Utility of Hemoccult Testing Before Therapeutic Anticoagulation in Venous Thromboembolism.

OBJECTIVES: Fecal occult blood testing (FOBT) is performed routinely before starting therapeutic anticoagulation in patients despite it never being validated to predict gastrointestinal bleeding (GIB) risk. Our objective was to determine the utility in checking the guaiac FOBT test (gFOBT) before initiating therapeutic anticoagulation in patients with a new diagnosis of venous thromboembolism (VTE). METHODS: This was a retrospective chart review that examined patients with a diagnosis of VTE admitted during a 2-year period in one mid-sized tertiary care center. The gFOBT was performed before initiating anticoagulation, excluding patients with overt GIB, and analysis was performed to determine GIB outcomes. In addition, demographics, laboratory data, and comorbidities were recorded at the time of admission, and an admission hypertension, abnormal renal/liver function, stroke history, GIB history or predisposition, labile international normalization ratio, elderly, drugs/alcohol concomitantly (HAS-BLED) score was recorded to determine other factors that were predictive of new-onset GIB when starting anticoagulation. RESULTS: Initially, 718 patients with a new diagnosis of VTE were screened for 2 years. Ultimately, 375 patients were prescribed anticoagulation therapy and 244 had documented gFOBT. Of these 375, 14 (3.73%) had a GIB episode. A positive gFOBT was present on admission in 85.7% of those who bled (P < 0.001). The negative predictive value of gFOBT was 99.02%; however, the positive predictive value was only 30.77%. A HAS-BLED score >2 at admission significantly predicted GIB during admission as well (median 2.4 for those with GIB and 1.6 for those without GIB, P = 0.02). CONCLUSIONS: Despite its beneficial negative predictive value, gFOBT before initiating therapeutic anticoagulation is unlikely to change the management of patients without evidence of overt GIB.

Heisenberg strikes again.

Systematic randomized clinical outcome data in BVS has largely been reported in straightforward lesions, and BVS performance in more complex anatomy is not well defined In this study, OCT-analysis of imaging outcomes in lesions with variable degrees of calcification demonstrated similar acute performance between second-generation DES and BVS Open questions as to the unintended effect of OCT-guidance on the results of the study as well as the longer-term clinical outcomes in these lesions remain.

Predictors of and survival after incident stroke in type 1 diabetes.

Few studies have examined stroke risk in type 1 diabetes mellitus (T1DM). Stroke incidence, predictors, and survival were thus explored in this study. Pittsburgh Epidemiology of Diabetes Complications (EDC) Study participants (n = 658) with childhood-onset T1DM were followed biennially for 18 years. Baseline (1986-1988) mean age and diabetes duration were 28 and 19 years respectively. Stroke incidence and type was determined via survey or physician interview and, when possible, confirmed with medical or autopsy records. During follow-up, 31 (4.7%) strokes occurred (21 ischaemic, 8 haemorrhagic, 2 unclassified) in participants of mean age = 40.2 years (range 23-60). In exploratory multivariable Cox modelling, diabetes duration, systolic blood pressure (SBP), non-high density lipoprotein cholesterol (non-HDLc), white blood cells (WBC), and pulse significantly predicted ischaemic stroke. Adding overt nephropathy (ON) (hazard ratio = 4.4, 95% CI, 1.5-12.4) to the model replaced SBP. Participant survival after stroke was 80.6%, 45.2%, and 9.6% at 1, 5, and 10 years, respectively, and significantly worse after haemorrhagic stroke (p = 0.03). These risk factors merit careful evaluation and management to prevent stroke in T1DM, which occurs at least 20 years earlier than in the general population.

The effects of modulating eNOS activity and coupling in ischemia/reperfusion (I/R).

The in vivo role of endothelial nitric oxide synthase (eNOS) uncoupling mediating oxidative stress in ischemia/reperfusion (I/R) injury has not been well established. In vitro, eNOS coupling refers to the reduction of molecular oxygen to L-arginine oxidation and generation of L-citrulline and nitric oxide NO synthesis in the presence of an essential cofactor, tetrahydrobiopterin (BH(4)). Whereas uncoupled eNOS refers to that the electron transfer becomes uncoupled to L-arginine oxidation and superoxide is generated when the dihydrobiopterin (BH(2)) to BH(4) ratio is increased. Superoxide is subsequently converted to hydrogen peroxide (H(2)O(2)). We tested the hypothesis that promoting eNOS coupling or attenuating uncoupling after I/R would decrease H(2)O(2)/increase NO release in blood and restore postreperfused cardiac function. We combined BH(4) or BH(2) with eNOS activity enhancer, protein kinase C epsilon (PKC ε) activator, or eNOS activity reducer, PKC ε inhibitor, in isolated rat hearts (ex vivo) and femoral arteries/veins (in vivo) subjected to I(20 min)/R(45 min). When given during reperfusion, PKC ε activator combined with BH(4), not BH(2), significantly restored postreperfused cardiac function and decreased leukocyte infiltration (p < 0.01) while increasing NO (p < 0.05) and reducing H(2)O(2) (p < 0.01) release in femoral I/R veins. These results provide indirect evidence suggesting that PKC ε activator combined with BH(4) enhances coupled eNOS activity, whereas it enhanced uncoupled eNOS activity when combined with BH(2). By contrast, the cardioprotective and anti-oxidative effects of the PKC ε inhibitor were unaffected by BH(4) or BH(2) suggesting that inhibition of eNOS uncoupling during reperfusion following sustained ischemia may be an important mechanism.

Pulse wave analysis and cardiac autonomic neuropathy in type 1 diabetes: a report from the Pittsburgh Epidemiology of Diabetes Complications Study.

BACKGROUND: The cross-sectional associations of cardiac autonomic neuropathy (CAN) with pulse wave analysis (PWA) measures (both arterial stiffness and myocardial perfusion) have not been explored in type 1 diabetes, despite recognition of an association of CAN with coronary artery disease. METHODS: Both CAN and PWA measures were obtained from 144 participants of the Pittsburgh Epidemiology of Diabetes Complications Study of childhood-onset type 1 diabetes at the 18-year follow-up examination. CAN was measured as variability in the R-R interval during deep breathing, and PWA was performed using SphgymoCor Px (AtCor Medical, Sydney, Australia). Other clinical and demographic factors were also assessed. Univariate and multivariable analyses for associations with CAN were performed for arterial stiffness measures (augmentation index [AIx] and augmentation pressure [AP]) and a myocardial perfusion measure (subendocardial viability ratio [SEVR]). RESULTS: Presence of CAN was univariately associated with all three PWA measures: AIx (odds ratio [OR]=1.5, P=0.03), AP (OR=2.1, P=0.001), and SEVR (OR=0.4, P<0.001). These relationships persisted after adjustment for potential PWA confounders. Adjusting for age and diabetes-related factors (glycosylated hemoglobin, systolic blood pressure, and overt nephropathy), CAN only remained significantly associated with SEVR (OR=0.3, P=0.005). CONCLUSIONS: CAN is cross-sectionally associated with measures of both increased arterial stiffness and decreased myocardial perfusion in type 1 diabetes; however, only the association with decreased estimated myocardial perfusion persisted in fully adjusted models. These results provide potential insight into the CAN association with coronary artery disease.

Pulse wave analysis and prevalent cardiovascular disease in type 1 diabetes.

OBJECTIVE: Type 1 diabetes (T1D) is associated with a high risk for and mortality from premature coronary artery disease (CAD), including coronary artery calcification (CAC), a subclinical marker, and lower extremity arterial disease (LEAD). Pulse wave analysis (PWA) arterial stiffness indices have been associated with cardiovascular disease (CVD) risk factors and outcomes in various populations, but little is known regarding these relationships in T1D. METHODS: PWA was performed using the SphygmoCor Px device on 144 participants in the Pittsburgh EDC Study of childhood-onset T1D. The cross-sectional associations between arterial stiffness indices, augmentation index (AIx) and augmentation pressure (AP), and subendocardial viability ratio (SEVR), an estimate of myocardial perfusion, with prevalent CAD, electron beam computed tomography-measured CAC and low (<0.90) ankle-brachial index (ABI) were examined. RESULTS: Higher AP (but not AIx) and lower SEVR were univariately associated with prevalent CAD, high CAC score, and low ABI. AP and SEVR's association with CAD and CAC did not, however, remain significant after adjustment for age. In individuals not using nitrates, which profoundly affect PWA measures, AP was significantly higher in those with CAD events and explained more of the variance than either age or brachial blood pressure measures. SEVR was associated with low ABI in multivariable models. CONCLUSIONS: Greater augmentation pressure is independently associated with prevalent CAD and estimated myocardial perfusion with low ABI in type 1 diabetes. These measures may thus help to better characterize CVD risk in type 1 diabetes and need to be examined prospectively.

Augmentation pressure and subendocardial viability ratio are associated with microalbuminuria and with poor renal function in type 1 diabetes.

In this report we explore the hypothesis that arterial stiffness indices, which predict cardiovascular disease, might also correlate with microalbuminuria (MA) in type 1 diabetes (T1D), and thus have potential for risk assessment. Three pulse wave analysis (PWA) indices, measured using the SphygmoCor device, were evaluated on 144 participants with childhood-onset T1D. These variables, augmentation index (AIx), augmentation pressure (AP) and subendocardial viability ratio (SEVR, an estimate of myocardial perfusion) (an estimate of myocardial perfusion), were each analysed cross-sectionally in relation to both prevalent MA (defined as albuminuria excretion rate (AER) = 20-199 microg/min) and renal function (assessed by both eGFR and serum cystatin C). AP and SEVR were each univariately associated with AER, estimated glomerular filtration rate (eGFR) and cystatin C. Lower SEVR was also independently related to the presence of MA and degree of albuminuria within normo- and microalbuminuric participants. SEVR, not AP, was independently and negatively associated with both measures of renal function. SEVR is a better predictor of AER than brachial blood pressure measures in those without clinical proteinuria, indicating a potential use for PWA in the early detection of individuals at risk for cardiovascular and renal complications of T1D.

Cardiovascular autonomic neuropathy, HDL cholesterol, and smoking correlate with arterial stiffness markers determined 18 years later in type 1 diabetes.

OBJECTIVE To examine the relationship between cardiovascular autonomic neuropathy and pulse waveform analysis (PWA) measures of arterial stiffness in a childhood-onset type 1 diabetes population. RESEARCH DESIGN AND METHODS Cardiac autonomic nerve function was measured in the baseline examination of the Pittsburgh Epidemiology of Diabetes Complications Study of childhood-onset type 1 diabetes by heart rate variability (R-R interval) during deep breathing and expressed as expiration-to-inspiration (E/I) ratio. Other cardiovascular and diabetes factors were also assessed. PWA was performed using SphgymoCor Px on 144 participants at the 18-year follow-up examination. Univariate and multivariate analyses for associations between baseline nerve function and other cardiovascular and diabetes-related factors were performed for augmentation index (AIx), augmentation pressure (AP), and subendocardial viability ratio (SEVR), a surrogate marker of myocardial perfusion. RESULTS E/I ratio correlated negatively with both AIx (r = -0.18, P = 0.03) and AP (r = -0.32, P < 0.001) and positively with SEVR (r = 0.47, P < 0.001) univariately. Lower baseline E/I ratio, HDL cholesterol, and a history of smoking were associated with higher follow-up (18 years later) AIx and AP and lower SEVR in multivariate analyses. Higher baseline HbA(1) was also associated with higher AP and lower SEVR multivariately. CONCLUSIONS Cardiovascular autonomic neuropathy is associated with increased arterial stiffness measures and decreased estimated myocardial perfusion in those with type 1 diabetes some 18 years later. This association persists after adjustment for potential confounders as well as for baseline HbA(1), HDL cholesterol, and smoking history, which were also associated with these PWA measures.

Retinal vessel diameter and the incidence of coronary artery disease in type 1 diabetes.

PURPOSE: To examine the relationship between retinal vessel diameter and coronary artery disease (CAD) incidence in type 1 diabetes (T1D) using data from the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study. DESIGN: Prospective cohort study of childhood-onset T1D. METHODS: Data are from 448 participants who had retinal photographs taken at baseline examination (May 1986 to November 1988) and no history of laser photocoagulation. Computer-assisted grading was used to measure retinal arteriolar and venular caliber. CAD incidence (CAD death, myocardial infarction, revascularization/stenosis > or =50%, ischemic electrocardiogram, or physician-diagnosed angina) was ascertained over a median follow-up time of 18 years (range, 2 months to 20.5 years). RESULTS: Mean baseline arteriolar and venular caliber were 180.0 microm (standard deviation [SD], 15.2 microm) and 273.3 microm (SD, 28.0 microm), respectively; 80 (17.9%) CAD events occurred during follow-up. After covariate adjustment for T1D duration, gender, hypertension, serum lipids, and smoking status, smaller arteriolar caliber was significantly associated with CAD (hazard ratio [HR], 1.42; P = .03), but larger venular caliber was not. A vessel diameter-gender interaction term was significant for arteriolar caliber (P = .006). Stratified by gender, smaller arteriolar caliber was significantly associated with the incidence of CAD in women (HR, 1.92; P = .004), but not men. Venular caliber was not associated with CAD in either gender. CONCLUSION: Smaller arteriolar caliber may indicate an increased risk of CAD in women, but not men, with T1D. Additional studies are needed to further examine the role of microvascular disease in the pathogenesis of CAD in women with T1D.

Progression of coronary artery calcium in type 1 diabetes mellitus.

Coronary artery calcium (CAC) has been previously associated with atherosclerotic plaque disease and coronary events. Thus, identifying predictors of CAC progression may provide new insights for early risk-factor intervention and subsequent reduction of the rates of more severe atherosclerotic disease. The aim of this study was to identify risk factors for CAC progression and evaluate whether risk-factor change was related to CAC progression in a cohort of patients with type 1 diabetes mellitus (DM). Participants in the Pittsburgh EDC Study, a prospective investigation of childhood-onset type 1 DM, who underwent 2 electron beam tomographic screenings 4 years apart were selected for study (n = 222). CAC was calculated using the Agatston method of scoring, and progression was defined as an increase >2.5 in the square root-transformed CAC score. Adjusting for DM duration and initial CAC score, body mass index (BMI; odds ratio [OR] 1.13, 95% confidence interval [CI] 1.01 to 1.26), non-high-density lipoprotein cholesterol (OR 1.01, 95% CI 1.003 to 1.03), and albumin excretion rate (OR 1.30, 95% CI 1.03 to 1.63) were associated with CAC progression. When considering change in risk factors, an increase in BMI (OR 1.38, 95% CI 1.10 to 1.72) was also associated with CAC progression after adjustment. In conclusion, in this cohort with type 1 DM, in addition to baseline BMI, non-high-density lipoprotein cholesterol, albumin excretion rate, and all known coronary artery disease risk factors, weight gain further added to the prediction of CAC progression. Thus, weight control, in addition to lipid and renal management, may help retard atherosclerosis progression in persons with type 1 DM.