Effect of regular smoking on flicker induced retinal vasodilatation in healthy subjects

Background

Habitual smoking is a risk factor for a variety of vascular diseases, including ocular pathologies. In the current study, we set out to investigate whether the regulation of retinal vascular tone is impaired in habitual smokers. For this purpose, vascular reactivity was tested during flicker light induced vasodilatation in smokers and in a non-smoking control group.

Methods

In this prospective, balanced, parallel group study 24 chronic smokers (28.1 ± 3.3 years) and 24 age-matched never-smoking volunteers (28.2 ± 4.0 years) were included. Flicker induced vasodilatation was measured in major retinal arteries and veins using a retinal vessel analyzer and flicker induced changes in retinal blood velocities were assessed in retinal veins by laser Doppler velocimetry. Three flicker periods of 60 s were scheduled. Blood cotinine concentration was determined and a Fagerstrom questionnaire was performed to evaluate nicotine dependency.

Results

In non-smoking subjects, stimulation with flicker light increased retinal venous diameter by + 7.7 ± 3.1%, + 6.9 ± 2.9% and + 7.1 ± 2.8% during the three flicker periods, respectively. Flicker induced vasodilatation in veins was significantly diminished in chronic smokers (+ 4.9 ± 2.4%, + 6.3 ± 3.1% and + 5.7 ± 3.4%, ANOVA between groups, p = 0.032) as compared to the non-smoking control group. Calculated retinal blood flow in the measured veins increased by a maximum of + 54 ± 21%, + 43 ± 18% and + 46 ± 19% during the three stimulation periods in the non-smoking subjects, respectively. The flicker induced increase in retinal blood flow as assessed in the veins was significantly reduced in chronic smokers as compared to the non-smoking control group (+ 19 ± 16%, + 26 ± 14%, + 24 ± 13%, ANOVA between groups, p = 0.013). In retinal arteries, flicker stimulation increased retinal arterial diameters by 5.2 ± 3.8%, 5.8 ± 4.8% and 5.5 ± 5.6% during the three flicker periods in the non-smoking group. In smokers, the flicker induced arterial vasodilatation was not significantly different compared to non-smokers (4.6 ± 4.1%, 3.8 ± 3.7% and 4.8 ± 3.4%, ANOVA between groups, p = 0.4).

Conclusion

Our data indicate that the flicker induced hemodynamic response of retinal veins is reduced in chronic smokers as compared to age matched healthy volunteers. This supports the hypothesis that chronic smoking leads to vascular dysfunction in the eye.     

Diurnal changes of critical flicker frequency in patients with liver cirrhosis and their relationship with sleep disturbances

BackgroundWe aimed to measure the diurnal changes of critical flicker frequency in healthy subjects and cirrhotic patients and to investigate their relationship with sleep disturbance.MethodsCirrhotic patients and healthy volunteers were included. All groups completed the Pittsburgh Sleep Quality Index and a simple sleep questionnaire. Sleep disturbance was defined as a Pittsburgh Sleep Quality Index score of >5. Critical flicker frequency was measured twice a day to detect diurnal abnormalities.ResultsOverall, 59 cirrhotic patients (54.2% males, Mean Age 59 ± 11 years) and 18 controls (39.9% males, Mean Age 58 ± 9 years) were included. Sleep disturbances were more common in cirrhotics (66.1%) than controls (38.9%, p < 0.05). In cirrhotics, the critical flicker frequency was not related to decompensation. The nocturnal values were higher than the morning values in cirrhotics (64.4%), but not in controls (p < 0.0001). Additionally, sleep disturbances were more common in cirrhotics who had higher nocturnal values (p < 0.05).ConclusionsChanges in the diurnal critical flicker frequency were observed in cirrhotics but not in controls. Sleep disturbances in cirrhotics appear to be associated with deviations of the diurnal rhythm of critical flicker frequency rather than with clinical parameters such as the clinical stages of cirrhosis and the Model For End-Stage Liver Disease and Child–Pugh scores.     

Change in left ventricular systolic function in patients with ST elevation myocardial infarction: Evidence for smoker's paradox or pseudo-paradox?

BackgroundThe ‘smoker's paradox’ refers to the observation of favorable prognosis in current smokers following an acute ST elevation myocardial infarction (STEMI) in the era of fibrinolysis, however, several STEMI studies have demonstrated conflicting results in patients undergoing primary percutaneous coronary intervention (p-PCI).ObjectiveAim of the current study was to evaluate the impact of cigarette smoking on left ventricular function in STEMI patients undergoing p-PCI.MethodsOur population is represented by 74 first-time anterior STEMI patients undergoing p-PCI, 37 of whom were smokers. We assessed left ventricular function by left ventricular ejection fraction (LVEF) on the second day after admission and at 3-month follow-up. Early predictors of adverse left ventricular remodelling after STEMI treated by p-PCI were examined.ResultsBasal demographics and comorbidities were similar between groups. Although the LVEF during the early phase was higher in smokers compared to non-smokers (44.95 ± 7.93% vs. 40.32 ± 7.28%; p = 0.011); it worsened in smokers at follow-up (mean decrease in LVEF: −2.70 ± 5.95%), whereas it improved in non-smokers (mean recovery of LVEF: +2.97 ± 8.45%). In univariate analysis, diabetes mellitus, peak troponin I, current smoking, and lower TIMI flow grade after p-PCI, pain-to-door time and door-to-balloon times were predictors of adverse left ventricular remodelling. After multivariate logistic regression analysis, smoking at admission, lower TIMI flow grade after p-PCI, the pain-to-door time and door-to-balloon times remained independent predictors of deterioration in LVEF.ConclusionTrue or persistent ‘smoker's paradox’ does not appear to be relevant among STEMI patients undergoing p-PCI. The ‘smoker's paradox’ is in fact a pseudo-paradox. Further studies with larger numbers may be warranted.     

Effects of carotid baroreceptor stimulation on retinal arteriole remodeling evaluated with adaptive optics camera in resistant hypertensive patients

Background and aimBaroreceptor activation therapy (BAT) leads to a decrease in blood pressure (BP) in patients affected by resistant hypertension (RH) by reducing sympathetic outflow. This study aimed at evaluating the effects of BAT on RH patients’ retinal arteriolar microvasculature, a territory devoid of adrenergic innervation.Patients and methodsFive patients defined as affected by RH after excluding secondary causes of hypertension and based on number of antihypertensive treatments, underwent the implantation of Barostim™ neo™. Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) were assessed by office and 24-hours ambulatory BP monitoring (ABPM). Adaptive Optics Camera RTX1^® (ImagineEye, Orsay, France) was used to measure wall thickness (WT), internal diameter (ID), wall cross-sectional area (WCSA) and wall-to-lumen ratio (WLR). A cohort of 21 not-controlled hypertensive patients matched for age, gender and follow-up time, undergoing standard-antihypertensive therapy changes, was selected as a control group. SBP and DBP were assessed by office and home BP monitoring (HBPM). Evaluations were performed at baseline and after 6 months mean follow-up.ResultsOffice SBP decreased by 9.7 ± 12.3% and 29.7 ± 12.4% in standard-therapy and BAT group respectively, while office DBP decreased by 7.6 ± 17.4% and 14.8 ± 15.7%. Concerning ABPM/HBPM, a mean reduction of both SBP and DBP of 7.9 ± 11% was observed for the standard-therapy while a reduction of 15.8 ± 10.5% and 15.8% ± 5.3% was observed for SBP and DBP respectively in BAT group. While in the standard-therapy group a significant reduction in WLR (–5.9%) due to both ID increase (+2.3%) and WT reduction (–5.7%) was observed, without changes in WCSA (–0.3%), RH patients had a significant reduction in WCSA (–12.1%), due to a trend in both WT and ID reduction (–6.5% and –1.7% respectively), without significant changes in WLR (–2%).ConclusionWhile a reverse eutrophic remodeling was observed in patients undergoing a standard-antihypertensive treatment, hypotrophic changes were found in RH patients undergoing BAT. Despite the lack of adrenergic receptors on retinal vessels, chronic baroreflex stimulation may exert an effect on retinal microvasculature in RH patients by more systemic than local mechanisms.     

Hypermethylation of Anti-oncogenic MicroRNA 7 is Increased in Emphysema Patients

IntroductionMicroRNA-7 (miR-7) has a suppressive role in lung cancer and alterations in its DNA methylation may contribute to tumorigenesis. As COPD patients with emphysema have a higher risk of lung cancer than other COPD phenotypes, we compared the miR-7 methylation status among smoker subjects and patients with various COPD phenotypes to identify its main determinants.Methods30 smoker subjects without airflow limitation and 136 COPD patients without evidence of cancer were recruited in a prospective study. Clinical and functional characteristics were assessed and patients were classified into: frequent exacerbator, emphysema, chronic bronchitis and asthma COPD overlap (ACO). DNA collected from buccal epithelial samples was isolated and bisulfite modified. miR-7 methylation status was evaluated by quantitative methylation-specific polymerase chain reaction (qMSP).ResultsmiR-7 Methylated levels were higher in COPD patients than in smokers without airflow limitation (23.7 ± 12.4 vs. 18.5 ± 8.8%, p = 0.018). Among COPD patients, those with emphysema had higher values of methylated miR-7 (27.1 ± 10.2%) than those with exacerbator (19.4 ± 9.9%, p = 0.004), chronic bronchitis (17.3 ± 9.0%, p = 0.002) or ACO phenotypes (16.0 ± 7.2%, p = 0.010). After adjusting for clinical parameters, differences between emphysematous patients and those with other phenotypes were retained. In COPD patients, advanced age, mild-moderate airflow limitation, reduced diffusing capacity and increased functional residual capacity were identified as independent predictors of methylated miR-7 levels.ConclusionThe increase of miR-7 methylation levels experienced by COPD patients occurs mainly at the expense of the emphysema phenotype, which might contribute to explain the higher incidence of lung cancer in these patients.     

Différences induites par la définition des périodes diurnes et nocturnes sur la pression artérielle et le dipping lors d’une mesure ambulatoire de la pression artérielle

Ambulatory blood pressure monitoring (ABPM) has become indispensable for the diagnosis and control of hypertension. However, no consensus exists on how daytime and nighttime periods should be defined.ObjectiveTo compare daytime and nighttime blood pressure (BP) defined by an actigraph and by body position with BP resulting from arbitrary daytime and nighttime periods.Patients and methodABPM, sleeping periods and body position were recorded simultaneously using an actigraph (SenseWear Armband^®) in patients referred for ABPM. BP results obtained with the actigraph (sleep and position) were compared to the results obtained with fixed daytime (7 a.m.–10 p.m.) and nighttime (10 p.m.–7 a.m.) periods.ResultsData from 103 participants were available. More than half of them were taking antihypertensive drugs. Nocturnal BP was lower (systolic BP: 2.08 ± 4.50 mmHg; diastolic BP: 1.84 ± 2.99 mmHg, P < 0.05) and dipping was more marked (systolic BP: 1.54 ± 3.76%; diastolic BP: 2.27 ± 3.48%, P < 0.05) when nighttime was defined with the actigraph. Standing BP was higher (systolic BP 1.07 ± 2.81 mmHg; diastolic BP: 1.34 ± 2.50 mmHg) than daytime BP defined by a fixed period.ConclusionDiurnal BP, nocturnal BP and dipping are influenced by the definition of daytime and nighttime periods. Studies evaluating the prognostic value of each method are needed to clarify which definition should be used.     

Metered dose inhaler delivery of treprostinil for the treatment of pulmonary hypertension

BackgroundThe stable prostanoid analogue treprostinil is approved as continuous infusion for treatment of pulmonary arterial hypertension. Unique drug characteristics may render this prostanoid feasible for inhalation therapy with a metered dose inhaler.Methods and resultsRandomised open label investigation of acute haemodynamic effects, safety and tolerability of inhaled treprostinil delivered in seconds by a metered dose inhaler (MDI-TRE). Inhaled nitric oxide (NO) and MDI-TRE were applied once during right heart catheter investigation to 39 consecutive patients with pre-capillary pulmonary hypertension. Doses of 30 μg, 45 μg and 60 μg MDI-TRE were investigated in separate groups of patients. Haemodynamics and blood gases were measured for 2 h following treprostinil application. Acute haemodynamic responses to NO and MDI-TRE were comparable. MDI-TRE significantly improved haemodynamics compared to placebo inhalation. MDI-TRE induced effects were comparable to a historical control group that inhaled treprostinil from an ultrasonic nebuliser. The 120 min area under the curve for PVR changes due to placebo, 30 μg, 45 μg or 60 μg MDI-TRE was 1114 ± 998, ?870 ± 940, ?2450 ± 2070 and ?2000 ± 900 min*%. Reduction of systemic vascular resistance and pressure were not clinically relevant. No significant side effects were observed. No impact on ventilation/perfusion matching by treprostinil was demonstrated in 5 patients with pre-existing gas exchange limitations by use of the multiple inert gas elimination technique.ConclusionsThe application of inhaled treprostinil with a metered dose inhaler is feasible and well tolerated. It induced a sustained pulmonary selective vasodilatation.     

Lipopolysaccharide responsiveness is an independent predictor of death in patients with chronic heart failure

BackgroundThe origin of pro-inflammatory activation in chronic heart failure (HF) remains a matter of debate. Lipopolysaccharide (LPS) may enter the blood stream through the morphologically altered and leaky gut barrier. We hypothesized that lower LPS reactivity would be associated with worse survival as compared to normal or higher LPS reactivity.MethodsLPS responsiveness was studied in 122 patients with chronic HF (mean ± SD: age 67.3 ± 10.3 years, 24 female, New York Heart Association class [NYHA] class: 2.5 ± 0.8, left ventricular ejection fraction [LVEF]: 33.5 ± 12.5%) and 27 control subjects of similar age (63.7 ± 7.7 years, p > 0.05). Reference LPS was added at increasing doses to ex vivo whole blood samples and necrosis factor-α (TNFα) was measured. Patients were subgrouped into good- and poor-responder status according to their potential to react to increasing doses of LPS (delta TNFα secretion). The optimal cut-off value was calculated by receiver–operator characteristic curve (ROC) analysis.ResultsA total of 56 patients with chronic HF died from any cause during follow-up. At 24 months, cumulative mortality was 16.4% (95% confidence interval 16.0–16.7%). The delta TNFα value representing the optimal cut-off for the prediction of mortality was 1522 pg/mL (24 months) with a sensitivity of 49.3% (95% confidence interval 37.2–61.4%) and specificity of 81.5% (95% confidence interval 61.9–93.6%). LPS responder status remained an independent predictor of death after multivariable adjustment (hazard ratio 0.09 for good- vs. poor-responders, 95% confidence interval 0.01–0.67, p < 0.05).ConclusionsLPS responsiveness in patients with chronic HF is an independent predictor of death.     

Short term effects of sildenafil citrate therapy in secondary pulmonary hypertension

ObjectivesTo study the short term effects of sildenafil citrate therapy in patients with secondary pulmonary hypertension.MethodsForty patients with known symptomatic secondary pulmonary hypertension due to valvular heart disease, chronic thromboembolic disease, chronic obstructive pulmonary disease, interstitial pulmonary fibrosis, and idiopathic dilated cardiomyopathy were included in this phase II study. Patients were allocated in a randomized, placebo controlled design to either sildenafil or placebo for 6 weeks. Baseline and 6 week follow up included assessment of hemodynamic parameters, functional class using the NYHA classification, echocardiographic measurements of pulmonary artery systolic pressure and left ventricular ejection fraction.ResultsThe mean NYHA class at 6 weeks was 2.05 ± 0.4 in the sildenafil group versus 2.6 ± 0.6 in the placebo group, p = 0.02. The mean systolic pulmonary artery pressure significantly decreased in the sildenafil group at 6 weeks (43 ± 4 mmHg), compared to placebo patients (53 ± 7 mmHg), p = 0.02. Ejection fraction was higher in the sildenafil group, 59 ± 12% versus 54 ± 14% in the placebo group, but did not reach statistically significant difference. Sildenafil was well tolerated with minimal side effects.ConclusionOur data suggest that sildenafil therapy may provide benefits to selected patients with pulmonary hypertension secondary to cardiac or pulmonary diseases.     

Acute effect of sildenafil on myocardial ischemic territories in patients with stable coronary artery disease

ObjectivesTo test the safety of sildenafil in patients with stable coronary artery disease (CAD).MethodsSixty-one patients with stable CAD, documented by coronary angiography were included in this phase I study. Patients were randomized to either single dose sildenafil or matched placebo. Speckle tracking echocardiography was done at baseline and 60 min after sildenafil/placebo intake to calculate peak systolic strain (PSS) of the most severely affected myocardial segments and the global longitudinal PSS.ResultsThe baseline mean segmental PSS in the sildenafil group changed by 52%, −3 ± 1% at baseline versus −7 ± 2% after sildenafil intake, P = 0.01. However, no significant changes were reported in the placebo group, −7 ± 3% at baseline versus −7.25 ± 3%, P = 0.1. The baseline mean global longitudinal PSS in the sildenafil group changed by 9% (−15 ± 4% at baseline versus −18 ± 3% after sildenafil, P = 0.03). In placebo patients, the change was only 3% from baseline (−14.8 ± 2% at baseline compared to −15 ± 2% after placebo intake, P = 0.1). Sildenafil was well tolerated without clinical or hemodynamic deterioration after its intake.ConclusionSildenafil intake is safe in patients with stable CAD, it induced marginal improvements in the peak systolic strain of different myocardial ischemic territories.     

Treatment of chronic hepatitis C in patients with chronic kidney disease with Sofosbuvir-basead regimes

BackgroundTo analyze the effectiveness and the safety of Sofosbuvir-based regimens to treat patients with chronic hepatitis C virus (HCV) infection and chronic kidney disease (CKD).MethodsA retrospective, observational study in patients with chronic HCV infection and CKD treated with Sofosbuvir-based regimens was performed. Liver fibrosis, comorbidities, HCV genotype and sustained virological resposnse (SVR) at 12th week post-treatment were evaluated. Kidney function was accessed by serum creatinine and glomerular filtration rate (GFR). The assumed level of significance was 5 %.ResultsThirty-five patients were treated. The mean age was 52.1 ± 10.9 years, 19 (54.3 %) were women, 32 (91.4 %) were already kidney transplanted and 3 (8.6 %) were on hemodialysis. The SVR by intention to treat was 88.6 %. The mean GFR was 65.8 ± 28.6 and 63.7 ± 28.3 ml/min pre- and post-treatment respectively (p > 0.05). Treatment was interrupted in 1 (2.85 %) patient due to anemia and in 2 (5.7 %) due to loss of kidney function.ConclusionSofosbuvir-based regimens are effective to treat HCV in patients with CKD. In patients with mild CKD this type of therapy seems to be safe.     

Retinal arteriolar remodeling evaluated with adaptive optics camera: Relationship with blood pressure levels

AimTo research a retinal arterioles wall-to-lumen ratio or lumen diameter cut-off that would discriminate hypertensive from normal subjects using adaptive optics camera.Patients and methodsOne thousand and five hundred subjects were consecutively recruited and Adaptive Optics Camera rtx1™ (Imagine-Eyes, Orsay, France) was used to measure wall thickness, internal diameter, to calculate wall-to-lumen ratio (WLR) and wall cross-sectional area of retinal arterioles. Sitting office blood pressure was measured once, just before retinal measurements and office blood pressure was defined as systolic blood pressure > = 140 mmHg and diastolic blood pressure > = 90 mmHg. ROC curves were constructed to determine cut-off values for retinal parameters to diagnose office hypertension. In another population of 276 subjects office BP, retinal arterioles evaluation and home blood pressure monitoring were obtained. The applicability of retinal WLR or diameter cut-off values were compared in patients with controlled, masked, white-coat and sustained hypertension.ResultsIn 1500 patients, a WLR > 0.31 discriminated office hypertensive subjects with a 0.57 sensitivity and 0.71 specificity. Lumen diameter < 78.2 μm discriminated office hypertension with a 0.73 sensitivity and a 0.52 specificity. In the other 276 patients, WLR was higher in sustained hypertension vs normotensive patients (0.330 ± 0.06 vs 0.292 ± 0.05; P < 0.001) and diameter was narrower in masked hypertensive vs normotensive subjects (73.0 ± 11.2 vs 78.5 ± 11.6 μm; P < 0.005).ConclusionA WLR higher than 0.31 is in favour of office arterial hypertension; a diameter under < 78 μm may indicate a masked hypertension. Retinal arterioles analysis through adaptive optics camera may help the diagnosis of arterial hypertension, in particular in case of masked hypertension.     

Extended-release Niacin Acutely Suppresses Postprandial Triglyceridemia

ObjectivePostprandial triglyceridemia predicts cardiovascular events. Niacin might lower postprandial triglycerides by restricting free fatty acids. Immediate-release niacin reduced postprandial triglycerides, but extended-release niacin failed to do so when dosed the night before a fat challenge. The study aims were to determine whether extended-release niacin dosed before a fat challenge suppresses postprandial triglycerides and whether postprandial triglycerides are related to free fatty acid restriction.MethodsA double-blinded, placebo-controlled, random-order crossover experiment was performed, in which healthy volunteers took 2 g extended-release niacin or placebo 1 hour before heavy cream. We sampled blood over 12 hours and report triglycerides and free fatty acid as means ± standard deviation for incremental area under the curve (AUC) and nadir.ResultsBy combining 43 fat challenges from 22 subjects, postprandial triglycerides incremental AUC was +312 ± 200 mg/dL*h on placebo versus +199 ± 200 mg/dL*h on extended-release niacin (33% decrease, P = .02). The incremental nadir for free fatty acid was ?0.07 ± 0.15 mmol/L on placebo versus ?0.27 ± 0.13 mmol/L on extended-release niacin (P < .0001), and free fatty acid incremental AUC decreased from +2.9 ± 1.5 mmol/L*h to +1.5 ± 1.5 mmol/L*h on extended-release niacin (20% decrease, P = .0015). The incremental AUC for triglycerides was strongly related to the post-dose decrease in free fatty acid (r = +0.58, P = .0007).ConclusionsGiven right before a fat meal, even a single dose of extended-release niacin suppresses postprandial triglyceridemia. This establishes that postprandial triglycerides suppression is an acute pharmacodynamic effect of extended-release niacin, probably the result of marked free fatty acid restriction. Further study is warranted to determine whether mealtime dosing would augment the clinical efficacy of extended-release niacin therapy.     

Tromboendarterectomía pulmonar en 106 pacientes con hipertensión pulmonar tromboembólica crónica

IntroductionPulmonary thromboendarterectomy is the treatment of choice in chronic thromboembolic pulmonary hypertension. We report our experience with this technique.MethodsBetween February 1996 and June 2014, we performed 106 pulmonary thromboendarterectomies. Patient population, morbidity and mortality and the long-term results of this technique (survival, functional improvement and resolution of pulmonary hypertension) are described.ResultsSubjects’ mean age was 53 ± 14 years. A total of 89% were WHO functional class III-IV, presurgery mean pulmonary pressure was 49 ± 13 mmHg and mean pulmonary vascular resistance was 831 ± 364 dynes.s.cm⁻⁵. In-hospital mortality was 6.6%. The most important post-operative morbidity was reperfusion pulmonary injury, in 20% of patients; this was an independent risk factor (p = 0.015) for hospital mortality. With a 31-month median follow-up (interquartile range: 50), 3- and 5-year survival was 90 and 84%. At 1 year, 91% were WHO functional class I-II; mean pulmonary pressure (27 ± 11 mmHg) and pulmonary vascular resistance (275 ± 218 dynes.s.cm⁻⁵) were significantly lower (p < 0.05) than before the intervention. Although residual pulmonary hypertension was detected in 14 patients, their survival at 3 and 5 years was 91 and 73%, respectively.ConclusionsPulmonary thromboendarterectomy offers excellent results in chronic thromboembolic pulmonary hypertension. Long-term survival is good, functional capacity improves, and pulmonary hypertension is resolved in most patients.     

Predictors of mortality in medically treated patients with congestive heart failure of nonrheumatic etiology and reduced systolic function

ObjectiveWe investigated the prognostic value of various parameters on the mortality of patients with nonrheumatic chronic heart failure and left ventricular (LV) systolic dysfunction.MethodsThis study included 132 consecutive patients with congestive heart failure and reduced LV systolic function without rheumatic valve disease. The primary outcome was mortality. Mean follow-up was 38 ± 6 months.ResultsDuring the follow-up period there were 47 deaths (35.6%). The age (64.1 ± 13.5 vs. 58.7 ± 11.8 years, P = 0.019), left bundle branch block (44.7% vs. 18.8%, P = 0.002), urea concentration (11.4 ± 5.3 vs. 8.9 ± 4.6 mmol/L, P = 0.006), LV end-diastolic and end-systolic dimensions (6.7 ± 0.8 vs. 6.4 ± 0.8 cm, P = 0.025 and 5.5 ± 0.8 vs. 4.9 ± 0.8 cm, P < 0.001, respectively), grade 3–4 mitral regurgitation (40.4 vs. 22.4%, P < 0.001), fractional shortening (16.7 ± 5.3% vs. 19.8 ± 5.7%, P = 0.002) and LV ejection fraction (32.9 ± 8.5% vs. 38.7 ± 11.3%, P = 0.003) were different between non-survivors and survivors. Multivariate analysis identified severity of mitral regurgitation (OR = 1.99, 95% CI 1.18–3.34; P = 0.009), age (OR = 1.07, 95% CI 1.02–1.12; P = 0.01) and LV end-systolic dimension (OR = 1.09, 95% CI 1.02–1.16; P = 0.014) as independent correlates of mortality.ConclusionsIn medically treated patients with nonrheumatic chronic heart failure and left ventricular systolic dysfunction, severity of mitral regurgitation, age and enlarged LV end-systolic dimension were independently associated with increased risk of death.     

Circulating Endothelial Progenitor Cells,Th1/Th2/Th17-Related Cytokines,and Endothelial Dysfunction in Resistant Hypertension

IntroductionA possible link between chronic vascular inflammation and arterial hypertension is now an object of intensive studies.ObjectiveTo compare Th1/Th2/Th17 cells-related cytokines, circulating endothelial progenitor cells (EPC), and endothelial function in subjects with resistant arterial hypertension (RAH) and controlled arterial hypertension (CAH).MethodsBlood pressure was measured by electronic sphygmomanometer. EPC were identified as CD34 +/ CD133 +/kinase insert domain receptor (KDR) + cells by flow cytometry. Th1/Th2/Th17 cells-related cytokines were identified using the Human Th1/Th2/Th17 Cytokines MultiAnalyte ELISArray Kit. Endothelium-dependent (FMD) vasodilatation of brachial artery was measured by Doppler ultrasound scanning.ResultsRAH group (n = 20) and CAH group (n = 20) and 17 healthy individuals (control group) were recruited. In the RAH group, lower blood levels of EPC number (42.4 ± 16.7 cells/mL) and EPC% (0.19 ± 0.08%) were observed than in the CAH group (93.1 ± 88.7 cells/mL; P = 0.017; 0.27 ± 0.17; P = 0.036) and control group (68.5 ± 63.6 cells/mL; P < 0.001; 0.28 ± 0.17%; P = 0.003), respectively. Plasma transforming growth factor-β1 levels were significantly higher in the RAH group (1767 ± 364 pg/mL) than in the CAH group (1292 ± 349; P < 0.001) and in control group (1203 ± 419 pg/mL; P < 0.001). In the RAH group, statistically significant negative correlation was observed between systolic blood pressure and EPC% (r = –0.72, P < 0.01). FMD in the RAH group was significantly lower (5.5 ± 0.8%) than in the CAH group (9.2 ± 1.4; P < 0.001) and in healthy controls (10.1 ± 1.1%; P < 0.001).ConclusionsRAH is characterized by reduced circulating EPC, substantial endothelial dysfunction, and increased plasma transforming growth factor-β1 levels.     

Increased maximum p wave duration in smoking patients with ST-elevation acute myocardial infarction and its relationship with inflammatory markers

IntroductionElectrocardiographic markers for atrial fibrillation and the relationship with inflammatory markers have not been evaluated in smoker patients with acute myocardial infarction.Material and methodsThis is a cross-sectional study developed between January 2012 and July 2014 at Hospital Universitario Celestino Hernández Robau from Santa Clara, Cuba. One hundred fifteen patients were included finally. The sample was divided into two groups (smokers and non-smokers). We obtained clinical and laboratory data and compared electrocardiographic markers for atrial fibrillation in both groups and with inflammatory markers.ResultsMaximum p wave duration was significantly higher in smoker than non-smoker patients (102 ± 12 vs. 97 ± 9; p = 0,020). Minimum p wave duration and p wave dispersion also are higher in smoker patients but not significantly (61 ± 10 vs. 60 ± 7; p = 0,476 and 41 ± 10 vs. 37 ± 9; p = 0,050). There is a positive and significant linear correlation between neutrophils count and maximum p wave duration in smokers (r = 0,45; p = 0,004), but not in non-smokers patients (r = 0,09; p = 0,49). There is a negative correlation between lymphocyte count and maximum p wave duration in smokers (r = -0,44; p = 0,004) and in non-smoker patients (r = -0,07; p = 0,62).ConclusionMaximum p wave duration is higher in smoker patients than non-smoker patients during ST-elevation acute myocardial infarction. Neutrophil count is positively associated with maximum p wave duration in smoker patients. Lymphocyte count has a negative association with maximum p wave duration.     

Endothelial function and cardiovascular risk in active inflammatory bowel diseases

BackgroundEndothelial dysfunction has been already reported in inflammatory bowel diseases (IBD). However, case series so far examined were rather heterogeneous as for disease severity and subsets investigated.ObjectiveWe evaluated endothelial dysfunction by brachial artery flow-mediated vasodilatation (FMD), and subclinical atherosclerosis by assessment of common carotid intima-media thickness (CCA-IMT) in a cohort of patients with Crohn's disease (CD) or Ulcerative colitis (UC) in active phase compared to healthy control subjects.MethodsForty-nine patients (mean age 41 ± 16 years), 25 with CD and 23 with UC, and forty controls (mean age 45 ± 15 years) were enrolled. Diagnosis was based on the standard clinical, endoscopic and histological criteria. Disease activity was assessed by Crohn's Disease Activity Index or Disease Activity Index. All patients, were under medical treatment as appropriate.ResultsFMD values were lower in IBD patients than controls (6.1 ± 3.0 vs 8.2 ± 3.4. p = 0.003); no difference was seen between UC/CD groups (5.9 ± 3.5 vs 6.3 ± 2.6, p = 0.67). No changes in statistical differences occurred after adjustment for age, gender, body mass index and family history of cardiovascular disease. Finally, no differences in IMT values were seen between IBD patients and controls. Disease duration and medical treatment did not affect endothelial function.ConclusionsOur study showed a lower FMD in IBD patients. Inflammation and immune response could explain endothelial dysfunction, which is the earliest stage of atherosclerotic process. IBD patients in active phase might therefore be at higher risk for atherosclerosis progression.     

Cigarette smoking and albuminuria are associated with impaired arterial smooth muscle function in patients with type 2 diabetes mellitus: a FIELD substudy

AimImpaired arterial function has been implicated in diabetes-related atherosclerosis, but its determinants in high-risk adults have not been well characterised. We investigated factors associated with impaired arterial function in adults with type 2 diabetes.MethodsFlow-mediated dilatation (a marker of endothelial function) and dilator response to glyceryl trinitrate (to assess smooth muscle function) of the brachial artery were assessed at baseline in 193 patients with type 2 diabetes from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Traditional risk factors were assessed and a multivariable model was constructed to identify factors independently associated with impaired arterial function.ResultsMedian age was 64 years (interquartile range, 58–69; 61% male) and duration of diabetes was 4 years (interquartile range, 2–9). Flow-mediated dilatation (3.06 ± 0.25%, mean ± SEM) was severely impaired but not significantly associated with other risk factors. Dilator responses to glyceryl trinitrate (10.56 ± 0.52%) were significantly and independently impaired in past and present cigarette smokers (P = 0.005) and in subjects with increased urinary albumin/creatinine ratio (P = 0.01).ConclusionsIn adults with type 2 diabetes and known or suspected atherosclerosis, arterial smooth muscle-dependent dilatation was shown to be significantly impaired in cigarette smokers and those with elevated urinary albumin levels.