Assessment of arterial medial characteristics in human carotid arteries using integrated backscatter ultrasound and its histological implications

Recently, ultrasound tissue characterization of the carotid arteries with an integrated backscatter (IB) analysis was shown to identify a high-risk group of atherosclerosis. To clarify whether IB ultrasound is useful in assessing arterial sclerosis as well as stiffness beta and whether IB values reflect the histological structure, we measured IB values of common carotid media in 52 subjects without coronary risk factors and in 10 patients with systemic sclerosis (SSc) in the clinical studies and 12 patients in the histological studies with a Philips Medical Systems Sonos 5500. IB values were correlated with age (r=0.69, P<0.0001), intima-media thickness (r=0.72, P<0.0001) and stiffness beta (r=0.80, P<0.0001) in the control subjects. IB values and stiffness beta in the SSc group were greater than in an age- and sex-matched control group (IB values: 9.6+/-2.7dB versus 16.1+/-1.8dB; stiffness beta: 11.5+/-4.5 versus 20.6+/-5.6, P<0.01). IB values of the media were correlated with the elastic fragmentation index (r=0.63, P=0.029) and the collagen fiber index (r=0.59, P=0.046). Measurements of IB values of carotid media are useful for non-invasively evaluating arterial sclerosis.     

Different effects of pravastatin and cerivastatin on the media of the carotid arteries as assessed by integrated backscatter ultrasound.

BACKGROUND: Currently, there are various types of statins used in the treatment of hyperlipidemia and coronary artery disease. The purpose of this study was to compare the effects of a lipophilic statin (cerivastatin) with those of a hydrophilic statin (pravastatin) on the carotid arterial media using integrated backscatter (IB) ultrasound. Cerivastatin (C) has a strong anti-proliferative effect (APE) on smooth muscle cells (SMCs), whereas pravastatin (P) has a weak effect. METHODS AND RESULTS: The IB values in the media of 72 segments of carotid arteries were measured in 36 patients with hyperlipidemia before and after statin therapy or diet for 6 months (C, n=13: P, n=12: diet, n=11). In addition, IB values of 34 segments of carotid arteries were measured in 34 patients without coronary risk factors. Intima - media thickness (IMT) and arterial stiffness (stiffness beta) were measured by conventional echo at the same time. IB values did not significantly change in the P group (12.8+/-3.5 vs 12.7+/-2.7 dB), but decreased in the C group (12.1 +/-2.9 vs 10.0+/-2.7 dB, p<0.01). Also, stiffness beta did not significantly change in the P group (8.3+/-3.1 vs 7.6+/-2.5), but decreased in the C group (10.1+/-4.3 vs 7.9+/-3.3, p<0.05). IB values correlated with age (r=0.70, p<0.01) and stiffness beta (r=0.67, p<0.01) in the 34 patients without coronary risk factors. CONCLUSIONS: Statin therapy with cerivastatin, but not pravastatin, decreased the IB values of the carotid media and arterial stiffness. The difference between these 2 statins may be related to their effective dose range.     

Fluvastatin improves arterial stiffness in patients with coronary artery disease and hyperlipidemia: a 5-year follow-up study.

BACKGROUND: The present study was designed to test the hypothesis that fluvastatin might improve arterial stiffness, as assessed with pulse wave velocity (PWV), in patients with coronary artery disease (CAD) and hyperlipidemia over the long term. METHODS AND RESULTS: Ninety-three patients were randomly assigned to either fluvastatin (group A, n=50) or bezafibrate (group B, n=43) and followed for 5 years. There was no difference in the clinical findings between the 2 groups. In group A, there was a progressive reduction in the brachial-ankle PWV along with a decrease in serum low-density lipoprotein-cholesterol (LDL-C) and C-reactive protein (CRP) by 12 months after fluvastatin, and the improvement was maintained until 5 years after treatment. In group B, despite identical lowering of the serum lipid, PWV was progressively increased. In group A, the percentage change in PWV correlated significantly with that of the serum CRP (r=0.49, p<0.001), but not with that of the serum LDL-C after treatment. CONCLUSIONS: The beneficial vascular effects of fluvastatin persisted for a long period in patients with CAD and hyperlipidemia. Its anti-inflammatory action might contribute to the favorable effects on arterial stiffness.     

Increased arterial stiffness as the marker of vascular involvement in systemic sclerosis

OBJECTIVE: Endothelial dysfunction and vasculopathy of the small and large vessels are crucial pathogenic factors in systemic sclerosis (SSc). Accelerated atherosclerosis and impaired flow-mediated vasodilation have been described in SSc. We evaluated arterial stiffness in patients with SSc compared to healthy controls. METHODS: Augmentation index (AI) and pulse wave velocity (PWV) of the brachial artery were measured in 40 patients with SSc and 35 age and sex matched healthy controls using an arteriograph system. RESULTS: AI was significantly higher in SSc patients (9.02) compared to controls (-41.15) (p < 0.0001). PWV was similarly higher in patients with SSc (9.67 m/s) than in controls (8.00 m/s) (p = 0.0017). PWV was significantly higher in patients with localized SSc (10.04 +/- 2.01 m/s) compared to those with diffuse SSc (8.39 +/- 1.87 m/s) (p = 0.034). There was a significant, positive linear correlation between AI and PWV (r = 0.32, p = 0.045). We also observed significant correlations between AI and age (r = 0.31, p = 0.048), PWV and age (r = 0.36, p = 0.021), and PWV and disease duration (r = 0.40, p = 0.011) in SSc patients. CONCLUSION: Increased AI and PWV of the aorta in comparison to age and sex matched healthy controls indicate increased large-vessel stiffness in patients with SSc. PWV and AI are reproducible indicators of the presence and degree of arterial stiffening. Because arterial stiffness may correlate with disease duration and age in patients with SSc, it may be a useful diagnostic test in the assessment of arterial function. Increased vascular stiffness may be therapeutically targeted by statins and other vasoprotective agents during the management of SSc.     

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.     

Relationship between arterial stiffness and myocardial damage in patients with newly diagnosed essential hypertension

BackgroundArterial stiffness increases in hypertensive individuals. Arterial stiffness is associated with impairment of systolic and diastolic myocardial function in hypertension (HT). However, the relationship between arterial stiffness and serum heart-type fatty acid-binding protein (H-FABP) levels, a sensitive marker of myocardial damage, has not been previously examined in patients with HT. We investigate the relationship between serum H-FABP levels and arterial stiffness in patients with newly diagnosed HT.MethodsWe studied 46 (48.5 +/- 10.6, years) never-treated patients with HT and age-matched control group of 40 (47 +/- 8.6, years) normotensive individuals. H-FABP levels were determined in all subjects. We evaluated arterial stiffness and wave reflections of study population, using applanation tonometry (Sphygmocor). Carotid-femoral pulse wave velocity (PWV) was measured as indices of elastic-type, aortic stiffness. The heart rate-corrected augmentation index (AIx@75) was estimated as a marker of wave reflections.ResultsCarotid-femoral PWV (10.5 +/- 2.2 vs. 8.7 +/- 1.6, m/s, P = 0.0001) and AIx@75 (22.7 +/- 9.5 vs. 15 +/- 11, %, P = 0.001) were significantly higher in patients with HT than control group. H-FABP levels were increased in hypertensive patients compared with control group (21.1 +/- 14.8 vs. 12.9 +/- 8.5, ng/ml, P = 0.002). In multiple linear regression analysis, we found that the body mass index (beta = 0.42, P = 0.0001) and carotid-femoral PWV (beta = 0.23, P = 0.03) were significant determinants of H-FABP levels.ConclusionArterial stiffness is associated with serum H-FABP levels, a sensitive marker of myocardial damage, in patients with newly diagnosed HT.American Journal of Hypertension (2008). doi 10.1038/ajh.2008.235American Journal of Hypertension (2008); 21, 9, 989-993. doi 10.1038/ajh.2008.235.     

Peroxisome proliferator-activated receptor gamma agonist improves arterial stiffness in patients with type 2 diabetes mellitus and coronary artery disease

Arterial stiffness is an independent risk factor for cardiovascular events in diabetic patients, and it can be assessed by measuring pulse wave velocity (PWV). We investigated the degree of arterial stiffness in diabetic patients with coronary artery disease (CAD) and the effect of the proliferator-activated receptor gamma (PPAR-gamma) agonist rosiglitazone on arterial stiffness in the potential mechanism of anti-arteriosclerosis in patients with type 2 diabetes mellitus and CAD. The 123 participants were divided into 3 groups: healthy controls (n = 36), diabetic patients (n = 41), and diabetic patients with CAD (n = 46). Forty-six diabetic patients with CAD were randomly divided into 2 groups: untreated diabetic patients with CAD and diabetic patients with CAD treated with 4 mg/d of rosiglitazone (n = 25) for 12 weeks. Pulse wave velocity was measured before treatment and at 12-week follow-up. Baseline PWV was significantly higher in patients with diabetes, diabetes and CAD, and diabetes and CAD with treatment as compared with the healthy control group (1,633 +/- 37.3, 1,669 +/- 53.8, 1,615 +/- 44.4, and 1,360 +/- 39.9 cm/s, respectively, P < .001). Pulse wave velocity in the rosiglitazone-treated group was significantly reduced, from 1,615 +/- 44.4 to 1,525 +/- 43.1 cm/s, after 12-week treatment, Furthermore, PWV was significantly decreased in the rosiglitazone-treated group compared with untreated group after 12 weeks (1525 +/- 43.1 and 1,670 +/- 41.3 cm/s, respectively). Pulse wave velocity in the untreated group did not differ from baseline levels after 12 weeks. In addition, plasma C-reactive protein level was decreased significantly in the rosiglitazone-treated group compared with values at baseline and for the untreated group after 12 weeks (0.73 +/- 0.09, 1.71 +/- 0.24, and 1.33 +/- 0.29 mg/L, respectively). Plasma level of monocyte chemoattractant protein 1 was decreased in the rosiglitazone group compared with the level at baseline (392 +/- 42 and 273 +/- 40 pg/mL, respectively). Moreover, the decrease in PWV was associated linearly both with improved homeostasis model assessment of insulin resistance and with decreased C-reactive protein level after PPAR-gamma agonist treatment. In conclusion, PPAR-gamma agonist rosiglitazone treatment may significantly decrease arterial stiffness in diabetic patients with CAD. Proliferator-activated receptor gamma agonists may play an important role in protecting against arteriosclerosis by normalizing the metabolic disorders and depressing chronic inflammation of the vascular system in patients with type 2 diabetes mellitus and serious vascular disease.     

Impaired myocardial function in newly onset type 2 diabetes associates with arterial stiffness.

AIM: The aim of this study was to evaluate myocardial function using pulsed and color-coded tissue Doppler imaging (TDI) and vascular wall elasticity using whole-body impedance cardiography (ICG) in patients with newly diagnosed Type 2 diabetes mellitus (DM2), and to compare the measurements with those of healthy controls. METHODS: Systolic (SBP) and diastolic (DBP) blood pressure and glycosylated hemoglobin (HbA1c) were measured in 49 men (mean age 52.3+/-5.6 years, duration of DM2 1.8 years), and 15 healthy male control subjects (48.3+/-7.4 years). Mitral annular peak systolic (Svm), early (Evm), and late (Avm) diastolic velocities as well as myocardial peak systolic (Sv), early (Ev) and late diastolic (Av) velocity from middle segments of the anterior, inferior and lateral wall and the inferior septum were measured by TDI. ICG at rest was used to measure cardiac index (CI) and pulse wave velocity (PWV). RESULTS: The patients had higher body mass index (BMI 29.1+/-3.7 vs. 25.2+/-2.4 kg/m(2), p=0.000) and SBP (142+/-15 vs. 120+/-7 mmHg, p=0.005) than the controls, CI was comparable (2.8+/-0.5 vs. 2.8+/-0.6l/min/m(2)). The patients had lower age adjusted myocardial Sv (3.8+/-1.1 vs. 4.8+/-1.1cm/s, p=0.002) and Ev (4.6+/-1.6 vs. 6.2+/-1.7 cm/s, p=0.011), and also mitral annulus peak early diastolic velocity (Evm 7.8+/-1.9 vs. 10.4+/-2.6 cm/s, p=0.001). In diabetic patients PWV (14.2+/-2.7 vs. 10.0+/-1.7 m/s, p=0.002) was higher. Age (r=-0.39, p=0.001), BMI (r=-0.44, p=0.000) and PWV (r=-0.52, p=0.000) correlated significantly with Evm. PWV correlated with age (r=0.50, p=0.000), SBP (r=0.67, p=0.000), and HBA1c (r=0.36, p=0.010). In stepwise regression analysis, PWV (beta=-0.39, p=0.000) was the major determinant of Evm. CONCLUSION: Myocardial function is impaired in asymptomatic patients with newly detected DM2 consistent with diabetic heart muscle disease. Arterial stiffness is strongly related to myocardial dynamics, and both may have the same pathophysiologic background.     

Impact of pulmonary regurgitation and age at surgical repair on textural and functional right ventricular myocardial properties in patients with tetralogy of Fallot.

BACKGROUND: The aim of this study was to identify non-invasively the potential impact of pulmonary regurgitation and age at surgical repair on the right ventricular (RV) textural and functional myocardial properties in patients operated on for tetralogy of Fallot (TOF). METHODS: We assessed the average intensity (Int.(1B)) and the cyclic variation (CV(IB)) of the echocardiographic backscatter curve in 30 TOF patients (mean age 16.2 +/- 8.3 years), who had undergone corrective surgery (mean age at repair 3.2 +/- 2.6 years, range 0.2-11 years). They were divided into three age- and body surface area (BSA)-matched subgroups according to the results of the surgical repair: 12 patients had no significant postsurgical sequelae (group I), 12 patients had isolated moderate-severe pulmonary regurgitation (group II), and 6 patients had pulmonary regurgitation associated with significant (> 30 mmHg) RV outflow tract obstruction (group III). In addition, 30 age-, sex- and BSA-matched normal subjects were identified as the control group. RESULTS: In our study population, CV(IB) was lower (7.86 +/- 2.5 vs 10.6 +/- 1.4 dB, p < 0.001) and Int.IB higher (-18.6 +/- 4.1 vs -21 +/- 2.8 dB, p = 0.01) compared to the control group. Comparison between the control group and each subgroup of TOF patients showed: a) comparable values of CV(IB) and Int.(IB) in group I (10.6 +/- 1.4 vs 9.4 +/- 2.3 dB, p = 0.07; and -21 +/- 2.8 vs -21.4 +/- 2.3 dB, p = 0.7, respectively); b) Int.(IB) was significantly different only in group III (-21 +/- 2.8 vs -13.3 +/- 4.6 dB, p < 0.0001), c) CV(IB) was different either in group II or III (10.6 +/- 1.4 vs 7.42 +/- 2, p < 0.001; and 10.6 +/- 1.4 vs 5.56 +/- 1.8, p < 0.001, respectively). In addition, comparison of integrated backscatter indexes among the TOF subgroups revealed significant differences of CV(IB) between group I and II (9.4 +/- 2.4 vs 7.4 +/- 2, p = 0.03) and between group I and III (9.4 +/- 2.4 vs 5.56 +/- 1.8, p = 0.004), and of Int.(IB) between group I and III (-21.4 +/- 2.3 vs -13.3 +/- 4.66, p < 0.001) and between group II and III (-21.4 +/- 2.3 vs -18.6 +/- 2.8, p = 0.006). Group III patients, who had the most significant RV dilation, expressed as the ratio between RV and left ventricular end-diastolic diameter (0.55 +/- 0.8) compared to group II (0.67 +/- 0.11, p = 0.038) and group I (0.55 +/- 0.87, p < 0.001), showed the lowest values of CV(IB) (5.56 +/- 1.8 dB) and the highest values of Int.(IB) (-13.3 +/- 4.6 dB) Finally, in our study population, both the degree of RV dilation and the age at surgical repair significantly correlated with Int.(IB) (r = 0.49 and r = 0.4, p = 0.06 and p = 0.033, respectively) and inversely correlated with CV(IB) (r = -0.55 and r = -0.53, p = 0.002 and p = 0.003, respectively). CONCLUSIONS: In patients operated on for TOF: a) integrated backscatter analysis may identify patients with significant RV myocardial abnormalities related to postsurgical sequelae; b) residual pulmonary regurgitation, particularly if associated with pulmonary stenosis, appears to affect RV myocardial properties; c) an earlier repair of TOF may result in better preservation of myocardial characteristics.     

Migraine is associated with enhanced arterial stiffness.

Migraine is a common subtype of headache. Epidemiological studies have revealed that migraine could be an independent risk factor for ischemic stroke even in elderly subjects. Arterial stiffness is one of the major pathophysiological bases of stroke. In the present study, we cross-sectionally investigated the possible relationship between migraine and arterial stiffness in community-dwelling subjects. The study subjects were independently recruited from two sources (Group A, n=134, 68+/-5 years; Group B, n=138, 68+/-7 years). Augmentation index (AI), the ratio of augmented pressure by the reflection pressure wave to the pulse pressure, was obtained from the radial arterial waveform as an index of arterial stiffness. Brachial blood pressure was also measured simultaneously. Migraine was diagnosed using a previously validated questionnaire. The prevalence of migraine was 5.2% (Group A) and 16.7% (Group B). Subjects with migraine had higher radial AI in both Group A (migraine, 101+/-15%; other headache, 88+/-12%; no headache, 86+/-12%, p=0.003) and Group B (95+/-11%, 90+/-11%, 91+/-14%, p=0.058). Multiple linear regression analysis revealed that migraine was an independent determinant of AI (beta=0.154, p=0.002) after adjustment for other confounding factors: age (beta=-0.024, p=0.654); sex (beta=0.141, p=0.069); body height (beta=-0.215, p=0.005); systolic blood pressure (beta=0.174, p=0.001); medication for hypertension, hyperlipidemia, and diabetes mellitus (beta=-0.014, p=0.787); and heart rate (beta=-0.539, p<0.001). In a separate analysis by sex, migraine was also a significant determinant for AI (male, beta=0.246, p=0.019; female, beta=0.159, p=0.008). Migraine in the elderly could be a clinical manifestation of enhanced arterial stiffness.     

Assessment of arterial stiffness index as a clinical parameter for atherosclerotic coronary artery disease.

BACKGROUND: The aim of the present study was to assess the feasibility and usefulness of the arterial stiffness index (ASI) measured non-invasively by computerized oscillometry and by comparing it with the pulse wave velocity (PWV). METHODS AND RESULTS: The study group comprised 60 consutive patients who underwent coronary angiography and whose aorto-femoral PWV were obtained with a Judkins catheter. The ASI was obtained using Cardio Vision MS-2000 (IMDP, Las Vegas, NV, USA): (i) baseline (ASI-B); (ii) hyperemia induced by compression of the arm with cuff pressure for 5 min (ASI-H); and (iii) sublingual nitroglycerin (ASI-N). In total, 34 patients had significant coronary artery disease (CAD). The PWV and all ASI were higher in patients with CAD than in those without CAD (ASI-B, 85.9+/-57.8 vs 48.2+/-24.5, p=0.001; ASI-H, 98.1+/-49.8 vs 48.1+/-21.3, p<0.01; ASI-N, 66.7+/-55.7 vs 33.2+/-27.9, p=0.002). However, only ASI-B and ASI-H were positively correlated to the PWV (ASI-B, r=0.27, p=0.03; ASI-H, r=0.49, p=0.001; ASI-N, r=0.19, p=0.16). The ASI was increased after hyperemia in patients with CAD (ASI-H, 85.9+/-57.8 to 98.1+/-49.8, p=0.01), but not in patients without CAD (ASI-H, 48.2+/-24.5 to 48.1+/-21.3, p>0.01). After adjusting their age, only ASI-H was correlated to the presence of CAD (r=0.33, p<0.01). CONCLUSIONS: It is feasible and useful to use the ASI for detection of atherosclerotic coronary disease. The findings of ASI-H suggests that in addition to stiffening of the arterial wall itself, the impairment of flow mediated vasodilation, because of endothelial dysfunction, further increases the arterial stiffness.     

Volumetric quantitative analysis of tissue characteristics of coronary plaques after statin therapy using three-dimensional integrated backscatter intravascular ultrasound

OBJECTIVES: The purpose of the present study was twofold: 1) to evaluate the usefulness of three-dimensional (3D) integrated backscatter (IB) intravascular ultrasound (IVUS) for quantitative tissue characterization of coronary plaques; and 2) to use this imaging technique to determine if six months of statin therapy alters the tissue characteristics of coronary plaques. BACKGROUND: Three-dimensional IVUS techniques for quantitative tissue characterization of plaque composition have not been developed. METHODS: Radiofrequency (RF) signals were obtained using an IVUS system with a 40-MHz catheter. The IB values of the RF signal were calculated and color-coded. The 3D reconstruction of the color-coded map was performed by computer software. A total of 18 IB IVUS images were captured at an interval of 1 mm in each plaque. A total of 52 patients with hyperlipidemia were randomized to treatment with pravastatin (20 mg/day, n = 17), atorvastatin (20 mg/day, n = 18), or diet (n = 17) for six months. The tissue characteristics of arterial plaque in each patient (one arterial segment per patient) were analyzed with 3D IB IVUS before and after treatment. RESULTS: Significant increases of fibrous volume (pravastatin: 25.4 +/- 6.5% to 28.1 +/- 6.1%; atorvastatin: 26.2 +/- 5.7% to 30.1 +/- 5.5%) and mixed lesion volume (atorvastatin: 25.5 +/- 6.6% to 28.7 +/- 5.1%) and a reduction of lipid volume (pravastatin: 25.5 +/- 5.7% to 21.9 +/- 5.3%; atorvastatin: 26.5 +/- 5.2% to 19.9 +/- 5.5%) were observed after statin therapy. CONCLUSIONS: Statin therapy reduced the lipid component in patients with stable angina without reducing the degree of stenosis. Three-dimensional IB IVUS offers the potential for quantitative volumetric tissue characterization of coronary atherosclerosis.     

Pulse wave velocity in familial combined hyperlipidemia

BACKGROUND: In the present cross-sectional study we investigated whether familial combined hyperlipidemia (FCH) is associated with an increased arterial wall stiffness, and whether measures of arterial wall stiffness in FCH family members could contribute to cardiovascular risk stratification. METHODS: Ninety-eight subjects with FCH and 230 unaffected relatives filled out a questionnaire about their smoking habits, medical history, and medication use. Fasting venous blood was drawn after discontinuation of any lipid-lowering medication. Pulse wave velocity (PWV) and augmentation index (AIx) were determined by applanation tonometry as surrogate markers of arterial stiffness. RESULTS: Patients with FCH had a significantly increased PWV compared to their unaffected relatives (9.07 +/- 2.75 v 8.28 +/- 2.62 m/sec, P = .005), whereas AIx was not increased (21.6 +/- 12.7 v 15.6 +/- 14.1, P = .96). Age- and gender-adjusted PWV was an equally good predictor of the presence of cardiovascular disease (CVD) in FCH family members as the most predictive combination of age- and gender-adjusted clinical and biochemical risk factors, including total cholesterol, HDL-cholesterol, and systolic blood pressure (area under the receiver operating curve (ROC) [AUC] 0.83 [0.76-0.90] v AUC 0.84 [0.78-0.91], P = .83). Addition of PWV to the multivariable prognostic model, including these age- and gender-adjusted traditional risk factors, did not increase the predictive ability for CVD (AUC 0.84 [0.79-0.89]). CONCLUSIONS: Patients with FCH are characterized by an increased arterial stiffness. The PWV predicts the presence of CVD equally well as any combination of clinical and traditional biochemical risk factors, but PWV has no additional value in addition to traditional risk factor screening in FCH families.     

A1166C polymorphism of angiotensin II type 1 receptor, blood pressure and arterial stiffness in hypertension

OBJECTIVE: To study the association of the AC polymorphism of angiotensin II type 1 receptor gene (AGTR1) with blood pressure and central arterial stiffness in a population of hypertensive patients referred to hospital for further work-up. METHODS: One hundred and eighty-five patients, referred to our department from April 1998 to February 2002, were included. Blood pressure was measured by conventional and 24-h ambulatory methods, and arterial stiffness by carotid-femoral pulse wave velocity (PWV) determination. Genotyping for the AGTR1 AC polymorphism was performed by polymerase chain reaction. RESULTS: AGTR1 AC polymorphism was not associated with systolic or diastolic blood pressure, measured either by conventional (P=0.89 and P=0.67, respectively) or by 24-h ambulatory (P=0.57 and P=0.56, respectively) methods. Conversely, this polymorphism was significantly associated with PWV (P=0.006) and had a dose-allele effect, PWV increasing with the number of A alleles (10.6 +/- 2.4 m/s in CC, 11.9 +/- 2.5 m/s in AC and 12.7 +/- 2.7 m/s in AA patients, P=0.002). Multiple regression analysis showed that AC polymorphism was still independently associated with PWV (P=0.01) and was the third most important determinant of PWV after age (P <0.0001) and 24-h mean blood pressure (P <0.0001). CONCLUSION: In our study population, central arterial stiffness assessed by PWV was significantly and independently associated with the AC polymorphism, increased PWV being associated with the presence of the A allele. Further investigations are required for identification of the underlying mechanisms.     

Microalbuminuria and arterial stiffness in a general population: the Shimanami Health Promoting Program (J-SHIPP) study.

Microalbuminuria is an early marker of renal damage and has been shown to predict future cardiovascular mortality and morbidity in patients with diabetes or hypertension, as well as in subjects in the general population. In this study, we investigated the hypothesis that the presence of microalbuminuria reflects the advancement of arterial stiffness by using a study group of 136 community residents who had no cardiovascular diseases except for hypertension and who were not taking any medications. Urinary albumin concentration was determined by the standard method and corrected by creatinine. Microalbuminuria was defined as a urinary albumin/creatinine ratio of 2.0-30.0 mg/mmol creatinine. Arterial stiffness was evaluated by pulse wave velocity (PWV) determined at three points: from the heart to the carotid artery, to the brachial artery, and to the ankle. Carotid arterial pressure was determined using a tonometric sensor. Carotid ultrasonography was performed to measure carotid intima-media thickness (IMT) and carotid arterial internal dimension. Subjects with microalbuminuria had higher blood pressure and wider pulse pressure not only in the brachial artery but also in the carotid artery. Microalbuminuria was associated with significantly higher PWV compared with that of normoalbuminuric subjects at all sites studied (mean PWV: 821.2+/-137.4 cm/s vs. 933.8+/-137.5 cm/s, p<0.0001). Stepwise regression analysis revealed that the presence of mircroalbuminuria (p=0.047) was a significant independent predictor of PWV in addition to age, sex, and systolic blood pressure. These findings suggest that microalbuminuria is associated with advanced atherosclerosis in the general population. Underlying arterial stiffness may explain the high cardiovascular mortality in subjects with microalbuminuria. Hypertension may be the mechanism linking microalbuminuria and arterial stiffness in the general population.     

Arterial stiffness is related to augmented seasonal variation of blood pressure in hypertensive patients

BACKGROUND: Seasonal variation in blood pressure (BP), a usual tendency of both systolic (SBP) and diastolic BP (DBP) to rise during winter in hypertensive patients, may be related to the higher cardiovascular mortality in winter. However, it is not yet clear what factors are relevant to the seasonal BP changes. We hypothesized that arterial stiffness is related to the BP changes between summer and winter. METHODS AND RESULTS: Eighty-five elderly (>55 years) patients with essential hypertension (33 males, 64+/-6.0 years) were enrolled. Seasonal BP profiles over at least 2 years were studied along with arterial stiffness and clinical variables (age, gender, smoking, duration of hypertension, anti-hypertensive medications and body mass index). Both SBP and DBP were significantly higher during winter compared with three other seasons (spring 128+/-10.0/79+/-7.3 mmHg, summer 127+/-9.8/78+/-7.1 mmHg, autumn 127+/-10.3/78+/-8.0 mmHg, winter 136+/-12.5/81+/-7.6 mmHg; SBP changes; p<0.001, DBP changes; p<0.001). There were no significant seasonal differences among spring, summer and autumn. Pulse wave velocity (PWV), a widely used clinical indicator of arterial stiffness was correlated with winter-summer differences in SBP (r = 0.272, p = 0.012), but not in DBP (r = 0.188, p = 0.085). Age, which was correlated with PWV strongly (p<0.001), was not significantly related to the seasonal changes in BP (SBP changes; p = 0.114, DBP changes; p = 0.298). No other clinical variables had significant correlation with seasonal BP changes. Multivariate regression analysis revealed that PWV is the only significant predictor for winter-summer SBP changes. CONCLUSIONS: Our results established a feasible link between arterial stiffness and seasonal BP variation. These findings may partly explain higher cardiovascular risk in patients with increased arterial stiffness.     

Significant association of C-reactive protein with arterial stiffness in treated non-diabetic hypertensive patients

C-reactive protein (CRP) has been known to be associated with vascular inflammation and hypertension. Pulse wave velocity (PWV) increases according to the degree of the arterial stiffness in hypertension patients. Therefore, PWV may be correlated with CRP levels in treated hypertensive patients, irrespective of medication. We sought to determine whether there is a correlation between hsCRP and arterial stiffness in non-diabetic treated hypertensive patients, independent of cardiovascular risk factor. This study consisted of 424 non-diabetic patients at least 45-years-old who were being treated for hypertension. At the time of enrollment, the patients underwent a baseline laboratory assessment of C-reactive protein levels and pulse wave velocity (PWV). Heart to femoral PWV (hfPWV) and brachial to ankle PWV (baPWV) were used as a marker of arterial stiffness. Subjects were categorized according to tertiles of hsCRP level [Group 1: first tertile (0.20-0.46 mg/L), Group 2: second tertile (0.47-1.15 mg/L), Group 3: third tertile (1.17-9.71 mg/L)]. Group 1 consisted of 141 patients (mean age 58+/-8 years), Group 2 had 142 patients (mean age 60+/-9 years) and Group 3 had 141 patients (mean age 61+/-8 years). The hfPWV and baPWV increased significantly along with the hsCRP level. Group 1, Group 2 and Group 3 demonstrated hfPWV and baPWV of 965+/-199 and 1438+/-246, 975+/-174 and 1487+/-258 and 1043+/-215 and 1566+/-252 cm/s, respectively (p<0.01). The hfPWV also showed a strong correlation with baPWV (r=0.698, p<0.001). The hsCRP level was independently associated with arterial stiffness (hfPWV: R(2)=0.273, p<0.001; baPWV: R(2)=0.284, p=0.001) after controlling for age, body mass index, systolic blood pressure (BP), heart rate, gender, HDL-cholesterol, triglyceride, glucose level and medications. In conclusion, hsCRP was associated with arterial stiffness, independent of age, systolic BP, gender, heart rate, glucose, lipid profiles and medications in treated hypertension. Therefore, hsCRP could be a useful marker of arterial stiffness in treated hypertension patients and a possible target for arterial inflammation in hypertension.     

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.     

Arterial stiffness is related to insulin resistance in nondiabetic hypertensive older adults

Hypertension, diabetes, obesity, and aging are associated with increased arterial stiffness. Both insulin resistance and hyperglycemia may contribute to the development of arterial stiffness. Older nondiabetic hypertensive adults were recruited to test the following hypotheses: (1) insulin resistance is associated with arterial stiffness, and (2) this relationship is independent of glucose tolerance status. Aortic pulse wave velocity (PWV), pulse pressure (PP), insulin sensitivity index (S(I), measured by insulin-assisted frequently sampled iv glucose test), glucose tolerance status, and abdominal fat mass were assessed in 37 older (23 male, 14 female, mean age 69.4 +/- 5.9 yr), nondiabetic, hypertensive adults after a 4-wk antihypertensive medication withdrawal. Both PWV and PP were negatively correlated with S(I) (r = -0.49, P = 0.002, and r = -0.38, P = 0.02, respectively). The mean PWV and PP in those with normal glucose tolerance were not significantly different from those with impaired glucose tolerance (9.8 +/- 2.4 vs. 10.0 +/- 3.1 m/sec, P = 0.79 and 71 +/- 17 vs. 72 +/- 18 mm Hg, P = 0.80, respectively). In multiple regression analysis, PWV and PP remained independently correlated with S(I) (P < 0.05) after adjusting for age, gender, fasting glucose, glucose tolerance status, body mass index, or abdominal fat mass. These results suggest that in hypertensive, nondiabetic, older adults, insulin resistance is associated with arterial stiffness independent of glucose tolerance status.     

Do eicosapentaenoic acid supplements attenuate age-related increases in arterial stiffness in patients with dyslipidemia?: A preliminary study.

The present study was conducted to examine the effect of eicosapentaenoic acid supplements on pulse wave velocity (PWV) in patients with dyslipidemia as a prospective open-labeled study. Eicosapentaenoic acid supplements (1,800 mg/day) were prescribed to 40 patients, and diet therapy in consultation with a nutritionist was conducted in 44 patients as a control group. These interventions were continued for 12 months, and PWV and blood examinations were performed at the start and end of these interventions. PWV increased in the control group but not in the eicosapentaenoic acid group. After adjustment for age, gender, the initial PWV, and the changes in mean blood pressure during the study period, a general linear model univariate analysis post hoc comparison demonstrated that the change in PWV during the period of study was significantly larger in the control group (42 +/- 20 cm/s) than in the eicosapentaenoic acid group (-9 +/- 19 cm/s) (p<0.05). Thus, this preliminary study suggested that eicosapentaenoic acid supplements attenuate age-related increases in arterial stiffness in patients with dyslipidemia. A further study with a larger number of subjects is proposed to confirm this beneficial effect of eicosapentaenoic acid supplements on arterial stiffness.