Hyperhomocysteinaemia and poor vitamin B status in chronic obstructive pulmonary disease

Background and aimsPatients with chronic obstructive pulmonary disease (COPD) are at increased atherothrombotic risk. Preliminary findings have suggested that COPD patients may have increased plasma total homocysteine (tHcy), a cardiovascular risk factor often caused by a poor B vitamin status, but plasma levels of such vitamins were not measured. The aim of this study was to investigate hyperhomocysteinaemia in COPD and to determine whether it may be secondary to poor plasma concentrations of B vitamins.Methods and resultsWe performed a case–control, cross-sectional study of 42 patients with COPD and 29 control subjects. Folate, vitamin B12, vitamin B6, tHcy, renal function, C-reactive protein, blood gases and lipids were measured in patients and controls. COPD patients had higher plasma tHcy (median: 13.9 μmol/l, interquantile range [IQR]: 12.1–18.5 versus 11.5, IQR: 10.1–14, p = 0.002) and lower circulating folate (median: 2.5 ng/ml, IQR: 1.2–3.3 versus 2.8, IQR: 2.1–4 of controls, p = 0.03) than controls had. Compared to the control group, COPD was associated with higher tHcy concentrations also after adjusting for smoking, heart failure, renal function and C-reactive protein with logistic regression analysis (OR 1.36, 95% CI 1.06–1.72, p = 0.01). In the COPD group, low levels of folate (β = −0.27, p = 0.02) and vitamin B12 (β = −0.24, p = 0.04), and hypertriglyceridaemia (β = 0.580, p < 0.0001) were independent predictors of the presence of high tHcy concentrations in a multiple linear regression model (adjusted R² = 0.522).ConclusionCOPD patients have a poor B vitamin status and, as a consequence, increased tHcy. These abnormalities may contribute to the COPD-related atherothrombotic risk.     

Transition from angiotensin-converting enzyme inhibitor/angiotensin-II-receptor-blocker to sacubitril/valsartan in chronic heart failure patients: Initial experiences in clinical practice

BackgroundSacubitril/valsartan (S/V) therapy has been demonstrated to improve prognosis of systolic heart failure (HF) patients when compared to standard therapy with ACEi. The purpose of this investigation was to document the safety and consequences of transition from ACEi/angiotensin-II receptor blocker (ARB) to S/V in chronic stable HF patients.MethodsA group of 12 stable HF outpatients (11 males, 1 female) was enrolled (NYHA 2.7 ± 0.7, 42% with coronary artery disease (CAD), average left-ventricle ejection fraction (LVEF) 26.5%). Patients were converted from ACEi/ARB to S/V. Laboratory evaluation, Minnesota Living with Heart Failure Questionnaire (MLHFQ), six-minute walk test (6MWT) were performed before the conversion and at 3-month follow-up visit.ResultsConversion from ACEi/ARB to S/V was not associated with any adverse event. After 3 months, S/V therapy decreased blood pressure (−14.8 mmHg for systolic BP, −9.6 mmHg for diastolic BP) and serum potassium (−0.27 mmol·l⁻¹, all p < 0.05). No worsening of renal function occurred (creatinine −7.8 μmol·l⁻¹, p = 0.12, estimated glomerular filtration rate +0.08 ml·s⁻¹·1.73 m⁻², p = 0.14). B-type natriuretic peptide (BNP) level remained unchanged (p = 0.18), but NT-proBNP level decreased significantly (median 1012 ng·l⁻¹ at baseline, 559.4 ng·l⁻¹ at follow-up, p = 0.005). A slight but significant decrease in high-sensitivity cardiac troponin T (hs-cTnT) was observed (median 14.76 ng·l⁻¹ at baseline, 12.63 ng·l⁻¹ at follow-up, p = 0.001). An improvement in MLHFQ total score (−8 points, p = 0.006) and in 6MWT by 55 m (p = 0.0007) was noted, which was not due to increased effort.ConclusionThe transition from ACEi/ARB to S/V therapy appears to be safe and leads to an improvement in exercise tolerance and quality of life.     

Peri-aortic fat,cardiovascular disease risk factors,and aortic calcification: The Framingham Heart Study

ObjectivePerivascular fat through the secretion of paracrine and pro-inflammatory mediators may play a role in obesity-mediated vascular disease. We sought to examine associations between adipose tissue depots immediately surrounding the thoracic aorta, metabolic risk factors, and vascular calcification.MethodsIn participants free of cardiovascular disease (CVD) from the Framingham Heart Study Offspring cohort who underwent computed tomography (n = 1067, mean age 59 years, 56.1% women), thoracic peri-aortic fat depots were quantified. Visceral abdominal tissue (VAT) and calcification of the thoracic and abdominal aorta were also measured.ResultsPeri-aortic fat depots were correlated with body mass index, waist circumference (WC), VAT (all p < 0.0001), hypertension (p = 0.007), low HDL (p < 0.0001), serum triglycerides (p < 0.0001), impaired fasting glucose (p = 0.005), and diabetes (p = 0.02). These associations generally remained significant after adjustment for BMI and WC (all p-values < 0.05), but not after VAT adjustment. Thoracic aortic fat was associated with thoracic calcification in models containing VAT (OR 1.31, 95% CI 1.01–1.71, p = 0.04), but was not significant after adjustment for CVD risk factors (OR 1.16, 95% CI 0.88–1.51, p = 0.30). Thoracic aortic fat, however, was associated with abdominal aortic calcification (OR 1.48, 95% CI 1.11–1.98, p = 0.008) and coronary artery calcification (OR 1.47, 95% CI 1.09–1.98, p = 0.001) even in models including CVD risk factors and VAT.ConclusionsThoracic peri-aortic fat is associated with measures of adiposity, metabolic risk factors, and coronary and abdominal aortic calcification.     

Aortic velocity propagation: A novel echocardiographic method in predicting atherosclerotic coronary artery disease burden

BackgroundThe major burden of cardiovascular disease mortality around the globe is due to atherosclerosis and its complications. Hence its early detection and management with easily accessible and noninvasive methods are valuable. Aortic velocity propagation (AVP) through color M-mode of the proximal descending aorta determines aortic stiffness, reflecting atherosclerosis. The aim of this study was to find the utility of AVP in predicting coronary artery disease (CAD) burden assessed through SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery) score and compared with carotid intima-media thickness (CIMT), which is an established surrogate marker of atherosclerosis.MethodsIn this cross-sectional comparative study, we measured AVP by color M-mode and CIMT by using Philips QLAB-IMT software in 100 patients, who underwent conventional coronary angiogram (CAG) between May 2013 and November 2014. Coronary artery disease is considered significant if >50% diameter stenosis is present in any epicardial coronary artery and insignificant if otherwise.ResultsInitially, to know the normal range we measured AVP and CIMT in 50 patients without any major risk factors for CAD but CAG was not done. Aortic velocity propagation ranged from 46 cm/s to 76 cm/s (mean = 58.62 ± 6.46 cm/s), CIMT ranged from 0.50 mm to 0.64 mm (mean = 0.55 ± 0.03 mm). Among 100 patients who underwent CAG we found 69% had significant CAD, 13% had insignificant CAD, and 18% had normal coronaries. Those with significant CAD had significantly lower AVP (41.65 ± 4.94 cm/s) [F (2,97) = 44.05, p < 0.0001] and significantly higher CIMT (0.86 ± 0.11 mm) [F (2,97) =35.78, p < 0.0001]. AVP had significant strong negative correlation with CIMT (r = −0.836, p < 0.0001, n = 100) and SYNTAX score (r = –0.803, p < 0.0001, n = 69), while CIMT was positively correlated with SYNTAX score significantly (r = 0.828, p < 0.0001, n = 69).ConclusionsAVP and CIMT can predict CAD burden in a robust way. AVP may emerge as an exquisite bedside tool to predict atherosclerotic burden and guide in implementing preventive therapy for cardiovascular disease.     

Uric acid and high sensitive C-reactive protein are associated with subclinical thoracic aortic atherosclerosis

Background and purposeThe detection of atherosclerotic lesions in the aorta by transesophageal echocardiography (TEE) is a marker of diffuse atherosclerotic disease. Hyperuricemia is a well-recognized risk factor for cardiovascular diseases. However, no data are available concerning the relationship between serum uric acid (UA) and subclinical thoracic aortic atherosclerosis. We aimed to investigate the association between thoracic aortic atherosclerosis and serum UA level.MethodsWe studied 181 patients (mean age 46.3 ± 8 years) who underwent TEE for various indications. Four different grades were determined according to intima–media thickness (IMT) of thoracic aorta. UA and other biochemical markers were measured with an automated chemistry analyzer.ResultsTEE evaluation characterized thoracic aortic intimal morphology as Grade 1 in 69 patients, Grade 2 in 52 patients, Grade 3 in 31 patients, and Grade 4 in 29 patients. The highest UA level was observed in patients with Grade 4 IMT when compared with Grade 1 and 2 IMT groups (p < 0.001 and p = 0.014, respectively). UA levels in patients with Grade 3 and Grade 2 IMT were also higher than patients with Grade 1 IMT group (p < 0.001, for all). In multiple linear regression analysis, IMT was independently associated with UA level (β = 0.350, p < 0.001), age (β = 0.219, p = 0.001), total cholesterol (β = ?0.212, p = 0.031), low-density lipoprotein cholesterol (β = 0.350, p = 0.001), and high sensitivity C-reactive protein (hsCRP) levels (β = 0.148, p = 0.014).ConclusionUric acid and hsCRP levels are independently and positively associated with subclinical thoracic atherosclerosis.     

Étude de la corrélation entre la sensibilité à l’insuline et les paramètres anthropométriques et métaboliques dans le diabète de type 2

AimThe aim of the study was to evaluate correlations between insulin sensitivity and insulinosecretion with anthropometric and metabolic parameters in type 2 diabetics.Materials and methodsWe conducted a cross-sectional study among patients with type 2 diabetes mellitus treated with oral antidiabetic medications. The evaluation of insulin resistance and insulinosecretion was based on the calculation of the HOMA-IR and HOMA-β indices.ResultsThe mean age for the 100 diabetes recruited was 56.4 ± 8.4 years. The mean body mass index (BMI) and waist circumference (WC) were 30.5 ± 5.7 kg/m² and 101.2 ± 11.9 cm respectively. The HOMA-IR and HOMA β indices were respectively 3.5 ± 2.8 and 48.9 ± 45.5. We have found a significantly positive correlation between HOMA-IR index and weight (r = 0.406, p < 10⁻³), BMI (r = 0.432, p < 10⁻³) and WC (r  =  0.412, p < 10⁻³). We noticed a significant negative correlation between HOMA β index and fasting glucose (r = −0.457, p < 10⁻³) and A1 C (r = −0.399, p < 10⁻³). A positive statistically significant correlation was noted between HOMA-IR and HOMA-β (r = 0.400, p < 10⁻³).ConclusionInsulin resistance is very related to overweight, especially the android distribution of fat hence the need for adequate management of this android obesity. It would also be interesting to evaluate the effects of weight loss on insulin resistance parameters.     

Clinical profile and impact of family history of premature coronary artery disease on clinical outcomes of patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction: analysis from the HORIZONS-AMI Trial

Background/PurposeFamily history of coronary artery disease (CAD) is a well-established risk factor of future cardiovascular events. The authors sought to examine the relationship between family history of CAD and clinical profile and prognosis of patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).Materials/MethodsBaseline features and clinical outcomes at 30 days and at 3 years from 3601 patients with STEMI enrolled in the HORIZONS-AMI trial were compared in patients with and without family history of premature CAD, which was present in 1059 patients (29.4%).ResultsThese patients were younger (median 56.7 vs. 62.1 years, P < 0.0001) and more often current smokers (52.4% vs. 43.5%, P < 0.0001), had more dyslipidemia (47.7% vs. 41.1%, P = 0.0003), less diabetes mellitus (14.1% vs. 17.5%, P = 0.01) and had shorter symptom onset to balloon times (median 213 vs. 225 min, P = 0.02). Patients with a family history of premature CAD had higher rates of final TIMI 3 flow (93.8% vs. 90.6%, P = 0.002), and myocardial blush grade 2 or 3 (83.2% vs. 78.0% P = 0.0008), and fewer procedural complications. Although the unadjusted 30-day and 3-year mortality rates were lower in patients with a family history of premature CAD (1.8% vs. 3.0%, P = 0.046 and 4.8% vs. 7.7%, P = 0.002, respectively), by multivariable analysis the presence of a family history of premature CAD was not an independent predictor of death at 3 years (HR [95%CI] = 1.00 [0.70, 1.44], P = 0.98).ConclusionsA family history of premature CAD is not an independent predictor of higher mortality.     

Effect of neighborhood factors on diabetes self-care behaviors in adults with type 2 diabetes

ObjectiveThe objective of this study was to identify latent variables for neighborhood factors and diabetes self-care and examine the effect of neighborhood factors on diabetes self-care in adults with type 2 diabetes.Research design and methods615 subjects were recruited from an academic medical center and a Veterans affairs medical center in the southeastern United States. Validated scales were used to assess neighborhood factors and diabetes-related self-care. Confirmatory factor analysis (CFA) was used to determine the latent constructs. Structural equation modeling (SEM) was then used to assess the relationship between neighborhood factors and diabetes self-care.ResultsBased on a theoretical framework, CFA yielded four latent variables for neighborhood factors (neighborhood violence, access to healthy food, social support, and neighborhood esthetics) and one latent variable diabetes self-care (including diet, exercise, foot care, blood sugar testing and medication adherence). SEM showed that social support (r = 0.28, p < 0.001) and access to healthy foods (r = −0.16, p = 0.003) were significantly associated with self-care behaviors, while neighborhood violence (r = −0.06, p < 0.001) and esthetics (r = −0.07, p = 0.278) were not χ² (180, N = 611) = 192, p = 0.26, RMSEA = 0.01, CFI = 0.999). In the final trimmed model, social support (r = 0.31, p < 0.001) and access to healthy foods (r = −0.20, p < 0.001) remained significantly associated with self-care behaviors χ² (76, N = 611) = 60, p = 0.91, RMSEA = 0.00, CFI = 1.0).ConclusionThis study developed latent factors for neighborhood characteristics and diabetes self-care and found that social support and access to healthy foods were significantly associated with diabetes self-care and should be considered as targets for future interventions.     

Genetic variation at chromosome 1p13.3 affects sortilin mRNA expression,cellular LDL-uptake and serum LDL levels which translates to the risk of coronary artery disease

BackgroundA single nucleotide polymorphism (SNP) rs599839 located at chromosome 1p13.3 has previously been associated with risk of coronary artery disease (CAD) and with serum levels of low-density lipoprotein cholesterol (LDL-C). A functional link explaining the association of SNP rs599839 with LDL-C levels and CAD risk has not yet been elucidated.MethodsWe analyzed the association of rs599839 with LDL-C in 6605 individuals across a wide age spectrum and with CAD in four case–control studies comprising 4287 cases and 7572 controls. Genome-wide expression array data was used to assess the association of SNP rs599839 with gene expression at chromosome 1p13. Finally, we overexpressed sortilin in transfected cells to study LDL-uptake in vitro.ResultsEach copy of the G-allele of rs599839 associated with a decrease of serum LDL-C by 0.14 mmol/L (90% confidence interval (CI) 0.09–0.17 mmol/L, p = 2.6 × 10^?11). Moreover, each copy of the G-allele associated with a 9% decrease of CAD risk (90% CI 4–14%) in the presently studied four case–control samples and with a 13% decrease (90% CI 10–17%, p = 2.18 × 10^?9) in a pooled meta-analysis including recent genome-wide association studies on CAD. The same allele was associated with higher mRNA-expression levels of the multiligand receptor sortilin (log transformed mRNA AA vs. GG = 8.31 vs. 8.55; p = 0.01). Overexpression of SORT1 cDNA resulted in a significant increase in LDL-particle uptake (+23%, p = 0.01).ConclusionsRs599839 associates with decreased LDL-C and a lower risk of CAD. Effects appear to be mediated by increased sortilin expression and subsequently enhanced LDL-uptake into cells.     

Usefulness of right atrial volume index in predicting outcome in chronic systolic heart failure

BackgroundRight ventricular (RV) dysfunction is associated with poor prognosis in patients with heart failure (HF). Echocardiographic assessment of RV systolic function is challenging. The ability to visualize the right atrium (RA) allows a quantitative, highly reproducible assessment of RA volume.ObjectiveThe aim is to study the relationship between the right atrial volume index (RAVI) and prognosis in patients with chronic systolic HF.Methods120 patients with chronic systolic HF and left ventricular ejection fraction (LVEF) <40% were enrolled. The RA volume was calculated by Simpson’s method using single-plane RA area and indexed to body surface area (RAVI). RV systolic assessment was done using the RV fractional area change (RVFAC), and peak systolic velocity (Sa_tri) using tissue Doppler imaging at the tricuspid annulus. The primary endpoint was death, urgent transplantation, or acute HF episode requiring hospital admission during a follow-up of 1 year.ResultsFollow up was complete for 117 of 120 patients. Fifty-two patients reached the primary endpoint. The mean RAVI was higher in patients with adverse events (45.5 ± 15 ml/m² versus 25.2 ± 11 ml/m², p < 0.001), and increased with worsening LVEF, RVFAC, Sa_tri (Spearman’s r = −0.46, r = −0.45, r = −0.59, p < 0.001 for all). RAVI was not correlated with estimates of RV diastolic dysfunction. The cut-off threshold for RAVI to predict the primary endpoint using receiver-operating characteristic curve was 29 ml/m² (area under the curve was 0.89%, 95% confidence interval: 0.82–0.95) with a sensitivity of 92%, and a specificity of 75%. NYHA > 2 (OR = 2.1, p < 0.01), and RAVI (OR = 1.6, p < 0.05) were found to be independent predictors of adverse outcome.ConclusionIn patients with chronic systolic HF, RAVI is an independent predictor of adverse outcome with a threshold value of 29 ml/m².     

HLA-DRB1 Alleles are Associated With COPD in a Latin American Admixed Population

IntroductionWhile the molecular mechanisms of COPD pathogenesis remain obscure, there is mounting evidence supporting a key role for autoimmunity. Although human leukocyte antigens (HLA) alleles have been repeatedly associated with autoimmune processes, the relation between HLA and COPD remains largely unexplored, especially in Latin American (LA) populations. Consequently, this study aimed to investigate the presence of HLA class I and II alleles in COPD patients and healthy controls in a LA population with admixed ancestry.MethodsCOPD patients (n = 214) and age-matched controls (n = 193) were genotyped using the Illumina Infinium Global Screening Array. The classic HLA alleles were imputed using HLA Genotype Imputation with Attribute Bagging (HIBAG) and the Hispanic reference panel. Finally, the distribution of HLA-DRB1 alleles was reexamined in 510 randomly recruited unrelated volunteers.ResultsCODP patients showed a higher HLA-DRB1*01:02 allele frequency (6.54%) than healthy controls (3.27%, p = 0.04, OR = 2.07). HLA-DRB1*01:02 was also significantly associated with FEV₁ (p = 0.04) and oxygen saturation (p = 0.02), and the FEV₁/FVC ratio was higher in HLA-DRB1*15:01-positive patients (p = 9 × 10⁻³).ConclusionWe report an association among HLA-DRB1 alleles, COPD risk and pulmonary function parameters for the first time in Latin Americans. Since HLA-DRB1 genetic variability relates to the individual autoimmune response, these results support a role of autoimmunity in the pathogenesis of COPD.     

Prediction of cardiovascular events in pre-dialysis chronic kidney disease patients with normal SPECT myocardial perfusion imaging

PurposePatients with normal stress myocardial perfusion imaging (MPI) results generally have an excellent prognosis with <1% cardiovascular events/year. Chronic kidney disease (CKD) is an established risk factor for cardiovascular events. However, the estimated glomerular filtration rate (eGFR) varies considerably among patients with CKD. We evaluated the prognostic value of eGFR for patients with CKD who did not undergo hemodialysis and had no evidence of coronary artery disease (CAD).Methods and subjectsPatients with CKD (n = 108; 58 males; mean age: 74 years) with no CAD [no previous CAD and normal stress MPI results; summed stress score (SSS) <4] and with no history of hemodialysis were followed-up (mean duration: 24 months). CKD was defined by eGFR of <60 ml/min/1.73 m² and/or persistent proteinuria. Cardiovascular events included cardiac death, non-fatal myocardial infarction, and unstable angina.ResultsCardiovascular events were observed in 8 patients with CKD (7%). The following were determined as significant predictors of these events: age (hazard ratio = 1.14; p = 0.019), hemoglobin levels (hazard ratio = 0.69; p = 0.021), eGFR (hazard ratio = 0.94; p = 0.008), SSS (hazard ratio = 2.31; p = 0.012), and summed difference score (hazard ratio = 2.33; p = 0.014).ConclusionsPatients with CKD and with no previous CAD and normal stress MPI results (SSS < 4) may not exhibit an excellent cardiovascular prognosis. Further, a lower eGFR and stress MPI results may be the predictors of cardiovascular events. Thus, patients with a lower eGFR and/or normal stress MPI results (SSS < 4) may require continuous follow-up.     

Role of the left atrial function on the pseudonormalization of the transmitral flow velocity pattern evaluated by two-dimensional tissue tracking technique

BackgroundMechanisms of the pseudonormalization (PN) of the transmitral flow (TMF) velocity pattern have been mainly attributed to left ventricular diastolic function.PurposeTo assess the influence of left atrial (LA) function on the PN with two-dimensional tissue tracking technique.MethodsThe subjects consisted of 21 healthy volunteers and 70 patients with various cardiac diseases. Images of one cardiac cycle in the apical four-chamber view were stored by the HIVISION 900 (Hitachi Medico, Chiba, Japan). The LA volume (LAV) loop was created using two-dimensional tissue tracking technique and LAV index (LAVI) at a given cardiac phase was calculated. A preload of 90 mmHg was applied using a customized lower body positive pressure (LBPP) system. Patients were divided into the PN group (n = 18) with their early diastolic TMF velocity (E) increased and late diastolic TMF velocity (A) decreased, and the non-(N)-PN group (n = 52) with both E and A wave velocities increased by LBPP.Results(1) During LBPP, the LAVI_max in both the groups increased significantly. (2) In the N-PN group, the LAVI_pass (p < 0.001), LAVI_act (p < 0.01), and LAVI_total (p < 0.0001) increased significantly. The dV/dt_s (p < 0.0001) and dV/dt_E (p < 0.0001) increased significantly with an increase in the dV/dt_A. On the other hand, there was no change in those parameters except LAVI_pass (p < 0.05) and dV/dt_E (p < 0.05) significantly increased in the PN group. (3) As a result, the LAVI_min was significantly greater in the PN group than in the N-PN group (p < 0.0001) during LBPP. The ratio of E velocity to early diastolic mitral annular velocity (E/E′) during LBPP was significantly greater in the PN group than in the N-PN group (p < 0.0001).ConclusionsThe lack of an increase in active LA emptying volume in response to an increase of preload leads to elevated LA pressure and the pseudonormalization of the TMF velocity pattern in patients with various cardiac diseases.     

Gas Exchange and Ventilatory Efficiency During Exercise in Pulmonary Vascular Diseases

Background and ObjectiveVentilatory inefficiency (high V′_E/V′CO₂) and resting hypocapnia are common in pulmonary vascular disease and are associated with poor prognosis. Low resting PaCO₂ suggests increased chemosensitivity or an altered PaCO₂ set-point. We aimed to determine the relationships between exercise gas exchange variables reflecting the PaCO₂ set-point, exercise capacity, hemodynamics and V′_E/V′CO₂.MethodsPulmonary arterial hypertension (n = 34), chronic thromboembolic pulmonary hypertension (CTEPH, n = 19) and pulmonary veno-occlusive disease (PVOD, n = 6) patients underwent rest and peak exercise arterial blood gas measurements during cardiopulmonary exercise testing. Patients were grouped according to resting PaCO₂: hypocapnic (PaCO₂ ≤34 mmHg) or normocapnic (PaCO₂ 35–45 mmHg). The PaCO₂ set-point was estimated by the maximal value of end-tidal PCO₂ (maximal P_ETCO₂) between the anaerobic threshold and respiratory compensation point.ResultsThe hypocapnic group (n = 39) had lower resting cardiac index (3.1 ±0.8 vs. 3.7 ±0.7 L/min/m², p < 0.01), lower peak V′O₂ (15.8 ± 3.5 vs. 20.7 ± 4.3 mL/kg/min, p < 0.01), and higher V′_E/V′CO₂ slope (60.6 ± 17.6 vs. 38.2 ± 8.0, p < 0.01). At peak exercise, hypocapic patients had lower PaO₂, higher V_D/V_T and higher P_(a-ET)CO₂. Maximal P_ETCO₂ (r = 0.59) and V_D/V_T (r = −0.59) were more related to cardiac index than PaO₂ or PaCO₂ at rest or peak exercise. Maximal P_ETCO₂ was the strongest correlate of V′_E/V′CO₂ slope (r = −0.86), peak V′O₂ (r = 0.64) and peak work rate (r = 0.49).ConclusionsResting hypocapnia is associated with worse cardiac function, more ventilatory inefficiency and reduced exercise capacity. This could be explained by elevated chemosensitivity and lower PaCO₂ set-point. Maximal P_ETCO₂ may be a useful non-invasive marker of PaCO₂ setpoint and disease severity even with submaximal effort.     

Diagnostic value of dobutamine stress Doppler tissue imaging in diabetic patients with suspected coronary artery disease

BackgroundCoronary artery disease (CAD) is often silent in diabetic patients, and it is typically in advanced stages of development by the time it manifests. Various forms of stress testing have been investigated to detect obstructive CAD in diabetes mellitus.ObjectivesTo assess the diagnostic value of dobutamine stress pulsed-wave Doppler tissue imaging (DTI) compared with standard wall motion analysis in detection of myocardial ischemia in diabetic patients with suspected CAD.MethodsThe study comprised 46 diabetic patients with suspected CAD who underwent dobutamine stress echocardiography (DSE) with DTI within 4 weeks before coronary angiography (CA). Dobutamine infusion started at 5 μ/kg/min and increased up to 40 μ/kg/min with additional atropine during submaximal heart rate responses. In addition to wall-motion score index (WMSI) analysis, pulsed-wave DTI examination of basal and mid segments of posteroseptal, lateral, anterior, inferior and anteroseptal walls was performed. Myocardial velocities were measured at rest in the apical 4, 3 and 2-chamber views. The measurements were repeated at low dose (10–15 μ/kg/min) and at peak stress (40 μ/kg/min). DTI measurements included peak systolic velocity (S), peak early diastolic velocity (E) and peak late diastolic velocity (A) and the results were compared to WMSI analysis. Patients were classified into two groups according to CA results; group (I) diabetics with positive CA (n = 27) and group (II) diabetics with negative CA (n = 19).ResultsThere was no significant difference between the two groups in duration of diabetes, global WMSI at rest or the Δ changes (stress-rest/rest) of WMSI (p > .05). Global S and global E were significantly lower in group I compared to group II at peak stress (11.3 ± 3.7 cm/s vs. 14.5 ± 2.2 cm/s, p < 0.01) and (11.3 ± 1.6 cm/s vs. 13.1 ± 2.1 cm/s, p < 0.01) respectively. The cutoff points for global S and global E to detect obstructive CAD in diabetics were 11.3 cm/s and 11.2 cm/s respectively with 75.7%, 73.4% sensitivity and 94.7%, 89.47% specificity respectively. An increment (Δ changes) less than 0.56 in S or 0.26 in E from rest to peak stress identified CAD with 78.8%, 89.3% sensitivity and 94.7%, 90.7% specificity respectively. The accuracy of DTI parameters during peak stress was higher than WMSI analysis (sensitivity 74.1% vs. 59.3% and specificity 90% vs. 79%, p < 0.01 for each). In multivariate regression analysis, only ΔS and ΔE were independent predictors of obstructive CAD in diabetics (odd ratio: 36.16, 95% CI, 1.34–532.01 and 63.77, 95% CI, 3.19–721.47) respectively.ConclusionQuantitative analysis, using DTI during DSE, adds new dimension in diagnosis of myocardial ischemia. It is more sensitive, specific, accurate and reproducible compared with standard wall motion analysis for recognition of significant CAD in diabetic patients.     

Anaemia,but not iron deficiency,is associated with clinical symptoms and quality of life in patients with severe heart failure and palliative home care: A substudy of the PREFER trial

BackgroundTo explore the relationships between anaemia or iron deficiency (ID) and symptoms, quality of life (QoL), morbidity, and mortality.MethodsA post-hoc, non-prespecified, explorative substudy of the prospective randomized PREFER trial. One centre study of outpatients with severe HF and palliative need managed with advanced home care. Associations between anaemia, ID, and the Edmonton Symptom Assessment Scale (ESAS), Euro QoL (EQ-5D), Kansas City Cardiomyopathy Questions (KCCQ) were examined only at baseline but at 6 months for morbidity and mortality.ResultsSeventy-two patients (51 males, 21 females), aged 79.2 ± 9.1 years. Thirty-nine patients (54%) had anaemia and 34 had ID (47%). Anaemia was correlated to depression (r = 0.37; p = 0.001), anxiety (r = 0.25; p = 0.04), and reduced well-being (r = 0.26; p = 0.03) in the ESAS; mobility (r = 0.33; p = 0.005), pain/discomfort (r = 0.27; p = 0.02), and visual analogue scale of health state (r = − 0.28; p = 0.02) in the EQ-5D; and physical limitation (r = − 0.27; p = 0.02), symptom stability; (r = − 0.43; p < 0.001); (r = − 0.25; p = 0.033), social limitation;(r = − 0.26; p = 0.03), overall summary score; (r = − 0.24, p = 0.046) and clinical summary score; (r = − 0.27; p = 0.02) in the KCCQ. ID did not correlate to any assessment item. Anaemia was univariably associated with any hospitalization (OR: 3.0; CI: 1.05–8.50, p = 0.04), but not to mortality. ID was not significantly associated with any hospitalization or mortality.ConclusionAnaemia, but not ID, was associated although weakly with symptoms and QoL in patients with advanced HF and palliative home care.     

Independent relationship of serum uric acid levels with leukocytes and coronary atherosclerotic burden

Background and AimEpidemiological studies have shown that increased serum uric acid (SUA) level is associated with coronary artery disease (CAD). Leukocytes have been shown to play an important role in the atherosclerotic process. The aim of the study was to investigate whether there is any relationship among SUA, leukocyte counts and coronary atherosclerotic burden in patients who are suspected of having CAD.Method and resultsWe enrolled 690 eligible patients who had undergone coronary angiography between October 2005 and June 2006 in a consecutive manner. The relationship of SUA with total and differential leukocyte counts and CAD was investigated. Serum uric acid levels (5.57 ± 1.64 vs 4.63 ± 1.27 mg/dl, p < 0.001) and leukocytes were higher in patients with CAD than those with normal coronary arteries (NCA). When we divided the patients into four groups according to the quartiles of SUA, we found that the monocyte count was prominently related with SUA (478 ± 165, 553 ± 177, 565 ± 199 and 607 ± 229 mm⁻³, Q1–Q4, p < 0.001). In multivariate analysis, SUA was an independent predictor of CAD (OR, 1.270; 95% CI, 1.087–1.484, p = 0.003). When we performed multiple linear regression analyses to determine the independent predictors of inflammatory cells in blood, we found a strong, positive and independent relationship between SUA with neutrophils (β ± SE: 206 ± 60, p = 0.001) and monocytes (β ± SE: 35 ± 7, p < 0.001).ConclusionOur study results demonstrated that neutrophils and monocytes which play an important role in inflammation and atherosclerosis were independently related with SUA. This finding suggests an important epidemiologic relation and may provide a possible causative mechanism of SUA in atherosclerotic process.     

The association between ectopic fat in the pancreas and subclinical atherosclerosis in type 2 diabetes

AimsEvidence that pancreatic fat accumulation has a role in obesity, metabolic syndrome and type 2 diabetes mellitus (DM) is emerging. However, data on the influence of pancreatic steatosis on subclinical atherosclerosis are lacking.MethodsWe examined 198 patients with type 2 DM. Pancreatic computed tomography (CT) attenuations were assessed using CT imaging. Obesity was defined as BMI ≥ 25 kg/m² according to the Asian-specific BMI cut-offs. We defined pancreatic steatosis as pancreatic attenuations below median levels.ResultsThe pancreatic attenuations was significantly correlated with age (r = −0.302, p < 0.001), visceral fat area (r = −0.194, p = 0.006) and vascular stiffness (r = −0.242, p = 0.001). In the non-obese group (BMI < 25 kg/m²), pancreatic steatosis was associated with a higher prevalence of carotid artery plaque and vascular stiffness. In the non-obese group, patients with pancreatic steatosis, compared with those without, had an odds ratio (OR) of 3.1 (95% CI 1.2–8.1) for carotid atherosclerosis, after adjusting for age, gender and BMI. However, significant associations between pancreatic steatosis and atherosclerosis were not found in the obese group.ConclusionEctopic fat in the pancreas is strongly associated with carotid atherosclerosis in non-obese subjects with type 2 DM. This finding highlights the importance of pancreatic fat deposits related to a higher risk of cardiovascular disease, especially in non-obese subjects.     

Elevated left ventricular filling pressure estimated by E/E′ ratio after exercise predicts development of new-onset atrial fibrillation independently of left atrial enlargement among elderly patients without obvious myocardial ischemia

ObjectiveTo determine whether elevated left ventricular (LV) filling pressure estimated by raised Doppler E velocity to tissue Doppler E′ velocity ratio (E/E′) after exercise is associated with increased risk of new-onset atrial fibrillation (AF) in non-ischemic elderly patients.BackgroundPrognostic importance of exercise induced LV diastolic dysfunction remains uncertain.Patients and methodsWe studied 147 elderly patients (73 ± 5 years) who underwent treadmill stress echocardiography. Patients with exercise induced LV wall motion abnormality were not included. Doppler and tissue Doppler measurements were done before treadmill exercise and immediately after the post-stress image acquisition, and E/E′ ratio was measured. Raised E/E′ was defined as E/E′ ≥ 15, and left atrial (LA) enlargement was defined as LA volume index ≥ 34 ml/m². Using Cox proportional hazards regression analysis, predictor of new-onset AF was determined. Using Kaplan–Meier analysis, we evaluated association between raised post-exercise E/E′ or LA enlargement with new-onset AF.ResultsDuring the follow-up period (median = 67 months), there were 25 new-onset AF. Cox proportional hazards regression analysis demonstrated that male gender [hazard ratio (HR) 3.294; p = 0.0117], LA enlargement (HR 3.576; p = 0.0017), and raised post-exercise E/E′ (HR 3147; p = 0.0068) were the best predictors of new-onset AF. Kaplan–Meier survival plot demonstrated that patients with both LA enlargement and raised post-exercise E/E′ developed new-onset AF most frequently. There was no significant difference in outcome between patients with isolated raised post-exercise E/E′ or isolated LA enlargement.ConclusionsRaised E/E′ ratio after exercise provides significant prognostic information for predicting new-onset AF in non-ischemic elderly patients. This prognostic value of raised post-exercise E/E′ is independent of and incremental to the LA enlargement.     

Epicardial adipose tissue volume as a marker of coronary artery disease severity in patients with diabetes independent of coronary artery calcium: Findings from the CTRAD study

AimsThe association between epicardial adipose tissue (EAT) volume and coronary artery disease (CAD) severity was evaluated, independent of traditional risk factors and coronary artery calcium (CAC) scores, in patients with diabetes type 2 (DM-2) using cardiac computed tomography angiography (CTA).MethodsA multivariate analysis was utilized to assess for an independent association after calculating EAT volume, CAD severity, and calcium scores in 92 patients with DM-II from the CTRAD study. We graded CAD severity as none (normal coronaries), mild-moderate (<70% stenosis), and severe (70% or greater stenosis).ResultsA total of 39 (42.3%) asymptomatic patients with diabetes did not have CAD; 30.4% had mild/moderate CAD; and 27.1% had severe CAD. Mean EAT volume was highest in patients with severe CAD (143.14 cm³) as compared to mild/moderate CAD (112.7 cm³), and no CAD (107.5 cm³) (p = 0.003). After adjustment of clinical risk factors, notably, CAC score, multivariate regression analysis showed EAT volume was an independent predictor of CAD severity in this sample (odds ratio 11.2, 95% confidence interval 1.7–73.8, p = 0.01).ConclusionsIncreasing EAT volume in asymptomatic patients with DM-II is associated with presence of severe CAD, independent of BMI and CAC, as well as traditional risk factors.