Venous Thromboembolism and Cerebrovascular Events in Patients with Giant Cell Arteritis: A Population-Based Retrospective Cohort Study

Objective

To investigate the incidence of venous thromboembolism (VTE) and cerebrovascular events in a community-based incidence cohort of patients with giant cell arteritis (GCA) compared to the general population.

Methods

A population-based inception cohort of patients with incident GCA between January 1, 1950 and December 31, 2009 in Olmsted County, Minnesota and a cohort of non-GCA subjects from the same population were assembled and followed until December 31, 2013. Confirmed VTE and cerebrovascular events were identified through direct medical record review.

Results

The study population included 244 patients with GCA with a mean ± SD age at diagnosis of 76.2 ± 8.2 years (79% women) and an average length of follow-up of 10.2 ± 6.8 years. Compared to non-GCA subjects of similar age and sex, patients diagnosed with GCA had a higher incidence (%) of amaurosis fugax (cumulative incidence ± SE: 2.1 ± 0.9 versus 0, respectively; p = 0.014) but similar rates of stroke, transient ischemic attack (TIA), and VTE. Among patients with GCA, neither baseline characteristics nor laboratory parameters at diagnosis reliably predicted risk of VTE or cerebrovascular events.

Conclusion

In this population-based study, the incidence of VTE, stroke and TIA was similar in patients with GCA compared to non-GCA subjects.     

Cardiovascular Health and Related Health Care Use of Moluccan-Dutch Immigrants

Objective

Studies regularly show a higher incidence, prevalence and mortality of cardiovascular disease among immigrant groups from low-income countries. Despite residing in the Netherlands for over 60 years, the Moluccan-Dutch cardiovascular disease profile and health care use are still unknown. We aimed to compare (a) the clinical prevalence of cardiovascular diseases and (b) the use of health care services by cardiovascular disease patients of 5,532 Moluccan-Dutch to an age-sex matched control group of 55,320 native Dutch.

Methods

We performed a cross-sectional analysis of data of the Achmea health insurance company for the period of 1 January 2009 to 31 December 2010. We collected information on health care use, including diagnostic information. Linear and logistic regression models were used for comparison.

Results

Moluccans had a higher clinical prevalence of ischemic heart diseases (odds ratio 1.26; 95% confidence interval 1.03–1.56), but tended to have a lower prevalence of cerebrovascular accidents (0.79; 0.56–1.11) and cardiac failure (0.67; 0.44–1.03). The clinical prevalence of cardiovascular diseases together tended to be lower among Moluccans (0.90; 0.80–1.00). Consultation of medical specialists did not differ. Angiotensin II inhibitors (1.42; 1.09–1.84), antiplatelet agents (1.27; 1.01–1.59) and statins (1.27; 1.00–1.60) were prescribed more frequently to Moluccans, as were cardiovascular agents in general (1.27; 0.94–1.71).

Conclusion

The experience of Moluccans in the Netherlands suggests that, in the long run, cardiovascular risk and related health care use of ethnic minority groups may converge towards that of the majority population.     

The Efficacy of Synchronous Combination of Chemotherapy and EGFR TKIs for the First-Line Treatment of NSCLC: A Systematic Analysis

Background

The combination of chemotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) currently has become the hotspot issue in the treatment of non-small lung cancer (NSCLC). This systematic review was conducted to compare the efficacy and safety of the synchronous combination of these two treatments with EGFR TKIs or chemotherapy alone in advanced NSCLC.

Methods

EMBASE, PubMed, the Central Registry of Controlled Trials in the Cochrane Library (CENTRAL), Chinese biomedical literature database (CNKI) and meeting summaries were searched. The Phase II/III randomized controlled trials were selected by which patients with advanced NSCLC were randomized to receive a combination of EGFR TKIs and chemotherapy by synchronous mode vs. EGFR TKIs or chemotherapy alone.

Results

A total of six randomized controlled trials (RCTs) including 4675 patients were enrolled in the systematic review. The meta-analysis demonstrated that the synchronous combination group of chemotherapy and EGFR TKIs did not reach satisfactory results; there was no significant difference in overall survival (OS), time to progression (TTP) and objective response rate (ORR), compared with monotherapy (OS: HR = 1.05, 95%CI = 0.98–1.12; TTP: HR = 0.94, 95%CI = 0.89–1.00; ORR: RR = 1.07, 95%CI = 0.98–1.17), and no significant difference in OS and progression-free survival (PFS), compared with EGFR TKIs alone (OS: HR = 1.10, 95% CI = 0.83–1.46; PFS: HR = 0.86, 95% CI = 0.67–1.10). The patients who received synchronous combined therapy presented with increased incidences of grade 3/4 anemia (RR = 1.40, 95% CI = 1.10–1.79) and rash (RR = 7.43, 95% CI = 4.56–12.09), compared with chemotherapy, grade 3/4 anemia (RR = 6.71, 95% CI = 1.25–35.93) and fatigue (RR = 9.60, 95% CI = 2.28–40.86) compared with EGFR TKI monotherapy.

Conclusions

The synchronous combination of chemotherapy and TKIs is not superior to chemotherapy or EGFR TKIs alone for the first-line treatment of NSCLC.     

Cardiovascular Outcomes of Sitagliptin in Type 2 Diabetic Patients with Acute Myocardial Infarction,a Population-Based Cohort Study in Taiwan

Background

The cardiovascular safety and efficacy of sitagliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, in type 2 diabetic patients after acute myocardial infarction (AMI) has so far remained uncertain.

Methods

We analyzed data from the National Health Insurance Research Database (NHIRD), a government-operated, population-based database, from March 1st, 2009 to December 31st, 2011. Type 2 diabetic patients hospitalized for AMI were included in our study. We compared subjects using sitagliptin with comparison group to evaluate its cardiovascular safety and efficacy. The primary endpoint was a composite of cardiovascular death, myocardial infarction, and ischemic stroke.

Results

We identified a total of 3,282 type 2 diabetic patients hospitalized for AMI (mean follow-up 1.15 years). Of these patients, 547 (16.7%) who were exposed to sitagliptin were defined as the sitagliptin group and 2,735 (83.3 %) who did not use sitagliptin were the comparison group. The incidence of primary composite cardiovascular outcomes was 9.50 per 100 person-years in the sitagliptin group and was 9.70 per 100 person-years in the comparison group (hazard ratio (HR), 0.97; 95% CI, 0.73–1.29, P=0.849). Compared to the non-sitagliptin group, the sitagliptin group had similar risks of all-cause mortality, hospitalization for heart failure (HF) or percutaneous coronary intervention (PCI) with a HR of 0.82 (95% CI, 0.61–1.11, P=0.195), 0.93 (95% CI, 0.67–1.29, P=0.660), and 0.93 (95% CI, 0.75–1.14, P=0.473), respectively.

Conclusion

The use of sitagliptin in type 2 diabetic patients with recent AMI was not associated with increased risk of adverse cardiovascular events.     

Association of PON1, P2Y12 and COX1 with Recurrent Ischemic Events in Patients with Extracranial or Intracranial Stenting

Background and Purpose

Short-term combined use of clopidogrel and aspirin improves cerebrovascular outcomes in patients with symptomatic extracranial or intracranial stenosis. Antiplatelet non-responsiveness is related to recurrent ischemic events, but the culprit genetic variants responsible for the non-responsiveness have not been well studied. We aimed to identify the genetic variants associated with poor clinical outcomes.

Methods

Patients with symptomatic extracranial or intracranial stenosis scheduled for stenting and receiving dual antiplatelets (clopidogrel 75 mg and aspirin 100 mg daily) for at least 5 days before intervention were enrolled. Ischemic events including recurrent transient ischemic attack, stroke, myocardial infarction, and vascular-related mortality within 12 months follow-up were recorded. We examined the influence of genetic polymorphisms on treatment outcome in our patients.

Results

A total of 268 patients were enrolled into our study and ischemic events were observed in 39 patients. For rs662 of paraoxonase 1 (PON1), allele C was associated with an increased risk of ischemic events (OR = 1.64, 95%CI = 1.03–2.62, P = 0.029). The A-allele carriers of rs2046934 of P2Y12 had a significant association with adverse events (OR = 2.01, 95%CI = 1.10–3.67, P = 0.041). The variant T-allele of cyclooxygenase-1 (COX1) rs1330344 significantly increased the risk of recurrent clinical events (OR = 1.85, 95%CI = 1.12–3.03, P = 0.017). The other single nucleotide polymorphism (SNP) had no association with ischemic events.

Conclusions

PON1, P2Y12 and COX1 polymorphisms were associated with poorer vascular outcomes. Testing for these polymorphisms may be valuable in the identification of patients at risk for recurrent ischemic events.     

Risk of Major Cardiovascular Events in People with Down Syndrome

Background

Improved medical care over more than five decades has markedly increased life expectancy, from 12 years to approximately 60 years, in people with Down syndrome (DS). With increased survival into late adulthood, there is now a greater need for the medical care of people with DS to prevent and treat aging-related disorders. In the wider population, acquired cardiovascular diseases such as stroke and coronary heart disease are common with increasing age, but the risks of these diseases in people with DS are unknown. There are no population-level data on the incidence of acquired major cerebrovascular and coronary diseases in DS, and no data examining how cardiovascular comorbidities or risk factors in DS might impact on cardiovascular event incidence. Such data would be also valuable to inform health care planning for people with DS. Our objective was therefore to conduct a population-level matched cohort study to quantify the risk of incident major cardiovascular events in DS.

Methods and Findings

A population-level matched cohort study compared the risk of incident cardiovascular events between hospitalized patients with and without DS, adjusting for sex, and vascular risk factors. The sample was derived from hospitalization data within the Australian state of Victoria from 1993–2010. For each DS admission, 4 exact age-matched non-DS admissions were randomly selected from all hospitalizations within a week of the relevant DS admission to form the comparison cohort. There were 4,081 people with DS and 16,324 without DS, with a total of 212,539 person-years of observation. Compared to the group without DS, there was a higher prevalence in the DS group of congenital heart disease, cardiac arrhythmia, dementia, pulmonary hypertension, diabetes and sleep apnea, and a lower prevalence of ever-smoking. DS was associated with a greater risk of incident cerebrovascular events (Risk Ratio, RR 2.70, 95% CI 2.08, 3.53) especially among females (RR 3.31, 95% CI 2.21, 4.94) and patients aged ≤50 years old. The association of DS with ischemic strokes was substantially attenuated on adjustment for cardioembolic risk (RR 1.93, 95% CI 1.04, 3.20), but unaffected by adjustment for atherosclerotic risk. DS was associated with a 40–70% reduced risk of any coronary event in males (RR 0.58, 95% CI 0.40, 0.84) but not in females (RR 1.14, 95% CI 0.73, 1.77).

Conclusions

DS is associated with a high risk of stroke, expressed across all ages. Ischemic stroke risk in DS appears mostly driven by cardioembolic risk. The greater risk of hemorrhagic stroke and lower risk of coronary events (in males) in DS remain unexplained.     

The Association between Triglyceride/High-Density Lipoprotein Cholesterol Ratio and All-Cause Mortality in Acute Coronary Syndrome after Coronary Revascularization

Aims

High triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) are cardiovascular risk factors. A positive correlation between elevated TG/HDL-C ratio and all-cause mortality and cardiovascular events exists in women. However, utility of TG to HDL-C ratio for prediction is unknown among acute coronary syndrome (ACS).

Methods

Fasting lipid profiles, detailed demographic data, and clinical data were obtained at baseline from 416 patients with ACS after coronary revascularization. Subjects were stratified into three levels of TG/HDL-C. We constructed multivariate Cox-proportional hazard models for all-cause mortality over a median follow-up of 3 years using log TG to HDL-C ratio as a predictor variable and analyzing traditional cardiovascular risk factors. We constructed a logistic regression model for major adverse cardiovascular events (MACEs) to prove that the TG/HDL-C ratio is a risk factor.

Results

The subject’s mean age was 64 ± 11 years; 54.5% were hypertensive, 21.8% diabetic, and 61.0% current or prior smokers. TG/HDL-C ratio ranged from 0.27 to 14.33. During the follow-up period, there were 43 deaths. In multivariate Cox models after adjusting for age, smoking, hypertension, diabetes, and severity of angiographic coronary disease, patients in the highest tertile of ACS had a 5.32-fold increased risk of mortality compared with the lowest tertile. After adjusting for conventional coronary heart disease risk factors by the logistic regression model, the TG/HDL-C ratio was associated with MACEs.

Conclusion

The TG to HDL-C ratio is a powerful independent predictor of all-cause mortality and is a risk factor of cardiovascular events.     

Serial Measurements of N-Terminal Pro-Brain Natriuretic Peptide in Patients with Coronary Heart Disease

Objective

To assess the prognostic value of 12-months N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) levels on adverse cardiovascular events in patients with stable coronary heart disease.

Methods

NT-proBNP concentrations were measured at baseline and at 12-months follow-up in participants of cardiac rehabilitation (median follow-up 8.96 years). Cox-proportional hazards models evaluated the prognostic value of log-transformed NT-proBNP levels, and of 12-months NT-proBNP relative changes on adverse cardiovascular events adjusting for established risk factors measured at baseline.

Results

Among 798 participants (84.7% men, mean age 59 years) there were 114 adverse cardiovascular events. 12-months NT-proBNP levels were higher than baseline levels in 60 patients (7.5%) and numerically more strongly associated with the outcome in multivariable analysis (HR 1.65 [95% CI 1.33–2.05] vs. HR 1.41 [95% CI 1.12–1.78], with a net reclassification improvement (NRI) of 0.098 [95% CI 0.002–0.194] compared to NRI of 0.047 [95% CI −0.0004–0.133] for baseline NT-proBNP levels. A 12-month 10% increment of NT-proBNP was associated with a HR of 1.35 [95% CI 1.12–1.63] for the onset of an adverse cardiovascular event. Subjects with a 12-month increment of NT-proBNP had a HR of 2.56 [95% CI 1.10–5.95] compared to those with the highest 12-months reduction.

Conclusions

Twelve-months NT-proBNP levels after an acute cardiovascular event are strongly associated with a subsequent event and may provide numerically better reclassification of patients at risk for an adverse cardiovascular event compared to NT-proBNP baseline levels after adjustment for established risk factors.     

Ischemic arterial events and atherosclerosis in patients with systemic sclerosis: a population-based case-control study

Introduction

While microvascular disease is well described in systemic sclerosis (SSc), it is still unclear whether the occurrence of ischemic macrovascular events and atherosclerosis is enhanced among patients with SSc.

Methods

In this study, 111 SSc patients (74% of prevalent cases in Stockholm County) and 105 age- and sex-comparable population controls were investigated. Previous ischemic arterial events were tabulated. As surrogate measures of atherosclerosis, plaque occurrence and intima-media thickness (IMT) were determined with carotid ultrasound and the ankle-brachial index (ABI) was calculated. Traditional cardiovascular risk factors were recorded and we also measured biomarkers indicating systemic inflammation and endothelial activation/dysfunction.

Results

Mean age was 62 ± 12 years for patients and controls. Ischemic arterial events were more common, due to increased occurrence of ischemic heart disease (IHD) and ischemic peripheral vascular disease (IPVD), in the patient group (12% vs. 4%, P = 0.03 and 9% vs. 0%, P = 0.003 respectively). On a group level, there was no difference regarding the occurrence of ischemic cerebrovascular disease, the frequency of plaques, IMT or ABI between SSc patients and controls. Subgroup analyses revealed that patients with anticentromere antibodies (ACA+) had more plaques and more ischemic arterial events compared to other SSc patients (67% vs. 39% and 32% vs. 11%; P = 0.006 and P = 0.01, respectively) and compared to controls (67% vs. 41% and 32% vs. 7%, P = 0.02 and P = 0.0003, respectively). Biomarkers of inflammation/endothelial activation were generally increased among SSc patients.

Conclusions

Patients with SSc are at enhanced risk for IHD and IPVD. The ACA+ SSc subgroup was particularly affected with both ischemic arterial events and premature atherosclerosis. The microvascular vulnerability of ACA+ patients is previously well documented. We demonstrate that ACA+ SSc patients have an enhanced risk of macrovascular injury as well. This group should be followed closely and modifiable cardiovascular risk factors should be treated at an early stage.     

Diagnostic Yield of Universal Urine Toxicology Screening in an Unselected Cohort of Stroke Patients

Background

Illicit drug use increases the risk of cerebrovascular events by a variety of mechanisms. A recent report suggested that universal urine toxicology (UTox) screening of patients with stroke may be warranted. We aimed to evaluate the diagnostic yield of urine drug screening among unselected patients admitted with acute stroke or transient ischemic attack (TIA).

Methods

Using a single-center prospective study design, we evaluated consecutive patients with acute ischemic stroke, TIA, intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH) over one year. Urine samples were collected within 48 hours of admission and analyzed for common classes of abused drugs. Prevalence of positive UTox screening was determined. We evaluated whether baseline demographics and clinical factors were associated with UTox results.

Results

Of 483 eligible patients (acute ischemic stroke 66.4%; TIA 18.8%; ICH 7.7%; SAH 7.0%), 414 (85.7%) completed UTox screening. The mean (standard deviation) age was 65.1 (15.6) years, 52.7% were male, and 64.3% were Caucasian. Twenty-two (4.6%) patients had positive screening—cannabinoids were detected in 13 cases (3.1%), cocaine in 5 cases (1.2%), amphetamines in 1 case, and phencyclidine in 1 case. The highest yield (14.1%) was observed in patients < 60 years old with history of tobacco use while it was < 5% in the remaining subgroups (p<0.01).

Conclusions

Consistent with current guidelines, a selective approach to UTox screening should be pursued in acute stroke evaluation. The highest diagnostic yield is likely to be for cannabinoids and cocaine testing in younger patients with a history of concurrent tobacco use.     

Early Complications Following Oesophagectomy for Cancer in Relation to Long-Term Healthcare Utilisation: A Prospective Population-Based Cohort Study

Background

Little is known about how early postoperative complications after oesophagectomy for cancer influence healthcare utilisation in the long-term. We hypothesised that these complications also increase healthcare utilisation long after the recovery period.

Methods

This was a prospective, nationwide Swedish population-based cohort study of patients who underwent curatively intended oesophagectomy for cancer in 2001-2005 and survived at least 1 year postoperatively (n = 390). Total days of in-hospitalisation, number of hospitalisations and number of visits to the outpatient clinic within 5 years of surgery were analysed using quasi-Poisson models with adjustment for patient, tumour and treatment characteristics and are expressed as incidence rate ratios (IRR) and 95% confidence intervals (CI).

Results

There was an increased in-hospitalisation period 1-5 years after surgery in patients with more than 1 complication (IRR 1.5, 95% CI 1.0-2.4). The IRR for the number of hospitalisations by number of complications was 1.1 (95% CI 0.7-1.6), and 1.2 (95% CI 0.9-1.6) for number of outpatient visits in patients with more than 1 complication. The IRR for in-hospitalisation period 1-5 years following oesophagectomy was 1.8 (95% CI 1.0-3.0) for patients with anastomotic insufficiency and 1.5 (95% CI 0.9-2.5) for patients with cardiovascular or cerebrovascular complications. We found no association with number of hospitalisations (IRR 1.2, 95% CI 0.7-2.0) or number of outpatient visits (IRR 1.3, 95% CI 0.9-1.7) after anastomotic insufficiency, or after cardiovascular or cerebrovascular complications (IRR 1.2, 95% CI 0.7-1.9) and (IRR 1.1, 95% CI 0.8-1.5) respectively.

Conclusion

This study showed an increased total in-hospitalisation period 1-5 years after oesophagectomy for cancer in patients with postoperative complications, particularly following anastomotic insufficiency.     

Short- and Long-Term Major Cardiovascular Adverse Events in Carotid Artery Interventions: A Nationwide Population-Based Cohort Study in Taiwan

Introduction

Carotid artery stenosis is one of the leading causes of ischemic stroke. Carotid artery stenting has become well-established as an effective treatment option for carotid artery stenosis. For this study, we aimed to determine the efficacy and safety of carotid stenting in a population-based large cohort of patients by analyzing the Taiwan National Healthcare Insurance (NHI) database.

Methods

2,849 patients who received carotid artery stents in the NHI database from 2004 to 2010 were identified. We analyzed the risk factors of outcomes including major adverse cardiovascular events including death, acute myocardial infarction, and cerebral vascular accidents at 30 days, 1 year, and overall period and further evaluated cause of death after carotid artery stenting.

Results

The periprocedural stroke rate was 2.7% and the recurrent stroke rate for the overall follow-up period was 20.3%. Male, diabetes mellitus, and heart failure were significant risk factors for overall recurrent stroke (Hazard Ratio (HR) = 1.35, p = 0.006; HR = 1.23, p = 0.014; HR = 1.61, p < 0.001, respectively). The periprocedural acute myocardial infarction rate was 0.3%. Age and Diabetes mellitus were the significant factors to predict periprocedural myocardial infarction (HR = 3.06, p = 0.019; HR = 1.68, p < 0.001, respectively). Periprocedural and overall mortality rates were 1.9% and 17.3%, respectively. The most significant periprocedural mortality risk factor was acute renal failure. Age, diabetes mellitus, acute or chronic renal failure, heart failure, liver disease, and malignancy were factors correlated to the overall period mortality.

Conclusion

Periprocedural acute renal failure significantly increased the mortality rate and the number of major adverse cardiovascular events, and the predict power persisted more than one year after the procedure. Age and diabetes mellitus were significant risk factors to predict acute myocardial infarction after carotid artery stenting.     

Carotid Artery Longitudinal Displacement,Cardiovascular Disease and Risk Factors: The Multi-Ethnic Study of Atherosclerosis

Background

Associations between carotid artery longitudinal displacement, cardiovascular disease risk factors, and events were evaluated in a large, multi-ethnic cohort.

Materials and Methods

A novel, reproducible protocol was developed for measuring right common carotid artery longitudinal displacement using ultrasound speckle-tracking. Total longitudinal displacement was measured in 389 randomly selected participants from the Multi-Ethnic Study of Atherosclerosis that were free of cardiovascular disease at baseline. Univariate analyses and Pearson Correlations were used to define relationships between longitudinal displacement with traditional cardiovascular risk factors and traditional measures of arterial stiffness. Hazard ratios of longitudinal displacement for cardiovascular disease and coronary heart disease events were compared using Cox proportional hazards models.

Results

Participants were a mean (standard deviation) 59.0 (8.7) years old, 48% female, 39% White, 26% Black, 22% Hispanic, and 14% Chinese. They had 19 (4.9%) cardiovascular disease and 14 (3.6%) coronary heart disease events over a mean 9.5 years of follow-up. Less longitudinal displacement was associated with Chinese (β = -0.11, p = 0.02) compared to White race/ethnicity and greater longitudinal displacement was associated with higher carotid intima-media thickness (β = 0.26, p = 0.004). Longitudinal displacement was not associated with other cardiovascular disease risk factors or markers of arterial stiffness. After adjustment for age and sex, and heart rate, Chinese race/ethnicity (β = -0.10, p = 0.04) and carotid intima-media thickness (β = 0.30 p = 0.003) were associated independently with longitudinal displacement. Longitudinal displacement predicted coronary heart disease (Hazard ratio [HR] 3.3, 95% Confidence intervals [CI] 0.96–11.14, p = 0.06) and cardiovascular disease (HR 2.1, 95% CI 0.6–7.3, p = 0.23) events.

Conclusions

Less longitudinal displacement is associated with Chinese ethnicity and greater carotid artery longitudinal displacement is associated with thicker intima-media thickness. Longitudinal displacement may predict adverse coronary heart disease and cardiovascular disease events.     

A Non-Invasive Method to Assess Cerebral Perfusion Pressure in Geriatric Patients with Suspected Cerebrovascular Disease

Background

Cerebral perfusion pressure (CPP) can adversely impact cerebrovascular hemodynamics but cannot be practically measured in most clinical settings. Here, we aimed to establish a representative mathematical model for CPP in geriatric patients with suspected cerebrovascular disease.

Methods

A total of 100 patients (54 males and 46 females between 60–80 years of age) with suspected cerebrovascular disease and no obvious cerebrovascular stenosis were selected for invasive CPP monitoring via catheterization of the middle segment of the common carotid arteries and openings of the vertebral arteries bilaterally. Curves were function-fitted using MATLAB 7.0, and data was statistically processed by SPSS 20.0.

Results

MATLAB 7.0 constructed eighth-order Fourier functions that fit all recorded CPP curves. Since the coefficients of the 100 functions were significantly different, all functions were standardized to derive one representative function. By manipulating the heart rate and maximum/minimum CPP of the representative function, estimated CPP curves can be constructed for patients with differing heart rates, intracranial pressures (ICPs) and blood pressures.

Conclusions

CPP can be well-modeled through an eighth-order Fourier function that can be constructed from a patient’s brachial artery blood pressure (BABP), ICP and heart rate. This function is representative of geriatric patients with cerebrovascular disease and can be used in the future study of cerebral hemodynamics.     

Efficacy of Standard and Intensive Statin Treatment for the Secondary Prevention of Cardiovascular and Cerebrovascular Events in Diabetes Patients: A Meta-Analysis

Aims

To estimate the efficacy of standard and intensive statin treatment in the secondary prevention of major cardiovascular and cerebrovascular events in diabetes patients.

Methods

A systematic search was conducted in Medline over the years 1990 to September 2013. Randomized, double-blind, clinical trials comparing a standard-dose statin with placebo or a standard-dose statin with an intensive-dose statin for the secondary prevention of cardiovascular and cerebrovascular events in diabetes patients were selected. Trial and patient characteristics were extracted independently by two researchers. The combined effect on the composite primary endpoint was measured with a fixed-effect model. Potential publication bias was examined with a funnel plot.

Results

Five trials were included in the analysis comparing standard-dose statins with placebo with a total of 4 351 participants. Four trials were included for comparing standard-dose with intensive-dose statins, including 4 805 participants. Compared with placebo, standard-dose statin treatment resulted in a significant relative risk (RR) reduction of 15% in the occurrence of any major cardiovascular or cerebrovascular event (RR 0.85, 95% CI 0.79–0.91). Compared with standard-dose statin treatment, intensive-dose statin treatment resulted in an additional 9% relative risk reduction (RR 0.91, 95% CI 0.84–0.98).

Conclusion

Treatment with standard-dose statins to prevent cardiovascular or cerebrovascular events in diabetes patients with manifest cardiovascular disease results in an estimated 15% relative risk reduction and intensive-dose statin treatment adds 9%. If proven cost-effective, more intensive statin treatment should be recommended for diabetes patients at high cardiovascular risk.     

Inhaled Long-Acting β2-Agonists Do Not Increase Fatal Cardiovascular Adverse Events in COPD: A Meta-Analysis

Background

The cardiovascular safety of inhaled long-acting β₂-agonists (LABAs) in patients with chronic obstructive pulmonary disease (COPD) is a controversial problem. Certain studies have suggested that inhaled LABAs lead to an increased risk of cardiovascular events in patients with COPD. This meta-analysis aimed to assess the cardiovascular safety of inhaled LABAs in COPD.

Methods

A meta-analysis of randomized, double-blind, parallel-group, placebo-controlled trials for LABA treatment of COPD with at least 3 months of follow-up was performed. The fixed-effects model was used to evaluate the effects of LABAs on fatal cardiovascular adverse events. Adverse events were collected for each trial, and the relative risk (RR) and 95% confidence intervals (CI) for LABA/placebo were estimated.

Results

There were 24 trials included in this meta-analysis. Compared with placebo, inhaled LABAs significantly decreased fatal cardiovascular adverse events in COPD patients (RR 0.65, 95% CI 0.50 to 0.86, P = 0.002). In sensitivity analysis, there was still no increased risk of fatal cardiovascular events (RR 0.68, 95%CI 0.46 to 1.01, P = 0.06) after excluding the trial with the largest weight. Among the different types of LABAs, only salmeterol had a significant effect (RR 0.64, 95% CI 0.46 to 0.90). In subgroup analyses, inhaled LABAs were able to significantly decrease fatal cardiovascular events in long-term trials (RR 0.64, 95% CI 0.47 to 0.87) and in trials with severe COPD patients (RR 0.69, 95% CI 0.50 to 0.96).

Conclusion

Inhaled LABAs do not increase the risk of fatal cardiovascular events in COPD patients.     

Vascular Disease and Risk Stratification for Ischemic Stroke and All-Cause Death in Heart Failure Patients without Diagnosed Atrial Fibrillation: A Nationwide Cohort Study

Background

Stroke and mortality risk among heart failure patients previously diagnosed with different manifestations of vascular disease is poorly described. We conducted an observational study to evaluate the stroke and mortality risk among heart failure patients without diagnosed atrial fibrillation and with peripheral artery disease (PAD) or prior myocardial infarction (MI).

Methods

Population-based cohort study of patients diagnosed with incident heart failure during 2000–2012 and without atrial fibrillation, identified by record linkage between nationwide registries in Denmark. Hazard rate ratios of ischemic stroke and all-cause death after 1 year of follow-up were used to compare patients with either: a PAD diagnosis; a prior MI diagnosis; or no vascular disease.

Results

39,357 heart failure patients were included. When compared to heart failure patients with no vascular disease, PAD was associated with a higher 1-year rate of ischemic stroke (adjusted hazard rate ratio [HR]: 1.34, 95% confidence interval [CI]: 1.08–1.65) and all-cause death (adjusted HR: 1.47, 95% CI: 1.35–1.59), whereas prior MI was not (adjusted HR: 1.00, 95% CI: 0.86–1.15 and 0.94, 95% CI: 0.89–1.00, for ischemic stroke and all-cause death, respectively). When comparing patients with PAD to patients with prior MI, PAD was associated with a higher rate of both outcomes.

Conclusions

Among incident heart failure patients without diagnosed atrial fibrillation, a previous diagnosis of PAD was associated with a significantly higher rate of the ischemic stroke and all-cause death compared to patients with no vascular disease or prior MI. Prevention strategies may be particularly relevant among HF patients with PAD.     

High-Maintenance-Dose Clopidogrel in Patients Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis

Background

Despite routine use of clopidogrel, adverse cardiovascular events recur among some patients undergoing percutaneous coronary intervention (PCI). To optimize antiplatelet therapies, we performed a meta-analysis to quantify the efficacy of high versus standard-maintenance-dose clopidogrel in these patients.

Methods

Randomized controlled trials (RCTs) comparing high (>75 mg) and standard maintenance doses of clopidogrel in patients undergoing PCI were included. The primary efficacy and safety end-points were major adverse cardiovascular/cerebrovascular events (MACE/MACCE) and major bleeding. The secondary end-points were other ischemic and bleeding adverse effects. The pooled odds ratio (OR) for each outcome was estimated.

Results

14 RCTs with 4424 patients were included. Compared with standard-maintenance-dose clopidogrel, high-maintenance-dose clopidogrel significantly reduced the incidence of MACE/MACCE (OR 0.60; 95% CI 0.43 to 0.83), stent thrombosis (OR 0.56; 95% CI 0.32 to 0.99) and target vessel revascularization (OR 0.38; 95% CI 0.20 to 0.74), without significant decrease of the risk of cardiovascular death (OR 0.92; 95% CI 0.74 to 1.13) and myocardial infarction (OR 0.83; 95% CI 0.51 to 1.33). For safety outcomes, it did not significantly increase the risk of major bleeding (OR 0.73; 95% CI 0.41 to 1.32), minor bleeding (OR 1.29; 95% CI 1.00 to 1.66) and any bleeding (OR 1.14; 95% CI 0.91 to 1.43).

Conclusion

High-maintenance-dose clopidogrel reduces the recurrence of most ischemic events in patients post-PCI without increasing the risk of bleeding complications.     

Osteoprotegerin CGA Haplotype Protection against Cerebrovascular Complications in Anti-CCP Negative Patients with Rheumatoid Arthritis

Introduction

Rheumatoid arthritis is an inflammatory disease with high incidence of cardiovascular disease due to accelerated atherosclerosis. Osteoprotegerin (OPG) has been associated with increased risk of atherosclerotic disease in the general population. Several polymorphisms in the OPG gene with functional effects on cardiovascular disease in non-rheumatic individuals have been described. Therefore, we aimed to analyze the effect of three of these functional OPG polymorphisms on the risk of cardiovascular disease in a large and well-characterized cohort of Spanish patients with rheumatoid arthritis.

Methods

Three OPG gene variants (rs3134063, rs2073618 and rs3134069) were genotyped by TaqMan assays in 2027 Spanish patients with rheumatoid arthritis. Anti-cyclic citrullinated peptide (anti-CCP) antibody testing was positive in 997 of 1714 tested. Also, 18.3% of the whole series had experienced cardiovascular events, including 5.4% with cerebrovascular accidents. The relationship between OPG variants and cardiovascular events was assessed using Cox regression.

Results

No association between OPG gene variants and cardiovascular disease was observed in the whole group of rheumatoid arthritis patients or in anti-CCP positive patients. Nevertheless, a protective effect of CGA haplotype on the risk of cardiovascular disease in general, and specifically in the risk of cerebrovascular complications after adjusting for sex, age at disease diagnosis and traditional cardiovascular risk factors was disclosed in anti-CCP negative patients (HR = 0.54; 95%CI: 0.31–0.95; p = 0.032 and HR = 0.17; 95%CI: 0.04–0.78; p = 0.022, respectively).

Conclusion

Our results indicate a protective effect of the OPG CGA haplotype on cardiovascular risk, mainly due to a protective effect against cerebrovascular events in anti-CCP negative rheumatoid arthritis patients.     

Increased Risk of Chronic Kidney Disease in Rheumatoid Arthritis Associated with Cardiovascular Complications – A National Population-Based Cohort Study

Background and Objectives

There have been few large population-based studies of the association between rheumatoid arthritis (RA) and chronic kidney disease (CKD) and glomerulonephritis. This nationwide cohort study investigated the risks of developing CKD and glomerulonephritis in patients with RA, and the associated risks for cardiovascular complications.

Methods

From the Taiwan National Health Insurance Research Database, we identified a study cohort of 12,579 patients with RA and randomly selected 37,737 subjects without RA as a control cohort. Each subject was individually followed for up for 5 years, and the risk of CKD was analyzed using Cox proportional hazards regression models.

Results

During the follow-up period, after adjusting for traditional cardiovascular risk factors RA was independently associated with a significantly increased risk of CKD (adjusted hazard ratio [aHR] 1.31; 95% confidence interval [CI] 1.23–1.40) and glomerulonephritis (aHR 1.55; 95% CI 1.37–1.76). Increased risk of CKD was also associated with the use of non-steroidal anti-inflammatory drugs, cyclosporine, glucocorticoids, mycophenolate mofetil, and cyclophosphamide. Patients with comorbidities had even greater increased risk of CKD. Moreover, RA patients with concurrent CKD had significantly higher likelihood of developing ischemic heart disease and stroke.

Conclusions

RA patients had higher risk of developing CKD and glomerulonephritis, independent of traditional cardiovascular risk factors. Their increased risk of CKD may be attributed to glomerulonephritis, chronic inflammation, comorbidities, and renal toxicity of antirheumatic drugs. Careful monitoring of renal function in RA patients and tight control of their comorbid diseases and cardiovascular risk factors are warranted.