Effect of atorvastatin on regional arterial stiffness in patients with type 2 diabetes mellitus

OBJECTIVE: A statin, a potent lipid-lowering drug, improves pain-free walking distance in patients with peripheral arterial disease (PAD) without increasing the ankle-brachial pressure index (ABI). Arterial stiffness affects the blood flow of peripheral arteries. The purpose of this study was to evaluate the effect of cholesterol-lowering with atorvastatin on regional arterial stiffness in patients with type 2 diabetes mellitus. METHODS: The subjects were 22 type 2 diabetic patients with hypercholesterolemia, who received atorvastatin at a daily dose of 10 mg for 6 months. Before and after the treatment with atorvastatin, we measured pulse wave velocity (PWV) in the heart-brachial, heart-carotid, heart-femoral and femoral-ankle segments. RESULTS: Following treatment with atorvastatin, femoral-ankle PWV showed a significant reduction. The PWV of other arterial segments tended to decrease, although the changes were not statistically significant. We found no significant changes in blood pressure, heart rate, ABI, or plasma concentrations of glucose, L-arginine and asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial function. CONCLUSIONS: Atorvastatin treatment was associated with an improvement in the stiffness of leg arteries in type 2 diabetes mellitus. This may partly explain the statin-mediated improvement of walking performance in those with PAD.     

Diabetes mellitus and renal failure: effects on large artery stiffness

Diabetes mellitus and end-stage renal disease are two pathologic entities associated with increased cardiovascular risk. Several studies have shown that arterial stiffness is increased in both cases and contributes to the increased risk. In order to determine the effect of diabetes and renal failure on arterial stiffness, we conducted a case-control study. One hundred and twenty-two diabetic patients were compared to 122 non-diabetic patients matched to the study group for sex, age, mean arterial pressure, number and localisation of the atherosclerotic alterations. Arterial stiffness was assessed by automatic measurement of the aortic pulse wave velocity (PWV) and by measuring the peripheral and carotid pulse pressure (PP) and reflected waves through analysis of the pulse wave using the principle of applanation tonometry. Aortic PWV was significantly higher in the diabetic subgroup as well as PP at the peripheral and central levels for the same age and mean arterial pressure. In addition, renal failure was independently associated with an increased aortic PWV but not PP in the general population. Independent of the degree of renal failure, a fall in the glomerular filtration rate was also associated with increased aortic PWV. No interaction was noted between renal failure and diabetes mellitus. In conclusion, this study shows that diabetic patients have higher arterial stiffness compared to non-diabetic ones having one or more cardiovascular risk factors, manifested by increased aortic PWV and PP. In addition, renal failure, irrespective of its degree and independent of diabetes mellitus, is associated with increased aortic PWV but not PP.     

Clustering of metabolic syndrome risk factors and arterial stiffness in young adults: the Northern Ireland Young Hearts Project

OBJECTIVES: This study aimed to investigate whether the clustering of the risk factors of the metabolic syndrome (MetS) is associated with stiffness of central and peripheral arterial segments; whether these associations are similar in men and women; and whether insulin resistance and low-grade inflammation mediate any such associations. BACKGROUND: Increased arterial stiffness may explain, at least in part, the increased cardiovascular and diabetes risk associated with the MetS. However, the mechanisms linking the MetS to an increased arterial stiffness are incompletely understood, and gender differences may exist. METHODS: Cross-sectional analyses of data on 313 young men and women (mean age 23 years) from the Northern Ireland Young Hearts Project. Subjects were categorized according to the number of traits of the MetS; in addition a continuous MetS score was calculated. Arterial stiffness was assessed by measuring pulse wave velocity (PWV) in three arterial segments using a non-invasive optical method. RESULTS: The prevalence of the MetS was similar for men (10.6%) and women (10.5%). After adjustment for potential confounders and other cardiovascular risk factors, PWV of the three arterial segments investigated increased with increasing traits of the MetS in women only. Women with the MetS, as compared to those without risk factors of the syndrome, had greater PWV of the aorto-iliac (+14.0%, P = 0.016), the aorto-radial (+13.2%, P = 0.010) and aorto-dorsalis pedis (+11.8%, P = 0.011) segments. A great deal (up to 75%) of the association between the MetS and aortic-iliac PWV was mediated by heart rate, inflammation markers [C-reactive protein (CRP) and fibrinogen] and insulin resistance [homeostatic model assessment-insulin resistance (HOMA-IR)], whereas these variables did not explain much of the association between the MetS and PWV of the peripheral segments. CONCLUSIONS: Young women with the MetS show increased stiffness of peripheral and central arteries, a mechanism that may explain their increased cardiovascular risk. Low-grade inflammation, insulin resistance and sympathetic activation explain much of the adverse impact of the MetS on central, but not peripheral, arterial stiffness.     

Determinants of arterial stiffness in an apparently healthy population over 60 years

Arterial stiffness assessed by the pulse wave velocity (PWV), a non-invasive and reproducible method, predicts cardiovascular morbidity and mortality. The main determinants of arterial stiffness are well established in younger and middle-aged populations, but much less in the elderly. The aim of this study was to describe the determinants of arterial stiffness in elderly apparently healthy subjects. The study included 221 voluntary subjects born before 1944 (mean age 67.4+/-5.0 years), who had a standard health check-up at the 'Centre de Médecine Préventive' of Nancy. Arterial stiffness was evaluated by measuring the carotid-femoral PWV with the PulsePen automatic device. Clinical and biological parameters were evaluated at the same day. Measurements were valid and analysed in 207 subjects (94 women). Mean PWV was 9.39+/-2.64 m/s. Men showed higher PWV values than women (9.99+/-2.56 vs 8.66+/-2.56, P<0.001). In univariate analysis, PWV was correlated with age (r=0.26, P<0.001) and mean arterial pressure (MAP) (r=0.40, P<0.001), and these relationships were similar in men and women. Subjects with hypertension (P<0.001), diabetes mellitus (P<0.001) and obesity (P<0.01) had higher values of PWV. In multiple regression analysis, PWV correlated positively and independently with age, male gender, MAP and diabetes mellitus. In conclusion, in an apparently healthy elderly population, the main determinants of arterial stiffness are the age, MAP, diabetes and gender. Our study also shows that the gender-related differences in arterial stiffness observed in middle-aged subjects are maintained in the elderly.     

Central pulse wave velocity is responsible for increased brachial-ankle pulse wave velocity in subclinical hypothyroidism

Objective Subclinical hypothyroidism affects 5–15% of the general population, and is associated with increased morbidity from cardiovascular disease. We recently reported a significant increase in brachial‐ankle pulse wave velocity (baPWV), a parameter of arterial stiffening and an independent predictor for the presence of cardiovascular disease, in subclinical hypothyroidism. The current study was performed to assess which arterial segment is responsible for enhanced baPWV in subclinical hypothyroidism. Patients and methods Central PWV (PWV in heart‐femoral segments), peripheral PWV (PWV in femoral‐ankle segments), and baPWV were measured in subclinical hypothyroid patients and normal subjects. Results Central PWV, baPWV, and peripheral PWV were significantly higher in subclinical hypothyroid patients than in normal subjects. BaPWV was significantly and positively correlated with central and peripheral PWV in both groups. However, a significant and positive correlation between central and peripheral PWV in normal subjects was not found in subclinical hypothyroid patients. Moreover, stepwise regression analysis showed that the association of central PWV with baPWV was stronger than that of peripheral PWV, whereas in normal subjects central PWV was not associated with baPWV. Conclusions Our results demonstrate that central and peripheral PWV are significantly higher in subclinical hypothyroid patients, and that the increase in baPWV depends more strongly on central PWV than on peripheral PWV in these patients. This suggests that increased elastic arterial stiffening of the aorta, rather than of peripheral muscular arteries, might be more responsible for increased general arterial stiffening in subclinical hypothyroid patients.     

Type 2 diabetes is associated with increased pulse wave velocity measured at different sites of the arterial system but not augmentation index in a Chinese population

Background:

Patients with type 2 diabetes have increased stiffness of central elastic arteries. However, whether peripheral muscular artery stiffness is equally affected by the disease remains sparsely examined. Moreover, the association between pulse wave velocity (PWV) and augmentation index (AIx) in diabetes is poorly understood.

Hypothesis:

Type 2 diabetes is associated with the alterations in arterial stiffness (PWV and AIx) in a community‐based population.

Methods:

A total of 79 Chinese patients with type 2 diabetes and 79 sex‐, age‐ (±3 years), and body mass index‐ (±2 kg/m²) matched healthy controls were studied. Carotid‐femoral pulse wave velocity (CF‐PWV), carotid‐radial pulse wave velocity (CR‐PWV), and carotid‐ankle pulse wave velocity (CA‐PWV) were calculated from tonometry waveforms and body surface measurements, whereas AIx was assessed using pulse wave analyses.

Results:

In univariate analysis, patients with type 2 diabetes showed increased CF‐PWV (P < 0.001), CR‐PWV (P = 0.012), and CA‐PWV (P = 0.016), and lower AIx (P = 0.017) than the control group. In multiple linear regression models adjusting for covariates, type 2 diabetes remained a significant determinant of CF‐PWV. Fasting glucose was associated with CR‐PWV but was not related to CA‐PWV or AIx.

Conclusions:

Our findings suggest that patients with type 2 diabetes have increased central and peripheral artery stiffness, but preserved AIx compared to controls. Diabetes was a predictor of central artery stiffness, and glucose was a determinant of peripheral artery stiffness. © 2011 Wiley Periodicals, Inc. This work was supported by a grant from the National Nature Science Foundation of China (30872713), Beijing Natural Science Foundation (7082083), and is a key project of the Capital Development Foundation (2009–2038) of Dr. Ping Ye. The authors have no other funding, financial relationships, or conflicts of interest to disclose. Dr. Zhang and Dr. Bai contributed equally to this work.     

High serum pentosidine concentrations are associated with increased arterial stiffness and thickness in patients with type 2 diabetes

Accumulation of advanced glycation end products in vessel walls may increase arterial stiffness and/or thickness, contributing to a high incidence of cardiovascular disease (CVD) in patients with diabetes. We investigated whether serum concentrations of pentosidine, a well-defined advanced glycation end product, are associated with arterial stiffness or thickness in patients with type 2 diabetes. Pentosidine was measured in sera from 98 patients with type 2 diabetes and 61 age-matched control subjects by a competitive enzyme-linked immunosorbent assay. Arterial stiffness was evaluated by heart-brachial and brachial-ankle pulse wave velocities (PWVs) measured using an automatic device. Arterial thickness was determined ultrasonographically as carotid intima-media wall thickness (IMT). Serum concentrations of pentosidine were significantly higher in patients with diabetes than in control subjects (64.4 +/- 21.0 vs 22.8 +/- 7.0 microg/L; P < .0001). In patients with diabetes, serum pentosidine correlated positively with heart-brachial PWV (r = 0.304; P < .01) but not with brachial-ankle PWV. Serum pentosidine also correlated positively with carotid IMT in patients with diabetes (r = 0.300; P < .01). Serum pentosidine concentrations were significantly higher in patients with diabetes with CVD than in those without (72.3 +/- 23.7 vs 62.3 +/- 19.8 microg/L; P = .0453). By multivariate analysis, only age (partial coefficient = 0.308; P < .05) and serum creatinine (partial coefficient = 0.328; P < .01) retained significant influence on serum pentosidine. After adjustment for renal function, carotid IMT still correlated positively with serum pentosidine (partial coefficient = 0.2736; P = .021). In conclusion, serum pentosidine was positively associated with both arterial stiffness and thickness and CVD in patients with type 2 diabetes.     

Arterial stiffness: Is it ready for prime time?

Recent interest in arterial stiffness as a possible new biomarker of cardiovascular (CV) disease has emerged. Arterial stiffness of the large, elastic conduit arteries is considered a risk marker of vascular aging; it leads to widened pulse pressure (PP) and the development of isolated systolic hypertension in the middle-aged and elderly population. However, increased PP is not always a good surrogate for arterial stiffening because of the frequent discrepancy between peripheral brachial and central aortic PP values caused by varying wave reflection activity. Therefore, noninvasive, easily performed methods for more direct measurement of arterial stiffness, such as pulse wave velocity (PWV) and pulse wave analysis (PWA) have been developed for clinical use. This article asks the question: How useful are PWV and PWA, when compared with traditional measurement of blood pressure components, as biomarkers of CV disease?     

Relationship between blood pressure parameters and pulse wave velocity in normotensive and hypertensive subjects: invasive study

Blood pressure (BP) is one of the most important contributing factors to pulse wave velocity (PWV), a classic measure of arterial stiffness. Although there have been many non-invasive studies to show the relation between arterial stiffness and BP, the results are controversial. The aim of this study is to evaluate the role of BP as an influencing factor on PWV using invasive method. We observed 174 normotensive and untreated hypertensive subjects using coronary angiography. Arterial stiffness was assessed through aorto-femoral PWV by foot-to-foot velocity method using fluid-filled system. And BP was measured by pressure wave at the right common femoral artery. From univariate analysis, age, diabetes mellitus (DM), hypertension, waist, waist-to-hip ratio, total cholesterol-to-high-density lipoprotein cholesterol ratio, systolic BP (SBP), pulse pressure (PP) and mean arterial pressure (MAP) showed significant association with PWV. To avoid multiple colinearity among SBP, PP and MAP, we performed multiple regression analysis predicting PWV thrice. Age, DM and each BP were significantly and consistently correlated to PWV. In the first and third modules, compared to age, SBP and MAP were less strong predictors, respectively. However, PP was the stronger predictor than age and DM in the second module. Lastly, we simultaneously forced MAP and PP with other variables in the fourth multivariate analysis. Age, DM and PP remained significantly correlated with PWV, but the significance of MAP was lost. This is the first invasive study to suggest that PP has the strongest correlation with PWV among a variety of BP parameters.     

Effects of coexisting hypertension and type II diabetes mellitus on arterial stiffness

Hypertension (HT) is frequently associated with diabetes mellitus (DM) and its prevalence doubles in diabetics compared to the general population. This high prevalence is associated with increased stiffness of large arteries, which often precedes macrovascular events. The aim of our study was to evaluate the influence of HT and type II DM on aortic stiffness in patients with one disease or the other compared to those with both HT and type II DM. We studied 220 patients, 50 with type II DM (Group A), 50 with HT (Group B), 85 with both diseases (Group C), and 35 healthy subjects (HS). Regional arterial stiffness was assessed by automatic measurement of the carotid-femoral pulse wave velocity (PWV). For each patient, we evaluated: age, sex, body mass index, smoking habit, heart rate, SBP/DBP, pulse pressure (PP), mean BP, fasting glucose, lipid profile, uric acid, and fibrinogen. Group C had significantly more women and non smokers and the highest PP (61+/-14 mmHg). Of biochemical parameters, only fibrinogen was higher in Group A and in Group C (P<0.01 and P<0.001, respectively). Group C had a significantly higher PWV than the other four groups (P<0.0001). Stepwise forward regression analysis showed that fasting glucose was the first independent determinant of PWV (P<0.0001). In conclusion, this study shows that patients with DM and HT have higher arterial stiffness compared to HS and those with one disease or the other. Fasting glucose is the major independent determinant of PWV, which may be used as a relevant tool to assess the influence of cardiovascular risk factors on arterial stiffness in high-risk patients.     

Relation between renal function within the normal range and central and peripheral arterial stiffness in hypertension

Chronic kidney disease is accompanied by increased large-artery stiffness, but the relation between glomerular filtration rate within the reference range and central or peripheral arterial stiffness has been understudied. The link between renal function and arterial stiffness was assessed in 305 patients with never-treated essential hypertension (men: 58%; age: 48+/-11 years, blood pressure: 151/95+/-20/11 mm Hg), free from overt cardiovascular disease and with serum creatinine values <1.4 mg/dL (men) and <1.2 mg/dL (women), who underwent noninvasive aortic and upper-limb pulse wave velocity (PWV) determination. Aortic PWV was strongly related to age (r=0.55; P<0.001), whereas upper-limb PWV had a weaker nonlinear relation with age (beta=1.392; P<0.001 for age; beta=-1.312; P<0.001 for age squared) and a weak relation with aortic PWV (r=0.22; P<0.001). Glomerular filtration rate (GFR), estimated according to the Mayo clinic equation for healthy subjects, was inversely correlated with large-artery stiffness, as assessed by aortic PWV (r=-0.34; P<0.001), and with peripheral artery stiffness, as assessed by upper-limb PWV (r=-0.25; P<0.001). In a multivariate linear regression, aortic PWV was independently predicted by age (beta=0.48; P<0.001), mean arterial pressure (beta=0.14; P=0.013), and GFR (beta=-0.13, P=0.029). Upper-limb PWV was predicted by GFR (beta=-0.24; P<0.001) and mean arterial pressure (beta=0.20; P<0.001). We conclude that, in hypertensive patients with normal renal function, an inverse relationship exists between GFR and stiffness of both central elastic and peripheral muscular arteries. These relations are in part independent from the effect of several confounders, including age, sex, and blood pressure values.     

Influence of age,risk factors,and cardiovascular and renal disease on arterial stiffness: clinical applications

Age is the main clinical determinant of large artery stiffness. Central arteries stiffen progressively with age, whereas peripheral muscular arteries change little with age. A number of clinical studies have analyzed the effects of age on aortic stiffness. Increase of central artery stiffness with age is responsible for earlier wave reflections and changes in pressure wave contours. The stiffening of aorta and other central arteries is a potential risk factor for increased cardiovascular morbidity and mortality. Arterial stiffening with aging is accompanied by an elevation in systolic blood pressure (BP) and pulse pressure (PP). Although arterial stiffening with age is a common situation, it has now been confirmed that older subjects with increased arterial stiffness and elevated PP have higher cardiovascular morbidity and mortality.

Increase in aortic stiffness with age occurs gradually and continuously, similarly for men and women. Cross-sectional studies have shown that aortic and carotid stiffness (evaluated by the pulse wave velocity) increase with age by approximately 10% to 15% during a period of 10 years. Women always have 5% to 10% lower stiffness than men of the same age.

Although large artery stiffness increases with age independently of the presence of cardiovascular risk factors or other associated conditions, the extent of this increase may depend on several environmental or genetic factors. Hypertension may increase arterial stiffness, especially in older subjects. Among other cardiovascular risk factors, diabetes type 1 and 2 accelerates arterial stiffness, whereas the role of dyslipidemia and tobacco smoking is unclear. Arterial stiffness is also present in several cardiovascular and renal diseases. Patients with heart failure, end stage renal disease, and those with atherosclerotic lesions often develop central artery stiffness. Decreased carotid distensibility, increased arterial thickness, and presence of calcifications and plaques often coexist in the same subject. However, relationships between these three alterations of the arterial wall remain to be explored.     

Arterial stiffness profiles: investigating various sections of the arterial tree of African and Caucasian people

In Africans, arterial stiffness progression seems more pronounced compared to Caucasians. We compared the arterial stiffness profiles of different age groups and focused on muscular arteries and two more central arterial segments in African and Caucasian people from South Africa. In African (N = 374) and Caucasian (N = 376) participants (20-70 years), we measured carotid-radial (C-R) and carotid-dorsalis pedis (C-DP) pulse wave velocity (PWV) and aortic characteristic impedance (Zao). Major findings were that normotensive and high-normal/hypertensive (HT) Caucasians indicated increased trends of C-R PWV with aging (P = .029 and P = .067), not seen in the African groups (P = .122 and P = .526). Both ethnic groups showed significant increases of C-DP PWV and Zao with aging. High-normal/hypertensive Africans had significantly stiffer arteries than hypertensive Caucasians for almost all age groups, and for all stiffness measures. African C-R PWV correlated significantly with blood pressure (BP), but not with age. Opposite results were observed for Caucasians. In conclusion, the stiffness of muscular arteries is already elevated in young Africans, in both those with normal or elevated BP. This is possibly due to an earlier deterioration during childhood, or perhaps already present from birth. Also, in Caucasians stiffness seems more age-related, while in Africans it seems to be more pressure-related.     

Brachial-ankle pulse wave velocity is useful for evaluation of complications in type 2 diabetic patients.

Pulse wave velocity (PWV) is useful for the evaluation of aortic stiffness. The brachial-ankle PWV (baPWV) and carotid PWV (from heart to carotid) were compared to study the relation of these two types of PWVs to diabetic complications in patients with type 2 diabetes mellitus. The baPWV was determined by oscillometrically measuring the pulse volume record at the upper arm and ankles. The carotid PWV was measured tonometrically. Ninety patients with type 2 diabetes mellitus were divided into tertile groups on the basis of baPWV or carotid PWV. The correlations of these variables with albuminuria, peripheral neuropathy, coefficient of variation of R-R intervals (CV R-R) on the electrocardiogram at rest, and retinopathy were examined by logistic regression analysis. After adjustment for age, systolic blood pressure, and duration of diabetes, logistic regression analysis showed that baPWV was directly related to the frequencies of albuminuria, decreased CV R-R, peripheral neuropathy, and retinopathy. In contrast, carotid PWV did not significantly correlate with any diabetic complications. We conclude that oscillometrically determined baPWV is related to the risk of diabetic microvascular disease in patients with type 2 diabetes mellitus and suggested to be useful for assessing risk factors of diabetic complications.     

Relationship between low serum endogenous androgen concentrations and arterial stiffness in men with type 2 diabetes mellitus

The aim of this study was to evaluate the relationship between arterial stiffness determined by pulse wave velocity (PWV) and serum endogenous androgen concentrations as well as major cardiovascular risk factors in men with type 2 diabetes mellitus. Serum free testosterone and dehydroepiandrosterone sulfate (DHEA-S) concentrations were measured in 268 men with type 2 diabetes mellitus. Relationships between PWV and serum endogenous androgen concentrations as well as major cardiovascular risk factors, including age, blood pressure, serum lipid concentration, glycemic control (hemoglobin A(1c)), body mass index, and degree of albuminuria, were evaluated. Positive correlations were found between PWV and age (r = 0.491, P < .0001), duration of diabetes (r = 0.320, P < .0001), systolic blood pressure (r = 0.292, P < .0001), and log (urinary albumin excretion) (r = 0.269, P < .0001). Inverse correlations were found between serum free testosterone concentration and PWV (r = -0.228, P = .0003) and between serum DHEA-S concentration and PWV (r = -0.252, P = .0002) in men with type 2 diabetes mellitus. Pulse wave velocity was significantly greater in patients with lower concentrations of free testosterone (<10 pg/mL) than in patients with higher concentrations of free testosterone (1864 +/- 359 vs 1736 +/- 327 cm/s; P = .0053). Pulse wave velocity also was significantly greater in patients with lower concentrations of DHEA-S (<1000 ng/mL) than in patients with higher concentrations of DHEA-S (1843 +/- 371 vs 1686 +/- 298 cm/s; P = .0008). Multiple regression analysis identified both serum free testosterone concentration (beta = -.151, P = .0150) and serum DHEA-S concentration (beta = -.200, P = .0017) as independent determinants of PWV. In conclusion, serum endogenous androgen concentrations are inversely associated with arterial stiffness determined by PWV in men with type 2 diabetes mellitus, which is true for men in general based on other works.     

Central and peripheral pulse wave velocities are associated with ankle-brachial pressure index

Background

Central Pulse Wave Velocity (PWV) is considered to be the gold standard measurement of arterial stiffness. In healthy subjects, cardiovascular risk factors such as age, hypertension, diabetes and end-stage renal disease are associated with increased central (Carotid-Femoral) and peripheral (Femoral-Ankle) PWV. However, little is known about PWV in patients with peripheral arterial disease and pathological Ankle-Brachial Index (ABI). The aim of this study was to study central and peripheral PWV in a population with various degree of peripheral arterial disease.

Methods

Central and peripheral PWV were measured in sixty-two hospitalized patients. Half were admitted for symptomatic peripheral vascular disease and the remainder for cardiac or carotid disease. The population was classified on basis of the Framingham-derived risk score for claudicants and on the ABI. For all patients, PWV was assessed on electrocardiogram-ultrasonographic images acquired at the four following sites: carotid, radial, femoral and tibial arteries.

Results

Carotid-Femoral PWV increased significantly with the Framingham-derived global risk score (p < 0.0001) but Femoral-Ankle PWV did not. With respect to the Ankle-Brachial Index, Carotid-Femoral and Femoral-Ankle PWV significantly increased (p = 0.05 and p = 0.02 respectively) with the severity of peripheral arterial scoring.

Conclusions

These results confirm that central PWV is the best indicator of general atherosclerosis, even in the presence of peripheral arterial disease. Both central and peripheral PWV can be considered as indicators of the severity of peripheral vascular disease.     

The T-allele of the C825T polymorphism is associated with higher arterial stiffness in young healthy males

Arterial stiffening is the major cause of increasing systolic blood pressure in arterial hypertension. Increased arterial stiffness is one major mechanism responsible for morbidity and mortality in hypertension. A C825T polymorphism was identified in the gene encoding the G-protein beta3 subunit (GNB3), and an association of the T-allele with hypertension was demonstrated in several studies. In order to identify a pathogenetic link between hypertension and arterial stiffness, we compared two indices of arterial stiffness, pulse wave velocity (PWV) and augmentation index, in young, healthy men with and without the 825T-allele under resting conditions. PWV was determined from pressure tracing over carotid and femoral arteries in 99 subjects (CC: n=43; CT&TT: n=56). Augmentation index was derived in 72 subjects (CC: n=30; CT&TT: n=42) by pulse wave analysis using radial applanation tonometry. Carriers of the 825T-allele exhibited a significantly higher PWV compared to subjects with the CC genotype (6.0+/-0.1 m/s (TC&TT) vs 5.7+/-0.1 m/s (CC); P=0.0251). There was also a significant difference (P = 0.0448) in augmentation index between carriers of the T-allele (CT&TT: 3.4+/-2.9%) and controls with the CC -genotype (-5.0+/-4.1 %). There was no difference in any other anthropometric (age, height, weight, body mass index) or haemodynamic (heart rate, peripheral and central blood pressure). In summary, the C825T polymorphism is associated with higher arterial stiffness in young, healthy males. Arterial stiffening may pathogenetically contribute to the development of hypertension in carriers of the T-allele.     

代谢综合征对老年糖尿病患者动脉僵硬度的影响

目的探讨老年糖尿病患者合并代谢综合征(MS)动脉僵硬度的变化及影响因素。方法选择老年糖尿病患者305例,根据是否合并MS分为MS组143例、非MS组162例;另选老年葡萄糖耐量试验正常者65例为对照组。检测颈-股脉搏波传导速度(PWV)、体重指数、腰围、血压、高敏C反应蛋白、血脂、空腹血糖、胰岛素及胰岛素抵抗指数,进行比较分析。结果 MS组和非MS组患者PWV明显高于对照组(P<0.05);随着MS组分增加,PWV呈阶梯样增加(P<0.05)。多元回归分析显示,PWV与年龄、血压、MS组分、高敏C反应蛋白、胰岛素抵抗指数及空腹血糖呈正相关(P<0.05)。结论老年糖尿病患者动脉僵硬度明显增加,合并MS加重动脉僵硬。     

Endothelial function is associated with pulse pressure, pulse wave velocity, and augmentation index in healthy humans

Arterial stiffness is an independent predictor of mortality and is regulated by a number of factors, including vascular smooth muscle tone. However, the relationship between endothelial function and definitive measures of arterial stiffness and wave reflections has not been described in healthy individuals. Therefore, we tested the hypothesis that endothelial function is inversely correlated with aortic pulse wave velocity (PWV), central pulse pressure, and augmentation index in healthy individuals. Peripheral and central pulse pressure and augmentation index were determined at rest, and global endothelial function was measured using pulse wave analysis and administration of sublingual nitroglycerin and inhaled albuterol. Aortic PWV was also determined at baseline in a subset of 89 subjects. In a separate group of subjects (n=89), aortic PWV was measured and brachial artery flow-mediated dilatation assessed as a measure of conduit artery endothelial function. Global endothelial function was significantly and inversely correlated with aortic PWV (r=-0.69; P<0.001), augmentation index (r=-0.59; P<0.001), and central (r=-0.34; P<0.001) and peripheral pulse pressure (r=-0.15; P=0.03). Moreover, there was a stronger correlation between central rather than peripheral pulse pressure. After adjusting for potential confounders, global endothelial function remained independently and inversely associated with aortic PWV and augmentation index. There was also a significant, inverse relationship between conduit artery endothelial function and aortic PWV (r=0.39, P<0.001), which remained independent after adjusting for confounding factors. In healthy individuals, a decline in endothelial function is associated with increased large artery stiffness, wave reflections, and central pulse pressure.     

Vascular dysfunction and autonomic neuropathy in Type 2 diabetes.

AIMS: To test the hypothesis that arterial dysfunction in Type 2 diabetes is related to autonomic neuropathy. METHODS: Arterial function and autonomic neuropathy were assessed over two consecutive days in 45 Type 2 diabetic and control subjects. Systemic arterial compliance (SAC), arterial stiffness (pulse-wave velocity, PWV) and carotid intima thickness (IMT) were assessed; these markers reflect early vascular disease and predict clinical vascular events. Autonomic neuropathy was assessed using heart rate variability with continuous ECG recording during various breathing and postural manoeuvres and an overall autonomic score was generated. Fasting metabolic parameters including glucose, insulin, HbA(1c) and lipid profile were measured. RESULTS: Autonomic neuropathy tests were all repeatable in diabetic subjects. Compared with controls, diabetic subjects had arterial dysfunction with increased PWV (P = 0.009), IMT (P < 0.001) and reduced SAC (P = 0.053). After adjustment for age, central PWV correlated with fasting insulin (r(2) = 0.45, P < 0.05) and autonomic score (r(2) = 0.44, P < 0.05), peripheral PWV correlated with autonomic score (r(2) = 0.51, P < 0.005) and IMT correlated with fasting insulin (r(2) = 0.5, P < 0.005). The presence of autonomic neuropathy correlated with fasting insulin (P = 0.015), but not age, duration diabetes, lipids or blood pressure. CONCLUSION: Using repeatable measures of autonomic neuropathy and vascular function in Type 2 diabetic subjects, we have demonstrated associations between autonomic neuropathy, vascular dysfunction and hyperinsulinaemia. This may help to explain the excess cardiovascular mortality seen in diabetic subjects with autonomic neuropathy.