Effect of streptozotocin-induced diabetes on myocardial blood flow reserve assessed by myocardial contrast echocardiography in rats

Background

Hypertension and type 2 diabetes are common co-morbidities. Preliminary studies suggest that thiazolidinediones reduce blood pressure (BP). We therefore used ambulatory BP to quantify BP lowering at 6–12 months with rosiglitazone used in combination with metformin or sulfonylureas compared to metformin and sulfonylureas in people with type 2 diabetes.

Methods

Participants (n = 759) in the multicentre RECORD study were studied. Those taking metformin were randomized (open label) to add-on rosiglitazone or sulfonylureas, and those on sulfonylurea to add-on rosiglitazone or metformin.

Results

24-Hour ambulatory BP was measured at baseline, 6 months and 12 months. At 6 and 12 months, reductions in 24-hour ambulatory systolic BP (sBP) were greater with rosiglitazone versus metformin (difference at 6 months 2.7 [95% CI 0.5–4.9] mmHg, p = 0.015; 12 months 2.5 [95% CI 0.2–4.8] mmHg, p = 0.031). Corresponding changes for ambulatory diastolic BP (dBP) were comparable (6 months 2.7 [95% CI 1.4–4.0] mmHg, p < 0.001; 12 months 3.1 [95% CI 1.8–4.5] mmHg, p < 0.001). Similar differences were observed for rosiglitazone versus sulfonylureas at 12 months (sBP 2.7 [95% CI 0.5–4.9] mmHg, p = 0.016; dBP 2.1 [95% CI 0.7–3.4] mmHg, p = 0.003), but differences were smaller and/or not statistically significant at 6 months (sBP 1.5 [95% CI -0.6 to 3.6] mmHg, p = NS; dBP 1.3 [95% CI 0.0–2.5] mmHg, p = 0.049). Changes in BP were not accompanied by compensatory increases in heart rate, did not correlate with basal insulin sensitivity estimates and were not explained by changes in antihypertensive therapy between the various strata.

Conclusion

When added to metformin or a sulfonylurea, 12-month treatment with rosiglitazone reduces ambulatory BP to a greater extent than when metformin and a sulfonylurea are combined.

Trial registration

NCT00379769 http://clinicaltrials.gov/     

Ultrasound settings significantly alter arterial lumen and wall thickness measurements

Background

Arterial diameter and intima-media thickness (IMT) enlargement may each be related to the atherosclerotic process. Their separate or combined enlargement may indicate different arterial phenotypes with different atherosclerosis risk.

Methods

We investigated cross-sectional (baseline 1987–89: n = 7956) and prospective (median follow-up = 5.9 years: n = 4845) associations between baseline right common carotid artery (RCCA) external diameter and IMT with existing and incident carotid atherosclerotic lesions detected by B-mode ultrasound in any right or left carotid segments. Logistic regression models (unadjusted, adjusted for IMT, or adjusted for IMT and risk factors) were used to relate baseline diameter to existing carotid lesions while comparably adjusted parametric survival models assessed baseline diameter associations with carotid atherosclerosis progression (incident carotid lesions). Four baseline arterial phenotypes were categorized as having 1) neither IMT nor diameter enlarged (reference), 2) isolated IMT thickening, 3) isolated diameter enlargement, and 4) enlargement of both IMT and diameter. The association between these phenotypes and progression to definitive carotid atherosclerotic lesions was assessed over the follow-up period.

Results

Each standard deviation increment of baseline RCCA diameter was associated with increasing carotid lesion prevalence (unadjusted odds ratio [OR] = 1.54, 95% confidence interval [CI] = 1.47–1.62) and with progression of carotid atherosclerosis (unadjusted hazards ratio (HR) = 1.37, 95% CI = 1.28–1.46); and the associations remained significant even after adjustment for IMT and risk factors (prevalence OR = 1.11, 95% CI = 1.04–1.18; progression HR = 1.11, 95% CI = 1.03–1.19). Controlling for gender, age and race, persons with both RCCA IMT and diameter in the upper 50^th percentiles had the greatest risk of progressing to clearly defined carotid atherosclerotic lesions (all HR = 1.71, 95% CI = 1.47–2.0; men HR = 1.88, 95% CI = 1.48–2.39; women HR = 1.59, 95% CI = 1.31–1.95) while RCCA IMT or diameter alone in the upper 50^th percentile produced significantly lower estimated risks.

Conclusion

RCCA IMT and external diameter provide partially overlapping information relating to carotid atherosclerotic lesions. More importantly, the RCCA phenotype of coexistent wall thickening with external diameter enlargement indicates higher atherosclerotic risk than isolated wall thickening or diameter enlargement.     

Reproducibility of Transcranial Doppler ultrasound in the middle cerebral artery

Background

Transcranial Doppler ultrasound remains the only imaging modality that is capable of real-time measurements of blood flow velocity and microembolic signals in the cerebral circulation. We here assessed the repeatability and reproducibility of transcranial Doppler ultrasound in healthy volunteers and patients with symptomatic carotid artery stenosis.

Methods

Between March and August 2017, we recruited 20 healthy volunteers and 20 patients with symptomatic carotid artery stenosis. In a quiet temperature-controlled room, two 1-h transcranial Doppler measurements of blood flow velocities and microembolic signals were performed sequentially on the same day (within-day repeatability) and a third 7–14 days later (between-day reproducibility). Levels of agreement were assessed by interclass correlation co-efficient.

Results

In healthy volunteers (31±9 years, 11 male), within-day repeatability of Doppler measurements were 0.880 (95% CI 0.726–0.950) for peak velocity, 0.867 (95% CI 0.700–0.945) for mean velocity, and 0.887 (95% CI 0.741–0.953) for end-diastolic velocity. Between-day reproducibility was similar but lower: 0.777 (95% CI 0.526–0.905), 0.795 (95% CI 0.558–0.913), and 0.674 (95% CI 0.349–0.856) respectively. In patients (72±11 years, 11 male), within-day repeatability of Doppler measurements were higher: 0.926 (95% CI 0.826–0.970) for peak velocity, 0.922 (95% CI 0.817–0.968) for mean velocity, and 0.868 (95% CI 0.701–0.945) for end-diastolic velocity. Similarly, between-day reproducibility revealed lower values: 0.800 (95% CI 0.567–0.915), 0.786 (95% CI 0.542–0.909), and 0.778 (95% CI 0.527–0.905) respectively. In both cohorts, the intra-observer Bland Altman analysis demonstrated acceptable mean measurement differences and limits of agreement between series of middle cerebral artery velocity measurements with very few outliers. In patients, the carotid stenoses were 30–40% (n?=?9), 40–50% (n?=?6), 50–70% (n?=?3) and?>?70% (n?=?2).No spontaneous embolisation was detected in either of the groups.

Conclusions

Transcranial Doppler generates reproducible data regarding the middle cerebral artery velocities. However, larger studies are needed to validate its clinical applicability.

Trial registration

ClinicalTrial.gov (ID NCT 03050567), retrospectively registered on 15/05/2017.

     

Predictors of severe stenosis at invasive coronary angiography in patients with normal myocardial perfusion imaging

Purpose

Normal myocardial perfusion imaging (MPI) is associated with excellent prognosis. However, in patients with persisting symptoms, it may be difficult to determine the patients in whom invasive angiography is justified to rule out false negative MPI. We evaluated predictors for severe stenosis at invasive angiography in patients with persisting symptoms after normal MPI.

Methods

229 consecutive patients with normal MPI, without previous bypass surgery, underwent invasive angiography within 6 months. Older age was defined as >65 years. Multivariable analyses were performed to adjust for differences in baseline variables.

Results

Mean age was 62?±?11 years, 48% were women. Severe stenosis was observed in 34%, and of these patients 60% had single-vessel disease (not left main coronary artery disease). After adjusting for several variables, including diabetes, smoking status, hypertension and hypercholesterolaemia, predictors of severe stenosis were male gender, odds ratio (OR) 2.7 (95% confidence interval (CI) 1.5–4.9), older age, OR 1.9 (95% CI 1.02–3.54) previous PCI, OR 2.0 (95% CI 1.0–4.3) and typical angina, OR 2.5 (95% CI 1.4–4.6).

Conclusions

Increasing age, male gender, previous PCI and typical symptoms are predictors of severe stenosis at invasive coronary angiography in patients with normal MPI. The majority of these patients have single-vessel disease.

     

Hypothermia in a surgical intensive care unit

Background

Inadvertent hypothermia is not uncommon in the immediate postoperative period and it is associated with impairment and abnormalities in various organs and systems that can lead to adverse outcomes. The aim of this study was to estimate the prevalence, the predictive factors and outcome of core hypothermia on admission to a surgical ICU.

Methods

All consecutive 185 adult patients who underwent scheduled or emergency noncardiac surgery admitted to a surgical ICU between April and July 2004 were admitted to the study. Tympanic membrane core temperature (Tc) was measured before surgery, on arrival at ICU and every two hours until 6 hours after admission. The following variables were also recorded: age, sex, body weight and height, ASA physical status, type of surgery, magnitude of surgical procedure, anesthesia technique, amount of intravenous fluids administered during anesthesia, use of temperature monitoring and warming techniques, duration of the anesthesia, ICU length of stay, hospital length of stay and SAPS II score. Patients were classified as either hypothermic (Tc ≤ 35°C) or normothermic (Tc> 35°C). Univariate analysis and multiple regression binary logistic with an odds ratio (OR) and its 95% Confidence Interval (95%CI) were used to compare the two groups of patients and assess the relationship between each clinical predictor and hypothermia. Outcome measured as ICU length of stay and mortality was also assessed.

Results

Prevalence of hypothermia on ICU admission was 57.8%. In univariate analysis temperature monitoring, use of warming techniques and higher previous body temperature were significant protective factors against core hypothermia. In this analysis independent predictors of hypothermia on admission to ICU were: magnitude of surgery, use of general anesthesia or combined epidural and general anesthesia, total intravenous crystalloids administrated and total packed erythrocytes administrated, anesthesia longer than 3 hours and SAPS II scores. In multiple logistic regression analysis significant predictors of hypothermia on admission to the ICU were magnitude of surgery (OR 3.9, 95% CI, 1.4–10.6, p = 0.008 for major surgery; OR 3.6, 95% CI, 1.5–9.0, p = 0.005 for medium surgery), intravenous administration of crystalloids (in litres) (OR 1.4, 95% CI, 1.1–1.7, p = 0.012) and SAPS score (OR 1.0, 95% CI 1.0–1.7, p = 0.014); higher previous temperature in ward was a significant protective factor (OR 0.3, 95% CI 0.1–0.7, p = 0.003). Hypothermia was neither a risk factor for hospital mortality nor a predictive factor for staying longer in ICU.

Conclusion

The prevalence of patient hypothermia on ICU arrival was high. Hypothermia at time of admission to the ICU was not an independent factor for mortality or for staying longer in ICU.     

The cardiovascular profile of soccer referees: an echocardiographic study

Background

Previous studies demonstrated a modest association between C-Reactive Protein (CRP), stenosis of carotid artery, and carotid Intima-Media Thickness (IMT) in general population. During present study, we aimed to evaluate the relationship between High Sensitivity C-Reactive Protein (hsCRP) and Common Carotid Intima-Media Thickness (CCIMT) in patients who candidate for Coronary Artery Bypass Grafting (CABG).

Methods

The study subjects were enrolled from patients with coronary arteries disease referred from Shahid Madani Hospital (Tabriz, Iran), who have been candidate for elective CABG from January 2005 to August 2007. The common carotid arteries were evaluated with high-resolution B-mode ultrasonography using a 7.5- MHz linear-array transducer to determine the IMT and grade of stenosis. Serum hsCRP level was measured using commercially available enzyme linked immunosorbent assay kit.

Results

Finally, information of 176 CABG candidates was analysed. The mean age of participants was 62.71 ± 9.45 years with 1.63 male to female ratio. The mean of CCIMT was 0.69 ± 0.54 mm. Although there was no significant correlation between serum hsCRP level and CCIMT in patients without carotid stenosis (p=0.113, r=0.186), participants with common carotid artery stenosis had higher levels of serum hsCRP than participants without stenosis (2.42+/-1.30 vs. 1.20+/-0.97 mg/dl; p=0.009).

Conclusion

Study results showed that there was no correlation between serum hsCRP level and CCIMT in patients without carotid stenosis, but patients with common carotid artery stenosis had higher levels of serum hsCRP than patients without stenosis.     

A new technique for assessing arterial pressure wave forms and central pressure with tissue Doppler

Background

Arterial diameters enlarge in response to wall thickening, plaques, and many atherosclerotic risk factors. We hypothesized that right common carotid artery (RCCA) diameter would be independently associated with cardiac disease and improve risk discrimination.

Methods

In a middle-aged, biracial population (baseline n = 11225), we examined associations between 1 standard deviation increments of baseline RCCA diameter with prevalent myocardial infarction (MI) and incident cardiac events (MI or cardiac death) using logistic regression and Cox proportional hazards models, respectively. Areas under the receiver operator characteristic curve (AUC) were used to estimate model discrimination.

Results

MI was present in 451 (4%) participants at baseline (1987–89), and incident cardiac events occurred among 646 (6%) others through 1999. Adjusting for IMT, RCCA diameter was associated with prevalent MI (female OR = 2.0, 95%CI = 1.61–2.49; male OR = 1.16, 95% CI = 1.04–1.30) and incident cardiac events (female HR = 1.75, 95% CI = 1.51–2.02; male HR = 1.27, 95% CI = 1.15–1.40). Associations were attenuated but persisted after adjustment for risk factors (not including IMT) (prevalent MI: female OR = 1.73, 95% CI = 1.40–2.14; male OR = 1.14, 95% CI = 1.02–1.28, and incident cardiac events: female HR = 1.26, 95% CI = 1.08–1.48; male HR = 1.19, 95% CI = 1.08–1.32). After additional adjustment for IMT, diameter was associated with incident cardiac events in women (HR = 1.18, 95% CI = 1.00–1.40) and men (HR = 1.17, 95% CI = 1.06–1.29), and with prevalent MI only in women (OR = 1.73; 95% CI = 1.37–2.17). In women, when adjustment was limited, diameter models had larger AUC than other models.

Conclusion

RCCA diameter is an important correlate of cardiac events, independent of IMT, but adds little to overall risk discrimination after risk factor adjustment.     

An observational study of associations among maternal fluids during parturition, neonatal output, and breastfed newborn weight loss

Background

Counselling human immunodeficiency virus (HIV) positive mothers on safer infant and young child feeding (IYCF) options is an important component of programmes to prevent mother to child transmission of HIV, but the quality of counselling is often inadequate. The aim of this study was to determine the effect the World Health Organization HIV and infant feeding cards on the quality of counselling provided to HIV positive mothers by health workers about safer infant feeding options.

Method

This was a un-blinded cluster-randomized controlled field trial in which 36 primary health facilities in Kafue and Lusaka districts in Zambia were randomized to intervention (IYCF counselling with counselling cards) or non- intervention arm (IYCF counselling without counselling cards). Counselling sessions with 10 HIV positive women attending each facility were observed and exit interviews were conducted by research assistants.

Results

Totals of 180 women in the intervention group and 180 women in the control group were attended to by health care providers and interviewed upon exiting the health facility. The health care providers in the intervention facilities more often discussed the advantages of disclosing their HIV status to a household member (RR = 1.46, 95% CI [1.11, 1.92]); used visual aids in explaining the risk of HIV transmission through breast milk (RR = 4.65, 95% CI [2.28, 9.46]); and discussed the advantages and disadvantages of infant feeding options for HIV positive mothers (all p values < 0.05). The differences also included exploration of the home situation (p < 0.05); involving the partner in the process of choosing a feeding option (RR = 1.38, 95% CI [1.09, 1.75]); and exploring how the mother will manage to feed the baby when she is at work (RR = 2.82, 95% CI [1.70, 4.67]). The clients in the intervention group felt that the provider was more caring and understanding (RR = 1.81, 95% CI [1.19, 2.75]).

Conclusion

The addition of counselling cards to the IYCF counselling session for HIV positive mothers were a valuable aid to counselling and significantly improved the quality of the counselling session.     

Carotid Atherosclerotic Disease Predicts Cardiovascular Events in Hemodialysis Patients: A Prospective Study

Background

To evaluate the predictive value of carotid atherosclerotic disease (CAD) and intima-media thickness (IMT) on incident cardiovascular disease and mortality in hemodialysis patients.

Methods

Multicenter, observational, prospective study including 110 patients, followed-up to 6 years. Carotid doppler ultrasonographic findings were classified in 4 degrees of severity: 1) IMT <0.9 mm, 2) IMT >0.9 mm, 3) carotid plaque with stenosis <50% and 4) plaque with stenosis >50%. The associations between IMT and CAD and cardiovascular events, total and cardiovascular mortality were assessed.

Results

83% of the patients had atherosclerotic plaques (CAD degrees 3-4). During follow-up, 29.1% of patients experienced cardiovascular events, and 28.2% died, 38.7% of cardiovascular origin. The presence of plaques was associated with cardiovascular events (p = 0.03) while calcified plaques were associated with both cardiovascular events (p = 0.01), cardiovascular mortality (p = 0.03) and non-significantly with overall mortality (p = 0.08) in the survival analysis. Carotid IMT was not associated with outcomes. Cardiovascular events correlated with CAD severity (HR 2.27, 95% CI 1.13-4.54), age (HR 1.04, 1.01-1.06), previous cardiovascular disease (HR 1.75, 1.05-4.42), dyslipidemia (HR 2.25, 1.11-4.53), lipoprotein (a) (HR 1.01, 1.00-1.02), troponin I (HR 3.89, 1.07-14.18), fibrinogen levels (HR 1.38, 0.98-1.94) and antiplatelet therapy (HR 2.14, 1.04-4.4). In an age-adjusted multivariate model, cardiovascular events were independently associated with previous coronary artery disease (HR 3.29, 1.52-7.15) and lipoprotein (a) (HR 1.01, 1.00-1.02).

Conclusions

The presence of carotid plaques and, especially, calcified plaques, are predictors of new cardiovascular events and cardiovascular mortality in hemodialysis patients, while IMT was not. The prognostic value of calcified plaques should be confirmed in future studies.     

Interference of breast implants with echocardiographic image acquisition and interpretation

Introduction

Mitral annulus calcification (MAC) is a common finding on echocardiographic examination. The goal of this study was to evaluate associations between MAC and cardiac abnormalities using a large echocardiographic database.

Methods

For this study we retrospectively reviewed 24,380 echocardiograms performed for clinical reasons between the years 1984 and 1998.

Results

MAC was reported in 1,494 (6.1%) subjects. Using multivariate analysis, age, left ventricular hypertrophy (LVH), mitral regurgitation (MR), tricuspid regurgitation (TR), aortic stenosis (AS), left atrial (LA) enlargement and reversed E/A ratio were independently associated with MAC.)MAC was noted in 11.7 % of patients with MR vs. 4.3% without MR (OR: 2.0, CI 1.6–2.6, p < 0.0001), in 13.9% of those with TR vs. 4.5% without TR (OR: 3.8, CI 2.9–4.8, p < 0.0001), in 10.6% with LVH vs. 4.2% without LVH (OR: 1.9, CI 1.5–2.4, p < 0.0001), in 14.8% with AS vs. 5.5% without AS (OR: 1.4, CI 1.08–1.9, p = 0.01), in 9.4% with reversed E/A ratio vs. 3.8% without reversed E/A ratio (OR: 1.7, CI 1.4–2.2, p < 0.0001) and in 8.2% with LA enlargement vs. 4.8% without LA enlargement (OR: 1.3, CI 1.06–1.7, p = 0.02).

Conclusion

In our study, MAC independently correlated with significant structural heart abnormalities. This suggests that identification of MAC may serve as a marker for other cardiac structural disorders.     

Predictors of mortality of patients with acute respiratory failure secondary to chronic obstructive pulmonary disease admitted to an intensive care unit: A one year study

Background

Patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) commonly require hospitalization and admission to intensive care unit (ICU). It is useful to identify patients at the time of admission who are likely to have poor outcome. This study was carried out to define the predictors of mortality in patients with acute exacerbation of COPD and to device a scoring system using the baseline physiological variables for prognosticating these patients.

Methods

Eighty-two patients with acute respiratory failure secondary to COPD admitted to medical ICU over a one-year period were included. Clinical and demographic profile at the time of admission to ICU including APACHE II score and Glasgow coma scale were recorded at the time of admission to ICU. In addition, acid base disorders, renal functions, liver functions and serum albumin, were recorded at the time of presentation. Primary outcome measure was hospital mortality.

Results

Invasive ventilation was required in 69 patients (84.1%). Fifty-two patients survived to hospital discharge (63.4%). APACHE II score at the time of admission to ICU {odds ratio (95 % CI): 1.32 (1.138–1.532); p < 0.001} and serum albumin (done within 24 hours of admission) {odds ratio (95 % CI): 0.114 (0.03-0.432); p = 0.001}. An equation, constructed using the adjusted odds ratio for the two parameters, had an area under the ROC curve of 91.3%. For the choice of cut-off, sensitivity, specificity, positive and negative predictive value for predicting outcome was 90%, 86.5%, 79.4% and 93.7%.

Conclusion

APACHE II score at admission and SA levels with in 24 hrs after admission are independent predictors of mortality for patients with COPD admitted to ICU. The equation derived from these two parameters is useful for predicting outcome of these patients.     

One-year health status outcomes of unstable angina versus myocardial infarction: a prospective, observational cohort study of ACS survivors

Background

Unstable angina (UA) patients have lower mortality and reinfarction risks than ST-elevation (STEMI) or non-ST elevation myocardial infarction (NSTEMI) patients and, accordingly, receive less aggressive treatment. Little is known, however, about the health status outcomes (angina, physical function, and quality of life) of UA versus MI patients among survivors of an ACS hospitalization.

Methods

In a cohort of 1,192 consecutively enrolled ACS survivors from two Kansas City hospitals, we evaluated the associations between ACS presentation (UA, NSTEMI, and STEMI) and one-year health status (angina, physical functioning and quality of life), one-year cardiac rehospitalization rates, and two-year mortality outcomes, using multivariable regression modeling.

Results

After multivariable adjustment for demographic, hospital, co-morbidity, baseline health status, and treatment characteristics, UA patients had a greater prevalence of angina at 1 year than STEMI patients (adjusted relative risk [RR] = 1.42; 95% CI [1.06, 1.90]) and similar rates as NSTEMI patients (adjusted RR = 1.1; 95% CI [0.85, 1.42]). In addition, UA patients fared no better than MI patients in Short Form-12 physical component scores (UA vs. STEMI score difference -0.05 points; 95% CI [-2.41, 2.3]; UA vs. NSTEMI score difference -1.91 points; 95% CI [-4.01, 0.18]) or Seattle Angina Questionnaire quality of life scores (UA vs. STEMI score difference -1.39 points; 95% CI [-5.63, 2.85]; UA vs. NSTEMI score difference -0.24 points 95% CI [-4.01, 3.54]). Finally, UA patients had similar rehospitalization rates as MI patients (UA vs. STEMI adjusted hazard ratio [HR] = 1.31; 95% CI [0.86, 1.99]; UA vs. NSTEMI adjusted HR = 1.03; 95% CI [0.73, 1.47]), despite better 2-year survival (UA vs. STEMI adjusted HR = 0.51; 95% confidence interval (CI) [0.28, 0.95]; UA vs. NSTEMI adjusted HR = 0.40; 95% CI [0.24, 0.65]).

Conclusion

Although UA patients have better survival rates, they have similar or worse one-year health status outcomes and cardiac rehospitalization rates as compared with MI patients. Clinicians should be aware of the adverse health status outcome risks for UA patients and consider close monitoring for the opportunity to improve their health status and minimize the need for subsequent rehospitalization.     

Lower Prevalence of Carotid Plaque Hemorrhage in Women,and Its Mediator Effect on Sex Differences in Recurrent Cerebrovascular Events

Background and Purpose

Women are at lower risk of stroke, and appear to benefit less from carotid endarterectomy (CEA) than men. We hypothesised that this is due to more benign carotid disease in women mediating a lower risk of recurrent cerebrovascular events. To test this, we investigated sex differences in the prevalence of MRI detectable plaque hemorrhage (MRI PH) as an index of plaque instability, and secondly whether MRI PH mediates sex differences in the rate of cerebrovascular recurrence.

Methods

Prevalence of PH between sexes was analysed in a single centre pooled cohort of 176 patients with recently symptomatic, significant carotid stenosis (106 severe [≥70%], 70 moderate [50–69%]) who underwent prospective carotid MRI scanning for identification of MRI PH. Further, a meta-analysis of published evidence was undertaken. Recurrent events were noted during clinical follow up for survival analysis.

Results

Women with symptomatic carotid stenosis (50%≥) were less likely to have plaque hemorrhage (PH) than men (46% vs. 70%) with an adjusted OR of 0.23 [95% CI 0.10–0.50, P<0.0001] controlling for other known vascular risk factors. This negative association was only significant for the severe stenosis subgroup (adjusted OR 0.18, 95% CI 0.067–0.50) not the moderate degree stenosis. Female sex in this subgroup also predicted a longer time to recurrent cerebral ischemic events (HR 0.38 95% CI 0.15–0.98, P = 0.045). Further addition of MRI PH or smoking abolished the sex effects with only MRI PH exerting a direct effect.Meta-analysis confirmed a protective effect of female sex on development of PH: unadjusted OR for presence of PH = 0.54 (95% CI 0.45–0.67, p<0.00001).

Conclusions

MRI PH is significantly less prevalent in women. Women with MRI PH and severe stenosis have a similar risk as men for recurrent cerebrovascular events. MRI PH thus allows overcoming the sex bias in selection for CEA.     

Combined forced oscillation and forced expiration measurements in mice for the assessment of airway hyperresponsiveness

Background

Acute exacerbations contribute to the morbidity and mortality associated with chronic obstructive pulmonary disease (COPD). This proof-of-concept study evaluates whether intermittent pulsed moxifloxacin treatment could reduce the frequency of these exacerbations.

Methods

Stable patients with COPD were randomized in a double-blind, placebo-controlled trial to receive moxifloxacin 400 mg PO once daily (N = 573) or placebo (N = 584) once a day for 5 days. Treatment was repeated every 8 weeks for a total of six courses. Patients were repeatedly assessed clinically and microbiologically during the 48-week treatment period, and for a further 24 weeks' follow-up.

Results

At 48 weeks the odds ratio (OR) for suffering an exacerbation favoured moxifloxacin: per-protocol (PP) population (N = 738, OR 0.75, 95% confidence interval (CI) 0.565-0.994, p = 0.046), intent-to-treat (ITT) population (N = 1149, OR 0.81, 95% CI 0.645-1.008, p = 0.059), and a post-hoc analysis of per-protocol (PP) patients with purulent/mucopurulent sputum production at baseline (N = 323, OR 0.55, 95% CI 0.36-0.84, p = 0.006). There were no significant differences between moxifloxacin and placebo in any pre-specified efficacy subgroup analyses or in hospitalization rates, mortality rates, lung function or changes in St George's Respiratory Questionnaire (SGRQ) total scores. There was, however, a significant difference in favour of moxifloxacin in the SGRQ symptom domain (ITT: -8.2 vs -3.8, p = 0.009; PP: -8.8 vs -4.4, p = 0.006). Moxifloxacin treatment was not associated with consistent changes in moxifloxacin susceptibility. There were more treatment-emergent, drug related adverse events with moxifloxacin vs placebo (p < 0.001) largely due to gastrointestinal events (4.7% vs 0.7%).

Conclusions

Intermittent pulsed therapy with moxifloxacin reduced the odds of exacerbation by 20% in the ITT population, by 25% among the PP population and by 45% in PP patients with purulent/mucopurulent sputum at baseline. There were no unexpected adverse events and there was no evidence of resistance development.

Trial registration

ClinicalTrials.gov number, NCT00473460 (ClincalTrials.gov).     

Impact of Aldosterone Antagonists on Sudden Cardiac Death Prevention in Heart Failure and Post-Myocardial Infarction Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background and Objectives

Sudden cardiac death (SCD) is a severe burden of modern medicine. Aldosterone antagonist is publicized as effective in reducing mortality in patients with heart failure (HF) or post myocardial infarction (MI). Our study aimed to assess the efficacy of AAs on mortality including SCD, hospitalization admission and several common adverse effects.

Methods

We searched Embase, PubMed, Web of Science, Cochrane library and clinicaltrial.gov for randomized controlled trials (RCTs) assigning AAs in patients with HF or post MI through May 2015. The comparator included standard medication or placebo, or both. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Event rates were compared using a random effects model. Prospective RCTs of AAs with durations of at least 8 weeks were selected if they included at least one of the following outcomes: SCD, all-cause/cardiovascular mortality, all-cause/cardiovascular hospitalization and common side effects (hyperkalemia, renal function degradation and gynecomastia).

Results

Data from 19,333 patients enrolled in 25 trials were included. In patients with HF, this treatment significantly reduced the risk of SCD by 19% (RR 0.81; 95% CI, 0.67–0.98; p = 0.03); all-cause mortality by 19% (RR 0.81; 95% CI, 0.74–0.88, p<0.00001) and cardiovascular death by 21% (RR 0.79; 95% CI, 0.70–0.89, p<0.00001). In patients with post-MI, the matching reduced risks were 20% (RR 0.80; 95% CI, 0.66–0.98; p = 0.03), 15% (RR 0.85; 95% CI, 0.76–0.95, p = 0.003) and 17% (RR 0.83; 95% CI, 0.74–0.94, p = 0.003), respectively. Concerning both subgroups, the relative risks respectively decreased by 19% (RR 0.81; 95% CI, 0.71–0.92; p = 0.002) for SCD, 18% (RR 0.82; 95% CI, 0.77–0.88, p < 0.0001) for all-cause mortality and 20% (RR 0.80; 95% CI, 0.74–0.87, p < 0.0001) for cardiovascular mortality in patients treated with AAs. As well, hospitalizations were significantly reduced, while common adverse effects were significantly increased.

Conclusion

Aldosterone antagonists appear to be effective in reducing SCD and other mortality events, compared with placebo or standard medication in patients with HF and/or after a MI.     

The effect of long-term homocysteine-lowering on carotid intima-media thickness and flow-mediated vasodilation in stroke patients: a randomized controlled trial and meta-analysis

Background

Experimental and epidemiological evidence suggests that homocysteine (tHcy) may be a causal risk factor for atherosclerosis. B-vitamin supplements reduce tHcy and improve endothelial function in short term trials, but the long-term effects of the treatment on vascular structure and function are unknown.

Methods

We conducted a sub-study of VITATOPS, a randomised, double-blind, placebo-controlled intervention trial designed to test the efficacy of long term B-vitamin supplementation (folic acid 2 mg, vitamin B₆ 25 mg and vitamin B₁₂ 0.5 mg) in the prevention of vascular events in patients with a history of stroke. We measured carotid intima-medial thickness (CIMT) and flow-mediated dilation (FMD) at least two years after randomisation in 162 VITATOPS participants. We also conducted a systematic review and meta-analysis of studies designed to test the effect of B-vitamin treatment on CIMT and FMD.

Results

After a mean treatment period of 3.9 ± 0.9 years, the vitamin-treated group had a significantly lower mean plasma homocysteine concentration than the placebo-treated group (7.9 μmol/L, 95% CI 7.5 to 8.4 versus 11.8 μmol/L, 95% CI 10.9 to 12.8, p < 0.001). Post-treatment CIMT (0.84 ± 0.17 mm vitamins versus 0.83 ± 0.18 mm placebo, p = 0.74) and FMD (median of 4.0%, IQR 0.9 to 7.2 vitamins versus 3.0%, IQR 0.6 to 6.6 placebo, p = 0.48) did not differ significantly between groups. A meta-analysis of published randomised data, including those from the current study, suggested that B-vitamin supplements should reduce CIMT (-0.10 mm, 95% CI -0.20 to -0.01 mm) and increase FMD (1.4%, 95% CI 0.7 to 2.1%). However, the improvement in endothelial function associated with homocysteine-lowering treatment was significant in short-term studies but not in longer trials.

Conclusion

Although short-term treatment with B-vitamins is associated with increased FMD, long-term homocysteine-lowering did not significantly improve FMD or CIMT in people with a history of stroke.

Trial Registration

Clinical Trial Registration URL: http://www.actr.org.au/ Trial Registration number: 12605000005651     

Photodynamic therapy and tumor imaging of hypericin-treated squamous cell carcinoma

Background

The use of cellular and cordless telephones has increased dramatically during the last decade. There is concern of health problems such as malignant diseases due to microwave exposure during the use of these devices. The brain is the main target organ.

Methods

Since the second part of the 1990's we have performed six case-control studies on this topic encompassing use of both cellular and cordless phones as well as other exposures. Three of the studies concerned brain tumours, one salivary gland tumours, one non-Hodgkin lymphoma (NHL) and one testicular cancer. Exposure was assessed by self-administered questionnaires.

Results

Regarding acoustic neuroma analogue cellular phones yielded odds ratio (OR) = 2.9, 95 % confidence interval (CI) = 2.0–4.3, digital cellular phones OR = 1.5, 95 % CI = 1.1–2.1 and cordless phones OR = 1.5, 95 % CI = 1.04–2.0. The corresponding results were for astrocytoma grade III-IV OR = 1.7, 95 % CI = 1.3–2.3; OR = 1.5, 95 % CI = 1.2–1.9 and OR = 1.5, 95 % CI = 1.1–1.9, respectively. The ORs increased with latency period with highest estimates using > 10 years time period from first use of these phone types. Lower ORs were calculated for astrocytoma grade I-II. No association was found with salivary gland tumours, NHL or testicular cancer although an association with NHL of T-cell type could not be ruled out.

Conclusion

We found for all studied phone types an increased risk for brain tumours, mainly acoustic neuroma and malignant brain tumours. OR increased with latency period, especially for astrocytoma grade III-IV. No consistent pattern of an increased risk was found for salivary gland tumours, NHL, or testicular cancer.     

Carotid artery intima-media thickness, carotid plaque and coronary heart disease and stroke in Chinese

Background

Our aim was to prospectively investigate the association between carotid artery intima-media thickness (IMT) as well as carotid plaque and incidence of coronary heart disease (CHD) and stroke in Chinese, among whom data are limited.

Methods and Findings

We conducted a community-based cohort study composed of 2190 participants free of cardiovascular disease at baseline in one community. During a median 10.5-year follow up, we documented 68 new cases of coronary heart disease and 94 cases of stroke. The multivariate relative risks (RRs) associated with a change of 1 standard deviation of maximal common carotid IMT were 1.38 (95% confidence interval [CI], 1.12–1.70) for CHD and 1.47 (95% CI, 1.28–1.69) for stroke. The corresponding RRs with internal carotid IMT were 1.47 (95% CI, 1.21–1.79) for CHD and 1.52 (95% CI, 1.31–1.76) for stroke. Carotid plaque measured by the degree of diameter stenosis was also significantly associated with increased risk of CHD (p for trend<0.0001) and stroke (p for trend<0.0001). However, these associations were largely attenuated when adjusting for IMT measurements.

Conclusions

This prospective study indicates a significant association between carotid IMT and incidence of CHD and stroke in Chinese adults. These measurements may be useful for cardiovascular risk assessment and stratification in Chinese.     

Optimal loading dose for the initiation of warfarin: a systematic review

Background

Selection of the right warfarin dose at the outset of treatment is not straightforward, and current evidence is lacking to determine the optimal strategy for initiation of therapy.

Methods

We included randomized controlled trials in patients commencing anticoagulation with warfarin, comparing different loading dose or different regimens. We searched Medline, EMBASE, the Cochrane Library and the NHS Health Economics Database up to June 2009. Primary outcomes were time to stable INR and adverse events. We summarised results as proportion of INRs in range from date of initiation and compared dichotomous outcomes using relative risks (RR) and calculated 95% confidence intervals (CIs).

Results

We included 11 studies of 1,340 patients newly initiated on warfarin. In two studies that used single INR measures, a loading dose of 10 mg compared to 5 mg led to more patients in range on day five. However, in two studies which measured two consecutive INRs, a loading dose of 10 mg compared to 5 mg did not lead to more patients in range on day five (RR = 0.86, 95% CI, 0.62 to 1.19, p = 0.37). Patients receiving a 2.5 mg initiation does took longer to achieve the therapeutic range, whilst those receiving a calculated initiation dose achieved target range 0.8 days quicker (4.2 days vs. 5 days, p = 0.007). More elderly patients receiving an age adjusted dose achieved a stable INR compared to the Fennerty protocol (48% vs. 22% p = 0.02) and significantly fewer patients on the age adjusted regimens had high out-of-range INRs. Two studies report no significant differences between genotype guided and 5 mg or 10 mg initiation doses and in the one significant genotype study the control group INRs were significantly lower than expected.

Conclusion

Our review findings suggest there is still considerable uncertainty between a 10 mg and a 5 mg loading dose for initiation of warfarin. In the elderly, lower initiation doses or age adjusted doses are more appropriate, leading to less higher INRs. Currently there is insufficient evidence to warrant genotype guided initiation, and adequately powered trials to detect effects on adverse events are currently warranted.     

Determinants of arterial stiffness in COPD

Background

Cardiovascular morbidity and mortality is high in patients with chronic obstructive pulmonary disease (COPD) and arterial stiffness is a potentially modifiable risk factor with added predictive value beyond that obtained from traditional risk factors. Arterial stiffness has been the target of pharmacologic and exercise interventions in patients with COPD, but the effects appear limited to those patients with more significant elevations in arterial stiffness. We aimed to identify predictors of increased arterial stiffness in a cohort with moderate to severe COPD.

Methods

Aortic pulse wave velocity (aPWV) was measured in subjects with moderate to severe COPD enrolled in a multicenter randomized controlled trial. Subjects were categorized into quartiles based on aPWV values and factors affecting high arterial stiffness were assessed. Multivariate models were created to identify independent predictors of high aPWV, and cardiovascular disease (CVD).

Results

153 patients were included. Mean age was 63.2 (SD 8.2) years and mean FEV₁ was 55.4 (SD 15.2) % predicted. Compared to the quartile with the lowest aPWV, subjects in the highest quartile were older, had higher systolic blood pressure (SBP), were more likely to be current smokers, and had greater burden of thoracic aortic calcification. On multivariate analyses, age (adjusted OR 1.14, 95%CI 1.05 to 1.25, p?=?0.003) and SBP (adjusted OR 1.06, 95% CI 1.02 to 1.09, p?=?0.001) were independent predictors of elevated aPWV. Body mass index, therapy with cholesterol lowering medications and coronary calcification were independent predictors of CVD.

Conclusions

Elevated arterial stiffness in patients with COPD can be predicted using age, blood pressure and thoracic aortic calcification. This will help identify subjects for enrollment in clinical trials using aPWV for assessing the impact of COPD therapies on CV outcomes.

Trial registration

Clinicaltrials.gov NCT00857766