Aortic stiffness, flow-mediated dilatation and carotid intima-media thickness in obstructive sleep apnea: non-invasive indicators of atherosclerosis

BACKGROUND AND OBJECTIVE: Obstructive sleep apnea (OSA) has a critical association with cardiovascular mortality and morbidity. Carotid intima-media thickness (IMT), flow-mediated dilatation (FMD) and aortic stiffness are early signs of atherosclerosis. The presence of subclinical atherosclerosis was assessed in OSA patients using these parameters. METHODS: 40 patients with OSA showing an apnea-hypopnea index (AHI) > or =5 (mean age 51.3 +/- 9 years, 32 males) and 24 controls (AHI < 5, mean age 51.9 +/- 5.2 years, 19 males) were enrolled in the study. In all subjects, polysomnographic examination and recordings were performed during sleep. IMT of the carotid artery, endothelium-dependent/-independent vasodilation of the brachial artery and aortic elastic parameters were investigated using high-resolution Doppler echocardiography. RESULTS: The demographic data of the patients with OSA and controls were not significantly different. Subjects with OSA demonstrated higher values of aortic stiffness (7.1 +/- 1.88 vs. 6.42 +/- 1.56, respectively) and IMT (0.85 +/- 0.13 vs. 0.63 +/- 0.11 mm, p = 0.0001, respectively) but lower distensibility (9.47 +/- 1.33 vs. 11.8 +/- 3.36 cm(2)/dyn/10(6)) and FMD (4.57 +/- 1.3 vs. 6.34 +/- 0.83%, p = 0.0001, respectively) than the controls. The respiratory disturbance index correlated positively with aortic stiffness and IMT and negatively with distensibility and FMD. CONCLUSION: We observed blunted endothelium-dependent dilatation, increased carotid IMT and aortic stiffness in patients with OSA compared with matched control subjects. This is evident in the absence of other diseases, suggesting that OSA is an independent cause of atherosclerosis. These simple and non-invasive methods help to detect subclinical atherosclerosis in OSA.     

Late systemic hypertension and aortic arch geometry after successful repair of coarctation of the aorta.

AIMS: To investigate the role of the geometry of the aortic arch in resting hypertension after successful repair of coarctation (CoA). METHODS AND RESULTS: 105 patients (15.3+/-6 years) with successful repair of aortic CoA underwent blood pressure (BP) measurements at rest and magnetic resonance imaging (MRI) of the aortic arch and left ventricle. Three categories of aortic arch shape were defined based on the global geometry of the aortic arch: gothic, crenel and normal. The ratio of the maximum height/transverse diameter of the aortic arch (A/T), the percentage of residual stenosis (RS), the growth index of the aortic arch segments (GIA), and the left ventricular mass index (LVMI) were calculated. Twenty-seven (25.7%) patients had hypertension (HT). HT was more frequent in patients with gothic arch geometry (20/44, 45.5%) than in crenel geometry (5/18, 27.8%) and in normal geometry (2/43, 4.6%) (P<0.001). Resting systolic BP and LVMI were significantly higher with gothic arch geometry. In multivariate analysis, the only correlates to HT, to level of systolic BP or to LVMI were A/T and gothic arch geometry. CONCLUSION: Gothic geometry of the aortic arch is associated with resting hypertension in patients having undergone successful repair of CoA. This raises concern about methods to harmoniously repair CoA in order to prevent or delay rest hypertension in adulthood.     

Interrelationship between noninvasive predictors of atherosclerosis: transthoracic coronary flow reserve, flow-mediated dilation, carotid intima-media thickness, aortic stiffness, aortic distensibility, elastic modulus, and brachial artery diameter

BACKGROUND: In this study, we searched for a correlation between transthoracic coronary flow reserve (CFR) and well-established surrogates of coronary atherosclerosis. METHODS: The study was conducted on 136 healthy subjects (mean age: 39.9 +/- 7.3 years) who were free of coronary risk factors. Transthoracic echocardiography was used to measure the aortic stiffness index (AoSI), aortic distensibility (AoD), and aortic elastic modulus (AoEM). High-resolution ultrasound was used to measure brachial artery endothelium-dependent and independent vasomotion and carotid intima-media thickness (IMT). In addition, transthoracic second harmonic Doppler echocardiography was used to measure CFR. RESULTS: All of the parameters significantly correlated with each other except brachial endothelium-independent dilation. CFR correlated significantly with brachial endothelium-dependent dilation (EDD) (r = 0.302, P < 0.01), carotid IMT (r =-0.388, P < 0.01), brachial artery diameter (r = 0.340, P < 0.01), AoD (r = 0.275, P < 0.01), AoS (r =-0.299, P < 0.01), and AoEM (r =-0.30,7 P < 0.01). Carotid IMT correlated significantly with brachial EDD and modestly with brachial artery diameter, AoD, AoS, and AoEM.In multivariate analysis, carotid IMT (beta=-0.323, P < 0.0001) and brachial artery diameter (beta = -0.259, P = 0.001) were significant independent predictors of CFR. The left ventricular mass index (beta= 0.371, P < 0.0001), brachial EDD (beta = -0.232, P = 0.002), and CFR (beta = -0.228, P = 0.003) were significant predictors for IMT. CONCLUSION: Transthoracic CFR correlated significantly with well-established noninvasive predictors of atherosclerosis, and we suggest that it can be used as a surrogate for coronary atherosclerosis.     

Close association of endothelial dysfunction with insulin resistance and carotid wall thickening in hypertension

BACKGROUND: Endothelial dysfunction has been regarded as an early stage in the atherosclerotic process. Endothelial dysfunction and insulin resistance were observed in hypertensive subjects and were associated with carotid wall thickening. METHODS: We examined the determinants of endothelial dysfunction including insulin sensitivity and carotid wall thickening. A total of 41 subjects with nondiabetic essential hypertension were studied. Endothelial function of brachial artery and carotid wall thickening were assessed noninvasively using ultrasound technique. In brachial artery, we measured flow-mediated endothelium-dependent vasodilation (FMD) and glyceryl trinitrate-induced endothelium-independent vasodilation (GTN). We estimated intima-media thickness of the common carotid artery (IMT). Insulin sensitivity was measured according to the steady-state plasma glucose (SSPG) method. High SSPG levels indicated insulin resistance. RESULTS: On univariate analysis, there were significant negative correlations between FMD and SSPG (r = -0.695, P <.0001) or IMT (r = -0.449, P <.004). The FMD was negatively correlated significantly with age and with systolic and diastolic blood pressures (BP). A significant negative correlation was observed between GTN and SSPG. There was a significant positive relation between SSPG and IMT. On multiple regression analysis including systolic BP, SSPG, and age as independent variables and FMD as a dependent variable, FMD was independently related to SSPG (P <.03) and systolic BP (P <.02). If the presence of SSPG, diastolic BP, and age were entered as independent variables against FMD, FMD was independently related to SSPG (P <.002). CONCLUSIONS: One of the major determinants of endothelial function was insulin resistance. Our findings suggest that endothelial dysfunction and early structural vascular changes were related to insulin resistance.     

Measurement of flow-mediated dilatation of the brachial artery is affected by local elastic vessel wall properties in high-risk patients

OBJECTIVES: To assess whether the validity of endothelial function measurement by flow-mediated dilatation (FMD) is affected by local brachial artery stiffness (distensibility coefficient; DC) and arterial wall thickness (intima-media thickness, IMT). BACKGROUND: FMD measurement relies on assessment of arterial diameter change. Increased IMT and decreased DC might physically limit dilatation of the brachial artery in spite of healthy endothelium. METHODS: DC, IMT and FMD of the brachial artery were simultaneously measured in 349 patients with advanced atherosclerosis or cardiovascular risk factors. The relations between FMD and age, and FMD and current smoking were regarded as a proxy for the relation between FMD and true endothelial function. RESULTS: The relations between FMD and age, and FMD and smoking, were significantly modified by brachial artery DC. No modification was found for IMT. The interaction terms were statistically significant (p=0.03 and 0.04, respectively). The relation between FMD and age, and FMD and smoking was progressively more pronounced in patients with more elastic arteries. CONCLUSION: The results of our study indicate that increased arterial stiffness may interfere with valid measurement of FMD and that patients with stiff arteries may be considered for exclusion from analyses involving FMD to ensure its validity.     

Relationship between carotid artery intima-media thickness and brachial artery flow-mediated dilation in middle-aged healthy men

OBJECTIVES: We aimed to determine the relationship between carotid intima-media thickness (IMT) and brachial artery flow-mediated dilation (FMD) in healthy middle-age men. BACKGROUND: Carotid IMT and brachial artery FMD are frequently used as surrogate measures of subclinical atherosclerosis. Whereas carotid IMT identifies early structural abnormalities, brachial artery FMD, considered a bioassay of endothelial function, measures functional vascular integrity. The relationship between carotid IMT and brachial artery FMD has not been well studied. METHODS: We measured traditional risk factors, carotid IMT, and brachial artery FMD in 1,578 middle-aged men without known cardiovascular disease and analyzed the relationship between carotid IMT and brachial FMD. RESULTS: Carotid IMT correlated with age, systolic blood pressure, body mass index, fasting glucose, total and low-density lipoprotein (LDL) cholesterol, and with the overall Framingham risk score (p < 0.001 for all), whereas impaired brachial artery FMD correlated with systolic and diastolic blood pressure (p < 0.01). No relationship was observed between carotid IMT and brachial artery FMD for the entire cohort (r = -0.006, p = 0.82) and in subgroups defined by traditional risk factors or by quintiles of carotid IMT and brachial FMD. CONCLUSIONS: In middle-aged healthy men, there is no significant correlation between carotid IMT and brachial artery FMD. This finding suggests that these are unique, independent surrogates that measure different aspects and stages of early atherosclerosis. Further studies are needed to define their role in clinical research and in cardiovascular risk assessment.     

Apolipoprotein A-I/C-III/A-IV SstI and apolipoprotein B XbaI polymorphisms do not affect early functional and structural changes in atherosclerosis: the Cardiovascular Risk in Young Finns study.

BACKGROUND: The present study was designed to investigate the effects of apoB XbaI and apoA-I/C-III/A-IV SstI polymorphisms to carotid artery intima-media thickness (IMT), carotid artery compliance (CAC) and brachial artery flow-mediated vasodilatation (FMD). METHODS AND RESULTS: As part of the Cardiovascular Risk in Young Finns Study, the carotid IMT, CAC and brachial FMD of 2,265 subjects (mean age +/- SD 32 +/-5 years) were measured with ultrasonography, and genotyping of the apolipoprotein polymorphisms was performed. The frequencies of the genotypes did not differ between the groups with high (above median 0.57 mm) and low (below median) IMT, CAC or FMD. The average carotid IMT differed between the 3 apoB XbaI genotypes (ANOVA, p=0.04), but not between the apoA-I/C-III/A-IV SstI genotypes (ANOVA, p=0.53). The relationship between the polymorphisms and carotid IMT was not significant in any of the covariate-adjusted logistic and linear regression analyses. CAC and FMD were not influenced by either of the polymorphisms in ANOVA and regression analyses. CONCLUSIONS: The polymorphisms apoA-I/C-III/A-IV SstI and apoB XbaI do not seem to affect carotid artery characteristics or brachial artery FMD in young adulthood.     

Flow-mediated vasodilatation of the brachial artery and intima-media thickness of carotid artery in never-treated subjects.

AIM: Data on the association between brachial artery flow-mediated dilatation (FMD) and common carotid intima-media thickness (IMT) are contrasting. The present study investigated the relationship between FMD and IMT and carotid atherosclerosis in never treated subjects. METHODS: Seventy-seven subjects were investigated: 46 had no coronary heart disease (CHD) risk factors, 21 had only one, and 10 had more than one risk factor. IMT of the common carotid was measured by ultrasonography and FMD was evaluated according to standardized methods. RESULTS: IMT increased with increasing number of risk factors (0.66+/-0.12, 0.69+/-0.12 and 0.8+/-0.17 mm, respectively, ANOVA P<0.05). FMD decreased with increasing number of risk factors (10.44+/-5.2, 6.52+/-7.11 and 7.35+/-4.42%, respectively, P<0.05). Endothelium-independent vasodilatation was similar in the 3 groups. IMT and FMD did not correlate neither in subjects without risk factors (r=-0.151, P=0.3), nor in those with 1 (r=-0.196, P=0.4) or with 2 or more risk factors (r=-0.387, P=0.2), while in the group as a whole the correlation was borderline significant (r=-0.217, P=0.058). Eleven subjects had carotid atherosclerosis and higher values of IMT, but not reduced FMD. In multiple regression analysis, diabetes and IMT, but not FMD, were associated with carotid atherosclerosis. CONCLUSIONS: The present findings indicate that, in never treated subjects, FMD is not strictly associated with IMT or atherosclerosis of the carotid arteries.     

Ambulatory blood pressure,left ventricular mass,and conduit artery function late after successful repair of coarctation of the aorta

OBJECTIVES: We sought to evaluate the determinants of hypertension during daily life and left ventricular (LV) hypertrophy in patients with successfully repaired coarctation of the aorta (CoA), as well as their relationship to abnormalities of arterial function. BACKGROUND: Arterial hypertension may recur late after repair of CoA, which is related to a more adverse outcome. Furthermore, patients with normal resting blood pressure (BP) may have hypertension during daily life and LV hypertrophy. The determinants of these two adverse prognostic factors have not been investigated. METHODS: We studied 72 patients (9 to 58 years of age) who underwent coarctation repair at age 0.1 to 480 months (42 [60%] at <1 year) and had been followed up for 155 +/- 76 months. They underwent ambulatory BP monitoring, echocardiography for LV mass, studies of brachial artery responses to flow (i.e., flow-mediated dilation [FMD]) and glyceryl trinitrate (GTN), and determination of pulse wave velocity (PWV) and measures of arterial reactivity and stiffness. Findings were compared with those of 53 healthy volunteers. RESULTS: Patients had higher 24-h systolic BP and LV mass than controls. Both endothelium-dependent FMD and the response to the smooth muscle dilator GTN were reduced, and PWV was increased. There was a negative independent correlation between GTN response and 24-h systolic BP in both patients and control subjects. Systolic BP at 24 h was an independent predictor of LV mass, having an accentuated impact in coarctation subjects as compared with controls. CONCLUSIONS: In patients with repaired coarctation, reduced vascular reactivity is associated with hypertension during daily life and with increased LV mass, both of which are important predictors for late morbidity and mortality.     

Predicting the risk of early atherosclerotic disease development in children after repair of aortic coarctation.

AIMS: Increased cardiovascular morbidity is manifested a long time after the repair of aortic coarctation (CoA). By way of impaired flow-mediated vasodilation (FMD) and increased intima media thickness (IMT), surrogate parameters of atherosclerosis, cardiovascular risk factors (RFs) can be correlated with early vascular wall changes in children. This study investigated whether changes in arterial wall function and morphology are detectable in children after coarctation repair. METHODS AND RESULTS: We examined 28 children after successful repair of CoA vs. 30 control subjects. All children underwent identical screening, with a broad RF profile and FMD/IMT measurements. CoA-children presented significantly (P < 0.001) impaired FMD (4.87 +/- 2.6 vs. 10.2 +/- 3.1%) and higher IMT values (P < 0.001) than the controls (0.48 +/- 0.08 vs. 0.38 +/- 0.05 mm). The blood pressure during rest and exercise and the left ventricular mass were significantly elevated, but no additional RF could be identified in CoA-children. Only a remaining pressure gradient related significantly to FMD. CONCLUSION: This study documents early vascular wall changes in children after successful coarctation repair. Arterial hypertension and a resting pressure gradient are the major contributing factors to early atherosclerotic development and should be primary targets for therapy. Vascular status should be monitored regularly by FMD and IMT.     

Comparison of carotid intima-media thickness,arterial stiffness,and brachial artery flow mediated dilatation in diabetic and nondiabetic subjects (The Chennai Urban Population Study [CUPS-9])

This study compares flow-mediated dilation (FMD) and the augmentation index (AI) in diabetic and nondiabetic subjects and correlates these measurements with carotid intima-media thickness (IMT). Fifty diabetic subjects and 50 age- and sex-matched nondiabetic control subjects were recruited from the Chennai Urban Population Study. IMT of the common carotid artery and FMD of the brachial artery were determined using high-resolution B-mode ultrasonography. AI was measured using the Sphygmocor apparatus. The mean AI of diabetic subjects was significantly higher than the nondiabetic subjects (27.48 +/- 7.41% vs 19.10 +/- 8.19%, p <0.0001). The FMD values were significantly lower among diabetic subjects compared with the nondiabetic subjects (2.1 +/- 2.95% vs 6.64 +/- 4.38%, p <0.0001). At any given age point, diabetic subjects had significantly higher AI and lower FMD values compared with nondiabetic subjects (p <0.05). In the total population, AI and FMD showed a correlation with age (p <0.001), fasting plasma glucose (p <0.01), glycosylated hemoglobin (p = 0.001), and IMT (p = 0.001). Among the nondiabetic subjects, FMD and AI showed a strong correlation with IMT. FMD also showed a strong correlation with age and systolic blood pressure, whereas AI showed a correlation with fasting plasma glucose in diabetic subjects. AI and FMD values showed a strong correlation with age. AI values increased and FMD values decreased with an increase in quartiles of IMT both in diabetic and nondiabetic subjects. Multivariate linear regression analyses in the total study population showed that age and glycosylated hemoglobin were the risk factors associated with AI and FMD, in addition to diastolic blood pressure with AI. Diabetic patients have decreased FMD and increased arterial stiffness compared with age- and sex-matched nondiabetic subjects. These functional changes correlate well with the structural changes of the arteries measured by IMT.     

Reduced vascular compliance is associated with impaired endothelium-dependent dilatation in the brachial artery of patients with congestive heart failure

BACKGROUND: Alterations in elastic properties and vascular structure of conduit vessels are important detrimental factors contributing to increased cardiac load and reduced tissue perfusion in patients with congestive heart failure (CHF). It has been demonstrated that endothelial function in the peripheral vasculature is impaired in this disorder, which may induce abnormal vascular elastic properties and remodeling. However, it remains unknown whether changes in vascular structure or mechanical properties are related to endothelial dysfunction in conduit arteries of patients with CHF. METHODS AND RESULTS: Twenty-five CHF patients with nonischemic heart disease and 20 sex/age-matched controls were enrolled. Brachial artery diameter, intima-media thickness (IMT), and vascular stiffness as represented by distensibility and compliance were determined using a high-frequency linear transducer attached to a high-quality ultrasound system. In addition, flow-mediated dilatation (FMD) after 5-minute forearm occlusion and sublingual nitroglycerin-induced dilatation (NTG) were measured in the brachial artery. Brachial arterial diameter was similar between CHF and controls; however, IMT and wall/lumen ratio were significantly greater in CHF patients than in controls (IMT, 0.37+/-0.01 versus 0.31+/-0.01 mm; wall/lumen, 18.7+/-0.8 versus 15.1+/-0.8%: both P<.01). In addition, vascular stiffness parameters were lower in CHF than in controls (distensibility; 1.09+/-0.14 versus 1.60+/-0.15%/kPa, P<.01: compliance; 0.17+/-0.02 versus 0.26+/-0.02 mm(2) kPa, P<.05). FMD and TNG were significantly reduced in CHF (both P<.001). Although stiffness parameters in CHF were not significantly correlated with vascular structure (ie, IMT, wall/lumen) or clinical parameters (ie, age, lipids, glucose, blood pressure), elastic parameters were significantly correlated with FMD (distensibility; r=0.579, P<.005: compliance; r=0.433, P<.05), but not with NTG. CONCLUSION: The present study found that, in limb muscle conduit artery in patients with CHF, there are hypertrophic remodeling and endothelial dysfunction-associated alterations in vascular wall elastic properties.     

Relation of apolipoprotein E polymorphism to markers of early atherosclerotic changes in young adults--the Cardiovascular Risk in Young Finns Study.

BACKGROUND: Carotid artery intima-media thickness (IMT), which is measured by ultrasound, is used in the assessment of early atherosclerotic changes, and has been associated with apolipoprotein E (APOE) polymorphism in many studies comprising elderly subjects. However, results are still inconclusive and data relating to young adults are missing. Whether common APOE polymorphism is related to carotid IMT was studied in a population of young adults. Also brachial flow-mediated dilatation (FMD) and carotid artery compliance (CAC) were determined to clarify their relation to this genetic factor. METHODS AND RESULTS: A total of 1,188 young adults (aged 24-39 years) participating in the Cardiovascular Risk in Young Finns Study with complete data of common APOE polymorphism underwent a carotid and brachial ultrasound. Patients' lipid levels and blood pressure were also examined. There was no significant association between the APOE phenotypes and carotid IMT, brachial FMD or CAC either in young men or in young women. The results were similar for systolic and diastolic blood pressure. In the same population, the well-known association between APOE phenotypes and lipids was seen. CONCLUSIONS: Common APOE polymorphism does not seem to be an independent genetic determinant of carotid IMT, brachial FMD or CAC.     

Arterial dysfunction after treatment of coarctation of the aorta

The long term follow-up after successful coarctation repair has a late cardiovascular morbidity, includes systemic hypertension at rest or/and after exercise. The pathophysiology mechanisms responsible have not been well determined. We studied 70 normotensive subjects at rest (age, 14 +/- 5 y; pressure, 116 +/- 13/56 +/- 9 mmHg), who had an isolated coarctation with a good repair defined by the absence of gradient between upper and lower right limb (0.-26 mmHg). After exercise testing we defined two groups: Coa HT: Hypertension at exercise equal or over 200 mmHg, n = 20 (228 +/- 23 mmHg) and Coa HT: Normotensive at exercise = 10 (163 +/- 24 mmHg). These subjects were mached sex-age and blood pressure to 70 controls (age, 13 +/- 3 y; pressure, 115 +/- 10/56 +/- 6 mmHg). Using a high-resolution echographic technique, we assessed the systolic, diastolic diameter and the intima media thickness (IMT) of the common carotid artery (CCA) to define mechanical indexes: Cross sectional compliance (CSC), distensibility (CSD) and incremental elastic modulus (Einc) in each group. CCA pressure waveform and the local pulse pressure were determined in 32 subjects to define augmentation index (AI). The changes of the brachial artery diameter in response to reactive hyperaemia (flow mediated dilation: FDM) and to glyceryltrinitrate (GTNMD) were measured. The IMT was significantly increased in the Coa group (by 8%, p < 0.001) and higher in the Coa HT group compared with the Coa NT group (0.57 +/- 0.04 mm vs 0.54 +/- 0.05 mm, p < 0.05). The CSD was lower and the Einc was higher in both groups. The carotid pulse pressure amplitude was significantly higher in the Coa HT Group (41 +/- 14 vs 33 +/- 7 mmHg; p < 0.05). The AI was higher in both Coa repair groups. Both flow-mediated dilation (FMD) and GTN-mediated dilation (GTNMD) of the brachial artery were lower in the Coa group (respectively 5 +/- 3 vs 7 +/- 3%; p < 0.01; 16 +/- 8 vs 23 +/- 9%; p < 0.01). GTNMD was inversely correlated with maximum systolic blood pressure on exercise (r = 0.31, p = 0.03). The IMT of the CCA was related to the local pulse pressure in both groups of coarctation repair. The combination of distensibility decrease in the proximal arterial bed with an impairment of distal artery reactivity would account for the elevation of exercise blood pressure in subjects who had coarctation repair. The increase of local pulse pressure influences the carotid wall hypertrophy.     

Interrelationship between non-invasive measurements of atherosclerosis: flow-mediated dilation of brachial artery, carotid intima-media thickness and pulse wave velocity

Flow-mediated dilation (FMD) of the brachial artery, carotid intima-media thickness (IMT) and pulse wave velocity (PWV) have been shown to be good surrogate markers of clinical atherosclerosis. We determined the interrelation between these measurements, and examined whether their combination would be of clinical significance. One hundred and thirty-five consecutive subjects (79 women/56 men) were enrolled, including 110 patients with risk factors for atherosclerosis, and 33 patients with atherosclerotic disease such as coronary heart disease, stroke or arteriosclerosis obliterans. IMT and plaque formation of the carotid artery and FMD of the brachial artery were assessed using ultrasonography. Brachial-ankle PWV (baPWV) was measured using an automated device (form ABI/PWV, Colin). Age, FMD, IMT and PWV were significantly correlated with each other. Multivariate analysis revealed an independent correlation between the parameters except for FMD, and all four parameters were independently correlated with each other in subjects <70 years. Next, we classified the subjects by tertile according to the values of FMD, IMT and PWV. Each of the worst tertiles was associated with a higher prevalence of atherosclerotic disease and carotid plaques compared to the other tertiles. Moreover, subjects with the worst tertiles of all three measurements had a markedly higher prevalence of atherosclerotic disease and carotid plaques. These results suggest that FMD, IMT and PWV are related to each other, but the combination of these measurements will be of stronger clinical relevance.     

Endothelial dysfunction predictor of structural changes of arterial wall in type I diabetes.

AIM: We examined whether alteration in vascular endothelial function exists in non-insulin dependent diabetes mellitus (NIDDM) and whether impaired endothelium-dependent responses in those patients are associated with increased intima-media thickness (IMT), the time sequence of their appearance and the role of individual risk factors in development of structural deterioration of arterial wall. METHODS: Ultrasound technique was used to measure brachial artery flow mediated dilation (FMD) response and carotid IMT in 38 young adults with type I diabetes aged 22-34 years and 35 healthy controls aged 22-36 years. RESULTS: Patients had significantly lower FMD than controls (4.15/2.8/ vs 11.3/3.6/, P<0.0001) and was in all diabetic patients below the mean value of controls. Further, carotid intima-media was in insulin dependent diabetes mellitus (IDDM) patients significantly thicker than in healthy subjects (0.65/0.04 vs 0.56/0.04, P=0.0001) and was related to body mass and body mass index, to the age of patients, the duration of diabetes and several risk variables. In a multivariate model FMD was most significantly and independently associated to IMT. However, significant thickening of intima-media was observed only in patients with progressed deterioration of FMD and it appeared in those subjects with long-lasting disease. IMT was also influenced by urinary albumin excretion and low-density lipoprotein (LDL) cholesterol concentration. CONCLUSIONS: Endothelium dependent FMD response is impaired in IDDM and is associated with increased carotid artery IMT. Significant thickening of intima-media appears in patients with advanced deterioration of FMD that is related to the duration of the disease. These data suggest that advanced endothelial dysfunction in IDDM may predispose to development of morphologic atherosclerotic lesions of arterial wall.     

Intrafamilial correlations of carotid intima-media thickness and flow-mediated dilation in a Siberian population

BACKGROUND: Intima-media thickening and impaired endothelium-dependent vasodilation are complex phenotypes determined by genetic and environmental factors. Few studies assessed these phenotypes in the same subjects. The goal of our study was to assess the sex-specific intrafamilial aggregation of ultrasonographic carotid intima-media thickness (IMT) and brachial flow-mediated vasodilation (FMD) in a Siberian population. METHODS: We randomly recruited 81 nuclear families of Caucasian ancestry (129 parents and 157 offspring, mean age 52.4 and 26.3 years) in Novosibirsk, Russia. Carotid artery IMT and brachial artery FMD were assessed by ultrasound. Intraclass correlation coefficients were calculated between first-degree relatives and between unrelated spouse pairs for IMT and FMD in age- adjusted, sex-adjusted, and multivariate-adjusted models. RESULTS: Multivariate-adjusted correlation coefficients in sib-sib pairs were 0.27 (P = .042) for IMT and 0.29 (P = .049) for FMD with heritabilities (h(2)= 2r) of 0.54 and 0.58, respectively. For IMT, the mother-offspring (r = 0.17, P = .051) and mother-daughter correlations (r = 0.28, P = .025) were significant, whereas the father-offspring correlation did not differ from zero (r = 0.11, P = .33). For FMD the father-offspring (r = 0.24, P = .042) and father-son correlations (r = 0.40, P = .051) were significant, whereas the mother-offspring correlation was only -0.09 (P = .39). The P value for the difference in familial aggregation of FMD between father-offspring and mother-offspring pairs was .018. CONCLUSIONS: Our findings confirm that a substantial proportion of the variability of carotid IMT and brachial FMD is attributable to genetic variation. They also suggest that offspring share more genetic or environmental determinants of FMD with fathers than their mothers.     

Normative values for intima-media thickness and distensibility of large arteries in healthy adolescents

OBJECTIVE: Sonographic evaluation of arterial wall morphology and elasticity is increasingly accepted as a non-invasive tool in cardiovascular assessment. Several studies suggest that intima-media thickness (IMT) and arterial elasticity indices may sensitively reflect different vasculopathic processes in children. However, normative values and the impact of adolescent growth are largely unknown. METHODS: We assessed the IMT of the common carotid (cIMT) and femoral arteries (fIMT), carotid elasticity indices and interacting anthropometric factors in 247 healthy subjects aged 10-20 years. RESULTS: cIMT, fIMT, incremental elastic modulus (Einc) and circumferential wall stress (CWS) were positively, and distensibility coefficient (DC) inversely, correlated with age, height, body mass index (BMI), systolic blood pressure (BP) and brachial pulse pressure (r = 0.56 to -0.45, P < 0.05 to 0.0001). DC (r = -0.29, P < 0.0001) and stiffness index beta (r = 0.25, P < 0.0001), but not Einc, were significantly associated with cIMT independently of age. All vascular parameters showed non-Gaussian distributions. Excessively high IMT was associated with BMI and pulse pressure above the 90th percentile, and elevated Einc with high-normal BMI. Multivariate analysis identified independent positive effects of standardized BMI and brachial pulse pressure on normalized cIMT, negative effects of systolic BP and cIMT on DC, a positive effect of cIMT on stiffness, and positive effects of systolic BP and BMI on Einc and CWS. CONCLUSIONS: Morphological and functional measures of large arteries should be normalized to take account of changes during adolescence and skewed distributions. Relative body mass, systolic blood pressure and/or pulse pressure are determinants of IMT and elasticity.     

Morphologic rather than functional or mechanical sonographic parameters of the brachial artery are related to angiographically evident coronary atherosclerosis

OBJECTIVES: The purpose of this study was to determine the relationship among coronary atherosclerosis and functional, morphologic, and mechanical parameters assessed noninvasively within the brachial artery (BA). BACKGROUND: Flow-mediated vasodilation (FMD) of the BA, intima-media thickness (IMT) of the carotid artery, and distensibility of the aorta have been correlated with the presence of coronary artery disease (CAD). METHODS: The BA was examined with high-resolution ultrasound (13 MHz) in 117 male patients, in whom coronary angiography was performed. Coronary artery disease (> or =30% diameter stenosis in > or =1 major branch) was found in 84 patients, and 33 patients had smooth coronary arteries (non-CAD). Wall cross-sectional area (WCSA) was calculated from resting diameter and IMT. RESULTS: The BA-WCSA (5.3 +/- 1.5 mm(2) vs. 4.4 +/- 1.4 mm(2), p = 0.002) and IMT (0.37 +/- 0.07 mm vs. 0.31 +/- 0.07 mm, p < 0.001) were significantly greater in patients with CAD compared with non-CAD patients. Flow-mediated vasodilation and distensibility were similar among groups. Using logistic regression analyses adjusting for age, positive family history, hypertension, hypercholesterolemia, smoking, FMD, and distensibility, only WCSA (p < 0.01) and IMT (p < 0.001) correlated independently with the presence of CAD. CONCLUSIONS: Morphologic but not functional and mechanical parameters of the BA are associated with the presence of CAD. Among BA sonographic parameters, IMT and WCSA seem to be the most accurate ones for the estimation of coronary atherosclerotic risk.     

Advanced glycation endproduct crosslink breaker (alagebrium) improves endothelial function in patients with isolated systolic hypertension

OBJECTIVES: Arterial stiffening and endothelial dysfunction are hallmarks of aging, and advanced glycation endproducts (AGE) may contribute to these changes. We tested the hypothesis that AGE crosslink breakers enhance endothelial flow-mediated dilation (FMD) in humans and examined the potential mechanisms for this effect. METHODS: Thirteen adults (nine men, aged 65 +/- 2 years) with isolated systolic hypertension (systolic blood pressure > 140 mmHg, diastolic blood pressure < 90 mmHg or pulse pressure > 60 mmHg) on stable antihypertensive therapy were studied. Subjects received placebo (2 weeks) then oral alagebrium (ALT-711; 210 mg twice a day for 8 weeks). Subjects and data analyses were blinded to treatment. Arterial stiffness was assessed by carotid augmentation index (AI) and brachial artery distensibility (ArtD) using applanation tonometry and Doppler echo, and endothelial function by brachial FMD. Serum markers of collagen metabolism and vascular inflammation were assessed. RESULTS: Alagebrium reduced carotid AI by 37% (P = 0.007) and augmented pressure (16.4 +/- 10 to 9.6 +/- 9 mmHg; P < 0.001). Heart rate, arterial pressures, and ArtD, were unchanged. FMD increased from 4.6 +/- 1.1 to 7.1 +/- 1.1% with alagebrium (P < 0.05), and was unrelated to altered shear stress or regional arterial distensibility. However, FMD change was inversely related to markers of collagen synthesis, p-selectin and intracellular cell adhesion molecule (all P < 0.05). Alagebrium-associated changes in plasma nitrite plus nitrate was inversely correlated with plasma matrix metalloproteinase 9 and type I collagen (P = 0.007). CONCLUSIONS: Alagebrium enhances peripheral artery endothelial function and improves overall impedance matching. Improved endothelial function correlates better with reduced vascular fibrosis and inflammation markers than with vessel distensibility. AGE-crosslink breakers may reduce cardiovascular risk in older adults by reduced central arterial stiffness and vascular remodeling.