Difference in carotid artery elasticity in subjects with different brachial artery kinetic of vasodilatation.

Increased carotid stiffness and impaired brachial artery flow-mediated dilatation (FMD) associate with cardiovascular events. We have previously reported three FMD patterns based on the time of maximal dilatation. The aim of the present study was to verify whether different FMD patterns associate with carotid artery stiffness. In all, 133 subjects were enrolled. All participants underwent complete clinical examination, blood sampling and ultrasound study. FMD was used as a measure of endothelial function. Based on the maximal brachial artery FMD, subjects were divided into Early dilators (peak FMD at 50 s), Late dilators (peak FMD over 50 s) and No dilators. Echo-Doppler evaluation of carotid arteries was performed in order to calculate elastic indexes (strain, ß-stiffness index and distensibility). In all, 64 subjects were classified as Early FMD, 36 as Late FMD and 33 as No dilators. Age, gender and cardiovascular risk factors were comparable among three groups. Early FMD had higher values of strain compared with both Late and no Dilators (P<0.001). Furthermore, Early dilators showed a significantly lower stiffness and higher distensibility compared with Late and No dilators. No significant differences between Late FMD and No Dilators were detected. Our results demonstrate that common carotid artery elasticity indexes significantly differ among Early, Late and No dilators. Subjects with delayed or absent brachial artery dilatation have stiffer common carotid arteries compared with subjects with early dilatation. In conclusion, our research suggests that the assessment of the kinetics of FMD in a clinical setting might represent a useful screening tool to improve the cardiovascular risk stratification.

Blood urea impairs brachial artery flow mediated dilation.

AIM: Urea, the main product of protein catabolism, is a biochemical marker of renal function. Though it is known that serum urea impairs vascular health, the relationship between its concentration and vascular reactivity in vivo has not been explored. Our study was undertaken to investigate possible association between serum urea and endothelial function in subjects without chronic kidney disease (CKD). METHODS: Eighty free-living subjects with serum creatinine ≤1 mg/dL and without CKD were enrolled for the present study. Serum analyses and evaluation of endothelial function were performed in all subjects. Endothelial function was measured using the flow-mediated dilation (FMD) technique. Simple and multiple regression analyses were used to test the association between FMD and considered variables. RESULTS: In correlation analyses FMD was found directly associated with HDL cholesterol (r=0.21; P=0.05) and eGFR (r=0.25; P=0.02) and inversely associated with age (r=-0.26; P=0.02), serum urea (r=-0.37; P<0.01), serum creatinine (r=-0.31; P<0.01) and brachial artery baseline diameter (r=-0.41; P<0.01). In multiple regression analysis only baseline artery diameter and serum urea predicted FMD; age, gender and cardiovascular risk factors did not relate with FMD. CONCLUSION: Our study demonstrates the association between serum urea and FMD, suggesting that the accumulation of waste products of protein metabolism may impair vascular health in subjects without CKD.

Time course analysis of brachial artery flow mediated dilatation in subjects with gingival inflammation.

AIM: Several investigations report an inverse association between periodontal disease and endothelial function measured by brachial artery Flow-Mediated-Dilatation (FMD) technique. These studies examined endothelial function by using the traditional approach to FMD calculation, that is from diameters assessed at 60 seconds after deflation. Nevertheless, possible relationship between gingival inflammation and endothelial dysfunction observed over this temporal threshold remains still unexplored. The purpose of our study was to explore the relationship between gingival inflammation and endothelial function, by considering the time course of brachial FMD. METHODS: Forty-six free-living white subjects, participating in a cardiovascular disease prevention campaign, were enrolled. FMD was measured at 60s and at 2 and 3 min after forearm ischemia. Maximal FMD was calculated (Peak FMD), for each patient. Gingival Index (GI) was evaluated as measure of gingival inflammation. RESULTS: In univariate analyses, GI was associated with both FMD at 60 sec (r=-0.30, P=0.038) and Peak FMD (r=-0.41, P=0.004). In multiple regression analyses including GI, age, gender, and known risk factors for atherosclerosis, only GI and age were independently and inversely associated with Peak FMD and FMD at 60 s, but this association was stronger with Peak FMD. Moreover, when we divided subjects on the basis of GI value, patients with GI > 1 presented lower Peak FMD and higher prevalence of absent FMD. CONCLUSION: The present study extends previous observations about the negative effects of periodontal disease on endothelial function, highlighting the importance of the evaluation of time course of vascular reactivity.

Markers of insulin resistance and carotid atherosclerosis. A comparison of the homeostasis model assessment and triglyceride glucose index.

AIMS: The present investigation was designed to test the association between carotid atherosclerosis and two simple markers of insulin resistance, i.e. HOMA-Index and TyG-Index. MATERIALS AND METHODS: The study was performed in two different cohorts. In the first cohort, 330 individuals were enrolled. Blood pressure, lipids, glucose, waist and cigarette smoking were evaluated. HOMA-IR and TyG-Index were calculated as markers of prevalent hepatic and muscular insulin resistance respectively. Carotid atherosclerosis was assessed by Doppler ultrasonography. The association between cardiovascular risk factors, markers of insulin resistance and carotid atherosclerosis was assessed by multiple logistic regression analyses. In the second cohort, limited to the evaluation of TyG-Index, 1432 subjects were studied. RESULTS: In the first cohort, TyG-Index was significantly associated with carotid atherosclerosis in a model including age, sex, diabetes, cigarette smoking and LDL cholesterol, while HOMA-IR was not. When components of metabolic syndrome were added to the model as dichotomous variables (absent/present), TyG-Index retained its predictive power. The same result was obtained when the metabolic syndrome was added to the model (absence/presence). The association between TyG-Index and carotid atherosclerosis was confirmed in the second cohort. CONCLUSIONS: The present findings suggest that TyG-Index is better associated with carotid atherosclerosis than HOMA-IR.

The effect of aging on blood and plasma viscosity. An 11.6 years follow-up study.

OBJECTIVE: Alterations of blood and plasma viscosity can promote atherosclerosis. The relationship between viscosity and aging is still controversial. The present study evaluated the influence of aging on blood and plasma viscosity in a group of subjects followed for 11.6 years. METHODS: Forty-five subjects have been evaluated twice 11.6 years apart for hemorheological parameters and coronary heart disease (CHD) risk factors. Plasma viscosity and blood viscosity have been measured with a cone-plate viscometer. Tk has been calculated as index of red blood cell rigidity. CHD risk factors, i.e. obesity, hypertension, hyperlipidemia and diabetes, have been evaluated by routine methods. RESULTS: Hematocrit and plasma viscosity did not change during the study, whereas blood viscosity (shear rate 225/sec: 4.46 ± 0.49 vs. 4.81 ± 0.54 cP, p < 0.0001; shear rate 45/sec: 6.19 ± 0.67 vs. 6.65 ± 0.79 cP, p < 0.0001) and Tk (0.80 ± 0.05 vs. 0.83 ± 0.06, p < 0.005) significantly increased. The percent variation in blood viscosity was not associated with the percent variation in any of the CHD risk factors. Furthermore, the increase in blood viscosity was similar in males and females and in subjects with CHD risk profile worsening or not. CONCLUSION: The present findings demonstrate that blood viscosity increases with age. This increase seems independent of classical CHD risk factors and is disjoined from haematocrit and plasma viscosity, suggesting a possible direct effect of aging on red blood cells.

Plasma and blood viscosity in metabolic syndrome.

BACKGROUND AND AIM: The relationship between metabolic syndrome (MS) and blood and plasma viscosity has been scarcely investigated. In the present study we have evaluated the difference in blood and plasma viscosity between subjects with and without MS, in order to verify whether viscosity measurement can add more information on the overall cardiovascular risk connected with the presence of the MS. METHODS AND RESULTS: Two hundred and sixty nine women and 520 men have been enrolled. Blood and plasma viscosity have been measured with a cone-plate viscometer equipped with a cp-40 spindle. MS has been defined according to the third report of the National Cholesterol Education Program, Adult Treatment Panel III. Eighty four women and 154 men fulfilled the criteria for MS. Hematocrit adjusted blood viscosity was higher in subjects with MS compared to those without the syndrome, both in males (shear rate 225 s(-1): 4.60+/-0.38 vs. 4.52+/-0.33 cP, p<0.01) and females (4.57+/-0.28 vs. 4.46+/-0.31 P, p<0.01). Blood viscosity was correlated with all components of MS but glucose, and after adjustment for them the difference between subjects with or without MS was completely abolished. Plasma viscosity was significantly higher only in females with MS. CONCLUSIONS: These data demonstrate that blood viscosity is increased in subjects with MS, but the increase seems to depend on the metabolic alterations of the syndrome. The independent contribution of the rise in blood viscosity to the cardiovascular risk connected with the presence of MS seems therefore negligible. The increased plasma viscosity in females with MS needs further clarification.

Association between wall shear stress and flow-mediated vasodilation in healthy men.

Wall shear stress contributes to the endothelial production of vasoactive mediators, like nitric oxide (NO). Brachial artery vasodilation that follows increased blood flow is regulated by NO release. Aim of the present study was to investigate whether resting wall shear stress of the brachial artery is related to flow-mediated vasodilation (FMD) induced by forearm ischemia. Wall shear stress was calculated according to the following formula: Wall shear stress=Blood viscosity x Blood velocity/Internal diameter. FMD was calculated as percentage change of brachial artery diameter following forearm ischemia. Twenty-seven healthy male subjects were investigated. Peak wall shear stress and FMD were 37.3+/-12.8 dynes/cm(2) and 110.7+/-5.6%, respectively (mean+/-S.D.). In simple regression analyses, age was inversely associated with wall shear stress (r=48, P<0.01) and, marginally, with FMD (r=0.33, P=0.08). Wall shear stress and FMD were directly related (r=0.60, P<0.001). In multiple regression analysis, including wall shear stress, age, blood pressure, lipids, glucose and Body Mass Index as independent variables, wall shear stress was the only variable independently associated with FMD (standardized beta coefficient=0.690, P

Genetic variation in human stromelysin gene promoter and common carotid geometry in healthy male subjects.

A common variant in the promoter of the human stromelysin gene, causing reduced enzyme expression, has been associated with the progression of coronary atherosclerosis. On the other hand, increased stromelysin activity may promote plaque rupture. The present study was undertaken to investigate the relationship between the genetic variation in the human stromelysin gene promoter and common carotid geometry. Forty-two healthy male subjects without major coronary heart disease risk factors were investigated. The polymorphism in the stromelysin gene promoter was studied through polymerase chain reaction amplification with the use of mutagenic primers. Age, blood pressure, lipids, glucose, viscosity, and body mass index were similar in homozygotes for the 5A allele (5A/5A), heterozygotes (5A/6A), and homozygotes for the 6A allele (6A/6A). Serum matrix metalloproteinase-3 levels did not differ significantly among genotypes. Common carotid diameters and intima-media thickness, measured by noninvasive ultrasonography, were significantly larger in 6A/6A subjects (for respective 6A/6A, 5A/6A, and 5A/5A subjects, diameter at the R wave was 0.63+/-0.09, 0.55+/-0.06, and 0.53+/-0.04 cm [mean+/-SD], P<0.005 by ANOVA; intima-media thickness was 765+/-116, 670+/-116, and 630+/-92 microm [mean+/-SD], P<0.05 by ANOVA). Wall shear stress, calculated as blood velocityxblood viscosity/internal diameter, was significantly lower in 6A/6A subjects (for respective 6A/6A, 5A/6A, and 5A/5A subjects, mean wall shear stress was 10.4+/-2.9, 13.5+/-3.5, and 12.6+/-1.9 dyne/cm(2) [mean+/-SD], P<0.05 by ANOVA). The results demonstrate that the gene polymorphism in the promoter region of stromelysin is associated with structural and functional characteristics of the common carotid artery in healthy male subjects without major risk factors for atherosclerosis. Individuals with the 6A/6A genotype (associated with lower enzyme activity) show a triad of events, namely, increased wall thickness, enlarged arterial lumen, and local reduction of wall shear stress, which might predispose them to atherosclerotic plaque localization.

Evaluation of common carotid hemodynamic forces. Relations with wall thickening.

The localization of atherosclerotic lesions is influenced by hemodynamic factors, namely, shear stress and tensive forces. The present study investigated the relationships between shear stress and circumferential wall tension and between these hemodynamic factors and the intima-media thickness (IMT) of the common carotid artery in healthy men. Fifty-eight subjects were studied. Shear stress was calculated as blood viscosityxblood velocity/internal diameter. Circumferential wall tension was calculated as blood pressurexinternal radius. Blood velocity, internal diameter, and IMT were measured by high-resolution echo-Doppler. Mean shear stress was 12.6+/-3.3 dynes/cm(2) (mean+/-SD; range, 4.8 to 20.4) and was inversely related with age, blood pressure, and body mass index (BMI). Mean circumferential wall tension was 3.4+/-0.6x10(4) dynes/cm (range 2.4 to 5.6) and was directly associated with age and BMI. IMT was inversely associated with shear stress (r=0.55, P<0. 0001) and directly associated with circumferential wall tension (r=0. 43, P<0.0001). Shear stress and circumferential wall tension were inversely correlated (r=0.66, P<0.0001). In multiple regression analysis, shear stress and (marginally) cholesterol were independently associated with IMT, whereas circumferential wall tension, age, and BMI were not. These findings confirm that common carotid shear stress varies among healthy individuals and decreases as age, blood pressure, and BMI increase. Our findings also demonstrate that circumferential wall tension is directly associated with wall thickness, age, and BMI and that shear stress is associated with common carotid IMT independent of other hemodynamic, clinical, or biochemical factors.

NIDDM is associated with lower wall shear stress of the common carotid artery.

The mechanisms underlying macrovascular complications in NIDDM are partially understood. In addition to increased prevalence and severity of systemic cardiovascular risk factors, local alterations of arterial wall and hemodynamics may play a role. Atherosclerotic lesions usually lie in regions of low wall shear stress. We therefore investigated the wall shear stress--that is, the frictional force acting tangentially to the endothelial surface--in the common carotid artery of diabetic and control subjects. Enrolled were 18 male NIDDM subjects and 18 age-matched control subjects. None of the participants were hypertensive, hyperlipidemic, or a cigarette smoker. Common carotid wall shear stress was calculated according to the following equation: blood viscosity x blood velocity/internal diameter. Blood viscosity was measured by use of a cone/plate viscometer. Blood velocity and internal diameter were measured by high-resolution echo-Doppler. Wall shear stress was significantly lower in NIDDM subjects than in control subjects (mean wall shear stress: 9.7 +/- 2.4 vs. 11.7 +/- 2.6 dynes/cm2, P < or = 0.005). Six diabetic participants had a plaque in one carotid tree and no lesions in the contralateral carotid. Among these subjects, mean wall shear stress was significantly lower in the side with lesion (8.1 +/- 1.6 vs. 10.5 +/- 2.4 dynes/cm2, P < or = 0.02). These findings suggest that diabetes is associated with a more atherosclerosis-prone carotid hemodynamic profile, which might represent an additional factor contributing to the increased prevalence and severity of carotid atherosclerosis in diabetic patients compared with general population.

Whole blood viscosity and haematocrit are associated with internal carotid atherosclerosis in men.

BACKGROUND: Alterations in blood viscosity and haematocrit have been described in patients with coronary and cerebrovascular diseases. The results have not been conclusive, as modifications of these parameters are often associated with the presence of coronary heart disease (CHD) risk factors. The aim of this study was to verify whether blood viscosity and haematocrit are increased in patients with carotid atherosclerosis, independently of the presence of CHD risk factors. METHODS: Male patients with internal carotid atherosclerosis (ICA+, n = 28) were selected from participants in a cardiovascular disease prevention campaign. Controls (ICA-, n = 28), also participating in the prevention campaign, were matched for age and all the classical CHD risk factors. Plasma lipids, glucose and fibrinogen were determined by routine methods. Cigarette smoking and current drug therapy was established by questionnaire. Whole blood viscosity was measured at shear rates of 450 and 225/s, using a cone-plate viscometer. Echo-Doppler of carotid arteries was performed with an ATL Ultramark 9 HDI using a 5-10 MHz multifrequency probe. RESULTS: Blood pressure, plasma lipids, glucose, body mass index, fibrinogen and plasma viscosity were similar in the two groups. ICA+ patients, compared with the ICA- group, had significantly greater values of blood viscosity (4.52 +/- 0.37 cP compared with 4.18 +/- 0.45 cP, P < 0.005 respectively; shear rate 450/s) and haematocrit (48.57 +/- 3.19% compared with 45.57 +/- 4.81%, P < 0.008 respectively). CONCLUSIONS: Our findings demonstrate that blood viscosity and haematocrit are increased in men with internal carotid atherosclerosis, independently of the presence of risk factors for atherosclerosis.

Awareness, treatment and control of hyperlipidaemia, hypertension and diabetes mellitus in a selected population of southern Italy.

The purpose of the present study was to assess the degree of awareness, treatment and control of hyperlipidaemia compared with hypertension and diabetes mellitus in a selected population of southern Italy. All participants to a cardiovascular disease prevention campaign examined between April 1994 and July 1995 were screened for hyperlipidaemia, hypertension and diabetes mellitus. Subjects received also ECG, echo-Doppler of carotid arteries and filled in a questionnaire concerning personal and familial cardiovascular diseases, smoking habit and drug consumption. Of the 742 participants, 327 were found to have hypertension, 73 to have diabetes mellitus, 287 to have mild hyperlipidaemia and 322 to have moderate-severe hyperlipidaemia. Among hypertensive subjects, 60.2% were aware of their condition, 53.5% were treated and 15.6% had their blood pressure controlled at the recommended level (< 140/90 mmHg). Among diabetic subjects, 76.7% were aware, 64.4% treated and 19.2% reached fasting blood glucose level of less than 7.77 mmol/l (140 mg/dl). Only 24.0% of subjects with mild hyperlipidaemia were aware of their condition. Of the subjects found to have moderate-severe hyperlipidaemia, 64.9% were aware, 32.3% were treated and 9.0% had plasma cholesterol and triglycerides concentration of less than 6.45 and 5.65 mmol/l (250 and 500 mg/dl), respectively (cutoffs chosen to separate mild from moderate-severe hyperlipidaemia). These results show that mild hyperlipidaemia is almost neglected whereas awareness of moderave-severe hyperlipidaemia is quite widespread and comparable to that of hypertension and diabetes mellitus. Prevalence of treatment and control of moderate-severe hyperlipidaemia is, however, much lower than that of hypertension and diabetes.

In vivo association between low wall shear stress and plaque in subjects with asymmetrical carotid atherosclerosis.

BACKGROUND AND PURPOSE: It is known that atherosclerosis does not involve both carotid arteries to the same extent. Pathological investigations have demonstrated that lesions develop in regions of low wall shear stress. The aims of the present study were to verify the degree of carotid atherosclerosis asymmetry in a population-based study and to evaluate whether wall shear stress is lower in carotids with atherosclerotic lesions than in carotids without lesions. METHODS: Participants in a cardiovascular disease prevention campaign (n = 1166) were screened for carotid atherosclerosis by echo-Doppler examination. Of these, 23 subjects who presented plaque in the common carotid or bulb of one side and no plaque in the contralateral carotid tree were enrolled for common carotid wall shear stress measurement. Shear stress was calculated according to the following formula: Shear Stress = Blood Viscosity x Blood Velocity/Internal Diameter. RESULTS: Of the 1166 subjects screened, 400 (34%) had plaque and/or stenosis in the carotids. Ninety subjects had lesions exclusively in the right carotid, 111 had lesions exclusively in the left, 70 had lesions in both carotids but with different degrees of severity, and only 129 had similar lesions in both carotids. In the 23 subjects in whom wall shear stress was measured, peak shear stress was 18.7 +/- 4.1 and 15.3 +/- 4.0 dynes.cm-2 (mean +/- SD) (P < .0001) in the side without and the side with plaque, respectively. Mean shear stress yielded similar results. CONCLUSIONS: The present results demonstrate that the atherosclerotic involvement of carotid arteries is usually asymmetrical and that wall shear stress is lower in the carotid arteries where plaques are present than in plaque-free arteries. These findings provide in vivo evidence for a strong association between shear stress and atherosclerotic lesions.

Association between intima-media thickness and wall shear stress in common carotid arteries in healthy male subjects.

BACKGROUND: Atherosclerotic lesions lie in regions of low wall shear stress. No relationship between wall shear stress and intima-media thickness in vivo has been reported. Aims of the present study were to verify the reproducibility of wall shear stress measurement in vivo and to evaluate its association with intima-media thickness in the common carotid artery in healthy subjects. METHODS AND RESULTS: Wall shear stress was calculated according to the following formula: Shear Stress = Blood Viscosity x Blood Velocity/Internal Diameter. Blood viscosity was measured by use of a cone/plate viscometer. Blood velocity, internal diameter, and intima-media thickness were measured by high-resolution echo Doppler. Twenty-one healthy male subjects were investigated. Peak and mean shear stress values were 29.5 +/- 8.2 and 12.1 +/- 3.1 dynes/cm-2 (mean +/- SD), respectively. Peak shear stress was inversely related to intima-media thickness (r = .62), age (r = .77), systolic blood pressure (r = .61), and body mass index (r = .59) (P < .001 for all coefficients). Mean shear stress yielded similar results. The relationship between shear stress and intima-media thickness was independent of age, blood pressure, and body mass index. The reproducibility, calculated by Kendall's W test, was statistically significant. CONCLUSIONS: Our results demonstrate that common carotid artery wall shear stress measurement in vivo is reproducible. It inversely relates to intima-media thickness, age, systolic blood pressure, and body mass index. These findings confirm in vivo the role of shear stress in intima-media thickening.

[Relationship between lipid profile and blood viscosity in a sample of Calabrian population]. / Rapporto tra profilo lipidico e viscositá ematica in un campione della popolazione calabrese.

Plasma viscosity is increased in subjects with risk factors for ischemic heart disease whereas the role of blood viscosity is controversial. Aim of the present study is to evaluate the relationship between blood lipids and blood viscosity. One hundred seventy eight male subjects have been enrolled, aged 35-70 years, participating in an atherosclerosis prevention campaign held in Catanzaro between September 1994 and April 1995. Subjects with previous myocardial infarction and/or plasma triglycerides > 400 mg/dl have been excluded. Blood pressure and body mass index (BMI) have been measured and blood has been withdrawn for determination of total cholesterol (T-CHOL), triglycerides, HDL-cholesterol (HDL-C), glucose and blood viscosity. Blood viscosity resulted significantly directly correlated to non HDL-C and inversely to HDL-C. The population has been divided in two groups according to T-CHOL/HDL-C ratio value. Subjects with T-CHOL/HDL-C > 5 showed increased values of blood viscosity, after adjustment for haematocrit, BMI and glucose. These results demonstrate that blood viscosity is strongly influenced by lipid profile. This might contribute to better understand the deleterious effects that elevated concentrations of blood lipids exert on arterial wall.

Intimal plus media thickness of common carotid arterial wall in subjects with hypertension.

Intimal plus media thickening has been described to be associated with several cardiovascular risk factors. Aim of the present study was to evaluate the intimal plus media thickness in male subjects with hypertension compared to age matched males normotensive controls. Twenty subjects with hypertension, defined as systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 95 mmHg and/or use of antihypertensive drugs, and forty age matched controls have been enrolled. Intimal plus media thickness has been measured from B-mode echography images by a computer. Plasma lipids have been measured by routine methods. A zero random sphygmomanometer has been used to detect blood pressure. Intima plus media thickness resulted enlarged in subjects with hypertension compared to normotensive controls. The thickening of intima-media complex seems related to atherosclerotic lesions, therefore its early detection by noninvasive techniques might improve the identification and the monitoring of high risk hypertensive subjects.