Plasma level of asymmetric dimethylarginine (ADMA) as a predictor of carotid intima-media thickness progression: six-year prospective study using carotid ultrasonography

This study was designed to determine the relationship between plasma asymmetric dimethylarginine (ADMA) and the development of carotid atherosclerosis. Cross-sectional studies have revealed that plasma ADMA concentration is correlated with the intima-media thickness (IMT) of the carotid artery, but no prospective studies have appeared. Therefore we prospectively investigated whether or not plasma ADMA level can predict IMT progression. In a community-based cohort, we enrolled 712 subjects who were over 40 years old and who had no apparent cardiovascular diseases according to high-resolution carotid ultrasonography. Blood chemistries including ADMA were measured at baseline. In 575 subjects, IMT was re-measured 6 years later. The value of baseline ADMA for predicting IMT changes was investigated by multivariable analysis. At baseline, there was a significant (beta=0.321; p<0.001) relationship between IMT and ADMA levels. Multiple linear regression analysis revealed that baseline ADMA (beta=0.241; p<0.01) was the only predictor of IMT progression after adjustments for age, sex, baseline IMT, and four major risk factors (hypertension, hypercholesterolemia, diabetes mellitus, and smoking) plus hyperuricacidemia. Plasma ADMA was a predictor of carotid IMT progression.     

Mild-to-moderate hypertriglyceridemia in young men is associated with endothelial dysfunction and increased plasma concentrations of asymmetric dimethylarginine.

OBJECTIVES: The aim of this study was to investigate endothelial function and common carotid intima-media thickness (IMT) in healthy young men with mild-to-moderate hypertriglyceridemia. Plasma asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, was measured to further elucidate the mechanisms involved. BACKGROUND: Hypertriglyceridemia is a risk factor for coronary heart disease although the mechanisms behind the increased risk remain to be defined. Acute elevation of plasma triglycerides induced by an intravenous fat load is associated with impaired endothelial function. The results of studies examining acute effects induced by a high-fat meal or effects of chronic hypertriglyceridemia on endothelial function are more inconsistent. METHODS: Flow-mediated vasodilation and nitroglycerin-induced vasodilation of the brachial artery and common carotid IMT were measured noninvasively by ultrasound technique in 15 hypertriglyceridemic (HTG) subjects and 15 matched controls, mean age 34 years. Plasma concentrations of ADMA were measured by high-performance liquid chromatography. RESULTS: Flow-mediated vasodilation was decreased in the HTG group (p < 0.0001), whereas nitroglycerin-induced vasodilation and carotid IMT did not differ significantly. Asymmetric dimethylarginine concentrations were higher in the HTG group (p < 0.05). CONCLUSIONS: Hypertriglyceridemia in young men is associated with endothelial dysfunction and increased plasma concentration of ADMA but not with increased IMT of the common carotid artery. The corollary is that chronic hypertriglyceridemia results in endothelial dysfunction, possibly due to increased ADMA concentration, and that endothelial dysfunction might precede increased IMT among the early manifestations of atherosclerosis.     

Elevated plasma phospholipid transfer protein activity is a determinant of carotid intima-media thickness in type 2 diabetes mellitus

Aim/hypothesis The plasma activity of phospholipid transfer protein (PLTP), which has putative pro- and anti-atherogenic roles in lipoprotein metabolism, is increased in type 2 diabetes mellitus. We analysed the relationship between carotid artery intima–media thickness (IMT), an established marker of atherosclerosis, and PLTP activity in diabetic patients and control subjects. Methods The IMT (mean of three segments in both carotid arteries by ultrasonography), clinical variables, plasma PLTP activity (phospholipid vesicle–HDL system), lipoproteins, C-reactive protein and insulin were measured in 87 non-smoking men and women, who had type 2 diabetes mellitus, no cardiovascular disease, and were not on insulin or lipid-lowering medication, and in 83 age-matched control subjects. Results In diabetic patients, carotid IMT (p=0.02), pulse pressure (p=0.003), plasma PLTP activity (p<0.001), triglycerides (p=0.01), C-reactive protein (p<0.01) and insulin (p<0.001) were higher, whereas HDL cholesterol was lower (p<0.001) than in control subjects. Multiple stepwise linear regression analysis demonstrated that in type 2 diabetic patients IMT was independently associated with age (p<0.001), sex (p=0.001), pulse pressure (p=0.003), plasma PLTP activity (p=0.03) and HDL cholesterol (p=0.03), but not with very low density lipoprotein+LDL cholesterol, triglycerides, C-reactive protein and insulin (all p>0.20). The relationship between plasma PLTP activity and IMT was not significant in control subjects. Conclusions/interpretation Plasma PLTP activity is a positive determinant of IMT in type 2 diabetes mellitus, suggesting that high PLTP activity is involved in accelerated atherosclerosis in this disease.     

Factors underlying the increase in carotid intima-media thickness in borderline hypertensives.

To define the role played by various risk and behavioral factors in the increase of carotid intima-media thickness (IMT) observed in borderline hypertensives. Using B-mode ultrasonography, we compared 97 borderline hypertensives enrolled in the HARVEST study to 27 normotensive controls. Intima-media thickness was measured in the right and left common carotid artery, bulb, and internal carotid artery. Mean IMT (m-IMT), maximum IMT (M-IMT), the mean of M-IMT (M-MAX), and the prevalence of raised lesions (IMT>1 mm) were established. Compared to the controls, higher systolic BP, diastolic BP, mean arterial blood pressure levels and body mass index (BMI) were present in the borderline hypertensives, whereas age, smoking, physical activity, serum cholesterol, and triglycerides were similar. After adjusting for age, sex, heart rate, BMI, smoking, serum cholesterol, triglycerides, and physical activity, higher values of m-IMT and M-IMT were present in most carotid segments of borderline hypertensives compared with controls. After further adjustment for systolic BP and diastolic BP, differences were no longer significant. The adjusted M-MAX was 0.59+/-0.12 in borderline hypertensives compared with 0.50+/-0.10 in controls (P<0.001). After adjustment for systolic BP and diastolic BP it was 0.58+/-0.11 in borderline hypertensives compared with 0.50+/-0.12 in controls (P<0.005). In the various carotid segments, the prevalence of raised lesions was 1. 2% in borderline hypertensives compared with 0.3% in controls (P<0. 001). In the multivariate analysis m-IMT, M-IMT, and M-MAX were related to ambulatory mean arterial pressure, systolic BP and diastolic BP, serum cholesterol and triglycerides, BMI, age, and physical activity. Higher IMT values were found in subjects who were physically active than in those who were sedentary. In borderline hypertensives, an increase in IMT takes place not only in the common carotid artery but also in the bulb and the internal carotid segment. Blood pressure levels are a main determinant of m-IMT while the interaction of BP with other risk factors such as age and plasma lipids is more relevant for advanced intima-media thickening such as M-MAX.     

Detection of early atherosclerosis using the ultrasound parameter of the intima-media thickness of the common carotid artery in families with familial combined hyperlipidemia.

AIM: The aim of the present study was to quantify intima-media thickness (IMT) of the common carotid artery (CCA) in clinically asymptomatic members of familial combined hyperlipidemia (FCHL) families and to evaluate its association with lipids, apoproteins, blood pressure, surrogate markers of insulin resistance, fibrinogen and hs-CRP. METHODS: The group under study consisted of 82 individuals from 29 FCHL families (47 hyperlipidemic [HL] and 35 normolipidemic [NL]). They were compared with the age and sex adjusted control groups of healthy subjects (HL-c, n=20 and NL-c, n=20). IMT was measured by ultrasound at a far wall of both common carotid arteries. RESULTS: Hyperlipidemic subjects had increased IMT compared with healthy controls (0.695+/-0.118 vs 0.599+/-0.074 mm), with an age and sex corrected difference of 86 mm (p<0.001). No difference in IMT was recorded in NL FCHL members in comparison with their healthy controls. In HL subjects, significantly positive univariate correlations were observed between IMT and age, total cholesterol, LDL-cholesterol, non-HDL-cholesterol, apolipoprotein B, SBP, DBP, BMI, waist, fasting glycemia, C-peptide and proinsulin, whereas in NL subjects IMT correlated only with age. Multivariate regression analysis in FCHL subjects (HL+NL) revealed that age (p<0.001), sex (p<0.001), non-HDL-cholesterol (p<0.01) and BMI (p<0.05) were significant and independent predictors of IMT. CONCLUSIONS: The increase of IMT CCA in hyperlipidemic still clinically asymptomatic FCHL subjects corresponds to acceleration of the clinically 'silent' atherosclerosis by about 8-14 years and is in agreement with their increased risk of atherosclerosis.     

Microcirculatory damage of common carotid artery wall in obese and non obese subjects

The objective of the present study was to determine whether the intima-media thickness (IMT) is independently related with obesity, and central fat accumulation in healthy subjects. Common carotid artery IMT, parameters of body fat accumulation and distribution (body mass index, waist circumference, waist-to-hip ratio), blood pressure levels, and circulating fasting insulin, glucose, and lipid (cholesterol, HDL-cholesterol, triglycerides, LDL-cholesterol) levels were determined in a population of non-diabetic normal weight and obese subjects. Smoking habits (packs-years) were also taken into account. 239 healthy subjects (143 women and 96 men), with age ranging between 18 and 45 years, were enrolled into the study. They were divided indo two groups according to the body mass index (BMI), obese (132 subjects, 77 woman and 55 men, with BMI greater than 27.0) and controls (107 subjects: 66 women and 41 men, with BMI lower than 27.0). Common carotid artery intima-media thickness was measured by B-mode ultrasound imaging. Fasting plasma metabolic parameters (glucose and lipids) and insulin levels were determined by enzymatic and radioimmunological assays, respectively. Insulin sensitivity was estimated by insulin tolerance test (ITT) and the rate constant for plasma glucose disappearance (KITT) during the 3- to 15-min period following the regular insulin injection was taken as a measure of in vivo insulin action. Obese patients showed higher IMT than controls, and IMT was significantly associated with BMI in the whole population (r = 0.316, p < 0.001). Age (r = 0.327, p < 0.001), KITT (r = -0.201, p < 0.01), fasting blood glucose (r = 0.187, p < 0.01), LDL-chol (r = 0.201, p < 0.01), smoking (r = 0.147, p < 0.05), MBP levels (r = 0.154, p < 0.05), cholesterol (r = 0.152, p < 0.05) and HDL-chol (r = -0.159, p < 0.05) were also significantly associated with IMT. Age (r = 0.330, p < 0.05), BMI (r = 0.299, p < 0.01), waist (r = 0.312, p < 0.001), WHR (r = 0.266, p < 0.001) and KITT (r = -0.259, p < 0.01) were the parameters most strongly correlated with IMT in women, and age (r = 0.324, p < 0.001), BMI (r = 0.338, p < 0.001) waist (r = 0.325, p < 0.001) and LDL-chol (r = 0.283, p < 0.01) where the parameters most strongly correlated with IMT in men. When a stepwise multiple regression analysis was performed for the whole population, only age (p < 0.001) and BMI (p < 0.001) maintained a significant positive relationship with IMT. When a stepwise multiple regression analysis was performed separately for men and women, BMI or waist circumference or WHR were alternatively entered into the model; interestingly, only age, BMI and waist were still significantly correlated with IMT, whereas WHR did not maintain a significant correlation with IMT. In conclusion, BMI and waist circumference, but not WHR, are strongly and independently associated with the IMT of common carotid artery. These results suggests that central fat accumulation may accelerate the development of earlier clinically silent stages of atherosclerosis, thus possibly explaining the higher prevalence of cardiovascular diseases in patients with abdominal obesity.     

Lower plasma adiponectin is a marker of increased intima-media thickness associated with type 2 diabetes mellitus and with male gender

OBJECTIVE: We tested the extent to which altered plasma adipokine levels may contribute to the increased carotid artery intima-media thickness (IMT) associated with type 2 diabetes mellitus and with male gender, independently of conventional cardiovascular risk factors, insulin resistance, and plasma C-reactive protein (CRP). DESIGN: IMT (mean of three segments of both carotid arteries by ultrasonography), insulin resistance (homeostasis model assessment; HOMA(ir)), plasma CRP, lipids, adiponectin, leptin, resistin, and tumor necrosis factor-alpha (TNF-alpha) were measured in 84 type 2 diabetic patients and 85 control subjects. RESULTS: In diabetic patients, IMT (P<0.001), mean arterial pressure (P<0.001), HOMA(ir) (P<0.001), plasma CRP (P=0.003), triglycerides (P=0.037), leptin (P=0.023), resistin (P=0.003), and TNF-alpha (P=0.003) levels were higher, whereas high-density lipoproteins (HDL) cholesterol (P<0.001) and adiponectin (P<0.001) levels were lower compared with control subjects. Plasma adiponectin (P<0.001) and leptin (P<0.001) were substantially lower in men than in women. IMT was positively and independently associated with age (P<0.001), diabetes (P=0.049), and male gender (P=0.002) in a multivariate regression model, not including other variables. Further analyses showed that IMT was positively related to age (P<0.001) and plasma triglycerides (P=0.038) and negatively to adiponectin (P<0.001), without independent effects of diabetes, gender, and HOMA(ir). CONCLUSIONS: Increased IMT in type 2 diabetes may in part be explained by lower plasma adiponectin and higher triglycerides, but not by leptin, resistin, and TNF-alpha. The gender effect on IMT is related to lower plasma adiponectin.     

Impact of multiple coronary risk factors on the intima-media thickness of different segments of carotid artery in healthy young adults (The Bogalusa Heart Study)

Although risk factors for coronary artery disease are also associated with increased carotid artery intima-media thickness (IMT) as measured by B-mode ultrasonography in middle-aged and older persons, information on the impact of multiple risk factors on the IMT of different segments of the carotid artery in young adults is limited. This relation was examined in a sample of 518 black and white subjects (mean age 32 years; 71% white, 39% male) enrolled in the Bogalusa Heart Study. IMT was thicker and more skewed in the bulb compared with other carotid segments. Race differences (blacks more than whites) were noted for the common carotid (p <0.001) and carotid bulb (bifurcation) IMT (women only, p <0.001). Men had a greater IMT in the common carotid (p <0.05), internal carotid (p <0.05), and carotid bulb (whites only, p <0.001). In a multivariate analysis, systolic blood pressure, race, age, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol weree entered into a model in that order and accounted for the 16.7% variance in the common carotid IMT; age, systolic blood pressure, HDL cholesterol, LDL cholesterol, race, and insulin levels explained the 19.4% variance in the carotid bulb IMT. Gender and body mass index (BMI) accounted for the 4.7% variance in the internal carotid IMT. Increases in IMT with increasing number of risk factors (cigarette smoking, higher total cholesterol to HDL cholesterol ratio, higher systolic blood pressure, greater waist circumference, and higher insulin level) were noted for the common carotid and carotid bulb segments (p for trend <0.001 for both). The observed deleterious trend of increasing IMT at different carotid segments with increasing number of risk factors in free-living, asymptomatic young subjects underscores the importance of profiling multiple risk factors early in life. Ultrasonography of carotid arteries, especially at the bifurcation, may be helpful along with measurements of risk factors for evaluation of asymptomatic atherosclerotic disease.     

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.     

Effect of Aging on Human Circulatory System in Normotensive Healthy Subjects

Aging is associated with degenerative changes in cardiac and endothelial function (EF). This study was done to assess whether age-related changes take place on EF, carotid intima-media thickness (IMT), blood pressure (BP), and echocardiographic measurements. All volunteers were healthy normotensive healthy subjects. They were divided into three groups. Group 1, young adults: < 40 years old; Group 2, middle age: between 40 and 60 years old; Group 3, elderly: > 60 years old. High-frequency vascular ultrasound was used to assess the baseline brachial artery dimension and flow velocity after reactive hyperemia. The carotid IMT and echocardiographic measurements including Doppler variables were recorded in all subjects. Systolic BP, left ventricular mass, and left ventricular end-diastolic volume increased progressively with age (p < 0.001). Left ventricular ejection fraction decreased progressively with age (male, p = 0.034; female, p = 0.001); E/A ratio of the left ventricular flow spectrum declined with age (p < 0.001). The ultrasonic EF variables of flow increased during reactive hyperemia and IMT increased with age (p < 0.001). Our study demonstrates that BP, body weight, and ultrasonic variables changed significantly with age. The aging-associated changes provide insight into progression to atherosclerosis.     

Dependence of morphological changes of the carotid arteries on essential hypertension and accompanying risk factors.

BACKGROUND: Aims: to evaluate morphological changes (intima-media thickness, IMT) of the carotid arteries in patients being treated for essential hypertension (EH), and to discover whether this abnormality can be detected in normotensive offspring of subjects with EH (familial trait, FT); and to investigate the interrelationship between IMT and accompanying risk factors. METHODS: Experimental design: cross-sectional study. Setting: angiology department, university teaching hospital. Subjects: the study encompassed 172 subjects, of whom 46 were treated hypertonics aged 40-55 (49) years, and 44 age matched, normotensive volunteers as controls. We also investigated 41 normotensives with FT for essential hypertension aged 20-30 (25) years and 41 age- and sex-matched controls without FT. Interventions: the hypertensive subjects were being treated either with long-acting calcium-channel antagonists or ACE-inhibitors. Measures: using high resolution ultrasound, IMT of the carotid bifurcation and of the common carotid artery was measured. RESULTS: In the hypertensives, the mean IMT was greater than that in the controls (0.92 (0.10) mm vs 0.72 (0.07) mm; p<0.00005). The IMT was independently related to accompanying risk factors: a positive family history of hypertension, age of the patient, duration of EH and the level of systolic/diastolic blood pressure (BP), body mass index and total/LDL-cholesterol. In subjects with FT, IMT was also greater compared to the control group (0.60 (0.05) mm vs 0.55 (0.04) mm; p<0.00005). IMT was not related to BP values. CONCLUSIONS: In treated essential patients with the EH, the IMT was increased. Individuals with FT also had greater IMT in the absence of elevated BP. The IMT in hypertensives was related to accompanying risk factors, which could be pathogenetic determinants of EH and/or its complications.     

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.     

Plasma asymmetric dimethylarginine (ADMA) levels and atherosclerotic disease in ankylosing spondylitis: a cross-sectional study

Conclusive data about the prevalence of endothelial dysfunction and atherosclerotic process in ankylosing spondylitis (AS) patients with respect to the general population are lacking. Elevated plasma levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, have been reported in clinical conditions associated with endothelial dysfunction and atherosclerotic disease. We performed a cross-sectional study to evaluate plasma ADMA levels and atherosclerotic disease in AS patients. Seventeen consecutive AS patients free of any cardiovascular disease and 17 healthy controls [strictly matched for sex, age (±5 years) and atherosclerotic risk factors] were recruited. Plasma ADMA levels were assessed by capillary electrophoresis. Common carotid artery intima–media thickness (CCA-IMT), flow-mediated dilatation (FMD) and arterial stiffness (aS) were registered as surrogate markers of atherosclerotic disease. Plasma ADMA levels appeared significantly (p = 0.001) higher in AS patients (0.65 ± 0.10 μmoli/L) than in the control subjects (0.54 ± 0.07 μmoli/L) while no statistically significant differences between AS and controls were demonstrated in CCA-IMT, FMD, and aS. AS patients showed increased plasma ADMA levels with respect to control subjects. On the contrary, we were not able to document a significant difference in atherosclerotic process between patients and controls.     

Increased human urotensin II levels are correlated with carotid atherosclerosis in essential hypertension

BACKGROUND: Circulating blood levels of human urotensin II (U-II), the most potent vasoconstrictor peptide identified to date, are increased in patients with essential hypertension. Our previous studies showed that U-II accelerates human macrophage foam cell formation and vascular smooth muscle cell proliferation, suggesting development of atherosclerotic plaque. In this study, we demonstrated a correlation between plasma U-II level and progression of atherosclerosis in hypertensive patients. METHODS: The intima-media thickness (IMT) and plaque score in the carotid artery, blood pressure (BP), plasma levels of U-II, and atherosclerotic parameters were determined in 50 hypertensive patients and 31 normotensive controls. RESULTS: Plasma U-II level, maximum IMT, plaque score, systolic BP, and homeostasis model assessment for insulin resistance (HOMA-IR) were significantly greater in hypertensive patients than normotensive controls. Age, gender, body mass index, and serum levels of high-sensitive C-reactive protein (CRP), HDL and LDL cholesterols, small dense LDL, triglycerides, lipoprotein(a), insulin, and fasting plasma glucose level were not significantly different between the two groups. In all subjects, plasma U-II level showed significant positive correlations with systolic BP, maximum IMT, plaque score, and HOMA-IR. Multiple logistic regression analysis indicated that the contribution of plasma U-II levels to carotid plaque formation (plaque score >/=1.1) was significantly still greater with a 60% increase than those of established risk factors, such as age, systolic BP, high-sensitive CRP, small dense LDL, and HOMA-IR. CONCLUSIONS: Our results suggest that increased levels of U-II may play a crucial role in the development of carotid atherosclerosis in hypertensive patients.     

Correlation of parents' longevity with carotid intima-media thickness in patients attending a Lipid Clinic

The relationship between carotid intima-media thickness (IMT) and the subject's parents' longevity has been investigated. The association between parents' age at death and IMT was estimated in 593 consecutive patients attending a Lipid Clinic by survival-analysis methods. Average maximum IMT (Avg-IMT), maximum IMT (Max-IMT), clinical and laboratory variables and parental age at death, were assessed. Kaplan-Meier analyses showed significant differences in survival curves, low IMTs being associated with long-lived parents (p=0.0003 and 0.001 by log-rank test for fathers and mothers, respectively). A Cox proportional hazards regression model showed that higher carotid IMT values were associated with father's and mother's deaths at an early age, even after adjusting for conventional cardiovascular risk factors. These data were confirmed after the stratification of patients into younger (<65 y) and older (>/=65 y) or into subjects with and without a family history of dyslipidemia or vascular diseases. In addition, by stratifying subjects into those with no, one or two long-lived parents, we observed a significant trend for the combination of father's and mother's longevity on their offspring's IMTs (p<0.01 and 0.05 for Avg-IMT and Max-IMT, respectively). These data highlight a significant relationship between carotid artery IMT and a familial predisposition to be long-lived that is independent of the individual's vascular risk profile.     

Association between asymmetric dimethylarginine and indices of vascular function in patients with essential hypertension

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and is associated with endothelial dysfunction. The aim of the present study was to investigate the relationship between ADMA, indices of arterial stiffness, endothelial function and carotid artery intima-media thickness (IMT) in hypertension patients. Eighty middle-aged (47 ± 10 years) untreated patients with mild to moderate essential hypertension underwent routine physical examination, pulse wave analysis (PWA), measurement of aortic pulse wave velocity (PWV) and IMT. In PWA, administration of salbutamol and nitroglycerine was used to assess endothelium-dependent (EDV) and endothelium-independent vasodilation, respectively. In univariate analysis, ADMA was correlated with EDV (r = -0.26; p = 0.02) and IMT (r = 0.32; p = 0.007). In multiple regression analysis, ADMA was independently associated with the female gender, EDV, IMT and total cholesterol (R(2) = 0.30; p < 0.001). No correlation was detected between ADMA and augmentation index, central/brachial blood pressure or aortic PWV. In hypertension patients, ADMA is independently correlated with IMT and EDV. Thus, ADMA is a marker of endothelial dysfunction and intima-media thickening in patients with hypertension.     

Intima-Media Thickness and Flow-Mediated Vasodilation in Asymptomatic Subjects with Newly Detected Severe Hypercholesterolemia

Background: The aim was to establish the predictors of early functional and structural vascular alterations (using intima-media thickness (IMT)) and flow-mediated vasodilation (%FMD) as well as to investigate the interrelationship between IMT and %FMD in asymptomatic, never-treated, severe hypercholesterolemia (HH). Methods: One hundred and twenty patients with asymptomatic, severe, untreated HH and 100 controls were included. ELISA was used for asymmetric dimethylarginine (ADMA) and cellular adhesion molecules, and fluid chromatography for total homocysteine (tHcy). Hewlett Packard SONOS 5500 with a 7.5 MHz transducer and MedicaSoft IMT software were used for evaluation of %FMD and IMT of common carotid artery (CCA). Results: Patients and controls differ with respect to all tested biomarkers (P < 0.05), except for P-selectin and E-selectin (P < 0.05). %FMD was lower in patients (P < 0.001). The IMT of the CCA was higher in patients (P < 0.001). Inverse correlations were found between %FMD and IMT mean and age, ADMA, Apo-B, Apo-B/Apo-A₁, and tHcy. ADMA was established as the most important factor related to %FMD. Age and Apo-B were established as the most important factors related to IMT mean. An inverse correlation was established between %FMD and IMT mean (r_xy= 0.546; P < 0.001)). If cases with IMT mean ≥1 were excluded, the correlation weakened. In patients with IMT mean ≥1 mm, the correlation did not change. Conclusion: In conclusion, asymptomatic, untreated patients with severe hypercholesterolemia are at high risk of having increased IMT of the CCA, especially if there is endothelial dysfunction, verified by %FMD of the brachial artery.     

Normative values of carotid artery intima-media thickness in healthy Korean adults and estimation of macrovascular diseases relative risk using this data in type 2 diabetes patients

The objectives of this study were to determine normative values of carotid intima-media thickness (IMT) in healthy Korean subjects and to use these values to estimate the relative risk of macrovascular diseases in patients with type 2 diabetes mellitus (T2DM). High-resolution B-mode ultrasonography was performed in 1,229 healthy subjects and 830 T2DM patients. Height, weight, blood pressure, fasting plasma glucose, total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, and fasting insulin level were measured. Subjects were classified as healthy subjects; T2DM patients without ischemic heart disease (IHD), stroke, and peripheral arterial occlusive diseases (PAOD); T2DM patients with IHD, stroke, or PAOD. IMT was significantly increased as age increased. Patients with T2DM had higher IMTs compared to healthy subjects. Independent risk factors of IMT were age, systolic blood pressure, BMI for healthy subjects, and age, duration of diabetes, LDL-cholesterol for T2DM subjects. According to presence of increased IMT, the relative risks of IHD, stroke, and PAOD in diabetic subjects, were 2.34 (CI; 1.32-4.14), 2.95 (CI; 1.46-5.54), and 3.64 (CI; 1.66-7.40), respectively. This study suggests normative values that can be used as an index for carotid artery IMT of healthy Korean subjects, and that IMT data reflects the risk of macrovascular diseases in T2DM.     

Parental history of premature myocardial infarction is a stronger predictor of increased carotid intima-media thickness than parental history of hypertension

An increased carotid intima-media thickness (IMT) is detectable in young subjects with parental history of premature myocardial infarction (PHPMI) or hypertension (PHH). In this study we evaluated if PHPMI and PHH exert a different influence on carotid IMT and if their conjunction produces additive effects.High-resolution B-mode ultrasonographic evaluation of common carotid artery IMT was acquired from 48 subjects without PHPMI and PHH (22 males, 26 females; mean age 22.1 ± 4.9 years; controls), 24 age- (±1 year) and sex-matched subjects with PHH without PHPMI (PHH-positive/PHPMI-negative subjects), 24 age- and sex-matched subjects with PHPMI without PHH (PHH-negative/PHPMI-positive subjects) and 24 age- and sex-matched subjects with both PHPMI and PHH (PHH/PHPMI-positive subjects). Lipid profile, resting blood pressure, smoking behaviour and body mass index (BMI) were also assessed. Carotid IMT was smaller in controls (0.41 ± 0.07 mm) compared to PHH-positive/PHPMI-negative subjects (0.47 ± 0.10, p = 0.023), to PHH-negative/PHPMI-positive subjects (0.54 ± 0.11, p < 0.001) and to PHH/PHPMI-positive subjects (0.52 ± 0.10 mm, p < 0.001). Carotid IMT was greater in PHH-negative/PHPMI-positive (p = 0.006) and in PHH/PHPMI-positive (p = 0.031) than in PHH-positive/PHPMI-negative subjects. No difference in carotid IMT was evident between PHH-negative/PHPMI-positive and PHH/PHPMI-positive subjects (p = 0.549). In the comparison among subjects using multiple regression analysis, only PHPMI, age and BMI were independently associated with carotid IMT.In healthy young subjects with PHPMI and/or PHH, carotid IMT is increased. PHPMI is a stronger predictor of increased carotid IMT than PHH. PHH in conjunction with PHPMI does not add any further detrimental effect on carotid IMT.     

Antioxidant vitamins and the risk of carotid atherosclerosis : The perth carotid ultrasound disease assessment study (CUDAS)

OBJECTIVES

This study examined whether dietary intake or plasma levels of antioxidant vitamins were independently associated with common carotid artery intima-media (wall) thickness (IMT) or focal plaque, or both, in a large, randomly selected community population.

BACKGROUND

Oxidation of low-density lipoprotein (LDL) cholesterol is thought to be important in early atherogenesis. Antioxidant micronutrients may therefore protect against lipid peroxidation and atherosclerotic vascular disease.

METHODS

We studied 1,111 subjects (558 men and 553 women; age 52 ± 13 years [mean ± SD], range 27 to 77). We measured dietary vitamin intake and fasting plasma levels of vitamins A, C and E, lycopene and alpha- and beta-carotene and performed bilateral carotid artery B-mode ultrasound imaging.

RESULTS

After adjustment for age and conventional risk factors, there was a progressive decrease in mean IMT, with increasing quartiles of dietary vitamin E intake in men (p = 0.02) and a nonsignificant trend in women (p = 0.10). Dietary vitamin E levels accounted for 1% of the variance in measured IMT in men. For plasma antioxidant vitamins, there was an inverse association between carotid artery mean IMT and plasma lycopene in women (p = 0.047), but not in men. None of the other dietary or plasma antioxidant vitamins, nor antioxidant vitamin supplements, were associated with carotid artery IMT or focal carotid artery plaque.

CONCLUSIONS

This study provides limited support for the hypothesis that increased dietary intake of vitamin E and increased plasma lycopene may decrease the risk of atherosclerosis. No benefit was demonstrated for supplemental antioxidant vitamin use.