Sex-specific associations between the environmental exposures and low-grade inflammation and increased blood pressure in young, healthy subjects.

Long-term exposures to environmental factors including airborne as well as noise pollutants, are associated with cardiovascular risk. However, the influence of environmental pollution on the young population is controversial. Accordingly, we aimed to investigate the relationships between long-term exposures to different environmental factors and major cardiovascular and inflammatory parameters and biomarkers in young, healthy subjects. Representative sample of permanent residents of two cities differing in air and noise pollution levels, aged 15-21 years, were recruited. Krakow and Lublin, both located in southern Poland, were chosen in relation to their similarities in demographic and geopolitical characteristics, but differences in air pollution (higher in Krakow) and noise parameters (higher in Lublin). A total of 576 subjects were studied: 292 in Krakow and 284 in Lublin. All subjects underwent health questionnaire, blood pressure measurements and biomarker determinations. Inflammatory biomarkers, such as CRP, hs-CRP, fibrinogen as well as homocysteine were all significantly higher in subjects living in Krakow as opposed to subjects living in Lublin (for hsCRP: 0.52 (0.32-0.98) mg/l vs. 0.35 (0.22-0.67) mg/l; p < 0.001). Increased inflammatory biomarker levels were observed in Krakow in both male and female young adults. Interestingly, significant differences were observed in blood pressure between male and female subjects. Males from Krakow had significantly higher mean systolic blood pressure (127.7 ± 10.4 mm/Hg vs. 122.4 ± 13.0 mm/Hg; p = 0.001), pulse pressure (58.7 ± 8.9 mm/Hg vs. 51.4 ± 12.3 mm/Hg; p < 0.001) and lower heart rate (p < 0.001) as compared to males living in Lublin. This was not observed in young adult females. Long-term exposure to environmental factors related to the place of residence can significantly influence inflammatory and cardiovascular parameters, even in young individuals. Interestingly, among otherwise healthy young adults, blood pressure differences exhibited significant variations based on biological sex.

Cardiac microRNAs: diagnostic and therapeutic potential.

MicroRNAs are small non-coding post-translational biomolecules which, when expressed, modify their target genes. It is estimated that microRNAs regulate production of approximately 60% of all human proteins and enzymes that are responsible for major physiological processes. In cardiovascular disease pathophysiology, there are several cells that produce microRNAs, including endothelial cells, vascular smooth muscle cells, macrophages, platelets, and cardiomyocytes. There is a constant crosstalk between microRNAs derived from various cell sources. Atherosclerosis initiation and progression are driven by many pro-inflammatory and pro-thrombotic microRNAs. Atherosclerotic plaque rupture is the leading cause of cardiovascular death resulting from acute coronary syndrome (ACS) and leads to cardiac remodeling and fibrosis following ACS. MicroRNAs are powerful modulators of plaque progression and transformation into a vulnerable state, which can eventually lead to plaque rupture. There is a growing body of evidence which demonstrates that following ACS, microRNAs might inhibit fibroblast proliferation and scarring, as well as harmful apoptosis of cardiomyocytes, and stimulate fibroblast reprogramming into induced cardiac progenitor cells. In this review, we focus on the role of cardiomyocyte-derived and cardiac fibroblast-derived microRNAs that are involved in the regulation of genes associated with cardiomyocyte and fibroblast function and in atherosclerosis-related cardiac ischemia. Understanding their mechanisms may lead to the development of microRNA cocktails that can potentially be used in regenerative cardiology.

Clinical Characteristics and Outcomes of Aortic Arch Emergencies: Takayasu Disease, Fibromuscular Dysplasia, and Aortic Arch Pathologies: A Retrospective Study and Review of the Literature.

Non-atherosclerotic aortic arch pathologies (NA-AAPs) and anatomical variants are characterized as rare cardiovascular diseases with a low incidence rate, below 1 case per 2000 population, but enormous heterogeneity in terms of anatomical variants, i.e., Takayasu disease (TAK) and fibromuscular dysplasia (FMD). In specific clinical scenarios, NA-AAPs constitute life-threatening disorders. METHODS: In this study, 82 (1.07%) consecutive patients with NA-AAPs (including 38 TAKs, 26 FMDs, and 18 other AAPs) out of 7645 patients who underwent endovascular treatment (EVT) for the aortic arch and its side-branch diseases at a single institution between 2002 and 2022 were retrospectively reviewed. The recorded demographic, biochemical, diagnostic, operative, and postoperative factors were reviewed, and the functional outcomes were determined during follow-up. A systematic review of the literature was also performed. RESULTS: The study group comprised 65 (79.3%) female and 17 (21.7%) male subjects with a mean age of 46.1 ± 14.9 years. Overall, 62 (75.6%) patients were diagnosed with either cerebral ischemia symptoms or aortic arch dissection on admission. The EVT was feasible in 59 (72%) patients, whereas 23 (28%) patients were referred for medical treatment. In EVT patients, severe periprocedural complications occurred in two (3.39%) patients, including one periprocedural death and one cerebral hyperperfusion syndrome. During a median follow-up period of 64 months, cardiovascular events occurred in 24 (29.6%) patients (5 deaths, 13 ISs, and 6 myocardial infarctions). Repeated EVT for the index lesion was performed in 21/59 (35.6%) patients, including 19/33 (57.6%) in TAK and 2/13 (15.4%) in FMD. In the AAP group, one patient required additional stent-graft implantation for progressing dissection to the iliac arteries at 12 months. A baseline white blood count (odds ratio [HR]: 1.25, 95% confidence interval [CI]: 1.11-1.39; p < 0.001) was the only independent prognostic factor for recurrent stenosis, while a baseline hemoglobin level (HR: 0.73, 95%CI: 0.59-0.89; p = 0.002) and coronary involvement (HR: 4.11, 95%CI: 1.74-9.71; p = 0.001) were independently associated with a risk of major cardiac and cerebral events according to the multivariate Cox proportional hazards regression analysis. CONCLUSIONS: This study showed that AAPs should not be neglected in clinical settings, as it can be a life-threatening condition requiring a multidisciplinary approach. The knowledge of prognostic risk factors for adverse outcomes may improve surveillance in this group of patients.

microRNAs Associated with Carotid Plaque Development and Vulnerability: The Clinician's Perspective.

Ischemic stroke (IS) related to atherosclerosis of large arteries is one of the leading causes of mortality and disability in developed countries. Atherosclerotic internal carotid artery stenosis (ICAS) contributes to 20% of all cerebral ischemia cases. Nowadays, atherosclerosis prevention and treatment measures aim at controlling the atherosclerosis risk factors, or at the interventional (surgical or endovascular) management of mature occlusive lesions. There is a definite lack of the established circulating biomarkers which, once modulated, could prevent development of atherosclerosis, and consequently prevent the carotid-artery-related IS. Recent studies emphasize that microRNA (miRNA) are the emerging particles that could potentially play a pivotal role in this approach. There are some research studies on the association between the expression of small non-coding microRNAs with a carotid plaque development and vulnerability. However, the data remain inconsistent. In addition, all major studies on carotid atherosclerotic plaque were conducted on cell culture or animal models; very few were conducted on humans, whereas the accumulating evidence demonstrates that it cannot be automatically extrapolated to processes in humans. Therefore, this paper aims to review the current knowledge on how miRNA participate in the process of carotid plaque formation and rupture, as well as stroke occurrence. We discuss potential target miRNA that could be used as a prognostic or therapeutic tool.

Clinical Application of Serum microRNAs in Atherosclerotic Coronary Artery Disease.

MicroRNAs (miRs) are promising diagnostic, prognostic and therapeutic biomolecules for atherosclerotic cardiovascular disease. Atherosclerotic occlusive disease concerns a large population of patients, carrying the highest incidence of fatal and non-fatal adverse events, such as myocardial infarction, ischemic stroke, and limb ischemia, worldwide. Consistently, miRs are involved in regulation and pathogenesis of atherosclerotic coronary artery disease (CAD), acute coronary syndromes (ACS), both with ST-segment (STEMI) and non-ST segment elevation myocardial infarctions (NSTEMI), as well as cardiac remodeling and fibrosis following ACS. However, the genetic and molecular mechanisms underlying adverse outcomes in CAD are multifactorial, and sometimes difficult to interpret for clinicians. Therefore, in the present review paper we have focused on the clinical meaning and the interpretation of various miRs findings, and their potential application in routine clinical practice.

Serum and Vascular Stiffness Biomarkers Associated with the Severity of Degenerative Aortic Valve Stenosis and Cardiovascular Outcomes.

Background: Although degenerative aortic valve stenosis (DAS) is the most prevalent growth-up congestive heart valve disease, still little known about relationships between DAS severity, vascular stiffness (VS), echocardiographic parameters, and serum biomarkers in patients undergoing transcatheter (TAVR) or surgical aortic valve replacement (SAVR). The objective of this study was to identify biomarkers associated with DAS severity, and those that are associated with cardiovascular death (CVD) and episodes of chronic heart failure (CHF) exacerbation. Methods: A total of 137 patients with initially moderate-to-severe DAS were prospectively evaluated for the relationship between DAS severity, baseline VS, and serum biomarkers (uPAR, GDF-15, Gal-3, IL-6Rα, ET-1, PCSK9, RANTES/CCL5, NT-proBNP, and hs-TnT), and were followed-up for 48 months. The prognostic significance of each variable for CVD and CHF risk was measured by hazard ratio of risk (HR), which was calculated by Cox's proportional hazard model. Results: DAS severity showed correlations with IL-6Rα (r = 0.306, p < 0.001), uPAR (r = 0.184, p = 0.032), and NT-proBNP (r = −0.389, p < 0.001). Levels of ET-1 and Gal-3 were strongly correlated with VS parameters (r = 0.674, p < 0.001; r = 0.724, p < 0.001). Out of 137 patients, 20 were referred to TAVR, 88 to SAVR, and 29 to OMT. In TAVR patients, the highest levels of ET-1, Gal-3, and VS were found as compared to other patients. The highest incidence of CVD was observed in patients who underwent TAVR (35%), compared to SAVR (8%) and OMT (10.3%) (p = 0.004). In a multivariate analysis, ET-1 occurred predictive of CVD risk (HR 25.1, p = 0.047), while Gal-3 > 11.5 ng/mL increased the risk of CHF exacerbation episodes requiring hospital admission by 12%. Conclusions: Our study indicated that ET-1 and Gal-3 levels may be associated with the outcomes in patients with DAS.

The Maintained Glycemic Target Goal and Renal Function Are Associated with Cardiovascular and Renal Outcomes in Diabetic Patients Following Stent-Supported Angioplasty for Renovascular Atherosclerotic Disease.

Patients with type 2 diabetes mellitus (T2DM) constitute a large proportion of patients with atherosclerotic renal artery stenosis (ARAS). However, the mechanism of impaired renal function and hypertension in this subset of patients is multifactorial. We aimed to investigate whether, in diabetic patients, renal function (RF), systolic (SBP) and diastolic blood pressure (DBP) values following stent-supported angioplasty (PTA) for ARAS have an impact on cardiovascular and renal outcomes. Methods: The study group included 93 patients with T2DM and resistant hypertension who underwent PTA for ARAS. The pre- and post-procedure (6 to 12, and 24 months) values of SBP, DBP, eGFR and glycaemia were obtained. The prospective follow-up of median 44 months was performed for combined outcome: major cardiac and cerebral events (MACCE) and progression to renal replacement therapy (RRT). Results: MACCE-RRT occurred in 46 (49.5%) patients, with higher incidence in patients with higher values of SBP (147.8 ± 25.8 vs. 136.7 ± 15.8 mmHg, p = 0.006), DBP (80.8 ± 13.3 vs. 74.4 ± 12.3 mmHg, p = 0.009), chronic kidney disease in stages 3B to 5 (p = 0.029) and those who have not obtained target glycemic goals compared to well-maintained T2DM (p = 0.007) at 24-months. On multivariate Cox analysis, well-maintained T2DM targets [Hazard Ratio (HR):0.27; 95% Confidence Interval (CI):0.13−0.57; p < 0.001], eGFR below 45 mL/min/m2 (HR: 2.20; 95%CI: 1.20−4.04; p = 0.011), previous stroke (HR:2.52; 95%CI:1.19−5.34; p = 0.015) retained their associations with MACCE-RRT, while BP values were not associated with the outcome. Conclusions: The post-procedural RF, maintained glycemic target goal and previous stroke are vital for the outcome in patients undergoing PTA for renovascular disease in diabetic patients.

MicroRNA-134-5p and the Extent of Arterial Occlusive Disease Are Associated with Risk of Future Adverse Cardiac and Cerebral Events in Diabetic Patients Undergoing Carotid Artery Stenting for Symptomatic Carotid Artery Disease.

There is little known about the prognostic value of serum microRNAs (miRs) in diabetic patients with symptomatic internal carotid artery disease (ICAS) who underwent stent supported angioplasty (PTA) for ICAS. The present study aimed to investigate expression levels of selected miRs for future major adverse cardiac and cerebral events (MACCE) as a marker in diabetic patients following ICAS-PTA. The expression levels of 11 chosen circulating serum miRs were compared in 37 diabetic patients with symptomatic ICAS and 64 control group patients with symptomatic ICAS, but free of diabetes. The prospective median follow-up of 84 months was performed for cardiovascular outcomes. Diabetic patients, as compared to control subjects, did not differ with respect to age (p = 0.159), distribution of gender (p = 0.375), hypertension (p = 0.872), hyperlipidemia (p = 0.203), smoking (p = 0.115), coronary heart disease (p = 0.182), lower extremities arterial disease (LEAD, p = 0.731), and miRs expressions except from lower miR-16-5p (p < 0.001). During the follow-up period, MACCE occurred in 16 (43.2%) diabetic and 26 (40.6%) non-diabetic patients (p = 0.624). On multivariate Cox analysis, hazard ratio (HR) and 95% Confidence Intervals (95%CI) for diabetic patients associated with MACCE were miR-134-5p (1.12; 1.05−1.21, p < 0.001), miR-499-5p (0.16; 0.02−1.32, p = 0.089), hs-CRP (1.14; 1.02−1.28; p = 0.022), prior myocardial infarction (8.56, 1.91−38.3, p = 0.004), LEAD (11.9; 2.99−47.9, p = 0.005), and RAS (20.2; 2.4−167.5, p = 0.005), while in non-diabetic subjects, only miR-16-5p (1.0006; 1.0001−1.0012, p = 0.016), miR-208b-3p (2.82; 0.91−8.71, p = 0.071), and hypertension (0.27, 0.08−0.95, p = 0.042) were associated with MACCE. Our study demonstrated that different circulating miRs may be prognostic for MACCE in diabetic versus non-diabetic patients with symptomatic ICAS. Higher expression levels of miR-134 were prognostic for MACCE in diabetic patients, while higher expression levels of miR-16 were prognostic in non-diabetic patients.

Association of Increased Vascular Stiffness with Cardiovascular Death and Heart Failure Episodes Following Intervention on Symptomatic Degenerative Aortic Stenosis.

BACKGROUND: The resistive (RI) and pulsatile (PI) indices are markers of vascular stiffness (VS) which are associated with outcomes in patients with cardiovascular disease. We aimed to assess whether VS might predict incidence of cardiovascular death (CVD) and heart failure (HF) episodes following intervention on degenerative aortic valve stenosis (DAS). METHODS: The distribution of increased VS (RI ≥ 0.7 and PI ≥ 1.3) from supra-aortic arteries was assessed in patients with symptomatic DAS who underwent aortic valve replacement (AVR, n = 127) or transcatheter aortic valve implantation (TAVI, n = 119). During a 3-year follow-up period (FU), incidences of composite endpoint (CVD and HF) were recorded. RESULTS: Increased VS was found in 100% of TAVI patients with adverse event vs. 88.9% event-free TAVI patients (p = 0.116), and in 93.3% of AVR patients with event vs. 70.5% event-free (p = 0.061). Kaplan-Mayer free-survival curves at 1-year and 3-year FU were 90.5% vs. 97.1 % and 78% vs. 97.1% for patients with increased vs. lower VS. (p = 0.014). In univariate Cox analysis, elevated VS (HR 7.97, p = 0.04) and age (HR 1.05, p = 0.024) were associated with risk of adverse outcomes; however, both failed in Cox multivariable analysis. CONCLUSIONS: Vascular stiffness is associated with outcome after DAS intervention. However, it cannot be used as an independent outcome predictor.

Compound motor action potentials in transient and persistent phrenic nerve injury - metanalysis.

BACKGROUND: The right phrenic nerve is vulnerable to injury (PNI) during cryoballoon ablation (CBA) isolation of the right pulmonary veins. The complication can be transient or persistent. The reported incidence of PNI fluctuates from 4.73% to 24.7% depending on changes over time, CBA generation, and selected protective methods. M e t h o d s: Through September 2019, a database search was performed on MEDLINE, EMBASE, and Cochrane Database. In the selected articles, the references were also extensively searched. The study provides a comprehensive meta-analysis of the overall prevalence of PNI, assesses the transient to persistent PNI ratio, the outcome of using compound motor action potentials (CMAP), and estimated average time to nerve recovery. R e s u l t s: From 2008 to 2019, 10,341 records from 48 trials were included. Out of 783 PNI retrieved from the studies, 589 (5.7%) and 194 (1.9%) were persistent. CMAP caused a significant reduction in the risk of persistent PNI from 2.3% to 1.1% (p = 0.05; odds ratio [OR] 2.13) in all CBA groups. The mean time to PNI recovery extended beyond the hospital discharge was significantly shorter in CMAP group at three months on average versus non CMAP at six months (p = 0.012). CMAP (in contrast to non-CMAP procedures) detects PNI earlier from 4 to 16 sec (p <0.05; I2 = 74.53%) and 3 to 9o (p <0.05; I2 = 97.24%) earlier. C o n c l u s i o n s: Right PNI extending beyond hospitalization is a relatively rare complication. CMAP use causes a significant decrease in the risk of prolonged injury and shortens the time to recovery.

Expression of miR-1-3p, miR-16-5p and miR-122-5p as Possible Risk Factors of Secondary Cardiovascular Events.

Ischemic event in one arterial territory increases the risk of a subsequent ischemic event. Circulating microRNAs (miRs) emerge as a potential clinical tool to assess risk of subsequent atherothrombotic events such as cardiovascular death (CVD), myocardial infarction (MI) and ischemic stroke (IS). In this prospective study, we searched for athero-specific miRs related to cardiovascular event risk in patients with symptomatic coronary, carotid lesion, or both territories involvements. The choice of particular miRs was based on database research (Pub-Med, Bethesda, MD, USA) taking into consideration the relationship with development of atherosclerosis and potential prognostic value. Levels of circulating miRs (miR-1-3p, miR-16-5p, miR-34a-5p, mir-122-5p, miR-124-3p, miR-133a-3p, miR-133b, miR-134-5p, miR-208b-3p, miR-375 and miR-499-5p) were compared in 142 patients with an acute ischemic event resulting from carotid and/or coronary artery stenosis, who underwent revascularization for symptomatic lesion. A 6-year prospective evaluation of CVD/MI/IS risk was performed. Patients with two-territory as compared to single-territory involvement differed in levels of miR-1-3p (p = 0.016), miR-16-5p (p < 0.001), miR-34a-5p (p = 0.018), miR-122-5p (p = 0.007), miR-124-3p (p < 0.001) and miR-499-5p (p < 0.001). During follow-up, 62 (43.7%) episodes of CVD/MI/IS occurred. In multivariate Cox analysis, miR-122-5p (HR = 1.0006, 95%CI = 1.0001-1.0011) and peripheral artery disease (PAD) (HR = 2.16, 95%CI = 1.26-3.70) were associated with CVD/MI/IS risk; miR-1-3p (HR = 2.73, 95%CI = 1.22-6.12) and PAD (HR = 3.47, 95%CI = 1.88-6.41) with CVD; miR-122-5p (HR = 1.0001, 95%CI = 1.000-1.0002) and creatinine level (HR = 1.02, 95%CI = 1.01-1.04) with IS, and miR-16-5p (HR = 1.0004, 95%CI = 1.0001-1.0008) with MI. Expression of miR-1-3p, miR-16-5p and miR-122-5p during incident ischemia may be possible risk factors of secondary cardiovascular event(s).

Importance of Increased Arterial Resistance in Risk Prediction in Patients with Cardiovascular Risk Factors and Degenerative Aortic Stenosis.

BACKGROUND: Cardiovascular disease is a leading cause of heart failure (HF) and major adverse cardiac and cerebral events (MACCE). OBJECTIVE: To evaluate impact of vascular resistance on HF and MACCE incidence in subjects with cardiovascular risk factors (CRF) and degenerative aortic valve stenosis (DAS). METHODS: From January 2016 to December 2018, in 404 patients with cardiovascular disease, including 267 patients with moderate-to-severe DAS and 137 patients with CRF, mean values of resistive index (RI) and pulsatile index (PI) were obtained from carotid and vertebral arteries. Patients were followed-up for 2.5 years, for primary outcome of HF and MACCE episodes. RESULTS: RI and PI values in patients with DAS compared to CRF were significantly higher, with optimal cut-offs discriminating arterial resistance of ≥0.7 for RI (sensitivity: 80.5%, specificity: 78.8%) and ≥1.3 for PI (sensitivity: 81.3%, specificity: 79.6%). Age, female gender, diabetes, and DAS were all independently associated with increased resistance. During the follow-up period, 68 (16.8%) episodes of HF-MACCE occurred. High RI (odds ratio 1.25, 95% CI 1.13-1.37) and PI (odds ratio 1.21, 95% CI 1.10-1.34) were associated with risk of HF-MACCE. CONCLUSIONS: An accurate assessment of vascular resistance may be used for HF-MACCE risk stratification in patients with DAS.

Assessment of the Willis circle flow changes and the severity of degenerative aortic stenosis and cognitive impairment.

BACKGROUND: Degenerative aortic stenosis (DAS) and cognitive function deterioration frequently coexist in elderly patients, which affects the prognosis. AIMS: We aimed to evaluate the Willis circle intracranial blood flow parameters and cognitive status in patients with DAS. METHODS: Ultrasonography of the Willis circle and the assessment of cerebral blood flow (CBF) volume, acceleration time (AT), pulsatile and resistive indexes (PI, RI), as well as cognition tests (Mini­Mental Status Examination [MMSE] and Montreal Cognitive Assessment [MoCA]) were performed in group 1-41 patients with severe DAS (aortic valve area indexed to the body surface area [AVAi] <0.5 cm2/m2) and group 2-41 patients with moderate DAS (AVAi [range], 0.51-0.99 cm2/m2). The control group comprised 52 patients without DAS. RESULTS: Compared with controls, mean (SD) CBF volume ingroups 1 and 2 was lower (1.37 [0.32] l/min vs 1.5 [0.44] l/min vs 1.71 [0.21] l/min, respectively; P <0.001), while AT (212 [20] ms vs 161 [33] ms vs 86 [21] ms, respectively; P <0.001), RI (0.64 [0.07] vs 0.65 [0.06] vs 0.59 [0.05], respectively; P <0.001), and PI (1.13 [0.21] vs 1.16 [0.17] vs 0.99 [0.12]; P <0.001) were higher. Both MMSE and MoCA scores did not differ according to CBF, RI, PI, and AT. In multivariable regression analysis, age, renal failure, left ventricular ejection fraction, and diabetes, yet not CBF parameters, were independently associated with cognitive function. CONCLUSIONS: Patients with DAS had significantly reduced CBF volume and increased arterial stiffness. However, cognitive impairment may be attributed to concomitant comorbidities rather than CBF parameters.

Simple clinical scores to predict blood pressure and renal function response to renal artery stenting for atherosclerotic renal artery stenosis.

INTRODUCTION: There are no systematic tools to predict blood pressure (BP) or renal function (RF) improvement after stent­assisted percutaneous transluminal angioplasty (PTA) for atherosclerotic renal artery stenosis (ARAS). OBJECTIVE: This study aimed to develop simple, clinically applicable scores based on preprocedural clinical and renal ultrasonography parameters in order to predict BP and RF improvement following ARAS­PTA. PATIENTS AND METHODS: A total of 202 patients who underwent ARAS­PTA were categorized as RF responders (eGFR increase ≥11 ml/min/1.73 m2) or BP responders (systolic and diastolic BP decrease ≥20 mm Hg and ≥5 mm Hg, respectively) at 12 months following ARAS­PTA. The variables associated with the RF or BP response in univariable analysis were included in a multivariable logistic regression model. Point­based response scales were developed proportionally to odds ratios in each of the 2 models to embrace the maximum score of 10. RESULTS: The BP response to ARAS­PTA was 93.3% in the high­probability category (6-10 points), 66.7% in the medium­probability category (3-5 points), and 25.3% in the low­probability category (0-2 points), with the preprocedural variables of systolic BP ≥145 mm Hg (3 points), diastolic BP ≥83 mm Hg (4 points), PTA of a single functioning kidney (2 points), and bilateral PTA (1 point). The RF response was 77.3% in the high­probability category (8-10 points), 33% in the medium­probability category (4-7 points), and 10.9% in the low­probability category (0-3 points) for serum creatinine levels >122 µmol/l and eGFR >30 ml/min/1.73 m2 (3 points), index kidney length >98 mm (3 points), renal artery end­diastolic velocity >1.1 m/s (2 points), and arterial resistive index <0.74 (2 points). CONCLUSIONS: Models of favorable BP and RF response may improve patient selection for ARAS­PTA. Further insights are expected from prospective validation.

Long-term outcomes and determinants of stenosis recurrence after renal artery angioplasty in hypertensive patients with renovascular disease.

INTRODUCTION: Restenosis (RS) following percutaneous angioplasty (PTA) of renal artery stenosis (RAS) might have an unfavourable impact on renal function and blood pressure (BP) outcomes. AIM: To evaluate the prevalence and predictors of RS in patients treated with PTA for RAS, and the relationship between BP and renal function (RF) changes with RS. MATERIAL AND METHODS: We analysed freedom from RS in 210 patients (age 64.6 ±12.8 years; range: 20-85), who underwent 248 successful stent-assisted PTAs in RAS. The change in levels of serum creatinine (SCC), estimated glomerular filtration rate (eGFR), systolic/diastolic BPs (SBP/DBP) were analysed prior to PTA, at 6-, 12-month, and final follow-up visits, and whenever RS was diagnosed. RESULTS: RS was identified in 30 (14.3%) patients, and there were 36 (14.5%) lesions. The Kaplan-Meier RS-free survival curves in fibromuscular dysplasia, atherosclerosis, and vasculitis at 1 and 7 years were: 100% and 100%; 95.6 and 83.9%; and 71.4 and 39.7%, respectively. Patients with RS, as compared to RS-free patients, presented with less pronounced changes in respect with: SBP (1.4 ±17.6 vs. -15.8 ±25.8 mm Hg; p = 0.01), DBP (2.64 ±10.1 vs. -6.5 ±14.1 mm Hg; p = 0.002), SCC (22.4 ±55.2 vs. -3.6 ±43.9 µmol/l; p = 0.002), and eGFR (-1.85 ±18 vs. -5.34 ±19.5 mm Hg; p = 0.045). In multivariate Cox regression analysis, independent predictors of RS occurred: lack of BP decrease (HR = 4.19, 95% CI: 1.67-10.3; p = 0.002), eGFR increase < 0.17 ml/min/1.73 m2 (HR = 2.93, 95% CI: 1.08-7.91; p = 0.033), stent diameter ≤ 5 mm (HR = 2.76, 95% CI: 1.09-6.97; p = 0.031), and vasculitis (HR = 5.61, 95% CI: 1.83-17.2; p = 0.003). RS was treated in 24 patients with RS recurrence in 20%. CONCLUSIONS: The RS rate differs depending on RAS aetiology. Lack of SBP/DBP and eGFR improvement, vasculitis, and stent diameter are associated with RS risk. Repeated PTA is effective, but recurrent RS occurs in 20% of cases.

Determinants of long-term outcome in patients after percutaneous stent-assisted intervention for renal artery steno-occlusive atherosclerotic disease.

INTRODUCTION: The effect of stent­assisted percutaneous transluminal angioplasty (PTA) for renal artery stenosis (RAS) on systolic (SBP) and diastolic blood pressure (DBP) as well as renal function, in comparison with medical therapy, is still debatable. Data on determinants of cardiovascular (CV) outcome after PTA are lacking. OBJECTIVES: We aimed to identify determinants of major cardiac and cerebral events (MACCEs) following PTA for RAS. PATIENTS AND METHODS: A total of 248 PTAs for RAS were performed in 211 patients with difficult­to­treat hypertension and/or progressive renal impairment. The primary outcomes were procedural success, in­hospital complications, renal function (estimated glomerular filtration rate [eGFR]), change in SBP or DBP, and an incidence of MACCEs during a median of 47 months (interquartile range [IQR], 18-78 months). RESULTS: Procedural success and complication rates were 99.2% and 4.7%, respectively. We observed significant differences in SBP, DBP, and eGFR at 12 months as compared with baseline. A total of 63 MACCEs (30.6%) were noted in 206 patients with available follow­up data. The receiver operating characteristic curve analysis indicated the following best cutoff values for the risk of CV death: an increase in eGFR by at least 11 ml/min/1.73 m2 and a decrease in SBP and DBP by at least 20 mm Hg and 5 mm Hg, respectively. At 12­month follow­up, an increase in eGFR of at least 11 ml/min/1.73 m2 was independently associated with a reduced risk of death (hazard ratio [HR], 0.42; 95% CI, 0.19-0.90; P = 0.02) and MACCEs (HR, 0.54; 95% CI, 0.32-0.93; P = 0.03), while a decrease of DBP by 5 mm Hg or higher, with a reduced risk of stroke (HR, 0.1; 95% CI, 0.02-0.39; P = 0.001). CONCLUSIONS: This study confirms the efficacy and safety of PTA as well as its significant effect on changes in blood pressure and eGFR values. Patients with an increase in eGFR of at least 11 ml/min/1.73 m2 have a significant risk reduction of MACCEs and CV death, while those with a decrease in DBP of at least 5 mm Hg, of stroke.

The role of serial carotid intima-media thickness assessment as a surrogate marker of atherosclerosis control in patients with recent myocardial infarction.

INTRODUCTION: Despite percutaneous coronary intervention (PCI), patients after their first myocardial infarction (MI) are at high risk of ischemic event recurrence. Therefore, there is a need for objective markers of adequate atherosclerosis control, independent of prescribed pharmacotherapy and patients' compliance. Such a potential indicator of major adverse cerebral and coronary event (MACCE) risk might be change in carotid intima-media thickness (CIMT), which indicates atherosclerosis growth. AIM: To evaluate the potential associations between CIMT changes and the incidence of MACCE and recurrent MI. MATERIAL AND METHODS: The CIMT assessments at baseline and during 2 follow-up visits were performed in 215 patients admitted with MI, in whom PCI was performed for an index lesion, followed by best medical treatment. The incidences of MACCE (cardiovascular death, recurrent MI, ischemic stroke) and new onset angina were recorded prospectively. RESULTS: The MACCE were recorded in 65 (30.2%) patients and angina due to coronary lesion progression (CLP) in 27 (12.5%) patients. Although initial CIMT values were similar in patients who suffered MACCE vs. MACCE-free patients (1.43 ±0.40 vs. 1.45 ±0.44 mm; p = 0.486), patients in whom MACCE occurred had greater annual CIMT growth as assessed at the first (0.024 ±0.12 vs. 0.009 ±0.16 mm/year; p < 0.001) and subsequent follow-up visit (0.050 ±0.1 vs. 0.001 ±0.1 mm/year; p < 0.001), in mean 36.5 ±29.3 and 53.3 ±37.1 months, respectively. An optimal cut-off value for annual CIMT change of > 0.003 mm/year (sensitivity: 84.5%, specificity: 49.3%) for MI plus CLP (AUC = 0.673) occurred an independent indicator of MACCE (HR = 3.00; 95% CI: 1.496-6.016), recurrent MI (HR = 4.59, 95% CI: 1.591-13.217), and MI plus CLP (HR = 3.50, 95% CI: 1.759-6.964). CONCLUSIONS: Annual CIMT change might be a potentially valuable marker of atherosclerosis response to post-MI treatment.

Chemokine RANTES and IL-1ß in mild therapeutic hypothermia-treated patients after out-of-hospital sudden cardiac arrest.

INTRODUCTION: CCL5/RANTES and IL-1ß, which regulate the immune response, may have an impact on survival in patients with acute coronary syndrome (ACS) and sudden cardiac arrest (SCA). AIM: To evaluate levels of CCL5/RANTES and IL-1ß in patients with ACS complicated by SCA, treated with coronary angioplasty (PCI) and mild therapeutic hypothermia (MTH), and these chemokines' impact on the 30- and 180-day survival. MATERIAL AND METHODS: Thirty-three unconscious patients admitted after SCA with ACS underwent PCI and MTH treatment. CCL5/RANTES and IL-1ß were evaluated on admission (T0), at 12-24 h (T1) and at 48-72 h (T2). All-cause mortality was recorded at 30 and 180 days. RESULTS: We observed a statistically significant decrease in median levels of CCL/RANTES at T0, T1 and T2 (24.69 ng/ml vs. 3.89 ng/ml vs. 2.71 ng/ml; p < 0.001), and significant differences in median levels of IL-1ß (0.196 pg/ml vs. 0.171 pg/ml vs. 0.214 pg/ml; p = 0.034). Initial levels of CCL5/RANTES and IL-1ß correlated significantly (r = -0.360; p = 0.045). At T2, CCL5/RANTES correlated with the maximum levels of hs-TnT and CK-MB (r = -0.594; p < 0.001 and r = -0.389; p = 0.030), and at T0 with BNP (r = -0.521; p = 0.003). Mortality rate at 30 days and 180 days was 18.2% and 45.5%, respectively. At 30 days, we observed a trend to significance for IL-1ß at T0 and T1 (p = 0.078 and p = 0.079), but not for CCL5/RANTES (p = 0.284 and p = 0.351). For 180-day survival curves, only the IL-1ß level at T1 was associated with mortality (p = 0.028). CONCLUSIONS: Although CCL5/RANTES levels correlate with cardiac injury and heart failure markers and they decrease during MTH, they failed to predict early and late mortality. In contrast, IL-1ß level was associated with 180-day survival.