Obstructive sleep apnea is common in adults with cardiovascular disease. Accumulating evidence suggests an association between obstructive sleep apnea and cardiovascular disease independent of the traditionally recognized cardiovascular disease risk factors. Observational studies indicate that obstructive sleep apnea is a risk factor for development of cardiovascular disease and that alleviation of obstructive events with positive airway pressure may improve cardiovascular disease outcomes. However, recent randomized controlled trials have not supported the beneficial effect of positive airway pressure in cardiac populations with concomitant obstructive sleep apnea. Some evidence suggests that the relationship between obstructive sleep apnea and traditionally recognized cardiovascular disease risk factors is bidirectional, suggesting that patients with cardiovascular disease may also develop obstructive sleep apnea and that efficient treatment of cardiovascular disease may improve obstructive sleep apnea. Recent data also indicate that the apnea–hypopnea index, which is commonly used as a diagnostic measure of obstructive sleep apnea severity, has limited value as a prognostic measure for cardiovascular disease outcomes. Novel markers of obstructive sleep apnea-associated hypoxic burden and cardiac autonomic response seem to be strong predictors of adverse cardiovascular disease outcomes and response to treatment of obstructive sleep apnea. This narrative review and position paper from the Turkish Collaboration of Sleep Apnea Cardiovascular Trialists aims to update the current evidence about the relationship between obstructive sleep apnea and cardiovascular disease and, consequently, raise awareness for health professionals who deal with cardiovascular and respiratory diseases to improve the ability to direct resources at patients most likely to benefit from treatment of obstructive sleep apnea and optimize treatment of the coexisting cardiovascular diseases. Moreover, the Turkish Collaboration of Sleep Apnea Cardiovascular Trialists aims to contribute to strengthening the efforts of the International Collaboration of Sleep Apnea Cardiovascular Trialists in this context.

Background: Quantitative flow ratio is a novel technology for the functional assessment of intermediate coronary stenoses. The authors sought to explore the influence of diabetes mellitus on the application of quantitative flow ratio and predictors of discrepancies between quantitative flow ratio and fractional flow reserve.

Methods: Quantitative flow ratio was calculated in 224 patients (317 vessels) who underwent fractional flow reserve measurement by professional technicians blinded to fractional flow reserve value. Patients were divided into the diabetes mellitus group and the non-diabetes mellitus group. The diagnostic performance of quantitative flow ratio was assessed using fractional flow reserve as a reference.

Results: Good correlation and agreement between quantitative flow ratio and fractional flow reserve can be found in the diabetes mellitus group (r = 0.834, P <.001; mean difference: 0.007 ± 0.108). Prior myocardial infarction showed a statistically significant association with increased classification discrepancy between quantitative flow ratio and fractional flow reserve [odds ratio 3.16 (95% confidence interval: 1.29-7.75), P =.01]. The area under the receiver-operating characteristic curve of quantitative flow ratio showed no significant difference in diabetes mellitus and non-diabetes mellitus groups, hemoglobin A1c ≥ 7% and hemoglobin A1c < 7% groups, diabetic duration ≥ 10 years and diabetic duration < 10 years groups (area under receiver-operating characteristic curve: 0.90 (95% confidence interval: 0.84-0.94) vs. 0.92 (95% confidence interval: 0.87-0.96), P =.54; 0.89 (95% confidence interval: 0.81-0.95) vs. 0.92 (95% confidence interval: 0.81-0.97), P =.65; 0.88 (95% confidence interval: 0.79-0.94) vs. 0.89 (95% confidence interval: 0.79-0.96), P =.83; respectively).

Conclusions: Clinical application of quantitative flow ratio is not limited to diabetic patients. The relationship between prior myocardial infarction and quantitative flow ratio needs to be further developed.

Background: Cardiac fibrosis increases with age. Fibroblast activation plays an essential role in cardiac fibrosis. Histone modifications are involved in various chromatin-dependent processes. Attenuation of the histone H3 trimethylation on lysine 27 demethylase UTX by RNA interference or heterozygous mutation extends lifespan in worm. The objective of this study was to explore whether epigenetic silencing of UTX mitigates aging-associated cardiac fibrosis.

Methods: Middle-aged mice (15 months old) were used and started to receive adeno-associated virus-scrambled-small hairpin RNA and adeno-associated virus-UTX-small hairpin RNA every 3 months from 15 months to 21 months, respectively. The mice were euthanized at 24 months of age (length of the study).

Results: Adeno-associated virus-UTX-small hairpin RNA delivery significantly attenuated aging-associated increase in blood pressure, especially in diastolic blood pressure, indicating silencing of UTX rescued aging-associated cardiac dysfunction. Aging-associated cardiac fibrosis is characterized by fibroblast activation and abundant extracellular matrix deposition, including collagen deposition and alpha smooth muscle actin activation. Silencing of UTX abolished collagen deposition and alpha smooth muscle actin activation, decreased serum transforming growth factor β, blocked cardiac fibroblasts-to-myofi brobl asts trans-differentiation by elevation of cardiac resident mature fibroblast markers, TCF21, and platelet-derived growth factor receptor alpha, which are important proteins for maintaining cardiac fibroblast physiological function. In the mechanistic study, adeno-associated virus-UTX-small hairpin RNA blocked transforming growth factor β-induced cardiac fibroblasts-to-myofibroblasts trans-differentiation in isolated fibroblasts from 24-month-old mouse heart. The same results demonstrated as the in vivo study.

Conclusions: Silencing of UTX attenuates aging-associated cardiac fibrosis via blocking cardiac fibroblasts-to-myofibroblasts trans-differentiation and consequently attenuates aging-associated cardiac dysfunction and cardiac fibrosis.

Background: This study aimed to assess the relationship between stent parameters and platelet function, as well as the platelet reactivity profiles over time in patients treated with the Xinsorb scaffold.

Methods: Adenosine diphosphate-induced maximal amplitude was measured as clopidogrel on-treatment platelet reactivity using thrombelastography. High residual platelet reactivity was defined as MAADP > 47 mm. Platelet function testing was induced at baseline, discharge, and 6- and 12-month visits.

Results: A total of 40 individuals undergoing Xinsorb scaffold implantation and platelet function testing were included. No adverse events were recorded during follow-up. No correlation was observed among thrombelastography indices, stent diameters, and stent coverage surface area. Significant correlation was found between MAADP and lengths of stents (Spearman rank correlation = 0.324, P =.031). Multiple logistic regression analyses demonstrated that high levels of high-density lipoprotein cholesterol was an independent protective factor for high residual platelet reactivity (odds ratio = 0.049, 95% con-fidence interval = 0.011-0.296, P =.016). No significant risk factors were identified; MAADP presented to be 20.6 [13.1-36.2] mm, 26.8 [18.2-35.0] mm, and 30.0 [19.6-33.4] mm 48 hours, 6 months, and 12 months after procedure, respectively; 12-month MAADP was sig-nificantly higher than the 48-hour MAADP (P =.026). There was no obvious trend for platelet response status over time.

Conclusion: Among patients on a clopidogrel-based dual antiplatelet treatment regimen following Xinsorb scaffold implantation, stent parameters had no significant effects on platelet reactivity. The high residual platelet reactivity phenotype is relatively stable over time. High residual platelet reactivity is more likely to occur in patients with lower high-density lipoprotein cholesterol levels.

Background: Activation of the reninangi otens in-aldosterone system has an important role in the pathophysiology of heart failure with reduced ejection fraction. While the effects of systemic reninangi otens in-aldosterone system activation on heart failure with reduced ejection fraction are well known, the impact of the local reninangi otens in-aldosterone system on heart failure with reduced ejection fraction is not fully understood because of limited clinical research. This study aimed to investigate the effect of urinary angiotensinogen level, an accepted indicator of local reninangi otens in-aldosterone system activation, on all-cause mortality in patients with heart failure with reduced ejection fraction.

Methods: This retrospective, single-center study included 60 patients with baseline urinary angiotensinogen data and survival/mortality data at 4 years. Urinary angiotensinogen values were standardized to the urinary creatinine value measured from the same urine sample. The median urinary angio tensi nogen /urin ary creatinine value among all patients (114 μg/g) was used as a cutoff to divide the patients into 2 groups. Mortality data were obtained from the national registry systems or by telephone.

Results: Comparison of all-cause mortality in the 2 groups showed that 22 deaths (71%) occurred in the group with a urinary angio tensinogen/urinary creatinine ratio above the median and 10 deaths (35.5%) occurred in the group of patients with urinary angio tensinogen/urinary creatinine equal to or below the median value (P =.005).

Conclusion: Our study suggests that urinary angiotensinogen can be used as a new biomarker in the prognosis and follow-up of heart failure patients.

Background: Pulmonary embolism severity index and simplified pulmonary embolism severity index have been utilized in initial risk evaluation in patients with acute pulmonary embolism. However, these models do not include any imaging measure of right ventricle function. In this study, we proposed a novel index and aimed to evaluate the clinical impact.

Methods: Our study population comprised retrospectively evaluated 502 patients with acute pulmonary embolism managed with different treatment modalities. Echocardiographic and computed tomographic pulmonary angiography evaluations were performed at admission to the emergency room within maximally 30 minutes. The formula of our index was as follows: (right ventricle diameter × systolic pulmonary arterial pressure-echo)/(right ventricle free-wall diameter × tricuspid annular plane systolic excursion).

Results: This index value showed significant correlations to clinical and hemodynamic severity measures. Only pulmonary embolism severity index, but not our index value, independently predicted in-hospital mortality. However, an index value higher than 17.8 predicted the long-term mortality with a sensitivity of 70% and specificity of 40% (areas under the curve = 0.652, 95% CI, 0.557-0.747, P =.001). According to the adjusted variable plot, the risk of long-term mortality increased until an index level of 30 but remained unchanged thereafter. The cumulative hazard curve also showed a higher mortality with high-index value versus low-index value.

Conclusions: Our index composed from measures of computed tomographic pulmonary angiography and transthoracic echocardiography may provide important insights regarding the adaptation status of right ventricle against pressure/wall stress in acute pulmonary embolism, and a higher value seems to be associated with severity of the clinical and hemodynamic status and long-term mortality but not with in-hospital mortality. However, the pulmonary embolism severity index remained as the only independent predictor for in-hospital mortality.