Michaela Kozakova

Fatty liver is associated with insulin resistance, risk of coronary heart disease, and early atherosclerosis in a large European population.

Patients with fatty liver (FL) disease have a high risk of developing diabetes and cardiovascular diseases. The aim was to evaluate the association between FL, insulin resistance (IR), coronary heart disease (CHD) risk, and early atherosclerosis in a large European population (RISC Study). In 1,307 nondiabetic subjects (age 30‐60 years) recruited at 19 centers, we evaluated liver enzymes, lipids, insulin sensitivity (by euglycemic‐hyperinsulinemic clamp), glucose tolerance (by 75 g oral glucose tolerance test), carotid atherosclerosis as intima media thickness (IMT), CHD risk by the Framingham Heart study prediction score, and physical activity (by accelerometer). The presence of FL was estimated using the fatty liver index (FLI; >60, likelihood >78% presence FL; FLI <20 likelihood >91% absence of FL). Subjects were divided into three groups: G1: FLI <20 (n = 608); G3: FLI >60 (n = 234), G2: intermediate group (n = 465). Compared to G1, G3 included more men (70% versus 24%) and people with impaired glucose tolerance (23% versus 5%). IMT increased with FLI (G3 = 0.64 ± 0.08 versus G1 = 0.58 ± 0.08 mm, P < 0.0001). FLI was associated with increased CHD risk (r = 0.48), low‐density lipoprotein cholesterol (r = 0.33), alanine aminotransferase (r = 0.48), aspartate aminotransferase (r = 0.25), systolic blood pressure (r = 0.39) and IMT (r = 0.30), and reduced insulin sensitivity (r = −0.43), high‐density lipoprotein cholesterol (r = −0.50), adiponectin (r = −0.42), and physical activity (r = −0.16, all P < 0.0001). The correlations hold also in multivariate analysis after adjusting for age, gender, and recruiting center. Conclusion: In middle‐age nondiabetic subjects, increased IMT, CHD risk, and reduced insulin sensitivity are associated with high values of FLI. (HEPATOLOGY 2009.)

α-Adrenergic Blockade Improves Recovery of Myocardial Perfusion and Function After Coronary Stenting in Patients With Acute Myocardial Infarction

Background—AMI reperfusion by thrombolysis does not improve TIMI flow and LV function. The role of infarct-related artery (IRA) stenosis and superimposed changes in coronary vasomotor tone in maintaining LV dysfunction must be elucidated. Methods and Results—Forty patients underwent diagnostic angiography 24 hours after thrombolysis. Seventy-two hours after thrombolysis, the culprit lesion was dilated with coronary stenting. During angioplasty, LV function was monitored by transesophageal echocardiography. Percent regional systolic thickening was quantitatively assessed before PTCA, soon after stenting, 15 minutes after stenting, and after phentolamine 12 μg/kg IC (n=10), the α1-blocker urapidil 600 μg/kg IV (n=10), or saline (n=10). Ten patients pretreated with β-blockers received urapidil 10 mg IC. Coronary stenting significantly improved thickening in IRA-dependent and in non–IRA-dependent myocardium (from 27±15% to 38±16% and from 40±15% to 45±15%, respectively). Simultaneously, TIMI frame count decre...

Fatty liver index, gamma‐glutamyltransferase, and early carotid plaques

An association between fatty liver and carotid atherosclerosis has been established; however, it is not clear whether this relationship is a consequence of shared conventional risk factors or whether it is determined by specific circulating factors originating from liver or adipose tissue. To identify the factors possibly linking fatty liver and atherosclerosis, we assessed, in 1,012 subjects free of confounding diseases (e.g., hypertension, diabetes, cardiovascular diseases, and dyslipidemia) and metabolic syndrome, the relationship between the presence of early plaques at carotid bifurcation and fatty liver index (FLI; a validated surrogate marker of fatty liver), as well as the associations between carotid plaque presence and established atherosclerotic risk factors, family history of cardiovascular disease (FH‐CVD) or diabetes, insulin sensitivity, serum liver enzymes, adipokines, fatty free acids, and high‐sensitivity C‐reactive protein (hsCRP). A total of 55 of 1,012 subjects (5.4%) had small plaque at carotid bifurcation. Subjects with plaque were older and had higher prevalence of FLI ≥60 and FH‐CVD, higher blood pressure, plasma low‐density lipoprotein cholesterol, glucose, gamma‐glutamyltransferase (GGT), and hsCRP, as compared to subjects without plaques (P < 0.05). In a logistic regression model, adjusted for sex, liver transaminase, and alcohol consumption, the independent predictors of plaque presence were age (P < 0.0005), FLI ≥60 (P < 0.0005), and current smoking (P < 0.05). When FLI in the model was replaced by variables used in its equation (e.g., body mass index, waist circumference, plasma triglycerides, and GGT), the independent determinants of plaque presence were age (P < 0.001), GGT (P = 0.001), and current smoking (P < 0.05). Conclusions: Our cross‐sectional study suggests that subjects with FLI ≥60 are at higher risk of atherosclerotic lesions, independently of established risk factors, and that serum GGT may represent a link between fatty liver and the development of early atherosclerosis. (HEPATOLOGY 2012)

Effects of Selective α1- and α2-Adrenergic Blockade on Coronary Flow Reserve After Coronary Stenting

BACKGROUND Coronary flow reserve (CFR) is not normalized shortly after coronary stenting. We hypothesized that alpha-adrenergic coronary vasoconstriction acts to limit CFR. METHODS AND RESULTS We assessed flow velocity by Doppler wires and cross-sectional area by angiography in 46 patients undergoing coronary culprit lesion stenting (81+/-4% stenosis). Hyperemia was induced by adenosine (24 micro g IC or 140 micro g/kg per minute IV) before and after stenting. Finally, either the alpha(1)-antagonist urapidil (10 mg IC) or the alpha(2)-antagonist yohimbine (3 mg IC) was randomly combined with adenosine. In 8 subjects with angiographically normal coronary arteries, CFR was increased from 3.21+/-0.30 to 3.74+/-0.43 by yohimbine and to 4.58+/-0.65 by urapidil, respectively (P=0.0001). Patients were divided according to the cutoff of CFR > or =3.0 (n=18) or <2.5 (n=28). Revascularization per se did not change CFR. However, 15 minutes after stenting, CFR decreased to 2.05+/-0.55 from CFR 3.64+/-0.58, whereas in patients with CFR 2.39+/-0.51, it remained unchanged. Yohimbine improved CFR to 3.26+/-0.42 and to 3.41+/-0.58 in patients with >3.0 and <2.05+/-0.55 baseline CFR, respectively. Urapidil improved CFR to 3.52+/-0.30 and 3.98+/-1.07, respectively. CONCLUSIONS Urapidil and yohimbine attenuated the CFR impairment occurring after revascularization by increasing both the epicardial vasodilator effect of adenosine and the blood flow velocity, thus suggesting that the adrenergic system plays an important role in limiting the capacity of the coronary circulation to dilate.

Ultrafast Three-Dimensional Ultrasound Application to Carotid Artery Imaging

BACKGROUND AND PURPOSE Three-dimensional (3-D) vascular ultrasound can be expected to improve qualitative evaluation of vessel pathology and to provide quantitative data on vascular morphology and function. The objective of this study was to develop an ultrafast 3-D vascular system and to validate its performance for quantitation of atherosclerosis and assessment of regional arterial distensibility. METHODS The quantitative analysis of focal atherosclerotic lesions was validated in vitro on 27 phantoms of fibroadipous plaques of known volume (range, 100 to 600 mm3). In vivo reproducibility of plaque volume measurement was tested in 33 patients who had a total of 47 predominantly fibroadipous carotid plaques. Distensibility assessment was validated indirectly through the evaluation of age-related changes in distensibility of common carotid artery in healthy and hypertensive subjects (25 men in each group). RESULTS The volume of plaque phantoms measured from the 3-D data set showed a very close correlation with the true volume (r=0.99; y=0.96x+12.38; P<0.01), with the mean difference between the 2 measurements being -3.12+/-15.1 mm3. High reproducibility was found for measurement of carotid plaque volume in vivo: the mean difference between measurements from 2 observers for the same data set was 0.60+/-11.2 mm3. Indexes of arterial distensibility decreased with age in healthy population, whereas this relationship was lost in hypertensive subjects. CONCLUSIONS Ultrafast 3-D ultrasound imaging of carotid artery demonstrates good accuracy and reproducibility for atherosclerotic plaque volume measurements. The system also allows the study of age-related degenerative vascular changes.

Effect of sedentary behaviour and vigorous physical activity on segment-specific carotid wall thickness and its progression in a healthy population

AIMS This study investigated whether sedentary behaviour and different activity levels have an independent association with carotid intima-media thickness (IMT) and with the 3-year IMT progression in different carotid segments. METHODS AND RESULTS The study population included 614 healthy men and women (mean age = 44 +/- 8 years) without carotid atherosclerosis and without increased coronary heart disease risk, who underwent B-mode carotid ultrasound and objective physical activity assessment by accelerometer (mean monitoring time = 5.7 +/- 1.5 days). Time spent in sedentary (57.6 +/- 9.1%), light (41.0 +/- 9.2%), moderate and vigorous activities was determined. Sedentary behaviour was expressed as the ratio of time spent in sedentary and light activity (sedentary/light ratio) as these two activities occupied the majority of waking time. In 495 subjects, the carotid ultrasound was repeated 3 years after the baseline examination. After adjustment for age and the established risk factors that were independent determinants of carotid wall thickness in our population, sedentary/light ratio was independently associated only with the common carotid artery (CCA) IMT. The 3-year increase in CCA IMT was significantly lower in subjects with periods of vigorous activity (7 +/- 40 microm) when compared with those with light activity only or with periods of moderate activity (22 +/- 51 and 19 +/- 46 microm, respectively, P < 0.05). CONCLUSION The healthy, young-to-middle age population of this study spent more than half of their waking time in sedentary activities. The proportion of time spent in sedentary activities was directly associated with baseline CCA IMT, independently of age and established atherosclerotic risk factors. In the longitudinal analysis, period of vigorous activity influenced the 3-year IMT progression in CCA.

Noninvasive detection of vascular dysfunction in alcoholic patients

Vasodilation is impaired in various conditions, such as hypercholesterolemia and tobacco use. We evaluated brachial artery flow-mediated vasodilation (FMD) after blood pressure (BP) cuff occlusion using high-resolution B-mode ultrasound in 20 alcoholics, without any coexisting conditions such as smoking, hypertension, or cholesterolemia, after a 3-month period of abstinence. They were compared with a control group of 20 alcohol-free healthy subjects. We measured the diameter of the brachial artery under baseline conditions, during reactive hyperemia (with increased flow causing endothelium-dependent dilatation), and after administration of sublingual glyceryl trinitrate (GTN), an endothelium-independent dilator. We performed an echocardiographic study (Esaote Au3) according to guidelines of the American Society of Echocardiography to assess left ventricular mass (LVM), wall thickness, systolic stress, and diastolic function changes. FMD (% diameter change) was significantly less in the alcoholic patients than in the controls (6.03+/-3.67 v 13.7+/-4.65; P < .05), whereas no difference was noted after GTN administration (13.7+/-7.97 v 16.0+/-5.12, P = NS). Echocardiographic study showed no differences between the study group for LVM, wall thickness, and systolic stress; diastolic function expressed as E/A ratio inversion was significantly impaired. These data demonstrate an impairment of endothelial-dependent vasodilatation in chronic alcohol abusers, which may contribute to the excess prevalence of cardiovascular diseases in these individuals.

Circulating endothelial progenitor cells and large artery structure and function in young subjects with uncomplicated Type 1 Diabetes

BackgroundCarotid intima-media thickness (IMT), indices of large artery stiffness and measures of endothelium function may be used as markers of early atherosclerosis in type 1 diabetes mellitus (T1DM). The aim of the present study was to compare the indices of large artery structure and function as well as endothelial function and regenerating capacity between adolescents with T1DM and healthy control of similar age. In addition, the associations of different vascular measures with endothelial progenitor cells (EPCs), glyco-metabolic control and serum levels of advanced glycation endproducts (AGEs), soluble receptors for AGEs (sRAGE) and adiponectin were evaluated.MethodsSixteen uncomplicated young T1DM patients (mean age 18 ± 2 years, history of disease 11 ± 5 years, HbA1c 7.7 ± 1.1%) and 26 controls (mean age 19 ± 2 years) were studied. A radiofrequency-based ultrasound system (Esaote MyLab 70) was used to measure carotid IMT and wave speed (WS, index of local stiffness), applanation tonometry (PulsePen) was applied to obtain central pulse pressure (PP) and augmentation index (AIx), and carotid-femoral pulse wave velocity (PWV, Complior) was used as index of aortic stiffness. Peripheral endothelium-dependent vasodilation was determined as reactive hyperemia index (RHI, EndoPAT). Circulating EPCs, glycometabolic profile, AGEs (autofluorescence method), sRAGE and adiponectin were also measured.ResultsAfter adjusting for age, sex and blood pressure, T1DM adolescents had significantly higher carotid IMT (456 ± 7 vs. 395 ± 63 μm, p < 0.005), carotid WS (p < 0.005), PWV (p = 0.01), AIx (p < 0.0001) and central PP (p < 0.01) and lower EPCs (p = 0.02) as compared to controls. RHI was reduced only in diabetic patients with HbA1c ≥7.5% (p < 0.05). In the overall population, EPCs were an independent determinant of carotid IMT (together with adiponectin), while fasting plasma glucose was an independent determinant of carotid WS, AIx and central PP.ConclusionsOur findings suggest that young subjects with relatively long-lasting T1DM have a generalized preclinical involvement of large artery structure and function, as well as a blunted endothelium regenerating capacity. Hyperglycemia and suboptimal chronic glycemic control seem to deteriorate the functional arterial characteristics, such as large arteries stiffness, wave reflection and peripheral endothelium-dependent vasodilation, whereas an impaired endothelium regenerating capacity and adiponectin levels seem to influence arterial structure.

Large Artery Remodeling and Dynamics following Simulated Microgravity by Prolonged Head-Down Tilt Bed Rest in Humans

The effects of simulated microgravity on the static and dynamic properties of large arteries are still mostly unknown. The present study evaluated, using an integrated vascular approach, changes in structure and function of the common carotid and femoral arteries (CCA and CFA) after prolonged head-down tilt bed rest (HDTBR). Ten healthy men were enrolled in a 5-week HDTBR study endorsed by the Italian Space Agency (ASI). Arterial geometry, flow, stiffness, and shear rate were evaluated by ultrasound. Local carotid pulse pressure and wave reflection were studied by applanation tonometry. After five weeks of HDTBR, CFA showed a decrease in lumen diameter without significant changes in wall thickness (IMT), resulting in an inward remodeling. Local carotid pulse pressure decreased and carotid-to-brachial pressure amplification increased. The ratio of systolic-to-diastolic volumetric flow in CFA decreased, whereas in CCA it tended to increase. Indices of arterial stiffness and shear rate did not change during HDTBR, either in CCA or CFA. In summary, prolonged HDTBR has a different impact on CCA and CFA structure and flow, probably depending on the characteristics of the vascular bed perfused.

Body Composition and Common Carotid Artery Remodeling in a Healthy Population

CONTEXT An independent association between obesity and preclinical carotid atherosclerosis has been demonstrated, however, the pathophysiological links were not clearly established. Body composition (BC) influences systemic hemodynamics and may participate in the remodeling of common carotid artery (CCA), independently of risk factors. OBJECTIVE This study evaluated the association between CCA structure and BC in a large population of healthy subjects. DESIGN This was a cross-sectional study. SETTINGS The study was conducted at 19 European centers. SUBJECTS The study included 627 healthy subjects (252 men, age 30-60 yr, body mass index 17-40 kg/m2). MAIN OUTCOME MEASURES CCA luminal diameter and intima-media thickness were measured on digitized ultrasound images. Acoustic properties of CCA wall were evaluated by digital densitometric analysis and described in terms of mean gray level. BC was assessed by electrical bioimpedance. Insulin sensitivity (euglycemic hyperinsulinemic clamp) and plasma adiponectin levels were measured. Associations between CCA structure, age, BC, and metabolic and atherosclerotic risk factors were analyzed by multivariate regression models. RESULTS Independent factors affecting CCA diameter were fat-free mass and waist girth (standardized r = 0.44 and 0.12; P < 0.01 and < 0.0001; R2 = 0.35); independent correlates of intima-media thickness were age, CCA diameter, systolic blood pressure, and low-density lipoprotein-cholesterol (standardized r = 0.39, 0.25, 0.10, and 0.14; P < 0.005-0.0001; R2 = 0.40). The mean gray level of carotid wall was independently associated with age and waist girth (standardized r = 0.23 and 0.12; P < 0.0001 and = 0.001; R2 = 0.30). CONCLUSIONS Findings of this cross-sectional study suggest that BC modulates CCA diameter, and may induce adaptive changes in carotid wall thickness, independently of metabolic and atherosclerotic factors. Central adiposity modifies the acoustic properties of carotid wall.