Vascular Disease In Type Research Articles

A Mini-Review of Reactive Oxygen Species in Urological Cancer: Correlation with NADPH Oxidases, Angiogenesis, and Apoptosis.

Oxidative stress refers to elevated reactive oxygen species (ROS) levels, and NADPH oxidases (NOXs), which are one of the most important sources of ROS. Oxidative stress plays important roles in the etiologies, pathological mechanisms, and treatment strategies of vascular diseases. Additionally, oxidative stress affects mechanisms of carcinogenesis, tumor growth, and prognosis in malignancies. Nearly all solid tumors show stimulation of neo-vascularity, termed angiogenesis, which is closely associated with malignant aggressiveness. Thus, cancers can be seen as a type of vascular disease. Oxidative stress-induced functions are regulated by complex endogenous mechanisms and exogenous factors, such as medication and diet. Although understanding these regulatory mechanisms is important for improving the prognosis of urothelial cancer, it is not sufficient, because there are controversial and conflicting opinions. Therefore, we believe that this knowledge is essential to discuss observations and treatment strategies in urothelial cancer. In this review, we describe the relationships between members of the NOX family and tumorigenesis, tumor growth, and pathological mechanisms in urological cancers including prostate cancer, renal cell carcinoma, and urothelial cancer. In addition, we introduce natural compounds and chemical agents that are associated with ROS-induced angiogenesis or apoptosis.

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OBJECTIVES/SPECIFIC AIMS: To determine the association between clinical characteristics and platelet reactivity in Hispanic patients on clopidogrel therapy. METHODS/STUDY POPULATION: A cross-sectional pilot study was performed in 58 Puerto Rican patients diagnosed with any type of vascular disease and actively receiving a maintenance dose of clopidogrel for at least 7 days. The study population was divided into 2 groups: Group I with non-high on-treatment platelet reactivity (TPR); Group II with high TPR. To determine the platelet function, P2Y12 reaction units (PRU) were obtained by VerifyNow® P2Y12 assay (Accumetrics, USA). RESULTS/ANTICIPATED RESULTS: We studied a heterogeneous cohort of patients with coronary artery disease (57%), peripheral artery disease (30%), carotid artery stenosis (7%), cerebral artery aneurysm (3%), and stroke (3%) on clopidogrel therapy for secondary prevention of thromboembolic events. The mean TPR was 205±49 PRU (range: 61–304), with a prevalence of 28% patients with high TPR (PRU≥230). No significant clinical differences were found between the non-high TPR and high-TPR groups (p>0.05). However, multivariable logistic regression analysis showed that both diabetes mellitus (OR=7.5; CI: 1.01–51.9) and proton-pump inhibitors (OR=13.6; CI: 1.3–142.0) were independently correlated with high TPR (p<0.05) after adjusting for other clinical variables. DISCUSSION/SIGNIFICANCE OF IMPACT: These results provide new insight into the importance of clinical characteristics on platelet reactivity in this Caribbean population. Further studies are warranted to determine whether important clopidogrel pharmacogenes are related with platelet function in Hispanics, as well as the role of TPR in guiding antiplatelet therapy and predicting future adverse cardiovascular events in this population.

Novel risk markers and risk prediction of saphenous vein graft disease after coronary artery bypass graft

Coronary artery bypass grafting (CABG) is an effective treatment of complex, multivessel coronary artery disease. The saphenous vein graft disease (SVGD) is a special type of vascular disease, which significantly affects the short-term and long-term prognosis of patients after CABG. SVGD also increases the likelihood of major adverse cardiac events, such as repeat revascularization, myocardial infarction, and death. It is of great significance to identify novel risk markers of SVGD for the identification of high-risk population and the implementation of targeted prevention and treatment. The new risk prediction indicators, which are reported at native and foreign are summarized, and provide a reference for early diagnosis and treatment of SVGD. Key words: Coronary artery bypass graft; Saphenous vein graft disease; Risk prediction

Exercise individualized by TRIMPi method reduces arterial stiffness in early onset type 2 diabetic patients: A randomized controlled trial with aerobic interval training

BackgroundArterial stiffness (AS) and baroreflex sensitivity (BRS) are subclinical markers of vascular diseases in type 2 diabetes (T2D). We evaluated the effects of aerobic interval training (AIT), with loads prescribed according to individual heart rate and lactate profiling obtained during a baseline treadmill test (TRIMPi method), on AS and BRS in patients with early-onset T2D without cardiovascular complications. Population study and methodsTwenty-two sedentary overweight T2D patients (aged 57±7years) were randomized to 12-weeks open-label of supervised AIT by TRIMPi (n=8) or unsupervised physical activity as per usual care (SOC) (n=11). Following parameters were evaluated (pre- and post-): anthropometrics; six-minute walking test (6MWT); fasting glucose, insulin, HbA1c; Pulse Wave Velocity (PWV) and Augmentation Index (AIxHR75) using radial approach (SphigmoCor System); BRS using Finapress method. ResultsBoth interventions significantly improved distance walked during 6MWT (AIT 52±21m; SOC 39±24m, p<0.001 for both). PWV significantly improved with AIT (p<0.001) whereas did not vary with SOC (p=0.47). Similar trend was observed for AIxHR75. Resulting percent changes from baseline were significantly better for AIT vs SOC, in both PWV (−15.8±2.1 vs +1.50±3.4%, p<0.001) and AIxHR75 (−28.9±3.2% vs +12.7±2.4%, p<0.001). BRS similarly improved in both groups (p<0.001 for both), as well as body weight, HbA1c and blood pressure. ConclusionIn sedentary T2D patients, 12-weeks AIT individualized by TRIMPi method improved AS to a greater extent than usual recommendation on physical activity, whilst exerting comparable effects on exercise capacity, glycemic control and body weight. Further researches are needed to ascertain durability of these effects.

The value of color Doppler ultrasound in the diagnosis of lower extremity vascular disease in type 2 diabetes and an analysis of related factors.

The aim of this paper is to explore the application and clinical significance of color Doppler ultrasound (CDU) in diagnosing lower extremity vascular disease in type 2 diabetes mellitus (T2DM) patients. The lower extremity arteries of 81 patients with T2DM and 50 control patients were examined by CDU for blood vessel diameter, intima-media thickness, plaque on the vessel wall, lumen stenosis and filling defect in blood flow. The occurrence of diabetes mellitus was investigated in additional T2DM patients of various ages. Left popliteal artery, left and right dorsal artery of the foot; the incidence of atherosclerotic plaque, stenosis and occlusion of the lower extremity vascular lumen of T2DM patients was significantly higher than that in the control group. Vascular disease in the lower extremities was mainly small and medium vascular disease (lower than popliteal artery), especially the dorsal artery of the foot, for which the difference was statistically significant (P<0.05). The elder patients had a greater chance of lower extremity arterial disease. CDU is the examination method of preference for T2DM patients with lower extremity vascular disease. It has a very important clinical significance for early diagnosis, prevention and treatment.

Multiscale Cross-Approximate Entropy Analysis of Bilateral Fingertips Photoplethysmographic Pulse Amplitudes among Middle-to-Old Aged Individuals with or without Type 2 Diabetes

Multiscale cross-approximate entropy (MC-ApEn) between two different physiological signals could evaluate cardiovascular health in diabetes. Whether MC-ApEn analysis between two similar signals such as photoplethysmographic (PPG) pulse amplitudes of bilateral fingertips can reflect diabetes status is unknown. From a middle-to-old-aged population free of prior cardiovascular disease, we selected the unaffected (no type 2 diabetes, n = 36), the well-controlled diabetes (glycated hemoglobin (HbA1c) &lt; 8%, n = 30), and the poorly- controlled diabetes (HbA1c ≥ 8%, n = 26) groups. MC-ApEn indexes were calculated from simultaneous consecutive 1500 PPG pulse amplitudes signals of bilateral index fingertips. The average of scale factors 1–5 (MC-ApEnSS) and of scale factors 6–10 (MC-ApEnLS) were defined as the small- and large-scales MC-ApEn, respectively. The MC-ApEnLS index was highest in the unaffected, followed by the well-controlled diabetes, and then the poorly-controlled diabetes (0.70, 0.62, and 0.53; all paired p-values were &lt;0.05); in contrast, the MC-ApEnSS index did not differ between groups. Our findings suggested that the bilateral fingertips large-scale MC-ApEnLS index of PPG pulse amplitudes might be able to evaluate the glycemic status and detect subtle vascular disease in type 2 diabetes.

Rodent Models of Vascular Cognitive Impairment.

Vascular cognitive impairment dementia (VCID), which is an increasingly important cause of dementia in the elderly, lacks effective treatments. Many different types of vascular disease are included under the diagnosis of VCID, including large vessel disease with multiple strokes and small vessel disease with lacunar infarcts and white matter disease. Animal models have been developed to study the multiple forms of VCID. Because of its progressive course, small vessel disease (SVD) is thought to be the optimal form of VCID for treatment. One theory is that the pathophysiology involves hypoxic hypoperfusion resulting in injury to the white matter and neuronal death. Bilateral occlusion of the common carotid arteries (BCAO) in a normotensive rat, which reduces cerebral blood flow, induces hypoxia with white matter damage; this model has been used to test drugs to block the injury. Another model is the spontaneously hypertensive/stroke prone rat (SHR/SP). Hypertension leads to small vessel disease resulting in progressive damage to the white matter, cortex, and hippocampus. Bilateral carotid artery stenosis (BCAS) with coils or ameroid constrictors produces a slower development of changes than BCAO, avoiding the acute ischemia. A few studies have been done with the two-clip, two-vessel occlusion renal model for induction of hypertension. There are benefits and drawbacks to each of these models with the model selected depending on the type of vascular damage that is to be studied. This review describes the most commonly used models, and the drugs that have been used to reduce the damage.

Abstract 436: Smooth Muscle Specific Knock-out of the Zinc-Finger Protein 148(ZFP148) Attenuates Atherosclerotic Lesion Formation via Regulation of Apoptotic Signaling Pathways

Objective: Zinc-finger protein 148 (ZFP148) plays a profound role in the modulation of aortic aneurysm formation in part via modulation of smooth muscle (SMC) genes. The current study objective was to determine whether smooth muscle specific knock-out of ZFP148 is critical in atherosclerotic lesion formation. Methods: ZFP148 was examined via immunohistochemistry and confocal microscopy in human atherosclerotic lesion samples (n=12/group). 6-8 week male (n=12/group) ZFP flx/flx Myh11 Cre+ ApoE-/-(SMC tamoxifen ZFP148 KO), Myh11 ZFP148 flx/wt Cre+ ApoE-/- and Myh11 ZFP wt/wt Cre+ ApoE-/- underwent tamoxifen injections followed by western diet feeding for either 13 or 25 weeks. A separate set of mice were fed western diet for 18 weeks and then administered tamoxifen injections. Aortic samples were evaluated with histology for α-actin, macrophages, neutrophils, TER119, caspase3, Ki67, picosirus red and movat staining. In vitro ZFP148 was knocked down using siRNA in smooth muscle cells and stimulated with the oxidized phospholipid POVPC. Results: ZFP148 expression was elevated in human atherosclerotic lesion samples and localized to smooth muscle cells. Lesion size was significantly reduced in SMC ZFP148 KO mice compared with controls in 25 week western diet fed mice(p&lt;0.0357). SMC ZFP148 KO demonstrated reduced macrophage, Caspase3, and TER119 staining. Conversely, SMC ZFP148 KO increased SMα-actin coverage. Lesion size was also decreased in mice that were administered tamoxifen injections following 18 weeks of western diet feeding(p&lt;0.0415). There were no significant changes in lesion size at 13 weeks of western diet feeding; however, macrophage staining was decreased. Knock-down of ZFP148 followed by treatment with POVPC attenuated the down-regulation of SM22α, SM-MHC, and SMαA. Knock-down of ZFP148 followed by POVPC treatment also prevented the up-regulation of Bax and BAD in vascular smooth muscle cells. Conclusions: While earlier studies documented a role for ZFP148 in aneurysm disease, the present study suggests that SMC ZFP148 KO attenuates atherosclerotic lesion formation in early and late atherosclerotic disease. ZFP148 represents a key regulator of multiple types of vascular disease.

The relation between apolipoprotein E (APOE) genotype and peripheral artery disease in patients at high risk for cardiovascular disease

IntroductionThe apolipoprotein E gene (APOE) is associated with coronary heart disease and stroke, but the relation with peripheral artery disease (PAD) is unknown. We investigated the relation of APOE genotype with PAD and other types of vascular disease. MethodsThe cross-sectional association between APOE genotype and ankle-brachial index (ABI) and vascular disease prevalence; and the prospective relation with incident PAD and other types of vascular disease (coronary artery disease, stroke and vascular mortality) were evaluated in 7418 patients from the Secondary Manifestations of ARTerial disease (SMART) study. This is a prospective cohort study in patients with cardiovascular disease or a cardiovascular risk factor. Analyses were adjusted for age and sex. ResultsMean age was 56.7 ± 12.4 years and 68% of the patients was male. APOE genotype frequencies were ε2ε2 1.3%; ε2ε3 9.9%; ε2ε4 2.4%; ε3ε3 56.9%; ε3ε4 26.7% and ε4ε4 2.8%. Median follow-up time was 8.1 years (IQR 5.4–11.4) in which 452 new PAD events occurred. The ε2ε2 genotype was significantly associated with a lower ABI (regression coefficient −0.04, 95%CI −0.07 to −0.01), increased PAD prevalence (prevalence ratio 1.54, 95%CI 1.01–2.17) and a higher risk of incident PAD (HR 2.31, 95%CI 1.29–4.12) compared with ε3ε3. No relations between APOE genotypes and other vascular disease were observed. ConclusionOf the six APOE genotypes, the ε2ε2 variant is associated with an increased risk for PAD in patients at high risk for cardiovascular disease. No association was observed between APOE genotype and coronary artery disease, stroke or vascular mortality in this population.

Comparison of colour Doppler ultrasound and ankle-brachial pressure index measurements in peripheral vascular disease in type 2 diabetic patients with foot infection

Background: Peripheral vascular disease is diagnosed by definitive history of intermittent claudication or if one or more of peripheral pulses are absent in one or both lower limbs. Diagnostic testing for peripheral vascular disease must be accurate, inexpensive, widely accessible, easy to perform and preferably non-invasive. A variety of non-invasive techniques are available to detect the presence of peripheral vascular disease as well as to localize areas of stenosis, assess severity of disease and follow patients for disease progression or response to therapy. In this study we compare the specificity and sensitivity of ankle brachial pressure index with colour Doppler ultrasound for diagnosis of peripheral vascular disease in type 2 diabetes. Methods: This prospective study was carried out in the department of General surgery, GMCH, Udaipur, Rajasthan, India, from September 2014 to February 2016 after taking the permission from institutional ethical committee. A total of 50 patients were selected. The selected patients were evaluated by detailed clinical history, physical examination, local examination, ankle brachial pressure index (ABPI), colour doppler study and other relevant investigations. The ABPI ratio was calculated in every patient and an ABPI less than 0.9 in either foot was defined to have PVD. Colour duplex ultrasound was done in all selected patients. Imaging of peripheral arteries of the lower limbs was done using high resolution colour duplex ultrasound. PVD was diagnosed if the stenosis in the artery was greater than 50% or presence of occlusion. Results: Total 50 patients having type 2 diabetes mellitus with foot infection were included and most of the patients were between 40-60 years of age (68%) with males preponderance. In our study 12 (24%) patients had normal ABPI of 1.0 to 1.29 and 22 (44%) patients were in the range of mild to moderate PVD with ABPI between 0.41 to 0.90. Colour doppler was used as a standard diagnostic test for PVD & out of 50 patients, 36 (72%) showed involvement of arteries and among them both anterior and posterior tibial arteries were involved in 12 (24%) patients. In our study colour doppler ultrasound was used as standard diagnostic method for PVD. The sensitivity, specificity, positive predictive value and negative predictive value of ABPI against colour duplex ultrasound were calculated. Conclusions: In our study it’s concluded that ABPI is a good initial screening tool for peripheral vascular disease, but some patients with significant stenosis or in whom collaterals have developed in lower extremity would be missed, if ABPI measurement alone is used for diagnosis of peripheral vascular disease.

Prevalence of asymptomatic peripheral vascular disease in patients with type 2 diabetes by color Doppler study

Background: A diagnosis of peripheral vascular disease in patients with diabetes mandates a multifaceted treatment approach, involving aggressive risk factor modification, anti-platelet therapy and revascularization procedures. Objective of the study is to study the prevalence of asymptomatic Peripheral vascular disease in patients with type 2 diabetes mellitus by color Doppler study and to correlate it with risk factors and ischemic heart disease. Methods: A total of 40 patients of type 2 diabetes mellitus patients attending outpatient department at Mamata General Hospital, Khammam during the period of August 2008 to August 2009 were selected randomly and a cross sectional analysis was done. The initial history was directed towards obtaining details regarding age/sex of the patient, symptoms/duration of type 2 diabetes, diet/treatment compliance, glycemic control based on HbA1c, presence of hypertension, habit of smoking, family history, symptoms suggestive of limb ischemia, past history of diabetic foot lesions, assessment of physical activity. Results: The prevalence of asymptomatic peripheral vascular disease in type 2 diabetes mellitus was found to be 30%. Age more than 50 years, male sex, smoking, duration of type 2 diabetes mellitus more than 10 years, poor glycemic control (HbA1c > 8%), increased waist hip ratio, overweight and obesity (BMI > 25 kg/m 2 ), increased waist circumference, increased serum cholesterol, increased serum LDL, increased serum Triglycerides, decreased serum HDL, hypertension, abnormal ECG, poor physical activity were found to be risk factors for peripheral vascular disease and they were statistically significant. But the factors like family history of diabetes, diet/treatment compliance were not found to be statistically significant. Conclusions: Age more than 50 years, male sex, smoking, duration of type 2 diabetes mellitus more than 10 years, poor glycemic control (HbA1c > 8%), increased waist hip ratio, overweight and obesity (BMI > 25 kg/m 2 ), increased waist circumference, increased serum cholesterol, increased serum LDL, increased serum Triglycerides, decreased serum HDL, hypertension, abnormal ECG, poor physical activity were found to be risk factors for peripheral vascular disease.

Plasma Prekallikrein Is Associated With Carotid Intima-Media Thickness in Type 1 Diabetes.

The hypothesis that plasma prekallikrein (PK) is a risk factor for the development of vascular complications was assessed in a study using the Diabetes Control and Complications Trial (DCCT)/Epidemiology and Diabetes Interventions and Complications (EDIC) cohort of subjects with type 1 diabetes. The circulating levels of plasma PK activity were measured in the plasma of 636 subjects with type 1 diabetes (EDIC years 3-5). Common and internal carotid intima-media thickness (IMT) were measured by B-mode ultrasonography in EDIC years 1 and 6. Plasma PK levels were positively and significantly associated with BMI, hemoglobin A1c, systolic blood pressure, total cholesterol, LDL cholesterol, and triglycerides but not with age, sex, duration of diabetes, or HDL cholesterol. Univariate and multivariable statistical models after controlling for other risk factors consistently demonstrated a positive association between plasma PK and progression of internal carotid IMT. Multivariate analysis using a general linear model showed plasma PK to be significantly associated with progression of both internal and combined IMT (Wilks Λ P value of 0.005). In addition, the mean internal carotid IMT levels were higher in subjects with plasma PK levels in the highest 10th percentile compared with subjects with plasma PK levels in the lower 10th percentile (P = 0.048). These novel findings implicate plasma PK as a risk factor for vascular disease in type 1 diabetes.

Association of plasma fetuin-A levels and peripheral vascular disease in type 2 diabetic patients

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

COX Inhibitor Indomethacin Attenuates Phenylephrine Induced Vasoconstriction: Differences in OLETF and LETO Vascular Response

Endothelial cell dysfunction contributes to the progression of vascular disease in type 2 diabetes (T2D). This is believed to be mediated by altered endothelial responsiveness to relaxing and/or constricting factors. We tested the hypotheses that constriction with α1-receptor agonist phenylephrine (PE) is altered by interaction with inhibitors including: cyclooxygenase (COX) inhibitor indomethacin (INDO), nitric oxide synthase inhibitor L-NAME, and their combination (LNAME+INDO) causing a loss of tone, i.e. relaxation. We used a rat model of T2D, the hyperphagic Otsuka Long-Evans Tokushima Fatty (OLETF) n=10, and their non-diabetic, normophagic control, Long-Evans Tokushima Otsuka (LETO) n=9. At 32 weeks old rats were euthanized, sequential rings of the abdominal aorta harvested, and function measured by fine wire myography. Vascular response was first confirmed with 80mM potassium chloride (KCl). After washout, inhibitors incubated with vessels for 20 minutes prior to PE with continuous recording. KCl response was not different between OLETF and LETO vessels (P=ns). In OLETF rats, PE-induced constriction diminished in INDO treated vessels compared with untreated, LNAME, and LNAME+INDO (P<0.05). In LETO rats, constriction diminished in INDO and LNAME+INDO vessels compared to both untreated and LNAME (P<0.05). We report a novel interaction for COX inhibition and PE dependent vasoconstriction. This relationship appears to effect T2D model OLETF vasculature differently than LETO controls and is an important consideration for future vascular studies. Support: HL036088 (MHL) and VHA-CDA2 1299-03 (RSR)

Frequent physical activity may not reduce vascular disease risk as much as moderate activity: large prospective study of women in the United Kingdom.

Although physical activity has generally been associated with reduced risk of vascular disease, there is limited evidence about the effects of the frequency and duration of various activities on the incidence of particular types of vascular disease. In 1998, on average, 1.1 million women without prior vascular disease reported their frequency of physical activity and many other personal characteristics. Three years later, they were asked about hours spent walking, cycling, gardening, and housework each week. Women were followed by record linkage to National Health Service cause-specific hospital admissions and death records. Cox regression was used to calculate adjusted relative risks for first vascular events in relation to physical activity. During an average of 9 years follow-up, 49,113 women had a first coronary heart disease event, 17,822 had a first cerebrovascular event, and 14,550 had a first venous thromboembolic event. In comparison with inactive women, those reporting moderate activity had significantly lower risks of all 3 conditions (P<0.001 for each). However, women reporting strenuous physical activity daily had higher risks of coronary heart disease (P=0.002), cerebrovascular disease (P<0.001), and venous thromboembolic events (P<0.001) than those reporting doing such activity 2 to 3 times per week. Risks did not differ between hemorrhagic and ischemic stroke, or between venous thromboembolic events with or without pulmonary embolism. Moderate physical activity is associated with a lower risk of coronary heart disease, venous thromboembolic event, and cerebrovascular disease than inactivity. However, among active women, there is little to suggest progressive reductions in risk of vascular diseases with increasing frequency of activity.

Blood pressure lowering in type 2 diabetes: a systematic review and meta-analysis.

Lowering blood pressure (BP) is widely used to reduce vascular risk in individuals with diabetes. To determine the associations between BP-lowering treatment and vascular disease in type 2 diabetes. We searched MEDLINE for large-scale randomized controlled trials of BP-lowering treatment including patients with diabetes, published between January 1966 and October 2014. Two reviewers independently extracted study characteristics and vascular outcome data. Estimates were stratified by baseline BP and achieved BP, and pooled using fixed-effects meta-analysis. All-cause mortality, cardiovascular events, coronary heart disease events, stroke, heart failure, retinopathy, new or worsening albuminuria, and renal failure. Forty trials judged to be of low risk of bias (100,354 participants) were included. Each 10-mm Hg lower systolic BP was associated with a significantly lower risk of mortality (relative risk [RR], 0.87; 95% CI, 0.78-0.96); absolute risk reduction (ARR) in events per 1000 patient-years (3.16; 95% CI, 0.90-5.22), cardiovascular events (RR, 0.89 [95% CI, 0.83-0.95]; ARR, 3.90 [95% CI, 1.57-6.06]), coronary heart disease (RR, 0.88 [95% CI, 0.80-0.98]; ARR, 1.81 [95% CI, 0.35-3.11]), stroke (RR, 0.73 [95% CI, 0.64-0.83]; ARR, 4.06 [95% CI, 2.53-5.40]), albuminuria (RR, 0.83 [95% CI, 0.79-0.87]; ARR, 9.33 [95% CI, 7.13-11.37]), and retinopathy (RR, 0.87 [95% CI, 0.76-0.99]; ARR, 2.23 [95% CI, 0.15-4.04]). When trials were stratified by mean baseline systolic BP at greater than or less than 140 mm Hg, RRs for outcomes other than stroke, retinopathy, and renal failure were lower in studies with greater baseline systolic BP (P interaction <0.1). The associations between BP-lowering treatments and outcomes were not significantly different, irrespective of drug class, except for stroke and heart failure. Estimates were similar when all trials, regardless of risk of bias, were included. Among patients with type 2 diabetes, BP lowering was associated with improved mortality and other clinical outcomes with lower RRs observed among those with baseline BP of 140 mm Hg and greater. These findings support the use of medications for BP lowering in these patients.

Abstract P217: Coagulation Factor IX Levels and Risk of Stroke and Coronary Heart Disease: The REasons for Geographic And Racial Differences in Stroke Study (REGARDS)

Introduction: The role of coagulation in coronary heart disease (CHD) and stroke remains controversial. We examined the association of levels of coagulation factor IX (FIX) with incident CHD and ischemic stroke in REGARDS. Methods: REGARDS recruited 30,239 participants in their homes across the contiguous U.S. between 2003-07; by design 41% were black, 55% female, and 56% lived in the southeast. Levels of FIX were measured in participants with incident CHD (n=654), incident stroke (n=646), and in a cohort random sample (n=1,104). Cox models were used to calculate the hazard ratio (HR) per standard deviation (SD) higher FIX level for incident CHD and stroke adjusting for traditional cardiovascular disease (CVD) risk factors, and testing a race by FIX interaction term. Participants with hemorrhagic stroke were excluded from the stroke analyses (n=73). Results: Levels of FIX were higher with increasing age, black race, female gender, diabetes, hypertension, dyslipidemia, and among those living in the southeastern U.S. (all p&lt;0.0001). As shown in the table, FIX levels (per 1 SD higher) were associated with CHD, but not stroke, after adjustment for CVD risk factors. When stratified by race, the association with CHD was stronger in blacks than whites (p-interaction = 0.08) with no association for stroke in either blacks or whites (p-interaction 0.71). Analyses of FIX by quintiles did not alter the results. Discussion: Levels of coagulation factor IX were significantly associated with incident CHD, but not stroke in blacks but not whites, after adjustment for CVD risk factors. These data suggest that higher levels of FIX are a risk factor for CHD in blacks but not whites, and may indicate different roles for hemostasis in vascular disease risk by race and by vascular disease type.

Plasma level of cyclophilin A is increased in patients with type 2 diabetes mellitus and suggests presence of vascular disease

Aims/hypothesisCyclophilin A, an immunophilin is secreted from human monocytes activated by high glucose. Given its role as an inflammatory mediator of vascular tissue damage associated with inflammation and oxidative stress, we examined plasma levels of cyclophilin A in normal healthy volunteers and patients with type 2 diabetes (DM), with or without coronary artery disease (CAD).MethodsStudy subjects comprised of 212 patients with DM and CAD,101 patients with diabetes, 122 patients with CAD and 121 normal healthy volunteers. Diabetes was assessed by HbA1c levels while coronary artery disease was established by a positive treadmill test and/or coronary angiography. Plasma cyclophilin A was measured using a cyclophilin A ELISA Kit. Relationship of plasma cyclophilin A levels with blood markers of type 2 diabetes, blood lipid levels and medication for diabetes and coronary artery disease were also explored.ResultsPlasma Cyclophilin levels were higher in diabetes patients with or without CAD compared to normal subjects (P < 0.001). Age, fasting blood sugar levels and HbA1C levels were positively associated with increased plasma cyclophilin. Patients using metformin had reduced levels of plasma cyclophilin (p < 0.001).Serum levels of total cholesterol, LDL cholesterol and triglycerides had no significant association with plasma cyclophilin levels. In patients with increased serum CRP levels, plasma cyclophilin A was also elevated (p = 0.016). Prevalence odds for DM, DM + CAD and CAD are higher in those with high cyclophilin values, compared to those with lower values, after adjusting for age and sex, indicating strong association of high cyclophilin values with diabetes and vascular disease.Conclusions/interpretationsOur study demonstrates that patients with type 2 diabetes have higher circulating levels of cyclophilin A than the normal population. Plasma cyclophilin levels were increased in patients with diabetes and coronary artery disease suggesting a role of this protein in accelerating vascular disease in type 2 diabetes. Considering the evidence that Cyclophilin A is an inflammatory mediator in atherogenesis, the mechanistic role of cyclophilin A in diabetic vascular disease progression deserves detailed investigation.

Brain structural changes and their correlation with vascular disease in type 2 diabetes mellitus patients: a voxel-based morphometric study.

Voxel-based morphometry has been used in the study of alterations in brain structure in type 1 diabetes mellitus patients. These changes are associated with clinical indices. The age at onset, pathogenesis, and treatment of type 1 diabetes mellitus are different from those for type 2 diabetes mellitus. Thus, type 1 and type 2 diabetes mellitus may have different impacts on brain structure. Only a few studies of the alterations in brain structure in type 2 diabetes mellitus patients using voxel-based morphometry have been conducted, with inconsistent results. We detected subtle changes in the brain structure of 23 cases of type 2 diabetes mellitus, and demonstrated that there was no significant difference between the total volume of gray and white matter of the brain of type 2 diabetes mellitus patients and that in controls. Regional atrophy of gray matter mainly occurred in the right temporal and left occipital cortex, while regional atrophy of white matter involved the right temporal lobe and the right cerebellar hemisphere. The ankle-brachial index in patients with type 2 diabetes mellitus strongly correlated with the volume of brain regions in the default mode network. The ankle-brachial index, followed by the level of glycosylated hemoglobin, most strongly correlated with the volume of gray matter in the right temporal lobe. These data suggest that voxel-based morphometry could detect small structural changes in patients with type 2 diabetes mellitus. Early macrovascular atherosclerosis may play a crucial role in subtle brain atrophy in type 2 diabetes mellitus patients, with chronic hyperglycemia playing a lesser role.

Vascular risk factors and mild cognitive impairment in the elderly population in Southwest China.

Increasing evidence has demonstrated that vascular risk factors (VRFs) contribute to cognitive impairment in the elderly population. Prevention and administration of VRFs can be a vital strategy for delaying cognitive impairment. This study aimed to determine the impact of VRFs on cognitive function of the aged people from Chongqing, Southwest China. A total of 597 participants (≥60 years) from hospital and community population were enrolled in the cross-sectional study. Participants were screened for hypertension, coronary heart disease (CHD), and cerebrovascular disease (CVD). Blood pressure (BP) and blood lipid were also measured. Cognitive function was assessed with Mini-Mental State Examination and Clinical Dementia Rating. Logistic regression analysis was used to look for VRFs impacting mild cognitive impairment (MCI). Then we investigated the relationship between different types of vascular diseases and MCI. A total of 457 participants showed normal cognitive function and 140 participants showed MCI. After adjusting for age, gender, and education, logistic regression analysis demonstrated that hypertension, CHD, systolic BP, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) were independently associated with MCI; however, CVD, diastolic BP, triglyceride, and high-density lipoprotein cholesterol were not associated with MCI. Moreover, vascular diseases significantly contributed to MCI compared with no vascular disease; however, no significant difference in incident MCI was found among different combinations of vascular diseases. Hypertension, CHD, TC, and LDL-C are independent risk factors for MCI. Moreover, patients with vascular diseases have a higher risk of MCI; however, the amount of vascular diseases does not increase the risk of MCI.