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.     

Reduction in HbA1c with SGLT2 inhibitors vs. DPP-4 inhibitors as add-ons to metformin monotherapy according to baseline HbA1c: A systematic review of randomized controlled trials

AimsThis study compared the reduction of glycated haemoglobin (HbA1c) with sodium-glucose cotransporter type-2 inhibitors (SGLT2is) vs. dipeptidyl peptidase-4 inhibitors (DPP-4is) as add-ons to metformin in patients with type 2 diabetes mellitus (T2DM), with a specific focus on HbA1c changes according to baseline HbA1c.Materials and methodsElectronic databases were scrutinized for randomized controlled trials (RCTs) evaluating the reduction of HbA1c from baseline (Δ HbA1c) with an SGLT2i or DPP-4i in patients with T2DM not well controlled by metformin monotherapy. The endpoint was Δ HbA1c using both indirect and direct comparisons.ResultsOverall, Δ HbA1c was slightly greater with SGLT2is (−0.80 ± 0.20% from 8.03 ± 0.35%; 44 analyses, 29 RCTs, 15 with two doses, n = 9321) than with DPP-4is (−0.71 ± 0.23% from 8.05 ± 0.43%; 61 analyses, 59 RCTs, n = 17,914; P = 0.0354). When the mean baseline HbA1c was < 8% ([64 mmol/mol] 7.79 ± 0.15% vs. 7.71 ± 0.23%), Δ HbA1c averaged −0.735 ± 0.17% vs. −0.62 ± 0.16% (P = 0.0117) with SGLT2is vs. DPP-4is, respectively. However, this difference vanished when the mean baseline HbA1c was ≥ 8% (−0.87 ± 0.22% from 8.27 ± 0.32% with SGLT2is vs. −0.80 ± 0.24% from 8.35 ± 0.33% with DPP-4is; P = 0.2756). The relationship between Δ HbA1c and baseline HbA1c was only slightly stronger with SGLT2is (slope: −0.39, r² = −0.43; P < 0.0001) than with DPP-4is (slope: −0.26, r² = −0.25; P < 0.0001).ConclusionBecause of the small difference in Δ HbA1c whatever the baseline HbA1c level with SGLT2is vs. DPP-4is as add-ons to metformin, choosing between these glucose-lowering agents in clinical practice should be based on other efficacy criteria (such as weight and blood pressure changes, cardiovascular and renal protection) or on safety profiles rather than on HbA1c levels.     

Angiotensin II receptor antagonism with telmisartan increases number of endothelial progenitor cells in normotensive patients with coronary artery disease: A randomized,double-blind,placebo-controlled study

IntroductionCirculating endothelial progenitor cells (EPCs) provide an endogenous repair mechanism of the dysfunctional endothelium and therefore can play a crucial role in the pathophysiology of coronary artery disease (CAD). Angiotensin II receptor antagonism has been shown to be able to increase EPCs in hypertension but its effect in patients with CAD is unknown. Aim of this study was to evaluate whether telmisartan, an angiotensin II receptor antagonist, can modify the number of subpopulations of EPCs and may in turn affect the endothelial function of normotensive patients with CAD.MethodsIn a prospective double-blind parallel group study, 40 normotensive patients with CAD were randomly treated with telmisartan (80 mg) or placebo for 4 weeks at time of coronary angiography. Measurements of EPCs and assessment of flow-mediated dilatation (FMD) of the brachial artery was performed before and after therapy.ResultsAbsolute number of EPCs was similar at baseline in the telmisartan and placebo groups. After 4 weeks treatment, CD34+/KDR+/CD45? cells increased significantly in the telmisartan group (from 0.010 ± 0.003 to 0.014 ± 0.004%, P = 0.0001) but not in the placebo group (from 0.009 ± 0.004 to 0.009 ± 0.005%, NS). Similarly, CD133+/KDR+/CD45? cells raised significantly with telmisartan (from 0.003 ± 0.002 to 0.006 ± 0.002%, P = 0.0001) but not with placebo (from 0.004 ± 0.003 to 0.003 ± 0.002%, NS). Also, CD14+/CD45+ cells increased significantly with telmisartan (from 0.005 ± 0.002 to 0.008 ± 0.002%, P = 0.0001) and were unchanged with placebo (0.006 ± 0.002 vs. 0.005 ± 0.003%, NS). FMD improved significantly in patients who received telmisartan (10.4 ± 3.9%, P = 0.0015 vs. baseline) but did not change in the placebo group (5.9 ± 2.8%; P = 0.32 vs. baseline; telmisartan vs. placebo, P = 0.002). A significant positive correlation was found in the telmisartan group between the improvement in FMD and the increase in CD34+/KDR+/CD45? cells and CD133+/KDR+/CD45? cells (r = 0.55, P < 0.01, and r = 0.49, P < 0.05, respectively).ConclusionAngiotensin II receptor antagonism with telmisartan increases the number of regenerative EPCs and improves endothelial function in normotensive patients with CAD. These novel effects are interrelated and can explain, at least in part, why telmisartan has beneficial cardiovascular effects independent of its blood pressure lowering action.     

Effect of free fatty acid inhibition on silent and symptomatic myocardial ischemia in diabetic patients with coronary artery disease

ObjectiveFree fatty acid inhibition with trimetazidine (TMZ) improves myocardial metabolism and myocardial ischemia in patients with coronary artery disease (CAD). Because of its effect on myocardial glucose utilization TMZ may represent a therapeutic option in diabetic patients with CAD. Aim of the present study was to evaluate whether the metabolic effect of TMZ may improve episodes of myocardial ischemia in diabetic patients with CAD.Research design and methodsWe assessed the effect of TMZ on 24 h ambulatory ECG monitoring (AEM) in 30 patients (22 males and 8 females, mean (SE) age 67 ± 6.5 years) with NIDDM and ischemic cardiomyopathy. Patients were randomized to receive on top of standard therapy either TMZ (20 mg, tds) or placebo (tds) and were evaluated at baseline and after 6 months.ResultsPatients randomized to TMZ or placebo were comparable regarding demographic data, distribution of CAD, and glicated haemoglobin levels. TMZ significantly reduced the number of episodes of transient myocardial ischemia (− 24% compared to baseline, p < 0.01; − 27% compared to placebo, p < 0.01), and Total Ischemic Burden (− 28% compared to baseline, p < 0.01; − 29% compared to placebo, p < 0.01). TMZ also significantly reduced the number of silent episodes of myocardial ischemia (− 42% compared to baseline and − 39% compared to placebo, p < 0.01) and the time of silent myocardial ischemia/24 h (− 37% compared to baseline and − 35% compared to placebo, p < 0.01). No significant changes in heart rate were detected between baseline, placebo and TMZ evaluations.ConclusionsTMZ is effective in reducing silent and symptomatic episodes of transient myocardial ischemia in diabetic patients with CAD on standard anti-anginal therapy.     

A randomised controlled trial of high dose vitamin D in recent-onset type 2 diabetes

AimsVitamin D insufficiency has been associated with impaired pancreatic beta-cell function. We aimed to determine if high dose oral vitamin D3 (D) improves beta-cell function and glycaemia in type 2 diabetes.MethodsFifty adults with type 2 diabetes diagnosed less than 12 months, with normal baseline serum 25-OH D (25D), were randomised to 6000 IU D (n = 26) or placebo (n = 24) daily for 6 months. Beta-cell function was measured by glucagon-stimulated serum C-peptide (delta C-peptide [DCP], nmol/l). Secondary outcome measures were fasting plasma glucose (FPG), post-prandial blood glucose (PPG), HbA1c and insulin resistance (HOMA-IR).ResultsIn the D group, median serum 25D (nmol/l) increased from 59 to 150 (3 months) and 128 (6 months) and median serum 1,25D (pmol/l) from 135 to 200 and 190. After 3 months, change in DCP from baseline in D (+0.04) and placebo (−0.08) was not different (P = 0.112). However, change in FPG (mmol/l) was significantly lower in D (−0.40) compared to placebo (+0.1) (P = 0.007), as was the change in PPG in D (−0.30) compared to placebo (+0.8) (P = 0.005). Change in HbA1c (%) between D (−0.20) and placebo (−0.10) was not different (P = 0.459). At 6 months, changes from baseline in DCP, FPG, PPG and HbA1c were not different between groups.ConclusionOral D3 supplementation in type 2 diabetes was associated with transient improvement in glycaemia, but without a measurable change in beta-cell function this effect is unlikely to be biologically significant. High dose D3 therefore appears to offer little or no therapeutic benefit in type 2 diabetes.     

The correlation between speckle tracking echocardiography and coronary artery disease in patients with suspected stable angina pectoris

BackgroundTo examine the value of speckle tracking echocardiography to detect the presence, extent and severity of coronary artery affection in patients with suspected stable angina pectoris.MethodsTwo hundred candidates with suspected stable angina pectoris and normal resting conventional echocardiography were subjected to speckle tracking echocardiography and coronary angiography. Global and segmental longitudinal peak systolic strain were assessed and were correlated to the results of coronary angiography for each patient.ResultsThere was a statistically significant difference in the mean of global longitudinal peak systolic strain between normal coronaries and different degrees of coronary artery disease (CAD) (−20.11 ± 0.8 for normal, −18.34 ± 2.52 for single vessel, −16.14 ± 2.85 for two vessels, −14.81 ± 2.12 for three vessels, −13.01 ± 2.92 for left main disease). GLPSS showed high sensitivity for the diagnosis of single vessel CAD (90%, specificity 95.1%, cutoff value: −18.44, AUC: 0.954); two vessels disease (90%, sensitivity 88.9%, cutoff value −17.35, AUC: 0.906) and for three vessels CAD (cutoff value −15.33, sensitivity 63% and specificity 72.2% AUC 0.681) segmental LPSS also showed statistical significance for localization of the affected vessel for left anterior descending, left circumflex and right coronary artery (ρ = 0.001) and inverse correlation with syntax score that was significant with high and intermediate score (ρ = 0.001) and insignificant for low syntax score (ρ value 0.05).ConclusionTwo-dimensional speckle tracking echocardiography has good sensitivity and specificity to predict the presence, extent and severity of CAD.     

Telemedicine and type 1 diabetes: Is technology per se sufficient to improve glycaemic control?

AimIn the TELEDIAB-1 study, the Diabeo system (a smartphone coupled to a website) improved HbA_1c by 0.9% vs controls in patients with chronic, poorly controlled type 1 diabetes. The system provided two main functions: automated advice on the insulin doses required; and remote monitoring by teleconsultation. The question is: how much did each function contribute to the improvement in HbA_1c?MethodsEach patient received a smartphone with an insulin dose advisor (IDA) and with (G3 group) or without (G2 group) the telemonitoring/teleconsultation function. Patients were classified as “high users” if the proportion of “informed” meals using the IDA exceeded 67% (median) and as “low users” if not. Also analyzed was the respective impact of the IDA function and teleconsultations on the final HbA_1c levels.ResultsAmong the high users, the proportion of informed meals remained stable from baseline to the end of the study 6 months later (from 78.1 ± 21.5% to 73.8 ± 25.1%; P = 0.107), but decreased in the low users (from 36.6 ± 29.4% to 26.7 ± 28.4%; P = 0.005). As expected, HbA_1c improved in high users from 8.7% [range: 8.3–9.2%] to 8.2% [range: 7.8–8.7%] in patients with (n = 26) vs without (n = 30) the benefit of telemonitoring/teleconsultation (−0.49 ± 0.60% vs −0.52 ± 0.73%, respectively; P = 0.879). However, although HbA_1c also improved in low users from 9.0% [8.5–10.1] to 8.5% [7.9–9.6], those receiving support via teleconsultation tended to show greater improvement than the others (−0.93 ± 0.97 vs −0.46 ± 1.05, respectively; P = 0.084).ConclusionThe Diabeo system improved glycaemic control in both high and low users who avidly used the IDA function, while the greatest improvement was seen in the low users who had the motivational support of teleconsultations.     

Les protéines purifiées à partir de sardines améliorent les chiffres tensionnels,l’équilibre glycémique,les voies métaboliques anti-athérogènes et la capacité anti-oxydante,chez le rat obèse

Aim of the studyThe effects of sardine by-products (SBy-P) and fillet proteins (SF-P) were compared to casein (Cas) ; these effects were assessed on blood pressure, glycemic control, reverse cholesterol transport, lipid peroxidation and total antioxidant capacity in obese rats.Materials and methodsEighteen male Wistar rats were subjected for three months, to a high-fat diet. The obese rats were divided into three groups and consumed the same high-fat diet for 28 days after addition of either, 20% SBy-P, SF-P or Cas.ResultsThe sardine proteins (SBy-P and SF-P) compared respectively to Cas, reduced diastolic (−14%, −11% P < 0.05) and systolic pressures (−12%, −8% P < 0.05), blood glucose (−24%, −21% P < 0.05), glycated hemoglobin (−28%, −21% P < 0.05), insulinemia (−29%, −18% P < 0.05) and HOMA-IR index (−29%, −18% P < 0.05). They improve the reverse cholesterol transport by increasing the lecithin: cholesterol acyltransferase (LCAT) activity (+43%, +30% P < 0.05) and high-density lipoproteins in cholesterol esters (+108%, +88% P < 0.05), and decreasing the atherogenicity ratios and membrane fluidity (P < 0.05). Furthermore, SBy-P and SF-P induced a reduction of reactive thiobarbituric acid substances concentrations in heart (−45%, −25% P < 0.05), aorta (−62%, −41% P < 0.05), liver (−40%, −21% P < 0.05) and adipose tissue (−50%, −37% P < 0.05) with an improvement in antioxidant capacity.ConclusionSardine proteins, in particular those extracted from by-products, because of their hypotensive, hypoglycemic, anti-atherogenic and antioxidant properties, may have protective effects against the cardiovascular risk associated with obesity.     

Fonction ventriculaire droite après un premier épisode d’embolie pulmonaire : apport du strain 2D

BackgroundAnalysis of right ventricular (RV) function during the acute phase of pulmonary embolism (PE) was widely reported in the literature. However, few studies analysed its function long term after the acute phase. Our aim was to evaluate the RV function long term after a first episode of PE.MethodsIn this study, we compared echocardiographic parameters of right ventricular function in 25 patients with a first episode of non-severe PE for more than six months with 25 healthy controls subject.ResultsIn the study of RV function, we noted that the mean values of the standard parameters were significantly lower in the EP group compared to the control group but their values remained within the normal range. The global RV longitudinal strain had a mean value lower than the control group statistically significant (−21 ± 4,8% vs. −25 ± 2,4%; P = 0,28). The longitudinal strain of the free wall of the RV was altered in the EP group, however, there was no significant difference between the EP group and the control group (−19,4 ± 16% vs. −24 ± 17%; P = 0,28).ConclusionThis study has shown that there is a systolic dysfunction late after a first episode of PE and this despite the absence of the symptoms and pulmonary hypertension.     

Impact of a simulation-based training on the experience of the beginning of residency

IntroductionWe aimed to evaluate the impact of an immersive simulation session on the experience of the beginning of residency.MethodsThe interventional group consisted of newly recruited residents in 2019, who participated in the workshop presenting four emergency scenarios frequently encountered during night shifts; the control group comprised residents who had begun their internship in 2018, without having participated in the simulation workshop. The level of psychological stress and self-confidence were self-estimated in the simulation group before and immediately after the workshop. During the second semester of residency, stress, self-efficacy and anxiety were evaluated in both groups with the Perceived Stress Scale (PSS), General Self-efficacy Scale (GSES), and Generalized Anxiety Disorder-7 (GAD-7) scale.ResultsIn the second semester 2020, the PSS, GSES and GAD-7 were 20.71 ± 8.15 and 22.44 ± 5.68 (P = 0.40); 26.88 ± 6.30 and 27.11 ± 3.95 (P = 0.87); 6.94 ± 5.25 and 8.89 ± 4.78 (P = 0.22) for the simulation (n = 17, 89.5% of participation) and control (n = 9, 75%) groups, respectively. In the simulation group, the level of self-confidence had significantly improved from 1.82 ± 0.95 before the session to 2.29 ± 1.16 after the session (P = 0.05). Interestingly, this improvement in self-confidence was significantly correlated with GAD-7 (P = 0.014) and PSS (P = 0.05), and tended to be correlated with GSES (P = 0.09).ConclusionOur study showed a significant improvement in self-confidence between before and after the simulation session. Residents who experienced an improvement in self-confidence saw their stress and anxiety levels decrease during the second semester reevaluation, in favor of a prolonged benefit from the session.     

Patterns of Physical Activity Progression in Patients With COPD

IntroductionAlthough mean physical activity in COPD patients declines by 400–500 steps/day annually, it is unknown whether the natural progression is the same for all patients. We aimed to identify distinct physical activity progression patterns using a hypothesis-free approach and to assess their determinants.MethodsWe pooled data from two cohorts (usual care arm of Urban Training [NCT01897298] and PROactive initial validation [NCT01388218] studies) measuring physical activity at baseline and 12 months (Dynaport MoveMonitor). We identified clusters (patterns) of physical activity progression (based on levels and changes of steps/day) using k-means, and compared baseline sociodemographic, interpersonal, environmental, clinical and psychological characteristics across patterns.ResultsIn 291 COPD patients (mean ± SD 68 ± 8 years, 81% male, FEV₁ 59 ± 19%_pred) we identified three distinct physical activity progression patterns: Inactive (n = 173 [59%], baseline: 4621 ± 1757 steps/day, 12-month change (Δ): −487 ± 1201 steps/day), Active Improvers (n = 49 [17%], baseline: 7727 ± 3275 steps/day, Δ: + 3378 ± 2203 steps/day) and Active Decliners (n = 69 [24%], baseline: 11 267 ± 3009 steps/day, Δ: −2217 ± 2085 steps/day). After adjustment in a mixed multinomial logistic regression model using Active Decliners as reference pattern, a lower 6-min walking distance (RRR [95% CI] 0.94 [0.90–0.98] per 10 m, P = .001) and a higher mMRC dyspnea score (1.71 [1.12–2.60] per 1 point, P = .012) were independently related with being Inactive. No baseline variable was independently associated with being an Active Improver.ConclusionsThe natural progression in physical activity over time in COPD patients is heterogeneous. While Inactive patients relate to worse scores for clinical COPD characteristics, Active Improvers and Decliners cannot be predicted at baseline.     

Altération de la fonction systolique longitudinale du ventricule gauche en strain bidimensionnel dans l’hyperaldostéronisme primaire : un nouveau marqueur d’atteinte d’organe cible

ObjectivePrimary hyperaldosteronism is the leading cause of secondary hypertension, and leads to frequent cardiovascular complications. Many studies have studied left ventricular geometry and function in this population, but longitudinal systolic function is still poorly described.MethodsWe studied 35 hypertensive patients with primary aldosteronism, and 35 with essential hypertension matched for age, sex, body mass index, and 24 h blood pressure. Patients benefited from an echocardiography to measure the mass and the geometry of the left ventricle, left ventricle ejection fraction, systolic longitudinal, circumferential, and radial strain, and diastolic function.ResultsCompared to essential hypertensive patients, patients with primary aldosteronism presented a significantly higher left ventricular mass index and relative wall thickness (60.3 ± 16.1 g/m² vs 47.3 ± 18.6, P = 0.003, and 0.44 ± 0.08 vs 0.36 ± 0.06, P = 0.00005, respectively), as well as a significantly reduced longitudinal systolic strain (−17.8 ± 3,4 vs −20.3 ± 3,6%, P = 0.004). There were no significant differences in the other parameters.ConclusionsPrimary aldosteronism is associated with a deterioration of longitudinal systolic function of the left ventricle compared with essential hypertensive patients. This marker of cardiac damage, reproducible and easily available in routine could help for the screening of these patients.     

Effects of a fish-based diet and administration of pure eicosapentaenoic acid on brachial-ankle pulse wave velocity in patients with cardiovascular risk factors

Background and purposeBrachial-ankle pulse wave velocity (baPWV) and ratio of plasma eicosapentaenoic acid to arachidonic acid (EPA/AA ratio) are surrogate markers for coronary artery disease (CAD). We aimed to evaluate the effects of a fish-based diet and administration of EPA on baPWV and plasma EPA/AA ratio.Methods and resultsThe changes in baPWV and plasma EPA/AA ratio were compared before and after a 6-month fish-based diet in 191 patients with cardiovascular risk factors. A fish-based diet resulted in significant increment of plasma EPA/AA ratio (0.40 ± 0.18 vs. 0.49 ± 0.27, p < 0.001), with baPWV remaining unchanged. Multivariate analysis revealed that systolic blood pressure (SBP) (6-month SBP-baseline SBP) and CAD were positively associated with increased baPWV (CAD: odds ratio = 2.040, p = 0.0436, SPB: odds ratio = 1.056, p = 0.0003). When the patients were divided into three groups: CAD, low-risk, and high-risk with no prior history of CAD according to the number of risk factors at baseline, comparison among the three groups disclosed an inter-group difference in the magnitude of change in baPWV (low-risk: −35 ± 164 cm/s, high-risk: −14 ± 190 cm/s, CAD: 39 ± 164 cm/s, p = 0.0071 for trend). In 191 patients who had received a 6-month fish-based diet, 21 patients (primarily CAD patients) sequentially received high purity EPA (1800 mg/day) for 6 months. It resulted in marked increment of plasma EPA/AA ratio (0.65 ± 0.57 vs. 1.19 ± 0.46, p < 0.001), accompanied by significant reduction in baPWV (1968 ± 344 cm/s vs. 1829 ± 344 cm/s, p = 0.0061). There was a significant negative correlation between changes in baPWV and changes in plasma EPA/AA ratio in patients with a fish-based diet and sequential administration of EPA (r = −0.446, p = 0.017).ConclusionA fish-based diet was effective against increased baPWV only in low-risk patients, with slight increment of plasma EPA/AA. In high-risk patients and CAD patients, administration of EPA for preventing progression of baPWV endorsed the validity of high purity EPA administration recommended in the current guidelines.     

Allelic variations of the vitamin D receptor (VDR) gene are associated with increased risk of coronary artery disease in type 2 diabetics: The DIABHYCAR prospective study

AimVitamin D deficiency is associated with coronary artery disease (CAD), and the actions of vitamin D are mediated by binding to a specific nuclear vitamin D receptor (VDR). This study investigated the associations of VDR gene variants with CAD in two cohorts of type 2 diabetes patients.MethodsA cohort of 3137 subjects from the prospective DIABHYCAR study (CAD incidence: 14.8%; follow-up: 4.4 ± 1.3 years) and an independent, hospital-based population of 713 subjects, 32.3% of whom had CAD, were assessed. Three SNPs in the VDR gene were genotyped: rs1544410 (BsmI); rs7975232 (ApaI); and rs731236 (TaqI).ResultsIn the DIABHYCAR cohort, an association was observed between the A allele of BsmI and incident cases of CAD (HR: 1.16, 95% CI: 1.05–1.29; P = 0.002). Associations were also observed between BsmI (P = 0.01) and TaqI (P = 0.04) alleles and baseline cases of CAD. The AAC haplotype (BsmI/ApaI/TaqI) was significantly associated with an increased CAD prevalence at the end of the study compared with the GCT haplotype (OR: 1.12, 95% CI: 1.02–1.28; P = 0.04). In a cross-sectional study of the independent hospital-based cohort, associations of ApaI (P = 0.009) and TaqI (P = 0.03) alleles with CAD were observed, with similar haplotype results (OR: 1.33, 95% CI: 1.03–1.73; P = 0.03).ConclusionThe haplotype comprising the minor allele of BsmI, major allele of ApaI and minor allele of TaqI of VDR (AAC) was associated with an increased risk of CAD in type 2 diabetes patients. This effect was independent of the effects of other known cardiovascular risk factors.     

Transition from angiotensin-converting enzyme inhibitor/angiotensin-II-receptor-blocker to sacubitril/valsartan in chronic heart failure patients: Initial experiences in clinical practice

BackgroundSacubitril/valsartan (S/V) therapy has been demonstrated to improve prognosis of systolic heart failure (HF) patients when compared to standard therapy with ACEi. The purpose of this investigation was to document the safety and consequences of transition from ACEi/angiotensin-II receptor blocker (ARB) to S/V in chronic stable HF patients.MethodsA group of 12 stable HF outpatients (11 males, 1 female) was enrolled (NYHA 2.7 ± 0.7, 42% with coronary artery disease (CAD), average left-ventricle ejection fraction (LVEF) 26.5%). Patients were converted from ACEi/ARB to S/V. Laboratory evaluation, Minnesota Living with Heart Failure Questionnaire (MLHFQ), six-minute walk test (6MWT) were performed before the conversion and at 3-month follow-up visit.ResultsConversion from ACEi/ARB to S/V was not associated with any adverse event. After 3 months, S/V therapy decreased blood pressure (−14.8 mmHg for systolic BP, −9.6 mmHg for diastolic BP) and serum potassium (−0.27 mmol·l⁻¹, all p < 0.05). No worsening of renal function occurred (creatinine −7.8 μmol·l⁻¹, p = 0.12, estimated glomerular filtration rate +0.08 ml·s⁻¹·1.73 m⁻², p = 0.14). B-type natriuretic peptide (BNP) level remained unchanged (p = 0.18), but NT-proBNP level decreased significantly (median 1012 ng·l⁻¹ at baseline, 559.4 ng·l⁻¹ at follow-up, p = 0.005). A slight but significant decrease in high-sensitivity cardiac troponin T (hs-cTnT) was observed (median 14.76 ng·l⁻¹ at baseline, 12.63 ng·l⁻¹ at follow-up, p = 0.001). An improvement in MLHFQ total score (−8 points, p = 0.006) and in 6MWT by 55 m (p = 0.0007) was noted, which was not due to increased effort.ConclusionThe transition from ACEi/ARB to S/V therapy appears to be safe and leads to an improvement in exercise tolerance and quality of life.     

Early changes in respiratory quotient and resting energy expenditure predict later weight changes in patients treated for poorly controlled type 2 diabetes

AimThis study looked at whether early changes in resting energy expenditure (REE) and respiratory quotient (RQ) are correlated with later weight changes in patients with type 2 diabetes (T2D) being treated with insulin or GLP-1 analogues, or diet.MethodsA total of 67 patients (age: 57 ± 9 years; BMI: 33.7 ± 5.0 kg/m²; HbA_1c: 9.9 ± 1.5%) began taking an insulin analogue at bedtime (INS, n = 28; initial dose: 0.2 IU/kg) or a GLP-1 analogue (GLP-1, n = 23), or only a dietary intervention (diet, n = 16; restricted carbohydrates and calories). Their respiratory exchanges were monitored on days 0, 1 and 2 before breakfast.ResultsTwo days after starting the bedtime insulin analogue, fasting glycaemia improved (INS: −65 ± 41 mg/dL; GLP-1: −29 ± 48 mg/dL; diet: −31 ± 46 mg/dL; P < 0.05), REE decreased (INS: −162 ± 241 kcal/24 h; GLP-1: 0 ± 141 kcal/24 h; diet: −41 ± 154 kcal/24 h; P < 0.05) and RQ increased (from 0.76 ± 0.04 to 0.80 ± 0.04; P < 0.01), whereas only RQ decreased with diet (from 0.79 ± 0.05 to 0.76 ± 0.04; P < 0.05) and remained unchanged with GLP-1 (P < 0.005 for ΔRQ across treatments). Only 33 patients attended the scheduled examination three months later. HbA_1c improved (INS, n = 16: −1.7 ± 1.4%; GLP-1, n = 12: −2.1 ± 1.4%; diet, n = 5: −1.7 ± 2.8%; NS), while weight changes differed (INS: +1.5 ± 4.3 kg; GLP-1: −2.8 ± 2.8 kg; diet: −2.2 ± 2.7 kg; P < 0.005). After three months, weight changes correlated with early changes in REE (r = −0.37, P < 0.05) and RQ (r = +0.43, P < 0.01), and remained correlated when both changes were included in a multivariate regression analysis (r = 0.58, P < 0.005).ConclusionIn poorly controlled patients with T2D and two days after the introduction of a bedtime insulin analogue, REE decreased by −9% while RQ increased by +5%, pointing to a reduction of lipid oxidation. These changes were predictive of later weight gain.     

Is Risk Factor Control and Guideline-Based Medical Therapy Optimal in Patients With Nonobstructive Coronary Artery Disease? A Veterans Affairs Study

BackgroundAggressive risk factor modification using evidence-based secondary prevention strategies is recommended in coronary artery disease (CAD). Utilization of such strategies was compared in patients with nonobstructive CAD (NOCAD) and obstructive CAD (OCAD).MethodsPatients undergoing coronary angiography (excluding normal coronary angiograms), between January 2006 and June 2006, at the Veterans Affairs Medical Center were included. Demographic, clinical and treatment data were compared between the groups at baseline and 1 year.ResultsOf the 354 patients who underwent coronary angiography, 222 (63%) had follow-up data available at 12 ± 2 months. The mean age in the NOCAD (n = 119) and OCAD (n = 103) groups was similar. There was a lower prevalence of hypertension and heart failure (P < 0.05) in the NOCAD group. Compared with the OCAD group, aspirin use was similar but statin use was lower in the NOCAD group (P = 0.008). At 1 year, statin use (P = 0001) and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use (P = 0.001) were significantly lower, whereas the use of aspirin was numerically lower (P = 0.06) in the NOCAD group. Mean low-density lipoprotein cholesterol levels were at goal (<100 mg/dL) in the NOCAD group at baseline and 1 year, whereas the same slightly worsened in the OCAD group at 1 year.ConclusionsThe use of evidence-based medical therapy is lower in patients with NOCAD compared with those with OCAD. Improved awareness among health care providers and a unified effort to implement secondary prevention strategies may help correct such deficiencies.     

Relationship of apolipoprotein E polymorphism with lipid profiles in atherosclerotic coronary artery disease

AimsThe aim was to determine the relationship between apolipoprotein E (ApoE) gene polymorphisms and lipid profile in patients with coronary artery diseases (CAD), and its role in the prediction of the severity of carotid and coronary atherosclerosis.Methods and resultsOne hundred patients were classified by coronary angiography: 80 patients with CAD and 20 controls (normal coronary angiography). Clinical data, carotid sonography, blood lipid profiles and ApoE genotyping (PCR-RFLP) were assessed. CAD patients had significantly increased plasma lipid profiles and carotid intimal-wall thickness (IMT) versus controls. In CAD patients; ApoE genotype frequencies were E3/E3 = 62.50%, E2/E3 = 18.75%, E3/E4 = 17.50%, E2/E4 = 1.25%, E4/E4 = 0 and E2/E2 = 0. But, E3/E4 genotype was significantly higher than controls (P < 0.05). Also, in CAD patients; ApoE allele frequencies were E3 = 80.6%, E2 = 10.0% and E4 = 9.4% but, ApoE4 alleles were associated with higher cholesterol (P = 0.034) and LDL-c (P = 0.003), while ApoE2 alleles were associated with higher triglycerides (P = 0.037) versus ApoE3 alleles. However, odds ratio of CAD patients had higher risk with E2/E3 genotypes (2.5-fold), E2 alleles (2.2-fold) and E4 alleles (2.1-fold). Moreover, CAD patients with ApoE4 alleles had significantly higher carotid IMT (1.23 ± 0.26 mm vs 0.97 ± 0.2 mm ApoE3, P = 0.006; however, non-significant vs 1.10 ± 0.40 mm ApoE2 and also, ApoE2 vs ApoE3 alleles, P = 0.633) and left anterior descending (LAD) coronary artery stenosis (vs ApoE3 alleles, P = 0.016).ConclusionIschemic patients with carotid and coronary atherosclerosis had significantly higher integration of dyslipidemia and ApoE alleles (ApoE2 with hypertriglyceridemia and ApoE4 with hypercholesterolemia and higher LDL-c). ApoE polymorphism may be an important diagnostic risk biomarker and may implicate therapeutic intervention in atherosclerotic ischemic patients.     

Comparison of the autoregulatory mechanisms between central retinal artery and posterior ciliary arteries after thigh cuff deflation in healthy subjects

PurposeTo compare dynamic autoregulation in the Central Retinal Artery (CRA) and the Posterior Ciliary Arteries (PCAs) after a step decrease in systemic blood pressure.MethodsTen healthy male young subjects were studied. Flow velocities in retrobulbar vessels and systemic blood pressure were recorded in each subject before, during, and after a step decrease in blood pressure. Continuous blood pressure recordings were made with a finger plethysmograph system and flow velocities in the CRA and the PCAs were continuously measured with color Doppler imaging. Large bilateral thigh cuffs were inflated and a pressure approximately 20 mm Hg above peak systolic blood pressure was maintained for 3 minutes. A decrease in blood pressure was induced by rapid deflation of bilateral thigh cuffs. Experiments were performed separately for the CRA and the PCAs.ResultsSystemic blood pressure showed a step decrease between − 9% and − 12% (p < 0.001 each) immediately after thigh cuff release and returned to baseline 6 to 7 pulse cycles later. Peak systolic flow velocity in the CRA decreased by − 10 ± 7% (p = 0.043) and returned to baseline earlier than systemic blood pressure, showing a delay of 3 pulse cycles after the blood pressure decrease. Peak systolic and end diastolic flow velocities in the PCAs decreased by − 13 ± 3% (p = 0.004) and by − 10 ± 1% (p = 0.0009), respectively and returned to baseline with a comparable time course to systemic blood pressure, reflecting no change in peripheral vascular resistance. There was a statistically significant difference in the time course of the velocity changes in the two selected arteries after thigh cuff release (p = 0.008).ConclusionsThe results of the present study indicate differences in the autoregulatory behavior of the vascular beds peripheral to the CRA and the PCAs. Our data indicate that the vascular bed distal to the CRA shows better autoregulatory properties as compared to the PCAs. Whether this is related to a myogenic mechanism remains to be investigated. The thigh cuff technique represents an interesting approach to study dynamic autoregulation in the human eye.     

Insulin glargine versus insulin degludec in patients failing on oral therapy in type 2 diabetes: A retrospective real world comparative data from India

ObjectiveTo compare the changes in various glycemic parameters in insulin-naïve type 2 diabetes mellitus (DM) patients who were initiated on insulin glargine or insulin degludec in a real world setting.MethodsRetrospective data were analyzed in consecutive type 2 DM patients in a real world setting, who failed oral therapy (at least 2 oral anti-diabetic drugs) and were initiated with either insulin glargine or insulin degludec. The parameters assessed were the changes in HbA1c, fasting plasma glucose, body weight, dose of Insulin and the total number of patient reported hypoglycemic episodes up to 6 months after initiation.ResultAt baseline, insulin glargine and insulin degludec groups were similar in terms of gender, age, weight, HbA1c and duration of diabetes. After 6 months follow up the change in HbA1c (−1.09 versus −1.45 P = 0.124), change in FPG (−72.81 mg/dl [−4mmol/L] versus −75.88 mg/dl [−4.2 mmol/L] P = 0.755), and the change in body weight (+1.65 versus +0.85 P = 0.082) were similar in glargine and degludec groups, respectively. Patients in insulin degludec group experienced significantly lesser patient reported hypoglycemic episodes (12 versus 40) and required significantly lesser dose (25.68 Units versus 18.61 Units per day; P = 0.002) compared to insulin glargine. 41% of the patients reached HbA1C target of ≤7% with insulin glargine compared to 69% with insulin degludec within the specified time period.ConclusionResults from this real world analysis suggest that among type 2 DM patients who were initiated on insulin degludec as compared to insulin glargine may be associated with significantly lesser patient reported hypoglycemic episodes and lesser dose of insulin while achieving similar glycemic control. This study is however limited by the retrospective nature of the data collection.