Independent inverse relationship between serum lycopene concentration and arterial stiffness

ObjectiveEmerging evidence suggests a role of lycopene in the primary prevention of cardiovascular disease. This study aimed to investigate the association of serum lycopene concentration with brachial-ankle pulse wave velocity (baPWV), a marker of arterial stiffness and markers of oxidative stress and inflammation.Methodshealthy women (n = 264, 31–75 yrs) were classified into tertiles according to serum lycopene concentration. Multivariate linear regression analyses were used to assess the relationship between serum lycopene and baPWV.ResultsSubjects in middle tertile (T2) and upper tertile (T3) had lower baPWV (1263 ± 23 and 1265 ± 14 cm/s vs. 1338 ± 21 cm/s; p = 0.009) and lower oxidized LDL (oxLDL) (53 ± 3 and 55 ± 3 U/L vs. 66 ± 3U/L; p < 0.001) than those in lower tertile (T1). Subjects in T3 showed higher LDL particle size (24.3 ± 0.08 nm vs. 24.0 ± 0.07 nm, p = 0.005) and lower C-reactive protein (hs-CRP) (0.80 ± 0.25 mg/dL vs. 1.27 ± 0.24 mg/dL, p = 0.015), compared with those in T1. Logistic regression analysis showed that baPWV decreased with the increment of lycopene concentration; log baPWV decreased by 0.21 cm/s (95% CI ?0.168;?0.045, p = 0.001) per unit change in lycopene. After adjustment for age, BMI, smoking, drinking, menopause and blood pressure, the estimated effect was attenuated by 35%, but remained statistically significant [?0.13 cm/s (95% CI ?0.112;?0.018, p = 0.006)]. Further adjustment for β-carotene, α-tocopherol, oxLDL, LDL particle size, and hs-CRP increased the strength of the association [β = ?0.221 (95% CI ?0.215;?0.012, p = 0.029)].ConclusionThis study supports the presence of an independent inverse relationship between circulating lycopene and baPWV. Additionally, reduced oxidative modification of LDL may be one of mediators on the mechanisms how lycopene reduces arterial stiffness.     

The ratio of eicosapentaenoic acid to arachidonic acid is a critical risk factor for acute coronary syndrome in middle-aged older patients as well as younger adult patients

BackgroundCoronary risk factors for the onset of acute coronary syndrome (ACS), including polyunsaturated fatty acids (PUFAs), in younger adult patients may be different from those in older patients.Methods and resultsWe enrolled 578 patients who underwent coronary angiography at Fukuoka Saiseikai Hospital, and divided them into a younger adult group (YG) (<50 years, n = 47) and a middle-aged older group (OG) (≥50 years, n = 531). In a multivariate analysis, lower levels of high-density lipoprotein cholesterol and the ratio of eicosapentaenoic acid (EPA) to arachidonic acid (AA) (EPA/AA), and less aspirin, oral hypoglycemic agent, and calcium channel blocker (CCB) use were independent risk factors for ACS in all patients. In YG, lower levels of EPA/AA and less angiotensin II receptor blocker/angiotensin-converting enzyme inhibitor use were the independent risk factors. In OG, smoking, lower levels of EPA/AA, less aspirin and CCB use were the risk factors. While lower levels of EPA/AA was the only risk factor for ACS that was common to all patients, YG and OG, docosahexaenoic acid/AA was not associated with ACS in YG and OG.ConclusionsLower level of EPA/AA is a common critical risk factor for ACS in middle-aged older patients as well as younger adult patients. Some of the risk factors for the onset of ACS in younger patients were different from those in older patients.     

The role of epicardial adipose tissue in coronary artery disease in non-obese patients

BackgroundEpicardial adipose tissue (EAT) surrounding the heart may contribute to the development of coronary artery disease (CAD) through its local secretion of adipocytokines. Although the quantity of EAT is associated with obesity and metabolic syndrome, the role of EAT in the development of CAD in non-obese patients remains to be determined.MethodsThis study included 41 patients with CAD who underwent coronary artery bypass graft surgery and 28 patients without CAD who underwent other cardiac surgery. EAT volume was measured by 64-slice multi-detector computed tomography before the surgery. We obtained pericardial fluid and epicardial and subcutaneous adipose tissue samples at the surgery. We investigated the relationship between EAT volume and adiponectin levels in pericardial fluid and incident CAD in patients with and without obesity (body mass index > 25 kg/m²).ResultsThere was no significant difference in EAT volume between obese patients with and without CAD (55.5 ± 40.2 mL vs. 40.1 ± 19.7 mL, p = 0.323). However, EAT volume was significantly greater in non-obese patients with CAD compared to those without CAD (35.0 ± 18.8 mL vs. 15.7 ± 11.0 mL, p < 0.001). Adiponectin concentrations in pericardial fluid were significantly lower in non-obese patients with CAD compared to those without CAD (2.7 ± 2.0 μg/mL vs. 4.3 ± 3.7 μg/mL, p = 0.049), whereas the adiponectin levels were decreased in obese patients regardless of the presence of CAD. Non-obese patients with CAD had significantly larger size adipocytes in EAT but not subcutaneous adipose tissue compared to those without CAD. Multiple logistic regression analysis showed that increased EAT volume was independently associated with incident CAD in non-obese patients.ConclusionIncreased EAT may play a crucial role in development of CAD through impairment of adiponectin secretion in non-obese patients.     

Increased level of resistin predicts development of atrial fibrillation

BackgroundResistin is a peptide hormone that is secreted from lipid cells and is linked to type-2 diabetes, obesity, and inflammation. Being an important adipocytokine, resistin was proven to play an important role in cardiovascular disease. We compared resistin levels in patients with and without atrial fibrillation (AF) to demonstrate the relationship between plasma resistin levels and AF.MethodOne hundred patients with AF and 58 control patients who were matched in terms of age, gender, and risk factors were included in the trial. Their clinical risk factors, biometric measurements, echocardiographic work up, biochemical parameters including resistin and high-sensitivity C-reactive protein (hs-CRP) levels were compared.ResultsIn patients with AF, plasma resistin levels (7.34 ± 1.63 ng/mL vs 6.67 ± 1.14 ng/mL; p = 0.003) and hs-CRP levels (3.01 ± 1.54 mg/L vs 2.16 ± 1.28 mg/L; p = 0.001) were higher than control group. In subgroup analysis, resistin levels were significantly higher in patients with paroxysmal (7.59 ± 1.57 ng/mL; p = 0.032) and persistent AF (7.73 ± 1.60 ng/mL; p = 0.006), but not in patients with permanent AF subgroups (6.86 ± 1.61 ng/mL; p = 0.92) compared to controls. However, hs-CRP levels were significantly higher only in permanent AF patients compared to control group (3.26 ± 1.46 mg/L vs 2.16 ± 1.28 mg/L; p = 0.02). In multivariate regression analysis using model adjusted for age, gender, body mas index, hypertension, diabetes mellitus, and creatinine levels, plasma resistin levels [odds ratio (OR): 1.30; 95% confidence interval (CI): 1.01–1.70; p = 0.04] and hs-CRP levels (OR: 1.44; 95% CI: 1.12–1.86; p = 0.004) were the only independent predictors of AF.ConclusionThe elevated levels of plasma resistin were related to paroxysmal AF group and persistent AF group, but not to permanent AF group.     

Paraoxonase 1 gene (Gln192–Arg) polymorphism and the risk of coronary artery disease in type 2 diabetes mellitus

BackgroundParaoxonase 1 (PON1) is reported to have antioxidant and cardioprotective properties. Recently, an association of glutamine (Gln) or type A/arginine (Arg) or type B polymorphism at position 192 of PON1 gene has been suggested with coronary artery disease (CAD) among patients with diabetes mellitus (DM). However, conflicting results have also been reported.ObjectivesTo investigate the relationship between PON1 gene (Gln¹⁹²–Arg) polymorphism and the presence, extent and severity of CAD in type 2 DM.MethodsThe study comprised 180 patients recruited from those undergoing coronary angiography for suspected CAD, who were divided according to the presence or absence of CAD and DM into four groups: Group I (n = 40 patients) nondiabetic subjects without CAD, Group II (n = 45 patients) diabetic patients without CAD, Group III (n = 47 patients) nondiabetic patients with CAD and Group IV (n = 48 patients) diabetic patients with CAD. PON1(Gln¹⁹²–Arg) genotype was assessed using polymerase chain reaction (PCR) followed by AlwI digestion.ResultsThe frequency of Gln allele (type A) was significantly higher in Group I and Group II compared to Group III and Group IV (62.5%, 60% vs. 38.3%, 31.25%, respectively, p < 0.001) while the frequency of Arg allele (type B + type AB) was significantly higher in ischemic groups (III and IV) compared to nonischemic groups (I and II) (61.7%, 68.75% vs. 37.5%, 40%, respectively, p < 0.001). Patients with CAD and DM (Group IV) have significantly higher severity score and vessel score than those with CAD only (Group III) (9.7 ± 2.97, 2.44 ± 0.56 vs. 6.99 ± 3.71, 1.67 ± 0.89, respectively, p < 0.001) Patients with vessel score 3 had significantly higher severity score and higher Arg allele frequency than patients with vessel score 2, the latter group had also significantly higher severity score and Arg allele frequency than patients with vessel score 1 (8.9 ± 2.79 vs. 5.21 ± 2.13 and 80.49% vs. 67.86%), (5.21 ± 2.13 vs. 3.11 ± 0.89 and 67.86% vs. 53.85%), p < 0.001 for all. In multivariate logistic regression analysis of different variables for prediction of CAD, age [OR 2.99, CI (1.11–10.5), p < 0.01], smoking [OR 4.13, CI (1.37–11.7), p < 0.001], low-density lipoprotein (LDL) cholesterol > 100 mg/dL [OR 4.31, CI (1.25–12.5), p < 0.001], high-density lipoprotein (HDL) cholesterol < 40 mg/dL [OR 5.11, CI (1.79–16.33), p < 0.001] and PON1 192 Arg allele [OR 4.62, CI (1.67–13.57), p < 0.001] were significantly independent predictors of CAD.ConclusionArg allele of PON1 192 gene polymorphism is an independent risk factor for CAD and is associated not only with the presence of CAD but also with its extent and severity and its impact is clearly more pronounced in diabetic patients.     

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.     

Matrix metalloproteinase-9 (MMP9) and high sensitivity C – Reactive protein (hs-CRP) in coronary artery ectasia

ObjectiveThe specific causative mechanisms of abnormal luminar dilatation in coronary artery ectasia (CAE) are essentially unknown. Destruction of the extracellular matrix may be responsible for ectasia formation. Thus, we investigated the role of matrix metalloproteinases (MMP9), and inflammatory marker (high-sensitive C-reactive protein) in CAE patients.MethodsThis study consisted of 30 consecutive CAE patients, 30 obstructive coronary artery disease (CAD) patients, and 20 controls with normal coronary arteries undergoing cardiac catheterization. Plasma levels of MMP-9, and hs-CRP were measured.ResultsHs-CRP level was significantly higher in the the CAE group than both in the CAD and control groups (2.3 ± 0.5, 1.19 ± 0.54, 0.8 ± 0.3 mg/l, respectively, both p < 0.001), while, MMP-9 level was significantly higher in both CAE group and CAD than control groups (27.71 ± 4.7, 25.2 ± 4.1, 18.6 ± 3.3 ng/ml, respectively , both p < 0.001). In subgroup analyses, MMP-9 level was significantly higher in CAE patients with multivessel involvement compared to those with single-vessel ectasia (29.4 ± 3.1 vs. 25.2 ± 5.5 ng/ml, P = 0.01), while hs CRP level was comparable in both groups (2.3 ± 0.52 vs. 2.4 ± 0.45 ng/ml, P = 0.82).ConclusionOur results suggest that the increased levels of MMP-9, hs-CRP may be responsible for ectasia formation in patients with CAE and plasma level of MMP-9 is correlated with the severity of CAE.     

Patterns of serum lipids derangements and cardiovascular risk assessment in patients with primary biliary cholangitis

Introduction and objectivesPrimary biliary cholangitis (PBC) is a chronic cholestatic autoimmune disease that disrupts the cholesterol metabolism. Our aim was to investigate the frequency of dyslipidemias and to evaluate the risk of cardiovascular events in a historic cohort of patients with PBC.PatientsAll patients attended from 2000 to 2009 with histological diagnosis of PBC were included and were compared with healthy controls. The 10-year cardiovascular risk was estimated by the Framingham risk score.ResultsFifty four patients with PBC were included and compared to 106 controls. Differences in total cholesterol (263.8 ± 123.9 mg/dl vs. 199.6 ± 40, p = 0.0001), LDL-cholesterol (179.3 ± 114.8 vs. 126.8 ± 34.7, p = 0.0001), HDL-cholesterol (62.4 ± 36.2 mg/dl vs. 47.3 ± 12.3, p = 0.0001) and triglycerides (149.1 ± 59.1 mg/dl vs. 126.4 ± 55.4, p = 0.001) were found. Hypercholesterolemia (>240 mg/dl) was found in 52.4% of the patients with PBC vs. 11% in the control group, high LDL-cholesterol (160–189 mg/dl) in 45.2% of the patients with PBC vs. 10% in controls and hyperalphalipoproteinemia (HDL-cholesterol >60 mg/dl) in 45.2% of the patients with PBC vs. 16% in controls. The 10-year cardiovascular risk was 5.3% ± 5.9 in the patients with PBC and 4.1% ± 5.7 in the control group (p = 0.723, IC 95% = 0.637–1.104). Only one cardiovascular event (stroke) in a patient with PBC was registered in a mean follow up time of 57.9 ± 36.5 months.ConclusionsMarked derangements in serum lipids and a high frequency of dyslipidemias are found in patients with PBC, however, these do not increase the risk of cardiovascular events.     

Adrenalectomy improves increased carotid intima-media thickness and arterial stiffness in patients with aldosterone producing adenoma

ContextPrimary aldosteronism (PA) is the most frequent cause of secondary hypertension, and is associated with more prominent vascular stiffness and atherosclerosis. However, the effect of adrenalectomy on reversibility of vascular damage is unclear.ObjectiveOur objective was to investigate the vascular changes and possibility of reversibility after adrenalectomy in PA patients.MethodsWe prospectively analyzed 20 patients with aldosterone producing adenoma (APA) that received adrenalectomy from October 2006 to December 2008 and 21 patients with essential hypertension (EH) were enrolled as the control group. Carotid intima media thickness (CIMT) measurement by B-mode ultrasound of the right common carotid arteries and pulse wave velocity (PWV) measurement including brachial–ankle PWV (baPWV) and heart–ankle PWV (haPWV) were performed in both groups. The follow-up measurements were performed one-year after adrenalectomy in APA group.ResultsAPA patients had significantly higher diastolic blood pressure, plasma aldosterone concentration (PAC) and aldosterone-renin ratio (ARR), but lower serum potassium level and plasma renin activity (PRA) than EH patients. APA patients had significantly higher CIMT (0.64 ± 0.13 vs. 0.53 ± 0.10 mm, p = 0.006), higher baPWV (1589 ± 296 vs. 1405 ± 187 cm/s, p = 0.024) and haPWV (1095 ± 150 vs. 987 ± 114 cm/s, p = 0.013) comparing with EH patients. One-year after adrenalectomy, CIMT reduced significantly from 0.64 ± 0.13 mm to 0.59 ± 0.14 mm (p = 0.014), and baPWV and haPWV also showed significant reduction (baPWV, 1589 ± 296 to 1463 ± 188 cm/s, p = 0.035; haPWV, 1095 ± 150 to 1017 ± 109 cm/s, p = 0.019).ConclusionAPA patients have higher degree of early atherosclerosis and vascular stiffness. Adrenalectomy not only corrects the high blood pressure and biochemical parameters but also reverse adverse vascular change in APA patients.     

Role of delayed contrast enhancement cardiovascular magnetic resonance at 3.0 Tesla in patients with chronic heart failure

IntroductionCardiovascular magnetic resonance (CMR) with delayed contrast enhancement (DCE) has been recently emerged as an easy-to-perform method for differentiation between normal and diseased myocardium. The aim of this study was to delineate the etiology of chronic heart failure (CHF) non-invasively using DCE-CMR at 3.0 Tesla.MethodsThirty-four patients with CHF, left ventricular ejection fraction (LVEF) <40%, and no clear history or objective evidence of coronary artery disease (CAD) were evaluated by contrast-enhanced CMR (Philips Achiva 3.0 T) and conventional coronary angiography. Significant CAD was defined as >50% diameter stenosis of major epicardial coronary vessel.ResultsFifteen patients showed subendocardial and/or transmural pattern of DCE (group A). Nineteen patients showed pattern of mid wall and/or subepicardial or no DCE (group B). Group A patients were older (52 ± 9 vs. 45 ± 10 years, p = 0.042), had higher prevalence of diabetes mellitus, hypertension and dyslipidemia, p = 0.001. LVEF was comparable in both groups. Coronary angiography showed significant CAD in 14/15 patients in group A. The other patient had coronary artery ectasia of the left anterior descending coronary artery. Normal angiogram was seen in 18/19 patients in group B. The other patient had 60% diameter stenosis of mid dominant right coronary artery. The sensitivity and specificity of DCE-CMR for detection of CAD were 93.3% and 94.7% respectively. The positive likelihood ratio was 17.74.ConclusionPattern of DCE-CMR at 3.0 Tesla may help delineation of etiology of CHF and makes clear distinction between ischemic and non-ischemic pathomorphology.     

Polymorphisms of TGFB1, TLE4 and MUC22 are associated with childhood asthma in Chinese population

ObjectiveTo investigate whether the genetic variants of TGFB1, TLE4, MUC22 and IKZF3 are associated with the development of asthma in Chinese children.Methods572 adolescent asthma patients and 590 age-matched healthy controls were included in this study. A total of four SNPs were genotyped, including rs2241715 of TGFB1, rs2378383 of TLE4, rs2523924 of MUC22, and rs907092 of IKZF3. Allele frequencies of the patients and the control group were compared by the Chi-square test. The Student t test was used to analyse the relationship between genotypes and clinical feature of the patients.ResultsPatients were found to have significantly different frequencies of allele A of rs2241715, allele G of rs2378383 and allele A of rs2523924 as compared with the controls (40.4% vs. 45.9%, p = 0.01 for rs2241715; 17.2% vs. 13.4%, p = 0.01 for rs2378383; 15.3% vs. 11.9%, p = 0.02 for rs2523924). For patients with severe asthma, those with genotype AA/AG of rs2241715 had remarkably higher FEV1% as compared with those with genotype GG (59.1 ± 4.3% vs. 55.4 ± 3.7%, p < 0.001). Moreover, those with genotype GG/GA of rs2378383 had remarkably lower FEV1% as compared with those with genotype AA (54.6 ± 2.9% vs. 58.6 ± 4.1%, p < 0.001).ConclusionsGenes TGFB1, TLE4 and MUC22 are associated with the risk of childhood asthma in Chinese population. Our results associating TGFB1 and TLE4 with clinical features of asthma suggest potential application of these parameters in the management of asthma children.     

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.     

Levels of plasma cell-free DNA and its correlation with disease activity in rheumatoid arthritis and systemic lupus erythematosus patients

BackgroundCell free deoxyribonucleic acid (cf-DNA) is now emerging as a useful tool for non-invasive diagnostic methods related to a wide range of clinical conditions including autoimmune diseases.Aim of the workTo estimate the concentration of plasma cf-DNA in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients compared with healthy subjects and to correlate the results with clinical and laboratory parameters of disease activity.Patients and methodsThe study included 30 RA patients, 35 SLE patients and 25 matched control. Plasma cf-DNA was estimated by real-time quantitative PCR. Disease activity parameters for each disease were assessed; Disease Activity Score-28 (DAS28) was used for RA and SLE disease activity index 2000 (SLEDAI-2K) for SLE patients.ResultsThe RA patients (F:M 4:1) had a mean age of 36.8 ± 9.6 years and disease duration of 8.3 ± 1.1 years while the SLE patients (F:M 7.75:1) had a mean age of 35.6 ± 8.8 years and disease duration of 8.1 ± 0.87 years. There was a highly significant increase in the cf-DNA level in SLE patients (17.33 ± 2.4 ng/ml) and RA patients (11.15 ± 2.3 ng/ml) compared to the level in the control (4.15 ± 1.4 ng/ml) (p = 0.0005). The cf-DNA significantly correlated with the erythrocyte sedimentation rate (ESR) (p = 0.04), C-reactive protein (p = 0.04) and the DAS28 (p = 0.005) in the RA patients and with the ESR (p = 0.03), anti-ds-DNA (p = 0.008), complement-4 (p = 0.04) and SLEDAI-2K (p = 0.002).ConclusionThe increased cf-DNA implicates a possible role in the pathogenesis of both RA and SLE and appears to be a useful marker of disease activity in addition to other laboratory tests.     

Early-stage atherosclerosis in newly diagnosed,untreated type 2 diabetes mellitus and impaired glucose tolerance

AimThe aim of this study was to investigate early-stage atherosclerosis in newly diagnosed, untreated type 2 diabetes mellitus (T2DM) and impaired glucose tolerance (IGT).MethodsThe study subjects underwent an oral glucose tolerance test (OGTT) and were then divided into three groups, according to plasma glucose level: those in the normal glucose tolerance (NGT) group had fasting plasma glucose (FPG) < 6.1 mmol/L and 2 h postload glucose (2hPPG) < 7.8 mmol/L; those in the IGT group had FPG < 6.1 mmol/L and 2hPPG ≥ 7.8 mmol/L; and those in the T2DM group had FPG ≥ 7.0 mmol/L or 2hPPG ≥ 11.1 mmol/L. Haemodynamic variables and brachial–ankle pulse-wave velocities (baPWV) in the three groups were compared.ResultsThe baPWV value increased with increases in plasma glucose, and was significantly and positively correlated to age, FPG, 2hPPG, systolic blood pressure (SBP), diastolic blood pressure (DBP), waist circumference and waist-to-hip ratio. Significant differences were found between the baPWV values in the NGT and IGT groups (1602 ± 347 vs 1707 ± 351 cm/s, respectively; P = 0.005), and between the NGT and DM groups (1602 ± 347 vs 1762 ± 381, respectively; P < 0.001). The results of multiple regression analyses showed that 2hPPG was closely related to baPWV as well as to SBP and DBP.ConclusionEarly-stage atherosclerosis is present in newly diagnosed, untreated T2DM and IGT patients, and it may be that its early assessment, along with good control of hypertension and hyperglycaemia, will help to delay its progression.     

Relationship of apolipoprotein E polymorphism with lipid profiles in atherosclerotic coronary artery disease

AimsThe aim was to determine the relationship between apolipoprotein E (ApoE) gene polymorphisms and lipid profile in patients with coronary artery diseases (CAD), and its role in the prediction of the severity of carotid and coronary atherosclerosis.Methods and resultsOne hundred patients were classified by coronary angiography: 80 patients with CAD and 20 controls (normal coronary angiography). Clinical data, carotid sonography, blood lipid profiles and ApoE genotyping (PCR-RFLP) were assessed. CAD patients had significantly increased plasma lipid profiles and carotid intimal-wall thickness (IMT) versus controls. In CAD patients; ApoE genotype frequencies were E3/E3 = 62.50%, E2/E3 = 18.75%, E3/E4 = 17.50%, E2/E4 = 1.25%, E4/E4 = 0 and E2/E2 = 0. But, E3/E4 genotype was significantly higher than controls (P < 0.05). Also, in CAD patients; ApoE allele frequencies were E3 = 80.6%, E2 = 10.0% and E4 = 9.4% but, ApoE4 alleles were associated with higher cholesterol (P = 0.034) and LDL-c (P = 0.003), while ApoE2 alleles were associated with higher triglycerides (P = 0.037) versus ApoE3 alleles. However, odds ratio of CAD patients had higher risk with E2/E3 genotypes (2.5-fold), E2 alleles (2.2-fold) and E4 alleles (2.1-fold). Moreover, CAD patients with ApoE4 alleles had significantly higher carotid IMT (1.23 ± 0.26 mm vs 0.97 ± 0.2 mm ApoE3, P = 0.006; however, non-significant vs 1.10 ± 0.40 mm ApoE2 and also, ApoE2 vs ApoE3 alleles, P = 0.633) and left anterior descending (LAD) coronary artery stenosis (vs ApoE3 alleles, P = 0.016).ConclusionIschemic patients with carotid and coronary atherosclerosis had significantly higher integration of dyslipidemia and ApoE alleles (ApoE2 with hypertriglyceridemia and ApoE4 with hypercholesterolemia and higher LDL-c). ApoE polymorphism may be an important diagnostic risk biomarker and may implicate therapeutic intervention in atherosclerotic ischemic patients.     

Aortic stiffness is increased in patients with premature coronary artery disease: A tissue Doppler imaging study

BackgroundAtherosclerosis and arterial stiffening may coexist and the correlation of these parameters in patients with premature coronary artery disease (CAD) has not been well elucidated. Tissue Doppler imaging of the ascending aorta may be used in the assessment of elastic properties of the great arteries.ObjectiveTo investigate the correlation between aortic stiffness and premature CAD using parameters derived from two-dimensional and tissue Doppler imaging (TDI) echocardiography of the ascending aorta.MethodsFifty consecutive subjects younger than 40 years old who were hospitalized with diagnosis of acute coronary syndrome and had undergone coronary angiography were recruited. The control group included 70 age–sex matched individuals without a diagnosis of CAD. Aortic stiffness index (SI), aortic distensibility (D), and pressure-strain elastic modulus (E_p) were calculated from the aortic diameters measured by two-dimensional M-mode echocardiography and blood pressure obtained by sphygmomanometry. Aortic systolic velocity (S_Ao), and early (E_Ao) and late (A_Ao) diastolic velocities were determined by pulse-wave TDI from the anterior wall of ascending aorta 3 cm above the aortic cusps in parasternal long-axis view.ResultsStiffness index was higher [median 5.40, interquartile range (IQR) 5.98 vs. median 4.14 IQR 2.43; p = 0.03] and distensibility was lower (median 2.86 × 10⁻⁶ cm²/dyn, IQR 2.51 × 10⁻⁶ cm²/dyn vs. median 3.46 × 10⁻⁶ cm²/dyn, IQR 2.38 × 10⁻⁶ cm²/dyn; p = 0.04) in patients with CAD compared to the control group. E_Ao was significantly lower in the CAD group (7.2 ± 1.8 cm/s vs. 9.2 ± 2.4 cm/s, p < 0.01). The difference in E_Ao remained significant when CAD patients with a left ventricular ejection fraction >55% was compared to the control group. S_Ao and A_Ao velocities of ascending aorta were similar in control and CAD groups. There was a significant correlation between E_Ao velocity and aortic stiffness index (r = −0.28, p = 0.01), distensibility (r = 0.19, p = 0.04) and elastic modulus (r = −0.24, p = 0.01). In multivariate regression analysis, decreased levels of high-density lipoprotein cholesterol [odds ratio (OR): 1.12 95% CI 1.06–1.19; p = 0.01] and E_Ao (OR: 1.41 95% CI 1.12–1.79; p = 0.01) measurements remained as the variables independently correlated with premature CAD in the study group.ConclusionArterial stiffness is increased in patients with premature CAD. E_Ao of the anterior wall of ascending aorta measured with pulse-wave TDI echocardiography is correlated with arterial stiffening and is decreased in patients with premature CAD.     

Prediction of atrial fibrillation after ischemic stroke using P-wave signal averaged electrocardiography

BackgroundAtrial fibrillation (AF) is highly prevalent in patients with ischemic stroke, but the diagnosis is often difficult.MethodsThis study consisted of 68 stroke patients in sinus rhythm without history of AF. All patients underwent P-wave signal-averaged electrocardiography (P-SAECG), echocardiography, 24-h Holter monitoring, and measurement of plasma B-type natriuretic peptide (BNP) concentrations at admission.ResultsAn abnormal P-SAECG was found in 34 of 68 stroke patients. In the follow-up period of 11 ± 4 months, AF developed in 17 patients (AF group). The remaining 51 patients were classified as the non-AF group. The prevalence of atrial late potentials (ALP) on P-SAECG, and the number of premature atrial contractions (PACs) were significantly higher in the AF group than those in the non-AF group (88.2% vs 37.3%; p < 0.001, 149 ± 120 vs 79 ± 69; p = 0.030, respectively). However, there were no significant differences in age, left atrial dimension, or BNP concentrations between both groups. Cox proportional hazards analysis revealed that the presence of ALP (risk ratio 11.15; p = 0.002) and frequent PACs (more than 100/24 h) (risk ratio 4.53; p = 0.007) had significant correlation to the occurrence of AF.ConclusionsALP may be a novel predictor of AF in stroke patients. P-SAECG should be considered in stroke of undetermined etiology.     

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.     

Neutrophil,lymphocyte and platelet ratio as a predictor of mortality in septic-acute kidney injury patients

BackgroundAKI is frequent in critically ill patients, in whom the leading cause of AKI is sepsis. The role of intrarenal and systemic inflammation appears to be significant in the pathophysiology of septic-AKI. The neutrophils to lymphocytes and platelets (N/LP) ratio is an indirect marker of inflammation. The aim of this study was to evaluate the prognostic ability of N/LP ratio at admission in septic-AKI patients admitted to an intensive care unit (ICU).MethodsThis is a retrospective analysis of 399 septic-AKI patients admitted to the Division of Intensive Medicine of the Centro Hospitalar Universitário Lisboa Norte between January 2008 and December 2014. The Kidney Disease Improving Global Outcomes (KDIGO) classification was used to define AKI. N/LP ratio was calculated as: (Neutrophil count × 100)/(Lymphocyte count × Platelet count).ResultsFifty-two percent of patients were KDIGO stage 3, 25.8% KDIGO stage 2 and 22.3% KDIGO stage 1. A higher N/LP ratio was an independent predictor of increased risk of in-hospital mortality in septic-AKI patients regardless of KDIGO stage (31.59 ± 126.8 vs 13.66 ± 22.64, p = 0.028; unadjusted OR 1.01 (95% CI 1.00–1.02), p = 0.027; adjusted OR 1.01 (95% CI 1.00–1.02), p = 0.015). The AUC for mortality prediction in septic-AKI was of 0.565 (95% CI (0.515–0.615), p = 0.034).ConclusionsThe N/LP ratio at ICU admission was independently associated with in-hospital mortality in septic-AKI patients.     

The alternative complement pathway activity may depend on plasma malondialdehyde level in systemic lupus erythematosus patients: Preliminary results

BackgroundMalondialdehyde (MDA) is a marker of oxidative stress (OS) and one of the major alternative complement pathway (ACP) activators associated with systemic lupus erythematosus (SLE) activity. ACP is the principal mediator of SLE inflammation and progression.Aim of the workTo investigate the association between the ACP functional activity and plasma MDA in SLE patients.Patients and methodsSixteen consecutive SLE patients were analyzed for their complement profile and oxidative stress measurement. 60 healthy subjects were included as a control group. The Complement components C3, C4 and properdin-factor B (PfB) were assessed, ACP activity was assayed according to alternative hemolytic 50 (AH₅₀). Plasma total lipid peroxide quantification was performed by assessing the plasma MDA. Total antioxidant capacity was measured with oxygen radical absorbance capacity (ORAC). OS ratio was calculated by dividing the total antioxidant capacity by MDA.ResultsSixteen patients (13 females and 3 males) with a mean age of 27.86 ± 6.26 years and a disease duration 69.65 ± 54.65 months were included. There was a significant increase of MDA in the patients (MFI = 613 ± 56.21) compared to the control (MFI = 460 ± 37.85) (p = 0.003). C3 was significantly consumed and MDA increased in the low AH50 compared to the normal AH50 patients (p = 0.02 and p = 0.01 respectively). AH50 significantly negatively correlated with the C3 (p = 0.02) and MDA (p = 0.048). There was lack of any association between ORAC and ACP. Properdin factor B significantly negatively correlated with C3 (p = 0.007).ConclusionsThese initial results encourage future in-depth studies on the association of OS–ACP in SLE pathogenesis.