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Carotid intima-media thickness (cIMT) is considered a marker of subclinical atherosclerosis and is related to target-organ damage in hypertensive patients. However, increased cIMT may be due to increases in the thickness of intima (cIT) and media (cMT) layers. This study evaluated whether cIMT layers (cIT and cMT) had a greater association with carotid atherosclerotic plaques and left ventricular hypertrophy (LVH) than cIMT in hypertensive subjects. We cross-sectionally evaluated clinical, carotid, and echocardiography characteristics of 186 hypertensive patients followed at an outpatient clinic. High-resolution images of common carotid arteries were obtained by ultrasonography equipped with 10-MHz transducers, and cIT, cMT, and cIMT were manually measured using an image-processing software. Among all participants (n = 186; age = 60.8 ± 10.9 years, 43% males), there were 58% with carotid plaques and 58% with LVH. Mean cIT, cMT, and cIMT values were 0.267 ± 0.060, 0.475 ± 0.107, and 0.742 ± 0.142 mm, respectively. In logistic regression analysis adjusted for relevant covariates, carotid plaques showed stronger association with cIT than with cMT and cIMT. Furthermore, cIT showed greater area under the ROC curve (0.92; 95% CI 0.87-0.96) than cIMT (0.79; 95% CI 0.72-0.85) and cMT (0.64; 95% CI 0.56-0.72) to identify plaques. Conversely, cIT, cMT, and cIMT had modest association and accuracy to identify LVH (area under the ROC curve = 0.61, 0.57, and 0.60, respectively). In conclusion, cIT is a more accurate marker of atherosclerosis than cMT or cIMT, while cIT and cMT provide no incremental value in identifying LVH when compared with cIMT among hypertensive subjects.

Aims Despite of recent advances in the pharmacological treatment, heart failure (HF) maintains significant morbidity and mortality rates. While serum potassium disorders are common and associated with adverse outcomes, the exact recommended potassium level for patients with HF are not entirely established. We aimed to investigate the prognostic role of potassium levels on a cohort of patients with symptomatic chronic HF. Methods and results Patients with symptomatic chronic HF were identified at the referral to 6 min walking test (6MWT) and were prospectively followed up for cardiovascular events. Clinical and laboratorial data were retrospectively obtained. The primary endpoint was the composite of cardiovascular death, hospitalization due to HF, and heart transplantation. The cohort included 178 patients with HF with the mean age of 51 ± 12.76 years, 39% were female, 85% of non‐ischaemic cardiomyopathy, and 38% had New York Heart Association Class III with a relatively high Meta‐Analysis Global Group in Chronic Heart Failure (MAGGIC) score (12.91 ± 6.6). The mean left ventricular ejection fraction was 39.98 ± 15.79%, and the mean 6MWT distance was 353 ± 136 m. After a median follow‐up of 516 days, there were 22 major cardiovascular events (4 cardiovascular deaths, 13 HF admissions, and 5 heart transplants). Patients were stratified according to cut‐point level of serum potassium of 4.7 mmol/L to predict combined cardiac events based on receiver operating characteristic analysis. Individuals with higher potassium levels had worse renal function (glomerular filtration rate, K ≤ 4.7: 102.8 ± 32.2 mL/min/1.73 m2 vs. K > 4.7: 85.42 ± 36.2 mL/min/1.73 m2, P = 0.004), higher proportion of New York Heart Association Class III patients (K ≤ 4.7: 28% vs. K > 4.7: 48%, P = 0.0029), and also higher MAGGIC score (K ≤ 4.7: 12.08 ± 5.7 vs. K > 4.7: 14.9 ± 7.9, P = 0.0089), without significant differences on the baseline pharmacological HF treatment. Both potassium levels [hazard ratio (HR) 4.26, 95% confidence interval (CI) 1.59–11.421, P = 0.003] and 6MWT distance (HR 0.99, 95% CI 0.993–0.999, P = 0.01) were independently associated with the primary outcome. After adjustments for MAGGIC score and 6MWT distance, potassium levels > 4.7 mmol/L maintained a significant association with outcomes (HR 3.57, 95% CI 1.305–9.807, P = 0.013). Patients with K > 4.7 mmol/L were more likely to present clinical events during the follow‐up (log rank = 0.005). Adding potassium levels to the model including 6MWT and MAGGIC significantly improved the prediction of events over 2 years (integrated discrimination index 0.105, 95% CI 0.018–0.281, P = 0.012 and net reclassification index 0.447, 95% CI 0.077–0.703, P = 0.028). Conclusions Potassium levels were independently associated with worse outcomes in patients with chronic symptomatic HF, also improving the accuracy model for prognostic prediction when added to MAGGIC score and 6MWT distance. The potassium levels above 4.7 mmol/L might identify those patients at an increased risk of cardiovascular events.

RATIONALE, AIMS AND OBJECTIVES Emergency short-stay unit (SSU) alleviates emergency department (ED) overcrowding, but may affect in-hospital indicators. Cardiology patients comprise a substantial part of patients admitted at SSU. This study evaluated whether SSU opening differentially modified in-hospital indicators at a whole general hospital and at its cardiology division (CARD). METHODS We retrospectively analysed indicators based on 859 686 ED visits, and 171 547 hospital admissions, including 12 110 CARD admissions, from 2007 to 2018 at a general tertiary hospital, and compared global ED indicators and in-hospital indicators at the hospital and CARD before (2007-2011) and after (2011-2018) SSU opening. RESULTS After SSU opening, monthly ED bed occupancy rate decreased (mean ± SD 200 ± 18% vs 187 ± 22%; P

Disagreements in office brachial and central blood pressure (BP) have resulted in the identification of novel hypertension phenotypes, namely isolated central hypertension (ICH) and isolated brachial hypertension (IBH). This study investigated the relationship of ICH and IBH with ambulatory BP phenotypes among 753 individuals (mean age = 47.6 ± 15.2 years, 48% males) who underwent office and 24‐hours brachial and central BP measures using a Mobil‐O‐Graph PWA monitor. Thresholds for elevated office central and brachial BP were 130/90 and 140/90 mm Hg. Results of multivariable analysis adjusted for potential confounders showed that ICH (n = 25) had 3.71‐fold (95% CI 1.48‐9.32; P = .005) greater risk of masked hypertension than normal brachial/central BP (n = 362), while IBH (n = 20) had 4.65‐fold (95% CI 1.76‐12.25; P = .002) greater risk of white coat hypertension compared with combined brachial/central hypertension (n = 346). These findings suggest that the diagnosis of ICH and IBH might be useful in identifying individuals at higher risk of presenting discordant office and ambulatory BP phenotypes.

Assessment of central blood pressure (BP), pulse wave velocity (PWV), and augmentation index (AIx) measurements may improve cardiovascular risk stratification. This study aimed to establish reference office values for central BP, PWV, and AIx by means of a Mobil-O-Graph PWA monitor and to evaluate the impact of cardiovascular risk factors (CVRFs) on these measurements. We cross-sectionally evaluated clinical characteristics, central BP, PWV, AIx, and peripheral BP measurements among 867 apparently healthy individuals (age = 46.0 ± 15.5 years, 39% males) who were free of obesity, hypertension, active smoking, dyslipidemia, and diabetes (CVRF-No) and 5632 individuals (age = 57.0 ± 14.7 years, 44% males) with at least one of these major CVRFs (CVRF-Yes). Reference values for central BP, PWV, and AIx were provided for the CVRF-No and CVRF-Yes groups, stratified by age and sex. PWV and AIx exhibited curvilinear increases with age, and there was an interaction between age and sex for central systolic BP and PWV in both the CVRF-No and CVRF-Yes groups. The results of a multivariable analysis including the whole sample (n = 6499) showed that obesity had a direct association with central BP, while diabetes was directly related to PWV. In addition, alcohol intake was directly associated with central BP, while performance of physical activity was inversely related to AIx. In conclusion, values of office-measured central BP, PWV, and AIx obtained in an apparently healthy population and in a population with CVRFs are now available according to age and sex and may be useful to build thresholds for use in clinical practice.

Background and aims Osteoporosis and coronary heart disease (CHD) are very common conditions among elderly people, and both represent a public health concern due to their prognostic consequences. Osteoporosis and CHD share many risk factors and pathophysiological mechanisms, such as calcification pathways. Clinical evidence associates lower bone mass with cardiovascular diseases and endothelial dysfunction. Hence, this study aims to investigate whether bone mass density is associated with subclinical atherosclerosis and/or endothelial dysfunction in the very elderly. Methods We performed a cross-sectional study of cohort enrolled individuals, ages 80 years or older (n = 208), who had never manifested cardiovascular diseases. Medical evaluation, blood tests, flow-mediated dilation (FMD), carotid intimal-media thickness (IMT), Dual Energy X-ray Absorptiometry (DEXA) and Coronary Calcium Score (CCS) were obtained. Odds Ratio (OR) was calculated by multivariate logistic regression models using CCS, FMD and IMT categories. Adjustments for covariates were done. Results Overall bone mass was independently and inversely associated with CCS categories [OR:1.68(1.16–8.85); p = 0.024] and IMT categories [OR:2.97(1.11–7.90); p = 0.030]. Conversely, overall bone mass was independent and directly associated with FMD categories [OR:2.73(1.36–70.39); p = 0.023]. Conclusions This study indicates that overall bone mass is independently and inversely associated with subclinical atherosclerosis, endothelial dysfunction and thickness of carotid in the very elderly.

There are limited data on the effects of anthracyclines on right ventricular (RV) structure, function, and tissue characteristics. The goal of this study was to investigate the effects of anthracyclines on the RV using cardiac magnetic resonance (CMR). This was a post-hoc analysis of a prospective study of 27 breast cancer (BC) patients (51.8 ± 8.9 years) using CMR prior, and up to 3-times after anthracyclines (240 mg/m2) to measure RV volumes and mass, RV extracellular volume (ECV) and cardiomyocyte mass (CM). Before anthracyclines, LVEF (69.4 ± 3.6%) and RVEF (55.6 ± 9%) were normal. The median follow-up after anthracyclines was 399 days (IQR 310–517). The RVEF reached its nadir (46.3 ± 6.8%) after 9-months (P 2 and 8.13 ± 2 g/m2, respectively, at 16-months after anthracyclines. The RV ECV expanded from 0.26 ± 0.07 by 0.14 (53%) to 0.40 ± 0.1 (P P

Data on the association of blood pressure (BP) phenotypes with office and out-of-office markers of vascular stiffness and pressure wave reflection are sparse. This study investigated office and 24-h measures of brachial BP, pulse wave velocity (PWV), and central augmentation index (AIx) across hypertension phenotypes among individuals not using BP-lowering medications [normotension (NT), white-coat hypertension (WH), masked hypertension (MH) and sustained hypertension (SH)] and those using BP-lowering medications [controlled hypertension (CH), white-coat uncontrolled hypertension (WUCH), masked uncontrolled hypertension (MUCH) and sustained uncontrolled hypertension (SUCH)]. We evaluated 454 untreated (age = 45 ± 15 years, 50% males) and 238 treated (age = 52 ± 15 years, 45% males) individuals who underwent office and 24-h brachial BP, PWV, and AIx measures using a Mobil-O-Graph PWA monitor. In the analysis adjusted for age and sex, WH had higher (p < 0.05) office PWV (7.53 ± 0.09 vs 6.89 ± 0.05), office AIx (27.9 ± 1.3 vs 23.8 ± 0.8), and daytime AIx (24.6 ± 0.7 vs 22.7 ± 0.4) compared with those of NT, while WUCH had higher (p < 0.05) office PWV (8.28 ± 0.11 vs 7.43 ± 0.08) and 24-h PWV (7.54 ± 0.09 vs 7.21 ± 0.07) than those of CH. MH had higher (p < 0.05) 24-h PWV (7.00 ± 0.09 vs 6.69 ± 0.04) and 24-h AIx (24.3 ± 0.9 vs 21.9 ± 0.4) than those of NT, whereas MUCH had higher (p < 0.05) 24-h PWV (7.64 ± 0.13 vs 7.21 ± 0.07) than that of CH. Lastly, SH or SUCH had significantly higher office and 24-h PWV and AIx than those of NT and CH, respectively. In conclusion, these results suggest that individuals with masked BP phenotypes are more predisposed to have adverse out-of-office vascular characteristics, while individuals with white-coat phenotypes have adverse office and out-of-office vascular characteristics compared with those of individuals with normal BP levels.

The values used to define the presence of white-coat or masked blood pressure (BP) effects are arbitrary. The aim of this study was to investigate the accuracy of several cutoff points based on the difference between office and home BP (ΔBP) values to detect white-coat uncontrolled (WUCH) and masked uncontrolled (MUCH) hypertension, which are phenotypes with adverse prognoses, in a large cohort of treated hypertensive patients. This multicenter cross-sectional study included 6,049 treated hypertensive patients (40% males, mean age 59.1 ± 14.4 years) who underwent office and home BP monitoring. We compared the sensitivity, specificity, area under curve (AUC), and positive (PPV) and negative (NPV) predictive values of several ΔBP cutoffs to detect WUCH and MUCH. The 15/9 mmHg cutoff, which reflects a 1.0 standard deviation of the ΔBP, showed the best AUC (0.783, 95% CI = 0.772-0.794) for the detection of WUCH, particularly in individuals with office grade 1 hypertension (AUC = 0.811, 95% CI = 0.793-0.829). The -1/-1 mmHg cutoff, which considers all individuals who had lower systolic or diastolic BP levels in the office than at home, had the highest AUC (0.822, 95% CI = 0.808-0.836) for the detection of MUCH. Both cutoff values also had the best performances for identifying all patients with higher and lower office-than-home BP grades. In conclusion, the 15/9 and -1/-1 mmHg cutoffs showed the best performance for the detection of treated hypertensive patients with WUCH and MUCH, respectively, and therefore might be markers of significant white-coat and masked effects and could be useful for identifying preferential targets for more routine home BP measures.

Background Endothelial dysfunction (ED) is a hallmark in type 2 diabetes mellitus (T2DM) that favor both atherogenesis and ischemia and reperfusion injury (IRI). Sodium-glucose-2 co-transporter inhibitors (SGLT2i) may hypothetically improve microvascular and macrovascular functions via a broad spectrum of mechanisms, being superior to traditional antidiabetic therapy such as sulfonylurea, even in subjects under equivalent glycemic control. Hence, the present clinical trial was designed to compare the effect of these two treatments on markers of arterial wall function and inflammation in T2DM patients as well as on the potential mediating parameters. Method and results ADDENDA-BHS2 is a prospective, single-center, active‐controlled, open, randomized trial. Ninety-eight participants (40–70 years old) with HbA1c 7–9% were randomized (1:1, stratified by gender, BMI and HbA1c levels) to either dapagliflozin 10 mg/day or glibenclamide 5 mg/day on top of metformin. The primary endpoint was the change of flow-mediated dilation (FMD) after a 12-week period of treatment evaluated at rest and after IRI between dapagliflozin and glibenclamide arms. Secondary outcomes were defined as the difference between treatments regarding: plasma nitric oxide (NO) change after FMD, plasma isoprostane, plasma levels of vascular inflammatory markers and systemic inflammatory markers, plasma levels of adipokines, anthropometric measures, glucose control parameters, office and ambulatory BP control. Safety endpoints were defined as systolic and diastolic function assessed by echocardiography and retinopathy change. Serious adverse events were recorded. The study protocol was approved by the Independent Scientific Advisory Committee. Conclusion The ADDENDA-BHS2 trial is an investigator-initiated clinical trial comparing the effect of dapagliflozin versus glibenclamide on several aspects of vascular function in high cardiovascular risk T2DM patients. Besides, a large clinical and biochemical phenotype assessment will be obtained for exploring potential mediations and associations. Trial registration Clinical trial registration: NCT 02919345 (September, 2016)

Background Myocardial infarction (MI) elicits an intense acute inflammatory response that is essential for cardiac repair. However, an excessive inflammatory response also favors myocardial apoptosis, cardiac remodeling, and cardiovascular mortality. Omega-3 polyunsaturated fatty acids (ω-3) bear anti-inflammatory effects, which may mitigate the inflammatory response during MI. This study investigated whether ω-3 intake is associated with attenuation of the MI-related inflammatory response and cardiac remodeling. Methods ST-elevation MI (STEMI) patients (n = 421) underwent clinical, biochemical, nutritional, 3D echocardiogram, Cardiac Magnetic Resonance imaging (CMRi) at 30 days and 3D echocardiogram imaging at six months after the MI. Blood tests were performed at day one (D1) and day five (D5) of hospitalization. Changes in inflammatory markers (ΔD5-D1) were calculated. A validated food frequency questionnaire estimated the nutritional consumption and ω-3 intake in the last 3 months before admission. Results The intake of ω-3 below the median (

Coronary reperfusion with HDL from healthy volunteers attenuates ischemia and reperfusion injury in animal models. In myocardial infarction (MI) patients, such an interaction is unclear. Hence, our first objective was to verify if there is interaction between HDL-C and MI mass in patients and the role of coronary reperfusion in the interaction. Furthermore, we investigated whether the effect in MI size of reperfusion with HDL obtained from healthy participants or MI patients could differ.HDL-C was measured the first day after MI and MI mass was quantified by cardiac magnetic resonance (n = 94) and peak CKMB (n = 393). In an ex vivo rat heart model, we compared MI area and dP/dt max after coronary reperfusion with HDL from MI patients or healthy volunteers.HDL-C above the median (35 mg/dL) was associated with higher peak CKMB [255 (145-415) vs. 136 (84-287) UI/L; p = 0.02], higher MI mass [17 (9-21) vs. 10 (6-14) g; p0.01] and lower left ventricular ejection fraction [47 (34-53) vs. 51 (43-59); p = 0.02] than their counterparts. In restricted cubic spline and multivariate linear regression, HDL-C was directly associated with peak CKMB (p0.01) and MI mass (p0.01) only in reperfused patients with time to reperfusion4 h. Reperfusion with healthy HDL, but not from MI patients, reduced MI mass (p0.01) and improved dP/dt max (p = 0.02).In MI patients undergoing early coronary reperfusion, HDL-C levels at admission are directly associated with MI size. In contrast to healthy HDL, reperfusion with HDL from MI patients do not reduce MI area in an ex vivo animal model.

OBJECTIVE Smoking increases the risk of peripheral artery disease, but the mechanisms are not well established. This study evaluated the association of local circumferential wall tension (CWT), markers of vascular remodeling and stiffness, and traditional risk factors with popliteal and carotid plaques among smokers and nonsmokers. METHODS Two hundred fifty-two individuals (126 smokers and 126 nonsmokers) underwent clinical, laboratory, and popliteal and carotid ultrasound analysis. Popliteal and carotid CWT measures were calculated in supine and orthostatic positions, and supine position, respectively. RESULTS Popliteal plaques were more common in smokers than nonsmokers (39 vs. 19%; P

This study investigated the impact of changing abnormal home blood pressure monitoring (HBPM) cutoff from 135/85 to 130/80 mmHg on the prevalence of hypertension phenotypes, considering an abnormal office blood pressure cutoff of 140/90 mmHg. We evaluated 57 768 individuals (26 876 untreated and 30 892 treated with antihypertensive medications) from 719 Brazilian centers who performed HBPM. Changing the HBPM cutoff was associated with increases in masked (from 10% to 22%) and sustained (from 27% to 35%) hypertension, and decreases in white‐coat hypertension (from 16% to 7%) and normotension (from 47% to 36%) among untreated participants, and increases in masked (from 11% to 22%) and sustained (from 29% to 36%) uncontrolled hypertension, and decreases in white‐coat uncontrolled hypertension (from 15% to 8%) and controlled hypertension (from 45% to 34%) among treated participants. In conclusion, adoption of an abnormal HBPM cutoff of 130/80 mmHg markedly increased the prevalence of out‐of‐office hypertension and uncontrolled hypertension phenotypes., Several studies published in last decade have suggested that abnormal home blood pressure monitoring (HBPM) levels should be considered when ≥130/80 mmHg rather than ≥135/85 mmHg. Shifting the HBPM cutoff from 135/85 to 130/80 mmHg and keeping the office abnormal cutoff at 140/90 mmHg led to a twofold increase in the prevalence of masked hypertension phenotypes, an approximate 50% decrease in the prevalence of white‐coat hypertension phenotypes, and increased the detection of sustained hypertension phenotypes and decreased the detection of normotension and controlled hypertension.

Background This study compared left ventricular (LV) characteristics between patients with type‐A and type‐B aortic dissection (AD) and evaluated the ability of LV remodeling phenotypes (hypertrophy, concentricity, or geometric patterns) to predict mortality in both AD types. Methods and Results We evaluated 236 patients with type A and 120 patients with type B who had echocardiograms within 60 days before or after AD diagnosis (median [25th, 75th percentiles] time difference between echocardiogram and AD diagnosis=1 [0, 6] days) from 3 centers. Patients were stratified according to LV phenotypes, and early (90‐day) and late (1‐year) mortality after AD diagnosis were assessed. In adjusted logistic regression analysis, patients with type A had higher and lower odds of concentric and eccentric hypertrophy (odds ratio [OR], 2.56; 95% CI, 1.50–4.36; P P =0.039, respectively) than those with type B. Results of multivariable Cox‐regression analysis showed that LV remodeling phenotypes were not related to mortality in patients with type B. By contrast, LV concentricity was associated with greater early and late mortality (hazard ratio [HR], 2.22; 95% CI, 1.24–3.96; P =0.007 and HR, 2.06; 95% CI, 1.20–3.54; P =0.009, respectively) in type A. In further analysis considering normal LV geometry as reference, LV concentric remodeling and concentric hypertrophy were associated with early mortality (HR, 7.78; 95% CI, 2.35–25.78; P P =0.008, respectively), whereas concentric remodeling was associated with late mortality (HR, 5.40; 95% CI, 1.91–15.26; P Conclusions LV geometric patterns derived from LV concentricity were associated with greater mortality among patients with type A and may be markers of adverse prognosis in this population.

Introduction: There are limited data characterizing the effect of anthracyclines on right ventricular (RV) structure and function. Hypothesis: The goal of this study was to test the effect of anthracyclines on RV myocardial remodeling using cardiac magnetic resonance (CMR). Methods: This was a prospective CMR and serum biomarker study of 27 women with breast cancer (BC) (51.8±8.9 years) who underwent a CMR prior, and up to 3-times after anthracycline therapy (240 mg/m 2 ). The primary measure of interest was the RV extracellular volume (ECV) and cardiomyocyte mass index (1-ECV). Additional measures of interest were the left ventricular (LV) ECV, and the LV and RV mass. Biomarkers included high-sensitive troponin T, and creatinine-kinase MB isoenzyme (CKMB). Results: Before anthracyclines, all subjects had normal LV ejection fraction (EF) (69.4±3.6%) and RVEF (55.6±9%). At 351-700 days after anthracyclines, the LVEF and LV mass index declined to 58±6% (P2 (P2 at (350-700] days (P Conclusions: In a prospective observational study among women with breast cancer, anthracyclines were associated with a decrease in the RV EF, an increase in the RV ECV and a decrease in the RV cardiomyocyte mass.

Introduction Intimal thickening is a characteristic and initial step of atherosclerosis. Carotid intima-media thickness (IMT) is considered a measure of subclinical atherosclerosis, but it can be influenced by increases not only of intima layer thickness (IT), but also of media layer thickness (MT). Hypertension is a risk factor for atherosclerosis, but may also stimulate media layer hypertrophy by increasing artery wall tension. However, little is known regarding the measures of carotid wall sublayers and their association with atherosclerosis in hypertensive subjects. Purpose To measure carotid IMT, MT and IT and evaluate their relationship with carotid atherosclerotic plaques in hypertensive subjects. Methods This cross-sectional study evaluated clinical and carotid characteristics of 186 hypertensive patients (age = 61±11 years, 43% men, BMI = 30.6±6.2 kg/m2) followed at a university outpatient clinic. High-resolution images of common carotid arteries wall and plaques were obtained by ultrasonography equipped with 10MHz-13MHz transducers. IMT, MT and IT were measured using an image processing software. Results Mean IT, MT and IMT values were 0.267±0.060, 0.475±0.107 and 0.742±0.142 mm, respectively. IMT showed stronger correlation with MT (r=0.92; p Conclusions MT is the main determinant of carotid IMT in hypertensive subjects. Conversely, IT showed stronger correlation and greater discriminatory value to identify atherosclerotic plaques than MT and IMT. These findings suggest that carotid IT may be a more accurate marker of atherosclerosis that MT or IMT in hypertensive subjects. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): CNPq

Background: Although there is strong evidence supporting the use of statin therapy after myocardial infarction (MI), some mechanistic gaps exist regarding the benefits of this therapy at the very onset of MI. Among the potential beneficial mechanisms, statins may improve myocardial electrical stability and reduce life-threatening ventricular arrhythmia, as reported in stable clinical conditions. This study was designed to evaluate whether this mechanism could also occur during the acute phase of MI. Methods: Consecutive patients with ST-segment elevation MI were treated without statin (n = 57) or with a simvastatin dose of 20 to 80 mg (n = 87) within the first 24 hours after MI symptom onset. Patients underwent digital electrocardiography within the first 24 hours and at the third and fifth days after MI. The QTC dispersion (QTcD) was measured both with and without the U waves. Results: Although QTcD values were equivalent between the groups at the first day (80.6 ± 36.0 vs 80.0 ± 32.1; P = 0.36), they were shorter among individuals using simvastatin than in those receiving no statins on the third (90.4 ± 38.6 vs 86.5 ± 36.9; P = .036) and fifth days (73.1 ± 31 vs 69.2 ± 32.6; P = .049). We obtained similar results when analyzing the QTcD duration including the U wave. All values were adjusted by an ANCOVA model after propensity-score matching. Conclusions: Statins administered within 24 hours of ST-segment elevation MI reduced QTc dispersion, which may potentially attenuate the substrate for life-threatening ventricular arrhythmias.

Although stress hyperglycemia after myocardial infarction (MI) is consistently associated with increased mortality, recent studies suggest that the addition of upstream markers of glucose metabolism may improve risk identification. Hence, our aim was to evaluate the association between insulin sensitivity changes during MI hospitalization and outcomes.A prospective cohort of 331 consecutive ST-Elevation MI (STEMI) patients without insulin provision therapy was used for the analyses. Blood samples were collected upon admission (D1) and after 5days (D5) of the inciting event. We measured blood glucose and insulin to estimate insulin sensitivity using the updated Homeostasis Model Assessment (HOMA2S). Patients were assessed for intra-hospital death and major adverse cardiac events (MACE) during follow-up.HOMA2S was 62%±52% on D1 and 86%±57% on D5 (p0.001). Total follow-up was a median of 2 (0.9-2.8) years and found a U-shaped relation between the change in HOMA2S from D1 to D5 (ΔHOMA2S) and major adverse cardiac events (MACE) (p=0.017). Fully adjusted cox-regression models showed that patients from T1 and T3 were about 2.5 times more prone to suffer from MACE than those in T2. Net Reclassification Index adding ΔHOMA2S as a categorical variable dichotomized as T2 and T1 or T3 to a model of GRACE risk score with glucose D1 yielded a better predictive model (0.184 [95% CI 0.124-0.264]; p=0.032).A U-shaped curve describes the relation between insulin sensitivity change and MACE during acute phase STEMI and, thus indicating that acute dysglycemia must be appreciated in light of a time spectrum and insulin levels.

Background The combinations of adipokines and body mass parameters to estimate carotid atherosclerotic disease have not been completely delineated. Objective To test the combinations of well-established, easily accessible body mass indices and circulating biomarkers to identify increased carotid intima-media thickness (cIMT) in a primary prevention setting. Design and patients In a cross-sectional analysis of 339 asymptomatic individuals with no history of cardiovascular events, inflammatory and insulin sensitivity biomarkers as well as adipokine levels were measured and combined with body mass parameters to evaluate the best marker for increased cIMT. Results As isolated parameters, body mass index (BMI) and adiponectin best identified abnormal cIMT (P = .04). Adiponectin levels were also linked to the relationship between BMI and cIMT (β = 0.0371; P = .01). Twenty-nine individuals with increased cIMT were missed by BMI alone but detected by combining BMI and adiponectin measurements. When compared with BMI alone, the combination of adiponectin plus BMI improved the c-statistic (0.549-0.567) and the integrated discrimination improvement index (0.01725; P = .021). Segregation of individuals by the combined use of BMI + adiponectin is associated with significant differences in insulin sensitivity, glomerular filtration rate, systemic inflammatory activity, dyslipidaemia and cIMT. Conclusions Combining plasma adiponectin measurements and BMI improves estimation of cIMT as compared to anthropometric parameters.

Background and aims Excess weight is a widespread condition related to increased risk of coronary heart disease (CHD). Sarcopenia is a catabolic pathway common of the aging process and also associated with CHD. In the elderly, both changes occur concurrently and it remains unclear the relative contribution on CHD risk. We aimed to investigate whether sarcopenia, excess weight, or both are associated with subclinical atherosclerosis and/or endothelial dysfunction in very elderly individuals. Methods We performed a cross-sectional study of cohort enrolled individuals, aged 80 years or older (n = 208), who had never manifested cardiovascular diseases. Blood tests, medical and nutritional evaluations, cardiac computed tomography, flow-mediated dilation (FMD) and physical performance tests were obtained at the study admission. Odds ratio (OR) was calculated by multivariate regression models using coronary calcium score (CCS) categories and FMD as dependent variables. Adjustment for potential confounders was done. Results Muscle mass, but not fatty mass, was inversely associated with CCS categories [OR:2.54(1.06–6.06); p = 0.018]. The lowering of gait speed was negatively related to CCS>100 [OR:2.36 (1.10–5.06); p = 0.028] and skeletal muscle index was directly associated with FMD [OR:5.44 (1.22–24.24); p = 0.026]. Total caloric intake was positively related to fatty mass [OR:2.71 (1.09–6.72); p = 0.031], but was not related to CCS. Conclusions This study reveals that sarcopenia - comprised by reduction of muscle mass and its strength - is associated with subclinical atherosclerosis and endothelial dysfunction. Surprisingly, the excess of fatty mass seems not to be related to atherosclerotic burden in very elderly individuals.

Background The expression and activity of neuronal nitric oxide sintetase (nNOS) in central and peripheral nervous system attenuate the sympathetic response and promote other cardioprotective effects in animal models. However, in humans those effects are uncertain. Recently, a polymorphism at the sequence rs41279104 G/T has been associated with a reduced expression of nNOS, but its clinical impact has never been studied in the context of ST elevation myocardial infarction (STEMI) in humans. Purpose We investigated the impact of the T allele at rs41279104 in sympathetic activation after STEMI and its influence in the incidence of recurrent major cardiovascular events (MACE). We sought to determine a pathway to autonomic nervous system modulation during STEMI and its possible clinical impact. Methods 297 patients were admitted in the first 24h (D1) after STEMI and followed prospectively. Blood samples and an electrocardiogram were obtained upon D1 and fifth day (D5). We assessed glycosylated hemoglobin, glucose, insulin, C-peptide, lipid profile and nitric oxide (NOx) plasma levels. We genotyped rs41279104 and grouped patients according to carrier status (GT+TT vs. GG). The heart rate variability was obtained with a 15min electrocardiogram recording and processed into spectral analysis variables including low (LF) and high frequencies (HF) and LF/HF ratio. Flow-mediated dilation (FMD) was performed after 30 days. Clinical follow–up was carried over until two years after MI and the endpoint was a composite of major cardiovascular events (MACE) consisting of fatal MI, non-fatal MI, unstable angina with hospitalization and cardiac sudden death. Results T-allele carriers showed a decreased parasympathetic activity and an increased sympathetic activity between D1 and D5 (ΔLF −68.43 (median) [IQR −324.76 to −6.29] vs −4.49 [−190.29 to 72.03], p Conclusions The presence of the T allele at nNOS gene rs41279104 sequence is associated with increased sympathetic tone at acute phase of STEMI and a higher incidence of recurrent MACE.

Background:Studies have shown significant benefits of exercise therapy in heart failure (HF) with a reduced ejection fraction (HFrEF) and HF with a preserved ejection fraction (HFpEF). The mechanisms responsible for the beneficial effect of exercise in HFrEF and HFpEF are still unclear. We hypothesized that the effect of exercise on myocardial remodeling may explain its beneficial effect.Methods:IMAGING-REHAB-HF is a single-center, randomized, controlled clinical trial using cardiac magnetic resonance imaging, vasomotor endothelial function, cardiac sympathetic activity imaging and serum biomarkers to compare the effect of exercise therapy in HFpEF (LVEF ≥ 45%) and HFrEF (LVEF < 45%). Subjects will be assessed at baseline and after 4 months. The exercise program will consist of three 60-min exercise sessions/week. The primary endpoints are the effect of exercise on myocardial extracellular volume (ECV), left ventricular (LV) systolic function, LV mass, LV mass-to-volume and LV cardiomyocyte volume. Secondary endpoints include the effect of exercise on vasomotor endothelial function, cardiac sympathetic activity and plasmatic biomarkers. Patients will be allocated in a 2:1 fashion to supervised exercise program or usual care. A total sample size of 90 patients, divided into two groups according to LVEF:HFpEF group (45 patients:30 in the intervention arm and 15 in the control arm) and HFrEF group (45 patients:30 in the intervention arm and 15 in the control arm) – will be necessary to achieve adequate power.Conclusion:This will be the first study to evaluate the benefits of a rehabilitation program on cardiac remodeling in HF patients. The unique design of our study may provide unique data to further elucidate the mechanisms involved in reverse cardiac remodeling after exercise in HFpEF and HFrEF patients.

International audience; It is now apparent that a variety of deleterious mechanisms intrinsic to myocardial infarction (MI) exists and underlies its high residual lethality. Indeed, despite effective coronary patency therapies, ischemia and reperfusion (I/R) injury accounts for about 50% of the infarcted mass. In this context, recent studies in animal models have demonstrated that coronary reperfusion with high-density lipoproteins (HDL) may reduce MI size in up to 30%. A spectrum of mechanisms mediated by either HDL-related apolipoproteins or phospholipids attenuates myocardial cell death. Hence, promising therapeutic approaches such as infusion of reconstituted HDL particles, new HDL by genomic therapy, or the infusion of apoA-I mimetic peptides have been sought as a way of ensuring protection against I/R injury. In this review, we will explore the limitations and potential therapeutic effects of HDL therapies during the acute phase of MI.

Hyperglycemia during myocardial infarction (MI) has a strong and direct association with mortality. In stable patients and experimental models, statins favor the elevation of glycaemia. The present study investigated whether short-course treatment with statins during MI can influence glucose homeostasis and thus the clinical outcome. In this prospective study, euglycemic hyperinsulinemic clamp (EHC) was performed at second (D2) and sixth (D6) day after MI in patients randomized to simvastatin (S)10 or 80 mg/day during hospitalization (n = 27). In addition, patients (n = 550) were treated without (WS) or with simvastatin (S) at 20, 40 or 80 mg/day had HOMA2S on admission (D1) and fifth (D5) day after MI. According to EHC, insulin sensitivity increased by 20 ± 60% in S10 and decreased by −6 ± 28% in S80 (p = 0.025). Consistently, the changes in HOMA2S between D1 and D5 were 40 ± 145% (WS), 22 ± 117% (S20), 16 ± 61% (S40) and −2% ± 88% (S80) (p = 0.001). In conclusion, statin during the acute phase of MI reduces insulin sensitivity in a dose-dependent manner.

Objective To determine whether regular performance of adapted sports is associated with long-term changes in carotid atherosclerosis in subjects with spinal cord injury (SCI). Design Prospective observational study. Setting Academic medical center. Participants Men with chronic (>1y) SCI and no preserved motor function below the injury level were evaluated in 2007 and 2012 (N=17). Nine subjects did not perform physical activity between the studied time points (control group), whereas 8 subjects entered competitive upper-body sports programs (rugby: n=5, basketball: n=1, jiu-jitsu: n=1, and tennis: n=1) after baseline and were regularly training at the time of the second evaluation (sports group). Interventions Not applicable. Main Outcome Measures Clinical, laboratory, hemodynamic, and carotid ultrasonography analysis. Results The studied groups showed no differences in all studied variables at baseline. After 5 years of follow-up, the control group showed increases in heart rate (87.0±3.1 vs 74.7±3.8 beats per minute; P =.004), but the participants had no significant changes in carotid intima-media thickness (IMT) (.65±.05 vs .67±.03mm; P =.73) or IMT/diameter (.118±.007 vs .136±.013; P =.24). In contrast, the sports group showed long-term decreases in carotid IMT (.56±.05 vs .74±.05mm; P =.001) and IMT/diameter (.097±.006 vs .141±.009; P Conclusions Regular upper-body sports activities are associated with long-term reductions in carotid atherosclerosis in subjects with SCI and might be a potential prevention strategy aiming to reduce cardiovascular risk in this population.

AIM/BACKGROUND Abundant evidence shows that coronary artery calcification (CAC) is a strong marker of structural and functional changes within the artery wall. Thus far, the implications of CAC in patients with acute coronary syndromes remain unclear. We aimed to investigate whether the CAC score is associated with impaired reperfusion during the acute phase of ST-elevation myocardial infarction (STEMI). METHODS We enrolled 60 consecutive STEMI patients to undergo cardiac computed tomography for assessment of the CAC score within 1 week after STEMI. Coronary thrombus burden, coronary blood flow (TIMI flow), and myocardial blush grade (MBG) were evaluated systematically. Patients with maximal TIMI flow and MBG were grouped as optimal reperfusion (n=27) and their counterparts as no-reflow (NR, n=33). RESULTS There were no differences in the clinical characteristics between groups. Patients in the NR group had higher heart rate, coronary angiographic severity, and CAC score. CAC score greater than 100 was associated independently with the presence of NR (odds ratio 4.4, 95% confidence interval 1.17-16.3). The CAC score of nonculprit coronary arteries was higher in NR individuals than in their counterparts (P=0.04). In addition, the CAC score of the isnfarct-related artery correlated negatively with the TIMI-flow rate (r=-0.54, P

Objective: In ST-elevation myocardial infarction, 7–15% of patients admitted as Killip I will develop symptomatic heart failure or decreased ejection fraction. However, available clinical scores do not predict the risk of severe outcomes well, such as heart failure, recurrent myocardial infarction, and sudden death in these Killip I individuals. Therefore, we evaluated whether one vs two measurements of BNP would improve prediction of adverse outcomes in addition to the GRACE score in ST-elevation myocardial infarction/Killip I individuals. Methods: Consecutive patients with ST-elevation myocardial infarction/Killip I ( n=167) were admitted and followed for 12 months. The GRACE score was calculated and plasma BNP levels were obtained in the first 12 h after symptom onset (D1) and at the fifth day (D5). Results: Fifteen percent of patients admitted as Killip I developed symptomatic heart failure and/or decreased ejection fraction in 12 months. The risk of developing symptomatic heart failure or ejection fraction Conclusions: Only BNP-change following myocardial infarction was associated with poorer short- and long-term outcomes. BNP-change also improves risk reclassification in addition to the GRACE score.

The occlusion of a coronary artery by a thrombus generated on a ruptured atherosclerotic plaque has been pursued in the last decades as a determining event for the clinical outcome after myocardial infarction (MI). Yet, MI causes a cell death wave front, which triggers an inflammatory response to clear cellular debris, and which in excess can double the myocardial lesion and influence the clinical prognosis in the short and long term. Accordingly, proper, timely regulated inflammatory response has now been considered a second pivotal player in cardiac recovery after MI justifying the search for pharmacological strategies to modulate inflammatory effectors. This chapter reviews the key events and the main effectors of inflammation after myocardial ischemic insult, as well as the contribution of this phenomenon to the progression of atherosclerosis.

OBJECTIVE The aim of this study was to evaluate the performance of common carotid artery diameter, flow velocity and flow velocity/artery diameter ratio as predictors of major adverse cardiovascular events (MACEs) in a sample of hypertensive patients. METHODS A cohort of 403 hypertensive patients was followed up for a median of 1260 (714) days, and 27 suffered MACEs. At baseline, participants were evaluated by clinical, laboratory, echocardiographic and carotid ultrasound analysis. RESULTS Patients with peak-systolic flow velocity (sFV) less than the median value and systolic artery diameter (sAD) greater than the median value presented the worst clinical outcome compared to those with isolated sFV less than the median value or sAD greater than the median value, suggesting an additive effect of these two variables. Further, Kaplan-Meier analysis demonstrated worse outcome for individuals with sFV/sAD ratio less than 85.7/s (optimal cut-off point obtained by receiver-operating characteristic analysis) compared to those with higher sFV/sAD values (log-rank test: P

Hypertensive patients are predisposed to left ventricular (LV) remodeling and frequently exhibit decline in lung function as compared with the general population. Here, we investigated the association between spirometric and echocardiographic data in non-smoking hypertensive subjects and the role of gender in this regard. In a cross-sectional study, 107 hypertensive patients (60 women) enrolled from a university outpatient clinic were evaluated by clinical, hemodynamic, laboratory and echocardiographic analysis. Vital capacity, forced vital capacity (FVC), forced expired volume in 1 s (FEV1) and in 6 s (FEV6), FEV1/FVC ratio and FEV1/FEV6 ratio were estimated by spirometry. In women, higher LV mass index and E/Em ratio correlated with markers of restrictive lung alterations, such as reduced FVC (r=−044; P

Objectives The goal of this study was to demonstrate that cardiac magnetic resonance could reveal anthracycline-induced early tissue remodeling and its relation to cardiac dysfunction and left ventricular (LV) atrophy. Background Serum biomarkers of cardiac dysfunction, although elevated after chemotherapy, lack specificity for the mechanism of myocardial tissue alterations. Methods A total of 27 women with breast cancer (mean age 51.8 ± 8.9 years, mean body mass index 26.9 ± 3.6 kg/m2), underwent cardiac magnetic resonance before and up to 3 times after anthracycline therapy. Cardiac magnetic resonance variables were LV ejection fraction, normalized T2-weighted signal intensity for myocardial edema, extracellular volume (ECV), LV cardiomyocyte mass, intracellular water lifetime (τic; a marker of cardiomyocyte size), and late gadolinium enhancement. Results At baseline, patients had a relatively low (10-year) Framingham cardiovascular event risk (median 5%), normal LV ejection fractions (mean 69.4 ± 3.6%), and normal LV mass index (51.4 ± 8.0 g/m2), a mean ECV of 0.32 ± 0.038, mean τic of 169 ± 69 ms, and no late gadolinium enhancement. At 351 to 700 days after anthracycline therapy (240 mg/m2), mean LV ejection fraction had declined by 12% to 58 ± 6% (p 10 pg/ml. There was no evidence for any significant interaction between 10-year cardiovascular event risk and the effect of anthracycline therapy. Conclusions A decrease in LV mass after anthracycline therapy may result from cardiomyocyte atrophy, demonstrating that mechanisms other than interstitial fibrosis and edema can raise ECV. The loss of LV cardiomyocyte mass increased with the degree of cardiomyocyte injury, assessed by peak cardiac troponin T after anthracycline treatment. (Doxorubicin-Associated Cardiac Remodeling Followed by CMR in Breast Cancer Patients; NCT03000036)

Summary Part I - Diagnosis and risk stratification page 1 1. Introduction page 1 2. Diagnosis page 12.a. Diagnosis of subclinical coronary artery disease (CAD) page 1 2.a.1. Diagnosis in symptomatic patients page 12.b. Diagnosis of manifest CAD page 2 2.b.1. History, physical examination, differential diagnosis page 2

Although low-density lipoprotein cholesterol (LDL-C) has been consistently demonstrated a predictor of atherosclerotic disease in a large spectrum of clinical settings, among individuals aged of 80 years or older this concept is uncertain. This study was evaluated in a carefully selected population if the association between LDL-C and coronary atherosclerotic burden remains significant in the very elderly. Individuals aged of 80 years or older (n = 208) who spontaneously sought primary prevention care and have never manifested cardiovascular disease, malnutrition, neoplastic or consumptive disease were enrolled for a cross-sectional analysis. Medical evaluation, anthropometric measurements, blood tests and cardiac computed tomography were obtained. In analyses adjusted for age, gender, diabetes, systolic and diastolic blood pressure, smoking and statin therapy, no association was found between coronary calcium score (CCS) and LDL-C [1.79 (0.75–4.29)]. There was no association between triglycerides and CCS. The association between high-density lipoprotein cholesterol (HDL-C) and CCS was significant and robust in unadjusted [0.32 (0.15–0.67)] as well as in the fully adjusted analysis [0.34 (0.15–0.75)]. The present study confirms in a healthy cohort of individuals aged of 80 years or more that while the association between LDL-C and coronary atherosclerosis weakens with aging, the opposite occurs with the levels of HDL-C.

Purpose Therapeutic strategies that modulate ventricular remodeling can be useful after acute myocardial infarction (MI). In particular, statins may exert effects on molecular pathways involved in collagen metabolism. The aim of this study was to determine whether treatment with atorvastatin for 4 weeks would lead to changes in collagen metabolism and ventricular remodeling in a rat model of MI. Methods Male Wistar rats were used in this study. MI was induced in rats by ligation of the left anterior descending coronary artery (LAD). Animals were randomized into three groups, according to treatment: sham surgery without LAD ligation (sham group, n = 14), LAD ligation followed by 10mg atorvastatin/kg/day for 4 weeks (atorvastatin group, n = 24), or LAD ligation followed by saline solution for 4 weeks (control group, n = 27). After 4 weeks, hemodynamic characteristics were obtained by a pressure-volume catheter. Hearts were removed, and the left ventricles were subjected to histologic analysis of the extents of fibrosis and collagen deposition, as well as the myocyte cross-sectional area. Expression levels of mediators involved in collagen metabolism and inflammation were also assessed. Results End-diastolic volume, fibrotic content, and myocyte cross-sectional area were significantly reduced in the atorvastatin compared to the control group. Atorvastatin modulated expression levels of proteins related to collagen metabolism, including MMP1, TIMP1, COL I, PCPE, and SPARC, in remote infarct regions. Atorvastatin had anti-inflammatory effects, as indicated by lower expression levels of TLR4, IL-1, and NF-kB p50. Conclusion Treatment with atorvastatin for 4 weeks was able to attenuate ventricular dysfunction, fibrosis, and left ventricular hypertrophy after MI in rats, perhaps in part through effects on collagen metabolism and inflammation. Atorvastatin may be useful for limiting ventricular remodeling after myocardial ischemic events.

Radiation therapy (RT) that involves the cardiac silhouette is associated with a 9-fold increase in incident heart failure (HF) among women with breast cancer (BC). Pathologically, RT-induced cardiotoxicity leads to myocardial fibrosis, atrophy and a reduction in cardiomyocyte mass; cardiac magnetic

BACKGROUND Aortic stiffness is associated with increased cardiovascular mortality. However, the determinants of aortic stiffness progression are not fully established. This study evaluated the predictive value of blood pressure (BP) response to cold pressor test (CPT) in the progression of carotid-femoral pulse wave velocity (PWV) in men and women. METHODS A total of 408 individuals (165 men, 243 women) from Vitoria, Brazil, underwent BP evaluation, clinical and laboratorial investigations, and CPT and PWV assessment. Five years later, the studied individuals were re-evaluated, except for the CPT. RESULTS In men, 5-year PWV change correlated inversely with baseline PWV (P < 0.001) and directly with BP response to CPT (P < 0.05) and 5-year BP change (P < 0.05). In women, 5-year PWV change correlated inversely with baseline PWV (P < 0.001) and directly with age (P < 0.01), glycemia (P < 0.05) and 5-year BP change (P < 0.05) but not with BP response to CPT. Further linear regression analysis showed that 5-year PWV change was associated with baseline PWV, systolic BP response to CPT, and 5-year systolic BP change in men and with baseline PWV, age, glycemia, and 5-year systolic BP change in women. CONCLUSIONS BP response to CPT was a predictor of PWV progression in men after 5 years of follow-up. These findings provide further insights into the pathophysiologic mechanisms of arterial stiffness, suggesting that elevated sympathetic reactivity may be a predisposing factor for future increases in aortic stiffness, at least in men.

ObjectiveDiastolic dysfunction (DD) is a frequent condition in hypertensive patients whose presence increases mortality and whose treatment remains unclear. The aim of this study was to investigate in a prospective, double-blinded, placebo-controlled randomized design the additive effect of simvastatin on DD in enalapril-treated hypertensive patients with average cholesterol levels.MethodsHypertensive patients with DD and LDL-cholesterol

ObjectiveEnhanced sodium intake increases volume overload, oxidative stress and production of proinflammatory cytokines. In animal models, increased sodium intake favours ventricular dysfunction after myocardial infarction (MI). The aim of this study was to investigate, in human subjects presenting with ST-segment elevation MI (STEMI), the impact of sodium intake prior the coronary event.MethodsConsecutive patients (n=372) admitted within the first 24h of STEMI were classified by a food intake questionnaire as having a chronic daily intake of sodium higher (HS) or lower (LS) than 1.2g in the last 90 days before MI. Plasma levels of 8-isoprostane, interleucin-2 (IL-2), tumour necrosis factor type α (TNF-α), C-reactive protein (CRP) and brain natriuretic peptide (BNP) were measured at admission and at the fifth day. Magnetic resonance imaging was performed immediately after discharge. Total mortality and recurrence of acute coronary events were investigated over 4 years of follow-up.ResultsThe decrease of 8-isoprostane was more prominent and the increase of IL-2, TNF-α and CRP less intense during the first 5 days in LS than in HS patients (p

To investigate the relationship of carotid artery intima-media thickness (IMT) and cardiac structure and function with adipocytokines in sedentary (S-SCI) and physically active (PA-SCI) subjects with spinal cord injury (SCI).Cross-sectional observational study.Academic medical center.Men with chronic (1y) SCI (N=41; 16 S-SCI, 25 PA-SCI) were evaluated. S-SCI subjects did not perform labor that required physical effort, recreational physical activity, or sports, while PA-SCI subjects included competing athletes who were regularly performing adapted sports.Not applicable.Clinical, laboratory, carotid ultrasonography, and echocardiography analysis. Plasma leptin, adiponectin, and plasminogen activating inhibitor-1 (PAI-1) levels were determined.PA-SCI subjects had similar levels of adipocytokines, but lower carotid IMT and carotid IMT/diameter, and better left ventricular diastolic function than S-SCI participants. Bivariate analysis showed that adiponectin was inversely correlated with triglycerides (r=-.85, P.001), low-density lipoprotein cholesterol (r=-.57, P.05), and carotid IMT/diameter (r=-.56, P.05) in S-SCI but not in PA-SCI participants. Additionally, the leptin-adiponectin ratio showed a direct correlation with triglycerides (r=.84, P.001) and low-density lipoprotein cholesterol (r=.53, P.05) in S-SCI but not in PA-SCI individuals. By contrast, the studied adipocytokines did not correlate with cardiac structure and function in PA-SCI and S-SCI participants.Lower adiponectin levels and higher leptin-adiponectin ratio are related to adverse vascular and/or metabolic characteristics in individuals with SCI. This relationship, however, appears to be mitigated by regular physical activity.

Endothelial dysfunction embodies roles of precursor and perpetuator of systemic atherosclerotic disease. Identifying and quantifying its impact would therefore provide insight on the genesis of atherosclerosis initiation and progression. However, endothelial dysfunction comprises a broad spectrum of impaired functionsdranging from vascular tone regulation to plaque stabilizing propertiesdand available clinical methods effectively estimate only singular aspects of the underlying condition. Functionally, vasomotor regulation reflects endothelial function and its regulation occurs at the macrovascular [1] and microvascular [2] levels. Substantial evidence indicates that impairment in vasomotor function signalizes subsequent atherosclerotic disease [3e5] and recurrence of cardiovascular events [6,7]. However, this discriminator is not an effective surrogate indicator in all populations [2,8]. Some studies suggest that microvascular dysfunction predicts risk more reliably in healthier and younger populations as opposed to patients with established systemic, macrovascular atherosclerosis [9]. Flow mediated dilation methods (FMD) provide a surrogate endpoint to evaluate the potential dilatatory response of a conduit (macrovascular) artery stimulated by reactive hyperemia. This observed response generally mimics the increase in myocardial blood flow to accommodate local metabolic demands, known as coronary flow reserve [10,11]. Arterial flow and vessel wall shear stress variables (stimulus for FMD) are not traditionally assessed