Sex differences in the prevalence and clinical outcomes of subclinical peripheral artery disease in the Health, Aging, and Body Composition (Health ABC) study

The objective of the study was to determine if there are sex-based differences in the prevalence and clinical outcomes of subclinical peripheral artery disease (PAD). We evaluated the sex-specific associations of ankle-brachial index (ABI) with clinical cardiovascular disease outcomes in 2797 participants without prevalent clinical PAD and with a baseline ABI measurement in the Health, Aging, and Body Composition study. The mean age was 74 years, 40% were black, and 52% were women. Median follow-up was 9.37 years. Women had a similar prevalence of ABI < 0.9 (12% women versus 11% men; P = 0.44), but a higher prevalence of ABI 0.9-1.0 (15% versus 10%, respectively; P < 0.001). In a fully adjusted model, ABI < 0.9 was significantly associated with higher coronary heart disease (CHD) mortality, incident clinical PAD and incident myocardial infarction in both women and men. ABI < 0.9 was significantly associated with incident stroke only in women. ABI 0.9-1.0 was significantly associated with CHD death in both women (hazard ratio 4.84, 1.53-15.31) and men (3.49, 1.39-8.72). However, ABI 0.9-1.0 was significantly associated with incident clinical PAD (3.33, 1.44-7.70) and incident stroke (2.45, 1.38-4.35) only in women. Subclinical PAD was strongly associated with adverse CV events in both women and men, but women had a higher prevalence of subclinical PAD.

Stent placement vs. balloon angioplasty for popliteal artery treatment: two-year results of a prospective, multicenter, randomized trial.

PURPOSE To investigate the 2-year technical and clinical results of primary nitinol stent placement in comparison with percutaneous transluminal angioplasty (PTA) in the treatment of de novo lesions of the popliteal artery. METHODS The ETAP study (Endovascular Treatment of Atherosclerotic Popliteal Artery Lesions: balloon angioplasty vs. primary stenting; www.ClinicalTrials.gov identifier NCT00712309) is a prospective, randomized trial that enrolled 246 patients (158 men; mean age 72 years) who were randomly assigned to receive a nitinol stent (n=119) or PTA (n=127) for lesions averaging 42.3 mm in length. The results of the primary study endpoint were published. Secondary outcome measures and endpoints included primary patency (freedom from duplex-detected target lesion restenosis), target lesion revascularization (TLR), secondary patency, changes in ankle-brachial index and Rutherford class, and event-free survival (freedom from target limb amputation, TLR, myocardial infarction, and death). RESULTS In total, 183 patients (89 stent and 94 PTA) were available for the 2-year analysis. The primary patency rate was significantly higher in the stent group (64.2%) than in the PTA group (31.3%, p=0.0001). TLR rates were 22.4% and 59.5%, respectively (p=0.0001). When provisional stent placement in the PTA arm was not considered as TLR and loss in patency, the differences prevailed between the study groups but were not significant (64.2% vs. 56.1% for primary patency, respectively; p=0.44). A significant improvement in ABI and Rutherford category was observed at 2 years in both groups. CONCLUSION In treatment of obstructive popliteal artery lesions, provisional stenting reveals equivalent patency in comparison to primary stenting. However, the 2-year results of this trial suggest the possibility of a shift toward higher patency rates in favor of primary stenting.

Endothelial progenitor cells as a biological marker of peripheral artery disease.

The role of endothelial progenitor cells (EPCs) in peripheral artery disease (PAD) remains unclear. We hypothesized that EPC mobilization and function play a central role in the development of endothelial dysfunction and directly influence the degree of atherosclerotic burden in peripheral artery vessels. The number of circulating EPCs, defined as CD34(+)/KDR(+) cells, were assessed by flow cytometry in 91 subjects classified according to a predefined sample size of 31 non-diabetic PAD patients, 30 diabetic PAD patients, and 30 healthy volunteers. Both PAD groups had undergone endovascular treatment in the past. As a functional parameter, EPC colony-forming units were determined ex vivo. Apart from a broad laboratory analysis, a series of clinical measures using the ankle-brachial index (ABI), flow-mediated dilatation (FMD) and carotid intima-media thickness (cIMT) were investigated. A significant reduction of EPC counts and proliferation indices in both PAD groups compared to healthy subjects were observed. Low EPC number and pathological findings in the clinical assessment were strongly correlated to the group allocation. Multivariate statistical analysis revealed these findings to be independent predictors of disease appearance. Linear regression analysis showed the ABI to be a predictor of circulating EPC number (p=0.02). Moreover, the functionality of EPCs was correlated by linear regression (p=0.017) to cIMT. The influence of diabetes mellitus on EPCs in our study has to be considered marginal in already disease-affected patients. This study demonstrated that EPCs could predict the prevalence and severity of symptomatic PAD, with ABI as the determinant of the state of EPC populations in disease-affected groups.

Ultrasound Mapping of Stimulated Finger Flexion During Infra-Clavicular Brachial Plexus Nerve Blockade for Elbow Arthroplasty and Its Correlation To Postoperative Analgesia

Background: Infraclavicular brachial plexus nerve blockade (ICNB) is a very common anesthetic procedure performed for upper extremity surgery at the elbow and distally, however the rate of adequate analgesia is variable among patients. Ultrasound guidance (US) has not been demonstrated to increase the success rate of ICNB when compared to nerve stimulator (NS) guidance. Combined US and NS guided ICNB have not been reported, although there is a call for more trials comparing the two techniques. This study was performed to observe if a specific anatomic region near the axillary artery of the brachial plexus identified by finger flexion with nerve stimulation results in improved postoperative analgesia. Method: Patients undergoing elective elbow arthroplasty received a postoperative ICNB. The angle of the nerve stimulator needle tip and the radial distance from the center of the arterial lumen at which an optimal finger flexion twitch response was observed were measured with ultrasound imaging. Pain scores and postoperative opioid dosages on discharge from the post anesthesia care unit and at 24 hours after surgery were recorded. Results: 11 patients enrolled in this study. Adequate finger flexion response to nerve stimulation that resulted in complete analgesia was more frequently observed when the needle was located in the postero-superior quadrant in relation to the axillary artery. Identifying a specific point near the brachial plexus in relation to the artery that consistently provides superior analgesia is desirable and would lead to improved analgesia and faster onset time of nerve blockade and would reduce the need for other approaches for brachial plexus blockade with their associated disadvantages.

The effect of exercise on large artery haemodynamics in healthy young men

Background Brachial blood pressure predicts cardiovascular outcome at rest and during exercise. However, because of pulse pressure amplification, there is a marked difference between brachial pressure and central (aortic) pressure. Although central pressure is likely to have greater clinical importance, very little data exist regarding the central haemodynamic response to exercise. The aim of the present study was to determine the central and peripheral haemodynamic response to incremental aerobic exercise. Materials and methods Twelve healthy men aged 31 +/- 1 years (mean +/- SEM) exercised at 50%, 60%, 70% and 80% of their maximal heart rate (HRmax) on a bicycle ergometer. Central blood pressure and estimated aortic pulse wave velocity, assessed by timing of the reflected wave (T-R), were obtained noninvasively using pulse wave analysis. Pulse pressure amplification was defined as the ratio of peripheral to central pulse pressure and, to assess the influence of wave reflection on amplification, the ratio of peripheral pulse pressure to nonaugmented central pulse pressure (PPP : CDBP-P-1) was also calculated. Results During exercise, there was a significant, intensity-related, increase in mean arterial pressure and heart rate (P < 0.001). There was also a significant increase in pulse pressure amplification and in PPP : CDBP-P-1 (P < 0.001), but both were independent of exercise intensity. Estimated aortic pulse wave velocity increased during exercise (P < 0.001), indicating increased aortic stiffness. There was also a positive association between aortic pulse wave velocity and mean arterial pressure (r = 0.54; P < 0.001). Conclusions Exercise significantly increases pulse pressure amplification and estimated aortic stiffness.

The Soluble Guanylyl Cyclase Activator Bay 60-2770 Potently Relaxes The Pulmonary Artery On Congenital Diaphragmatic Hernia Rabbit Model.

Congenital diaphragmatic hernia (CDH) is associated with pulmonary hypertension which is often difficult to manage, and a significant cause of morbidity and mortality. In this study, we have used a rabbit model of CDH to evaluate the effects of BAY 60-2770 on the in vitro reactivity of left pulmonary artery. CDH was performed in New Zealand rabbit fetuses (n = 10 per group) and compared to controls. Measurements of body, total and left lung weights (BW, TLW, LLW) were done. Pulmonary artery rings were pre-contracted with phenylephrine (10 μM), after which cumulative concentration-response curves to glyceryl trinitrate (GTN; NO donor), tadalafil (PDE5 inhibitor) and BAY 60-2770 (sGC activator) were obtained as well as the levels of NO (NO3/NO2). LLW, TLW and LBR were decreased in CDH (p < 0.05). In left pulmonary artery, the potency (pEC50) for GTN was markedly lower in CDH (8.25 ± 0.02 versus 9.27 ± 0.03; p < 0.01). In contrast, the potency for BAY 60-2770 was markedly greater in CDH (11.7 ± 0.03 versus 10.5 ± 0.06; p < 0.01). The NO2/NO3 levels were 62 % higher in CDH (p < 0.05). BAY 60-2770 exhibits a greater potency to relax the pulmonary artery in CDH, indicating a potential use for pulmonary hypertension in this disease.

Implantation Of Transcatheter Aortic Valve Prosthesis Through The Ascending Aorta Concomitant With Coronary Artery Bypass Grafting Without Cardiopulmonary Bypass.

Introdution: The transcatheter aortic valve implantation in the treatment of high-risk symptomatic aortic stenosis has increased the number of implants every year. The learning curve for transcatheter aortic valve implantation has improved since the last 12 years, allowing access alternatives. The aim of this study is to approach the implantation of transcatheter aortic valve through transaortic via associated with off-pump cardiopulmonary bypass surgery in a 67-year-old man, with chronic obstructive pulmonary disease, arterial hypertension and kidney transplant. Off-pump coronary artery bypass surgery was performed and the valve in the aortic position was released successfully. There were no complications in the intraoperative and postoperative period. Gradient reduction, effective orifice increasing of the prosthesis and absence of valvular regurgitation after implantation were observed by transesophageal echocardiography. Procedural success demonstrates that implantation of transcatheter aortic valve through the ascending aorta associated with coronary artery bypass surgery without CPB is a new option for these patients.

Enhanced Endothelium-dependent Relaxation Of Rat Pulmonary Artery Following β-adrenergic Overstimulation: Involvement Of The No/cgmp/vasp Pathway.

The aim of this study was to investigate whether β-adrenoceptor (β-AR) overstimulation induced by in vivo treatment with isoproterenol (ISO) alters vascular reactivity and nitric oxide (NO) production and signaling in pulmonary arteries. Vehicle or ISO (0.3mgkg(-1)day(-1)) was administered daily to male Wistar rats. After 7days, the jugular vein was cannulated to assess right ventricular (RV) systolic pressure (SP) and end diastolic pressure (EDP). The extralobar pulmonary arteries were isolated to evaluate the relaxation responses, protein expression (Western blot), NO production (diaminofluorescein-2 fluorescence), and cyclic guanosine 3',5'-monophosphate (cGMP) levels (enzyme immunoassay kit). ISO treatment induced RV hypertrophy; however, no differences in RV-SP and EDP were observed. The pulmonary arteries from the ISO-treated group showed enhanced relaxation to acetylcholine that was abolished by the NO synthase (NOS) inhibitor N(ω)-nitro-l-arginine methyl ester (l-NAME); whereas relaxation elicited by sodium nitroprusside, ISO, metaproterenol, mirabegron, or KCl was not affected by ISO treatment. ISO-treated rats displayed enhanced endothelial NOS (eNOS) and vasodilator-stimulated phosphoprotein (VASP) expression in the pulmonary arteries, while phosphodiesterase-5 protein expression decreased. ISO treatment increased NO and cGMP levels and did not induce eNOS uncoupling. The present data indicate that β-AR overactivation enhances the endothelium-dependent relaxation of pulmonary arteries. This effect was linked to an increase in eNOS-derived NO production, cGMP formation and VASP content and to a decrease in phosphodiesterase-5 expression. Therefore, elevated NO bioactivity through cGMP/VASP signaling could represent a protective mechanism of β-AR overactivation on pulmonary circulation.

Quality Of Life Of Coronary Artery Disease Patients After The Implementation Of Planning Strategies For Medication Adherence.

to compare the general and specific health-related quality of life (HRQoL) between the Intervention (IG) and Control (CG) groups of coronary artery disease patients after the implementation of Action Planning and Coping Planning strategies for medication adherence and to verify the relationship between adherence and HRQoL. this was a controlled and randomized study. the sample (n=115) was randomized into two groups, IG (n=59) and CG (n=56). Measures of medication adherence and general and specific HRQoL were obtained in the baseline and after two months of monitoring. the findings showed that the combination of intervention strategies - Action Planning and Coping Planning for medication adherence did not affect the HRQoL of coronary artery disease patients in outpatient monitoring.

Metabolic syndrome and dietary components are associated with coronary artery disease risk score in free-living adults: a cross-sectional study

Background: Coronary artery disease (CAD) is among the main causes of death in developed countries, and diet and lifestyle can influence CAD incidence. Objective: To evaluate the association of coronary artery disease risk score with dietary, anthropometric and biochemical components in adults clinically selected for a lifestyle modification program. Methods: 362 adults (96 men, 266 women, 53.9 +/- 9.4 years) fulfilled the inclusion criteria by presenting all the required data. The Framingham score was calculated and the IV Brazilian Guideline on Dyslipidemia and Prevention of Atherosclerosis was adopted for classification of the CAD risks. Anthropometric assessments included waist circumference (WC), body fat and calculated BMI (kg/m(2)) and muscle-mass index (MMI kg/m(2)). Dietary intake was estimated through 24 h dietary recall. Fasting blood was used for biochemical analysis. Metabolic Syndrome (MS) was diagnosed using NCEP-ATPIII (2001) criteria. Logistic regression was used to determine the odds of CAD risks according to the altered components of MS, dietary, anthropometric, and biochemical components. Results: For a sample with a BMI 28.5 +/- 5.0 kg/m(2) the association with lower risk (<10% CAD) were lower age (<60 years old), and plasma values of uric acid. The presence of MS within low, intermediary, and high CAD risk categories was 30.8%, 55.5%, and 69.8%, respectively. The independent risk factors associated with CAD risk score was MS and uric acid, and the protective factors were recommended intake of saturated fat and fiber and muscle mass index. Conclusion: Recommended intake of saturated fat and dietary fiber, together with proper muscle mass, are inversely associated with CAD risk score. On the other hand, the presence of MS and high plasma uric acid are associated with CAD risk score.

Motor Nerve-Conduction Studies in Obstetric Brachial Plexopathy for a Selection of Patients with a Poor Outcome

Background: The criteria and timing for nerve surgery in infants with obstetric brachial plexopathy remain controversial. Our aim was to develop a new method for early prognostic assessment to assist this decision process. Methods: Fifty-four patients with unilateral obstetric brachial plexopathy who were ten to sixty days old underwent bilateral motor-nerve-conduction studies of the axillary, musculocutaneous, proximal radial, distal radial, median, and ulnar nerves. The ratio between the amplitude of the compound muscle action potential of the affected limb and that of the healthy side was called the axonal viability index. The patients were followed and classified in three groups according to the clinical outcome. We analyzed the receiver operating characteristic curve of each index to define the best cutoff point to detect patients with a poor recovery. Results: The best cutoff points on the axonal viability index for each nerve (and its sensitivity and specificity) were <10% (88% and 89%, respectively) for the axillary nerve, 0% (88% and 73%) for the musculocutaneous nerve, <20% (82% and 97%) for the proximal radial nerve, <50% (82% and 97%) for the distal radial nerve, and <50% (59% and 97%) for the ulnar nerve. The indices from the proximal radial, distal radial, and ulnar nerves had better specificities compared with the most frequently used clinical criterion: absence of biceps function at three months of age. Conclusions: The axonal viability index yields an earlier and more specific prognostic estimation of obstetric brachial plexopathy than does the clinical criterion of biceps function, and we believe it may be useful in determining surgical indications in these patients.

TCF7L2 Polymorphism rs7903146 Is Associated with Coronary Artery Disease Severity and Mortality

Background: TCF7L2 polymorphisms have been consistently associated with type 2 diabetes mellitus in different populations and type 2 diabetes mellitus is a major risk factor for cardiovascular disease, especially coronary artery disease. This study aimed to evaluate the association between TCF7L2 polymorphism rs7903146 and coronary artery disease in diabetic and non-diabetic subjects. Methods and Results: two populations were studied in order to assess severity of coronary artery disease and cardiovascular events incidence. Eight-hundred and eighty nine subjects who were referred for cardiac catheterization for coronary artery disease diagnosis were cross-sectionally evaluated for coronary lesions (atherosclerotic burden) and 559 subjects from the MASS-II Trial were prospectively followed-up for 5 years and assessed for major cardiovascular events incidence. As expected, rs7903146 T allele was associated with diabetes. Although diabetic patients had a higher prevalence of coronary lesions, no association between TCF7L2 genotype and coronary lesions was found in this subgroup. However, non-diabetic individuals carrying the T allele were associated with a significantly higher frequency of coronary lesions than non-diabetic non-carriers of the risk allele (adjusted OR = 2.32 95% CI 1.27-4.24, p = 0.006). Moreover, presence of multi-vessel coronary artery disease was also associated with the CT or TT genotypes in non-diabetics. Similarly, from the prospective sample analysis, non-diabetics carrying the CT/TT genotypes had significantly more composite cardiovascular end-points events than CC carriers (p = 0.049), mainly due to an increased incidence of death (p = 0.004). Conclusions: rs7903146 T allele is associated with diabetes and, in non-diabetic individuals, with a higher prevalence and severity of coronary artery disease and cardiovascular events. name of registry site (see list below), registration number, trial registration URL in brackets.

Genetic Variants of Diabetes Risk and Incident Cardiovascular Events in Chronic Coronary Artery Disease

Objective: To determine whether information from genetic risk variants for diabetes is associated with cardiovascular events incidence. Methods: From the about 30 known genes associated with diabetes, we genotyped single-nucleotide polymorphisms at the 10 loci most associated with type-2 diabetes in 425 subjects from the MASS-II Study, a randomized study in patients with multi-vessel coronary artery disease. The combined genetic information was evaluated by number of risk alleles for diabetes. Performance of genetic models relative to major cardiovascular events incidence was analyzed through Kaplan-Meier curve comparison and Cox Hazard Models and the discriminatory ability of models was assessed for cardiovascular events by calculating the area under the ROC curve. Results: Genetic information was able to predict 5-year incidence of major cardiovascular events and overall-mortality in non-diabetic individuals, even after adjustment for potential confounders including fasting glycemia. Non-diabetic individuals with high genetic risk had a similar incidence of events then diabetic individuals (cumulative hazard of 33.0 versus 35.1% of diabetic subjects). The addition of combined genetic information to clinical predictors significantly improved the AUC for cardiovascular events incidence (AUC = 0.641 versus 0.610). Conclusions: Combined information of genetic variants for diabetes risk is associated to major cardiovascular events incidence, including overall mortality, in non-diabetic individuals with coronary artery disease.

Effect of the effluent released from the canine internal mammary artery after intraluminal and extraluminal perfusion of acetylcholine and adenosine diphosphate

Segments of the canine internal mammary artery (35 mm in length) were suspended in vitro in an organ chamber containing physiological salt solution (95% O(2)/5% CO(2), pH = 7.4, 37 degrees C). Segments were individually cannulated and perfused at 5 ml/minute using a roller pump. Vasorelaxant activity of the effluent from the perfused internal mammary arteries was bioassayed by measuring the decrease in tension induced by the effluent of the coronary artery endothelium-free ring which had been contracted with prostaglandin F(2 alpha) (2 x 10(-6) M). Intraluminal perfusion of adenosine diphosphate (10(-5) M) induced significant increase in relaxant activity in the effluent from the perfused blood vessel. However, when adenosine diphosphate (10(-5) M) was added extraluminally to the internal mammary artery, no change in relaxant activity in the effluent was noted. In contrast, acetylcholine produced significant increase in the relaxant activity on the effluent of the perfused internal mammary artery with both intraluminal and extraluminal perfusion. The intraluminal and extraluminal release of endothelium-derived relaxing factor (EDRF) by acetylcholine (10(-5) M) can be inhibited by site-specific administration of atropine (10(-5) M). These experiments indicate that certain agonists can induce the release of EDRF only by binding to intravascular receptors while other agonists can induce endothelium-dependent vasodilatation by acting on neural side receptors.

Fat and fiber consumption are associated with peripheral arterial disease in a cross-sectional study of a Japanese-Brazilian population

Background The Western diet plays a role for the epidemics of obesity and related diseases. This study examined a possible association between peripheral arterial disease (PAD) and the dietary components of Japanese immigrants living in Brazil. Methods and Results In this cross-sectional study, 1,267 subjects (aged 30 years) with complete dietary, clinical and laboratory data were studied according to a standardized protocol. Ankle-to-brachial index was used to identify subjects with PAD. The overall prevalence of PAD was 14.6%. Subjects with PAD were older, had lower education and higher mean values of blood pressure, triglycerides, and fasting and 2-h plasma glucose levels compared with those without the disease. Among the subjects with PAD, the consumption of fiber from whole grains (3.0 vs 3.4g, p=0.001) and linoleic acids (11.0 vs 11.7g, p=0.017) were lower and intake of total (72.8 vs 69.1 a, p=0.016) and saturated fatty acids (17.4 vs 16.3g, p=0.012) were higher than those without PAD. Results of multiple logistic regression analysis showed a significant association between PAD with high total fat intake, low intake of fiber from fruit and oleic acid, independently of other variables. Conclusions Despite limitations in examining the cause-effect relationship, the data support the notion that diet could be important in reducing the occurrence of PAD.