-
1.
Exploring the complexity: the interplay between the angiotensin-converting enzyme insertion/deletion polymorphism and the sympathetic response to hemodialysis.
Ribas Ribeiro, L, Flores de Oliveira, J, Bueno Orcy, R, Castilho Barros, C, Damé Hense, J, Santos, F, Irigoyen, MC, Gonzalez, MC, Oses, JP, Böhlke, M
American journal of physiology. Heart and circulatory physiology. 2018;(4):H1002-H1011
Abstract
Patients on hemodialysis (HD) are at increased risk for arrhythmias and sudden cardiac death. Autonomic nervous system (ANS) dysfunction seems to participate in the arrhythmogenic process. Genetic factors have an impact on ANS modulation, but the specific role of the insertion/deletion (I/D) polymorphism in the gene for angiotensin-converting enzyme (ACE) has not been investigated. Since the D allele increases gene expression, it is a candidate polymorphism to interact with the ANS. The aim of the present study was to compare the behavior of heart rate variability (HRV) during HD, as a surrogate for ANS response to stressors, between the ACE genotypes. In a sample of patients with chronic kidney disease I/D ACE genotypes were assessed with PCR and HRV was measured before, in the second hour, and after a HD session. HRV parameters in the time and frequency domains were analyzed by repeated-measures mixed models according to the time of measurement and ACE polymorphism. HRV parameters in the frequency domain presented significantly different variations during the HD session between patients with or without the D allele. Only patients with the II genotype presented an increase in low-frequency normalized units and in the low frequency-to-high frequency ratio throughout HD. Patients with the II genotype seemed to have a more physiological response to the volemic and electrolytic changes that occur during HD, with greater sympathetic activation than patients with ID and DD genotypes. NEW & NOTEWORTHY Adding to the effort to understand the complexity of cardiovascular system regulation, we have found that the autonomic nervous system response to the acute volume removal during hemodialysis may be different between angiotensin-converting enzyme insertion/deletion polymorphisms. To our knowledge, this is the first time that this specific interaction was analyzed during a volume removal intervention.
-
2.
Serum 25-hydroxyvitamin D level is negatively associated with serum phosphorus level among stage 3a-5 chronic kidney disease patients.
Fayed, A, El Nokeety, MM, Heikal, AA, Marzouk, K, Hammad, H, Abdulazim, DO, Salem, MM, Sharaf El Din, UA, ,
Nefrologia. 2018;(5):514-519
Abstract
BACKGROUND Serum 25-hydroxyvitamin D (25(OH)D) negatively correlates with serum phosphorus level of stage 3a-5 chronic kidney disease (CKD) patients. So far, no explanation has been provided for this negative association. OBJECTIVE To confirm this negative association and determine if this relationship is mediated through other known co-morbid factors. CASES AND METHODS One hundred (57 male and 43 female) pre-dialysis stage 3a-5 CKD patients were selected. Estimated glomerular filtration rate (eGFR), serum calcium (Ca), phosphorus (P), 25(OH)D, parathyroid hormone (PTH), and intact fibroblast growth factor-23 (FGF23) were assessed. A correlation analysis between serum 25(OH)D and the different parameters studied was performed. Multivariate linear regression analysis was carried out to determine predictors of 25(OH)D. RESULTS The negative association between serum 25(OH)D and serum P was confirmed in univariate and multivariate correlation analysis. On the other hand, we failed to detect a significant association between 25(OH)D and serum FGF23. Serum P is the most important independent predictor of 25(OH)D in these patients (partial R2=0.15, p<0.0001). CONCLUSION Serum P is likely to have a direct negative impact on serum 25(OH)D. Further studies are needed to determine the underlying mechanism.
-
3.
Central and Brachial Blood Pressures, Statins, and Low-Density Lipoprotein Cholesterol: A Mediation Analysis.
Lamarche, F, Agharazii, M, Nadeau-Fredette, AC, Madore, F, Goupil, R
Hypertension (Dallas, Tex. : 1979). 2018;(3):415-421
Abstract
Central blood pressure may be a better predictor of cardiovascular disease than brachial pressure. Although statins reduce brachial pressure, their impact on central pressure remains unknown. Furthermore, whether this effect is mediated through a decrease in low-density lipoprotein cholesterol (LDL-c) is unknown. This study aims to characterize the association of statins and LDL-c with central and brachial blood pressures and to quantify their respective effects. Of the 20 004 CARTaGENE participants, 16 507 had available central blood pressure, LDL-c, and Framingham risk score. Multivariate analyses were used to evaluate the association between central pressure and LDL-c in subjects with or without statins. The impact of LDL-c on the association between statin and pressure parameters was determined through mediation analyses. LDL-c was positively associated with systolic and diastolic central pressure in nonusers (β=0.077 and 0.106; P<0.001) and in participants with statins for primary (β=0.086 and 0.114; P<0.001) and secondary prevention (β=0.120 and 0.194; P<0.003). Statins as primary prevention were associated with lower central systolic, diastolic, and pulse pressures (-3.0, -1.6, and -1.3 mm Hg; P<0.001). Mediation analyses showed that LDL-c reduction contributed to 15% of central systolic and 44% of central diastolic pressure changes associated with statins and attenuated 22% of the effects on central pulse pressure. Similar results were found with brachial pressure components. In conclusion, reduction of LDL-c was associated with only a fraction of the lower blood pressures in statin user and seemed to be mostly associated with improvement of steady (diastolic) pressure, whereas non-LDL-c-mediated pathways were mostly associated with changes in pulsatile pressure components.
-
4.
Impact of Mon2 monocyte-platelet aggregates on human coronary artery disease.
Brown, RA, Lip, GYH, Varma, C, Shantsila, E
European journal of clinical investigation. 2018;(5):e12911
Abstract
BACKGROUND Monocyte-platelet aggregates (MPAs) form when Mon1, Mon2 or Mon3 monocyte subsets adhere to platelets. They are pathophysiologically linked to coronary artery disease (CAD). However, their individual roles in the occurrence of diffuse CAD remain unknown. MATERIALS AND METHODS Peripheral blood from 50 patients with diffuse CAD, 40 patients with focal CAD and 50 age-matched patients with normal coronary arteries was analysed by flow cytometry to quantify MPAs associated with individual monocyte subsets. Cutaneous forearm microcirculation was assessed using laser Doppler flowmetry at rest and after iontophoresis of acetylcholine (endothelium-dependent vasodilation) and sodium nitroprusside (endothelium-independent vasodilation) at 100 μA for 60 seconds. Patients with CAD had repeat assessment at 6 and 12 months. RESULTS Baseline counts of MPAs with Mon2 subset (CD14++CD16+CC2+ monocytes) were significantly higher in patients with diffuse CAD compared to focal CAD (P = .001) and patients without CAD (P = .006). On multivariate regression, MPAs with Mon2 independently predicted diffuse CAD (odds ratio 1.10, 95% confidence interval 1.02-1.19, P = .01) and correlated negatively with endothelium-dependent microvascular vasodilation (r = -.37, P = .008), an association which persisted after adjustment for covariates. Longitudinal observation confirmed the persistence of an inverse relationship between MPAs with Mon2 and endothelium-dependent microvascular function. CONCLUSION Monocyte-platelet aggregates with Mon2 are increased in patients with diffuse CAD and therefore could represent an important contributor to accelerated coronary atherosclerotic progression by a mechanism involving microvascular endothelial dysfunction.
-
5.
Tooth-borne distraction osteogenesis versus conventional Le Fort I in maxillary advancement of cleft lip and palate patients.
Jamilian, A, Showkatbakhsh, R, Behnaz, M, Ghassemi, A, Kamalee, Z, Perillo, L
Minerva stomatologica. 2018;(3):117-124
Abstract
BACKGROUND Distraction osteogenesis (DO) is rapidly becoming a mainstream surgical technique for correction of maxillary deficiency. The aim of this study was to compare the effectiveness of a newly designed tooth-borne osteogenic distraction device with conventional Le Fort 1 osteotomy in maxillary advancement of cleft lip and palate patients. METHODS The DO group consisted of 10 subjects (7 males, 3 females) with a mean age of 21.2 (SD 4.2) years. In these patients, the newly designed distraction device which exerted force anteroposteriorly was cemented after mobilization of the maxilla. After a latency period of 7 days, the distractor was activated twice daily by a total amount of 0.5 mm per day. The activation was continued for 3 weeks. After an 8-week consolidation period, the distraction appliance was removed. Cephalograms of DO patients were obtained at the start of distraction and at the end of consolidation. The Le Fort 1 group consisted of 11 subjects (6 males, 5 females) with a mean age of 22.3 (SD 3.7) years. Pre and postsurgery lateral cephalograms were obtained. t-test and paired t-test were used to evaluate the data. RESULTS At the end of treatment, the SNA angle of Le Fort 1 patients increased by 5.5° (SD 2.3) (P<0.001) and the SNA angle of DO patients increased by 3.4° (SD 2) (P<0.001). CONCLUSIONS Current evidence suggests that both conventional Le Fort 1 and tooth-borne osteogenic distraction device can effectively advance the maxilla forward in patients with cleft lip.
-
6.
Heterogeneity in blood pressure in UK Bangladeshi, Indian and Pakistani, compared to White, populations: divergence of adults and children.
Battu, HS, Bhopal, R, Agyemang, C
Journal of human hypertension. 2018;32(11):725-744
-
-
Free full text
-
Abstract
Blood pressure (BP) and hypertension prevalence differences between UK South Asians (Bangladeshis, Indians and Pakistanis) and White Europeans exist in childhood and adulthood. This meta-analysis sought to quantify these differences. We searched MEDLINE (1946-2017), EMBASE (1974-2017) and GLOBAL HEALTH (1973-2017) for comparative studies and pooled the data with Revman (Cochrane Collaboration). Twenty-two studies were included-fourteen on adults and eight on children. South Asian adults had lower systolic and slightly lower diastolic BP. However, stark heterogeneity existed between South Asian subgroups: Bangladeshis had markedly lower systolic BP (mean difference: -11.7 mmHg in men and women), Indians slightly lower (-2.0 mmHg in men and -4.5 mmHg in women) and Pakistanis intermediately lower (-7.9 mmHg in men and -8.6 mmHg in women), compared to White Europeans. However, South Asian children did not have lower systolic or diastolic BP compared to White children, and their BP was often higher. This intergenerational change in BP difference mirrored the change in body mass index difference, particularly in Bangladeshis. We conclude that ethnicity-related BP differences are heterogeneous and dependent on age, sex and South Asian subgroup. South Asian children do not have lower BP than White Europeans in contrast to their adult counterparts. There is concern that this pattern may continue into adulthood, worsening the already high cardiovascular disease burden in South Asians in future years. Further research is needed to ascertain the causes of this evolving issue.
-
7.
Anti-Inflammatory Effects of a Vegan Diet Versus the American Heart Association-Recommended Diet in Coronary Artery Disease Trial.
Shah, B, Newman, JD, Woolf, K, Ganguzza, L, Guo, Y, Allen, N, Zhong, J, Fisher, EA, Slater, J
Journal of the American Heart Association. 2018;7(23):e011367
-
-
-
Free full text
Plain language summary
Inflammation plays a central role in the progression of atherosclerosis and is associated with adverse cardiovascular events. The aim of this study was to determine the effects of a vegan versus American Heart Association (AHA)-recommended diet on high-sensitivity C-reactive protein (hsCRP) [a type of protein found in blood plasma], as well as other markers of inflammation, glucometabolic markers, and lipid profiles in patients with established coronary artery disease (CAD) on guideline-directed medical therapy. This study is a prospective, randomized, open-label, blinded end point study design. The active study duration was 8 weeks, with an interim visit at 4 weeks and a final visit at 8 weeks. Results show: - a significantly greater reduction in hsCRP with a vegan versus AHA-recommended diet in patients with established CAD on guideline-directed medical therapy. - that the degree of weight loss, as measured by both body mass index and waist circumference, did not significantly differ between the 2 diet groups. - that markers of glycaemic control and lipid profiles, overall, also did not significantly differ in the vegan diet group when compared with the AHA-recommended diet group. Authors conclude that in patients with CAD and an elevated hsCRP, despite guideline-directed medical therapy, a vegan diet may be considered to further lower the parameters of inflammation.
Abstract
Background Dietary interventions may play a role in secondary cardiovascular prevention. hsCRP (High-sensitivity C-reactive protein) is a marker of risk for major adverse cardiovascular outcomes in coronary artery disease. Methods and Results The open-label, blinded end-point, EVADE CAD (Effects of a Vegan Versus the American Heart Association-Recommended Diet in Coronary Artery Disease) trial randomized participants (n=100) with coronary artery disease to 8 weeks of a vegan or American Heart Association-recommended diet with provision of groceries, tools to measure dietary intake, and dietary counseling. The primary end point was high-sensitivity C-reactive protein. A linear regression model compared end points after 8 weeks of a vegan versus American Heart Association diet and adjusted for baseline concentration of the end point. Significance levels for the primary and secondary end points were set at 0.05 and 0.0015, respectively. A vegan diet resulted in a significant 32% lower high-sensitivity C-reactive protein (β, 0.68, 95% confidence interval [0.49-0.94]; P=0.02) when compared with the American Heart Association diet. Results were consistent after adjustment for age, race, baseline waist circumference, diabetes mellitus, and prior myocardial infarction (adjusted β, 0.67 [0.47-0.94], P=0.02). The degree of reduction in body mass index and waist circumference did not significantly differ between the 2 diet groups (adjusted β, 0.99 [0.97-1.00], P=0.10; and adjusted β, 1.00 [0.98-1.01], P=0.66, respectively). There were also no significant differences in markers of glycemic control between the 2 diet groups. There was a nonsignificant 13% reduction in low-density lipoprotein cholesterol with the vegan diet when compared with the American Heart Association diet (adjusted β, 0.87 [0.78-0.97], P=0.01). There were no significant differences in other lipid parameters. Conclusions In patients with coronary artery disease on guideline-directed medical therapy, a vegan diet may be considered to lower high-sensitivity C-reactive protein as a risk marker of adverse outcomes. Clinical Trial Registration URL http://www.clinicaltrials.gov . Unique identifier: NCT 02135939.
-
8.
Effect of food on the pharmacokinetic characteristics of a single oral dose of LCB01-0371, a novel oxazolidinone antibiotic.
Sunwoo, J, Kim, YK, Choi, Y, Yu, KS, Nam, H, Cho, YL, Yoon, S, Chung, JY
Drug design, development and therapy. 2018;:1707-1714
Abstract
BACKGROUND LCB01-0371 is a novel oxazolidinone antibiotic that blocks protein production by binding to bacterial 23S ribosomes. This antibiotic is active against Gram-positive bacteria. This study aimed to evaluate the effect of food on the pharmacokinetics (PKs) of LCB01-0371 and evaluate its safety profile. SUBJECTS AND METHODS A randomized, open-label, two-way crossover study was performed in 18 healthy Korean male subjects. All subjects received a single oral 800 mg dose of LCB01-0371 in each period under fed or fasting condition with a 7-day washout in between. The fed condition was defined as consumption of a meal of 800-1,000 kcal containinĝ50% of fat content. Serial blood samples were collected over 24 h after dosing, and the PK parameters were calculated by noncompartment analysis. All available data of the subjects who received LCB01-0371 at least once were included in the safety data summaries. RESULTS In the fed condition, both the maximum plasma concentration (Cmax) and the total systemic exposure (area under the plasma concentration-time curve from time zero to the last observed time point [AUClast]) decreased by ~33% and 10%, respectively. The time to reach Cmax was delayed by ~1.25 h in the fed condition, whereas the mean elimination half-life remained similar in both conditions. In the fed/fasting condition, the geometric mean ratios and 90% CI of the Cmax and AUClast were 0.666 (0.470-0.945) and 0.897 (0.761-1.057), respectively. There were no drug-related adverse events (AEs) or serious AEs. CONCLUSION Although the Tmax after a single oral 800 mg dose of LCB01-0371 was slightly delayed under the fed condition compared to the fasting condition, the total systemic exposure was similar under both conditions. Therefore, LCB01-0371 could be administered regardless of food intake.
-
9.
Randomized controlled European multicenter trial on the prevention of cystoid macular edema after cataract surgery in diabetics: ESCRS PREMED Study Report 2.
Wielders, LHP, Schouten, JSAG, Winkens, B, van den Biggelaar, FJHM, Veldhuizen, CA, Murta, JCN, Goslings, WRO, Kohnen, T, Tassignon, MJ, Joosse, MV, et al
Journal of cataract and refractive surgery. 2018;(7):836-847
Abstract
PURPOSE To compare the efficacy of perioperative treatment strategies, in addition to topical bromfenac 0.09% and dexamethasone 0.1%, to reduce the risk for developing cystoid macular edema (CME) after uneventful cataract surgery in diabetic patients. SETTING Twelve European study centers. DESIGN Randomized clinical trial. METHODS Diabetic patients having phacoemulsification cataract surgery were randomly allocated to receive no additional treatment, a subconjunctival injection with 40 mg triamcinolone acetonide, an intravitreal injection with 1.25 mg bevacizumab, or a combination of both. The main outcomes were the difference in central subfield mean macular thickness, corrected distance visual acuity, and the incidence of CME and clinically significant macular edema within 6 and 12 weeks postoperatively. RESULTS The study comprised 213 patients. At 6 and 12 weeks postoperatively, the central subfield mean macular thickness was 12.3 μm and 9.7 μm lower, respectively, in patients who received subconjunctival triamcinolone acetonide than patients who did not (P = .007 and P = .014, respectively). No patient who received subconjunctival triamcinolone acetonide developed CME. Intravitreal bevacizumab had no significant effect on macular thickness. CONCLUSIONS Diabetic patients who received a subconjunctival injection with triamcinolone acetonide at the end of cataract surgery had a lower macular thickness and macular volume at 6 and 12 weeks postoperatively than patients who did not. Intravitreal bevacizumab had no significant effect.
-
10.
Randomized cross-over trial comparing the diagnosis of gestational diabetes by oral glucose tolerance test and a designed breakfast glucose profile.
Marais, C, Hall, DR, van Wyk, L, Conradie, M
International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. 2018;(1):85-90
Abstract
OBJECTIVE To compare a glucose test based on a standardized, designed breakfast to the 75-g oral glucose tolerance test (OGTT), comparing venous and capillary glucose values for the diagnosis of gestational diabetes mellitus (GDM). METHODS The present prospective, randomized, cross-over trial enrolled patients at high risk of developing GDM who were attending the High-Risk Antenatal Clinic of Tygerberg Hospital, Cape Town, South Africa, between March 1 and December 31, 2015. Patients were randomized to initial testing with either the OGTT or a designed breakfast glucose profile (DBGP) glucose test before the alternate test was performed 1 week later; no dietary or other interventions were applied in the intervening period. Venous and capillary fasting and 2-hour glucose values were measured and were compared between the OGTT and DBGP, and between OGTT and laboratory venous samples. RESULTS There were 51 patients included in the study. The fasting and 2-hour capillary glucose values from the OGTT correlated significantly with the laboratory venous samples (P<0.001 at both time intervals). The 2-hour capillary glucose values from the DBGP demonstrated a satisfactory correlation with those from the OGTT (P<0.001). CONCLUSIONS The DBGP provided a sufficiently accurate alternate test for the diagnosis of GDM; it warrants further investigation.