Carotid intima-media thickness measurements are not affected by the ultrasound frequency

Objective: Carotid intima‐media thickness (IMT) is a B‐mode ultrasound measure of subclinical atherosclerosis predictive of future cardiovascular risk. Carotid IMT measurements were historically obtained at an ultrasound frequency of 8 MHz or lower, but it is unknown whether measurements obtained at higher frequencies using newer, more advanced ultrasound technology allow for valid comparison to the older general population databases that are commonly used for the interpretation of carotid IMT results. Methods: Carotid IMT studies were conducted in 35 consecutive patients at standard (8 MHz) and high (14 MHz) frequencies and measurements were performed by two independent expert readers. Systematic bias was assessed by using the paired t‐test and agreement was analyzed with the Bland–Altman method. Results: The sample mean carotid IMT obtained at 14 MHz was 0.006 mm lower than that obtained at 8 MHz. The 95% confidence interval (CI) for the mean difference between frequencies indicated that the population mean for 14 MHz is unlikely to be more than 0.02 mm lower than for 8 MHz (95% CI –0.017 to 0.004). The 95% reference range for the difference between the two transducer frequencies indicated that the thickness obtained at 14 MHz was within 0.05 mm of that obtained at 8 MHz for 95% of subjects. Conclusions: Carotid IMT measurements obtained at higher transducer frequencies are similar to those obtained at standard frequency. This finding has important clinical implications because it validates comparison of carotid IMT measurements obtained with newer, more advanced ultrasound technology with the landmark reference carotid IMT studies commonly used for interpretation of carotid IMT results. (Echocardiography 2012;29:354‐357)     

原发性高血压患者血清抵抗素水平与颈动脉内膜中层厚度的关系

目的:探讨不同体质指数(BMI)的原发性高血压患者血清抵抗素(Res)水平的变化以及与颈动脉内膜中层厚度(IMT)的相关关系.方法:51例原发性高血压患者按BMI分为:肥胖组(BMI≥24,A组,23例)与非肥胖组(BMI<24,B组,28例),另选26例体检正常者作为对照组(C组),采用酶联免疫吸附法检测空腹血清Res水平;同时检测血脂、血压、身高、体重,计算BMI;采用彩色超声诊断仪测定IMT.结果:与C组空腹血清Res水平[(20.92±1.42)μg/L]相比,A组[(24.26±1.98)μg/L]和B组[(22.03±2.15)μg/L]明显升高,分别为P<0.01和P<0.05;A组与B组比较,Res水平差异有统计学意义(P<0.01);A组和B组Res均与收缩压(r=0.554,P<0.05;r=0.411,P<0.05)、TG(r=0.453,P<0.05;r=0.482,P<0.05)正相关,A组Res还与BMI(r=0.390,P<0.05)正相关,C组Res与收缩压(r=0.397,P<0.05)正相关.A组IMT[(1.17±0.48)mm]显著高于B组[(0.94±0.55)mm]和C组[(0.85±0.42)mm],均P<0.05;IMT与Res、年龄正相关.结论:Res与IMT、高血压、肥胖正相关,在动脉粥样硬化的发生和发展中起重要作用.     

Local carotid stiffness and intima-media thickness assessment by a novel ultrasound-based system in essential hypertension

ObjectiveTo evaluate local carotid stiffness (CS) and intima-medial thickness (C-IMT) in hypertensive patients with different cardiovascular risk profile, using a new user-friendly ultrasound-based system, previously validated vs. RF-based echotracking device.MethodsWe investigated a population with different cardiovascular risk: 45 healthy normotensives (NT), 90 non-diabetic hypertensives (HT), and 48 patients with hypertension and type-2 diabetes (DM). Framingham risk factor score (FRS) was calculated. PWV was assessed by applanation tonometry. The relative stroke change in diameter (ΔD) and C-IMT were measured on carotid scans. Distensibility coefficient (DC) was calculated as ΔA/(A*ΔP), where A = diastolic lumen area, ΔA = stroke change in lumen area, and ΔP = carotid pulse pressure. CS (m/s) was calculated as (ρ*DC) ? 1/2 (ρ = blood density).ResultsCS, C-IMT, PWV were significantly increased in HT and DM vs. NT. C-IMT and PWV were significantly higher in DM than HT. ΔD and DC were significantly lower in HT and DM vs. NT. FRS ≥10% group showed increased carotid diameter, C-IMT and CS than the FRS <10%. FRS was (p < 0.001) correlated with CS (r = 0.35); ΔD (r = ?0.36), DC (r = 0.35), C-IMT (r = 0.48), PWV (r = 0.38). CS correlated (p < 0.05) with PWV in the entire population (r = 0.37), in the NT (r = 0.35), in the HT and DM (r = 0.20). PWV (r = 0.50) and CS (r = 0.33) were correlated with age. Determinants of aortic and carotid stiffness were identified by multivariate stepwise analysis.ConclusionsThe proposed B-mode ultrasound-based system is a reliable and user-friendly method that could serve to investigate the predictive value of CS for cardiovascular events in future large clinical studies.     

Carotid plaques, but not common carotid intima-media thickness, are independently associated with aortic stiffness.

OBJECTIVE: It has been suggested that non-invasive aortic stiffness measurements can be used as an indicator of atherosclerosis. The relationships of arterial stiffness with arterial wall hypertrophy and atherosclerosis however, have rarely been investigated in large-scale studies. The present study reports the associations of carotid arterial structure assessed by B-mode ultrasound with carotid-femoral pulse-wave velocity in hypertensive and non-hypertensive subjects. DESIGN AND METHODS: Free health examinations were performed on 564 subjects (age 58.2 +/- 10.8 years, 31.9% of women, 53.2% of all were hypertensive). Carotid-femoral pulse-wave velocity (PWV) was used to assess aortic stiffness. Carotid ultrasound examination included measurements (at sites free of plaques) of intima-media thickness (IMT) at the common carotid arteries (CCA), CCA-lumen diameter, and assessment of atherosclerotic plaques in the extracranial carotid arteries. RESULTS: Subjects with carotid plaques had significantly higher mean sex-adjusted values of PWV than those without carotid plaques (12.7 +/- 0.2 versus 11.1 +/- 0.1 m/s, P < 0.001). Multivariate analyses showed that this association was independent of sex, age, height, body mass index, mean blood pressure, pulse pressure, diabetes, hypercholesterolaemia and smoking habits (P < 0.009). PWV was positively associated with CCA-IMT and CCA-lumen diameter in sex-adjusted analysis (partial correlation coefficients (r ) were respectively 0.39 and 0.42, P < 0.001 for each). However, the association of PWV with CCA-IMT, but not that with CCA-lumen diameter, disappeared after further adjustment for age and blood pressure measurements (mean blood pressure and/or pulse pressure). CONCLUSION: This study shows that there is a differential association of PWV with CCA-IMT and carotid plaques. The nature of the independent positive association between atherosclerosis and arterial stiffness should be thoroughly investigated.     

Carotid intimal-medial thickness in active professional American football players aged 23 to 35 years

Risk of cardiovascular disease and death in retired professional American football players may be higher than that in the general population. Previously published data have demonstrated that American football players have less glucose intolerance, less smoking, similar lipid profiles, and higher blood pressure despite a much larger body compared to the general population, although the presence of subclinical atherosclerosis in these subjects has not been evaluated. This study compared the prevalence of subclinical atherosclerosis in active professional American football players to that in age-, gender-, and race-matched controls derived from the Bogalusa Heart Study. Carotid intimal-medial thickness (CIMT) was used as an indicator of subclinical atherosclerosis in 75 active American football players (23 to 35 years old, 31 white, 44 African-American) as measured by B-mode ultrasonography at Mayo Clinic, Scottsdale, Arizona, on September 13 and 14, 2009. CIMT measurements of 75 athletes were compared to those of 518 matched controls who had CIMT determinations in 1995 and 1996. Two-group t tests determined population similarities between groups. In a generalized linear model, players (overall and by race) had lower CIMT values than controls after age and race adjustment (p <0.001 for all comparisons). Nonlinemen and linemen had lower CIMT values than controls (p < 0.001 and p = 0.004, respectively). In conclusion, active professional American football players, regardless of position, had mean CIMT values similar to or lower than those in a matched general population cohort, suggesting that if the prevalence of subclinical atherosclerosis is increased in retired professional American football players, this occurs after retirement.     

Acute reduction of blood pressure by nitroglycerin does not normalize large artery stiffness in essential hypertension

Stiffness of large elastic arteries is elevated in subjects with hypertension, an effect that could potentially be explained by increased distending pressure. We examined effects of an acute change in blood pressure on carotid-femoral pulse wave velocity and carotid artery distensibility (inversely related to stiffness) in normotensive control subjects (n=20, mean age 42) with mean arterial pressure (MAP) 84+/-1.7 mm Hg (mean+/-SE) and subjects with essential hypertension (n=20, mean age 45, MAP 104+/-2.0 mm Hg). Normotensive subjects received intravenous nitroglycerin (NTG) and angiotensin II to lower/increase blood pressure. Hypertensive subjects received NTG to lower blood pressure. Pulse wave velocity was 24% (95% CI: 12% to 35%) higher and carotid distensibility 47% (95% CI: 32% to 63%) lower in hypertensive subjects compared with controls. In normotensive subjects, acute changes in blood pressure produced expected changes in stiffness. However, in hypertensive subjects, despite reducing MAP by 22 mm Hg to the same level as in normotensive subjects, there was no detectable reduction in arterial stiffness: pulse wave velocity remained 24% (95% CI: 10% to 38%) higher and carotid distensibility 48% (95% CI: 31% to 63%) lower in hypertensive compared with normotensive subjects. Because blood pressure-independent effects of NTG are, if anything, to reduce stiffness, these results indicate that elevated carotid and aortic stiffness in hypertensive subjects is not explained by elevated blood pressure but relates to structural change in the arterial wall.     

Nifedipine therapy in uncomplicated essential hypertension and hypertensive problem cases

In altogether 54 patients with high blood pressure of the clinical degrees of severity I-IV the blood pressure-reducing effectiveness of the calcium antagonist nifedipine was investigated both in the framework of an oral long-term therapy and especially in problematic situations of high blood pressure. According to the results of own treatment nifedipine is particularly suited for the antihypertensive combination therapy with beta-receptor blockers. Monotherapeutically favourable possibilities of application exist in hypokinetic types of the regulation of circulation as well as in elderly hypertensives. Therapy-resistant as well as crisis-like developments of high blood pressure react with excessive, well tolerable and persisting reductions of blood pressure. Above all with regard to this still little considered indication in the meantime nifedipine represents an unavoidable enrichment in the therapeutic basis spectre of the hypertonus.     

Carotid plaque, arterial stiffness gradient, and remodeling in hypertension

The analysis of plaque mechanics along the longitudinal axis (bending strain) may provide useful information because repetitive bending strain of an atherosclerotic plaque can fatigue the wall material and result in plaque rupture. Whether essential hypertension is associated with a specific pattern of bending strain has not yet been determined. The study included 92 patients with an atherosclerotic plaque on the common carotid artery: 66 patients with essential hypertension, either treated or not, and 26 normotensive patients. A novel noninvasive echotracking system (ArtLab; Esaote, The Netherlands) was used to measure intima-media thickness, diameter, and distensibility at 128 sites on a 4-cm-long carotid segment. Carotid plaque was either less elastic than adjacent carotid artery (inward strain) or more elastic (outward strain). Inward strain was more frequently associated with an inward plaque remodeling, whereas an outward strain was more frequently associated with an outer remodeling. In multivariate logistic regression analysis, patients with essential hypertension were more likely to exhibit an inward strain of carotid plaque (odds ratio=6.9 [1.4 to 34.9]; P<0.02), independently of 2 factors favoring inward strain: an outer remodeling (odds ratio=4.6 [1.7 to 13.4]; P<0.005) and the absence of renin-angiotensin system blockers (odds ratio=4.8 [1.1 to 20.4]; P<0.05). In conclusion, arterial wall material of hypertensive patients was less elastic at the site of the plaque than upstream, and carotid was inwardly strained in the zone affected by plaque. This may generate a high level of stress concentrations and fatigue, exposing the plaque to a greater risk of rupture.     

Carotid intima-media thickness and stiffness in relation to type 2 diabetes in Chinese

We investigated carotid intima-media thickness (IMT) and quantitative carotid stiffness (QCS) index in relation to plasma glycosylated hemoglobin A_1C (HbA_1C) and duration of diabetes mellitus in 337 Chinese diabetic patients. In categorical analyses, carotid IMT was 710 μm in subjects with a duration of diabetes mellitus ≤2 years, 760 μm in subjects with a duration of diabetes mellitus more than two years and with plasma HbA_1C < 6.5% (P < 0.05), and 790 μm in subjects with a duration of diabetes mellitus more than two years but with plasma HbA_1C ≥ 6.5% (P < 0.01). The corresponding values for QCS values were 4.5, 4.6 and 5.1 (P < 0.05), respectively. In multiple stepwise regression analyses carotid IMT was significantly associated with the duration of diabetes mellitus, systolic blood pressure and serum concentration of total cholesterol, whereas QCS was significantly associated with age, HbA_1C, systolic and diastolic blood pressure (P < 0.05). In conclusion, carotid IMT as a structural measure of arterial wall is increased in patients with a longer history of diabetes mellitus, whereas QCS as functional index is mainly influenced by the quality of blood glucose control.     

History of gestational hypertension is associated with the metabolic syndrome and masked hypertension but not arterial stiffness in women with essential hypertension

The underlying mechanisms of subsequent increased risk of cardiovascular disease with a history of gestational hypertension (GH) are not known. Untreated hypertensive women (n=155, age 43+/-1 years) underwent ambulatory blood pressure (BP) monitoring and assessment of aortic pulse wave velocity (PWV) and augmentation index (AIx). Despite identical clinic BP readings, the group of women with GH (n=54) had higher (P=.002) ambulatory daytime systolic BP levels and a greater number of extreme nocturnal dippers (P=.005) than the group without GH. Women with GH had higher body mass index (P=.003), greater waist circumference (P=.02), higher levels of triglycerides (P=.002), lower levels of high-density lipoprotein cholesterol (P=.004), a higher prevalence of the metabolic syndrome (P<.05) and microalbuminuria (P=.004), higher plasma renin activity (P=.03), and higher aldosterone levels (P=.01). There was no significant difference in PWV and AIx between the 2 groups. The higher prevalence of the metabolic syndrome, microalbuminuria, masked hypertension, and activation of the renin-angiotensin-aldosterone system but not arterial stiffness may explain the subsequent propensity to high BP and cardiovascular disease in women with GH.     

Brain metabolism and spatial memory are affected by portal hypertension

Portal hypertension is a major complication of cirrhosis that frequently leads to a neuropsychiatric disorder that affects cognition. The present study was undertaken in order to compare the performance of sham-operated rats (SHAM) and portal hypertension rats (PH) in reference memory tasks in the Morris water maze (MWM). Two groups of animals were used: SHAM group (n = 12) was used as a control group and PH group (n = 12) by the triple portal vein ligation method was used as an animal model of early evolutive phase of PH. The portal pressure was measured in the splenic parenchyma. Our work shows that spatial learning in the MWM is not impaired in PH group although this group showed a one-day delay in the task acquisition compared to the SHAM group. We assessed the brain metabolic activity of the animals by means of cytochrome c-oxidase (COx) histochemistry. Significant changes were found in the CA3, dentate gyrus, basolateral, medial, lateral and central amygdala, showing lower COx activity in the PH group as compared to the SHAM group in all cases. We found no changes in metabolic activity in prefrontal cortex and CA1 area between groups. In fact, different neural networks were shown according to the execution level of the subjects. The early PH evolution induced changes in brain metabolic activity without biggest alterations in spatial memory.     

Endogenous androgens and carotid intimal-medial thickness in women.

The influence of endogenous androgens on atherosclerotic disease in women is unknown. In this study involving 101 pre- and post-menopausal females, we evaluated the relationship between serum androgen levels and both carotid artery intimal-medial thickness (IMT) and major cardiovascular risk factors. In addition to evaluation of blood pressure, body mass index, and waist-to-hip ratio, serum dehydroepiandrosterone sulfate (DHEA-S), androstenedione (A), total testosterone (TTS), free testosterone (FTS), insulin, cholesterol (total and high density lipoproteins), triglycerides, and glucose were measured. All women underwent carotid ultrasonography. Spearman correlation coefficients showed that serum DHEA-S and A levels were negatively related (P < 0.03-0.0004) to several IMT measures. Higher tertiles of DHEA-S, A, and FTS corresponded to significantly lower measures of carotid thickness. DHEA-S, and all androgens were inversely related to age (P < 0.03 or less), showing no unfavorable association with major cardiovascular risk factors. In contrast, serum DHEA-S was negatively associated with WHR (P < 0.02), while A was negatively associated with body mass index (P < 0.02). Stepwise multiple regression analysis indicated that A and FTS showed an inverse association with IMT measures (P < 0.05-0.001). In conclusion, our data indicate that in women serum DHEA-S and androgens decline with age and that normal hormonal levels are not associated with major cardiovascular risk factors. They also show that higher DHEA-S and androgen concentrations are related to lower carotid wall thickness; for A this association is independent of cardiovascular risk factors. Our results suggest that, in the physiological range, DHEA-S and androgens in women are correlated with lower risk of carotid artery atherosclerosis.     

Soluble receptor for advanced glycation end-product levels are related to albuminuria and arterial stiffness in essential hypertension

Background and aimsEmerging evidence suggests that the soluble receptor for advanced glycation end-products (sRAGE) is implicated in the development of vascular disease. We investigated the interrelationships of sRAGE with albumin to creatinine ratio (ACR) and arterial stiffness in essential hypertension.Methods and resultsIn 309 untreated non-diabetic hypertensives, ACR values were determined as the mean of three non-consecutive morning spot urine samples and aortic stiffness was evaluated on the basis of carotid to femoral pulse wave velocity (c-f PWV). In all subjects, venous blood sampling was performed for the estimation of sRAGE levels. Patients with low (n = 155) compared to those with high sRAGE values (n = 154) had greater 24-h systolic BP (140 ± 8 vs. 134 ± 7 mmHg, p < 0.0001), exhibited higher ACR (36.3 ± 51.6 vs. 17.2 ± 1.2 mg g^?1, p < 0.0001) and c-f PWV (8.3 ± 1.5 vs. 7.8 ± 1.1 m s^?1, p = 0.003), independently of confounding factors. Multiple regression analyses revealed that age, male sex, 24-h systolic BP and sRAGE were the ‘independent correlates’ of ACR (R² = 0.493, p < 0.0001), while age, 24-h systolic BP and sRAGE were the ‘independent correlates’ of c-f PWV (R² = 0.428, p < 0.0001).ConclusionIn hypertensives, decreased sRAGE levels are accompanied by pronounced albuminuria and arterial stiffening. The association of sRAGE with ACR and c-f PWV suggests involvement of sRAGE in the progression of hypertensive vascular damage.     

Circadian rhythm of calcitonin gene-related peptide in uncomplicated essential hypertension.

OBJECTIVE: To assess the existence of an altered circulating pattern of calcitonin gene-related peptide (CGRP) in hypertension. DESIGN: The 24 h variation in plasma CGRP was measured and compared in 10 patients affected by uncomplicated essential hypertension and in nine age- and sex-matched healthy volunteers. The diurnal variations in blood pressure, atrial natriuretic peptide (ANP), plasma renin activity (PRA), plasma aldosterone and plasma cortisol were also assessed. METHODS: Recumbency studies were performed under standardized, drug-free conditions beginning at 0800 h. Venous samples were drawn every 4 h for 24 h and hormone levels were assessed with specific radioimmunoassays. The blood pressure was measured every 15 min with a SpaceLabs 90207 monitor. RESULTS: The mean 24-h plasma CGRP concentrations were significantly lower in the hypertensive group than in the control group. In both groups a circadian rhythm was present with the same pattern, but at a lower level in hypertension. A temporal sequence starting with the nocturnal rise in plasma CGRP concentrations and progressing with the elevations of ANP, PRA, and plasma aldosterone and cortisol was apparent in both groups. The nocturnal rise in the CGRP and ANP concentrations coincided with the blood pressure and the heart rate falls. CONCLUSIONS: Our data show that CGRP is lower than normal but maintains its circadian variability and its relationship with the diurnal variations in blood pressure and other hormones known to be active on the cardiovascular system.     

HDL steady state levels are not affected, but HDL apoA-I turnover is enhanced by Lifibrol in patients with hypercholesterolemia and mixed hyperlipidemia

Lifibrol (4-(4'-tert-butylphenyl)-1-(4'carboxyphenoxy)-2-butanol) is a new hypocholesterolemic drug effectively reducing total cholesterol, LDL cholesterol, and apolipoprotein (apo) B in experimental animals and in humans. In contrast to fibrates and HMG-CoA reductase inhibitors the cholesterol and triglyceride lowering effect of Lifibrol is not accompanied by increases in HDL cholesterol and apoA-I levels. We examined the impact of Lifibrol on the metabolism of HDL apoA-I in patients with hyperlipoproteinemia, using endogenous labeling with stable isotopes. Kinetic studies were performed in five male hypercholesterolemic individuals (type IIa), before and on treatment with 450 mg of Lifibrol daily for 4 weeks and in five male individuals suffering from mixed hyperlipidemia (type IIb), before and on therapy, for 12 weeks. Lifibrol reduced total cholesterol by 14% (P=0.02) and LDL cholesterol by 16% (P=0. 014) in all patients, and decreased triglycerides by 34% in type IIb patients. During Lifibrol therapy, HDL cholesterol and ApoA-I concentrations did not change. Tracer kinetics revealed that the fractional catabolic rate (FCR) of HDL apoA-I increased by 22% (P=0. 013). This increase in the apoA-I FCR was accompanied by a 23% increase in HDL apoA-I production rate (P=0.006). We conclude that Lifibrol, although not changing HDL steady state concentrations, enhances the turnover of apoA-I containing HDL particles.     

Carotid remodeling in essential hypertension: role of blood pressure, indexed parameters, and association with cardiac mass and aortic stiffness

The role of blood pressure on carotid remodeling, using no indexed and indexed parameters, was studied in essential hypertension. Carotid parameters were also compared to cardiac mass and aortic stiffness. Forty untreated hypertensive men had echocardiography, carotid ultrasonography and carotidfemoral pulse wave velocity measurements. Cross-sectional area index was associated essentially with the 24-hour systolic blood pressure whereas intima-media thickness was related especially to the 24-hour pulse pressure. Carotid intima-media thickness and cross-sectional area indexes were less related to blood pressure variables than non-indexed parameters. There is an independent association between 24-hour pulse pressure and left ventricular mass index and pulse wave velocity. To conclude, blood pressure, particularly pulse pressure, is associated with vascular and cardiac alterations. The indexation by the body surface area do not provide any additional information in the association between carotid and blood pressure parameters.