ICA, non-obstructive CAD was found in 5 pts (15.6%) in the CTA-guided arm and 60 (58.3%) in the usual care arm (p&lt;0.001 Mean cumulative radiation exposure related to diagnostic work up was similar in both groups (6±14 vs 5±14mSv, p=0.152). Both DY (84.4% vs 41.7, p&lt;0.001) and RY (71.9% vs 38.8%, p=0.001) yields were significantly higher for CTA-guided ICA as compared to standard FT-guided ICA. The rate of the primary safety endpoint was similar between both groups (1.9% vs 0%, p=0.244), as well as the rates of UP (0.9% vs 0.9%, p=1.000) and SS (persistent angina: 29.6% vs 24.8%, p=0.425). Conclusions In pts with suspected CAD and mild to moderately abnormal ischemia test, a diagnostic strategy including CTA as gatekeeper is safe, effective and significantly improves diagnostic and revascularization yields of ICA. Funding Acknowledgement Type of funding source: None


Medicina ◽  
2021 ◽  
Vol 57 (6) ◽  
pp. 595
Author(s):  
Mircea Bajdechi ◽  
Cosmin Mihai ◽  
Alexandru Scafa-Udriste ◽  
Ali Cherry ◽  
Diana Zamfir ◽  
...  

The pathophysiology of accelerated atherosclerosis in people living with Human Immunofediciency virus (HIV) is complex. Coronary artery disease (CAD) has become an important cause of mortality in these patients. They often have atypical symptoms, leading to frequently missed diagnoses. We report a case of a 51-year-old male undergoing antiretroviral therapy who was admitted for acute coronary syndrome. He had severe coronary artery disease that involved difficult management.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Otsuka ◽  
M Villiger ◽  
L.J.C Van Zandvoort ◽  
T Neleman ◽  
A Karanasos ◽  
...  

Abstract Background Intracoronary polarimetry with polarization-sensitive (PS-) optical frequency domain imaging (OFDI) measures polarization properties, including birefringence and depolarization, in parallel with structural features of conventional OFDI (Figure 1A). Collagen, which imparts mechanical integrity to fibrous caps, and collagen-synthesizing smooth muscle cells exhibit elevated birefringence. Depolarization is increased by the presence of macrophages and lipid/necrotic cores. Purpose This study aimed to compare conventional OFDI and polarimetric signatures of coronary lesions between patients with acute coronary syndrome (ACS) and chronic coronary syndrome (CCS). Furthermore, we aimed to determine a birefringence cut-off value for identifying which fibrous caps belong to ACS culprit lesions. Methods This study consisted of 37 patients with ACS (n=23) or CCS (n=14). ACS culprit lesions (ACS-lesions) and CCS stenotic lesions (CCS-lesions) were included in the analysis (820 mm). Qualitative and quantitative conventional OFDI analysis included the presence of plaque rupture, macrophage infiltration, micro-vessels, thrombus, stenosis severity, fibrous cap thickness (FCT), lipid arc, lipid-burden and calcium-burden index. Birefringence and depolarization of the coronary lesions and fibrous caps were measured in the cross-sectional images showing the minimum FCT or minimum luminal area. Predictors of ACS-lesions were investigated by multivariate regression analysis. Receiver operating characteristic (ROC) analysis was used to determine the birefringence cut-off value identifying ACS fibrous caps (ACS-caps). Results There were no significant differences in clinical characteristics between the two groups, except for previous history of coronary artery disease. Compared to CCS-lesions, ACS-lesions featured higher lipid-burden index and maximum lipid arc (both p&lt;0.05). ACS-lesions featured lower birefringence and higher depolarization than CCS-lesions (p&lt;0.05). Multivariable regression demonstrated an independent association of birefringence with ACS-lesions (p&lt;0.05), even after adjusting for the conventional OFDI findings. Limiting the analysis to the fibrous caps, ACS-caps exhibited significantly lower birefringence (p&lt;0.05) and higher depolarization (p&lt;0.05) that CCS-caps. ROC analysis for differentiating ACS-caps from CCS-caps found that a birefringence value of 0.0004 results in a sensitivity and specificity of 88% and 82%, respectively (Figure 1B, AUC = 0.82). Conclusions Intracoronary polarimetry provides quantitative assessment of coronary lesions related to their composition. Birefringence was an independent robust predictor of ACS-lesions. Decreased birefringence and pronounced depolarization within the ACS-caps may indicate increased collagenolytic activity and macrophage infiltration, respectively. These results suggest that polarization properties may serve as quantitative imaging markers for assessing plaque vulnerability. Figure 1 Funding Acknowledgement Type of funding source: Other. Main funding source(s): This work was supported by the National Institutes of Health and by Terumo Corporation.


2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
KA Krychtiuk ◽  
M Lenz ◽  
P Hohensinner ◽  
K Distelmaier ◽  
L Schrutka ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): FWF Background and aims Proprotein convertase subtilisin/kexin type-9 (PCSK9) is an enzyme promoting the degradation of low-density lipoprotein receptors (LDL-R) in hepatocytes. Inhibition of PCSK9 has emerged as a novel target for lipid-lowering therapy. Monocytes are crucially involved in the pathogenesis of atherosclerosis and can be divided into three subsets. The aim of this study was to examine whether circulating levels of PCSK9 are associated with monocyte subsets. Methods We included 69 patients with stable coronary artery disease. PCSK9 levels were measured and monocyte subsets were assessed by flow cytometry and divided into classical monocytes (CD14++CD16-; CM), intermediate monocytes (CD14++CD16+; IM) and non-classical monocytes (CD14 + CD16++; NCM). Results Mean age was 64 years and 80% of patients were male. Patients on statin treatment (n = 55) showed higher PCSK9-levels (245.4 (206.0-305.5) ng/mL) as opposed to those without statin treatment (186.1 (162.3-275.4) ng/mL; p = 0.05). In patients on statin treatment, CM correlated with circulating PCSK9 levels (R = 0.29; p = 0.04), while NCM showed an inverse correlation with PCSK9 levels (R=-0.33; p = 0.02). Patients with PCSK9 levels above the median showed a significantly higher proportion of CM as compared to patients with PCSK-9 below the median (83.5 IQR 79.2-86.7 vs. 80.4, IQR 76.5-85.2%; p = 0.05). Conversely, PCSK9 levels &gt;median were associated with a significantly lower proportion of NCM as compared to those with PCSK9 &lt;median (10.2, IQR 7.3-14.6 vs. 14.3, IQR 10.9-18.7%; p = 0.02). In contrast, IM showed no association with PCSK-9 levels. Conclusions We hereby provide a novel link between PCSK9 regulation, innate immunity and atherosclerotic disease in statin-treated patients.


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