To assess the effect of two hypoglycemic drugs on ischemic preconditioning (IPC) patients with type 2 diabetes and coronary artery disease (CAD).
We performed a prospective study of 96 consecutive ...patients allocated into two groups: 42 to group repaglinide (R) and 54 to group vildagliptin (V). All patients underwent two consecutive exercise tests (ET1 and ET2) in phase 1 without drugs. In phase 2, 1 day after ET1 and -2, 2 mg repaglinide three times daily or 50 mg vildagliptin twice daily was given orally to patients in the respective group for 6 days. On the seventh day, 60 min after 6 mg repaglinide or 100 mg vildagliptin, all patients underwent two consecutive exercise tests (ET3 and ET4).
In phase 1, IPC was demonstrated by improvement in the time to 1.0 mm ST-segment depression and rate pressure product (RPP). All patients developed ischemia in ET3; however, 83.3% of patients in group R experienced ischemia earlier in ET4, without significant improvement in RPP, indicating the cessation of IPC (P < 0.0001). In group V, only 28% of patients demonstrated IPC cessation, with 72% still having the protective effect (P < 0.0069).
Repaglinide eliminated myocardial IPC, probably by its effect on the KATP channel. Vildagliptin did not damage this protective mechanism in a relevant way in patients with type 2 diabetes and CAD, suggesting a good alternative treatment in this population.
Dual antiplatelet therapy is recommended for patients with acute coronary syndromes (ACS). Approximately 10% to 15% of these patients will undergo coronary artery bypass graft (CABG) surgery for ...index events, and current guidelines recommend stopping clopidogrel at least 5 days before CABG. This waiting time has clinical and economic implications.
This study aimed to evaluate if a platelet reactivity-based strategy is noninferior to standard of care for 24-h post-CABG bleeding.
In this randomized, open label noninferiority trial, 190 patients admitted with ACS with indications for CABG and on aspirin and P2Y12 receptor inhibitors, were assigned to either control group, P2Y12 receptor inhibitor withdrawn 5 to 7 days before CABG, or intervention group, daily measurements of platelet reactivity by Multiplate analyzer (Roche Diagnostics GmbH, Vienna, Austria) with CABG planned the next working day after platelet reactivity normalization (pre-defined as ≥46 aggregation units).
Within the first 24 h of CABG, the median chest tube drainage was 350 ml (interquartile range IQR: 250 to 475 ml) and 350 ml (IQR: 255 to 500 ml) in the intervention and control groups, respectively (p for noninferiority <0.001). The median waiting period between the decision to undergo CABG and the procedure was 112 h (IQR: 66 to 142 h) and 136 h (IQR: 112 to 161 h) (p < 0.001), respectively. In the intention-to-treat analysis, a 6.4% decrease in the median in-hospital expenses was observed in the intervention group (p = 0.014), with 11.2% decrease in the analysis per protocol (p = 0.003).
A strategy based on platelet reactivity-guided is noninferior to the standard of care in patients with ACS awaiting CABG regarding peri-operative bleeding, significantly shortens the waiting time to CABG, and decreases hospital expenses. (Evaluation of Platelet Aggregability in the Release of CABG in Patients With ACS With DAPT; NCT02516267)
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Traditional strategies for primary cardiovascular prevention have been insufficient in reducing the high rates of coronary ischemic events in women, probably because these women are often stratified ...into low-risk groups. However, cardiovascular diseases continue to be the main cause of morbidity and mortality in women worldwide. We hypothesized that carotid atherosclerosis (CA) is common in middle-aged women.
We prospectively evaluated asymptomatic peri- and post-menopausal women with no cardiovascular diseases or the use of hormone therapy from two gynecologic clinics. All the patients underwent full clinical and laboratory evaluation and underwent a B-mode ultrasound for carotid evaluations. The presence of CA was defined as the presence of plaque and/or carotid intima-media thickness (CIMT)>1.00 mm. We performed logistic regression to evaluate independent predictors of CA.
We studied 823 women (age: 54.4±5.4 years; body mass index-BMI: 28.5±4.9 kg/m2; diabetes:10%; hypertension: 58%). The prevalence of CA was 12.7% for the entire population and 11% for the low-risk sub-group as defined by a Framingham risk score <5%. In the multivariate model, age: odds ratio (OR) = 1.54, 95% confidence interval (CI) = 1.25-1.89,p<0.001; current smoker status: OR = 2.69, 95% CI = 1.48-4.91, p = 0.001; total cholesterol: OR = 1.13, 95% CI = 1.03-1.24, p = 0.008; and systolic blood pressure: OR = 1.01, 95% CI = 1.00-1.02, p = 0.030 remained independently associated with CA.
Subclinical CA is common among asymptomatic middle-aged women, and traditional risk factors are independently associated with CA. These findings are particularly relevant for improving cardiovascular health in women.
Introduction
Lipoprotein (
a
) Lp(
a
) is a risk factor for coronary artery disease (CAD). To the best of our knowledge, this is the first study addressing the relationship between Lp(
a
) and ...platelet reactivity in primary and secondary prevention.
Methods
Lp(
a
) was evaluated in 396 individuals with (82.3%) and without (17.7%) obstructive CAD. The population was divided into two groups according to Lp(
a
) concentrations with a cutoff value of 50 mg/dL. The primary objective was to evaluate the association between Lp(
a
) and adenosine diphosphate (ADP)-induced platelet reactivity using the VerifyNow™ P2Y
12
assay. Platelet reactivity was also induced by arachidonic acid and collagen–epinephrine (C-EPI) and assessed by Multiplate™, platelet function analyzer™ 100 (PFA-100), and light transmission aggregometry (LTA) assays. Secondary objectives included the assessment of the primary endpoint in individuals with or without CAD.
Results
Overall, 294 (74.2%) individuals had Lp(
a
) < 50 mg/dL median (IQR) 13.2 (5.8–27.9) mg/dL and 102 (25.8%) had Lp(
a
) ≥ 50 mg/dL 82.5 (67.6–114.5) mg/dL,
P
< 0.001. Univariate analysis in the entire population revealed no differences in ADP-induced platelet reactivity between individuals with Lp(
a
) ≥ 50 mg/dL (249.4 ± 43.8 PRU) versus Lp(
a
) < 50 mg/dL (243.1 ± 52.2 PRU),
P
= 0.277. Similar findings were present in individuals with (
P
= 0.228) and without (
P
= 0.669) CAD, and regardless of the agonist used or method of analysis (all
P
> 0.05). Finally, multivariable analysis did not show a significant association between ADP-induced platelet reactivity and Lp(
a
) ≥ 50 mg/dL adjusted OR = 1.00 (95% CI 0.99–1.01),
P
= 0.590.
Conclusion
In individuals with or without CAD, Lp(
a
) ≥ 50 mg/dL was not associated with higher platelet reactivity.
This study investigated the relationship between angiographic complexities of coronary artery disease (CAD) assessed by SYNTAX Score synergy between percutaneous coronary intervention with taxus and ...cardiac surgery score (SYNTAX Score) and cardiac biomarker elevation after revascularization procedures.This is a post-hoc analysis of the medicine, angioplasty or surgery study V study of patients with stable CAD. High-sensitivity troponin 1 (hs-TnI) and creatinine kinase-muscle/brain (CK-MB) were assessed before and after cardiovascular procedures. Baselines SYNTAX Scores (SXScores) were calculated by blinded investigators to patient characteristics.Of the 202 patients studied, the mean SXScore was 21.25 ± 9.24; 40.10 ± 7.09 in the high SXScore group and 19.06 ± 6.61 in low/mid SXscore group (P < .0001). Positive correlations existed between SXScore and median peaks after procedural hs-TnI (r = 0.18, P = .009) and CK-MB (r = 0.24, P = .001) levels. In patients with high SXScores (≥33), the median peaks of post-procedural hs-TnI (P = .034)and CK-MB (P = .004) levels were higher than in low/mid SXScore group (<33).The release of hs-TnI at 6 (P = .002), 12 (P = .008), and 24 hours (P = .039) was higher in high SXScore group than in low/mid SXscore group (<33) as was the release of CK-MB at 6 (P < .0001), 12 (P < .0001), 24 (P = .001), 36 (P = .007), 48 (P = .008), and 72 hours (P = .023). After multivariable analysis, high SXScore was a significant independent predictor of release of CK-MB and hs-TnI peaks higher than the median.The increase in release of cardiac biomarkers was significantly associated with the extent of atherosclerosis identified by the SYNTAX Score.
Thromboembolic events are associated with high mortality and morbidity indexes. In this context, warfarin is the most widely prescribed oral anticoagulant agent for preventing and treating these ...events. This medication has a narrow therapeutic range and, consequently, patients usually have difficulty in achieving and maintaining stable target therapeutics. Some studies on the literature about oral anticoagulant management showed that pharmacists could improve the efficiency of anticoagulant therapy. However, the majority of these studies included general patients retrospectively. The aim of this study was to prospectively evaluate a pharmacist's warfarin management in patients with poor quality of anticoagulation therapy (Time in the Therapeutic Range- TTR < 50%). We included 268 patients with atrial fibrillation (AF) and without stable dose of warfarin (TTR < 50%, based on the last three values of International Normalized Ratio-INR). We followed them up for 12 weeks, INR values were evaluated and, when necessary, the dose adjustments were performed. During the first four visits, patient's INR was measured every 7 days. Then, if INR was within the target therapeutic range (INR: 2-3), the patient was asked to return in 30 days. However, if INR was out the therapeutic target, the patient was asked to return in 7 days. Adherence evaluation was measured through questionnaires and by counting the pills taken. Comparison between basal TTR (which was calculated based on the three last INR values before prospective phase) and TTR of 4 weeks (calculated by considering the INR tests from visits 0 to 4, in the prospective phase of the study) and basal TTR and TTR of 12 weeks (calculated based on the INR tests from visits 0 to 12, in the prospective phase of the study) revealed significant statistical differences (0.144 ± 0.010 vs. 0.382 ± 0.016; and 0.144 ± 0.010 vs. 0.543 ± 0.014,
< 0.001, respectively). We also observed that the mean TTR of 1 year before (retrospective phase) was lower than TTR value after 12 weeks of pharmacist-driven treatment (prospective phase) (0.320 ± 0.015; 0.540 ± 0.015,
< 0.001). In conclusion, pharmaceutical care was able to improve TTR values in patients with AF and poor quality of anticoagulation with warfarin.
Abstract Background Sirtuin 1 (Sirt1) plays an important role in vascular biology, and influences aspects of age-dependent atherosclerosis. In animals, the sirtuin system is strongly influenced by ...resveratrol and caloric restriction, but its expression in humans is controversial. This study investigated the effects of resveratrol and caloric restriction on Sirt1 serum concentrations and vascular biomarkers in a healthy human population. Methods and results Forty-eight healthy participants (24 women) aged 55–65 years were randomized to either 30 days of resveratrol administration (500 mg/day) or caloric restriction (1000 cal/day). Blood was collected at baseline and day 30. Laboratory data analyzed were triglycerides, total cholesterol, HDL, VLDL, LDL, apolipoprotein A1, apolipoprotein B, lipoprotein (a), non-esterified fatty acids (NEFA), glucose, insulin, oxidative stress, C-reactive protein, and Sirt1. Expression of the Sirt1 gene was analyzed using real-time PCR. Caloric restriction diminished the abdominal circumference and improved the lipid profile, but not resveratrol intervention. Resveratrol and caloric restriction increased serum concentrations of Sirt1, from 1.06 ± 0.71 to 5.75 ± 2.98 ng/mL; p < 0.0001, and from 1.65 ± 1.81 to 5.80 ± 2.23 ng/mL; p < 0.0001, respectively. Sirt1 increased in women and men in both interventions. On the other hand expression of Sirt1 mRNA was not different after caloric restriction and resveratrol treatment. Conclusions Caloric restriction and resveratrol significantly increased plasma concentrations of Sirt1. The long-term impact of these interventions on atherosclerosis should be assessed.
The recommendations for adjustment of citrate volume in sample tubes with high hematocrit (Ht) are based on indirect studies of underfilled tubes or artificially constructed Ht values. The aim of ...this study was to evaluate the effect of citrate volume adjustment in sample tubes from patients with hematocrit >55% using two different prothrombin time (PT) tests.
Paired citrate-adjusted and unadjusted blood specimens were obtained from 181 patients from the pulmonary hypertension ambulatory with high Ht values and on warfarin therapy. The samples were tested using recombinant human tissue factor (RTF) and reagents extracted from rabbit brain (HS Plus). The results are expressed as the international normalized ratio (INR). The correlation and percent change (% change) between sample pairs were calculated.
INR-RTF results from adjusted and unadjusted citrate blood specimens showed a strong correlation (R2 = 0.8226, p < 0.0001). The INR median was 2.25 (95% CI 2.10 to 2.41) for citrate-adjusted samples and was 2.22 (95% CI 2.06 to 2.38) for citrate-unadjusted samples. For samples with Ht >62%, the % change between sample pairs was >10%. Results using HS Plus showed a moderate correlation between citrate-adjusted and unadjusted samples (R2 = 0.4267, p < 0.0001). The INR median was 2.51 (95% CI 2.35 to 2.68) for citrate-adjusted samples and 3.45 (95% CI 3.11 to 3.80) for citrate-unadjusted samples. For samples with Ht>55%, the % change between sample pairs was higher than 10%.
Our data demonstrate that in patients with polycythemia on warfarin therapy, INR-RTF does not require anticoagulant adjustment for assessment of samples with Ht <62%.
•Recombinant human tissue factor thromboplastin can correct citrate from samples with 62% hematocrit.•Each laboratory could perform its own validation.•For HS Plus thromboplastin reagent samples, >55% Ht required adjustment of citrate concentration.•Care should be taken with unadjusted samples for patients with Ht >55%.
Dabigatran and rivaroxaban, direct oral anticoagulants (DOACs), affect coagulation tests, and knowledge of their effects is important for therapeutic monitoring. Our aim was to examine the ...association between DOAC levels and routine coagulation tests in patients with nonvalvular atrial fibrillation. Samples from patients receiving dabigatran (150 mg) and patients receiving rivaroxaban (20 mg) were collected 2 hours after drug intake. Direct oral anticoagulant concentrations were determined using direct Hemoclot thrombin inhibitor (HTI) assay (HTI test) and a direct Xa inhibitor (Anti Xa-Riva). The routine coagulation measured included activated partial thromboplastin time (aPTT) and prothrombin time (PT). The median plasmatic dabigatran was 128.3 ng/mL (95% confidence interval CI: 93.7-222.6 ng/mL). The HTI exhibited a good correlation with aPTT (R2 = 0.74; P < .0001). The median plasmatic rivaroxaban was 223.9 ng/mL (95% CI: 212.3-238.9 ng/mL). Anti-Xa-Riva correlated with PT (R2
= 0.69, P< .0001) and aPTT (R2
= 0.36, P < .001), but prolonged PT results were obtained, even below the rivaroxaban therapeutic range (20%). The routine coagulation tests were able to identify out of therapeutic range concentrations for dabigatran and rivaroxaban. We suggest the use of these screening tests to better understand and monitor the subtherapeutic concentrations of these DOACs.
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