Independent Predictors Of Intima-media Thickness Research Articles

Adipokines as atherothrombotic risk factors in obese subjects: Associations with haemostatic markers and common carotid wall thickness

Background and aimsSome crucial associations between obesity-related altered adipokine levels and the main factors of atherosclerotic, atherothrombotic processes are not fully known. We analysed the relationships of classic adipokines, namely leptin, resistin, adiponectin, tumour necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) with the markers of platelet activation, including mean platelet volume (MPV), platelet surface/soluble P-selectin, platelet-derived microparticles (PMPs), the parameters of coagulation abnormalities and common carotid intima-media thickness (IMT) in obese patients with or without atherosclerotic comorbidities in comparison to age- and sex-matched controls. Methods and resultsWe enrolled 154 obese individuals, including 98 suffering from atherosclerotic concomitant conditions, 56 free of atherosclerotic comorbidities and 62 healthy controls. Plasma levels of leptin, resistin, adiponectin, TNF-α, IL-6, soluble P-selectin, and plasminogen activator inhibitor-1 antigen (PAI-1 ag) were analysed by ELISA. Platelet surface P-selectin and PMPs were measured by flow cytometry. IMT was detected by ultrasonography. Adipokines were closely associated with markers of platelet hyperactivity, hypercoagulability, hypofibrinolysis and IMT. Significant independent associations were found between leptin and platelet count (p < 0.0001), MPV (p = 0.019), PMPs (p < 0.0001), fibrinogen (p = 0.001), factor VIII (FVIII) activity (p = 0.035); adiponectin and PAI-1 ag (p = 0.035); resistin and soluble P-selectin (p = 0.002); TNF-α and PAI-1 ag (p < 0.0001); and IL-6 and fibrinogen (p = 0.011). Finally, leptin (p = 0.0005), adiponectin (p = 0.019), IL-6 (p = 0.001), MPV (p = 0.0003), PMP (p = 0.008), and FVIII activity (p = 0.043) were independent predictors of IMT. ConclusionOverall, we suggest that in obese subjects altered adipokine levels play a key role in common carotid atherosclerosis both directly and through haemostatic parameters.

Increased intima-media thickness is not associated with stiffer arteries in children.

Subclinical atherosclerosis can be assessed via sonographic measurement of intima-media thickness and carotid artery distensibility, both may already be pathologically altered in childhood. Therefore, the purpose of this study was to provide reference percentiles and investigate possible associations between alterations of intima-media thickness and distensibility. Carotid intima-media thickness and distensibility was measured via B- and M-mode ultrasound. Distensibility was defined by arterial compliance, elastic modulus, stiffness parameter β, and local pulse wave velocity β. Age- and height-dependent reference values were calculated separately for boys and girls among 690 (intima-media thickness) and 870 (distensibility) non-obese children aged 7-17 years. Intima-media thickness and distensibility did not increase significantly with age or differ between boys and girls. Systolic blood pressure and body mass index were independent predictors of intima-media thickness, while an increased systolic blood pressure or pulse pressure was associated with stiffer arteries. Increased intima-media thickness was accompanied by higher arterial compliance and lower stiffness. Using this healthy cohort, we describe a functional and non-pathological arterial adaptation wherein an increase in intima-media thickness is not associated with stiffer arteries.

Two Variants in the Fibulin2 Gene Are Associated with Lower Systolic Blood Pressure and Decreased Risk of Hypertension

Arterial stiffness is an important factor in hypertension. Fibulin 2 is an extracellular matrix scaffold protein involved in arterial stiffness and, hence, the fibulin 2 (FBLN2) gene may be a candidate for hypertension susceptibility. 4 single nucleotide polymorphisms (SNPs) of FBLN2 were evaluated in an association case-control study containing 447 hypertensive patients and 344 normotensive control subjects. The minor allele frequencies of rs3732666 and rs1061376 were significantly lower in hypertensives. The odds ratios (OR) for having the protective G (rs3732666) and T (rs1061376) alleles were 0.75 (95%CI: 0.58 to 0.96) and 0.83 (95%CI: 0.66 to 1.02), respectively. For rs3732666, the OR for hypertension in AG+GG subjects, compared with AA, was 0.71 (95%CI: 0.52 to 0.95). The protective genotype AG+GG was associated with significantly lower systolic blood pressure (SBP) [−3.6 mmHg (P = 0.048)]. There was a significant age interaction with rs3732666; the effect decreasing with increasing age. For rs1061376, TT subjects had an OR for hypertension of 0.53 (95%CI: 0.32 to 0.87) compared with CC subjects, with reduced SBP (−7.91 mmHg; P = 0.008) and diastolic BP (DBP) (−3.69 mmHg; P = 0.015). The presence of a G allele was an independent predictor of intima-media thickness (IMT); G carrier’s having lower mean IMT (−0.037 mm, P = 0.027) compared with AA. Our results provide the first evidence for FBLN2 as a new gene associated with hypertension.

Thinking Beyond Traditional Cardiovascular Risk Factors

In this issue of Angiology, Ticulescu et al assess the role of arterial stiffness in relation to established risk factors in predicting cardiovascular (CV) remodeling. They assessed left ventricular mass index (LVMi) and carotid intima media thickness (IMT) in patients with moderate renal impairment. Outpatients with stage III chronic kidney disease ([CKD] n 1⁄4 89) and with stage II CKD (n 1⁄4 52) underwent echocardiographic and supra-aortic trunk scanning; carotid IMT was measured 1 cm beneath the carotid bifurcation, whereas arterial stiffness was assessed at the right carotid as the b index. As Ticulescu et al point out, this echotracking estimation of arterial stiffness represents a useful and feasible technique that allows the evaluation of both heart and vessels during one examination. The 2 groups were similar for established CV risk factors (ie, age, gender, hypertension, hypercholesterolemia, diabetes mellitus [DM], and smoking) and relevant drug treatment. No significant differences were found in terms of blood pressure, biochemical parameters (except for creatinine clearance), IMT, LVMi, and presence of carotid plaques. After multivariate analysis, the b index of arterial stiffness was an independent predictor of IMT (along with age, DM, and hypercholesterolemia) in patients with stage III CKD; the most powerful predictor was DM, followed by age, b index, and hypercholesterolemia. In the stage II CKD group, DM was the only independent predictor of IMT. As discussed by Ticulescu et al, this finding could reflect the functional effect of arterial wall remodeling at different stages of CKD; the intimal layer plays a main role in atherogenesis during earlier stages of CKD, whereas in more advanced CKD, the atherosclerotic process mainly involves the medial layer. Chronic kidney disease is recognized as a CV risk factor, and these patients should be treated accordingly. On the other hand, arterial stiffness, regulated by numerous factors, such as mean arterial pressure, structural alterations of the arterial wall, endothelial dysfunction, and inflammation, may accelerate the atherosclerotic process. There are several different noninvasive methods for the assessment of arterial stiffness including pulse wave velocity (PWV), relating change in vessel diameter (or area) to distending pressure, arterial pulse waveform analysis, ambulatory arterial stiffness index, augmentation index, and b index; PWV is the most recognized and established index of arterial stiffness. Arterial stiffness and CKD are closely linked by shared risk factors and associated increased CV mortality. In a cohort of hemodialysis patients, both carotid IMT and b index of arterial stiffness were independently predictive of CV mortality even after adjustment for other relevant covariates, implicating the distinct roles of stiffness and thickness of arterial wall in the pathogenesis of CV disease. Furthermore, arterial stiffness assessed by aortofemoral PWV was the only arterial index (among carotid IMT, systemic arterial compliance, and carotid-derived augmentation index) independently associated with CV outcome in patients with stages IV and V CKD. It should be noted that arterial stiffness is a predictor for CV events not only in renal patients but also in the general population, in patients with hypertension, impaired glucose intolerance, and coronary artery disease. Furthermore, a recent meta-analysis showed that aortic PWV was a strong predictor of CV events and all-cause mortality in 15 877 individuals; the higher the baseline CV risk, the higher the predictive ability of arterial stiffness. Interestingly, aortic PWV was a stronger independent predictor (r 1⁄4 .48; P 1⁄4 .002) of a 25% decline in renal function or initiation of renal replacement therapy compared with systolic blood pressure (r 1⁄4 .17; P 1⁄4 .039) and urine-proteinto-creatinine ratio (r 1⁄4 .20; P 1⁄4 .021) in patients with stages III and IV CKD.

Aging, components of metabolic syndrome and serum C-reactive protein showed significant relationship with carotid atherosclerosis

Objective: metabolic syndrome (MetS) is known to be associated with an increased risk for cerebro- as well as cardio-vascular disease. Prediction of carotid atherosclerosis by components of MetS, serum C-reactive protein, aging and related factors was conducted for Japanese inhabitants. Methods: A total of 887 subjects (761 males, 126 females) were included in the present study. Early atherosclerosis was assessed by measurement of the intima-media thickness of the common carotid arteries. Results: The carotid arterial intima-media thickness on both the right and left sides significantly increased as the number of components of MetS increased. The maximum intima-media thickness values in the right (left) carotid arteries in the male and female subjects who fulfilled the criteria for MetS were 0.65 ± 0.18 (0.66 ± 0.17) mm and 0.58 ± 0.12 (0.59 ± 0.11) mm, respectively. After adjustment for several factors, the intima-media thickness related significantly with aging, some components of MetS and serum C-reactive protein by multiple regression analysis. β-coefficient of age was largest, presenting 0.457 in right side and 0.479 in left side. Conclusions: Aging, metabolic components and serum C-reactive protein are independent predictors of intima-media thickness in subjects.

Stress-induced cardiovascular reactivity and atherogenesis in adolescents

ObjectiveTo examine the association between cardiovascular reactivity to a set of psychological stressors and carotid artery intima-media thickness, a marker of subclinical cardiovascular disease in healthy adolescents. MethodsParticipants were 25 boys and 23 girls age 14.2±0.9 years who were measured for heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure reactivity to mirror-tracing, reaction time, speech preparation and ad lib speech tasks and for common carotid artery intima-media thickness. Sequential regression analyses were used to establish the incremental increase in R2(Rinc2) for the prediction of intima-media thickness due to cardiovascular reactivity independent of age, BMI percentile, sex, socioeconomic status, and resting HR or BP. ResultsSBP reactivity while preparing (β=0.0019, Rinc2=0.09) and giving the speech (β=0.0014, Rinc2=0.10) and an aggregate reactivity score based on all 4 tasks (β=0.0026, Rinc2=0.11) independently predicted (p≤0.05) mean carotid artery intima-media thickness. Neither DBP reactivity nor HR reactivity during any task were independent predictors of intima-media thickness. ConclusionStress-induced cardiovascular reactivity, and especially SBP reactivity, is associated with carotid intima-media thickness and the early pathogenesis of cardiovascular disease. The use of an aggregate stress reactivity index provides a more reliable reflection of trait SBP reactivity to psychological stress and increases the confidence that youth with greater cardiovascular stress reactivity may indeed have greater progression of subclinical cardiovascular disease.

Serum amyloid A is independently associated with metabolic risk factors but not with early atherosclerosis: the Cardiovascular Risk in Young Finns Study

Serum amyloid A (SAA) is a sensitive marker of inflammation and its elevation has been implicated in obesity and in cardiovascular disease, yet data on its regulation in young adults or on its role in early atherosclerosis is scarce. We investigated which factors explain the variation in SAA and analysed whether SAA could be associated with preclinical atherosclerosis. Serum amyloid A levels were measured in participants of the Cardiovascular Risk in Young Finns Study (n = 2280, n = 1254 women, n = 1026 men). Correlates and determinants of SAA were analysed and the effect of SAA on subclinical atherosclerosis, measured as intima-media thickness (IMT) and carotid artery compliance, was evaluated with risk-factor adjusted models. Serum amyloid A correlated directly and independently of BMI with C-reactive protein (CRP), waist circumference and leptin in both sexes, with total cholesterol, LDL cholesterol and ApolipoproteinA1 (ApoA1) in women and with triglycerides, insulin levels and insulin resistance in men. Use of combined oral contraceptives and intrauterine device was also associated with SAA levels. Determinants for SAA included CRP, leptin and ApoA1 in women, and CRP, leptin and HDL cholesterol in men. SAA levels correlated with carotid compliance in both sexes and with IMT in men, yet SAA had no independent effect on IMT or carotid compliance in multivariable analysis. Serum amyloid A was associated with several metabolic risk factors but was not an independent predictor of IMT or carotid artery compliance. Further longitudinal studies will show whether SAA holds a prognostic value as a risk marker, analogously to CRP.

Cardiovascular risk factors and non-invasive assessment of subclinical atherosclerosis in youth

Our understanding of the natural history of atherosclerosis in childhood and its response to cardiovascular (CV) risk factor reduction have been hampered by the lack of a reliable, non-invasive measure of atherosclerosis. Carotid intima media thickness (IMT), a surrogate marker of atherosclerosis in adults, is increased in youth heterozygous for familial hypercholesterolemia (FH) and declines with lipid lowering pharmacotherapy. The age at which vascular changes can be reliably identified using IMT and the influence of CV risk factors beyond FH on IMT remains unclear. ObjectiveTo examine the influence of demographic, family history, anthropometric characteristics and traditional CV risk factors on IMT in children 5–16 years of age (mean age 11 year). MethodsIn a cross-sectional study, we assessed IMT in 148 children (51 with elevated low density lipoprotein (LDL)-cholesterol, 44 with overweight and 53 controls). Measures included: family history of premature coronary heart disease (CHD), physical activity, pubertal stage, smoking history, fasting glucose, insulin, lipid profile, apolipoproteins A1 and B, anthropometry, blood pressure and IMT. ResultsThe groups were similar for age and family history of premature CHD. Compared to controls, average maximum IMT (0.403±0.04 vs 0.387±0.029) and average mean IMT were elevated in the hyperlipidemia group (p<0.05), but not in the overweight group (max IMT 0.393±0.034; p vs control=0.17). Using multiple regression modelling, age, family history of premature CHD and apoliprotein A1 and B predicted 17% of the variability in IMT. No measure of adiposity predicted IMT. ConclusionAge is an important predictor of IMT in youth. Among traditional CV risk factors, dyslipidemia and family history of premature CHD are independent predictors of IMT.

112: Leptin: Adiponectin ratio is an independent predictor of intima-media thickness of the common carotid artery

112: Leptin: Adiponectin ratio is an independent predictor of intima-media thickness of the common carotid artery

Correlates of preclinical cardiovascular disease in Indigenous and Non-Indigenous Australians: a case control study

BackgroundThe high frequency of premature death from cardiovascular disease in indigenous Australians is often attributed to the high prevalence of risk factors, especially type II diabetes mellitus (DM). We evaluated the relationship of ethnicity to atherosclerotic burden, as evidenced by carotid intima-media thickness (IMT), independent of risk factor status.MethodsWe studied 227 subjects (147 men; 50 ± 13 y): 119 indigenous subjects with (IDM, n = 54), and without DM (InDM, n = 65), 108 Caucasian subjects with (CDM, n = 52), and without DM (CnDM, n = 56). IMT was measured according to standard methods and compared with clinical data and cardiovascular risk factors.ResultsIn subjects both with and without DM, IMT was significantly greater in indigenous subjects. There were no significant differences in gender, body mass index (BMI), systolic blood pressure (SBP), or diastolic blood pressure (DBP) between any of the groups, and subjects with DM showed no difference in plasma HbA1c. Cardiovascular risk factors were significantly more prevalent in indigenous subjects. Nonetheless, ethnicity (β = -0.34; p < 0.0001), age (β = 0.48; p < 0.0001), and smoking (β = 0.13; p < 0.007) were independent predictors of IMT in multiple linear regression models.ConclusionEthnicity appears to be an independent correlate of preclinical cardiovascular disease, even after correction for the high prevalence of cardiovascular risk factors in indigenous Australians. Standard approaches to control currently known risk factors are vital to reduce the burden of cardiovascular disease, but in themselves may be insufficient to fully address the high prevalence in this population.

Response to Letter by Kotani et al

Response: We thank Dr Kotani and colleagues for their interest in our article “Leptin: adiponectin ratio is an independent predictor of intima-media thickness of the common carotid artery”.1 We much appreciate their contribution to investigate the possible role of the leptin:adiponectin ratio in different asymptomatic populations, and we believe that their findings in old asymptomatic females add new information. Indeed Kotani …

Structural and functional arterial properties in patients with obstructive sleep apnoea syndrome and cardiovascular comorbidities

The increased severity of obstructive sleep apnoea syndrome (OSAS) is associated with a parallel increase in the incidence of cardiovascular events. Whether the increased severity of OSAS is in fact associated with impaired arterial properties has never been thoroughly studied. In patients with OSAS who carry a high burden of cardiovascular risk factors, we investigated whether the severity of OSAS is associated with deterioration in the arterial properties, independent of classical cardiovascular risk factors. In 74 consecutive patients with OSAS, we non-invasively assessed, by means of tonometry and high-resolution ultrasound: carotid intima-media thickness (IMT), carotid diameter and plaques, carotid-femoral pulse wave velocity (PWV), central augmentation index (AI) and central blood pressures. The respiratory disturbance index was an independent predictor of IMT and PWV but not of carotid plaques, carotid diameter, AI or central blood pressures. Several parameters of nocturnal hypoxaemia were independently correlated with carotid IMT and PWV. In conclusion, arterial stiffening and thickening are modulated by the severity of OSAS, independently from age and cardiovascular risk factors.

Global vasomotor dysfunction and accelerated vascular aging in β-thalassemia major

Background Patients with β-thalassemia major (β-TM) demonstrate an increased incidence of vascular complications, which are thought to result from a procoagulant/proinflammatory environment. We investigated the arterial vasorelaxing capacity and sought for early carotid atherosclerosis and underlying pathophysiological correlates in these transfusion-dependent patients. Methods and results The vasodilatory properties of the brachial artery and the carotid intima-media thickness (IMT) were examined with ultrasonography in 35 non-diabetic young adults with β-TM (patient group) and 35 control subjects (control group). Among thalassemic patients, both endothelium-dependent (FMD) and -independent dilatation (FID) as well as their ratio was impaired, whereas IMT was increased ( p < 0.01). Patients on optimal, as compared with those on non-optimal chelation treatment had a non-significantly lower IMT. Vasodilatory capacity in the patient group was inversely correlated with IMT and independently associated either with the quality of chelation therapy (FMD) or serum ferritin levels (FID). Plasma concentrations of D-dimers, circulating markers of endothelial activation, inflammation and apoptosis were higher, while plasma cholesterol and fibrinogen levels were lower-than-normal in the patient group. Independent predictors of IMT among thalassemic patients were tumor necrosis factor-α levels and age. Conclusions Young adults with β-TM exhibit both a global impairment of arterial vasorelaxation and early carotid atherosclerosis. A procoagulant/proinflammatory state in these transfusion-dependent patients may overwhelm atheroprotective mechanisms, including an optimal chelation regimen, and promote vascular injury and atherogenesis.

Awake Systolic Blood Pressure Variability Correlates With Target-Organ Damage in Hypertensive Subjects

Growing evidence associates blood pressure (BP) variability with cardiovascular events in hypertensive patients. Here we tested the existence of a relationship between awake BP variability and target-organ damage in subjects referred for suspected hypertension. Systolic and diastolic BP variability were assessed as the standard deviation of the mean out of 24-hour, awake and asleep BP recordings in 180 untreated subjects, referred for suspected hypertension. Measurements were done at 15-minute intervals during daytime and 30-minute intervals during nighttime. Left ventricular mass index (by echo), intima-media thickness (by carotid ultrasonography), and microalbuminuria were assessed as indices of cardiac, vascular and renal damage, respectively. Intima-media thickness and left ventricular mass index progressively increased across tertiles of awake systolic BP variability (P for trend=0.001 and 0.003, respectively). Conversely, microalbuminuria was similar in the 3 tertiles (P=NS). Multivariable analysis identified age (P=0.0001), awake systolic BP (P=0.001), awake systolic BP variability (P=0.015) and diastolic BP load (P=0.01) as independent predictors of intima-media thickness; age (P=0.0001), male sex (P=0.012), awake systolic (P=0.0001) and diastolic BP (P=0.035), and awake systolic BP variability (P=0.028) as independent predictors of left ventricular mass index; awake systolic BP variability (P=0.01) and diastolic BP load (P=0.01) as independent predictors of microalbuminuria. Therefore, awake systolic BP variability by non-invasive ambulatory BP monitoring correlates with sub-clinical target-organ damage, independent of mean BP levels. Such relationship, found in subjects referred for recently suspected hypertension, likely appears early in the natural history of hypertension.

The relative impact of different measures of adiposity on markers of early atherosclerosis

Background Although there are several methods available to assess adiposity, there is still controversy on the relative clinical utility of each of these methods. This study examines the relative impact of different measures of adiposity on markers of early atherosclerosis. In particular weight changes over time have been poorly assessed in this setting. Methods Eighty-six healthy individuals (31 men, age 36.5 ± 8.9 years) with a wide range of body-mass index (28.7 ± 7.0, 18.9–57.9 kg/m 2) without hypertension, diabetes or smoking were examined. In addition to waist circumference and waist-to-hip ratio self-reported weight change since adolescence was also calculated. Ultrasonography was used to measure abdominal fat layers and their ratio. Flow-mediated dilatation of the brachial artery, serum levels of intercellular adhesion molecule (sICAM-1) and mean intima-media thickness of the carotid artery were measured as markers of early atherosclerosis. Results Stepwise multivariate regression analysis showed waist circumference and waist-to-hip ratio as the only independent predictor of flow-mediated dilatation. Waist circumference and weight change but not current body-mass index were independent predictors of intima-media thickness. These correlations were not influenced by ultrasonographically measured fat layers, C-reactive protein and basal insulin resistance. Body-mass index and weight gain were associated with sICAM-1 but not independently of basal insulin resistance and C-reactive protein. Conclusions Waist circumference and weight gain were the strongest predictors of early atherosclerosis in a population of apparently healthy adults. The ultrasonographically measured fat layers did not provide additional information in this population.

Traditional and non-traditional risk factors contribute to the development of accelerated atherosclerosis in patients with systemic lupus erythematosus

To determine risk factors of accelerated atherosclerosis in patients with systemic lupus erythematosus (SLE), 72 patients with inactive disease and 36 age- and sex-matched controls were included. The intima-media thickness (IMT) of the common carotid artery was determined by ultrasound. Traditional risk factors and disease-related factors were recorded. Cardiovascular risk was estimated using SCORE (systematic coronary risk evaluation). Markers of inflammation, endothelial activation and vascular remodelling (matrix metalloproteinases (MMP-3, MMP-9) and tissue inhibitor of metalloproteinase- 1 (TIMP- 1)) were determined. IMT was increased in patients (0.67 mm+/-0.13 versus 0.61 mm+/-0.11, P < 0.05). Prevalence of hypertension (33% versus 6%, P < 0.001), SCORE (2.2 (1.7-4.2) versus 1.7 (1.3-2.1), P < 0.001), as well as parameters of inflammation (CRP 1.8 (0.6-5.8) mg/L versus 0.6 (0.2-1.0) mg/L, P < 0.001) and endothelial activation (VCAM-1 505 (389-683) ng/mL versus 374 (322-427) ng/mL, P < 0.001) and von Willebrand factor (138 (59-208)% versus 48 (24-92)%, P < 0.001), were increased in patients. Vascular remodelling was altered: MMP-3 and TIMP-1 were increased (18 (10-29) ng/mL versus 8 (5-11) ng/mL, P < 0.001, and 275 (216-352) ng/mL versus 230 (197-268) ng/mL, P < 0.001, respectively), and MMP-9 was decreased in SLE (266 (147-412) ng/mL versus 348 (226-530) ng/mL, P < 0.05). Univariate analyses revealed that in patients IMT was associated with age, systolic blood pressure, SCORE and disease duration. In multivariate analysis, age and SCORE were independent predictors of IMT. In conclusion, SLE patients have an increased IMT, which is associated with traditional risk factors. Non-traditional risk factors, such as endothelial activation, altered vascular remodelling and disease duration, might play an additional role.

Remnant particles are the major determinant of an increased intima media thickness in patients with familial combined hyperlipidemia (FCH)

Introduction Familial combined hyperlipidemia (FCH) is characterized by several phenotypes, including an atherogenic lipoprotein profile, low grade inflammation, visceral obesity, insulin resistance, and hypertension. In this study, we investigated which of the clinical and biochemical characteristics of FCH patients contributes most to their increased risk of cardiovascular disease, by determining the association of a broad variety cardiovascular risk factors with the intima media thickness (IMT) of the common carotid artery (CCA) in 94 FCH patients and 216 non-affected relatives. Methods All subjects filled out a questionnaire about their smoking and drinking habits, medical history and medication use, and venous blood was drawn in the fasting state after discontinuation of lipid lowering medication (if used). IMT of the far wall and near wall of both CCAs was measured by high-resolution B-mode ultrasonography. Results The mean IMT in FCH patients (adjusted for age and gender) was 33 μm thicker when compared to their non-affected relatives ( p = 0.006). In multivariate analysis, the waist-to-hip ratio, the apoB concentration and the pulse pressure were significant and independent predictors of IMT in both FCH patients and their normolipidemic relatives. The most important independent predictor of IMT in FCH patients however, was the VLDL-c/TG ratio, explaining 32.8% of the variation in age- and gender-adjusted IMT, whereas this ratio was not an independent predictor of IMT at all in their unaffected relatives. Conclusion Abdominal obesity, a higher blood pressure and dyslipidemia characterised by both an increased number of atherogenic particles and the presence of highly atherogenic remnant lipoproteins play an important role in the development of cardiovascular disease in FCH-patients.

Renal transplant recipients with coronary artery disease exhibit impairment in fibrinolysis and structural changes in carotid arteries

Cardiovascular disease (CVD) is the main cause of mortality and morbidity among kidney transplant recipients (Tx). Intima-media thickness (IMT) of the common carotid artery is related to CVD. Hemostatic disturbances may contribute to the CVD pathogenesis in Tx. The aim of the study was to evaluate some hemostatic factors in Tx with and without coronary artery disease (CAD) and their correlations with IMT. Patients with CAD were significantly older, with thicker IMT, lower plasmin-antiplasmin complexes (PAP), higher fibrinogen, cholesterol, triglycerides, Thrombin-activatable fibrinolysis inhibitor (TAFI) antigen and activity, prolonged euglobulin clot lysis time when compared to those without CAD. Kidney transplant recipients have higher mean blood pressure, serum lipids, fibrinogen, TAFI antigen, TAFI activity, markers of coagulation and fibrinolysis, thicker IMT and lower PAP relative to healthy volunteers. In univariate analysis, IMT correlated significantly with age, time on dialysis prior to transplantation, PAP, fibrinogen, hematocrit, body mass index (BMI). Multiple regression analysis showed that only age, hematocrit, PAP, and time on dialysis prior to transplantation were positive independent predictors of IMT. Hypofibrinolysis may contribute to the arterial remodeling in Tx. Dialysis therapy before transplantation makes detrimental changes in arterial vasculature.

Subclinical atherosclerosis is increased in type 2 diabetic patients with microalbuminuria evaluated by intima-media thickness and pulse wave velocity

Microalbuminuria appears to be a risk marker for atherosclerosis. However, little is known about the direct association between microalbuminuria and vascular wall properties. Subjects were 306 type 2 diabetic patients with normoalbuminuria (N= 200) and microalbuminuria (N= 106). Those who had macroalbuminuria, atherosclerotic vascular disease, and/or ankle brachial index being less than 0.9 were not included. Brachial-ankle pulse wave velocity (PWV) was measured by automatic oscillometric method. Intima-media thickness (IMT) of the common carotid artery was measured using high-resolution B-mode ultrasonography and a computerized image-analyzing system. Average IMT, maximum IMT, and PWV were significantly higher in patients with microalbuminuria than in patients with normoalbuminuria. Both average and maximum IMT increased significantly as albuminuria increased in the microalbuminuric range. Average IMT and maximum IMT correlated significantly with PWV (P < 0.0001), although some patients exhibited increased levels of only PWV or IMT. By a multiple linear regression, age and albuminuria were independent predictors of IMT and PWV. Waist circumference was an independent predictor of IMT. Hypertension and hemoglobin A(1c) (HbA(1c)) were independent predictors of PWV. After adjustment for conventional cardiovascular risk factors including age, sex, waist circumference, HbA(1c), hypertension, hyperlipidemia, and smoking, albuminuria revealed a significant association with average IMT, maximum IMT, and PWV (P < 0.05, P < 0.0001, and P < 0.05, respectively). A slight elevation of albuminuria is a significant determinant of IMT and PWV independent of conventional cardiovascular risk factors in type 2 diabetic patients with no clinical nephropathy or any vascular diseases. This significant association might point to a link in the pathogenesis of atherosclerosis and diabetic nephropathy.

Progression of atherosclerosis as assessed by carotid intima-media thickness in patients with HIV infection.

HIV-infected patients may be at increased risk for coronary events. The purpose of this study was to identify predictors of carotid intima-media thickness (IMT) in HIV patients at baseline and to measure IMT progression over 1 year. We measured blood lipids, inflammatory markers, and IMT in 148 HIV-infected adults (mean age, 45+/-8 years) and in 63 age- and sex-matched HIV-uninfected control subjects. The mean duration of HIV infection was 11 years, and the median duration of protease inhibitor treatment was 3.3 years. Mean baseline IMT was 0.91+/-0.33 mm in HIV patients and 0.74+/-0.17 mm in control subjects (P=0.0001). Multivariable predictors of baseline IMT in HIV patients were age (P<0.001), LDL cholesterol (P<0.001), cigarette pack-years (P=0.005), Latino race (P=0.062), and hypertension (P=0.074). When the control group was added to the analysis, HIV infection was an independent predictor of IMT (P=0.001). The rate of progression among the 121 HIV patients with a repeated IMT measurement at 1 year was 0.074+/-0.13 mm, compared with -0.006+/-0.05 mm in 27 control subjects (P=0.002). Age (P<0.001), Latino race (P=0.02), and nadir CD4 count < or =200 (P=0.082) were multivariable predictors of IMT progression. Carotid IMT is higher in HIV patients than in age-matched control subjects and progresses much more rapidly than previously reported rates in non-HIV cohorts. In HIV patients, carotid IMT is associated with classic coronary risk factors and with nadir CD4 count < or =200, suggesting that immunodeficiency and traditional coronary risk factors may contribute to atherosclerosis.