Total Adiponectin, Adipocyte Fatty Acid Binding Protein, Fibroblast Growth Factor 21 and Proinflammatory Marker Levels During the Early Stage of Acute Pancreatitis--A Pilot Study.

BACKGROUND: Recently, an increasing interest has been extended to the secretory products of fat tissue adipokines and their role in the course of acute pancreatitis (AP). The study aimed to evaluate the levels of adiponectin (ADP), adipocyte fatty acid binding protein (A-FABP), fibroblast growth factor (FGF 21), and selected proinflammatory markers during the early stage of acute pancreatitis. The parameters were measured for identification of the patients with the high risk of severe AP. METHODS: 84 subjects (47 males, 37 females) with AP were divided into the subgroups according to body mass index (BMI), disease severity score (mild AP vs. severe AP) and computer tomography severity index score (CTSI A vs. CTSI B vs. CTSI C). All laboratory examinations were determined on day 1 and day 4 after admission. Adipokines were analyzed using the ELISA kit methods. RESULTS: No significant variance was found in adipokine levels between subjects with mild and severe AP, but C-reactive protein (CRP) and interleukin 6 (IL-6) were significantly elevated in patients with severe AP on day 4 (CRP medians: 209.8 mg/L vs. 51.2 mg/L, p < 0.000; IL-6 medians: 79.5 ng/L vs. 25.9 ng/L, p < 0.01). FGF 21 medians were distinctly higher on day 1 in all observed subgroups compared to day 4 (mild AP: 669.9 ng/L vs. 261.7 ng/L; severe AP: 619.4 ng/L vs. 468.0 ng/L; CTSI A: 631.4 ng/L vs. 246.2 ng/L; CTSI B: 2226.3 ng/L vs. 693.1 ng/L; CTSI C: 572.6 ng/L vs. 310.8 ng/L). Similarly, this phenomenon was found for A-FABP and IL-6 as well. A-FABP and FGF 21 levels decreased during the first four days together, but independently of the IL-6 decline, regardless of AP severity. CONCLUSIONS: Elevated levels of CRP and IL-6 in subjects with severe form of AP on day 4 indicate a diagnostic utility of both parameters in the disease severity prediction. Increased FGF 21 at admission compared to day 4 suggests its potential role as an immediate response gene during pancreatic injury. The dynamics of FGF 21 and A-FABP levels probably reflect the improvement of clinical condition in the early stage of AP.

Total and High Molecular Weight Adiponectin Levels and Prediction of Cardiovascular Risk in Diabetic Patients.

The study aimed at assessing the potential use of lower total and HMW adiponectin levels for predicting cardiovascular risk in patients with type 2 diabetes mellitus (T2DM). Concentrations of total adiponectin or high molecular weight (HMW) adiponectin decrease in association with the development of metabolic dysfunction such as obesity, insulin resistance, or T2DM. Increased adiponectin levels are associated with a lower risk for coronary heart disease. A total of 551 individuals were assessed. The first group comprised metabolically healthy participants (143 females, and 126 males) and the second group were T2DM patients (164 females, and 118 males). Both total adiponectin and HMW adiponectin in diabetic patients were significantly lower when compared with the group of metabolically healthy individuals. There was a weak monotonic correlation between HMW adiponectin levels and triglycerides levels. Binary logistic regression analysis, gender adjusted, showed a higher cardiovascular risk in diabetic persons when both total adiponectin (OR = 1.700) and HMW adiponectin (OR = 2.785) levels were decreased. A decrease in total adiponectin levels as well as a decrease in its HMW adiponectin is associated with a higher cardiovascular risk in individuals with T2DM. This association suggests that adiponectin levels may be potentially used as an epidemiological marker for cardiovascular risk in diabetic patients.

The influence of apolipoprotein A5 T-1131C and apolipoprotein E common genetic variants on the levels of hemostatic markers in dyslipidemic patients.

OBJECTIVES: The aim of this study was to evaluate the relationships of the T-1131C (rs662799) polymorphism variants of apolipoprotein A5 (Apo A5) gene and variants of apolipoprotein E (Apo E) gene common polymorphism (rs429358, rs7412) to selected hemostatic markers. STUDY DESIGN AND METHODS: We examined 590 asymptomatic dyslipidemic patients, subsequently divided into MetS+ (n=146) and MetS- (n=444) groups according to the criteria for identification of the metabolic syndrome (MetS). We compared variant frequencies and differences in levels of hemostatic markers according to Apo A5, Apo E and Apo A5/Apo E common variants. RESULTS: The -1131C Apo A5 minor variant was associated with elevated tissue plasminogen activator (tPA) in comparison to TT genotype (p<0.001), but not in the MetS+ group. The analysis of Apo A5/Apo E common variants in all subjects revealed that the presence of -1131C minor allele has always been associated with higher levels of tPA in comparison with T allele, regardless of Apo E genotype. Also the presence of minor Apo E2 allele led to elevated tPA concentrations in both T and C carriers. In addition, common -1131C/E2 variant was associated with the highest tPA levels. CONCLUSION: We demonstrated a remarkable association especially between the -1131C Apo A5 variant and increased tPA levels in asymptomatic dyslipidemic patients.

Genetic variants of apolipoprotein A5 T-1131C and apolipoprotein E common polymorphisms and their relationship to features of metabolic syndrome in adult dyslipidemic patients.

OBJECTIVES: The aim was to evaluate the relationships of the T-1131C (rs662799) polymorphism variants of apolipoprotein A5 (Apo A5) gene and variants of apolipoprotein E (Apo E) gene common polymorphism (rs429358, rs7412) to signs of metabolic syndrome (MetS). DESIGN AND METHODS: We examined 590 asymptomatic dyslipidemic patients divided into MetS+ (n=146) and MetS- (n=444) groups according to criteria of NCEP ATPIII Panel. We evaluated genotype frequencies and differences in MetS features between individual groups. Logistic regression analysis was used for the evaluation of Apo A5/Apo E variants as possible risk factors for MetS. RESULTS: We found no statistical differences between genotype and allele frequencies for both Apo A5 and Apo E polymorphisms between MetS+ and MetS- groups. In all subjects and MetS- group, we confirmed well-known association of the -1131C Apo A5 minor allele with elevated triglycerides (TG, p<0.001). The Apo E gene E2 and E4 variants were associated with higher levels of TG (p<0.01) in comparison to E33 common variant. However, no statistical differences were observed in MetS+ subjects, regardless of significantly higher TG levels in this group. Apo A5/Apo E variant analysis in all dyslipidemic patients revealed significant increase of TG levels in all subgroups in comparison to common -1131T/E3 variant carriers, the most in -1131C/E4 variant subgroup. Logistic regression analysis models showed no association of Apo A5, Apo E and all Apo A5/Apo E variants with metabolic syndrome, even after adjustment for age and sex. CONCLUSION: Our study refined the role of Apo A5 and Apo E genetic variants in the group of adult dyslipidemic patients. We demonstrate that except of TG, Apo A5 T-1131C (rs662799) and Apo E (rs429358, rs7412) polymorphisms have no remarkable effect on MetS characteristics.

Intima media thickness measurement as a marker of subclinical atherosclerosis in SLE patient.

AIM: Accelerated atherosclerosis in systemic lupus erythematosus (SLE) is an important cause of morbidity and mortality. The pathophysiology of accelerated atherosclerosis in SLE is mediated by factors such as inflammatory processes in the vascular wall, specific antibodies, dyslipoproteinemia, endothelial dysfunction and the high prevalence of traditional risk factors for cardiovascular diseases. In this context, we evaluated the clinical significance of ultrasound examination of the carotic arteries in the early diagnosis of atherosclerosis. METHODS: The study included 63 patients with SLE (female: male 53:10, mean age 38.4±12.7 years, mean disease duration 143.0±82.6 months), 24 patients had lupus nephritis. The control group consisted of 24 volunteers (female: male 20:4 mean age 31.04±8.59). Intima media thickness (IMT) was measured by ultrasound on both sides. The results were correlated with markers of lipid spectrum, anti-dsDNA, antinucleosomal and anticardiolipin antibodies, lupus anticoagulant and complement components. Clinical disease activity and damage were evaluated by SLEDAI and SLICC indices. Lifestyle and other important factors were examined per protocol and by questionnaire. RESULTS: A significant difference of IMT (P≤0.03) was found between the lupus patients and sex-age adjusted healthy controls with an in mean IMT in SLE patients of 0.569±0.11 mm, in control group 0.495±0.05 mm. A significant correlation between IMT and disease duration, age, positivity of lupus anticoagulant, use of ACE inhibitors, glomerular filtration and serum creatinine were found. No difference in IMT was found between patients with or without lupus nephritis. CONCLUSION: IMT measurement could be used as a clinical predictor of risk of accelerated atherosclerosis in lupus patients.

Positive association of adiponectin with soluble thrombomodulin, von Willebrand factor and soluble VCAM-1 in dyslipidemic subjects.

OBJECTIVES: Both decreased and increased risk of cardiovascular events/mortality have been reported with high adiponectin levels. Only a few studies have reported an association of adiponectin with markers of hemostasis/endothelial dysfunction which might explain the reported discrepancies. DESIGN AND METHODS: We evaluated the association of total adiponectin with von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (t-PA), soluble thrombomodulin (sTM), adhesion molecules sICAM-1 and sVCAM-1, lipids and markers of insulin resistance (IR) in 308 asymptomatic dyslipidemic subjects and healthy controls. Subjects were divided into 4 dyslipidemic phenotypes (DLP): DLP1 (TG < 1.5 mmol/L + ApoB < 1.2 g/L), DLP2 (TG ≥ 1.5 + ApoB < 1.2), DLP3 (TG < 1.5 + ApoB ≥ 1.2) and DLP4 (TG ≥ 1.5 + ApoB ≥ 1.2). The results were evaluated also according to the presence (+) and absence (-) of metabolic syndrome (MS). RESULTS: In hyperlipidemic subjects (DLP2-4), PAI-1, t-PA and sICAM-1 correlated with markers of IR but only t-PA correlated inversely with adiponectin. In contrast positive association of adiponectin with vWF, sTM and sVCAM-1 was found but none of these parameters correlated with markers of insulin resistance. In multiple regression analysis, adiponectin remained independently associated with vWF [in DLP3, DLP4, DLP2-4, MS(-)], with sTM [in DLP2, DLP4, DLP2-4, MS(+)] and with sVCAM-1 [in DLP2, DLP3, DLP4, DLP2-4, MS(+)]. In healthy controls (DLP1), no association between adiponectin and markers of hemostasis/endothelial dysfunction was found. CONCLUSION: The independent positive association of adiponectin with vWF, sTM and sVCAM-1 deserves further evaluation in connection with the risk of atherothrombotic cardiovascular events.

Prehypertension in dyslipidemic individuals; relationship to metabolic parameters and intima-media thickness.

INTRODUCTION: Like hypertension, prehypertension is associated with cardiovascular disease. AIMS: The aim of this study was to evaluate: a) the prevalence of prehypertension/hypertension in individuals with various dyslipidemic phenotypes; b) the relation between blood pressure (BP) and other risk factors for atherosclerosis; c) atherogenic potential of prehypertension by the assessment of intima-media thickness of the arteria carotis communis (IMT). METHODS: 667 clinically asymptomatic subjects were divided into four dyslipidemic phenotypes (DLP) according to apolipoprotein B (apoB) and triglycerides (TG): DLP1 (n=198, normo-apoB/normo-TG), DLP2 (n=179, normo-apoB/hyper-TG), DLP3 (n=87, hyper-apoB/normo-TG), DLP4 (n=203, hyper-apoB/hyper-TG). DLP1 served as a control group. RESULTS: There was significantly higher prevalence of prehypertension and hypertension in subjects with dyslipidemia (DLP2 43.0%, 41.3%; DLP3 42.5%, 29.9%; DLP4 42.4%, 47.8%) than in normolipidemic individuals (DLP1 32.8%, 20.2%). Systolic and diastolic blood pressure (SBP + DBP) correlated with age, total cholesterol, TG, non-HDL-cholesterol, body mass index and waist circumference; SBP additionally with C-peptide, fasting glycemia; DBP additionally with apoB, homeostasis model assessment (HOMA) and plasminogen activator inhibitor-1. The IMT of hypertensive and of prehypertensive subjects was higher than that of subjects with normal BP in all DLPs. CONCLUSIONS: The prevalence of prehypertension was higher in all dyslipidemic patients. The common prevalence of prehypertension/hypertension was highest in the hypertriglyceridemic subjects. Prehypertensive and hypertensive patients had higher IMT than normotensive individuals in all DLPs.

Relationship between serum adipocyte fatty acid-binding protein and endothelial/hemostatic markers in dyslipidemic subjects.

OBJECTIVES: Some findings support the role of serum adipocyte fatty acid-binding protein (A-FABP) as a key pro-inflammatory mediator that links obesity with cardiovascular diseases. The aim of the study was to evaluate the association of A-FABP with endothelial/hemostatic markers [von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1), tissue-plasminogen activator (t-PA), soluble intercellular cell adhesion molecule-1 (s-ICAM-1) and soluble vascular cell adhesion molecule-1 (s-VCAM-1)] in asymptomatic dyslipidemic subjects. DESIGN: We examined 105 dyslipidemic patients (with apolipoprotein B concentration ≥1.2 g/l and/or triglyceride (TG) concentration ≥1.5 mmol/l) without clinical manifestation of atherosclerosis and 50 normolipidemic healthy subjects, who served as a control group. Except of endothelial/hemostatic markers, anthropometric and lipid parameters, markers of insulin resistance and inflammation were assessed. RESULTS: In dyslipidemic patients, A-FABP positively correlated with age (p<0.05), TG (p<0.05), insulin (p<0.05), homeostatic model assessment (HOMA) index (p<0.05), body mass index (p<0.001), waist circumference (p<0.05), high sensitivity C reactive protein (p<0.01), and vWF (p<0.05) and negatively with male gender (p<0.05). There were no correlations between A-FABP and PAI-1, t-PA, s-VCAM-1 or s-ICAM-1. By using linear multivariate regression analysis the positive association between A-FABP and vWF was independent of age, gender, insulin resistance, and visceral obesity. CONCLUSION: Study displayed an independent positive association of A-FABP with vWF in clinically asymptomatic dyslipidemic subjects. Contribution of A-FABP in the process of endothelial dysfunction could help to explain the role of obesity in cardiovascular damage.

Total adiponectin levels in dyslipidemic individuals: relationship to metabolic parameters and intima-media thickness.

INTRODUCTION: Adiponectin is adipocytokin with anti-inflammatory and anti-atherogenic effects. However, studies examining the relationship between adiponectin and cardiovascular diseases have shown inconsistent results. AIMS: The aim of this study was to evaluate the plasma levels of adiponectin in clinically asymptomatic subjects with various dyslipidemic phenotypes. The associations between adiponectin and risk factors for atherosclerosis, markers of insulin resistance, and the intima-media thickness of the common carotid artery (IMT) were also evaluated. METHODS: 234 asymptomatic subjects were divided into four dyslipidemic phenotypes (DLP) according to apolipoprotein B (apoB) and triglycerides (TG): DLP1 (n=58, apoB<1.2 g/l and TG<1.5 mmol/l), DLP2 (n=47, apoB<1.2 g/l and TG≥1.5 mmol/l), DLP3 (n=31, apoB≥1.2 g/l and TG<1.5 mmol/l) and DLP4 (n=98, apoB≥1.2 g/l and TG≥1.5 mmol/l). DLP1 (normo-apoB/normo-TG) served as a control group. RESULTS: Significant differences in adiponectin levels between normolipidemic phenotype - DLP1 (16.1[10.3-20.8] mg/l) and hypertriglyceridemic phenotypes - DLP2 (9.5[6.8-13.0] mg/l, p<0.01) and DLP4 (10.1[7.4-16.8] mg/l, p<0.01) after adjustment for age, sex and body mass index were found. Adiponectin correlated positively with highdensity lipoprotein cholesterol and apolipoprotein A1 (apoA1), negatively with triglycerides, apoB/apoA1, highsensitivity C-reactive protein, insulin, homeostasis model assessment and waist circumference. ApoA1 and insulin were detected as independent predictors for adiponectin levels in multivariate regression analysis. Adiponectin did not correlate with IMT. CONCLUSIONS: Individuals with hypertriglyceridemic phenotypes showed decreased adiponectin levels in comparison with normolipidemic subjects. Adiponectin was associated with lipid parameters, markers of insulin resistance, chronic inflammation and visceral obesity. But no association between adiponectin and IMT was found.

Prothrombotic markers in asymptomatic dyslipidemic subjects.

The aim of this study was to evaluate the plasma levels of prothrombotic markers--von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (t-PA)--in asymptomatic subjects with dyslipidemia. Asymptomatic subjects with dyslipidemia and their relatives (n = 234) were assessed for lipids and prothrombotic markers. Individuals were divided into four dyslipidemic phenotypes (DLP) according to apolipoprotein B (apoB) and triglycerides (TG): DLP1 (n = 58, apoB < 1.2 g/l and TG < 1.5 mmol/l), DLP2 (n = 47, apoB < 1.2 g/l and TG ≥ 1.5 mmol/l), DLP3 (n = 31, apoB ≥ 1.2 g/l and TG < 1.5 mmol/l) and DLP4 (n = 98, apoB ≥ 1.2 g/l and TG ≥ 1.5 mmol/l). Associations between prothrombotic markers and risk factors for atherosclerosis, markers of insulin resistance, and the intima-media thickness of the common carotid artery (IMT) were assessed too. Significant differences in PAI-1 between normolipidemic phenotype--DLP1 (62.5 (35.9-82.9) ng/ml) and hypertriglyceridemic phenotypes--DLP2 (82.2 (61.1-122.1) ng/ml, p < 0.01) and DLP4 (91.4 (63.5-111.8) ng/ml, p < 0.001) after adjustment for age, sex and body mass index, were found. Levels of t-PA were different only between DLP1 and DLP4 (1.9 (0.9-3.3) ng/ml vs. 5.3 (2.5-8.6) ng/ml, p < 0.05). There were no significant differences of vWF between DLPs. PAI-1 and t-PA correlated with lipid parameters, markers of insulin resistance, blood pressure and obesity. VWF was independently associated with IMT, which was increased in DLP4. Individuals with hypertriglyceridemic phenotypes showed increased levels of PAI-1 in comparison with normolipidemic subjects. The elevation of t-PA was presented only in patients with simultaneously elevated TG and apoB. The significant increase of IMT confirmed in the patients with DLP4 reveals individuals with the highest risk for atherosclerosis manifestation.

Apolipoprotein B versus LDL-cholesterol: Association with other risk factors for atherosclerosis.

OBJECTIVE: To characterize the differences in various risk factors for atherosclerosis between individuals with apoB higher (H) and lower (L) than predicted from regression equation apoB vs LDL-C. METHODS: We evaluated 391 dyslipidemic subjects not treated with hypolipidemic drugs. The measured parameters included lipid profile, apolipoproteins A-1 and B, markers of insulin resistance and inflammation/hemostasis. RESULTS: Correlation coefficient between apoB and LDL-C was 0.9 (p<0.0001). Individuals with H apoB compared to L apoB had significantly higher sex and age adjusted BMI, waist circumference, insulin, HOMA (fasting insulinglucose/22.5), C-peptide, proinsulin, PAI-1, sICAM-1, sVCAM-1, t-PA, vWF, frequency of metabolic syndrome and lower values of TC, LDL-C and HDL-C (p<0.05 to <0.001 for all parameters). CONCLUSION: Individuals with apoB higher than predicted by their LDL-C levels are more insulin resistant and have more atherogenic risk profile. Thus, at least for dyslipidemic patients with high cardiometabolic risk, apoB is a more appropriate marker of risk than LDL-C.

Benefits of three-month continuous glucose monitoring for persons with diabetes using insulin pumps and sensors.

BACKGROUND: The latest Paradigm 722 insulin pump, Medtronic MiniMed, USA, enables daily reading of 288 interstitial fluid glucose concentrations determined by a sensor inserted into subcutaneous tissue; the sensor signals are transmitted into the insulin pump, enabling the patient to see real-time glucose concentration on the display and adapt further treatment. AIMS: To assess the evolution of HbA1c over the course of a 3-month period in two cohorts of persons with type 1 (n=39) or type 2 (n=3) diabetes (PWD): 1) PWD on Paradigm 722 using sensors for continuous glucose monitoring (CGM group), 2) PWD on other types of insulin pumps performing intensive self-monitoring as before (3 to 6 times/d) on glucometer Linus, Wellion, Agamatrix (control group). METHODS: Compliant PWDs using insulin pump with insulin aspart for several previous months were included in the study. Seventeen were put on Paradigm 722 with CGM and 25 were included in the control group. Paired t-test and the statistical program SPSS v.15.0 were used to analyze the data. RESULTS: There was no significant difference in age between the two groups (P=0.996), in diabetes duration (P=0.482) or in daily insulin dose (P=0.469). In the CGM group (but not in the control group) HbA1c/IFCC dropped from 6.98+/-0.43 % to 5.98+/-0.36 % (P=0.006) within 1 month and remained reduced. CONCLUSION: The use of the Paradigm 722 insulin pump with CGM resulted in significant improvement in HbA1c which appeared within one month and remained throughout the whole 3-month study period. No significant improvement in HbA1c was seen in the control group.

Endothelial haemostatic markers in members of families with familial combined hyperlipidemia.

INTRODUCTION: The aim of this study was to evaluate the plasma levels of endothelial haemostatic markers - von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (t-PA) and soluble thrombomodulin (sTM) - in asymptomatic, nonsmoking members of families with familial combined hyperlipidemia (FCH). We investigated the association between these factors and the intima-media thickness (IMT) of the common carotid artery, selected risk factors of atherosclerosis and markers of insulin resistance. METHODS: 82 members of 29 FCH families were divided into two groups: HL (probands and hyperlipidemic first-degree relatives, n=47) and NL (normolipidemic first-degree relatives, n=35). The control groups C-HL (n=20) and C-NL (n=20) consisted of sex- and age-matched healthy individuals. IMT was measured by ultrasound at a far wall of both common carotid arteries. RESULTS: Compared with healthy controls, hyperlipidemic subjects had significantly higher levels of vWF (146.4+/-73.2% versus 112.2+/-29.4%, p<0.05), of PAI-1 (102.4[83.0-117.0] ng/ml versus 63.5[31.8-87.3] ng/ml, p<0.01) and of t-PA (5.1[2.5-7.9] ng/ml versus 3.4[1.4-5.8] ng/ml, p<0.05). They had increased IMT, which correlated with vWF (r=0.29, p<0.05). Their normolipidemic relatives had significantly higher levels of vWF (137.2+/-42.8% versus 106.6+/-24.0%, p<0.01) and of PAI-1 (75.3[53.2-92.0] ng/ml versus 48.6[37.4-85.9] ng/ml, p<0.05). Levels of vWF, PAI-l and t-PA were independently associated with several markers of insulin resistance. CONCLUSIONS: Asymptomatic members of FCH families have increased endothelial haemostatic factors- vWF, PAI-1, t-PA, which are associated with insulin resistance. VWF correlates with morphological vascular changes, detected by the increase of IMT, presented in only hyperlipidemic subjects.

Positive association of adiponectin with soluble vascular cell adhesion molecule sVCAM-1 levels in patients with vascular disease or dyslipidemia.

The aim of our study was to evaluate the relationship of adiponectin to soluble forms of vascular cell adhesion molecule-1 (sVCAM-1) and intercellular cell adhesion molecule-1 (sICAM-1) in patients with cardiovascular disease or dyslipidemia. Two hundred and sixty-four patients (134 men/130 women, mean age 43.8+/-14.8/46.0+/-14.9 years) of Lipid Center, University Hospital Olomouc, off hypolipidemic therapy for at least 6 weeks, participated in the study. In multiple regression analysis, adiponectin was independently positively associated with serum HDL-cholesterol (p<0.0001) and sVCAM-1 (p<0.0001), female gender (p<0.0001) and negatively with hs-CRP (p=0.014). Serum concentration of adiponectin and sICAM-1 did not correlate but sICAM-1 was independently, positively associated with sVCAM-1 (p<0.0001) and negatively with markers of insulin resistance and inflammation, namely atherogenic index log[triglycerides/HDL-cholesterol] (p<0.0001), hs-CRP (p<0.001) and HOMA (p<0.05). Positive association of adiponectin with HDL-C and negative association with hs-CRP indicate anti-atherogenic properties of adiponectin. The finding of the positive association of adiponectin with sVCAM-1 in patients at risk is unexpected. We hypothesize that adiponectin may be involved (directly or indirectly) in shedding of ectodomains of VCAM-1 from endothelial surface and in this way down-regulates their effects. This process may be protective in the initial stages of atherosclerosis.

Soluble cell adhesion molecules s-VCAM-1 and s-ICAM-1 in subjects with familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCH) is the most common familial hyperlipidemia with a high risk for early atherosclerosis. The aim of this study was to compare levels of soluble intercellular cell adhesion molecule 1 (s-ICAM-1) and soluble vascular cell adhesion molecule 1 (s-VCAM-1) in asymptomatic members of FCH families with healthy controls and to determine the relation between s-ICAM-1, s-VCAM-1 and risk factors accompanying FCH. We also investigated the association between adhesion molecules and the intima-media thickness (IMT) of the common carotid artery, a recognized morphological marker of early atherosclerosis. 82 members of 29 FCH families were divided into the 2 groups: HL (probands and hyperlipidemic first-degree relatives, n = 47) and NL (normolipidemic first-degree relatives, n = 35). The control groups--HL-C (n = 20) and NL-C (n = 20)--consisted of sex- and age-matched healthy individuals. Hyperlipidemic members had significantly higher concentration of s-ICAM-1 (633.7 +/- 169.6 ng/ml versus 546.2 +/- 155.9 ng/ml, p < 0.05). The elevation of s-VCAM-1 was not significant (880.8 +/- 202.9 ng/ml versus 826.5 +/- 174.6 ng/ml, N.S.). Levels of s-ICAM-1 and of s-VCAM-1 in normolipidemic relatives were not significantly different from the control group (530.8 +/- 113.9 ng/ml versus 530.0 +/- 101.0 ng/ml and 860.2 +/- 265.7 ng/ml versus 822.1 +/- 197.0 ng/ml respectively). There was a significant correlation between s-ICAM-1 and apoB (r = 0.42; p < 0.01) in hyperlipidemic subjects and between s-ICAM-1 and proinsulin (r = 0.54; p < 0.01) in normolipidemic subjects. S-ICAM-1 correlated with IMT (r = 0.32; p < 0.05) in all members of FCH families. The increase of s-ICAM-1 in asymptomatic hyperlipidemic members of FCH families reflects their high cardiovascular risk. The positive association between s-ICAM-1 and IMT could indicate s-ICAM-1 as a potential predictor of atherosclerosis manifestation.

Comparison of apolipoprotein B and plasma lipids as targets for lipid lowering treatment.

OBJECTIVE: To assess the discrepancies between LDL-cholesterol and apo B targets in patients at risk for vascular disease; namely, those with diabetes or hypertriglyceridemia and those with triglycerides <1.7 mmol/L and normal glucose homeostasis. METHODS: Lipid clinic patients were divided into two groups: Group 1 consisted of 182 patients whose triglyceride levels were >1.7 mmol/L or who had impaired fasting glucose or type 2 diabetes. In Group 2, there were 42 patients with triglycerides <1.7 mmol/L and normal glucose homeostasis. LDL-cholesterol and apo B were estimated during lipid clinic visits with patients on appropriate lipid lowering therapy. RESULTS: 46% of the patients in Group 1 who reached the high risk LDL-cholesterol target of <2.5 mmol/L did not reach apo B target of <0.9 g/L, while in Group 2, only 19% of those who reached the LDL-cholesterol target had apo B >0.9 g/L. CONCLUSION: Our findings demonstrate that a large percentage of patients with hypertriglyceridemia or impaired glucose tolerance, treated with lipid lowering agents, reach the LDL-cholesterol but not the apo B treatment targets.