Effects of cognac on coronary flow reserve and plasma antioxidant status in healthy young men

<p>Abstract</p> <p>Background</p> <p>The cardioprotective effects of certain alcoholic beverages are partly related to their polyphenol content, which may improve the vasodilatory reactivity of arteries. Effect of cognac on coronary circulation, however, remains unknown. The purpose of this randomized controlled cross-over study was to determine whether moderate doses of cognac improve coronary reactivity as assessed with cold pressor testing (CPT) and coronary flow reserve (CFR) measument.</p> <p>Methods</p> <p>Study group consisted of 23 subjects. Coronary flow velocity and epicardial diameter was assessed using transthoracic echocardiography at rest, during CPT and adenosine infusion-derived CFR measurements before drinking, after a moderate (1.2 ± 0.1 dl) and an escalating high dose (total amount 2.4 ± 0.3 dl) of cognac. To explore the bioavailability of antioxidants, the antioxidant contents of cognac was measured and the absorption from the digestive tract was verified by plasma antioxidant capacity determination.</p> <p>Results</p> <p>Serum alcohol levels increased to 1.2 ± 0.2‰ and plasma antioxidant capacity from 301 ± 43.9 μmol/l to 320 ± 25.0 μmol/l by 7.6 ± 11.8%, (p = 0.01) after high doses of cognac. There was no significant change in flow velocity during CPT after cognac ingestion compared to control day. CFR was 4.4 ± 0.8, 4.1 ± 0.9 (p = NS), and 4.5 ± 1.2 (p = NS) before drinking and after moderate and high doses on cognac day, and 4.5 ± 1.4, and 4.0 ± 1.2 (p = NS) on control day.</p> <p>Conclusion</p> <p>Cognac increased plasma antioxidant capacity, but it had no effect on coronary circulation in healthy young men.</p> <p>Trial Registration</p> <p>NCT00330213</p

Measurement of cardiac vagal outflow by beat-to-beat R-R interval dynamics

Abstract Analysis of beat-to-beat heart rate variability (HRV) provides information of cardiac vagal outflow to the sinus node. Some methodological problems might, however, be involved in the analysis of cardiac vagal outflow from ambulatory Holter recordings, such as saturation, physical activity, and abrubt prolongations of R-R intervals unrelated to respiration. The purpose of this thesis was to assess the physiological basis of beat-to-beat HRV and to develop and assess new methods for the quantification of cardiac autonomic modulation from ambulatory Holter recordings. The study population consisted of 89 healthy volunteers (age 24 ± 4 years) and 590 patients with a recent acute myocardial infarction (AMI, age 61 ± 10 years). The relationship between R-R interval length and the high-frequency (HF) spectral power of the R-R intervals was assessed in 76 healthy subjects and 82 post-AMI patients. The effects of aerobic exercise training on the dynamics between R-R interval and HF power were evaluated by means of a controlled 8-week training intervention (n = 17). The effects of sympathetic activation and concomitant sympathetic and vagal outflow on beat-to-beat HR dynamics were studied in laboratory conditions (n = 13). A new method for quantifying beat-to-beat HRV from the R-R interval lengths where the relationship between HF power and R-R interval is most linear was developed to avoid the confounding effects of possible saturation, physical activity, and random R-R interval dynamics. The clinical significance of the new method was assessed in a series of 590 post-AMI patients. Saturated HF R-R interval dynamics, expressed as a lack of increase in HF power despite an increased R-R interval, was observed in 35 healthy subjects and 9 post-AMI patients. In the training study, 7 subjects out of a total of 17 had saturated HF power before the intervention. After the training period, 5 new cases of saturated HF power were observed. In laboratory conditions, co-activation of sympathetic and vagal outflow resulted in random R-R interval dynamics. In post-AMI patients, HF power analyzed exclusively from the R-R intervals where the relationship between the R-R interval and HF power was most linear (Vindex) predicted independently the occurrence of SCD among post-AMI patients, while traditionally analyzed HF power did not. In conclusion, the saturation of beat-to-beat HRV in ambulatory conditions is a common phenomenon. The prevalence of saturated HF power increases due to enhanced cardiac vagal outflow induced by aerobic training. Finally, the novel analysis of vagally mediated HRV (Vindex) provides unique information that cannot be obtained by traditional analysis of HF R-R interval dynamics

Accumulation patterns of sedentary time and breaks and their association with cardiometabolic health markers in adults

Abstract Breaking up sedentary time with physical activity (PA) could modify the detrimental cardiometabolic health effects of sedentary time. Our aim was to identify profiles according to distinct accumulation patterns of sedentary time and breaks in adults, and to investigate how these profiles are associated with cardiometabolic outcomes. Participants (n = 4439) of the Northern Finland Birth Cohort 1966 at age 46 years wore a hip-worn accelerometer for 7 consecutive days during waking hours. Uninterrupted ≥1-min sedentary bouts were identified, and non-sedentary bouts in between two consecutive sedentary bouts were considered as sedentary breaks. K-means clustering was performed with 65 variables characterizing how sedentary time was accumulated and interrupted. Linear regression was used to determine the association of accumulation patterns with cardiometabolic health markers. Four distinct groups were formed as follows: “Couch potatoes” (n = 1222), “Prolonged sitters” (n = 1179), “Shortened sitters” (n = 1529), and “Breakers” (n = 509). Couch potatoes had the highest level of sedentariness and the shortest sedentary breaks. Prolonged sitters, accumulating sedentary time in bouts of ≥15–30 min, had no differences in cardiometabolic outcomes compared with Couch potatoes. Shortened sitters accumulated sedentary time in bouts lasting &lt;15 min and performed more light-intensity PA in their sedentary breaks, and Breakers performed more light-intensity and moderate-to-vigorous PA. These latter two profiles had lower levels of adiposity, blood lipids, and insulin sensitivity, compared with Couch potatoes (1.1–25.0% lower values depending on the cardiometabolic health outcome, group, and adjustments for potential confounders). Avoiding uninterrupted sedentary time with any active behavior from light-intensity upwards could be beneficial for cardiometabolic health in adults

Resistin is a risk factor for all-cause mortality in elderly Finnish population:a prospective study in the OPERA cohort

Abstract Objective: Resistin is a small, cysteine-rich proinflammatory molecule that is primarily secreted by peripheral blood mononuclear cells and macrophages in humans. Previous studies have shown resistin to participate in various pathological processes including atherosclerosis and cancer progression but not many studies have assessed the role of resistin as a risk factor for all-cause mortality. The objective of this prospective study was to evaluate whether resistin predicts mortality among elderly Finnish people. Methods: The study population consisted of 599 elderly (71.7 ± 5.4 years) patients and the follow-up was approximately six years. A thorough clinical examination including anthropometric and other clinical measurements such as blood pressure as well as various laboratory parameters (including resistin) was conducted at baseline. Results: After the follow-up, 65 (11%) of the patients died. Resistin was a significant risk factor for all-cause mortality (HR 3.02, 95% CI: 1.64–5.56, p&lt;0.001) when the highest tertile was compared to the lowest. Resistin remained as a significant risk factor even after adjusting for various covariates such as age, sex, systolic blood pressure, smoking habits, alcohol consumption, medications (antihypertensive, lipid-lowering, glucose-lowering), hsCRP and leisure time physical activity. Receiver operating characteristic (ROC) curve analysis for resistin demonstrated area under the curve (AUC) of 0.656 (95% CI: 0.577–0.734), p&lt;0.001 and an optimal cutoff value of 12.88 ng/ml. Conclusions: Our results indicate that resistin is a significant risk factor for all-cause mortality among elderly Finnish subjects, independent from traditional cardiovascular risk factors

Abdominal aorta plaques are better in predicting future cardiovascular events compared to carotid intima-media thickness:a 20-year prospective study

Abstract Background and aims: Both carotid intima-media thickness (IMT) and arterial plaques have been shown to predict future CV events. Since there are no previous studies on the subject, our objective was to compare carotid IMT and the length of plaques in abdominal-pelvic main arteries in CV risk assessment in a prospective study setting with a follow-up of over 20 years. Methods: A total of 1007 patients (50% men), aged 51 ± 6.0 years, participated in the current study. Carotid IMT and the summarized plaque length (SUM) from abdominal aorta to common femoral arteries were ultrasonographically assessed. Patients were followed-up a median (1st-3rd quartile) of 22.5 (17.5–23.2) years for CV events. Results: SUM significantly predicted CV events (HR per every 10 mm increase: 1.035, 95% CI: 1.027–1.044, p &lt; 0.001). Those in the highest SUM tertile had over 3-fold risk for CV event (HR: 3.392, 95% CI: 2.427–4.741, p &lt; 0.001) when compared to those in the lowest tertile. SUM significantly predicted CV events even after adjusting for age, sex, hypertension, diabetes, smoking (pack-years), LDL cholesterol and IMT. Adding SUM to the established model improved C-index (95% CI) from 0.706 (0.674–0.738) to 0.718 (0.688–0.747) as well as both discrimination (p &lt; 0.001) and reclassification (p &lt; 0.001) of the patients. In contrast, IMT predicted cardiovascular events only in univariate analysis and it did not improve discrimination or reclassification of the patients. Conclusions: In light of our findings, SUM is a superior indicator and clinical tool for evaluating the overall CV risk compared to carotid IMT

Home monitoring of heart rate as a predictor of imminent cardiovascular events

Abstract Introduction: Previous studies have documented that day-to-day variability of heart rate (HR) has prognostic significance for cardiovascular (CV) events in general population. It is unknown how HR dynamics variate before imminent CV event in patients with coronary artery disease (CAD). Our aim was to study day-to-day variation in HR dynamics before the occurrence of CV event in patients with initially stable CAD. Methods: Forty-four patients with angiographically documented CAD from ARTEMIS study measured R-R intervals on a weekly basis at home for 2 years. Home measurements were performed in controlled conditions (3 min at supine and sitting) 1–2 times per week. Eleven patients had a CV event (7 acute coronary syndromes, 1 cardiac death, 2 new onset of arrhythmia needing hospitalization and 1 stroke), which occurred 11 ± 7 months after enrolment. Mean R-R interval was analyzed prospectively from the home measurements. For the patients with new CV event, average, and standard deviation (SD) of the mean R-R interval over 8 weeks preceding the CV event were calculated. For the patients without new CV event, corresponding period was determined by the median follow-up at the occurrence of new CV event. Results: There were no differences in the mean R-R interval analyzed over 8 weeks between the patients with and without new CV event. The variability of mean R-R interval over 8 weeks was greater in the patients with new CV event compared to the patients without new CV event at the supine (95 ± 34 vs. 59 ± 26 ms, p &lt; 0.001) and sitting positions (92 ± 28 vs. 62 ± 24 ms, p &lt; 0.001). Conclusion: Day-to-day variability of mean R-R interval is greater before the new CV event in CAD patients suggesting to a more unstable cardiac autonomic regulation preceding these events

Human adult astrocyte extracellular vesicle transcriptomics study identifies specific RNAs which are preferentially secreted as EV luminal cargo

Abstract Astrocytes are central nervous system (CNS)-restricted glial cells involved in synaptic function and CNS blood flow regulation. Astrocyte extracellular vesicles (EVs) participate in neuronal regulation. EVs carry RNAs, either surface-bound or luminal, which can be transferred to recipient cells. We characterized the secreted EVs and RNA cargo of human astrocytes derived from an adult brain. EVs were isolated by serial centrifugation and characterized with nanoparticle tracking analysis (NTA), Exoview, and immuno-transmission electron microscopy (TEM). RNA from cells, EVs, and proteinase K/RNase-treated EVs was analyzed by miRNA-seq. Human adult astrocyte EVs ranged in sizes from 50 to 200 nm, with CD81 as the main tetraspanin marker and larger EVs positive for integrin β1. Comparison of the RNA between the cells and EVs identified RNA preferentially secreted in the EVs. In the case of miRNAs, enrichment analysis of their mRNA targets indicates that they are good candidates for mediating EV effects on recipient cells. The most abundant cellular miRNAs were also abundant in EVs, and the majority of their mRNA targets were found to be downregulated in mRNA-seq data, but the enrichment analysis lacked neuronal specificity. Proteinase K/RNase treatment of EV-enriched preparations identified RNAs secreted independently of EVs. Comparing the distribution of cellular and secreted RNA identifies the RNAs involved in intercellular communication via EVs

Effects of a two-year home-based exercise training program on oxidized LDL and HDL lipids in coronary artery disease patients with and without type-2 diabetes

Abstract We investigated the effect of two-year home-based exercise training program on oxidized low-density lipoprotein LDL (ox-LDL) and high-density lipoprotein HDL (ox-HDL) lipids in patients with coronary artery disease (CAD), both with and without type-2 diabetes (T2D). Analysis of lipoprotein-oxidized lipids was based on the determination of baseline conjugated dienes in lipoprotein lipids. In order to study the effect of an exercise load on ox-LDL and ox-HDL lipids patients in both CAD and CAD + T2D intervention, groups were divided in three based on exercise load (high, medium, and low). During the two-year home-based exercise training program, the study showed that only higher training volume resulted in a decreased concentration of ox-LDL, while the two groups with lower training volumes showed no change. This result indicates that the training load needs to be sufficiently high in order to decrease the concentration of atherogenic ox-LDL lipids in patients with CAD and CAD + T2D. Interestingly, the concentration of ox-HDL did not change in any of the subgroups. This could indicate that the lipid peroxide-transporting capacity of HDL, suggested by results from exercise training studies in healthy adults, may not function similarly in CAD patients with or without T2D. Moreover, the lipid-lowering medication used may have had an influence on these results

Prognostic value of heart rate variability in patients with coronary artery disease in the current treatment era

Abstract Coronary artery disease (CAD) mortality has declined substantially over the past decades thanks to advancing medical and interventional/surgical treatments; therefore, the prognostic value of the heart rate variability in CAD in the current treatment era is not well established. We evaluated the prognostic significance of baseline heart rate variability in 1,757 ARTEMIS study patients with angiographically verified CAD. During an average follow-up time of 8.7 ± 2.2 years, a total of 285 (16.2%) patients died. Of the patients, 63 (3.6%) suffered sudden cardiac death or were resuscitated from sudden cardiac arrest (SCD/SCA), 60 (3.4%) experienced non-sudden cardiac death (NSCD), and death attributable to non-cardiac causes (NCD) occurred in 162 (9.2%) patients. For every 10 ms decrease in standard deviation of normal to normal intervals the risk for SCD/SCA, NSCD and NCD increased significantly: HR 1.153 (95% CI 1.075–1.236, p&lt;0.001), HR 1.187 (95% CI 1.102–1.278, p&lt;0.001) and HR 1.080 (95% CI 1.037–1.125, p&lt;0.001), respectively. The natural logarithm of the low-frequency component of the power spectrum and the short-term scaling exponent of the detrended fluctuation analysis also had significant association with all modes of death (p&lt;0.001). After relevant adjustment, standard deviation of normal-to-normal intervals retained its association with NSCD and NCD (p&lt;0.01), the natural logarithm of the low-frequency component of the power spectrum with all modes of death (p from &lt;0.05 to &lt;0.01), and the short-term scaling exponent of the detrended fluctuation analysis with SCD/SCA (p&lt;0.05) and NCD (p&lt;0.001). In conclusion, impairment of many measures of heart rate variability predicts mortality but is not associated with any specific mode of death in patients with stable CAD during the current treatment era, limiting the clinical applicability of heart rate variability to targeting therapy