Blood Pressure-Lowering Effect of Newer Antihyperglycemic Agents (SGLT-2 Inhibitors, GLP-1 Receptor Agonists, and DPP-4 Inhibitors).

The prevalence of arterial hypertension is high in patients with diabetes mellitus (DM). When DM and hypertension coexist, they constitute a dual cardiovascular threat and should be adequately controlled. Novel antihyperglycemic agents, including sodium-glucose co-transporter 2 (SGLT-2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and dipeptidyl peptidase-4 (DPP-4) inhibitors, have recently been used in the treatment of DM. Beyond their glucose-lowering effects, these drugs have shown beneficial pleiotropic cardiovascular effects, including lowering of arterial blood pressure (BP), as acknowledged in the 2019 European Society of Cardiology/European Association for the Study of Diabetes guidelines on diabetes, prediabetes, and cardiovascular diseases. The purpose of this review was to summarize the available information on the BP-reducing effects of these new glucose-lowering drug classes and provide a brief report on underlying pathophysiological mechanisms. We also compare the three drug classes (SGLT-2 inhibitors, GLP-1 RAs, and DPP-4 inhibitors) in terms of their BP-lowering effect and show that the greater BP reduction seems to be achieved with SGLT-2 inhibitors, whereas DPP-4 inhibitors have probably the mildest antihypertensive effect.

Sodium Glucose Cotransporter 2 (SGLT2) Inhibitors Across the Spectrum of Hypertension.

Sodium glucose cotransporter 2 (SGLT2) inhibitors represent a novel class of oral antihyperglycemic drugs that have been approved over the last decade for the management of type 2 diabetes mellitus. Except the glucose-lowering effects, robust evidence also suggests that SGLT2 inhibitors confer benefits in cardiovascular system. The purpose of this review was to investigate the effects of SGLT2 inhibitors across the spectrum of arterial hypertension.

The impact of financial crisis on coronary artery disease burden in Greece.

BACKGROUND: Economic crisis poses an immense threat to public health worldwide and has been linked to cardiovascular morbidity and mortality. Greece is facing a distinctive recession over the recent years. However, the exact impact on coronary artery disease (CAD) burden has not been adequately addressed. METHODS: Demographic, clinical, and angiographic data of 3895 hospitalized patients were retrospectively studied. Patients were classified into two groups: those before crisis (2006-2007, n = 1228) and those during crisis (2011-2015, n = 2667). RESULTS: All data before and during crisis were compared. During crisis, patients presented with less acute coronary syndrome (ACS - 45.5% vs. 39.9%, p < 0.001). Subsequently, there were more patients without CAD (23.7% vs. 35.1%, p < 0.001) or one-vessel disease (20.5% vs. 23%, p < 0.001). The prevalence of traditional risk factors decreased significantly or remained stable except obesity (26.3% vs. 31.4%, p = 0.002). A significant increase in the examined females (23.6% vs. 26.7%, p = 0.04) was also observed. CONCLUSIONS: The burden of CAD in Greece was partially affected during the financial crisis. Even though the incidence of ACS was decreased, more women and more patients with no- or single-vessel disease were referred for cardiac catheterization. In addition, the prevalence of traditional risk factors for CAD did not increase except obesity confirming the "obesity paradox." It seems that the impact of traditional risk factors for CAD is not an immediate process and is somewhat related to living conditions or other exogenous and social factors.

Computational imaging of aortic vasa vasorum and neovascularization in rabbits using contrast-enhanced intravascular ultrasound: Association with histological analysis.

OBJECTIVE: Neoangiogenesis is pathophysiologically related to atherosclerotic plaque growth and vulnerability. We examined the in vivo performance of a computational method using contrast-enhanced intravascular ultrasound (CE-IVUS) to detect and quantify aortic wall neovascularization in rabbits. We also compared these findings with histological data. METHODS: Nine rabbits were fed with a hyperlipidemic diet. IVUS image sequences were continuously recorded before and after the injection of a contrast agent. Mean enhancement of intensity of a region of interest (MEIR) was calculated using differential imaging algorithm. The percent difference of MEIR before and after the injection of microbubbles (d_MEIR) was used as an index of the density of plaque or/and adventitial neovascularization. Aortic segments were excised for histological analysis. RESULTS: CE-IVUS and histological analysis were performed in 11 arterial segments. MEIR was significantly increased (~20%) after microbubble injection (from 8.1±0.9 to 9.7±1.8, p=0.016). Segments with increased VV/neovessels in the tunica adventitia (histological scores 2 and 3) had significantly higher d_MEIR compared with segments with low presence of VV/neovessels (score 1); 40.5±22.9 vs. 8±14.6, p=0.024, respectively. CONCLUSION: It is possible to detect VV or neovessels in vivo using computational analysis of CE-IVUS images, which is in agreement with histological data. These findings may have critical implications on vulnerable plaque assessment and risk stratification.

Renal Fibromuscular Dysplasia: A Not So Common Entity of Secondary Hypertension.

Fibromuscular dysplasia is a rare noninflammatory vascular disease characterized by nonatheroslerotic stenosis predominantly seen in young women, whereas the majority of cases involve the renal arteries causing secondary hypertension. Most noninvasive screening tests are not quite sensitive or reproducible to rule out renal artery stenosis, but renal angiography usually confirms the diagnosis. Percutaneous renal artery angioplasty is the treatment of choice; however, it may not result in normalization of blood pressure if diagnosis is delayed. Continued follow-up is necessary since stenosis reoccurs.

Impact of atherosclerotic plaque components and their distribution on stent deployment: an intravascular-ultrasound virtual histology observational study.

BACKGROUND: The aim of this study was to evaluate how the spatial distribution of each plaque element, defined by intravascular-ultrasound virtual histology (IVUS-VH), may affect stent deployment even at high inflation pressures. METHODS: Thirty-two patients undergoing direct percutaneous coronary intervention and IVUS were evaluated. Fifty-two lesions were treated with drug-eluting stents. Pre-stenting lumen area and real (Rcssla) and average cross-sectional stent lumen area (Acssla) were measured along the whole lesion. Ideal cross-sectional stent lumen area (Icssla) was calculated. Plaque composition was characterized by IVUS-VH. The spatial distribution of each plaque element was quantified by a novel image analysis tool measuring the area and percentage of each plaque component that was adjacent to the lumen. Average stent deployment was defined as: [1 - (Icssla-Acssla)/Icssla]×100%. RESULTS: Stent expansion was significantly less at the site of maximum calcification compared to the average stent deployment (80±9% vs. 85±13%, P=0.044, respectively). Furthermore, wherever calcium was adjacent to the lumen, stent expansion was impaired compared to sites where calcium was non-luminal (70±23% vs. 80±9%, P=0.01, respectively). In contrast, at the site of maximum necrotic core, stent deployment showed a trend to be less compromised, compared to the average stent deployment. CONCLUSIONS: An interaction was found between plaque components and their distribution and stent deployment even at high inflation pressures.

Apelin and Visfatin Plasma Levels in Healthy Individuals With High Normal Blood Pressure.

BACKGROUND: High normal blood pressure (BP; 130-139/85-89 mm Hg) is related with increased cardiovascular (CV) risk compared to normal BP (120-129/80-84 mm Hg) or/and optimal BP (<120/80 mm Hg). Low apelin plasma levels have been associated with arterial hypertension and atherosclerosis, while high visfatin plasma levels may promote vascular inflammation and atherosclerotic plaque destabilization and have been evaluated as a marker for identifying stages of essential hypertension. We sought to compare the apelin and visfatin plasma levels between subjects with high normal BP and subjects with normal or optimal BP matched for age, gender, smoking, and body mass index (BMI). METHODS: Twenty-five subjects with high normal BP (office BP 136±3/88±2 mm Hg, age 57±4 years, 76% males, 32% smokers, BMI 24.0±1.7 kg/m2) and 35 subjects with normal or optimal BP (office BP 118±2/78±2 mm Hg, age 55±7 years, 63% males, 29% smokers, BMI 23.2±1.4 kg/m2) were studied. The apelin and visfatin plasma levels were determined with the enzyme-linked immunosorbent assay. RESULTS: Compared to normal or optimal BP subjects, apelin levels were significantly lower (205±108 vs. 325±152 pg/ml, P < 0.001) and visfatin levels significantly higher (11.0±2.0 vs. 7.2±0.9 ng/ml, P = 0.002) in high normal BP subjects. No significant differences were found between the 2 groups (P = NS) regarding the basic clinical characteristics, the glycemic/lipid profile, and the renal function parameters. CONCLUSIONS: The emerging, from the present study, data raise the hypothesis that lower apelin and higher visfatin plasma levels in high normal BP subjects compared to normal or optimal BP individuals could partially explain the higher CV risk of the high normal BP group.

Long-term clinical outcomes after percutaneous coronary intervention for chronic total occlusions.

Optimal treatment of chronic total occlusions (CTOs) remains one of the major challenges in interventional cardiology. A number of factors, including both patient clinical conditions and technical procedural considerations, have been identified to affect percutaneous coronary intervention (PCI) success and long-term outcomes, in large multicenter cohorts as well as smaller patient groups. As opposed to patient-centered factors, technical factors can be managed and as a result, a lot of research aims at improving stent technology and imaging guidance, toward enhancing PCI efficiency, in regards to patient safety.

D-dimer levels predict ischemic and hemorrhagic outcomes after acute myocardial infarction: a HORIZONS-AMI biomarker substudy.

D-dimer is a product of cross linked fibrin degradation and is a measure of the amount of fibrin turnover. As such, D-dimer might be of utility in the prediction of both thrombotic and hemorrhagic events. Therefore, the aim of the present study was to evaluate whether elevated D-dimer levels on admission and at discharge could predict subsequent ischemic and hemorrhagic events in patients with acute myocardial infarction (AMI). D-dimer was measured on admission and at discharge in 461 out of a total of 3,602 patients in the HORIZONS-AMI trial, as part of the formal prespecified biomarker substudy. The predictive value for major adverse cardiovascular events (MACE) and non-CABG major bleeding after 3 year follow up was investigated by stratifying patients in groups of D-dimer level and comparing event rates using Kaplan-Meier and calculating hazard ratios using Cox proportional hazards models. D-dimer levels ≥ 0.71 µg/mL on admission were associated with an adjusted hazard ratio of 2.58 for MACE (p = 0.0014) and 4.61 for major bleeding (p = 0.0018). A discharge D-dimer level ≥ 1.26 µg/mL was associated with a higher risk for MACE by univariate analysis (HR 1.88, p = 0.037), but lost its significance after multivariate adjustment (HR 1.77, p = 0.070). High D-dimer levels on admission were associated with a higher risk of MACE and non-CABG major bleeding in STEMI patients undergoing pPCI.

Outcomes in diabetic patients undergoing primary percutaneous coronary intervention for acute anterior myocardial infarction: results from the INFUSE-AMI study.

OBJECTIVES: To evaluate the clinical, angiographic, and cardiac magnetic resonance imaging (cMRI) results in patients with and without diabetes mellitus (DM) undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). BACKGROUND: DM has been associated with increased mortality in patients with STEMI, yet the mechanisms underpinning this association have not been completely elucidated. METHODS: Overall, 451 patients (51 diabetics) from the INFUSE-AMI trial were studied. They presented with an anterior STEMI due to an occluded left anterior descending artery (LAD) and underwent bivalirudin-supported primary PCI with or without intralesion abciximab and with or without thrombus aspiration. Angiographic baseline and post-procedure parameters, cMRI at 30 days, and clinical follow-up at 30 days and at 1 year were compared between diabetic and nondiabetic patients. RESULTS: Patients with DM had significantly more comorbidities and more extensive LAD disease than nondiabetics. Primary PCI was equally effective in restoring coronary flow in both groups and the infarct size at 30 days was similar (14.3% [7.1, 24.5] vs. 17.3% [8.1, 23.6], respectively, P = 0.55). Diabetic patients had more major cardiovascular and cerebrovascular events at 1 year (16.5% vs. 8.0%, P = 0.04). Stent thrombosis within 30 days after primary PCI was higher in diabetic than in nondiabetic subjects (4.3% vs. 0.8%, P = 0.03). CONCLUSIONS: Patients with DM presenting with STEMI had a higher baseline risk profile than those without DM. Although reperfusion success and infarct size were similar, diabetic patients experienced more death, reinfarction, stent thrombosis, and revascularization than nondiabetics.

Enhanced stent imaging improves the diagnosis of stent underexpansion and optimizes stent deployment.

OBJECTIVES: To investigate the clinical value and diagnostic accuracy of enhanced stent imaging (ESI) as compared with quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS). BACKGROUND: ESI is an image acquisition and processing angiography-based software that improves visualization and provides measurements of deployed stents. METHODS: A total of 40 consecutive patients (42 stents) were studied. Stent deployment was evaluated sequentially and independently by angiography, ESI, and IVUS. Following each imaging modality, the operator determined the necessity of postdilation unrelated to the other modalities. Stent diameters were measured off-line by QCA, ESI, and IVUS at several sites along the deployed stent and compared. RESULTS: Following stent deployment and based solely on angiography, the operator decided to postdilate seven of the 42 stents (16.7%). This decision was not changed after reviewing the ESI images of these seven stents. Of the 35 stents not requiring postdilation based on angiography alone, ESI influenced the operator to change the decision and postdilate 10 of 35 stents (28.6%). The ESI-based measurements had better correlation with IVUS (r = 0.721, P < 0.0001) than did QCA with IVUS (r = 0.563, P < 0.0001). Bland-Altman analysis showed a trend towards better agreement between ESI and IVUS than between QCA and IVUS (mean differences = 0.038 vs. 0.121; P = 0.19, respectively). CONCLUSIONS: ESI is an easy to use modality that enhances stent visualization, helps in the decision making process whether to postdilate the stent, and provides estimation of stent expansion with better correlations than QCA when compared to IVUS. © 2012 Wiley Periodicals, Inc.

Volumetric intravascular ultrasound assessment of mechanisms and results of stent expansion in heart transplant patients.

BACKGROUND: Percutaneous coronary intervention with stent placement for the treatment of patients with cardiac allograft vasculopathy is common, but data regarding stent behavior in this setting is lacking. OBJECTIVES: We investigated mechanisms and potential differences in stent expansion among transplant patients vs. patients with native coronary artery atherosclerotic disease ("controls"). METHODS: We compared pre- and poststent intravascular ultrasound in 12 transplant patients (17 lesions) and 33 control patients (34 lesions) matched according to age (60.1 ± 9.2 years), diabetes mellitus, and lesion location. Planar and volumetric analysis was conducted for every 1 mm at the lesion site as well as the first 5 mm proximal and distal to the stent edge. Focal stent expansion was defined as minimum stent area (MSA) divided by mean reference lumen area. Diffuse stent expansion was defined as mean stent area divided by mean reference lumen area. RESULTS: Transplant patients had more plaque than "controls" prestenting, but similar MSA and focal and diffuse stent expansion afterwards. The increase in mean lumen area correlated with the increase in mean vessel area in both groups, transplant (R = 0.64, P = 0.008) and controls (R = 0.70, P < 0.0001), but correlated inversely with changes in mean plaque area only in the transplant group (R = 0.55, P = 0.027). There were no differences in calcification between the two groups and no axial plaque distribution from the lesion into the reference segments in either group. CONCLUSIONS: The mechanism of stent expansion in transplant vasculopathy appears to be similar to de novo atherosclerosis-i.e., mainly vessel expansion to achieve similar acute results.

Relationship between biomarkers and subsequent bleeding risk in ST-segment elevation myocardial infarction patients treated with paclitaxel-eluting stents: a HORIZONS-AMI substudy.

Major bleeding complications in STEMI patients result in significant mortality, morbidity and healthcare cost. Identification of patients at increased risk of bleeding is therefore essential. New biomarkers might be of incremental value to identify patients at risk for bleeding after primary PCI. A total of 26 biomarkers were measured at enrolment and analyzed at a central core laboratory in 464 STEMI patients in the HORIZONS-AMI trial. We investigated the relationship between tertiles of biomarker and in hospital non-CABG major bleeding. In hospital non-CABG major bleeding occurred in 3.7% of patients (n = 17). Increasing levels of cystatin C and D-dimer at admission were associated with higher rates of in hospital major bleeding. After adjustment for a risk score for bleeding, the odds ratio for in hospital major bleeding was 3.13 for cystatin C > 2.04 mg/L (p = 0.046) and 3.28 for ESAM > 34 ng/mL (p = 0.037). In this exploratory analysis of the HORIZONS-AMI biomarker substudy, high cystatin C and ESAM levels were associated with a higher risk of major bleeding. Larger studies are warranted to confirm the prognostic value of cystatin C and ESAM for major bleeding in STEMI patients.

Relationship between biomarkers and subsequent clinical and angiographic restenosis after paclitaxel-eluting stents for treatment of STEMI: a HORIZONS-AMI substudy.

Drug-eluting stents (DES) reduce the incidence of in-stent restenosis (ISR) after primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). Whether the use of biomarkers might be of utility to identify patients who remain at risk for DES ISR after primary PCI has never been examined. A total of 26 biomarkers were measured at enrollment and 30 days and analyzed at a central core laboratory in 501 STEMI patients from the HORIZONS-AMI trial. All patients underwent primary PCI with the TAXUS paclitaxel-eluting stent (PES), were scheduled for routine angiographic follow-up at 13 months, and were followed for 3 years. Mean in-stent late-loss was 0.28 ± 0.57 mm, and target lesion revascularization (TLR) at 3 years occurred in 9.1 % of patients. Low levels of interleukin-6 (IL-6) and placental growth factor (PLGF) at admission were associated with both higher in-stent late loss and ischemia-driven TLR. Additionally, low admission levels of cardiotrophin-1 (CT-1) were associated with higher rates of ischemia-driven TLR. At 30-day follow-up lower values of IL-1ra (IL-1ra), matrix metalloproteinase 9 (MMP9), and myeloperoxidase (MPO), and a decline relative to admission in IL-1ra, monocyte chemotactic protein-1 (MCP-1), and MMP9 were associated with higher in-stent late loss. Low values of IL-6 at 30 days were also associated with ischemia-driven TLR. After multivariate adjustment, only MPO at 30 days and a decline of MCP-1 between admission and 30 days were associated with in-stent late loss, and only CT-1 was associated with TLR. MPO at 30 days and a decline of MCP-1 between admission and 30 days were independently associated with in-stent late loss, and CT-1 was associated with TLR. Additional studies to confirm and validate the utility of these biomarkers are warranted.

Adverse cardiovascular events arising from atherosclerotic lesions with and without angiographic disease progression.

OBJECTIVES: The aim of this study was to use angiography and grayscale and intravascular ultrasound-virtual histology to assess coronary lesions that caused events during a median follow-up period of 3.4 years. BACKGROUND: Vulnerable plaque-related events are assumed to be the result of substantial progression of insignificant lesions. METHODS: In the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study, 697 patients with acute coronary syndromes underwent treatment of all culprit lesions followed by 3-vessel imaging to assess the natural history of culprit and untreated nonculprit (NC) lesions. Future adverse cardiovascular events adjudicated to NC lesions were divided into those with versus without substantial lesion progression (SLP) (≥ 20% angiographic diameter stenosis increase). RESULTS: NC lesion events occurred in 72 patients, 44 (61%) with and 28 (39%) without SLP. Myocardial infarctions (n = 6) occurred only in patients with SLP. Conversely, patients without SLP presented only with unstable or increasing angina requiring rehospitalization. Lesions with versus without SLP occurred later (median time to event 401 vs. 223 days, p = 0.07); were less severe at baseline (median diameter stenosis 26.4% vs. 53.8%, p < 0.0001) but more severe at the time of the event (mean diameter stenosis 73.8% vs. 56%, p < 0.0001); and had comparable baseline median plaque burden (68.7% vs. 70.1%, p = 0.17), minimum luminal area (3.7 vs. 4.0 mm(2), p = 0.60), and intravascular ultrasound-virtual histology phenotype (83.3% vs. 90.9%, p = 0.68; classified as fibroatheromas at baseline). CONCLUSIONS: NC lesions responsible for future cardiovascular events showed angiographic increase during 3.4 years of follow-up, whereas SLP underlay many but not all of them. NC events due to lesions with SLP were angiographically less severe and presented with a delayed time course but were otherwise indistinguishable from NC events that were not associated with SLP.

Endovascular treatment of infrarenal aortic stenosis: importance of multimodality imaging.

We sought to describe the evolution in imaging and interventional options for endovascular treatment of significant infrarenal aortic stenosis. Balloon angioplasty and stent implantation for infrarenal aortic stenosis has generally required large-sized arterial access sheaths in the past, and was typically guided by visual size assessment. Computerized tomography angiography enables accurate preprocedural assessment of severity and extent of aortic atherosclerosis, degree of calcification, and luminal dimensions at both stenosis and reference sites, and visualizes possible aneurysm. Intraprocedural pressure gradient measurements evaluate the hemodynamic response to revascularization. On the other hand, intravascular ultrasound can further verify accuracy of equipment sizing. Small-profile stents and balloons can be used via small-sized sheaths, thereby rendering the procedure possible in patients with extensive peripheral arterial disease or small iliofemoral arteries. Improved non-invasive and intravascular imaging can guide with great accuracy infrarenal aortic stenosis procedures and may enable the use of reduced-size access sheaths and devices in fragile patients with vasculopathies.