Altered lipidome and antioxidative activity of small,dense HDL in normolipidemic rheumatoid arthritis: Relevance of inflammation

Objective: High-density lipoprotein (HDL) particles exert potent antiatherogenic activities, including antioxidative actions, which are relevant to attenuation of atherosclerosis progression. Such activities are enriched in small, dense HDL and can be compromised under conditions of chronic inflammation like rheumatoid arthritis (RA). However, structure–function relationships of HDL largely remain indeterminate. Methods: The relationships between HDL structure and function were evaluated in normolipidemic patients with active RA (DAS28 > 3.2; n = 12) and in normolipidemic age-matched controls (n = 10). Small, dense HDL3b and 3c particles were isolated from plasma or serum by density gradient ultracentrifugation and their physicochemical characteristics, lipidome (by LC/MS/MS) and antioxidative function (as protection of normolipidemic LDL from free radical-induced oxidation) were evaluated. Results: As expected, active RA patients featured significantly elevated plasma levels of high-sensitivity C-reactive protein (hsCRP; p < 0.001) and serum amyloid A (SAA; p < 0.01) relative to controls. Antioxidative activity and weight % chemical composition of small, dense HDL did not differ between RA patients and controls (p > 0.05), whereas HDL phosphosphingolipidome was significantly altered in RA. Subgroup analyses revealed that RA patients featuring high levels of inflammation (hsCRP>10 mg/l) possessed small, dense HDL with reduced antioxidative activities (p < 0.01). Furthermore, antioxidative activity of HDL was inversely correlated with plasma hsCRP (p < 0.01). Conclusions: These data revealed that (i) despite normolipidemic state, the lipidome of small, dense HDL was altered in RA and (ii) high levels of inflammation can be responsible for the functional deficiency of small, dense HDL in RA.     

Angiopoietin-like protein 4 significantly predicts future cardiovascular events in coronary patients

Background: Angiopoietin-like protein 4 (ANGPTL4) has been associated with cardiometabolic disorders including dyslipidemia and atherosclerosis in animal studies; in humans, however, its impact on metabolic traits and cardiovascular risk remains unclear. Methods: We examined the association of plasma ANGPTL4 levels with the metabolic syndrome (harmonized consensus definition), with angiographically determined coronary artery disease (CAD), and with the risk of future cardiovascular events in a cohort of 490 patients undergoing coronary angiography for the evaluation of stable CAD. In addition, we investigated the influence of the tagging single nucleotide polymorphisms (SNPs) rs4076317, rs2278236, rs1044250, and rs11672433 as well as variant rs116843064 (E40K) of the ANGPTL4 gene on cardiovascular risk in a larger sample of 983 angiographied coronary patients including the above mentioned 490 subjects. Results: Plasma ANGPTL4 was significantly higher in patients with the metabolic syndrome than in subjects without the metabolic syndrome (26.0 ± 19.4 ng/ml vs. 22.2 ± 19.7 ng/ml; p = 0.008). No significant association was found between ANGPTL4 and angiographically characterized coronary atherosclerosis. Prospectively, however, plasma ANGPTL4 significantly predicted future cardiovascular events both univariately (HR1.45 [1.16–1.82], p = 0.001) and after adjustment for standard cardiovascular risk factors (1.26 [1.01–1.58]; p = 0.045). Concordantly, rs4076317, rs2278236, and rs1044250 significantly affected the risk of future cardiovascular events (adjusted HRs 0.70 [0.54–0.90]; p = 0.005, 0.76 [0.61–0.94]; p = 0.012, and 1.30 [1.03–1.62]; p = 0.025, respectively). Conclusions: We conclude that plasma ANGPTL4 levels as well as ANGPTL4 variants significantly predict cardiovascular events independently of conventional cardiovascular risk factors.     

Serum glucose and lipid levels in adult congenital heart disease patients

Atherosclerosis has been correlated with known cardiovascular risk factors such as serum glucose or lipid levels. Because congenital heart disease patients tend to survive until adulthood, atherosclerosis has also become a matter of concern in these patients. One hundred fifty-eight congenital heart disease patients and 152 patients selected at random from the population were studied and compared to determine serum glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, and triglycerides levels. Both groups had similar socioeconomic status levels and the same environmental influences. Significant differences were seen between congenital heart disease patients and the control group, after sex, age, and body mass index adjustment, in fasting plasma glucose (97.7 [94.2-101.2] vs 86.9 [83.2-90.7], P < .001), total cholesterol (171.5 [165.7-177.3] vs 199.8 [90.7-206.0], P < .001), LDL cholesterol (103.9 [98.8-108.8] vs 123.8 [118.5-129.1], P < .001), and high-density lipoprotein cholesterol (48.1 [46.2-50.0] vs 54.2 [52.1-56.2], P < .001) levels. Nonsignificant differences were seen in triglycerides concentrations. Those patients with ventricular septal defect, coarctation of the aorta, and cyanosis had the lowest total cholesterol and LDL cholesterol concentrations. Congenital heart disease patients have lower plasma cholesterol concentrations and higher serum glucose levels than noncongenital ones.     

Impact of counterbalance between macrophage migration inhibitory factor and its inhibitor Gremlin-1 in patients with coronary artery disease

Objective: Monocyte infiltration is a critical step in the pathophysiology of plaque instability in coronary artery disease (CAD). Macrophage migration inhibitory factor (MIF) is involved in atherosclerotic plaque progression and instability leading to intracoronary thrombosis. Gremlin-1 (Grem1) has been recently identified as endogenous inhibitor of MIF. To date there are no data on the clinical impact of this interaction in cardiovascular patients. Methods and results: Plasma levels of MIF and Grem1 were determined by enzyme-linked immunoassay in patients with acute coronary syndromes (ACS, n = 120; stable CAD, n = 166 and healthy control subjects, n = 25). MIF levels were significantly increased in ACS compared to stable CAD and healthy control (ACS: median 2.85; IQR 3.52 ng/ml; versus SAP: median 1.22; IQR 2.99 ng/ml; versus healthy control: median 0.10; IQR 0.09 ng/ml, p < 0.001). Grem1 levels were significantly higher in ACS and stable CAD patients compared to healthy control (ACS: median 211.00; IQR 130.47 ng/ml; SAP: median 220.20; IQR 120.93 ng/ml, versus healthy control: median 90.57; IQR 97.68 ng/ml, p < 0.001). Grem1/MIF ratio was independently associated with ACS, whereas the single parameters were not associated with the presence of ACS. Furthermore, Grem1/MIF ratio was associated with angiographic signs of intracoronary thrombi and severity of thrombus burden. Conclusion: These novel findings suggest a potential role of Grem1/MIF ratio to indicate acuity of CAD and the grade of plaque stability. Prospective angiographic cohort studies involving plaque imaging techniques are warranted to further characterize the prognostic role of this novel risk marker in CAD patients.     

LDL cholesterol as a novel risk factor for contrast-induced acute kidney injury in patients undergoing percutaneous coronary intervention

Background: Low density lipoprotein cholesterol (LDL-C) is associated with endothelial dysfunction, inflammation and increased vasoconstriction, which are involved in the development of contrast-induced acute kidney injury (CI-AKI). However, whether LDL-C is an independent risk factor of CI-AKI in patients undergoing percutaneous coronary intervention (PCI) is unknown. Methods: We prospectively enrolled 3236 consecutive patients undergoing PCI between January 2010 and September 2012. Multivariate logistic regression analysis was used to determine whether LDL-C is an independent risk factor of CI-AKI. CI-AKI was defined as an absolute increase in serum creatinine of ≥0.5 mg/dL or ≥25% over the baseline value within 48–72 h after contrast exposure. Results: CI-AKI was observed in 338 patients (10.4%). Patients with CI-AKI had a significantly higher rate of in hospital mortality (4.4% vs. 0.5%, p < 0.001), and significantly higher rates of other in hospital complications compared with those without CI-AKI. The LDL-C quartiles were as follows: Q1 (<2.04 mmol/L), Q2 (2.04–2.61 mmol/L), Q3 (2.61–3.21 mmol/L) and Q4 (>3.21 mmol/L). Patients with high baseline LDL-C levels were more likely to develop CI-AKI and composite end points including all-cause mortality, renal replacement therapy, non-fatal myocardial infarction, acute heart failure, target vessel revascularization or cerebrovascular accident during the observation period of hospitalization (8.9%, 9.9%, 10.5%, 12.6%, p = 0.001, and 5.0%, 5.2%, 6.1%, 8.1%, respectively; p = 0.007). Univariate logistic analysis showed that LDL-C levels (increment 1 mmol/L) were significantly associated with CI-AKI (odds ratio = 1.25, 95% confidence interval (CI), 1.11–1.39, p < 0.001). Furthermore, LDL-C remained a significant risk factor of CI-AKI (odds ratio = 1.23, 95% CI, 1.04–1.45, p = 0.014), even after adjusting for potential confounding risk factors. Conclusions: Measurement of plasma LDL-C concentrations in patients undergoing PCI may be helpful to identify those who are at risk of CI-AKI and poor in hospital outcomes.     

Intact parathyroid hormone levels are associated with increased carotid intima media thickness in HIV infected patients

Aim. Preliminary evidence suggests that intact parathyroid hormone (iPTH) and bone mineral abnormalities may contribute to the development of vascular disease and are associated with reduced survival in the general population. Whether iPTH is associated with subclinical atherosclerosis in HIV-infected individuals has not been elucidated. Methods. Cross-sectional study of 470 consecutive HIV-infected patients in whom we measured carotid intima-media thickness (cIMT), and collected demographical, clinical and laboratory data. High-cIMT was defined as a mean IMT above the 75th percentile for the study cohort. Parametric, non-parametric tests and logistic regression analyses were used to compare patients' characteristics between low- and high-cIMT and to test the association between high-cIMT and log-transformed iPTH. Results. Of the 470 patients, 130 had high-cIMT. High-cIMT subjects were older and more likely to be male and have a history of cardiovascular disease. Glucose, lipid and iPTH levels were lower among low-cIMT subjects (p < 0.05). Unadjusted and multivariable adjusted analyses demonstrated an independent association between high-cIMT and iPTH (fully adjusted OR: 1.74; 95%CI: 1.08–2.79; p = 0.021). Bootstrap and sensitivity analyses confirmed these findings. Conclusions. Elevated iPTH was associated with subclinical atherosclerosis in HIV-infected subjects. Of note this association was statistically significant even for iPTH values within the range of normality. The existence of a causal relationship between iPTH and atherosclerosis needs to be fully explored in future investigations.     

Non-HDL cholesterol is a better target for predicting periprocedural myocardial injury following percutaneous coronary intervention in type 2 diabetes

Objective: Non-HDL cholesterol (non-HDL-C) has recently been recommended as a first target for dyslipidemia management. We previously reported that LDL cholesterol (LDL-C) and non-HDL-C levels were similarly associated with periprocedural myocardial injury (PMI) following percutaneous coronary intervention (PCI) in patients with coronary artery disease. Here we investigated the comparative prognostic value of non-HDL-C and LDL-C for PMI following PCI in type 2 diabetes (T2D). Methods: We prospectively enrolled 1194 consecutive T2D patients with normal preprocedural cTnI undergoing PCI. Patients were divided into the two groups: group A [glycated hemoglobin (HbA1c) < 7%, n = 567] and group B (HbA1c ≥ 7%, n = 627). PMI was evaluated by cTnI analysis within 24 h. The relationship of preprocedural non-HDL-C and LDL-C levels with peak cTnI values after PCI was examined. Results: Patients in group B, with higher preprocedural non-HDL-C levels, had higher postprocedural cTnI levels (β = 0.102, P = 0.011). In the multivariable model, a 1-SD increase in non-HDL-C produced a 30% and 33% increased risk of postprocedural cTnI >3 × upper limit of normal (ULN) and >5 × ULN in group B, respectively. However, neither LDL-C nor group A patients were affected. Furthermore, patients with non-HDL-C levels ≥130 mg/dl compared with non-HDL-C levels ≤100 mg/dl were associated with a 83.3% and 71.7% increased risk of postprocedural cTnI >3 × ULN and >5 × ULN in group B, respectively. Conclusions: In poorly-controlled diabetic patients (HbA1c ≥ 7%) undergoing PCI, non-HDL-C but not LDL-C was independently associated with and increased risk of PMI, and non-HDL-C levels ≥130 mg/dl had a worse PMI risk profile compared with non-HDL-C levels <100 mg/dl.     

Positive correlation between malondialdehyde-modified low-density lipoprotein cholesterol and vascular inflammation evaluated by F-FDG PET/CT

Objective: The purpose of this study was to investigate the relationship between serum levels of malondialdehyde-modified low-density lipoprotein cholesterol (MDA-LDL) and vascular inflammation evaluated by fluorine-18 fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT). Methods/results: The study involved 106 consecutive patients (75 males and 31 female, mean age 62.5 ± 7.7 years) who visited our hospital for cardiovascular risk screening and underwent carotid ultrasonography, ¹⁸F-FDG PET/CT, complete history, physical examinations, and determination of blood chemistry including high-sensitivity C-reactive protein (hsCRP), asymmetric dimethylarginine (ADMA), and MDA-LDL. Vascular inflammation, was measured as blood-normalized standardized ¹⁸F-FDG uptake value, known as the target-to-background ratio (TBR) of carotid arteries. Univariate and multiple stepwise regression analyses were performed for determining independent correlates of carotid TBR values. Median MDA-LDL, mean carotid TBR values and carotid intima-media thickness (IMT) were 127.5 (IQR 92.0–147.8) U/l, 1.55 ± 0.22, and 0.72 ± 0.15 mm, respectively. Univariate analysis revealed that carotid TBR values positively correlated with MDA-LDL (p = 0.043) and carotid IMT (p = 0.049). Multiple stepwise regression analysis demonstrated that MDA-LDL (p = 0.043) and carotid IMT (p = 0.038) were independently associated with carotid TBR values. Conclusion: The present study reveals that serum levels of MDA-LDL are independently associated with vascular inflammation evaluated by ¹⁸F-FDG PET/CT. Circulating MDA-LDL may be a more useful clinical biomarker for vascular inflammation within the atherosclerotic plaques than hsCRP or ADMA.     

b-Gamma-glutamyltransferase activity in human vulnerable carotid plaques

Objective: The atherosclerotic plaque that is vulnerable to rupture and to superimposed thrombosis is mainly represented by a thin-cap fibroatheroma with or without ulceration/thrombosis and inflammatory infiltrates. Total serum gamma-glutamyltransferase (GGT) activity is an independent predictor for cardiovascular events. Four GGT fractions have been identified in plasma and only one of them (b-GGT) in atherosclerotic plaques, but the possible role of GGT in plaque pathophysiology has not been assessed yet. We investigated the relationships between plaque b-GGT activity and the histological features of plaque vulnerability. Methods and results: Plaque GGT activity was investigated in 65 patients undergoing carotid endarterectomy; plaques were histologically characterized and immunostained for GGT. Intra-plaque total and fractional GGT activity was determined by a cost-effective test of molecular size exclusion chromatography, and compared with histological markers of plaque vulnerability. Plaque cholesterol content was also measured by chromatography. b-GGT was the only fraction detected within the atherosclerotic plaques and intra-plaque b-GGT activity correlated to plaque cholesterol content (r = 0.667, P < 0.0001), plasma b-GGT and f-GGT fractions (r = 0.249; r = 0.298, both P < 0.05). Higher b-GGT activity was found in thin-cap fibroatheromas and it was associated to histological markers of vulnerable plaques, i.e., larger necrotic areas, greater macrophage infiltration and higher cholesterol content (P < 0.05). Conclusions: intra-plaque b-GGT activity correlates with the histological markers of vulnerable plaque and with plasma b-GGT in human carotid atherosclerosis; these data support the possible role of b-GGT in clinically significant atherosclerotic disease.     

Metabolic risk factors in first acute coronary syndrome (MERIFACS) Study

ObjectivesIn acute coronary syndrome (ACS) patients the focus is on major conventional risk factors - CRF [diabetes, hypertension, elevated low-density cholesterol (LDL-C) and smoking] whereas others - specific metabolic risk factors - MRF [high-density lipoprotein cholesterol (HDL-C), body-mass index (BMI), waist-hip ratio (WHR), and triglycerides, and HbA1c get less attention.MethodsThis is a prospective case–control observational study from 15 tertiary care hospitals in India. CRF and MRF in patients presenting with first incidence of ACS (n = 2153) were compared with matched controls (n = 1210).ResultsPropensity score matching (PSM) yielded 1193 cases and matched 1210 controls. Risk factor prevalence in cases vs. controls were CRF: hypertension - 39.4% vs 16.4% (p < 0.0001), diabetes - 42.6% vs 12.7% (p < 0.0001), smoking - 28.3% vs 9.3% (p < 0.0001) and elevated LDL-C - 70.2% vs 57.9% (p < 0.0001). MRF: High BMI - 54.7% vs 55.1% (p = 0.84), increased waist: hip ratio 79.5% vs 63.6% (p < 0.0001), high HbA1c - 37.8% vs 14.9% (p < 0.0001), low HDL-C - 56.2% vs 42.8% (p < 0.0001) and elevated triglycerides - 49.7% vs 44.2% (p = 0.007). Adjusted Odds ratios by multivariate analysis were CRF: hypertension - 2.3 (p < 0.001), diabetes - 4.7 (p < 0.001), high LDL-C - 3.3 (p < 0.001) and smoking- 6.3 (p < 0.001). MRF: High waist: hip ratio - 2.4 (p < 0.001) high HbA1c - 3.2 (p < 0.001), low HDL-C 2.2 (p < 0.001) and elevated triglycerides - 0.878 p = 0.17.ConclusionIn India, the risk of ACS conferred by specific metabolic risk factors (High waist: hip ratio, Low HDL-C and High HbA1c) is comparable to that caused by CRF.     

Small high-density lipoprotein is associated with monocyte subsets in stable coronary artery disease

Objective: High-density lipoprotein (HDL) particles are heterogeneous in structure and function and the role of HDL subfractions in atherogenesis is not well understood. It has been suggested that small HDL may be dysfunctional in patients with coronary artery disease (CAD). Monocytes are considered to play a key role in atherosclerotic diseases. Circulating monocytes can be divided into three subtypes according to their surface expression of CD14 and CD16. Our aim was to examine whether monocyte subsets are associated with HDL subfractions in patients with atherosclerosis. Methods: We included 90 patients with angiographically stable CAD. Monocyte subsets were defined as classical monocytes (CD14++CD16-; CM), intermediate monocytes (CD14++CD16+; IM) and non-classical monocytes (CD14+CD16++; NCM). HDL subfractions were measured by electrophoresis on polyacrylamide gel. Results: Serum levels of small HDL correlated with circulating pro-inflammatory NCM and showed an inverse relationship to circulating CM independently from other lipid parameters, risk factors, inflammatory parameters or statin treatment regime, respectively. IM were not associated with small HDL. In particular, patients with small HDL levels in the highest tertile showed dramatically increased levels of NCM (14.7 ± 7% vs. 10.7 ± 5% and 10.8 ± 5%; p = 0.006) and a decreased proportion of CM (79.3 ± 7% vs. 83.7 ± 6% and 83.9 ± 6%; p = 0.004) compared to patients in the two lower tertiles. In contrast, intermediate HDL, large HDL and total HDL were not associated with monocyte subset distribution. Conclusion: Small HDL levels are associated with pro-inflammatory NCM and inversely correlated with CM. This may suggest that small HDL could have dysfunctional anti-inflammatory properties in patients with established CAD.     

Is cardiovascular remodeling in patients with essential hypertension related to more than high blood pressure? A LIFE substudy. Losartan Intervention For Endpoint-Reduction in Hypertension

Background Blocking the renin-aldosterone-angiotensin II system has been hypothesized to induce blood pressure-dependent as well as blood pressure-independent regression of cardiovascular hypertrophy. However, the relative influence of elevated blood pressure (BP) and various neurohormonal factors on cardiovascular remodeling in hypertension is unclear. Methods In 43 untreated patients with hypertension with electrocardiographic left ventricular hypertrophy, we measured relative wall thickness and left ventricular mass index by echocardiography and by magnetic resonance imaging (n = 32), intima-media cross-sectional area, and distensibility of the common carotid arteries by ultrasound, media/lumen ratio of isolated subcutaneous resistance arteries by myography, and median 24-hour systolic BP (n = 40), serum insulin, and plasma levels of epinephrine, norepinephrine, renin, angiotensin II, aldosterone, and endothelin. Results In multiple regression analyses, left ventricular mass index by echocardiography (R² = 0.14, P < .05) and by magnetic resonance imaging (R² = 0.32, P = .001) were associated with 24-hour systolic BP, whereas relative wall thickness was associated with plasma epinephrine (R² = 0.12, P < .05) and aldosterone (R² = 0.10, P < .05). Intima-media cross-sectional area/height was associated with 24-hour systolic BP (β = 0.40) and plasma epinephrine (β = 0.43) (adjusted R² = 0.32, P < .001), whereas carotid distensibility was associated with 24-hour systolic BP (β = 0.40) and plasma angiotensin II (β = −0.41) (adjusted R² = 0.30, P < .001). Media/lumen ratio in subcutaneous resistance arteries was associated with plasma epinephrine (R² = 0.22, P < .01). Conclusion Apart from being associated with a high BP burden, cardiovascular remodeling was associated with high levels of circulating epinephrine, aldosterone, as well as angiotensin II, suggesting a beneficial effect above and beyond the effect of BP reduction when using antihypertensive agents blocking the receptors of these neurohormonal factors. (Am Heart J 2002;144:530-7.)     

Plasma adiponectin concentration is strongly associated with VLDL-TG catabolism in postmenopausal women

Background and aims

To investigate associations between plasma adiponectin concentration and very-low density lipoprotein-triglyceride (VLDL-TG) secretion and catabolism in postmenopausal women.

Methods and results

This cross-sectional study included 30 postmenopausal women. Plasma adiponectin concentration was measured by ELISA. Insulin sensitivity was assessed by a 2-h euglycemic-hyperinsulinemic clamp. Fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPG) were measured during an oral glucose tolerance test. The calculation of VLDL-TG fractional catabolic rate (FCR) and VLDL-TG total secretion rate (TSR) were based on the monoexponential decrease of TG-[²H₅] glycerol values obtained following the administration of a ²H₅-glycerol bolus. Plasma adiponectin concentration was negatively associated with VLDL-TG TSR (r = −0.50; p = 0.005) and positively associated with VLDL-TG FCR (r = 0.54; p < 0.002). This latter association remained significant after further adjustments for insulin sensitivity, visceral adipose tissue, HDL-C, FPG and 2hPG concentrations. In a multivariate model including adiponectin, insulin sensitivity and 2hPG, plasma adiponectin level was the strongest correlate of VLDL-TG FCR.

Conclusions

Elevated plasma adiponectin concentration is associated with a favourable VLDL-TG metabolism.     

Association between chronic kidney disease and thoracic aortic atherosclerosis detected using transesophageal echocardiography

Objective: Accelerated atherosclerosis occurs with a high frequency in patients with chronic kidney disease (CKD). We evaluated the association between CKD and thoracic aortic plaques using transesophageal echocardiography (TEE). Methods: This study population consisted of 297 patients who underwent TEE. Aortic plaques were evaluated in the proximal thoracic aorta (PTA) (from the ascending aorta to the aortic arch) and the distal thoracic aorta (DTA) (the descending aorta) using TEE. Aortic plaques were defined as complex plaques of ≥4 mm thickness and with ulceration or mobile components. CKD was defined as the estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m². The association between CKD and aortic plaques was evaluated using multivariate analysis after adjusting for traditional atherosclerotic risk factors. Results: Patients with CKD (n = 144) had a higher incidence of any plaques and complex plaques compared with those without CKD (n = 153) (85% vs. 47% and 42% vs. 17%, respectively, both P < 0.001). Univariate analysis indicated that the presence of CKD was significantly associated with complex plaques both in the DTA and the PTA (both, P < 0.001); however, multivariate analysis indicated that the presence of CKD was associated with only complex plaques in the DTA (P < 0.05), but not with those in the PTA. Conclusion: The presence of CKD was associated with complex aortic plaques, with this association being stronger for complex plaques in the DTA than those in the PTA.     

Serum concentrations of galectin-3 in patients with cardiac syndrome X

Objective: Microvascular dysfunction has been reported in cardiac syndrome X (CSX), even though the underlying mechanisms still remain uncertain. Galectin-3 has been recently recognized as a biomarker of cardiovascular fibrosis and inflammation. We sought to investigate the role of galectin-3 in the CSX. Methods: We studied 115 consecutive CSX patients (mean age 55.43 ± 8.71 years, 36 men) and 74 healthy controls (mean age 54.53 ± 10.07 years, 31 men). Serum concentrations of galectin-3 and high-sensitive C-reactive protein (hs-CRP) were measured on the blood samples. Results: Galectin-3 concentrations were significantly higher in patients with CSX compared to controls (0.90 ng/ml; IQR, 0.40–1.70 ng/ml vs 0.40 ng/ml; IQR, 0.36–0.44 ng/ml, p < 0.0001). Although, the prevalence of diabetes mellitus, hypertension and family history of coronary artery disease (CAD) were significantly higher among patients with CSX, following adjustment for diabetes mellitus, hypertension, and family history of CAD, serum galectin-3 concentrations were still found significantly increased in patients with CSX. Galectin-3 concentrations correlated positively with hs-CRP (r = 0.16, p = 0.03). In addition, concentrations of galectin-3, hs-CRP, fasting glucose, uric acid and family history of CAD were determined as independent predictors of the CSX. Conclusion: It was found that galectin-3 serum concentrations are higher in patients with CSX compared to healthy controls. Further studies on larger population are needed to confirm the relation between the fibrosis and the CSX, as well as to explore the potential role of galectin-3 in the CSX.     

Elevated serum uric acid levels are associated with diastolic dysfunction in patients with dilated cardiomyopathy

Objective To assess whether serum uric acid, which is a marker of impaired oxidative metabolism, might correlate with left ventricular systolic and diastolic dysfunction in patients with chronic heart failure (CHF). Background Uric acid levels, which are frequently elevated in patients with CHF, correlate with leg vascular resistance. The effects of elevated levels of uric acid on cardiac function in patients with CHF have never been evaluated. Methods We studied 150 outpatients with CHF who came to our heart failure clinic. Patients underwent a complete echo-Doppler examination, with measurement of mitral E wave and mitral A wave velocities, E/A ratio, E wave deceleration time (DtE), left ventricular volumes, ejection fraction, and stroke volume. A restrictive mitral filling pattern (RMFP) was defined as either E/A ratio >2 or E/A >1 and DtE <140 milliseconds. Results Mean age was 62.2 ± 7.8 years (86% male); 24 patients (16%) had an RMFP. Patients with an RMFP had significantly higher uric acid levels compared with patients without RMFP (0.48 ± 0.14 mmol/L vs 0.38 ± 0.08 mmol/L, respectively, P < .001). Uric acid levels correlated significantly with mitral E wave velocity (r = .22, P < .01), E/A ratio (r = .21, P < .05), DtE (r = .26, P < .01), and RMFP (P = .0001). There was no correlation between uric acid and left ventricular volumes, ejection fraction, or stroke volume. In a multivariate model, uric acid predicted DtE independently of renal function, diuretic dose, and left ventricular volumes. Conclusion Elevated uric acid levels are associated with diastolic dysfunction in CHF. Xanthine oxydase inhibition in patients with CHF might theoretically result in an improvement of diastolic function. (Am Heart J 2002;143:1107-11.)     

Increased subclinical atherosclerosis in patients with chronic plaque psoriasis

Background: Psoriasis is an immune-mediated inflammatory skin condition of unknown aetiology which usually requires life-long treatment. It is regarded a systemic inflammatory disease with a possible increased risk of cardiovascular disease. The aim of this study was to assess carotid intima-media thickness (IMT), plaque prevalence and carotid stenosis as surrogate measures for cardiovascular disease in psoriasis patients and healthy controls. Methods: Sixty-two patients with psoriasis and thirty-one healthy controls were included in the study. All were examined by Colour duplex ultrasound of the carotid arteries to compare carotid IMT values, carotid plaques and carotid stenosis in the two groups. Adjustments were made for traditional cardiovascular risk factors. Results: Patients with psoriasis had increased carotid IMT values compared to the controls: mean ± SD 0.71 ± 0.17 mm vs. 0.59 ± 0.08 mm; p = 0.001. When adjusted for known atherosclerotic risk factors this difference remained significant (p = 0.04). Carotid plaques were also more common (p = 0.03) in patients with psoriasis 13 (21%) compared to controls 1 (3%). There was no difference with regard to the number of carotid stenoses in patients and controls. Conclusion: The results of this study support previous evidence which suggests that psoriasis is associated with an increased risk for atherosclerosis and subsequent cardiovascular disease.     

Blood pressure disturbances and endothelial dysfunction markers in children and adolescents with type 1 diabetes

Objective: Being the earliest step on the way to atherosclerosis, endothelial dysfunction is particularly escalated in diabetes. This study aimed at assessing endothelial dysfunction and blood pressure disturbances in young patients with type 1 diabetes mellitus (T1DM) and defining their interrelations. Methods: The study group comprised 52 children and adolescents aged 14.07 ± 3.03 years, with T1DM duration 5.13 ± 2.18 years. 20 healthy controls with similar age and sex distribution were included. Chosen serum biochemical markers of endothelial damage: intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), sE-selectin, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) as well as ambulatory blood pressure monitoring (ABPM) were performed in all subjects. Results: Patients with T1DM displayed significantly higher concentrations of chosen markers of endothelial dysfunction compared to controls (sVCAM-1 (ng/ml): 951.56 ± 330.68 vs. 710.35 ± 162.12, TNF-α (pg/ml): 16.63 ± 8.32 vs. 9.41 ± 4.23, IL-6 (pg/ml): 3.38 ± 1.31 vs. 2.45 ± 0.81; p < 0.05). Within the study group subjects with an abnormal ABPM reading had significantly higher concentrations of sE-selectin compared with subjects with normal ABPM (in ng/ml: 45.71 ± 15.63 vs. 32.42 ± 11.95; p < 0.01). The study revealed a significant positive correlation between sE-selectin and systolic as well as diastolic pressure loads during the day period (respectively: r = 0.46, r = 0.60; p < 0.01). Conclusions: Endothelium dysfunction may be present early in the course of T1DM in children and adolescents. It seems to be related with blood pressure disturbances which highlights the need to intensify treatment in this group of patients.     

Body mass index is the most important determining factor for the degree of insulin resistance in non-obese type 2 diabetic patients in Korea

With obesity, increased insulin secretion is needed to compensate for the additional demands and to maintain euglycemia. In contrast to Caucasians, the majority of type 2 diabetic patients belong to the non-obese category in Korea. There appears to be an ethnic difference underlying the pathogenesis in type 2 diabetes mellitus. However, there is only limited data on these subjects. The degree of insulin resistance in 267 Korean non-obese (body mass index [BMI] < 25 kg/m²) ≥ patients with type 2 diabetes mellitus was analyzed, and the factors responsible for the insulin resistance were examined. The mean age and BMI of the patients were 50.8 ± 10.6 years and 22.6 ± 1.8 kg/m². Homeostasis model assessment-insulin resistance (HOMA-IR) ≥ 2.5 was defined as being insulin resistant according to our data (mean ± 1.5 SD of 1,917 normal subjects). There was no significant difference according to age, the duration of disease, and the glycosylated hemoglobin (HbA_lc) levels between the subjects with or without insulin resistance. The HOMA-IR values in the patients with insulin resistance and normal insulin sensitivity were 4.2 ± 1.4 and 1.5 ± 0.6, respectively. In the insulin-resistant group, the log-transformed triglyceride (TG) levels were higher and the high-density lipoprotein-cholesterol (HDL-C) levels were lower than those of the insulin-sensitive group (log-transformed TG: 5.2 ± .6 v 4.9 ± .7 and HDL-C: 1.13 ± 0.3 v 1.25 ± 0.3mmol/L). These differences were still observed after adjusting for BMI. The HOMA-IR value was independently predicted by BMI and HDL-C levels, which explained 7% and 3% in the variability of insulin resistance, respectively. However, the TG levels were not independently associated with the HOMA-IR. Logistic regression analysis showed that the significant factor associated with HOMA-IR was only BMI. These results suggest that the BMI is the most important determinant of insulin resistance, while TG and HDL-C levels might be good markers of insulin resistance in non-obese patients with type 2 diabetes mellitus in Korea.     

Persistent epicardial adipose tissue accumulation is associated with coronary plaque vulnerability and future acute coronary syndrome in non-obese subjects with coronary artery disease

Objective. Epicardial adipose tissue (EAT) is recognized as a novel risk factor for coronary artery disease (CAD), and its contribution is thought to be stronger in non-obese patients than in obese patients. However, the prognostic impact of the progression of EAT accumulation after comprehensive management for atherosclerotic risk factors remains unclear. This study aimed to investigate whether an increase of the EAT volume during follow-up predicts future acute coronary syndrome (ACS) events in non-obese CAD patients. Methods. This study consisted of 517 non-obese CAD patients (368 men; age, 66 ± 10 years) who underwent serial multidetector computed tomography (MDCT) examinations to evaluate coronary atherosclerosis progression. The MDCT examination was used to assess the severity of stenosis, plaque characteristics, and EAT volume. All patients received comprehensive management to reduce CAD risk factors after the first MDCT examination. The MDCT examination was repeated at 6–24 months, and patients were followed-up for more than 1 year or until the occurrence of ACS events. Results. Of 517 patients, 159 (31%) patients were classified into increase of EAT volume during follow-up, 91 (18%) into decrease of EAT volume during follow-up, and 267 (51%) patients into constant of EAT volume during follow-up. The prevalence of obstructive plaques and MDCT-derived vulnerable features of coronary plaques were significantly elevated in patients with increase of EAT volume during follow-up. In contrast, no significant changes were observed in the other 2 groups. During the follow-up period of 4.1 ± 1.8 years (median 4.4 years) after the second MDCT examination, ACS occurred in 43 (8.3%) patients. Multivariate Cox regression analysis showed that the presence of low-attenuation plaque (hazard ratio [HR]; 1.78, p = 0.04) and napkin-ring sign (HR; 3.74, p < 0.001) at second MDCT examination, and changes of EAT volume per 10 ml (HR; 1.34, p = 0.004) were associated with future ACS events. Conclusion. Patients with increase of EAT volume during follow-up despite comprehensive management for CAD risks had an increased prevalence of obstructive plaques and plaques with high-risk features, which could be associated with unfavorable ACS outcomes in non-obese CAD patients.