Clonal Hematopoiesis and Its Impact on Human Health.

Aging is associated with increased mutational burden in every tissue studied. Occasionally, fitness-increasing mutations will arise, leading to stem cell clonal expansion. This process occurs in several tissues but has been best studied in blood. Clonal hematopoiesis is associated with an increased risk of blood cancers, such as acute myeloid leukemia, which result if additional cooperating mutations occur. Surprisingly, it is also associated with an increased risk of nonmalignant diseases, such as atherosclerotic cardiovascular disease. This may be due to enhanced inflammation in mutated innate immune cells, which could be targeted clinically with anti-inflammatory drugs. Recent studies have uncovered other factors that predict poor outcomes in patients with clonal hematopoiesis, such as size of the mutant clone, mutated driver genes, and epigenetic aging. Though clonality is inevitable and largely a function of time, recent work has shown that inherited genetic variation can also influence this process. Clonal hematopoiesis provides a paradigm for understanding how age-related changes in tissue stem cell composition and function influence human health.

Role of dysregulated macrophage subpopulation ratios and functional changes in the development of coronary atherosclerosis.

Coronary heart disease is one of the most significant risk factors affecting human health worldwide. Its pathogenesis is intricate, with atherosclerosis being widely regarded as the leading cause. Aberrant lipid metabolism in macrophages is recognized as one of the triggering factors in atherosclerosis development. To investigate the role of macrophages in the formation of coronary artery atherosclerosis, we utilized single-cell data from wild-type mice obtained from the aortic roots and ascending aortas after long-term high-fat diet feeding, as deposited in GSE131776. Seurat software was employed to refine the single-cell data in terms of scale and cell types, facilitating the identification of differentially expressed genes. Through the application of differential expression genes, we conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses at 0, 8 and 16 weeks, aiming to uncover pathways with the most pronounced functional alterations as the high-fat diet progressed. The AddModuleScore function was employed to score the expression of these pathways across different cell types. Subsequently, macrophages were isolated and further subdivided into subtypes, followed by an investigation into intercellular communication within these subtypes. Subsequent to this, we induced THP-1 cells to generate foam cells, validating critical genes identified in prior studies. The results revealed that macrophages underwent the most substantial functional changes as the high-fat diet progressed. Furthermore, two clusters were identified as potentially playing pivotal roles in macrophage functional regulation during high-fat diet progression. Additionally, macrophage subtypes displayed intricate functionalities, with mutual functional counterbalances observed among these subtypes. The proportions of macrophage subtypes and the modulation of anti-inflammatory and pro-inflammatory functions played significant roles in the development of coronary artery atherosclerosis.

Coronary artery bypass grafting (CABG) induces pro-inflammatory and immunomodulatory phenotype of platelets in the absence of a pro-aggregatory state.

BACKGROUND: Coronary artery bypass grafting (CABG) is considered the choice treatment for patients suffering from coronary artery disease (CAD). In the inflammatory milieu of cardiopulmonary bypass (CPB), systemic inflammatory response syndrome (SIRS) can induce a platelet pro-inflammatory state which could exacerbate post-CABG inflammatory status while affecting hemostatic function in patients. Therefore, focusing on platelets, the study presented here attempted to evaluate the pro-inflammatory and immunomodulatory profile of platelets as well as pro-aggregatory status during CABG. METHODS: Platelets from patients undergoing CABG were subjected to flowcytometry analysis to evaluate P-selectin and CD40L expressions and PAC-1 binding in five intervals of 24 h before surgery, immediately, 2 h, 24 h, and one week after surgery. Moreover, intra-platelet TGF-ß1 was also examined with western blotting. RESULTS: Data showed increases of P-selectin and CD40L expressions in patients, with the meaningful loss of platelet contents of TGF-ß1 after CABG (p < 0.001), where the changes tended to recover by day 7 of surgery while remaining above baseline (p < 0.001). Meanwhile, no significant change in PAC-1 binding capacity was shown. CONCLUSION: The study presented here suggests that although the release of pro-inflammatory substances from platelets during CABG supports the post-operative inflammatory state, platelets are not pro-aggregatory enough to enhance thrombotic events after surgery. Whilst these observations could be due to successful medical interventions to optimize hemostasis during and after surgery, post-CABG reversal of anticoagulant by protamine is considered as another factor that may also have contributed to preventing pro-aggregatory but not pro-inflammatory and immunomodulatory functions of platelets.

Impact of preexisting coronary artery and peripheral artery disease on outcomes in diabetic patients after kidney transplant.

BACKGROUND: Atherosclerotic cardiovascular disease is highly prevalent in patients with end-stage kidney disease (ESKD). Kidney transplant (KT) improves patient survival and cardiovascular outcomes. The impact of preexisting coronary artery disease (CAD) and peripheral artery disease (PAD) on posttransplant outcomes remains unclear. METHODS: This is a retrospective study utilizing the United States Renal Data System. Adult diabetic dialysis patients who underwent first KT between 2006 and 2017 were included. The study population was divided into four cohorts based on presence of CAD/PAD: (1) polyvascular disease (CAD + PAD); (2) CAD without PAD; (3) PAD without CAD; (4) no CAD or PAD (reference cohort). The primary outcome was 3-year all-cause mortality. Secondary outcomes were incidence of posttransplant myocardial infarction (MI), cerebrovascular accidents (CVA), and graft failure. RESULTS: The study population included 19,329 patients with 64.4% men, mean age 55.4 years, and median dialysis duration of 2.8 years. Atherosclerotic cardiovascular disease was present in 28% of patients. The median follow up was 3 years. All-cause mortality and incidence of posttransplant MI were higher with CAD and highest in patients with polyvascular disease. The cohort with polyvascular disease had twofold higher all-cause mortality (16.7%, adjusted hazard ratio (aHR) 1.5, p < 0.0001) and a fourfold higher incidence of MI (12.7%, aHR 3.3, p < 0.0001) compared to the reference cohort (8.0% and 3.1%, respectively). There was a higher incidence of posttransplant CVA in the cohort with PAD (3.4%, aHR 1.5, p = 0.01) compared to the reference cohort (2.0%). The cohorts had no difference in graft failure rates. CONCLUSIONS: Preexisting CAD and/or PAD result in worse posttransplant survival and cardiovascular outcomes in patients with diabetes mellitus and ESKD without a reduction in graft survival.

Clinical study of two-dimensional speckle tracking to evaluate abnormal myocardial motion due to coronary lesions.

OBJECTIVE: To investigate the predictive ability of global longitudinal strain (GLS) and mechanical dispersion for coronary stenosis and provide a more reliable noninvasive method for diagnosis of obstructive coronary artery disease(OCAD). METHODS: Sixty-seven patients diagnosed with suspected CAD were included in the study. Patients with coronary stenosis greater than 50% were assigned as OCAD, while the others were assigned as non obstructive coronary artery disease(NOCAD). General information was collected and patients underwent speckle tracking echocardiogram(STE). RESULTS: Spearman's correlation analysis showed that GLS and mechanical dispersion were positively correlated with the degree of coronary stenosis (r = 0.383, 0.342, p < 0.05), and there was also a positive correlation between GLS and mechanical dispersion (r = 0.327, p < 0.05). GLS, longitudinal strain (LS) of each chamber, and mechanical dispersion were higher in the OCAD group than in the NOCAD group (p < 0.05). Univariate regression analysis showed that GLS, each lumen LS and mechanical dispersion were statistically significant (p < 0.05). Multifactorial regression analysis showed that elevated GLS (p = 0.007) and elevated mechanical dispersion (p = 0.030) were independent risk factors for OCAD. The ROC curves showed that GLS predicted OCAD (AUC area 0.745, 95% CI 0.624 to 0.865) versus mechanical discrete prediction of OCAD (AUC area 0.702, 95% CI 0.569 to 0.834) were more diagnostic than conventional cardiac ultrasound observations of ventricular wall motion abnormalities (AUC area 0.566, 95% CI 0.463 to 0.669). CONCLUSIONS: Combining GLS with mechanical dispersion can rapidly assess OCAD in a very short period, which has strong promotion value and in-depth research value.

Association of exosomes in patients with compromised myocardial perfusion on functional imaging.

OBJECTIVES: Exosomes are membrane vesicles that are actively secreted in response to microenvironmental stimuli. In this study, we quantified the amount of exosomes in patients with significant coronary artery disease (CAD) and evaluated its relationship with myocardial perfusion imaging (MPI) results. METHODS: Patients who underwent both MPI and coronary angiography were recruited. Plasma was collected during angiography, and exosomes were extracted via the precipitation method. The summed stress scores (SSS), summed difference scores, and ventricular functional parameters were calculated from the MPI and compared with the amounts of exosomes and extracted miRNAs. RESULTS: In total, 115 patients were enrolled (males: 78 %; mean age: 66.6 ± 10.6 years). Those with abnormal SSS according to the MPI had significantly fewer exosomes (p = 0.032). After multivariate analysis, the SSS remained significantly related to the amount of exosomes (p = 0.035). In forty randomly selected samples, miRNA-432-5p and miRNA-382-3p were upregulated in patients with abnormal SSS. CONCLUSIONS: Patients with compromised poststress myocardial perfusion on MPI tended to have fewer exosomes in association with CAD-related miRNAs. This is the first study to clarify the fundamental and pathophysiological causes of CAD using radiographic examinations.

Single Cell High Dimensional Analysis of Human Peripheral Blood Mononuclear Cells Reveals Unique Intermediate Monocyte Subsets Associated with Sex Differences in Coronary Artery Disease.

Monocytes are associated with human cardiovascular disease progression. Monocytes are segregated into three major subsets: classical (cMo), intermediate (iMo), and nonclassical (nMo). Recent studies have identified heterogeneity within each of these main monocyte classes, yet the extent to which these subsets contribute to heart disease progression is not known. Peripheral blood mononuclear cells (PBMC) were obtained from 61 human subjects within the Coronary Assessment of Virginia (CAVA) Cohort. Coronary atherosclerosis severity was quantified using the Gensini Score (GS). We employed high-dimensional single-cell transcriptome and protein methods to define how human monocytes differ in subjects with low to severe coronary artery disease. We analyzed 487 immune-related genes and 49 surface proteins at the single-cell level using Antibody-Seq (Ab-Seq). We identified six subsets of myeloid cells (cMo, iMo, nMo, plasmacytoid DC, classical DC, and DC3) at the single-cell level based on surface proteins, and we associated these subsets with coronary artery disease (CAD) incidence based on Gensini score (GS) in each subject. Only frequencies of iMo were associated with high CAD (GS > 32), adj.p = 0.024. Spearman correlation analysis with GS from each subject revealed a positive correlation with iMo frequencies (r = 0.314, p = 0.014) and further showed a robust sex-dependent positive correlation in female subjects (r = 0.663, p = 0.004). cMo frequencies did not correlate with CAD severity. Key gene pathways differed in iMo among low and high CAD subjects and between males and females. Further single-cell analysis of iMo revealed three iMo subsets in human PBMC, distinguished by the expression of HLA-DR, CXCR3, and CD206. We found that the frequency of immunoregulatory iMo_HLA-DR+CXCR3+CD206+ was associated with CAD severity (adj.p = 0.006). The immunoregulatory iMo subset positively correlated with GS in both females (r = 0.660, p = 0.004) and males (r = 0.315, p = 0.037). Cell interaction analyses identified strong interactions of iMo with CD4+ effector/memory T cells and Tregs from the same subjects. This study shows the importance of iMo in CAD progression and suggests that iMo may have important functional roles in modulating CAD risk, particularly among females.

Serum Albumin was Associated with a Long Term Cardiovascular Mortality among Elderly Patients with Stable Coronary Artery Disease.

Background: Serum albumin (SA), a multifunction protein, contributes to maintaining a variety of physiological functions. Studies have linked SA to atherosclerosis with possible mechanisms including a response to inflammation. The contribution of albumin to cardiovascular (CV) mortality in elderly patients with stable coronary artery disease (CAD) remains unclear. Methods: We investigated 321 elderly patients with stable CAD undergoing coronary angiography between 2003 and 2006. CV mortality data were obtained from the National Registry of Deaths in Taiwan. CV mortality included deaths attributable to ischemic heart disease, congestive heart disease, and stroke. The association between baseline SA and CV mortality was assessed using a Cox model and Fine-Gray model when non-CV mortality was considered a competing event. Results: During a median follow-up of 97 months, 39 (12.1%) participants died from CV disease and 76 (23.7%) died from non-CV diseases. After adjusting for covariates, patients in the SA ≥ 3.75 g/dL group had a lower frequency of CV mortality compared with those in the SA < 3.75 g/dL group [hazard ratio (HR): 0.20; 95% confidence interval (CI): 0.08-0.49; p < 0.001]. Similarly, compared to the participants with non-CV mortality, the SA ≥ 3.75 g/dL group had a lower frequency of CV mortality compared with the SA < 3.75 g/dL group (subdistribution HR: 0.27; 95% CI: 0.11-0.65; p < 0.001) in adjusted competing risk models. Conclusions: A SA level ≥ 3.75 g/dL at admission was associated with decreased long-term CV mortality and may be useful for risk prediction in elderly patients with stable CAD.

Cytomegalovirus Immunoglobulin G (IgG) Titer and Coronary Artery Disease in People With Human Immunodeficiency Virus (HIV).

BACKGROUND: Cytomegalovirus (CMV) infection is thought to result in increased immune activation in people with human immunodeficiency virus (HIV, PWH). Although some data have linked asymptomatic CMV infection to cardiovascular disease among PWH, it remains unknown whether CMV is associated with increased or high-risk coronary plaque. METHODS: The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) enrolled PWH aged 40-75 years on stable antiretroviral therapy (ART) with low-to-moderate atherosclerotic cardiovascular disease (ASCVD) risk. Among a subset of US REPRIEVE participants, coronary plaque was assessed by coronary computed tomography angiography. Here, we assessed the relationship between CMV immunoglobulin G (IgG) titer and (1) levels of immune activation, (2) inflammatory biomarkers, and (3) coronary plaque phenotypes at study entry. RESULTS: Of 672 participants, mean age was 51 years, 83% were men, median ASCVD risk score was 4.5%, and 66% had current CD4+ T-cell count ≥500 cells/mm3. Higher CMV IgG quartile group was associated with older age and lower current and nadir CD4+ T-cell counts. CMV IgG titer was associated with specific inflammatory biomarkers (sCD163, MCP-1, interleukin [IL]-6, hsCRP) in univariate analysis, but not after controlling for HIV-specific factors. In contrast, CMV IgG titer was not associated with coronary artery disease indexes, including presence of plaque, coronary artery calcium (CAC) score >0, vulnerable plaque presence, or Leaman score >5. CONCLUSIONS: No meaningful association was seen between CMV IgG titer and coronary artery disease indexes among ART-treated PWH at study enrollment. Longitudinal assessments in REPRIEVE will determine the relationship of CMV IgG titer to plaque progression and cardiovascular events. CLINICAL TRIALS REGISTRATION: NCT02344290.

Circular RNAs Variously Participate in Coronary Atherogenesis.

Over the past decade, numerous studies have shown that circular RNAs (circRNAs) play a significant role in coronary artery atherogenesis and other cardiovascular diseases. They belong to the class of non-coding RNAs and arise as a result of non-canonical splicing of premature RNA, which results in the formation of closed single-stranded circRNA molecules that lack 5'-end caps and 3'-end poly(A) tails. circRNAs have broad post-transcriptional regulatory activity. Acting as a sponge for miRNAs, circRNAs compete with mRNAs for binding to miRNAs, acting as competing endogenous RNAs. Numerous circRNAs are involved in the circRNA-miRNA-mRNA regulatory axes associated with the pathogenesis of cardiomyopathy, chronic heart failure, hypertension, atherosclerosis, and coronary artery disease. Recent studies have shown that сirc_0001445, circ_0000345, circ_0093887, сircSmoc1-2, and circ_0003423 are involved in the pathogenesis of coronary artery disease (CAD) with an atheroprotective effect, while circ_0002984, circ_0029589, circ_0124644, circ_0091822, and circ_0050486 possess a proatherogenic effect. With their high resistance to endonucleases, circRNAs are promising diagnostic biomarkers and therapeutic targets. This review aims to provide updated information on the involvement of atherogenesis-related circRNAs in the pathogenesis of CAD. We also discuss the main modern approaches to detecting and studying circRNA-miRNA-mRNA interactions, as well as the prospects for using circRNAs as biomarkers and therapeutic targets for the treatment of cardiovascular diseases.

COVID-19 STEMI related to microthrombi may lead to coronary microvascular dysfunction.

Coronavirus disease 2019 (COVID-19) increases the risk of ST-segment elevation myocardial infarction (STEMI), and is associated with a higher occurrence of nonobstructive coronary artery disease. We present a unique case of STEMI with concomitant COVID-19 infection in a young female found to have slow flow in multiple vessels on angiography, likely due to microvascular thrombi. Three months later, the patient developed coronary microvascular dysfunction (CMD), suggesting an evolution of microvascular thrombi and injury into subsequent CMD.

Impact of COVID-19 on percutaneous coronary intervention utilization and mortality in New York.

BACKGROUND: COVID-19 has disrupted the care of all patients, and little is known about its impact on the utilization and short-term mortality of percutaneous coronary intervention (PCI) patients, particularly nonemergency patients. METHODS: New York State's PCI registry was used to study the utilization of PCI and the presence of COVID-19 in four patient subgroups ranging in severity from ST-elevation myocardial infarction (STEMI) to elective patients before (December 01, 2018-February 29, 2020) and during the COVID-19 era (March 01, 2020-May 31, 2021), as well as to examine the impact of different COVID severity levels on the mortality of different types of PCI patients. RESULTS: Decreases in the mean quarterly PCI volume from the prepandemic period to the first quarter of the pandemic ranged from 20% for STEMI patients to 61% for elective patients, with the other two subgroups having decreases in between these values. PCI quarterly volume rebounds from the prepandemic period to the second quarter of 2021 were in excess of 90% for all patient subgroups, and 99.7% for elective patients. Existing COVID-19 was rare among PCI patients, ranging from 1.74% for STEMI patients to 3.66% for elective patients. PCI patients with COVID-19 and acute respiratory distress syndrome (ARDS) who were not intubated, and PCI patients with COVID-19 and ARDS who were either intubated or were not intubated because of Do Not Resuscitate//Do Not Intubate status had higher risk-adjusted mortality ([adjusted ORs = 10.81 [4.39, 26.63] and 24.53 [12.06, 49.88], respectively]) than patients who never had COVID-19. CONCLUSIONS: There were large decreases in the utilization of PCI during COVID-19, with the percentage of decrease being highly sensitive to patient acuity. By the second quarter of 2021, prepandemic volumes were nearly restored for all patient subgroups. Very few PCI patients had current COVID-19 throughout the pandemic period, but the number of PCI patients with a COVID-19 history increased steadily during the pandemic. PCI patients with COVID-19 accompanied by ARDS were at much higher risk of short-term mortality than patients who never had COVID-19. COVID-19 without ARDS and history of COVID-19 were not associated with higher mortality for PCI patients as of the second quarter of 2021.

Stingray CART (K14 technique): A novel antegrade dissection reentry strategy.

A novel device based CART technique (K14 technique) has been described with 2 case examples to illustrate the same. This CART has been performed after ADR and Reverse-CART were unsuccessful.

Angiography-derived functional assessment of left main coronary stenoses.

OBJECTIVES: We aimed to evaluate the diagnostic accuracy of quantitative flow ratio (QFR) in left main (LM) coronary stenoses, using Fractional Flow Reserve (FFR) as reference. BACKGROUND: QFR has demonstrated a high accuracy in determining the functional relevance of coronary stenoses in non-LM. However, there is an important paucity of data regarding its diagnostic value in the specific anatomical subset of LM disease. METHODS: This is a retrospective, observational, multicenter, international, and blinded study including patients with LM stenoses. Cases with significant ostial LM disease were excluded. QFR was calculated from conventional angiograms at blinded fashion with respect to FFR. RESULTS: Sixty-seven patients with LM stenoses were analyzed. Overall, LM had intermediate severity, both from angiographic (diameter stenosis [%DS] 43.8 ± 11.1%) and functional perspective (FFR 0.756 ± 0.105). Mean QFR was 0.733 ± 0.159. Correlation between QFR and FFR was moderate (r = 0.590). Positive and negative predictive value, sensitivity and specificity were 85.4%, 64%, 85.4%, and 69.6% respectively. Classification agreement of QFR and FFR in terms of functional stenosis severity was 78.1%. Area under the receiver operating characteristics of QFR using FFR as reference was 0.82 [95% confidence interval [CI], 0.71-0.93], and significantly better than angiographic evaluation including %DS (area under the receiver-operating characteristic curve [AUC] 0.45 [95% CI, 0.32-0.58], p < 0.001) and minimum lumen diameter (AUC 0.60 [95% CI, 0.47-0.74], p < 0.001). CONCLUSIONS: Compared with FFR, QFR has acceptable diagnostic performance in determining the functional relevance of LM stenosis, being better than conventional angiographic assessment. Nonetheless, caution should be taken when applying functional angiography techniques for the assessment of LM stenosis given its particular anatomical characteristics.

Ping-pong snaring of a totally dislodged stent across left main ostium: "All is not lost".

Undeployed stent loss is a rare but potentially serious complication of percutaneous coronary intervention. Its management is not assisted by well-defined guidelines, and it is made even more difficult when the dislodged stent is not protected by in situ guidewire. In this work, we present the case of a total stent loss with a crushed device protruding out of the left main. In this hopeless circumstance, an innovative ping-pong technique was used to contralaterally perform a successful stent retrieval.

The impact of chronic total occlusions in patients undergoing transcatheter aortic valve replacement: A systematic review and meta-analysis.

Coronary artery disease (CAD) is frequently encountered in patients evaluated for transcatheter aortic valve replacement (TAVR) due to severe aortic stenosis. The prognostic relevance of chronic total occlusions (CTOs) in this setting is poorly understood. We conducted a search of MEDLINE and EMBASE to identify studies evaluating patients who underwent TAVR and evaluated outcomes depending on the presence of coronary CTOs. Pooled analysis was performed to estimate the rate and risk ratio for mortality. Four studies involving 25,432 patients fulfilled the inclusion criteria. The follow up ranged from in-hospital outcomes to 8-years follow-up. Coronary artery disease was present in 67.8% to 75.5% of patients in 3 studies which reported this variable. The prevalence of CTOs varied between 2% and 12.6% in this cohort. The presence of CTOs was associated with increase in length of stay (8.1 ± 8.2 vs. 5.9 ± 6.5, p < 0.01), cardiogenic shock (5.1% vs. 1.7%, p < 0.01), acute myocardial infarction (5.8% vs. 2.8%, p = 0.02) and acute kidney injury (18.6% vs. 13.9%, p = 0.048). The pooled 1-year death rate revealed 41 deaths in 165 patients in the CTO group and 396 deaths in 1663 patients with no CTO ((24.8%) vs. (23.8%)). The meta-analysis of death with CTO versus no CTO showed a nonsignificant trend toward increased mortality with CTOs (risk ratio 1.11 95% CI 0.90-1.40, I2 = 0%). Our analysis suggests that concomitant CTO lesions in patients undergoing TAVR are common, and its presence was associated with increased in-hospital complications. However, CTO presence by itself was not associated with increased long-term mortality, only a nonsignificant trend toward an increased risk of death in patients with CTO was found. Further studies are warranted to assess the prognostic relevance of CTO lesion in TAVR patients.

Acute coronary syndrome in an anomalous mid-LAD right coronary artery: Don't forget to look twice before turning left.

A 68-year-old female with past medical history of hypertension, hyperlipidemia, multiple sclerosis, diverticulitis, and tobacco use presented with 1 day of atypical chest pain after a recent diverticulitis flare. Initial workup was notable for a normal electrocardiogram but elevated high sensitivity troponin T (616 ng/L). Due to persistent symptoms, the patient was given antiplatelet therapy and taken urgently to the catheterization lab where she was found to have complete occlusion of an anomalous right coronary artery branching off the mid-left anterior descending artery. Angioplasty was performed with a drug-eluting stent and her symptoms resolved. The patient recovered well and was discharged on appropriate medical therapy. This case demonstrates a case of acute coronary syndrome in an extremely rare coronary congenital abnormality. Further research is needed on when to be suspicious for coronary anomalies on patients presenting with myocardial infarction.

Exploring nitric oxide as a crucial prognostic biomarker of coronary artery disease.

PURPOSE: The study aimed to examine if the polymorphism of the endothelial nitric oxide synthase (eNOS) gene variable number of tandem repeats (VNTR) and the serum NO levels are associated with CAD. MATERIALS/METHODS: Case-control study, 70 CAD and 30 control subjects were enrolled. The eNOS gene polymorphism was measured by polymerase chain reaction-agarose gel electrophoresis and the serum NO was assessed by using an ELISA plate and reader covering 540 nm. RESULTS: Uncovering the area under curve (AUC) for serum NO, which was (0.6821), indicating that NO seemed to be a critical prognostic biomarker of CAD; also, glucose, serum creatinine and total bilirubin proved to be significant predictors of CAD with AUC (0.6793, 0.6717 and 0.6662) respectively. Furthermore, higher serum NO levels were associated with the eNOS (ab) genotype. Revealing the intron (a) allele was protective against CAD. Moreover, diminished levels of serum NO in CAD groups compared to controls (P < 0.05). Additionally, Multiple logistic regression analysis shows a significantly high Odds ratio associated with CAD in the Duhok population. CONCLUSIONS: The eNOS (ab) variant seems to be a protective CAD factor for patients. Low serum NO levels are another risk factor for the advancement of CAD, suggesting their involvement in atherosclerosis. The (a) allele's protective effect is mediated through changes in eNOS promoter activity and higher NO levels.

Rest/stress myocardial perfusion imaging by positron emission tomography with 18F-Flurpiridaz: A feasibility study in mice.

BACKGROUND: Myocardial perfusion imaging by positron emission tomography (PET-MPI) is the current gold standard for quantification of myocardial blood flow. 18F-flurpiridaz was recently introduced as a valid alternative to currently used PET-MPI probes. Nonetheless, optimum scan duration and time interval for image analysis are currently unknown. Further, it is unclear whether rest/stress PET-MPI with 18F-flurpiridaz is feasible in mice. METHODS: Rest/stress PET-MPI was performed with 18F-flurpiridaz (0.6-3.0 MBq) in 27 mice aged 7-8 months. Regadenoson (0.1 µg/g) was used for induction of vasodilator stress. Kinetic modeling was performed using a metabolite-corrected arterial input function. Image-derived myocardial 18F-flurpiridaz uptake was assessed for different time intervals by placing a volume of interest in the left ventricular myocardium. RESULTS: Tracer kinetics were best described by a two-tissue compartment model. K1 ranged from 6.7 to 20.0 mL·cm-3·min-1, while myocardial volumes of distribution (VT) were between 34.6 and 83.6 mL·cm-3. Of note, myocardial 18F-flurpiridaz uptake (%ID/g) was significantly correlated with K1 at rest and following pharmacological vasodilation for all time intervals assessed. However, while Spearman's coefficients (rs) ranged between 0.478 and 0.681, R2 values were generally low. In contrast, an excellent correlation of myocardial 18F-flurpiridaz uptake with VT was obtained, particularly when employing the averaged myocardial uptake from 20 to 40 min post tracer injection (R2 ≥ 0.98). Notably, K1 and VT were similarly sensitive to pharmacological vasodilation induction. Further, mean stress-to-rest ratios of K1, VT, and %ID/g 18F-flurpiridaz were virtually identical, suggesting that %ID/g 18F-flurpiridaz can be used to estimate coronary flow reserve (CFR) in mice. CONCLUSION: Our findings suggest that a simplified assessment of relative myocardial perfusion and CFR, based on image-derived tracer uptake, is feasible with 18F-flurpiridaz in mice, enabling high-throughput mechanistic CFR studies in rodents.

AT1R gene rs389566 polymorphism contributes to MACCEs in hypertension patients.

OBJECTIVE: To investigate the possible association between AT1R gene polymorphisms and major adverse cardiovascular and cerebrovascular events (MACCEs) in hypertension patients combined with or without coronary artery disease (CAD) in Xinjiang. METHODS: 374 CAD patients and 341 non-CAD individuals were enrolled as study participants and all of them have a hypertension diagnosis. AT1R gene polymorphisms were genotyped by SNPscan™ typing assays. During the follow-up in the clinic or by telephone interview, MACCEs were recorded. Kaplan-Meier curves and Cox survival analyses were used to explore the association between AT1R gene polymorphisms and the occurrence of MACCEs. RESULTS: AT1R gene rs389566 was associated with MACCEs. The TT genotype of the AT1R gene rs389566 had a significantly higher probability of MACCEs than the AA + AT genotype (75.2% vs. 24.8%, P = 0.033). Older age (OR = 1.028, 95% CI: 1.009-1.0047, P = 0.003) and TT genotype of rs389566 (OR = 1.770, 95% CI: 1.148-2.729, P = 0.01) were risk factors of MACCEs. AT1R gene rs389566 TT genotype may be a predisposing factor for the occurrence of MACCEs in hypertensive patients. CONCLUSION: We should also pay more attention to the prevent of MACCEs in hypertension patients combined with CAD. Especially those elderly hypertensive patients carrying AT1R rs389566 TT genotype requires avoidance of unhealthy lifestyle, better management of blood pressure control and reduce the occurrence of MACCEs.