Relationship between accessory renal arteries and resistant hypertension: A cohort study.

BACKGROUND: Resistant hypertension (RHT) is a major health care concern affecting 20 to 30% of hypertensive patients and increasing cardiovascular risk. Recent renal denervation trials have suggested a high prevalence of accessory renal arteries (ARA) in RHT. Our objective was to compare the prevalence of ARA in RHT vs. non-resistant hypertension (NRHT). METHODS: Eighty-six patients with essential hypertension who benefited from an abdominal CT-scan or MRI during their initial workup were retrospectively recruited in 6 French ESH (European Society of Hypertension) centers. At the end of a follow-up period of at least 6 months, patients were classified between RHT or NRHT. RHT was defined as uncontrolled blood pressure despite the optimal doses of three antihypertensive agents of which one is a diuretic or similar, or controlled by ≥ 4 medications. Blinded independent central review of all radiologic renal artery charts was performed. RESULTS: Baseline characteristics were: age 50±15 years, 62% males, BP 145±22/87±13mmHg. Fifty-three (62%) patients had RHT and 25 (29%) had at least one ARA. Prevalence of ARA was comparable between RHT (25%) and NRHT patients (33%, P=0.62), but there were more ARA per patient in NRHT (2±0.9) vs. RHT (1.3±0.5, P=0.05), and renin levels were higher in ARA group (51.6±41.7 mUI/L vs. 20.4±25.4 mUI/L, P=0.001). ARA were similar in diameter or length between the 2 groups. CONCLUSIONS: In this retrospective series of 86 essential hypertension patients, we found no difference in the prevalence of ARA in RHT and NRHT. More comprehensive studies are needed to answer this question.

Effects of single and multiple sessions of lower body diastole-synchronized compressions using a pulsating pneumatic suit on endothelium function and metabolic parameters in patients with type 2 diabetes: two controlled cross-over studies.

BACKGROUND: Endothelium function is often impaired in patients with type 2 diabetes. We hypothesized that by improving endothelial function using diastole-synchronized compressions/decompressions (DSCD) to the lower body may improve the metabolic profile. The objective of this research was to evaluate the effects of single and multiple DSCD sessions on microcirculation, endothelium function and metabolic parameters of patients with type 2 diabetes. METHODS: Two monocentric, controlled, randomized cross-over studies (Study 1 and Study 2) were performed. In Study 1, 16 patients received one 20 min DSCD and one simulated (control) session at 2 week intervals; continuous glucose monitoring and cutaneous blood flow were recorded continuously before, during and after DSCD or Control session; other vascular assessments were performed before and after DSCD and control sessions. In Study 2, 38 patients received 60 min DSCD sessions three times/week for three months followed by a 4-6 week washout and 3 month control period (without simulated sessions); vascular, metabolic, body composition, physical activity and quality of life assessments were performed before and after 3 months. RESULTS: Both studies showed significant, multiplex effects of DSCD sessions. In Study 1, cutaneous blood flow and endothelium function increased, and plasma and interstitial glucose levels after a standard breakfast decreased after DSCD sessions. In Study 2, cutaneous endothelium function improved, LDL-cholesterol and non-HDL cholesterol decreased, extra-cell water decreased and SF-36 Vitality score increased after 3 months of DSCD sessions. CONCLUSIONS: Our findings support the beneficial effect of DSCD on the endothelium and show concomitant beneficial metabolic and vitality effects. Future clinical trials need to test whether DSCD use translates into a preventive measure against microvascular diabetic complications and its progression. Trial registration ClinicalTrials.gov identifiers: NCT02293135 and NCT02359461.

Grapefruit Juice Flavanones Modulate the Expression of Genes Regulating Inflammation, Cell Interactions and Vascular Function in Peripheral Blood Mononuclear Cells of Postmenopausal Women.

Grapefruit is a rich source of flavanones, phytochemicals suggested excreting vasculoprotective effects. We previously showed that flavanones in grapefruit juice (GFJ) reduced postmenopausal women's pulse-wave velocity (PWV), a measure of arterial stiffness. However, mechanisms of flavanone action in humans are largely unknown. This study aimed to decipher molecular mechanisms of flavanones by multi-omics analysis in PBMCs of volunteers consuming GFJ and flavanone-free control drink for 6 months. Modulated genes and microRNAs (miRNAs) were identified using microarrays. Bioinformatics analyses assessed their functions, interactions and correlations with previously observed changes in PWV. GFJ modified gene and miRNA expressions. Integrated analysis of modulated genes and miRNA-target genes suggests regulation of inflammation, immune response, cell interaction and mobility. Bioinformatics identified putative mediators of the observed nutrigenomic effect (STAT3, NF-κB) and molecular docking demonstrated potential binding of flavanone metabolites to transcription factors and cell-signaling proteins. We also observed 34 significant correlations between changes in gene expression and PWV. Moreover, global gene expression was negatively correlated with gene expression profiles in arterial stiffness and hypertension. This study revealed molecular mechanisms underlying vasculoprotective effects of flavanones, including interactions with transcription factors and gene and miRNA expression changes that inversely correlate with gene expression profiles associated with cardiovascular risk factors. Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT01272167].

Resistant Hypertension: Novel Insights.

Hypertension is the most common chronic disease and the leading risk factor for disability and premature deaths in the world, accounting for more than 9 million deaths annually. Resistant hypertension is a particularly severe form of hypertension. It was described 50 years ago and since then has been a very active field of research. This review aims at summarizing the most recent findings on resistant hypertension. The recent concepts of apparent- and true-resistant hypertension have stimulated a more precise definition of resistant hypertension taking into account not only the accuracy of blood pressure measurement and pharmacological class of prescribed drugs but also patient adherence to drugs and life-style recommendations. Recent epidemiological studies have reported a 10% prevalence of resistant hypertension among hypertensive subjects and demonstrated the high cardiovascular risk of these patients. In addition, these studies identified subgroups of patients with even higher morbidity and mortality risk, probably requiring a more aggressive medical management. In the meantime, guidelines provided more standardized clinical work-up to identify potentially reversible causes for resistant hypertension such as secondary hypertension. The debate is however still ongoing on which would be the optimal method(s) to screen for non-adherence to hypertension therapy, recognized as the major cause for (pseudo)-resistance to treatment. Recent randomized clinical trials have demonstrated the strong benefit of anti-aldosterone drugs (mostly spironolocatone) as fourth-line therapies in resistant hypertension whereas clinical trials with device-based therapies displayed contrasting results. New trials with improved devices and more carefully selected patients with resistant hypertension are ongoing.

Innovative invasive management without stent implantation guided by optical coherence tomography in acute coronary syndrome.

BACKGROUND: A two-step strategy of invasive management without stenting, guided by optical coherence tomography (OCT), in selected patients with acute coronary syndrome (ACS), might avoid systematic stent implantation and allow medical therapy alone. AIMS: To assess the feasibility and safety of such a procedure, and to define coronary imaging characteristics in a specific population. METHODS: This single-centre proof-of-concept study included all patients with ACS who benefited from a two-step revascularization procedure with optimal reperfusion during primary percutaneous coronary intervention followed by delayed angiography and OCT. OCT imaging determined medical therapy treatment alone without stenting in case of absence of vulnerable plaque rupture and <70% stenosis. Follow-up consisted of screening for major adverse cardiac events (MACE) at 12months. RESULTS: Forty-six patients were included, mainly men (86.9%) and smokers (65.2%), with a mean age of 47.1years. Most cases (80.4%) were large thrombus burden lesions. Delayed angiography and OCT were performed in a median period of 6 [3-10] days. No adverse events occurred between the initial and second angiograms. Plaque rupture was detected in 39.1% of patients, plaque erosion in 54.3% and calcified nodule in 6.5%. Twenty-three patients benefited from systematic delayed OCT over a median period of 171days, showing an increase in minimal lumen area. At 12months, two patients (4.3%) presented MACE and were stented. No sudden death or myocardial infarction recurrence occurred. CONCLUSIONS: Analysing ACS mechanisms by OCT might facilitate treatment decisions in patients with ST-segment elevation myocardial infarction managed by a two-step procedure. Conservative treatment with antithrombotic therapy without stenting seems to be a reliable option in a selected population.

Impact of video on the understanding and satisfaction of patients receiving informed consent before elective inpatient coronary angiography: A randomized trial.

BACKGROUND: Appropriate information about the benefits and risks of invasive procedures is crucial, but limited data is available in this field. The aim of this study was to evaluate the incremental value of a short video about coronary angiography compared with standard information, in terms of patient understanding, satisfaction and anxiety. METHODS: This prospective multicenter study included patients admitted for scheduled coronary angiography, who were randomized to receive either standard information or video information by watching a three-dimensional educational video. After information was delivered, patients were asked to complete a dedicated 16-point information questionnaire, as well as satisfaction and anxiety scales. RESULTS: From 21 September to 4 October 2015, 821 consecutive patients were randomized to receive either standard information (n=415) or standard information with an added educational video (n=406). The information score was higher in the video information group than in the standard group (11.8±2.8 vs 9.5±3.1; P<.001). This result was consistent across age and education level subgroups. Self-reported satisfaction was also higher in the video information group (8.4±1.9 vs. 7.7±2.3; P<.001), while anxiety level did not differ between groups. The variables associated with a higher information score were the use of the educational video, younger age, higher level of education, previous follow-up by a cardiologist, prior information about coronary angiography and previous coronary angiography. CONCLUSIONS: In comparison with standard information, viewing a dedicated educational video improved patients' understanding and satisfaction before scheduled coronary angiography. These results are in favor of widespread use of this incremental information tool.

Substantial Variability Across Individuals in the Vascular and Nutrigenomic Response to an Acute Intake of Curcumin: A Randomized Controlled Trial.

SCOPE: Curcumin exerts biological activities of interest in cardiovascular prevention. However, its vascular protective effect is still poorly investigated in humans. The present study aims to assess vascular effect of an acute intake of curcumin and its nutrigenomic impact in circulating immune cells. METHODS AND RESULTS: In a randomized, double-blind, crossover design, 18 healthy smokers consume a placebo or a 5-g curcumin. Before and 2 h after the intake, vascular function measurements are performed by using flow-mediated dilation (FMD). In addition, endothelial function in the microcirculation and blood pressure are evaluated. Plasma curcumin concentrations and changes in gene expression in peripheral blood mononuclear cells (PBMC) are analyzed. No significant effect of curcumin on FMD is observed when considering the entire study population, mainly due to a high interindividual variability. A subgroup analysis according to the gender or the cardiovascular-risk score reveals a significant effect of curcumin on FMD in women and in subjects presenting lower cardiovascular risk. No change in gene expression is observed when data are analyzed for all volunteers but changes in expression are observed when analyzed according to gender. CONCLUSIONS: This clinical trial highlights that a substantial variability in efficacy of curcumin exists across individuals.

Predictive factors for successful renal denervation: should we use them in clinical trials?

Renal denervation (RDN) is facing various challenges to its initial claimed value in hypertension treatment. Major concerns are the choice of the patients and the technical efficacy of the RDN. Different factors have been described as predicting the capacity of RDN to decrease blood pressure. These factors are related to the patients, the procedure and the tools to confirm successful neural ablation. Their use in future trials should help to improve RDN trials understanding and outcomes. This review summarizes the different predictive factors available and their potential benefits in patient selection and in procedure guidance.

Curcumin modulates endothelial permeability and monocyte transendothelial migration by affecting endothelial cell dynamics.

Curcumin is a phenolic compound that exhibits beneficial properties for cardiometabolic health. We previously showed that curcumin reduced the infiltration of immune cells into the vascular wall and prevented atherosclerosis development in mice. This study aimed to investigate the effect of curcumin on monocyte adhesion and transendothelial migration (TEM) and to decipher the underlying mechanisms of these actions. Human umbilical vein endothelial cells (HUVECs) were exposed to curcumin (0.5-1µM) for 3h prior to their activation by Tumor Necrosis Factor alpha (TNF-α). Endothelial permeability, monocyte adhesion and transendothelial migration assays were conducted under static condition and shear stress that mimics blood flow. We further investigated the impact of curcumin on signaling pathways and on the expression of genes using macroarrays. Pre-exposure of endothelial cells to curcumin reduced monocyte adhesion and their transendothelial migration in both static and shear stress conditions. Curcumin also prevented changes in both endothelial permeability and the area of HUVECs when induced by TNF-α. We showed that curcumin modulated the expression of 15 genes involved in the control of cytoskeleton and endothelial junction dynamic. Finally, we showed that curcumin inhibited NF-κB signaling likely through an antagonist interplay with several kinases as suggested by molecular docking analysis. Our findings demonstrate the ability of curcumin to reduce monocyte TEM through a multimodal regulation of the endothelial cell dynamics with a potential benefit on the vascular endothelial function barrier.

Management of ST-elevation myocardial infarction in young patients by limiting implantation of durable intracoronary devices and guided by optical frequency domain imaging: "proof of concept" study.

AIMS: The aim of this study was to demonstrate the feasibility and safety of ST-elevation myocardial infarction (STEMI) management in young patients by limiting implantation of durable intracoronary devices (using a bioresorbable stent or medical treatment alone). METHODS AND RESULTS: Patients <50 years old admitted for STEMI with single-vessel disease received a two-stage management strategy. During a second coronary angiography performed between day 2 and day 7, optical frequency domain imaging (OFDI) guided the decision on therapeutic management, i.e., i) in the case of a stenosis greater than 70% or plaque prolapse, implantation of a BVS; or ii) in the other cases, continuation of medical management alone without stenting. All patients underwent systematic angiographic control with OFDI imaging at six months. Among the 653 patients admitted for STEMI, 124 patients were under 50 years old and 45 patients were included. Early management was performed on average at day 3.9 (day 2 - day 7). Thirty-four (34) patients received BVS implantation and 11 were treated medically. Only one major adverse cardiac event (MACE) had occurred at six months. CONCLUSIONS: In a selected younger population, the management of STEMI guided by OFDI and based on the concept of limiting implantation of durable intracoronary devices appears to be a feasible and safe therapeutic option.

How and when to suspect spontaneous coronary artery dissection: novel insights from a single-centre series on prevalence and angiographic appearance.

AIMS: Spontaneous coronary artery dissection (SCAD) is an underdiagnosed entity of acute coronary syndrome (ACS). Its prevalence remains unclear due to a challenging diagnosis, particularly in instances of intramural haematoma without intimal rupture. In the present study, we aimed to: 1) estimate the prevalence of SCAD among acute coronary syndrome (ACS) patients managed in a French coronary care centre, 2) demonstrate the value of specific angiographic signs for diagnosing SCAD, and 3) confirm the incremental value of intracoronary imaging in ambiguous cases. METHODS AND RESULTS: From 1999 to 2014, 55 cases of SCAD (all women, mean age 50.1 years) were diagnosed. Ignoring age, 51 (92.7%) had ≤2 cardiovascular risk factors. Thirty-six were diagnosed prospectively during the latter period (2012-2014). Among these, SCAD accounted for 35.7% of ACS (20/56) in women <60 years with ≤1 cardiovascular risk factor. Upon close investigation, five angiographic features commonly observed with SCAD were identified: 1) absence of atheroma on other coronary arteries, 2) radiolucent flap(s), 3) contrast dye staining of the arterial wall, 4) starting and/or ending of the angiographic ambiguity on a side branch, 5) long narrowing of lumen calibre: smooth and linear, or stenosis of varying severity mimicking a "stick insect" or "radish" aspect. Three of the above five signs were present in 51 (92.7%) cases. Optical computed tomography (OCT) was performed in 19 cases with no complication. All explored arteries had evidence of intramural haematoma and/or intimomedial membrane separation. An intimal rupture was observed in 10 (52.6%) patients. The diseased segment initiated or ended on a side branch in 14 (73.7%) patients. CONCLUSIONS: SCAD accounts for approximately one third of ACS in young women with ≤1 CRF. The combination of specific angiographic signs and OCT imaging facilitates the diagnosis of ambiguous cases without intimal rupture.

Contribution of optical coherence tomography imaging in management of iatrogenic coronary dissection.

Iatrogenic coronary dissection is a rare but potentially serious complication of coronary angiography and angioplasty. Treatment with angioplasty guided only by angiography is often difficult. Optical coherence tomography imaging seems to be an interesting technique to lead the management of iatrogenic coronary dissection. Diagnosis can be made by optical coherence tomography; it can also eliminate differential diagnosis. Furthermore, this technique can guide safely the endovascular treatment.

Flavanones protect from arterial stiffness in postmenopausal women consuming grapefruit juice for 6 mo: a randomized, controlled, crossover trial.

BACKGROUND: The consumption of citrus fruits is associated with health benefits. However, clinical data regarding the effects of grapefruit flavanone consumption on vascular function are lacking. OBJECTIVE: The objective of the present study was to address the role of flavanones in the long-term effects induced by grapefruit juice (GFJ) consumption on vascular function in healthy postmenopausal women. DESIGN: Forty-eight healthy postmenopausal women aged 50-65 y within 3-10 y since menopause, a body mass index (in kg/m(2)) of 19-30, and a waist size >88 cm completed this double-blind, randomized, controlled, crossover trial. These volunteers were randomly assigned to consume 340 mL GFJ/d, providing 210 mg naringenin glycosides, or a matched control drink without flavanones for 6 mo each, with a 2-mo washout between beverages. The primary endpoint was the assessment of endothelial function in the brachial artery by using flow-mediated dilation. Blood pressure, arterial stiffness, and endothelial function in the peripheral arterial bed were also evaluated as indicators of vascular function. These measurements and blood collection for clinical biochemical markers were performed in overnight-fasted subjects before and after the 6-mo treatment periods. RESULTS: The mean ± SD carotid-femoral pulse wave velocity, which reflects central aortic stiffness, was statistically significantly lower after consumption of GFJ (7.36 ± 1.15 m/s) than after consumption of the matched control drink without flavanones (7.70 ± 1.36 m/s), with a P value of 0.019 for the treatment effect. Endothelial function in macro- and microcirculation, blood pressure, anthropometric measures, glucose metabolism, and biomarkers of inflammation and oxidative stress were not affected by the intervention. CONCLUSIONS: Regular GFJ consumption by middle-aged, healthy postmenopausal women is beneficial for arterial stiffness. This effect may be related to flavanones present in grapefruit. This trial was registered at clinicaltrials.gov as NCT01272167.

Cardiovascular risk in rheumatoid arthritis.

The objectives of this review are to discuss data on the cardiovascular risk increase associated with rheumatoid arthritis (RA), the effects of RA treatments on the cardiovascular risk level, and the management of cardiovascular risk factors in patients with RA. Overall, the risk of cardiovascular disease is increased 2-fold in RA patients compared to the general population, due to the combined effects of RA and conventional risk factors. There is some evidence that the cardiovascular risk increase associated with nonsteroidal anti-inflammatory drug therapy may be smaller in RA patients than in the general population. Glucocorticoid therapy increases the cardiovascular risk in proportion to both the current dose and the cumulative dose. Methotrexate and TNFα antagonists diminish cardiovascular morbidity and mortality rates. The management of dyslipidemia remains suboptimal. Risk equations may perform poorly in RA patients even when corrected using the multiplication factors suggested by the EUropean League Against Rheumatism (EULAR) (multiply the score by 1.5 when two of the following three criteria are met: disease duration longer than 10 years, presence of rheumatoid factor or anti-cyclic citrullinated peptide (CCP) antibodies, and extraarticular manifestations). Doppler ultrasonography of the carotid arteries in patients at moderate cardiovascular risk may allow a more aggressive approach to dyslipidemia management via reclassification into the high-risk category of patients with an intima-media thickness greater than 0.9 mm or atheroma plaque.

Very late stent thrombosis related to incomplete neointimal coverage or neoatherosclerotic plaque rupture identified by optical coherence tomography imaging.

AIMS: Recent data have reported that neoatherosclerosis could develop long after stent implantation and lead to subsequent rupture and acute coronary syndrome (ACS). We sought to identify the presence of in-stent neoatheroma (ISNA) in patients with very late stent thrombosis (VLST) using optical coherence tomography (OCT). METHODS AND RESULTS: All patients from two catheterization centres who presented with ACS related to VLST underwent a standard coronary angiography and intra-coronary OCT. ISNA was defined as the combination of diffuse neointimal proliferation, lipid-laden intima with plaque organization, and fibrous cap rupture with no evidence of an uncovered strut. Out of 2139 ACS patients, 20 presented with definite VLST, including 10 with evidence of ISNA lesions, detected using OCT. The mean delay between initial percutaneous coronary intervention and VLST was longer in the ISNA patients compared with non-ISNA patients (10.5 ± 1.6 vs. 4.0 ± 0.6 years, P = 0.003). The mean LDL-cholesterol tended to be higher in ISNA patients compared with non-ISNA patients. OCT analysis revealed significantly thicker neointimal coverage as well as a lower number of uncovered struts in ISNA lesions compared with the other patients. LDL-cholesterol levels were correlated with the average neointima thickness (Spearman's rho = 0.46, P = 0.04). All the ISNA lesions were treated through initial thrombectomy followed by redo stenting in nine patients. CONCLUSION: Our data show that ISNA is frequent in patients with VLST. These results suggest that OCT imaging is helpful in identifying the underlying mechanisms of VLST and, therefore, in the clinical decision-making process.