Exercise training improves cardiopulmonary and endothelial function in women with breast cancer: findings from the Diana-5 dietary intervention study

To investigate whether exercise training (ET) improves cardiopulmonary and endothelial function in women with breast cancer (BC). Fifty-one female patients (aged between 39 and 72 years) with a history of primary invasive BC within the previous 5 years and enrolled in the Mediterranean diet-based DIANA (diet and androgens)-5 Trial were subdivided into 2 groups: an ET group (n = 25) followed a formal ET program of moderate intensity (3 session/week on a bicycle at 60–70 % VO₂peak for 3 months, followed by one session/week until 1-year follow-up), while a control group (n = 26) did not perform any formal ET. At baseline and at 1-year follow-up, all patients underwent cardiopulmonary exercise stress test (CPET) and measurements of vascular endothelial function by peripheral artery tonometry (Reactive Hyperemia Index, RHI). There were no significant differences between the groups in baseline anthropometrical, BC characteristics, and metabolic profile. No differences in baseline CPET and RHI parameters were found. Peak oxygen consumption (VO₂peak) significantly increased in ET group (from 12.4 ± 2.9 to 14.3 ± 3.3 mL/kg/min, p < 0.001) compared to the control group (from 12.8 ± 2.5 to 12.6 ± 2.8 mL/kg/min, p = 0.55; p < 0.001 between groups). Compared to the control group (from 2.0 ± 0.4 to 1.9 ± 0.4, p = 0.62), the ET group showed a significant improvement of RHI after 1 year (from 2.1 ± 0.7 to 2.5 ± 0.8, p < 0.001). Changes in VO₂peak were correlated with changes in RHI (ΔVO₂peak vs. ΔRHI: r = 0.47, p = 0.017). In BC survivors, ET program improves cardiopulmonary functional capacity and vascular endothelial function after 12 months. Whether these changes may favorably modulate some of the pathophysiological mechanisms implied in cancer evolution should be investigated.     

Endothelial function and cardiovascular events in chronic kidney disease

Background

As patients with chronic kidney disease (CKD) are at high risk of developing coronary artery disease (CAD), it is important to stratify their cardiovascular risk. We investigated whether peripheral endothelial dysfunction is associated with the presence of CAD in patients with CKD and is a predictor of cardiovascular events.

Methods

We enrolled 383 CKD patients with at least one coronary risk factor. Peripheral endothelial function was assessed by reactive hyperemia peripheral arterial tonometry index (RHI). The presence of CAD was determined by coronary angiography. Cardiovascular events were assessed during follow-up.

Results

Ln-RHI was significantly lower in risk factor-matched CKD patients (n = 323) than risk factor-matched non-CKD patients (n = 323) (0.527 ± 0.192 vs. 0.580 ± 0.218, p = 0.001). In CKD patients (n = 383), Ln-RHI was significantly lower in CAD (0.499 ± 0.183, n = 262) than non-CAD (0.582 ± 0.206, n = 121) (p < 0.001) patients. Multivariate logistic regression analysis identified Ln-RHI as an independent factor associated with the presence of CAD (p = 0.001). During a mean follow-up period of 30 months, 90 cardiovascular events were recorded in CKD patients. Multivariate Cox hazard analysis identified low-Ln-RHI as an independent predictor of cardiovascular events (hazard ratio = 2.70, 95% confidence interval = 1.62–4.51, p < 0.001). The predictive value of combined Ln-RHI and Framingham risk score (FRS) was evaluated by net reclassification index (NRI) and C-statistics, which showed significant improvement (NRI = 22%, p < 0.001) (C-statistics: FRS = 0.49, FRS + Ln-RHI = 0.62, p = 0.005).

Conclusions

Endothelial function was significantly impaired in CKD patients and correlated with the presence of CAD. Severe endothelial dysfunction was an independent and incremental predictor of cardiovascular events in CKD.     

Subendocardial viability ratio in patients with rheumatoid arthritis: comparison with healthy controls and identification of prognostic factors

Cardiac involvement is common in rheumatoid arthritis. Subendocardial viability ratio (SEVR) is a non-invasive measure of microvascular coronary perfusion, yet it remains unclear whether it is affected in rheumatoid arthritis patients. We additionally sought predictors of SEVR in rheumatoid arthritis among a wide range of disease-related parameters, cardiac and hemodynamic factors, and markers of atherosclerosis, arteriosclerosis, and endothelial dysfunction. SEVR was estimated in rheumatoid arthritis patients and healthy controls by applanation tonometry, which was also used to evaluate arterial stiffness (pulse wave velocity and augmentation index). In the rheumatoid arthritis group, carotid intima–media thickness (cIMT) was additionally estimated by ultrasound, cardiac and hemodynamic parameters by impedance cardiography, and endothelial dysfunction by measurement of asymmetric dimethylarginine (ADMA). In a total of 122 participants, SEVR was lower among 91 patients with rheumatoid arthritis compared to 31 controls (141.4 ± 21.9 vs 153.1 ± 18.7%, p = 0.009) and remained so among 29 rheumatoid arthritis patients without hypertension, diabetes, or cardiovascular diseases, compared to the control group (139.7 ± 21.7 vs 153.1 ± 18.7%, p = 0.013). SEVR did not significantly correlate with arterial stiffness, cIMT, ADMA, or disease-related parameters. Multivariate analysis revealed gender (p = 0.007), blood pressure (p = 0.028), heart rate (p = 0.025), cholesterol levels (p = 0.008), cardiac index (p < 0.001) and left ventricular ejection time (p = 0.004) as independent predictors of SEVR among patients with rheumatoid arthritis. Patients with rheumatoid arthritis exhibit lower values of SEVR compared to healthy individuals. Cardiac and hemodynamic parameters, rather than functional indices of endothelial and macrovascular dysfunction, may be useful as predictors of myocardial perfusion in rheumatoid arthritis.     

Three-question set from Michigan Neuropathy Screening Instrument adds independent prognostic information on cardiovascular outcomes: analysis of ALTITUDE trial

Aims/hypothesis

The self-administered Michigan Neuropathy Screening Instrument (MNSI) is used to diagnose diabetic peripheral neuropathy. We examined whether the MNSI might also provide information on risk of death and cardiovascular outcomes.

Methods

In this post hoc analysis of the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE) trial, we divided 8463 participants with type 2 diabetes and chronic kidney disease (CKD) and/or cardiovascular disease (CVD) into independent training (n = 3252) and validation (n = 5211) sets. In the training set, we identified specific questions that were independently associated with a cardiovascular composite outcome (cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction/stroke, heart failure hospitalisation). We then evaluated the performance of these questions in the validation set.

Results

In the training set, three questions (‘Are your legs numb?’, ‘Have you ever had an open sore on your foot?’ and ‘Do your legs hurt when you walk?’) were significantly associated with the cardiovascular composite outcome. In the validation set, after multivariable adjustment for key covariates, one or more positive responses (n = 3079, 59.1%) was associated with a higher risk of the cardiovascular composite outcome (HR 1.54 [95% CI 1.28, 1.85], p < 0.001), heart failure hospitalisation (HR 1.74 [95% CI 1.29, 2.35], p < 0.001), myocardial infarction (HR 1.81 [95% CI 1.23, 2.69], p = 0.003), stroke (HR 1.75 [95% CI 1.20, 2.56], p = 0.003) and three-point major adverse cardiovascular events (MACE) (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke) (HR 1.49 [95% CI 1.20, 1.85], p < 0.001) relative to no positive responses to all questions. Associations were stronger if participants answered positively to all three questions (n = 552, 11%). The addition of the total number of affirmative responses to existing models significantly improved Harrell’s C statistic for the cardiovascular composite outcome (0.70 vs 0.71, p = 0.010), continuous net reclassification improvement (+22% [+10%, +31%], p = 0.027) and integrated discrimination improvement (+0.9% [+0.4%, +2.1%], p = 0.007).

Conclusions/interpretation

We identified three questions from the MNSI that provide additional prognostic information for individuals with type 2 diabetes and CKD and/or CVD. If externally validated, these questions may be integrated into the clinical history to augment prediction of CV events in high-risk individuals with type 2 diabetes.

     

Effect of glycemic state on postprandial hyperlipidemia and hyperinsulinemia in patients with coronary artery disease

Both postprandial hyperlipidemia and hyperinsulinemia have been thought to play an important role in the development of atherosclerosis, and to be a potent risk factor for cardiovascular event. To examine effects of glycemic state on postprandial hyperlipidemia and hyperinsulinemia in patients with coronary artery disease (CAD), a total of 112 consecutive male patients with angiographically confirmed CAD were loaded with a high-fat and high-glucose test meal. CAD patients were divided into three groups as “non-diabetic”, “prediabetic”, and “diabetic” CAD groups. The serum triglyceride (TG) and remnant-like particle cholesterol (RLP-C) levels at the 6th hour in diabetic CAD group showed significantly higher than non-diabetic CAD group, and the incremental area under the curves (iAUCs) of these levels in diabetic CAD group were significantly greater than non-diabetic CAD group (TG, P = 0.0194; RLP-C, P = 0.0219). There were no significant differences in the iAUCs of TG or RLP-C between prediabetic and non-diabetic CAD group. The AUCs of plasma insulin levels or insulin resistance index (IRI): (AUCs of insulin) × (AUCs of glucose) as the insulin resistance marker were greater in diabetic CAD group than non-diabetic CAD group (insulin, P = 0.0373; IRI, P = 0.0228). The AUCs of serum TG or RLP-C levels showed a correlation with the AUCs of plasma insulin (AUC-TG, r = 0.5437, P < 0.0001; AUC-RLP-C, r = 0.6847, P < 0.0001), and they correlated well with the insulin resistance index (AUC-TG, r = 0.7724, P < 0.0001; AUC-RLP-C, r = 0.7645, P < 0.0001). We found that the insulin resistance showed a close relationship with postprandial hyperlipidemia in CAD patients. Diabetic, but not prediabetic state, may be a risk for postprandial impaired lipid metabolism in CAD patients.     

Cardiovascular risk assessment in patients with rheumatoid arthritis: a correlative study of noninvasive arterial health testing

This study aimed to determine the relationship between noninvasive measures of arterial health and both estimated 10-year cardiovascular risk and measures of disease activity over time in established rheumatoid arthritis. Fifty rheumatoid arthritis patients underwent noninvasive arterial health testing (brachial artery reactivity, aortic augmentation index [AIx], pulse wave velocity, carotid artery intima-media thickness, and carotid artery plaque presence) and assessment of clinical disease activity (tender or swollen joint counts, Clinical Disease Activity Index [CDAI], and Health Assessment Questionnaire II [HAQ-II]). Clinical measures during 3 years before the study visit were averaged. Arterial health testing was compared with the American Heart Association/American College of Cardiology (AHA/ACC) Pooled Cohort Equation. Spearman methods identified correlations between disease activity measures, cardiac biomarkers, and arterial health parameters. Among the patients (mean age, 57.5 years), disease activity was moderate (mean [SD] CDAI, 16.9 [15.3]). At the study visit, corrected aortic augmentation index correlated with CDAI (r = 0.37, P = .009) and HAQ-II (r = 0.33, P = .02). AIx correlated with time-averaged tender joint count (r = 0.37, P = .008), CDAI (r = 0.36, P = .01), HAQ-II (r = 0.36, P = .01), swollen joint count (r = 0.36, P = .10), patient global assessment (r = 0.33, P = .02), physician global assessment (r = 0.35, P = .01), and pain score (r = 0.38, P = .007). The AHA/ACC low-risk group (<5% 10-year risk) had highest prevalence of carotid plaques. Arterial health testing may identify increased risk of cardiovascular disease compared with risk obtained through AHA/ACC Pooled Cohort Equation. Measures of arterial stiffness correlate with the burden of disease activity over time.     

Effect of rhBNP on renal function in STEMI-HF patients with mild renal insufficiency undergoing primary PCI

This study aims to investigate the effect of recombinant human brain natriuretic peptide (rhBNP) on renal function and contrast-induced nephropathy (CIN) incidence in ST-segment elevation myocardial infarction and heart failure (STEMI-HF) patients with mild renal insufficiency undergoing primary percutaneous coronary intervention (PCI). A total of 116 participants were randomized into rhBNP (rhBNP, n = 57) and nitroglycerin group (NIT, n = 59), receiving intravenous rhBNP or nitroglycerin from admission to 72 h after PCI. Renal function was assessed by serum creatinine (SCr), estimated glomerular filtration rate (eGFR), Cystatin-C (Cys-C) and β₂-microglobulin before and after primary PCI, and calculated the incidence of CIN within 72 h after PCI. There were no significant differences in SCr, eGFR and β₂-microglobulin between the two groups (P > 0.05, respectively). Compared with the NIT group, the total urinary volume within 72 h was higher while the level of Cys-C at 24 and 72 h after PCI was lower in the rhBNP group. rhBNP was associated with a decline in the incidence of CIN (12.28 vs. 28.81 %, P < 0.05). No differences were detected in mortality and re-hospitalization in 3 months between the two groups. The incidence of renal injury was not different between rhBNP and nitroglycerin in STEMI-HF patients with mild renal insufficiency. However, infusion of rhBNP was associated with a decline in incidence of CIN.     

Impact of oral beta-blocker therapy on mortality after primary percutaneous coronary intervention for Killip class 1 myocardial infarction

The use of beta-blockers therapy has been recommended to reduce mortality in patients with left ventricular dysfunction after acute myocardial infarction (AMI). Primary percutaneous coronary intervention (PCI), which has become the mainstay of treatment for AMI, is associated with a lower mortality than fibrinolysis. The benefits of beta-blockers after primary PCI in AMI patients without pump failure are unclear. We hypothesized that oral beta-blocker therapy after primary PCI might reduce the mortality in AMI patients without pump failure. The assessment of lipophilic vs. hydrophilic statin therapy in acute myocardial infarction (ALPS-AMI) study was a multi-center study that enrolled 508 AMI patients to compare the efficacy of hydrophilic and lipophilic statins in secondary prevention after myocardial infarction. We prospectively tracked cardiovascular events for 3 years in 444 ALPS-AMI patients (median age 66 years; 18.2 % women) who had Killip class 1 on admission and were discharged alive. The primary endpoint was all-cause mortality. The 3-year follow-up was completed in 413 patients (93.0 %). During this follow-up, 21 patients (4.7 %) died. In Kaplan–Meier analysis, patients on beta-blockers had a significantly lower incidence of all-cause mortality (2.7 vs. 7.3 %, log-rank p = 0.025). After adjusting for the calculated propensity score for using beta-blockers, their use remained an independent predictor of all-cause mortality (hazard ratio 0.309; 95 % confidence interval 0.116–0.824; p = 0.019). In the statin era, the use of beta-blocker therapy after primary PCI is associated with lower mortality in AMI patients with Killip class 1 on admission.     

Lower 1,5-anhydroglucitol is associated with adverse clinical events after percutaneous coronary intervention

Diabetes mellitus and impaired glucose tolerance are well-known risk factors for coronary artery disease (CAD) and adverse clinical events after percutaneous coronary intervention (PCI). Postprandial hyperglycemia is an important risk factor for CAD and serum 1,5-anhydroglucitol (1,5-AG) reflects postprandial hyperglycemia more robustly than hemoglobin (Hb)A1c. We aimed to clarify the relationship between serum 1,5-AG level and adverse clinical events after PCI. We enrolled 141 patients after PCI with follow-up coronary angiography. We evaluated associations between glycemic biomarkers including HbA1c and 1,5-AG and cardiovascular events during follow-up. Median serum 1,5-AG level was significantly lower in patients with any coronary revascularization and target lesion revascularization (TLR) [13.4 µg/ml (first quartile, third quartile 9.80, 18.3) vs. 18.7 (12.8, 24.2), p = 0.005; 13.4 µg/ml (10.2, 16.4) vs. 18.7 (12.9, 24.2), p = 0.001, respectively]. Multivariate logistic analysis showed lower 1,5-AG was independently associated with any coronary revascularization and TLR (odds ratio 0.93, 95 % confidence interval 0.86–0.99, p = 0.04; 0.90, 0.81–0.99, p = 0.044, respectively), whereas higher HbA1c was not. Postprandial hyperglycemia and lower 1,5-AG are important risk factors for adverse clinical events after PCI.     

Paclitaxel-eluting stents versus sirolimus-eluting stents in patients with diabetes mellitus undergoing percutaneous coronary intervention: a systematic review and meta-analysis of randomized controlled trials

Uncertainties exist with regard to the efficacy of paclitaxel-eluting stents (PES) versus sirolimus-eluting stents (SES) in diabetes patients undergoing percutaneous coronary intervention (PCI). We performed a meta-analysis of randomized controlled trials (RCTs) to investigate the outcome of PES versus SES in diabetes patients undergoing PCI. A literature search was started, and we found all studies conducted from 2005 to 2016. We systematically searched the literature through the MEDLINE, Cochrane library, and EMBASE. Quality assessments were evaluated with the Jadad scale. Data were extracted considering the characteristics of efficacy and the safety of the designs. 12 RCTs satisfy the inclusion criteria. There is a significant decrease of target lesion revascularization (TLR) (MD = 0.65, 95 % CI = 0.42–1.00, P = 0.05) in a year and more than 1 year (MD = 0.54, 95 % CI = 0.37–0.78, P = 0.00010). A significant decrease of target vessel revascularization (TVR) in more than 1 year is (MD = 0.62, 95 % CI = 0.47–0.81, P = 0.0004). A significant decrease of major adverse cardiac events (MACE) in more than 1 year is (MD = 0.73, 95 % CI = 0.60–0.89, P = 0.002). Nevertheless, there is no significant difference in mortality (MD = 0.85, 95 % CI = 0.66–1.11, P = 0.24), stent thrombosis (ST) (MD = 0.65, 95 % CI = 0.35–1.21, P = 0.18), or myocardial infarction (MD = 1.04, 95 % CI = 0.71–1.51, P = 0.84). SES may be more significant in decreasing TLR, TVR, and MACE than PES without significantly increasing mortality, ST and MI in diabetes patients.     

Association between absolute blood eosinophil count and CKD stages among cardiac patients

Elevated eosinophil count was shown to be associated with the development of cholesterol embolization syndrome, a potentially life-threatening condition, after catheter-based procedures. We investigated the association between stages of chronic kidney disease (CKD) and the absolute eosinophil count (AEC) among cardiac patients. CKD stages were determined solely on the estimated glomerular filtration rate or requirement for hemodialysis. Eosinophilia is defined as an eosinophil count exceeding 500/μL. A total of 1022 patients were enrolled in the current study, and eosinophil counts (/μL) in the first through fourth eosinophil count quartiles were <88, 88 to 154, 155 to <238, and 238≤, respectively, and 29 patients (2.8 %) had eosinophilia. Correlation coefficient between the AEC and age was ?0.188 (P = 0.001) in women and ?0.042 (n.s.) in men (by Spearman’s correlation test). Patients with higher CKD stages had a higher prevalence of the highest AEC quartile or eosinophilia. Logistic regression analysis using severe renal dysfunction (i.e., CKD stage 4 or 5) as the dependent variable, the highest AEC quartile had a significant positive association with an odds ratio of 1.99 (95 % confidence interval, 1.20–3.31, P < 0.01) after adjustment for sex, age, systolic blood pressure, and total white blood cell count. Similarly, after adjustment for the same variables, eosinophilia was associated with severe renal dysfunction with an odds ratio of 2.60 (95 % confidence interval, 1.08–6.26, P < 0.05). Eosinophil count was positively associated with higher CKD stages among cardiology patients, some fraction of which might be related to subclinical cholesterol embolization.     

Lipid peroxidation as risk factor for endothelial dysfunction in antiphospholipid syndrome patients

The aim of this study was to evaluate oxidative stress markers and it relations to endothelial damage as risk factor for thrombosis in patients with primary (PAPS) and secondary (SAPS) antiphospholipid syndrome (APS) in correlation to traditional risk factors. Flow-mediated (FMD) and nitroglycerine (NMD)-induced dilation of the brachial artery were studied in 140 APS patients (90 PAPS, 50 SAPS) and 40 controls matched by age, sex, and conventional risk factors for atherosclerosis. Markers of oxidative stress, lipid hydroperoxydes (LOOH), advanced oxidation protein products (AOPP), total sulfhydryl groups (tSHG), and paraoxonase 1 activity (PON1) were determined by spectrophotometric method. Oxidative stress dominates in APS patients. LOOH and AOPP correlate to lipid fractions (p < 0.05), unlike PON1, tSHG that correlated to antiphospholipid antibody positivity (p < 0.05). FMD was lower in APS patients comparing to controls (p < 0.001). Cholesterol is independent variable for FMD impairment in control group (p = 0.011); LOOH in PAPS (p = 0.004); LOOH, aCL, and triglycerides in SAPS patients (p = 0.009, p = 0.049, and p = 0.012, respectively). Combined predictive of aCL and LOOH is better for FMD impairment than LOOH alone in both PAPS and SAPS patients (AUC 0.727, p = 0.001, 95 % CI 0.616–0.837 and AUC 0.824, p?0.001, 95 % CI 0.690–0.957, respectively). Lipid peroxidation is independent predictor for endothelial dysfunction in APS patients. We demonstrated synergistic effect of aCL and LOOH as risk for endothelial impairment in both PAPS and SAPS patients.     

Extracellular matrix turnover in coronary artery ectasia patients

Dysregulation of the metabolism of the extracellular matrix (ECM) may contribute to coronary artery ectasia (CAE). This study evaluated the turnover of main ECM components and related proteolytic enzymes activities. In this study, thirty patients with CAE, 30 patients with coronary artery disease (CAD) and 30 subjects with normal coronary arteries (Control) were selected. The following circulating ECM metabolism markers were measured: soluble elastin (sElastin), collagen type I cross-linked telopeptides (ICTP), procollagen type I carboxy terminal peptide (PICP), protocollagen III N-terminal propeptide (PIIINP), and procollagen a1(III) C-terminal propeptide (PIIICP). Serum total elastase activity and total matrix metalloproteinase (MMP) activity were also determined. The level of sElastin was higher in the CAE group than in the CAD and Control groups (P1 = 0.009, P2 = 0.000). There was no difference in ICTP (P = 0.168) or PIIICP (P = 0.079) among the three groups. PICP was significantly elevated in CAE (P1 = 0.001, P2 = 0.002). PIIINP was also significantly increased in CAE (P1 = 0.002, P2 = 0.007). Total elastase activity was higher in the CAE group than in the other two groups (P1 = 0.006, P2 = 0.022). Total MMP activity was significantly higher in the CAE group than the Control group (P2 = 0.013) but not higher than the CAD group (P1 = 0.477). In conclusion, within CAE patients the main changes in ECM metabolism were increased degradation of elastin fibres and the transition of collagen from type III to type I. Elastase and MMPs appear to be associated with this kind of ECM turnover.     

Persistent infiltration and pro-inflammatory differentiation of monocytes cause unresolved inflammation in brain arteriovenous malformation

An abnormally high number of macrophages are present in human brain arteriovenous malformations (bAVM) with or without evidence of prior hemorrhage, causing unresolved inflammation that may enhance abnormal vascular remodeling and exacerbate the bAVM phenotype. The reasons for macrophage accumulation at the bAVM sites are not known. We tested the hypothesis that persistent infiltration and pro-inflammatory differentiation of monocytes in angiogenic tissues increase the macrophage burden in bAVM using two mouse models and human monocytes. Mouse bAVM was induced through deletion of AVM causative genes, Endoglin (Eng) globally or Alk1 focally, plus brain focal angiogenic stimulation. An endothelial cell and vascular smooth muscle cell co-culture system was used to analyze monocyte differentiation in the angiogenic niche. After angiogenic stimulation, the Eng-deleted mice had fewer CD68⁺ cells at 2 weeks (P = 0.02), similar numbers at 4 weeks (P = 0.97), and more at 8 weeks (P = 0.01) in the brain angiogenic region compared with wild-type (WT) mice. Alk1-deficient mice also had a trend toward more macrophages/microglia 8 weeks (P = 0.064) after angiogenic stimulation and more RFP⁺ bone marrow-derived macrophages than WT mice (P = 0.01). More CD34⁺ cells isolated from peripheral blood of patients with ENG or ALK1 gene mutation differentiated into macrophages than those from healthy controls (P < 0.001). These data indicate that persistent infiltration and pro-inflammatory differentiation of monocytes might contribute to macrophage accumulation in bAVM. Blocking macrophage homing to bAVM lesions should be tested as a strategy to reduce the severity of bAVM.     

Assessment of risk factors and left ventricular function in patients with slow coronary flow

Slow coronary flow (SCF) is characterized by delayed distal vessel opacification in the absence of significant epicardial coronary disease. Life-threatening arrhythmias and sudden cardiac death can occur; however, the pathological mechanism and influence on left ventricular function remain undetermined. We aimed to assess the risk factors and left ventricular (LV) function in SCF and evaluate the relationships between thrombolysis in myocardial infarction frame count (TFC) and the number of involved coronary arteries with LV function in patients with SCF. We included 124 patients who underwent coronary angiography because of symptoms of angina; 71 patients with angiographically proven SCF and 53 cases with normal coronary flow pattern. SCF was diagnosed as TFC >27 in at least one coronary artery. Complete blood count and biochemical parameters were compared between the two groups. Conventional echocardiography and tissue Doppler imaging were used to assess LV systolic and diastolic function. Platelet aggregation rate induced by ADP was an independent predictor of SCF and positively correlated with coronary artery mean TFC (mTFC) (r = 0.514, P < 0.001) and the number of coronary arteries with SCF (r = 0.628, P < 0.001). Early diastolic mitral inflow velocity (E) (0.66 ± 0.15 vs. 0.74 ± 0.17, P = 0.008), ratio of early to late diastolic mitral inflow velocity (E/A) (0.95 ± 0.29 vs. 1.15 ± 0.35, P = 0.002), global myocardial peak early diastolic velocity (gVe) (4.41 ± 1.25 vs. 4.96 ± 1.45, P = 0.037), and ratio of global myocardial peak early to late diastolic velocity (gVe/gVa: 1.09 ± 0.45 vs. 1.36 ± 0.58, P = 0.006) were decreased in patients with SCF compared with controls. gVe (3 vs. 0 branches, 4.08 ± 1.14 vs. 4.97 ± 1.45, respectively, P = 0.008) deteriorated significantly in patients with SCF involving three coronary arteries. mTFC negatively correlated with E and E/A (r = ?0.22, P = 0.02; r = ?0.20, P = 0.04, respectively). The number of coronary arteries with SCF negatively correlated with E, E/A, gVe and gVe/gVa (r = ?0.23, P = 0.02; r = ?0.25, P = 0.009; r = ?0.25, P = 0.008; r = ?0.21, P = 0.03, respectively). Platelet aggregation rate induced by ADP was an independent predictor of SCF and positively correlated with coronary artery TFC and the number of affected coronary arteries. Left ventricular global and regional diastolic function was impaired in SCF patients. Furthermore, the number of coronary arteries involved rather than coronary artery TFC determined the severity of left ventricular dysfunction in patients with SCF.     

Lack of correlation between platelet reactivity and glycaemic control in type 2 diabetes mellitus patients treated with aspirin and clopidogrel

The relationship between glycaemic control and platelet reactivity in patients with type 2 diabetes mellitus (DM) on dual antiplatelet therapy is still unclear. A total of 155 consecutive stable angina patients with type 2 DM scheduled for elective percutaneous coronary intervention (PCI) were recruited. All patients were taking aspirin and received a 600-mg loading dose of clopidogrel at least 12 h before intervention. Platelet reactivity was assessed prior to PCI using the VerifyNow^® device (Accumetrics Inc., San Diego, California). High platelet reactivity on clopidogrel (HPR_Clopidogrel) was defined as a PRU value ≥240. HPR on aspirin (HPR_Aspirin) defined as an ARU value ≥550. Poor glycaemic control was defined as a HbA1C value >7 mg/dL. There was no significant difference in either PRU or ARU values in patients with poor glycaemic control compared to those with good glycaemic control (PRU: 230 ± 92 vs. 228 ± 110, P = 0.90; ARU: 440 ± 63 vs. 435 ± 60, P = 0.61). Patients with and without poor glycaemic control did not show significantly different prevalence of HPR_Aspirin (8 vs. 6%; P = 0.23) or HPR_Clopidogrel (46 and 44%; P = 0.80). There was no significant correlation found between HbA1C and either ARU values (r = 0.040, P = 0.71) or PRU values (r = 0.018, P = 0.87). Overall these data suggest that glycaemic control does not appear to influence platelet reactivity in patients with type 2 DM following a loading dose of 600 mg of clopidogrel and aspirin treatment.     

Does really previous stenting affect graft patency following CABG? A 5-year follow-up

The aim of this study was to compare the graft patency rates among patients who had a previous history of percutaneous coronary intervention (PCI) followed by coronary artery bypass grafting surgery (CABG) with the patients who had experienced CABG surgery alone. The 69 patients who were included in the study had a history of bare metal stent implantation prior to CABG (group 1). The coronary angiography results were compared with 69 patients who had a previous history of CABG (group 2). Graft patency rates of the left anterior descending artery and circumflex anastomoses are statistically significant for both groups, whereas the right coronary artery anastomoses are not statistically significant (p = 0.008; 0.009; 0.2). Graft patency rate of LIMA–LAD anastomoses was 43.9 ± 10.8 % in group 1 and 86.2 ± 6 % in group 2 for means of 60 months (p = 0.0001) and circumflex coronary artery anastomosis is 28.9 ± 0.9 % in group 1, 65.7 ± 10.8 % in group 2 (p = 0.0001) and the right coronary artery anastomosis is 37.2 ± 13.6 % in group 1, 56.4 ± 8.9 % in group 2 (p = 0.0001). The graft patency rates of coronary arteries without previous stent implantation were higher than the patients with previous stent implantation and experienced CABG. The results suggest that prior PCI may induce atherosclerotic events in the vessel that can adversely affect graft patency after surgery.     

Increased cystatin C levels as a risk factor of cardiovascular events in patients with preserved estimated glomerular filtration rate after elective percutaneous coronary intervention with drug-eluting stents

Chronic kidney disease (CKD) is an important risk factor for coronary artery disease (CAD) and cardiovascular events. Cystatin C (CysC) has been proposed as a sensitive marker for CKD. However, the predictive value of CysC for cardiovascular events in CAD patients with preserved estimated glomerular filtration rate (eGFR) is unclear. We enrolled 277 consecutive patients undergoing elective percutaneous coronary intervention with sirolimus-eluting stents (SES). Patients with an eGFR ≤60 ml/min/1.73 m² were excluded. Serum CysC levels were measured immediately before SES implantation. Major adverse cardiac and cerebrovascular events (MACCE) were defined as cardiovascular death, acute coronary syndrome, stroke, and hospitalization because of congestive heart failure. After a median follow-up of 63 months, 29 patients had MACCE. The subjects were divided into 2 groups based on median serum CysC levels and eGFR (0.637 mg/L and 72.43 ml/min/1.73 m², respectively). Kaplan–Meier curves showed that the high CysC group had a significantly higher occurrence of MACCE than the low CysC group (p = 0.006), although a low level of eGFR was not significantly associated with an increased risk for occurrence of MACCE. Multivariate analysis revealed that serum CysC levels were an independent predictor of MACCE [hazards ratio: 1.30 per 0.1 mg/L (1.01–1.63), p = 0.038]. These data suggested that serum CysC level is an independent predictor of MACCE, even in patients with preserved eGFR after elective SES implantation.     

Association between gait characteristics and endothelial oxidative stress and inflammation in patients with symptomatic peripheral artery disease

The aim of the study was to determine whether gait characteristics were associated with endothelial cell inflammation, oxidative stress, and apoptosis and with circulating biomarkers of inflammation and antioxidant capacity in older patients with symptomatic peripheral artery disease (PAD). Gait measurements of 231 symptomatic men and women with PAD were assessed during a 4-m walk test. Patients were further characterized on endothelial effects of circulating factors present in the sera using a cell culture-based bioassay on primary human arterial endothelial cells and on circulating inflammatory and vascular biomarkers. In a multivariate regression model for gait speed, the significant independent variables were age (p < 0.001), intercellular cell adhesion molecule-1 (ICAM-1) (p < 0.001), diabetes (p = 0.003), sex (p = 0.003), and history of cerebrovascular accidents (p = 0.021). In multivariate analyses for gait cadence, the significant independent predictors included high-sensitivity C-reactive protein (HsCRP) (p < 0.001), diabetes (p = 0.001), and hypertension (p = 0.001). In a multivariate regression model for gait stride length, the significant independent variables were HsCRP (p < 0.001), age (p < 0.001), ICAM-1 (p < 0.001), hypertension (p = 0.002), cellular reactive oxygen species production (p = 0.007), and sex (p = 0.008). Higher levels of circulating biomarkers of inflammation and endothelial cell oxidative stress were associated with slower gait speed, slower cadence, and shorter stride length in older symptomatic patients with PAD. Additionally, this profile of impaired gait was more evident in older patients, in women, and in those with diabetes, hypertension, and history of cerebrovascular accidents.     

Survival protection by bodyweight in isolated scleroderma-related pulmonary artery hypertension

In chronic heart failure (CHF) due to systemic cardiovascular disease, obese patients have better survival. Bodyweight versus survival was analyzed post hoc in subjects with limited scleroderma (SSc) and isolated pulmonary artery hypertension (PAH), i.e. with CHF due to pulmonary vascular disease. Rheumatologists referred scleroderma subjects for evaluation, and PAH was ascertained by right heart catheterization (RHC). Forty-nine SSc-PAH subjects were stratified by body mass index (BMI): obese 7 (14.3 %), overweight 11 (22.4 %), normal weight 21 (42.9 %), and underweight 10 (20.4 %) for 24-month follow-up and pooled together for long-term 72-month follow-up. Survival was analyzed by Kaplan–Meier method. Multivariate Cox proportional hazards modeling helped to assess variables associated to survival. At 24 months (17 events), survival increases with BMI across four groups (logrank for trend P = 0.031). By Cox multivariate mortality, best model included: BMI (P = 0.043), low lung diffusion (DLco, P = 0.007), and reduced stroke volume index (SVI, P = 0.017). At 72 month (37 events), higher BMI values were associated with better survival but not significantly (P = 0.076). By multivariate modeling BMI did not enter any model, whereas low DLco entered all (P < 0.001). Also low SVI (P = 0.02) and low mixed venous saturation (SvO₂, P = 0.009) were associated with the prognosis. From PAH diagnosis to final event, BMI had small (5.4 %), but significant decline (P < 0.001). This is ascribed to CHF progression, and may explain BMI predictive power weakening. The results suggest BMI decline should be contrasted, DLco is useful for screening and with SVI and SvO₂ for assessing prognosis and treatment.