Abstract Background and aim Low plasma vitamin D levels have been associated with heart failure (HF). This research attempts to explain the role of vitamin D supplementation on myocardial function in ...elderly patients with HF. Methods and results Twenty-three chronic HF patients were randomized in a small parallel group, double-blind, placebo-controlled trial. All patients, with a mean age of 74 years and vitamin D levels <30 ng/mL, received 800,000 IU (4000 IU/daily) of cholecalciferol or placebo for 6 months. The outcomes measured at baseline and after 6 months were ejection fraction (EF) and other echocardiography parameters, carboxyterminal propeptide of procollagen type I (PIP), natriuretic peptides, lipid profile, renin, parathyroid hormone, blood pressure, and body mass index (BMI). In 13 patients under active treatment for 6 months, mean plasma 25-hydroxy vitamin D concentrations (15.51 vs. −1.40 ng/mL, p < 0.001) and plasma calcium (from 9.3 to 9.6 mmol/L, p < 0.05) increased significantly. However, other biomarkers of bone metabolism did not differ between the treatment and placebo groups. EF increased significantly in the intervention group (6.71 vs. −4.3%; p < 0.001), and the serum concentration of PIP increased only in the placebo group after 6 months (1140.98 vs. −145 mcg/L; p < 0.05). Systolic blood pressure was lower after 6 months of cholecalciferol treatment (from 129.6 to 122.7 mm Hg, p < 0.05). No significant variations were observed for other parameters. Conclusions Six months of vitamin D supplementation significantly improves EF in elderly patients with HF and vitamin D deficiency.
OBJECTIVE:Drug utilization and clinical outcomes in hypertensive patients are suboptimal in different Countries, including Italy, leaving a large proportion of patients not at target blood pressure ...(BP).
DESIGN AND METHOD:We designed an observational study to define the number of patients diagnosed as hypertensive within the general adult population, the number of drugs prescribed to each patients and the number of hypertensive patients who were effectively treated. To this aim, clinical data collected by 150 General Practitioners (GPs) from 228.406 subjects living in the province of Verona (approximately 30% of the adult population) were analyzed after anonymization. Data retrieved from GPs official database concerned age, gender, number of antihypertensive agents prescribed at the same time over a period of 24 months, BP defined as categorical variable (cutoff 140/90 mmHg).
RESULTS:Data concerning the number of prescribed antihypertensive agents and BP control in relation to age are shown in the graph. A total of 43.526 subjects had a diagnosis of arterial hypertension (19% of the entire population, females 53%), 66% of them were aged 65 years or more and 86% received antihypertensive medications in the previous 2 years. The number of prescriptions increased with age. BP recordings were missing in 38% of cases. One third of all patients did not reach normal BP. Approximately 15% of patients could be considered as having resistant hypertension since requiring 4 drugs or not reaching normal BP with 3 drugs. Younger subjects (less than 65 years) more likely had BP not recorded (46%) and often received 1 or 2 antihypertensive agents, whether or not BP was controlled. Elderly patients (65 years or more) often required complex antihypertensive treatment (29% received 3–4 drugs) and their BP, in spite of a more stringent clinical follow up (66% had BP recorded), was uncontrolled in 48% of cases.(Figure is included in full-text article.)
CONCLUSIONS:BP control is not achieved in a large proportion of hypertensives, particularly the elderly patients although receiving a larger number of antihypertensive drugs. The present investigation helps to define the patients who may benefit from active monitoring and intervention aimed at improving the clinical outcomes.
A systematic review and a meta‐analysis were performed to quantify the accumulated information from genetic association studies investigating the impact of the CYP4F2 rs2108622 (p.V433M) polymorphism ...on coumarin dose requirement. An additional aim was to explore the contribution of the CYP4F2 variant in comparison with, as well as after stratification for, the VKORC1 and CYP2C9 variants. Thirty studies involving 9,470 participants met prespecified inclusion criteria. As compared with CC‐homozygotes, T‐allele carriers required an 8.3% (95% confidence interval (CI): 5.6–11.1%; P < 0.0001) higher mean daily coumarin dose than CC homozygotes to reach a stable international normalized ratio (INR). There was no evidence of publication bias. Heterogeneity among studies was present (I2 = 43%). Our results show that the CYP4F2 p.V433M polymorphism is associated with interindividual variability in response to coumarin drugs, but with a low effect size that is confirmed to be lower than those contributed by VKORC1 and CYP2C9 polymorphisms.
Clinical Pharmacology & Therapeutics (2012); 92 6, 746–756. doi:10.1038/clpt.2012.184
OBJECTIVE:Epoxyeicosatrienoic acids (EETs) act as vasodilators activating high conductance calcium-operated potassium (K) channels (Kca1.1, also named BK, MAXI-K). We found expression of MAXI-K ...channel in platelets. The present study aimed at defining its functionality in platelet using an in vitro model of platelet thrombosis.
DESIGN AND METHOD:We tested the effects of 5 μmol/L 11,12-EET and the pharmacological modulation of MAXI-K channel (agonists5 and 20 μmol/L BMS 191011, 5 μmol/L NS1619, 5 μmol/L NS11021). Platelet rich plasma was used to assess adhesion-induced thrombi formation under flow by microfluidics technology with collagen-coated microchips mimicking arterial blood flow. The kinetic of platelet responses to scalar doses of 0.3–10 μmol/L ADP, 0.05–2 μmol/L U46619 0.5–10 μg/mL collagen was determined by paired analysis using Born aggregometry. Flow-cytometry was used to analyse the expression of active fibrinogen receptor and P-selectin in stimulated platelets. The effects of 100 μmol/L aspirin and 1 μmol/L ticagrelor were also assessed.
RESULTS:In vitro thrombi formation was halved (expressed as platelet-covered area) by pre-treatment with either 11,12-EET (−45 ± 11%, n = 5, P < 0.001 vs control, Mean ± SD), aspirin (−66 ± 8%, n = 4, P < 0.001) or ticagrelor (−55 ± 8%, n = 4, P < 0.001). Similar results were obtained using BMS 5 μmol/L (−54 ± 17%, n = 6, P < 0.001), NS1619 (−50 ± 19%, n = 9, P < 0.001), NS11021 (−60 ± 21%, n = 6, P < 0.001). The addition of 20 μmol/L BMS191011 prior to platelet aggregation (EC502.67 μmol/L, 95%CI0.97–7.29, n = 36) significantly shifted to the right the dose response-curve to ADP (EC500.91 μmol/L, 0.43–1.92, n = 36). Platelet aggregation was further blunted by the addition of aspirin to BMS191011 (EC506.18 μmol/L, 2.11–18.09, n = 36). U46619- and collagen-induced aggregation was not altered. ADP-induced activation of the fibrinogen receptor (−48 ± 14% to −62 ± 10%, n = 7, P < 0.05) and P-selectin expression (−37 ± 15% to −41 ± 13%, n = 7, P < 0.01) were blunted by the activators of MAXI-K channel.
CONCLUSIONS:Activation of the MAXI-K channel by 11,12-EET and all the tested synthetic compounds is associated with reduced sensitivity to ADP and reduced thrombus generation through the inhibition of the amplificatory phase of platelet activation. The present results reveal new mechanisms of platelet activation and suggest that targeting MAXI-K might be of potential pharmacological interest for the prevention of atherothrombosis.
OBJECTIVE:Opportunistic screening outside medical clinics using easily available devices measuring blood pressure while simultaneously detecting irregular pulse could be potentially useful to ...identify patients with asymptomatic or unknown atrial fibrillation, thus reducing the burden of cardiovascular events, primarily systemic thromboembolism (NICE medical technology guidance 13, 2015). We performed a cross-sectional observational study aimed at evaluate the prevalence of atrial fibrillation and associated clinical conditions in adults older than 50 years living in the province of Verona.
DESIGN AND METHOD:All the citizens aged 50 or more were invited through an information campaign to reach their pharmacy to have their blood pressure and heart rate monitored with the Microlife Afib® device, which utilises an algorithm to calculate the irregularity of interval times between heartbeats and identify atrial fibrillation. Pharmacists collected for 6 months also anthropometric and demographic data of the participants, along with information concerning their personal history of cardiovascular disease and the use of anti-hypertensive and anti-thrombotic agents. All those who were positive to the screening for atrial fibrillation were referred to their medical doctor.
RESULTS:A total number of 3109 citizens took part in the study; 1605 of them were hypertensive, 297 diabetic and 372 obese. Positive for atrial fibrillation were 99 subjects (56 males). Only 44 of them had a previous diagnosis of atrial fibrillation and were receiving anticoagulation agents (77%) or aspirin (7%). Although subject positive to the screening were hypertensive, diabetic or obese in the same proportion of the negative ones, they had in a larger proportion a previous stroke (7% versus 2%, P < 0.01).
CONCLUSIONS:Aim of our investigation was to obtain epidemiological data concerning the prevalence of atrial fibrillation, to identify previously non-detected cases and to promote consciousness in the population concerning the risk factors and the clinical consequences of atrial fibrillation. The results of our study indicate that opportunistic screening for atrial fibrillation in the pharmacies is feasible and allows identify a large number of subjects with silent, non-previously diagnosed atrial fibrillation, and is potentially useful in large-scale projects aimed at the prevention of cardiovascular mortality.
OBJECTIVE:We aimed at investigating the influence of weight excess and traditional cardiovascular risk factors on vascular structure and function in a sample of obese children.
DESIGN AND ...METHOD:Overweight or obese children (BMI > 90th percentile for sex and age) included in this observational study underwent office and ambulatory BP measurements (ABPM) and the assessment of carotid intima-media thickness (cIMT), endothelial function by the Flow Mediated Dilation (FMD) technique, carotid distensibility (cDC) by ultrasounds and stiffness index (SI) by digital photopletismography.
RESULTS:Sixty-six obese and 4 overweight children were enrolled (age 11.5 ± 2.4 years; female n30). Carotid IMT directly correlated with 24h- and nighttime SBP; cDC showed inverse correlations with BMI and waist circumference and 24h-BP. Unexpectedly, SI resulted inversely related with several indexes of weight excess. Most of these correlations remained significant after adjustment for age, sex, BMI and BP. In a replication set of 40 obese children SI, but not Pulse Wave Velocity (PWV), was still inversely associated with BMI.
CONCLUSIONS:These data suggest that arterial structure and elasticity are negatively affected by weight excess and BP levels, even in childhood. Surprisingly, SI might not be a reliable marker of vascular stiffness in obese children, because this measure is probably confounded by other factors including vasodilation.
Abstract Background and aims Magnesium plays an important role in the modulation of vascular tone and endothelial function and can regulate glucose and lipid metabolism. Patients with hypertension, ...metabolic syndrome (MetS) and diabetes mellitus (T2DM) have low body magnesium content; indeed, magnesium supplementation has been shown to have a positive effect on blood pressure (BP) and gluco-metabolic parameters. The aim of our study was to evaluate the effect of magnesium supplements on hemodynamic and metabolic parameters in healthy men with a positive family history of MetS or T2DM. Methods and results In a randomized, double-blind, placebo-controlled 8-week crossover trial with a 4 week wash-out period, oral supplements of 8.1 mmol of magnesium-pidolate or placebo were administered twice a day to 14 healthy normomagnesemic participants, aged 23–33 years. The primary endpoint was office BP, measured with a semiautomatic oscillometric device. Secondary endpoints included characteristics of the MetS, namely endothelial function, arterial stiffness and inflammation. Plasma and urinary magnesium were measured in all participants while free intracellular magnesium was measured only in a subsample. There was no significant difference in either systolic and diastolic BP in participants post-magnesium supplementation and post-placebo treatment when compared to baseline BP measurements. Further, the metabolic, inflammatory and hemodynamic parameters did not vary significantly during the study. Conclusions Our study showed no beneficial effect of magnesium supplements on BP, vascular function and glycolipid profile in young men with a family history of MetS/T2DM (trial registration at clinicaltrial.gov ID: NCT01181830 ; 12th of Aug 2010).
OBJECTIVE:Type 1 diabetes mellitus (T1DM) is associated with early development of atherosclerosis. The aim of this study was to measure some indices of vascular damage in a group of children and ...adolescents with T1DM and their relationship with haemodynamic and metabolic parameters.
DESIGN AND METHOD:In a cross-sectional study, peripheral (pSBP/pDBP) and central systolic and diastolic blood pressure (cSBP/cDPB), carotid intima media thickness (cIMT) and carotid distensibility (cDC), pulse wave velocity (PWV) were measured using ultrasound and the SphygmoCor XCel device. Metabolic parameters, including triglycerides, LDL and HDL-cholesterol, were measured and glycated haemoglobin (HbA1c; average of the last two years) was calculated.
RESULTS:126 subjects with T1DM (61 females and 65 males, mean age 15.9 ± 2.6 years) followed at the Paediatric Diabetology Unit of Verona were evaluated at the Vascular Laboratory of the General Medicine & Hypertension Unit. Eighteen per cent of the sample had cDC under the 5th percentiles and 60% had cIMT higher than the 95th percentiles per sex and height. Both cSBP and pSBP were positively correlated with BMI (respectively r = 0.404; p < 0.0001 and r = 0.279; p < 0.01). A significant correlation between cSBP and all the measures of vascular damage was foundcDC (r = −0.410; p < 0.0001), PWV (r = 0.447; p < 0.0001), cIMT (r = 0.227; p < 0.01). The duration of diabetes, LDL-cholesterol and the average HbA1c were not correlated to any vascular phenotype. In linear regression analysis, after adjustment for all metabolic and anthropometric parameters, central SBP remained independently associated with subclinical carotid damage (for cIMT β = 0.002; p = 0.023; for cDC β = −0.343; p = 0.003) and PWV (β = 0.025; p < 0.001) whereas LDL-cholesterol with cIMT (β = 0.001; p < 0.05) and PWV (β = 0.025; p < 0.01).
CONCLUSIONS:Subclinical vascular damages are present in a high proportion of children and adolescents with T1DM. cSBP, more than pBP, is independently associated with indexes of vascular subclinical atherosclerosis, suggesting a pivotal role of blood pressure homeostasis, along with LDL-cholesterol, in determining vascular damage even during childhood and adolescence in patients with T1DM.
OBJECTIVE:Dietary and circulating fatty acids (FA) and desaturases activity, involved in FA metabolism, are associated with metabolic and cardiovascular disorders. In particular, a lower delta-5 ...desaturase activity (D5D) in contrast to a higher delta-6 desaturase (D6D) and stearoyl-CoA desaturase (SCD-16; the enzyme that metabolizes palmitic (PA) to palmitoleic acid (PtA)) activities were related to obesity and metabolic disorders.
DESIGN AND METHOD:FA profile was determined on whole blood drop in 244 children (50.2 % females; mean age 8.6 ± 0.72 years) participating in a school-based cross-sectional study. The possible associations between individual FA and desaturases activity (evaluated as product:precursor ratios) with indices of adiposity and blood pressure (BP) was investigated.
RESULTS:Omega-3 Index, marker of long-term eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) dietary intake, was low (3.9 ± 0.88 %). DHA inversely correlated with BMI and waist/height ratio, whereas oleic acid, PA and individual omega-6 PUFAs were not associated with either obesity or BP, except for a direct correlation of dihomo-gamma-linoleic acid (DGLA) with some indices of adiposity. PtA, an omega-7 FA, was directly associated with adiposity (BMIr = 0.408, p < 0.01; waist circumferencer = 0.368, p < 0.01; fat massr = 0.402, p < 0.01) and BP (Systolicr = 0.203, p < 0.01; Diastolicr = 0.167, p < 0.01). D5D inversely correlated with waist circumference, D6D directly with waist/height ratio and SCD-16 directly with most adiposity indices and BP. Children with excess weight (BMI > 85th percentile) showed higher concentrations of PA, PtA and a higher SCD-16 activity compared to normal-weight children. In the excess-weight group PA directly correlated with some anthropometric measurements and PtA confirmed the direct association with obesity and BP. Even SCD-16 directly correlated with anthropometric features and BP. Caucasian children (66.8%) had higher D6D activity than non-Caucasians (33.2%), and in Caucasians D6D directly correlated with obesity. In this subgroup PA, PtA and SCD-16 directly correlated with anthropometric characteristics and BP.
CONCLUSIONS:PtA and SCD-16 directly correlated with indices of adiposity and BP, especially in obese children. D6D activity is likely influenced by ethnicity, showing an apparent harmful effect especially in Caucasians.
PDF
