Dabigatran 150 mg twice daily was shown to be superior to warfarin in preventing stroke in subjects with nonvalvular atrial fibrillation (SPAF) in the RE-LY (Randomized Evaluation of Long-term anticoagulation therapY) trial. Numerically, more myocardial infarctions occurred in patients receiving dabigatran compared with well-controlled warfarin. This observation prompted a comprehensive analysis of cardiovascular outcomes, including myocardial infarction, in all completed Phase II and III trials of dabigatran etexilate.
The analysis included comparisons of dabigatran with warfarin, enoxaparin, and placebo. Data were analyzed for the occurrence of cardiovascular events from 14 comparative trials (n = 42,484) in five different indications. Individual study data were evaluated, as well as pooled subject-level data grouped by comparator.
In the pooled analysis of individual patient data comparing dabigatran with warfarin (SPAF and venous thromboembolism treatment indications), myocardial infarction occurrence favored warfarin (odds ratio [OR] 1.30, 95% confidence interval [CI] 0.96–1.76 for dabigatran 110 mg twice daily and OR 1.42, 95% CI 1.07–1.88 for dabigatran 150 mg twice daily). The clinically relevant composite endpoint of myocardial infarction, total stroke, and vascular death demonstrated numerically fewer events in dabigatran 150 mg patients (OR 0.87, 95% CI 0.77–1.00), but was similar for dabigatran 110 mg (OR 0.99, 95% CI 0.87–1.13). Dabigatran had similar myocardial infarction rates when compared with enoxaparin or placebo.
These analyses suggest a more protective effect of well-controlled warfarin, but not enoxaparin, compared with dabigatran in preventing myocardial infarction in multiple clinical settings. Dabigatran showed an overall positive benefit-risk ratio for multiple clinically important cardiovascular composite endpoints in all evaluated clinical indications. In conclusion, these data suggest that myocardial infarction is not an adverse drug reaction associated with use of dabigatran.
cardiovascular events; stroke; myocardial infarction; dabigatran etexilate; warfarin; atrial fibrillation
Edoxaban is an oral, once-daily, selective, direct factor Xa inhibitor approved in Japan for the prevention of venous thromboembolism following major orthopedic surgery. Currently, edoxaban is in Phase III clinical development for the prevention of stroke and systemic embolic events in patients with atrial fibrillation, and for the treatment and prevention of recurrences of venous thromboembolism. This report describes the adverse drug reactions (ADRs) spontaneously reported during early postmarketing phase vigilance from the time of its commercial launch in Japan.
Materials and methods
All spontaneously reported ADRs following edoxaban use received by Daiichi Sankyo during early postmarketing phase vigilance from July 19, 2011, to January 18, 2012, were entered into the safety database and included in this review. Approximately 20,000 patients were estimated to have been treated with edoxaban.
The mean age of patients was 74.2 years, their mean weight was 59.4 kg, and approximately 70% were female. A total of 67 ADRs were reported in 56 patients, of which the majority included bleeding events (51 ADRs in 42 patients). Of these, 15 ADRs (in 14 patients) were serious, including cerebral hemorrhage (n = 1), gastric hemorrhage (n = 2; gastric hemorrhage [n = 1] and gastric ulcer hemorrhage [n = 1]), and surgical-site hemorrhage (n = 12; hemorrhage [n = 6], subcutaneous hemorrhage [n = 3], wound hemorrhage [n = 2], and wound hematoma [n = 1]). Most ADRs occurred within the first week of treatment and there were no fatalities. Nonserious ADRs associated with bleeding that occurred in >1 patient included subcutaneous hemorrhage (n = 9), wound hemorrhage (n = 5), postprocedural hematoma (n = 4), anemia (n = 4), and hemarthrosis (n = 3). Other nonserious ADRs not associated with bleeding and occurring in >1 patient included abnormal hepatic function (n = 4) and diarrhea (n = 2).
Safety data from the first 6 months of postmarketing experience with edoxaban did not identify any unforeseen safety signals, consistent with the known safety profile of edoxaban.
edoxaban; venous thromboembolism; factor Xa; early postmarketing phase vigilance; thromboprophylaxis; spontaneous reporting
Hypertension represents a major health problem, affecting more than one billion adults worldwide. Irbesartan, an angiotensin II receptor blocker, is considered to be a highly effective treatment in the management of hypertension. The purpose of this review is to evaluate the efficacy, safety and tolerability profile , and cost-effectiveness of treatment with irbesartan in hypertension.
A review of the literature was conducted using the electronic PubMed and Cochrane Library databases and the Health Economic Evaluations Database of search terms relating to irbesartan efficacy, tolerability, and cost-effectiveness, and the results were utilized.
Findings from the present analysis show that irbesartan either as monotherapy or in combination with other antihypertensive agents can achieve significant reductions in blood pressure, both systolic and diastolic, compared with alternative treatment options. Irbesartan was also found to have a renoprotective effect independent of its blood pressure-lowering in patients with type 2 diabetes and nephropathy. Furthermore, irbesartan demonstrated an excellent safety and tolerability profile , with either lower or equal adverse events compared with placebo and other alternative treatments. In terms of economic analyses, compared with other antihypertensive therapy alternatives, irbesartan was found to be a preferred option, that is less costly and more effective.
The evidence indicates that treating patients with hypertension alone or with type 2 diabetes and nephropathy using irbesartan can control hypertension, prolong life, and reduce costs in relation to existing alternatives.
irbesartan; tolerability; safety; efficacy; cost-effectiveness; economic evaluation
While several studies have identified an increased incidence of cardiovascular disorders in opiate dependence, neither opiates as a cardiovascular risk factor nor their effect on central arterial function has been considered.
Pulse wave analysis (SphygmoCor, AtCorMedical Pty Limited, Sydney, NSW, Australia) was undertaken on a cohort of controls and opiate dependent patients and the results compared to their lifetime opiate exposure.
Controls (N = 401) were compared with 465 opiate dependent men. The mean (log) ages were different and were found to be 28.80 ± 0.49 years versus 35.02 ± 0.39 years (P < 0.0001), respectively. Of the opiate dependent group, 87.7% were treated with buprenorphine, 8.8% with methadone, and 3.4% with naltrexone. Multiple regression analysis was used to adjust for chronologic age (CA). At CA of 60 years, the modeled age in the controls was 66.40 years, and that in the addicted group was 73.11 years, an advancement of 6.71 years, or 10.10%. Exacerbations of age dependent changes in central arterial stiffness, central pressures, pulse rate, ejection duration, diastolic duration, and subendocardial perfusion ratio by opiate dependence were all noted (P < 0.05). Current heroin dose, heroin duration, and the dose duration interaction were all significantly related to the vascular (or “reference”) age (RA)/CA ratio (all P < 0.006). After multivariate adjustment, the opiate dose duration was independently predictive of RA (P < 0.02). Opiate dose and/or duration were included in a further 25 terms.
These data show that opiate use is not benign for the male cardiovascular system, but has a dose response relationship to central arterial stiffness and thus cardiovascular aging, acting independently and interactively with established cardiovascular risk factors. These findings imply accelerated organismal aging.
arterial stiffness; heroin; opiate dependence; vascular aging; human aging; methadone
The systemic bioavailability of free fatty acid (FFA) forms of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) compared with ethyl ester (EE) forms is dependent on the presence of intestinal lipases and is highest during consumption of high-fat meals. Given that patients with cardiovascular disease are advised to reduce dietary fat intake, potentially lowering the bioavailability and therapeutic benefit, the hypothesis that FFA forms provide for higher bioavailability compared with EE forms under low-fat diet conditions was tested where the pharmacokinetics of the FFA form (Epanova™) were compared with those of an ethyl ester form (Lovaza®) following repeat dosing. Fifty-two healthy male and female subjects were equally allocated to one of two open-label, parallel-group cohorts. Following a Therapeutic Lifestyle Changes diet for a minimum of 7 days, blood samples were drawn for endogenous values for EPA and DHA over a 24-hour period. Subjects were then administered 4 × 1 g capsules of either Epanova (OM3 FFA) or Lovaza (OM3 EE) once daily for 14 days, following which serial blood samples were drawn over a 24-hour period to characterize the bioavailability of EPA and DHA from the respective formulations. In addition, changes from baseline in lipid profile were explored. Systemic bioavailability, as measured by area under the curve from time zero to 24 hours (AUC0-τ) and the maximum measured plasma concentrations during the 0–24 hour dosing interval (Cmax,ss) of unadjusted total plasma EPA + DHA were approximately 3-fold and 3.9-fold higher, respectively, for Epanova relative to Lovaza. Following baseline adjustment, the magnitude of difference in bioavailability was approximately 5.8-fold and 6.5-fold higher in AUC0-τ and Cmax, respectively, for Epanova relative to Lovaza. Serum triglycerides were reduced by a significantly greater extent (P = 0.013) for Epanova relative to Lovaza (21% versus 8%). The bioavailability of the FFA forms of EPA and DHA in Epanova are significantly greater than the bioavailability from the EE forms present in Lovaza under low-fat dietary conditions normally recommended for patients with cardiovascular disease. This increased bioavailability may lead to improved triglyceride-lowering in patients with hypertriglyceridemia.
hypertriglyceridemia; eicosapentaenoic acid; docosahexaenoic acid; pharmacokinetics
The aim of this study was to compare the antihypertensive efficacy of losartan 100 mg + hydrochlorothiazide (HCTZ) 25 mg versus bisoprolol 10 mg + HCTZ 25 mg and their influence on arterial stiffness and central blood pressure (BP).
Of 60 patients with a mean BP of 173.3 ± 1.7/98.4 ± 1.2 mmHg, 59 were random-ized to losartan + HCTZ (n = 32) or bisoprolol + HCTZ (n = 27). Amlodipine was added if target BP was not achieved at 1 month, and doxazosin was added if target BP was not achieved after 3 months. Body mass index, office and 24-hour ambulatory BP, pulse wave velocity (carotid-femoral [PWVE] and radial [PWVM]), noninvasive central systolic BP, augmentation index (AIx), laboratory investigations, and electrocardiography were done at baseline and after 6 months of treatment.
Losartan + HCTZ was as effective as bisoprolol + HCTZ, with target office BP achieved in 96.9% and 92.6% of patients and target 24-hour BP in 75% and 66.7% of patients, respectively, after 6 months. Effective treatment of BP led to significant lowering of central systolic BP, but this was decreased to a significantly (P < 0.05) greater extent by losartan + HCTZ (−23.0 ± 2.3 mmHg) than by bisoprolol + HCTZ (−15.4 ± 2.9 mmHg) despite equal lowering of brachial BP. Factors correlated with central systolic BP and its lowering differed between the treatment groups. Losartan + HCTZ did not alter arterial stiffness patterns significantly, but bisoprolol + HCTZ significantly increased AIx. We noted differences in ΔPWVE, ΔPWVM, and ΔAIx between the groups in favor of losartan + HCTZ. Decreased heart rate was associated with higher central systolic BP and AIx in the bisoprolol + HCTZ group, but was not associated with increased AIx in the losartan + HCTZ group.
Although both treatments decreased both office and 24-hour BP, losartan + HCTZ significantly decreased central systolic BP and had a more positive influence on pulse wave velocity, with a less negative effect of decreased heart rate on AIx and central systolic BP.
arterial hypertension; combination therapy; central blood pressure; arterial stiffness
Diabetes mellitus (DM) is on the increase globally. Cardiovascular complications, such as left ventricular dysfunction is a major cause of death in patients with type II DM. Prior to the development of symptomatic heart failure, subclinical left ventricular dysfunction (systolic and diastolic) may exist for some time.
The aim of the study was to determine the prevalence of left ventricular dysfunction in non-hypertensive type II DM patients.
A cross sectional study of left ventricular function in 90 normotensive type II diabetes mellitus patients using echocardiography was carried out. Healthy normotensive controls matched for age, sex, and body mass index were selected for comparison. Patients and controls who had hypertension (blood pressure of >140/90 mmHg), history of smoking, significant alcohol history, pregnancy, features of thyroid disease, or valvular heart disease were excluded. Left ventricular diastolic and systolic functions were assessed.
Ninety patients, (39 males and 51 females) and 90 healthy controls (39 males and 51 females) were enrolled. Mean age of patients was 50.76 ± 9.13 years and 51.33 ± 7.84 years for controls. Mean body mass index was 26.88 ± 4.73 kg/m2 in patients and 27.09 ± 4.04 kg/m2 in controls. Mean ejection fraction was 62.4% ± 8.47% and 68.52% ± 7.94% in patients and controls, respectively (P < 0.001). Fourteen (15.56%) patients had ejection fraction less than 55% compared to four (4.44%) in controls (P < 0.001; odds ratio = 3.96). Impaired diastolic function was found in 65.6% of patients compared to 3.3% of controls (P < 0.001). Left ventricular mass index of >99 kg/m2 in females and >115 kg/m2 in males was considered abnormal. The left ventricular mass index was also higher in patients than in controls (95.17 ± 25.67 g/m2 versus 85.40 ± 18.0 g/m2; P = 0.004).
Normotensive diabetic patients have a high prevalence of left ventricular dysfunction even in the absence of cardiac symptoms
type II diabetes mellitus; diastolic dysfunction; systolic dysfunction
This review discusses the rationale for earlier use of single-pill combinations (SPCs) of antihypertensive drugs, with a focus on telmisartan/amlodipine (T/A) and telmisartan/hydrochlorothiazide (T/H) SPCs. Compared with the respective monotherapies, the once-daily T/A and T/H SPCs have been shown to result in significantly higher blood pressure (BP) reductions, BP goal rates, and response rates in patients at all stages of hypertension. As expected, BP reductions are highest with the highest dose (T80/A10 and T80/H25) SPCs. Subgroup analyses of the telmisartan trials have reported the efficacy of both SPCs to be consistent, regardless of the patients’ age, race, and coexisting diabetes, obesity, or renal impairment. In patients with mild-to-moderate hypertension, the T/A combination provides superior 24-hour BP-lowering efficacy compared with either treatment administered as monotherapy. Similarly, the T/H SPC treatment provides superior 24-hour BP-lowering efficacy, especially in the last 6 hours relative to other renin–angiotensin system inhibitor-based SPCs. The T/A SPC is associated with a lower incidence of edema than amlodipine monotherapy, and the T/H SPC with a lower incidence of hypokalemia than hydrochlorothiazide monotherapy. Existing evidence supports the use of the T/A SPC for the treatment of hypertensive patients with prediabetes, diabetes, or metabolic syndrome, due to the metabolic neutrality of both component drugs, and the use of the T/H SPC for those patients with edema or in need of volume reduction.
calcium-channel blocker; essential hypertension; diuretic; primary care physician; renin-angiotensin system inhibitor
Human immunodeficiency virus (HIV) and its therapy are associated with increased aortic stiffness and metabolic syndrome (MetS) phenotype in Caucasian patients. We hypothesized that, independently of antiretroviral therapy, HIV infection in native black African patients is associated with increased burden of cardiometabolic risk factors that may accelerate arterial structural damage and translate into increased aortic stiffness.
Patients and methods
Ninety-six apparently healthy Cameroonian subjects (controls) were compared to 108 untreated Cameroonian HIV+ patients (HIV-UT) of similar age. In each participant, pulse wave velocity (Complior), aortic augmentation index (SphygmoCor), brachial blood pressure (Omron 705 IT), fasting plasma glucose (FPG), and lipids were recorded, as well as the prevalence and severity of MetS, based on the American Heart Association/National Heart, Lung, and Blood Institute score ≥3/5.
Prevalence of impaired fasting glucose (FPG 100–125 mg · dL−1) and of diabetes (FPG > 125 mg · dL−1) was higher in HIV-UT than in controls (47% versus 27%, and 26% versus 1%, respectively; both P < 0.01). Fasting triglycerides and the atherogenic dyslipidemia ratio were significantly higher in HIV-UT than in controls. Hypertension prevalence was high and comparable in both groups (41% versus 44%, respectively; not significant). HIV-UT patients exhibited a twice-higher prevalence of MetS than controls (47% versus 21%; P = 0.02). Age- and sex-adjusted pulse wave velocity was higher in HIV-UT than in controls (7.5 ± 2.2 m/s versus 6.9 ± 1.7 m/s, respectively; P = 0.02), whereas aortic augmentation index was significantly lower (6% ± 4% versus 8% ± 7%, respectively; P = 0.01).
Similar to Caucasian populations, native Cameroonian HIV-UT patients showed a higher prevalence of MetS and its phenotype, associated with increased aortic stiffness, an early marker of atherosclerosis.
metabolic syndrome; HIV; arterial; stiffness; Cameroon
Numerous studies have reported that low calcium intake is related to a higher prevalence of cardiovascular disease. However, the relationship between serum calcium and coronary heart disease is unclear. The purpose of this study was to compare serum calcium levels in patients with coronary heart disease and those in healthy individuals.
This retrospective, case-control study conducted in the People’s Republic of China comprised 380 cases and 379 controls. Serum calcium levels, blood lipids, and anthropometric measurements were measured in both groups. The Student’s unpaired t-test or Chi-square test was used to compare differences between cases and controls. Pearson’s partial correlation coefficient was used to determine the association between serum calcium, blood lipids, and blood pressure in both groups.
Our results indicate that the average level of serum calcium in cases was higher than in controls. Serum calcium levels showed no correlation with any parameter except for triglycerides in either group.
Overall, these data suggest that serum calcium has no influence on coronary heart disease or triglyceride levels in the general population.
serum calcium; hypertension; blood lipids
Cardiovascular diseases (CVD) are the leading cause of mortality in middle-income countries, such as Brazil. However, given the diversity in health care systems in Brazil, access to proven services, such as cardiac rehabilitation (CR), varies widely.
To describe and compare multilevel barriers to CR enrollment and participation in three Brazilian cohorts: (1) cardiac outpatients not attending CR (public or private system); (2) cardiac outpatients paying for CR; and (3) residents at high-risk of CVD with access to a free comprehensive exercise program but not making use of the program.
Brazilian residents from two cities were invited to participate – Florianopolis, an urban center; and Luzerna, a rural center. Respondents completed a survey including the Cardiac Rehabilitation Barriers Scale. Mann–Whitney U tests were used to compare barriers between cohorts cross-sectionally.
Six hundred twenty-eight Brazilians consented to participate: 237 (37.7%) from Florianopolis, of which 139 (22.1%) participated in CR; and 391 (62.3%) from Luzerna. The mean total CR barriers for the sample were 1.66 ± 0.6 and differed significantly by cohort (P < 0.001). CR nonattendees from Florianopolis (eg, distance and not knowing about CR) and participants from Luzerna (eg, work and family responsibilities) reported significantly higher barriers than CR attendees from Florianopolis.
CR nonattendees reported significantly greater barriers than CR attendees. It is hoped that the provision of CR will increase, and that the development of the programs will be in a manner which mitigates the chief barriers identified herein.
cardiac rehabilitation; barriers; participation; enrollment; comparison study
To translate, cross-culturally adapt, and validate the Questionnaire for Diabetes-Related Foot Disease (Q-DFD), originally created and validated in Australia, for its use in Spanish-speaking patients with diabetes mellitus.
Patients and methods
The translation and cross-cultural adaptation were based on international guidelines. The Spanish version of the survey was applied to a community-based (sample A) and a hospital clinic-based sample (samples B and C). Samples A and B were used to determine criterion and construct validity comparing the survey findings with clinical evaluation and medical records, respectively; while sample C was used to determine intra- and inter-rater reliability.
After completing the rigorous translation process, only four items were considered problematic and required a new translation. In total, 127 patients were included in the validation study: 76 to determine criterion and construct validity and 41 to establish intra- and inter-rater reliability. For an overall diagnosis of diabetes-related foot disease, a substantial level of agreement was obtained when we compared the Q-DFD with the clinical assessment (kappa 0.77, sensitivity 80.4%, specificity 91.5%, positive likelihood ratio [LR+] 9.46, negative likelihood ratio [LR−] 0.21); while an almost perfect level of agreement was obtained when it was compared with medical records (kappa 0.88, sensitivity 87%, specificity 97%, LR+ 29.0, LR− 0.13). Survey reliability showed substantial levels of agreement, with kappa scores of 0.63 and 0.73 for intra- and inter-rater reliability, respectively.
The translated and cross-culturally adapted Q-DFD showed good psychometric properties (validity, reproducibility, and reliability) that allow its use in Spanish-speaking diabetic populations.
diabetes mellitus; peripheral vascular disease; diabetic neuropathy; foot ulcers
Patients with HIV infection are at increased risk for coronary artery disease (CAD), and growing evidence suggests a possible link between vitamin D deficiency and clinical/subclinical CAD. However, the relationship between vitamin D deficiency and coronary artery calcification (CAC), a sensitive marker for subclinical CAD, in those with HIV infection is not well investigated.
CAC was quantified using a Siemens Cardiac 64 scanner, and vitamin D levels and the presence of traditional and novel risk factors for CAD were obtained in 846 HIV-infected African American (AA) participants aged 25 years or older in Baltimore, MD, USA without symptoms or clinical evidence of CAD.
The prevalence of vitamin D deficiency (25-hydroxy vitamin D <10 ng/mL) was 18.7%. CAC was present in 238 (28.1%) of the 846 participants. Logistic regression analysis revealed that the following factors were independently associated with CAC: age (adjusted odds ratio [OR]: 1.11; 95% confidence interval [CI]: 1.08–1.14); male sex (adjusted OR: 1.71; 95% CI: 1.18–2.49); family history of CAD (adjusted OR: 1.53; 95% CI: 1.05–2.23); total cholesterol (adjusted OR: 1.006; 95% CI: 1.002–1.010); high-density lipoprotein cholesterol (adjusted OR: 0.989; 95% CI: 0.979–0.999); years of cocaine use (adjusted OR: 1.02; 95% CI: 1.001–1.04); duration of exposure to protease inhibitors (adjusted OR: 1.004; 95% CI: 1.001–1.007); and vitamin D deficiency (adjusted OR: 1.98; 95% CI: 1.31–3.00).
Both vitamin D deficiency and CAC are prevalent in AAs with HIV infection. In order to reduce the risk for CAD in HIV-infected AAs, vitamin D levels should be closely monitored. These data also suggest that clinical trials should be conducted to examine whether vitamin D supplementations reduce the risk of CAD in this AA population.
African Americans; HIV infection; antiretroviral therapy; coronary artery calcification; vitamin D deficiency
The safety and efficacy of olmesartan 40 mg and hydrochlorothiazide (HCTZ) as a fixed-dose combination has been investigated in clinical trials leading to its approval. The aims of the present study were to confirm these data in an unselected patient population in daily practice and to determine the impact of physical activity on blood pressure control.
In a multicenter, noninterventional study, 3,333 patients with either insufficient blood pressure control on olmesartan 40 mg alone or on a fixed/free combination of olmesartan 40 mg and HCTZ 12.5/25 mg were primarily assessed for safety and tolerability of the fixed-dose combination of olmesartan 40 mg and HCTZ 12.5/25 mg at 24 ± 2 weeks. Secondary objectives were blood pressure reduction, treatment compliance, and impact of physical activity as measured by the sum of weekly energy costs.
The mean patient age was 63.2 ± 11.46 years, mean baseline blood pressure was 159.6 ± 15.28/93.5 ± 9.52 mmHg, and 70.9% had at least one additional cardiovascular risk factor. Adverse drug reactions were rare (n = 19), and no serious adverse drug reactions occurred. Compliance with drug therapy was at least sufficient in more than 99% of patients at the end of the study. Blood pressure at the last available visit was reduced by 26.1 ± 15.5/13.0 ± 10.1 mmHg versus baseline (P < 0.0001), but had reduced effectiveness in patients ≥75 years with diabetes or impaired renal function. In 69% of patients, blood pressure was normalized (<140/90 mmHg). No noteworthy differences in baseline characteristics or baseline blood pressure were found between patients with an activity level (sum of weekly energy costs) above or below the median of 9,460.6. A higher versus lower physical activity score had no impact on blood pressure reduction.
Our data confirm randomized trial data concerning safe and efficient blood pressure reduction using a fixed-dose combination of olmesartan 40 mg and HCTZ 12.5/25 mg in a large, unselected patient population, independent of physical activity level.
blood pressure; antihypertensive agents; administration; dosage; physical activity
We sought to examine the prognostic value of heart rate turbulence derived from electrocardiographic recordings initiated in the emergency department for patients with non-ST elevation myocardial infarction (NSTEMI) or unstable angina.
Twenty-four-hour Holter recordings were started in patients with cardiac symptoms approximately 45 minutes after arrival in the emergency department. Patients subsequently diagnosed with NSTEMI or unstable angina who had recordings with ≥18 hours of sinus rhythm and sufficient data to compute Thrombolysis In Myocardial Infarction (TIMI) risk scores were chosen for analysis (n = 166). Endpoints were emergent re-entry to the cardiac emergency department and/or death at 30 days and one year.
In Cox regression models, heart rate turbulence and TIMI risk scores together were significant predictors of 30-day (model chi square 13.200, P = 0.001, C-statistic 0.725) and one-year (model chi square 31.160, P < 0.001, C-statistic 0.695) endpoints, outperforming either measure alone.
Measurement of heart rate turbulence, initiated upon arrival at the emergency department, may provide additional incremental value in the risk assessment for patients with NSTEMI or unstable angina.
acute coronary syndrome; electrocardiographic monitoring; heart rate turbulence; non-ST elevation myocardial infarction; outcomes; prognosis; unstable angina
The purpose of this study was to assess specific vacuum-venipuncture skills and the influence of the time involved in skin puncture and blood collection.
Thirty subjects undergoing venipuncture in which video analysis was possible were included. These procedures were carried out by four nurses and recorded with a digital camera. Venipuncture skills classified by our observations were delineated on the basis of frame-by-frame video images, and a graph of x and y coordinates was created.
With the first blood-collection tube, strong blood flow required the practitioner to push the tube back in to compensate for the strong repulsive force in approximately 46% of cases. By the third blood-collection tube, the blood flow had weakened; therefore, the tube was moved up and down. In cases that required a second venipuncture, the tube was already pierced, so the time required to fill it to 5 mL was significantly longer.
Hand movement of the practitioner is adjusted according to blood flow. Reflex movement in response to strong blood flow may increase the risk of pushing the needle through the vein with excessive force. The time required to fill the tube varies among nurses, tube order, and level of venipuncture skills.
blood collection; blood-collection tube; clinical practice; venipuncture skill
Inflammation has been implicated in the development of atherosclerosis in patients with acute coronary syndrome. C-reactive protein is an established nonspecific prognostic inflammatory biomarker for patients with acute coronary syndrome in the medical literature. This has led to a concerted effort to identify circulating inflammatory biomarkers to facilitate predicting the risk for and diagnosing coronary artery disease in at-risk subjects. The objective of this study was to search after novel inflammatory biomarkers reported as useful for diagnosing coronary artery disease.
The PubMed database was searched for reports published from January 1, 2000 to June 30, 2012 of novel circulating biomarkers for coronary artery disease in addition to the established biomarker, C-reactive protein. The search terms used were “infarction”, “biomarkers”, and “markers”, and only original articles describing clinical trials that were written in English were included. All published articles were separately examined carefully after novel inflammatory markers for acute coronary syndrome. All irrelevant publications without content pertaining to inflammatory biomarkers for acute coronary syndrome were excluded from this study. Our results reflect all articles concerning biomarkers in humans.
The PubMed search yielded 4,415 research articles. After further analysis, all relevant published original articles examining 53 biomarkers were included in this review, which identified 46 inflammation biomarkers useful for detecting coronary artery disease.
The emergence of diverse novel biomarkers for coronary artery disease has provided insight into the varied pathophysiology of this disease. Inflammatory biomarkers have tremendous potential in aiding the prediction of acute coronary syndrome and recurrent ischemic episodes, and will eventually help improve patient care and management.
arteriosclerosis; biomarkers; coronary artery disease; myocardial infarction; inflammation; markers
The implications of reactive oxygen species in cardiovascular disease have been known for some
decades. Rationally, therapeutic antioxidant strategies combating oxidative stress have been
developed, but the results of clinical trials have not been as good as expected. Therefore, to move
forward in the design of new therapeutic strategies for cardiovascular disease based on prevention
of production of reactive oxygen species, steps must be taken on two fronts, ie, comprehension of
reduction-oxidation signaling pathways and the pathophysiologic roles of reactive oxygen species,
and development of new, less toxic, and more selective nicotinamide adenine dinucleotide phosphate
(NADPH) oxidase inhibitors, to clarify both the role of each NADPH oxidase isoform and their utility
in clinical practice. In this review, we analyze the value of NADPH oxidase as a therapeutic target
for cardiovascular disease and the old and new pharmacologic agents or strategies to prevent NADPH
oxidase activity. Some inhibitors and different direct or indirect approaches are available.
Regarding direct NADPH oxidase inhibition, the specificity of NADPH oxidase is the focus of current
investigations, whereas the chemical structure-activity relationship studies of known inhibitors
have provided pharmacophore models with which to search for new molecules. From a general point of
view, small-molecule inhibitors are preferred because of their hydrosolubility and oral
bioavailability. However, other possibilities are not closed, with peptide inhibitors or monoclonal
antibodies against NADPH oxidase isoforms continuing to be under investigation as well as the
ongoing search for naturally occurring compounds. Likewise, some different approaches include
inhibition of assembly of the NADPH oxidase complex, subcellular translocation, post-transductional
modifications, calcium entry/release, electron transfer, and genetic expression. High-throughput
screens for any of these activities could provide new inhibitors. All this knowledge and the
research presently underway will likely result in development of new drugs for inhibition of NADPH
oxidase and application of therapeutic approaches based on their action, for the treatment of
cardiovascular disease in the next few years.
nicotinamide adenine dinucleotide phosphate oxidase; NOX; cardiovascular therapeutic targets; inhibitors; pharmacophore models
Pioglitazone and other thiazolidinediones (TZDs) initially showed great promise as unique
receptor-mediated oral therapy for type 2 diabetes, but a host of serious side effects, primarily
cardiovascular, have limited their utility. It is crucial at this point to perform a risk–
benefit analysis to determine what role pioglitazone should play in our current treatment of type 2
diabetes and where the future of this class of drugs is headed. This review provides a comprehensive
overview of the present literature. Clinical data currently available indicate that pioglitazone is
an effective and generally well-tolerated treatment option for use in patients with type 2 diabetes.
Pioglitazone can still reduce adverse cardiovascular risk.
pioglitazone; diabetes; cardiovascular risk
This randomized crossover trial assessed the effects of 5 weeks of consuming low-fat dairy (one serving/day each of 1% fluid milk, low-fat cheese, and low-fat yogurt) versus nondairy products (one serving/day each of apple juice, pretzels, and cereal bar) on systolic and diastolic blood pressures (SBP and DBP), vascular function (reactive hyperemia index [RHI] and augmentation index), and plasma lipids.
Patients were 62 men and women (mean age 54.5 years, body mass index 29.2 kg/m2) with prehypertension or stage 1 hypertension (mean resting SBP/DBP 129.8 mmHg/80.8 mmHg) while not receiving antihypertensive medications. A standard breakfast meal challenge including two servings of study products was administered at the end of each treatment period.
Dairy and nondairy treatments did not produce significantly different mean SBP or DBP in the resting postprandial state or from premeal to 3.5 hours postmeal (SBP, 126.3 mmHg versus 124.9 mmHg; DBP, 76.5 mmHg versus 75.7 mmHg), premeal (2.35 versus 2.20) or 2 hours postmeal (2.33 versus 2.30) RHI, and premeal (22.5 versus 23.8) or 2 hours postmeal (12.4 versus 13.2) augmentation index. Among subjects with endothelial dysfunction (RHI ≤ 1.67; n = 14) during the control treatment, premeal RHI was significantly higher in the dairy versus nondairy condition (2.32 versus 1.50, P = 0.002). Fasting lipoprotein lipid values were not significantly different between treatments overall, or in subgroup analyses.
No significant effects of consuming low-fat dairy products, compared with low-fat nondairy products, were observed for blood pressures, measures of vascular function, or lipid variables in the overall sample, but results from subgroup analyses were consistent with the hypothesis that dairy foods might improve RHI in those with endothelial dysfunction.
blood pressure; dairy; endothelial function; hypertension; lipids
Complications resulting from venipuncture include vein and nerve damage, hematoma, and neuropathic pain. Although the basic procedures are understood, few analyses of actual data exist. It is important to improve the safety standards of this technique during venipuncture. This study aimed to obtain data on actual needle movement during vacuum venipuncture in order to develop appropriate educational procedures.
Six experienced nurses were recruited to collect blood samples from 64 subjects. These procedures were recorded using a digital camera. Software was then used to track and analyze motion without the use of a marker in order to maintain the sterility of the needle. Movement along the X- and Y-axes during blood sampling was examined.
Approximately 2.5 cm of the needle was inserted into the body, of which 6 mm resulted from advancing or moving the needle following puncture. The mean calculated puncture angle was 15.2°. Given the hazards posed by attaching and removing the blood collection tube, as well as by manipulating the needle to fix its position, the needle became unstable whether it was fixed or not fixed.
This study examined venipuncture procedures and showed that the method was influenced by increased needle movement. Focusing on skills for puncturing the skin, inserting the needle into the vein, and changing hands while being conscious of needle-tip stability may be essential for improving the safety of venipuncture.
blood collection; nerve damage; motion analysis; patient safety; puncture angle; clinical education
The Global Vascular Risk Management (GVRM) Study is a 5-year prospective observational study of 87,863 patients (61% females) with hypertension and associated cardiovascular risk factors began January 1, 2010. Data are gathered electronically and cardiovascular risk is evaluated using the Consortium for Southeastern Hypertension Control™ (COSEHC™)-11 risk score. Here, we report the results obtained at the completion of 33 months since study initiation. De-identified electronic medical records of enrolled patients were used to compare clinical indicators, antihypertensive medication usage, and COSEHC™ risk scores across sex and diabetic status subgroups. The results from each subgroup, assessed at baseline and at regular follow-up periods, are reported since the project initiation. Inference testing was performed to look for statistically significant differences between goal attainments rates between sexes. At-goal rates for systolic blood pressure (SBP) were improved during the 33 months of the study, with females achieving higher goal rates when compared to males. On the other hand, at-goal control rates for total and low-density lipoprotein (LDL) cholesterol (chol) were better in males compared to females. Diabetic patients had lower at-goal rates for SBP and triglycerides but higher rates for LDL-chol. The LDL-chol at-goal rates were higher for males, while high-density lipoprotein (HDL)-chol rates were higher for females. Utilization of antihypertensive medications was similar during and after the baseline period for both men and women. Patients taking two or more antihypertensive medications had higher mean COSEHC™-11 scores compared to those on monotherapy. With treatment, hypertensive patients can reach SBP and cholesterol goals; however, population-wide improvement in treatment goal adherence continues to be a challenge for physicians. The COSEHC™ GVRM Study shows, however, that continuous monitoring and feedback to physicians of accurate longitudinal data is an effective tool in achieving better control rates of cardiovascular risk factors.
cardiovascular risk; coronary heart disease; dyslipidemia; electronic medical records; hypertension; metabolic syndrome
Systemic thromboembolism is a serious, major complication in patients with an atrial septal aneurysm (ASA). Paroxysmal atrial fibrillation (AF) is more common in patients with ASA than in the normal population. Neutrophil/lymphocyte ratio (NLR) has been associated with postoperative AF development in patients who have undergone cardiac surgery. This study investigated NLR in a group of ASA patients compared with a control group of healthy volunteers.
Patients and methods
The study group consisted of 40 patients with ASA; the control group consisted of 30 age-, sex-, and body mass index-matched healthy volunteers. All patients and control subjects underwent echocardiographic examination. No patient had a recent history of an acute infection or an inflammatory disease. Baseline NLR was measured by dividing neutrophil count by lymphocyte count.
No statistically significant difference was found between the two groups in terms of basic characteristics. Mean NLR was significantly higher among persons with ASA compared with controls (3.4 ± 1.5 vs 1.6 ± 0.97, P < 0.001).
Our results suggest that a higher NLR, an emerging marker of inflammation, has a positive correlation with ASA. The measurement of NLR may be used to indicate an increased risk of arrhythmia, such as AF, in ASA patients.
neutrophil-lymphocyte ratio; inflammation; arrhythmia
Elevated total plasma homocysteine is an independent risk factor for arterial and venous thrombosis in patients with normal renal function. Patients on hemodialysis have a high prevalence of mild to moderate hyperhomocysteinemia. Conflicting retrospective analyses and prospective studies have been reported regarding the association between total homocysteine levels and hemodialysis vascular thrombosis. The purpose of this retrospective study was to investigate the relationship between hyperhomocysteinemia and vascular access thrombosis (VAT) in patients on hemodialysis.
One hundred and twenty-five patients undergoing dialysis were selected as subjects. The experimental group participants were identified as those having one or more VAT during the previous 13 months and the control group participants had no access thrombosis during the same period. Additional subgroup analysis included the presence of hypertension, diabetes, low-density lipoprotein levels, sex, and use of aspirin.
No statistically significant difference was found in total homocysteine levels between the two groups (P = 0.27). No association was found between VAT and sex (P = 0.09), VAT and hypertension (P = 0.96), VAT and diabetes (P = 0.49), nor VAT and low-density lipoprotein level (P = 0.04). A lower rate of VAT was associated with aspirin intake (P = 0.04).
This study did not demonstrate a relationship between total homocysteine concentrations and risk of VAT in patients with end-stage renal disease on hemodialysis. There were no significant differences in the number of VAT across additional variables of sex and previous morbidity. Aspirin intake was associated with a lower incidence of VAT.
hyperhomocysteinemia; vascular access thrombosis; hemodialysis
Intracranial hypertension is commonly encountered in poor-grade aneurysmal subarachnoid hemorrhage patients. Refractory raised intracranial pressure is associated with poor prognosis. The management of raised intracranial pressure is commonly referenced to experiences in traumatic brain injury. However, pathophysiologically, aneurysmal subarachnoid hemorrhage is different from traumatic brain injury. Currently, there is a paucity of consensus on the management of refractory raised intracranial pressure in spontaneous subarachnoid hemorrhage. We discuss in this paper the role of hyperosmolar agents, hypothermia, barbiturates, and decompressive craniectomy in managing raised intracranial pressure refractory to first-line treatment, in which preliminary data supported the use of hypertonic saline and secondary decompressive craniectomy. Future clinical trials should be carried out to delineate better their roles in management of raised intracranial pressure in aneurysmal subarachnoid hemorrhage patients.
aneurysm; intracranial pressure; intracranial hypertension; subarachnoid hemorrhage