Damage Of Large Arteries Research Articles

Clinicopathologic Associations in a Large International Cohort of Patients With Giant Cell Arteritis

In addition to aiding in diagnosis, histopathologic findings from temporal artery biopsy (TAB) specimens in giant cell arteritis (GCA) may be valuable for their associations with clinical features of the disease. This study was undertaken to compare histopathologic findings on TAB with biopsy interpretation and demographic, clinical, and imaging features at time of diagnosis. Patients with a clinical diagnosis of GCA who had a TAB were selected from an international, multicenter observational cohort of vasculitis. Associations between demographic, clinical, radiographic, and histopathologic features were identified using bivariate testing and multivariate regression modeling. Of 705 patients with GCA who underwent TAB, 69% had histopathologic evidence of definite vasculitis. Specific histopathologic findings included the presence of giant cells (51%), fragmentation of the internal elastic lamina (41%), intimal thickening (33%), and predominantly mononuclear leukocyte infiltration (32%). Histopathologic interpretation of definite vasculitis was independently associated with giant cells (odds ratio [OR] 151.8 [95% confidence interval (95% CI) 60.2-551.6]), predominantly mononuclear leukocyte infiltration (OR 11.8 [95% CI 5.9-24.9]), and fragmentation of the internal elastic lamina (OR 3.7 [95% CI 1.9-7.4]). A halo sign on temporal artery ultrasound and luminal damage of large arteries on angiography were significantly associated with presence of giant cells (OR 2.6 [95% CI 1.1-6.5] and OR 2.4 [95% CI 1.1-5.2], respectively). Specific histopathologic findings were associated with older age, but no associations were identified with vision loss or other clinical features. Histopathologic findings in GCA are strongly associated with the clinical diagnosis of GCA but have a limited role in identifying patterns of disease.

Low testosterone accelerates vascular damage in hypertensive smokers with more than a 20-pack-year smoking history

Abstract Purpose Testosterone deficiency and cigarette smoking are both associated with increased cardiovascular (CV) mortality risk. Aim of the study is to investigate the impact of low testosterone level on vascular function and structure changes related to cumulative tobacco smoke exposure in patients with arterial hypertension. Methods Indices of vascular function and structure including carotid-femoral pulse wave velocity (PWV) and carotid intima media thickness (cIMT) were measured in 263 hypertensive males divided into 4 age-matched groups according to pack-years of smoking as never smokers (0.0 pack-years), light smokers (0.1–20.0 pack-years), moderate smokers (20.1–40.0 pack-years), and heavy smokers (>40 pack-years). Plasma total testosterone (TT) levels were measured in all patients. Results PWV and cIMT progressively increased from never smokers and light smokers to moderate and heavy smokers (overall P<0.001 and P<0.01 respectively). The hypertensive males of each smoking group were further classified according to measured low or normal TT levels (low TT<3.5 ng/ml). Figure shows mean PWV and cIMT of the smoking/TT groups. Systolic and diastolic BP was higher in patients with TD compared to subjects with normal TT in moderate and severe heavy smokers (all P<0.05) and similar in light and never smokers. LDL-C levels were comparable between men with TD and normal TT across the four smoking groups. The difference in aortic PWV between TD and normal TT shows a progressive increase from light to moderate and heavy smokers. Similarly, the difference in cIMT between TD and normal TT is also positively correlated with cumulative tobacco exposure. All associations remained statistically significant even after adjustment for BP differences. Conclusions The deficiency in TT levels accelerates vascular wall damage of large arteries among hypertensive smokers with more than 20 pack-years tobacco exposure. Considering the predictive value of vascular biomarkers, the findings of this study imply the possibility that the measurement of baseline testosterone level could be an unfavourable marker of smoking-related cardiovascular risk among moderate and heavy smokers with arterial hypertension. Funding Acknowledgement Type of funding sources: None. TT, tobacco smoke exposure, PWV and IMT

WHITE COAT HYPERTENSION AND ARTERIAL STIFFNESS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Objective: Arterial damage of large arteries, addressed as carotid-femoral pulse wave velocity (c-f PWV), is recognized as independent predictor for future cardiovascular disease. The aim of this study was to investigate the impact of white coat hypertension on c-f PWV, in an untreated population. Design and method: PubMed and Cochrane Library were searched systematically to identify studies comparing c-f PWV levels between normotensives, hypertensives and white-coat hypertensives (WCH). Meta-analysis was performed to compare the difference c-f PWV levels between these groups. New Castle Ottawa quality assessment scale for case-control studies was used to assess study quality. Results: WCH patients had significantly increased c-f PWV values compared to the normotensive groups (d = 0.87 95% CI: 0.52 to 1.21, P < 0.01). Moreover, the hypertensive population was found to have statistically significant increased values of c-f PWV compared to WCH population (d = -0.74, 95% CI: -1.43 to -0.05, P < 0.01). Finally, there was no statistically significant difference between masked hypertension and WCH population (d = 0.06, 95% CI: -1.04 to 1.15, P < 0.001). Conclusions: WCH population have statistically significant increased values of c-f PWV compared to the normotensive group. These results demonstrate that WCH is not clinically innocent, in the untreated population.

Masked and white coat hypertension, the double trouble of large arteries: A systematic review and meta-analysis.

Arterial damage of large arteries, addressed as c-f PWV, is recognized as independent predictor for future cardiovascular disease. The aim of this study was to systematically investigate the association of the four hypertension phenotypes with carotid-femoral pulse wave velocity (c-f PWV), in untreated patients. PubMed and Cochrane Library were searched to identify studies comparing c-f PWV levels between normotensives, sustained hypertensives, white-coat hypertensives (WCH), and masked hypertensives (MH). Meta-analysis was performed to compare the difference c-f PWV levels between these groups. Newcastle-Ottawa quality assessment scale for cross-sectional studies was used to assess study quality. MH and WCH patients had significantly increased c-f PWV values compared to the normotensive groups (d=0.96m/s, 95% CI: 0.49-1.42; I2=85%, P<.01 for MH and d=0.85m/s, 95% CI: 0.48-1.22; I2=89%, for WCH). Moreover, the sustained hypertensive population was found to have significantly increased values of c-f PWV compared to MH (d=-0.70m/s, 95% CI: -0.87 to -0.54; I2=12%, P=.33) but not compared to WCH population (d=-0.75m/s, 95% CI: -1.52-0.02; I2 =96%,). Finally, there was no significant difference between MH and WCH population (d=0.06m/s, 95% CI: -1.04 to 1.15; I2 =96%,). MH and WCH population may have increased values of c-f PWV compared to the normotensive group. These results demonstrate that these phenotypes are not clinically innocent, in the untreated population.

Sickle Cell Anemia Mediates Carotid Artery Expansive Remodeling That Can Be Prevented by Inhibition of JNK (c-Jun N-Terminal Kinase).

Sickle cell anemia (SCA) causes chronic inflammation and multiorgan damage. Less understood are the arterial complications, most evident by increased strokes among children. Proteolytic mechanisms, biomechanical consequences, and pharmaceutical inhibitory strategies were studied in a mouse model to provide a platform for mechanistic and intervention studies of large artery damage due to sickle cell disease. Approach and Results: Townes humanized transgenic mouse model of SCA was used to test the hypothesis that elastic lamina and structural damage in carotid arteries increased with age and was accelerated in mice homozygous for SCA (sickle cell anemia homozygous genotype [SS]) due to inflammatory signaling pathways activating proteolytic enzymes. Elastic lamina fragmentation observed by 1 month in SS mice compared with heterozygous littermate controls (sickle cell trait heterozygous genotype [AS]). Positive immunostaining for cathepsin K, a powerful collagenase and elastase, confirmed accelerated proteolytic activity in SS carotids. Larger cross-sectional areas were quantified by magnetic resonance angiography and increased arterial compliance in SS carotids were also measured. Inhibiting JNK (c-jun N-terminal kinase) signaling with SP600125 significantly reduced cathepsin K expression, elastin fragmentation, and carotid artery perimeters in SS mice. By 5 months of age, continued medial thinning and collagen degradation was mitigated by treatment of SS mice with JNK inhibitor. Arterial remodeling due to SCA is mediated by JNK signaling, cathepsin proteolytic upregulation, and degradation of elastin and collagen. Demonstration in Townes mice establishes their utility for mechanistic studies of arterial vasculopathy, related complications, and therapeutic interventions for large artery damage due to SCA.

P6136Intense daily cigarette smoking accelerates vascular damage of smokers with a moderate cumulative tobacco smoke exposure

Abstract Purpose Coronary artery disease death has been associated with increased cigarette smoking intensity. Aim of the study is to investigate the impact of cigarette smoking intensity on vascular function and structure changes among male smokers with similar age at starting smoking and moderate cumulative tobacco smoke exposure. Methods Indices of vascular function and structure including carotid-femoral pulse wave velocity (PWV), brachial flow-mediated dilation (bFMD), carotid intima media thickness (cIMT) and microvascular damage (penile vasculature) were measured in 118 smokers consuming up to 1 pack (20 cigarettes)/day and 58 patients smoking &gt;1 pack (20 cigarettes)/day. The two groups had a similar mean cigarette smoking exposure (32 pack/years). Microvascular damage was examined by measuring penile peak systolic velocity (PSV) with a dynamic penile color Doppler ultrasonography after intracavernous injection of prostanglandin E1. Lower PSV values indicate severe penile vascular disease. Results The individuals smoking more than 1 pack/day were 10 years younger than smokers consuming up to 1 pack/day, however systolic, diastolic blood pressure, body-mass index, fasting blood glucose levels, lipid profile, C-reactive protein and total testosterone concentration were similar between the two groups. Figure shows mean bFMD, penile PSV, PWV and cIMT of the two groups. Interestingly, despite the similar cumulative smoking exposure between the two groups, the younger in age individuals with the intense cigarette smoking history had significantly lower mean bFMD and penile PSV (all P&lt;0.05) and similar PWV and cIMT compared to the mean values of older subjects smoking up to 1 pack/day. Smoking intensity and vascular changes Conclusions Intense daily smoking accelerates damage of large arteries and significantly impairs microvascular and systemic endothelial function. Considering the predictive value of vascular biomarkers, the findings of this study imply the possibility that baseline daily smoking intensity could be a better summary measure of smoking-related cardiovascular risk among young heavy smokers, relative to total pack-years of smoking.

Arterial damage and cognitive decline in chronic kidney disease patients.

In the general population aortic stiffening, assessed by carotid femoral pulse wave velocity (cf-PWV), is associated with cognitive dysfunction (CO/DY). Data in chronic kidney disease (CKD) are limited. This study tests the hypothesis that large artery stiffness and microvascular damage in CKD patients are related to the damage of brain microcirculation reflected by impaired cognitive function. A cross-sectional study enrolled 151 patients (mean age 58.4years; 64.5% males; 44 patients with CKD stage 1; 47 with stage 2; 25 with stage 3; and 35 with stage 4). Cognitive impairment, assessed by the Mini Mental State Examination (MMSE), the Clock - drawing test (Clock-test), and the Instrumental Activity of Daily Living (IADL), was considered as primary outcome. We measured systolic and pulse pressures at the brachial and aortic sites and cf-PWV. Our patients revealed a significant linear deterioration in all the domains of cognitive function according to CKD stages. High values of cf-PWV (P=0.029) and aortic pulse pressure (aPP) (P<0.026) were independent determinants of cognitive decline assessed by the MMSE. The present trial supports the hypothesis of an interaction between the kidney, large artery damage, central pressure pulsatility, and the injury of brain microcirculation. In clinical practice, cf-PWV and aPP measurements may help to predict cognitive decline. Whether the reduction in aortic stiffness following an aggressive treatment translates into improved cognitive outcomes remains to be determined.

PS 05-77 SEXAGENARIAN AS A TURNING POINT OF ARTERIAL STIFFNESS IN HYPERTENSIVE PATIENTS WITHOUT ANGINA PECTORIS

Objective: Large artery damage is an important contributory factor to cardiovascular morbidity and mortality of patients with hypertension. Arterial stiffness increases with age and hypertension. Pulse wave velocity (PWV) can be used as a measure of arterial stiffness. The purpose of this study was to investigate the turning point of arterial stiffness change in hypertensive patients without angina pectoris. Design and Method: One thousand three hundred eighteen patients with hypertension without cardiovascular complication or cerebral infarction were included. We analyzed echocardiographic data, PWV data, demographic information, and risk factors for cardiovascular disease, medical history, medication, and biochemical data. Patients with history of arrhythmia or significant valvular heart disease were excluded. Results: Among 1,318 hypertensive patients, 500 women (mean age; 55 ± 11 years old) and 818 men (mean age; 50 ± 12 years old) were included. PWV showed positive correlation with age (r = 0.324, p < 0.001), systolic blood pressure (r = 0.177, p < 0.001) and pulse pressure (r = 0.196, p < 0.001) in hypertensive men. PWV showed positive correlation with age (r = 0.453, p < 0.001), systolic blood pressure (r = 0.176, p = 0.003) and pulse pressure (r = 0.253, p < 0.001) in hypertensive women. PWV demonstrated positive correlation with systolic and diastolic blood pressure and pulse pressure after adjustment for age in both men and women. Sexagenarian showed significantly higher PWV compared with hypertensive persons in their fifties (1686.1 ± 316.0 cm/sec vs. 1546.3 ± 262.1 cm/sec, p = 0.015). Conclusions: Sexagenarian is a turning point of arterial stiffness in hypertensive patients without angina pectoris. We should pay attention to sexagenarian to prevent cardiovascular events in hypertensive patients.

PP.LB03.11] CAN ARTERIAL STIFFNESS PREDICT LARGE ARTERY DAMAGE IN SHORT TERM IN PATIENTS ON DIALYSIS?

Objective: To study a short term aortic pulse wave velocity measurement value for predicting cerebrovascular and cardiovascular events in patients on dialysis. Design and method: 26 stable dialysis patients (mean age 57.27 ± 13.97) without previous large artery damage were prospectively studied. Blood tests within 6 month were accomplished. All patients underwent two carotid-femoral pulse wave velocity measurements at the beginning of the study and after 6 months. Carotid-femoral PWV assessment was performed on the non dialysis day. We collected data about cerebrovascular and cardiovascular events during 6 month follow-up and according this divided patients into two groups (with and without events). Statistical analysis was performed using R Statistical Software. Results: During a 6 month follow-up, 2 non cardiovascular deaths, 7 cardiovascular events (atrial fibrillation, myocardial infarction) and 1 cerebrovascular (stroke) event were registered. Cerebrovascular and cardiovascular pathology was associated with an increase in beta2-microglobulin concentration (46.91 vs 33.51, 46.91, p = 0.0626) and in carotid-femoral PWV at the beginning of the study (11.4 vs 10.9, p = 0.6707) and during follow-up (12.55 vs 10.00, p = 0.0369). There was no difference between groups while comparing other laboratory parameters (albumin, cholesterol, parathyroid hormone concentration, CRP, hemoglobin concentration, calcium and phosphate level) and no correlation between carotid-femoral PWV and beta2-microglobulin values. Patients with carotid-femoral PWV >10 m/s had 2,6 higher event risk. Conclusions: Carotid-femoral PWV even in a short term follow-up helps indicate patients with higher cerebrovascular and cardiovascular risk.

Изменение показателей эндотелиальной функции и жесткости артериального русла у больных ревматоидным артритом на фоне терапии лефлуномидом

The article presents the results of evaluation of leflunomide impact on endothelial function and vascular stiffness parameters in patients with rheumatoid arthritis (RA), but without cardiovascular diseases. 46 patients with RA satisfying ACR (1987) or ACR/EULAR (2010) classification criteria were examined. Investigations of endothelial function and arterial stiffness, based on the pulse wave contour analysis and the reactive hyperemia test (“AngioScan-01” device used), were conducted before the treatment and 12 months thereafter. It was determined that patients with RA suffered from subclinical damage of large arteries, characterized by endothelial dysfunction at micro- and macrocirculatory levels, and the increase in augmentation (AIp), stiffness (SI), and reflection (RI) indices, whose value correlated with RA duration, DAS28 activity index, RF level, and ACCP concentration. Leflunomide use in patients with RA was accompanied by statistically significant decrease in DAS28 index. It was shown that along with high anti-inflammatory activity leflunomide is also able of decreasing the signs of subclinical arterial damage, which is confirmed by the restoration of the endothelial function both in the system of small resistant vessels (increase in amplitude occlusion index) and large muscular arteries (increase in the value of phase shift between channels), and the decrease in stiffness of large arteries.

Pulse wave velocity distribution in a cohort study: from arterial stiffness to early vascular aging.

By contrast with other southern European people, north Portuguese population registers an especially high prevalence of hypertension and stroke incidence. We designed a cohort study to identify individuals presenting accelerated and premature arterial aging in the Portuguese population. Pulse wave velocity (PWV) was measured in randomly sampled population dwellers aged 18-96 years from northern Portugal, and used as a marker of early vascular aging (EVA). Of the 3038 individuals enrolled, 2542 completed the evaluation. Mean PWV value for the entire population was 8.4 m/s (men: 8.6 m/s; women: 8.2 m/s; P < 0.02). The individuals were classified with EVA if their PWV was at least 97.5th percentile of z-score for mean PWV values adjusted for age (using normal European reference values as comparators). The overall prevalence of EVA was 12.5%; 26.1% of individuals below 30 years presented this feature and 40.2% of individuals in that same age strata were placed above the 90th percentile of PWV; and 18.7% of the population exhibited PWV values above 10 m/s, with male predominance (17.2% of men aged 40-49 years had PWV > 10 m/s). Logistic regression models indicated gender differences concerning the risk of developing large artery damage, with women having the same odds of PWV above 10 m/s 10 years later than men. The population PWV values were higher than expected in a low cardiovascular risk area (Portugal). High prevalence rates of EVA and noteworthy large artery damage in young ages were found.

The relationship between carotid blood pressure reactivity to mental stress and carotid intima-media thickness

BackgroundBrachial blood pressure (BP) reactivity to stress predicts large artery damage and future cardiovascular (CV) events. Central BP is an emerging risk factor associated with target organ damage (TOD). Currently, little is known about the central BP response to mental stress and its association to TOD. Methods and resultsTwenty-five healthy, non-obese adults completed a computerized mental stress test. Brachial and carotid systolic (S)BP reactivity to stress were calculated as SBP during stress minus resting SBP. Resting carotid intima-media thickness (IMT) was also measured. Carotid SBP reactivity to stress was significantly associated with carotid IMT, independent of age, sex, body mass index, non-high density lipoprotein cholesterol and brachial SBP reactivity to stress (r = 0.386, p < 0.05). ConclusionThe relationship between carotid SBP reactivity and carotid IMT suggests that the central BP response to stress may prove to be an early risk marker for potential subclinical TOD.

Association of self-reported race/ethnicity and genetic ancestry with arterial elasticity: the Multi-Ethnic Study of Atherosclerosis (MESA)

African Americans have a disproportionate burden of hypertension compared with white, whereas data on Hispanics is less well-defined. Mechanisms underlying these differences are unclear, but could be in part because of ancestral background and vascular function. We studied 660 African Americans and 635 Hispanics from the Multi-Ethnic Study of Atherosclerosis (MESA) with complete data on genetic ancestry, pulse pressure (PP), and large and small arterial elasticity (LAE, SAE). LAE and SAE were obtained using the HDI PulseWave CR-2000 Research CardioVascular Profiling Instrument. Among African Americans, higher European ancestry was marginally associated with higher LAE ( P = .05) and lower PP ( P = .05); results for LAE were attenuated after adjustment for potential mediators ( P = .30). Among Hispanics, higher Native American ancestry was associated with higher SAE ( P = .0006); higher African ancestry was marginally associated with lower SAE ( P = .07). Ancestry was not significantly associated with LAE or PP in Hispanics. Among African Americans, higher European ancestry may be associated with less large artery damage, as measured by LAE and PP, although these associations warrant further study. Among Hispanics, ancestry is strongly associated with SAE. Future studies should consider genetic ancestry when studying hypertension in race/ethnic minorities, particularly among Hispanics.

Arterial Stiffness and Stroke in Hypertension

Stroke is the second leading cause of mortality worldwide, and the leading cause of death in China and Japan. Its prevention represents a major goal. Identification of primary stroke risk, particularly through newly individualised risk factors including biomarkers of large artery damage such as arterial stiffening, is necessary for determining the appropriate level of intervention. The purpose of this review is to focus on the pathophysiology of arterial stiffness, its predictive value for stroke and the therapeutic implications of this risk factor for stroke prevention. The predictive value of arterial stiffness for stroke was demonstrated in a longitudinal study that included 1715 patients with essential hypertension and measurements of carotid-femoral pulse wave velocity (PWV) [an indicator of arterial stiffness] at entry. Over a mean follow-up period of 7.9 years, during which 25 fatal strokes occurred, PWV significantly predicted stroke (relative risk = 1.39 [(95% CI 1.08, 1.72]; p = 0.02 for each 4 m/sec increase) independently of classical cardiovascular risk factors, including age, cholesterol level, diabetes mellitus, smoking and mean blood pressure. Additional longitudinal studies are needed to confirm the predictive value of aortic stiffness on primary and secondary events, in low- and high-risk populations, in various countries, and using different methodologies of arterial stiffness measurement. Drug treatment could prevent stroke through a reduction in arterial stiffness in parallel with correction of cardiovascular risk factors such as hypertension, dyslipidaemia, diabetes mellitus and smoking, all of which are associated with arterial stiffening. In view of the important local actions of angiotensin II on arterial stiffening, drugs interfering with the renin-angiotensin-aldosterone system should be particularly effective. Promising therapeutic strategies to reduce arterial stiffness include taking advantage of the non-lipid-lowering effects of statins and directly targeting the molecular events leading to arterial stiffening, such as formation of advanced glycation end products.

Gefäßwandeigenschaften großer Arterien - Was ist wichtig für das klassische Hypertoniemanagement?

Decisions about the management of patients with hypertension should not be based on the level of blood pressure alone but also on the presence of target organ damage. Apart of classical sites of target organ damage - kidney and heart - the assessment of functional and structural alterations of large arteries is of increasing clinical importance. Modern non-invasive procedures allow the assessment of large artery wall properties within the clinical routine. Hypertension associated large artery damage may present as structural and functional alterations. Structural alterations comprise intima-media thickening, plaque formation, stenosis of the artery and formation of aneurysms. Functional alterations comprise endothelial dysfunction and alterations of the mechanical properties of the arterial wall with increasing stiffness and loss of the Windkessel function. Loss of central artery elastic properties will ensue an early reflection of the pulse wave with a resulting increase in central systolic and central diastolic pressure. This causes an increase in left ventricular afterload and a reduction in diastolic perfusion of the myocardium. In the last decade the relevance of large artery structural alterations, endothelial dysfunction and arterial stiffness for the risk of cardiovascular morbidity and mortality in hypertensive patients could be demonstrated convincingly. Measurement of intima-media-thickness therefore is part of the standard evaluation of hypertensive patients. Because of the equal prognostic relevance of functional properties of the arterial wall, assessment of large artery functional alterations is helpful for the risk stratification of hypertensive patients. Modern antihypertensive drugs have favourable effects on arterial wall properties. Therefore, the quantification of large artery wall properties should be part of the management of hypertensive patients.

ENDOTHELIAL CELL ACTIVATION IN MEN WITH ERECTILE DYSFUNCTION WITHOUT CARDIOVASCULAR RISK FACTORS AND OVERT VASCULAR DAMAGE

Endothelial cell activation (ECA) is an initiating event in atherosclerosis. Biochemical measures of ECA were evaluated in patients with erectile dysfunction (ED) associated or not associated with cardiovascular risk factors (VRFs) to assess whether ED is a sentinel of atherosclerosis. Circulating soluble P-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and endothelin-1 concentrations were assessed in 45 men with ED but no VRFs, 45 men with ED associated with VRFs and 25 healthy men. Ultrasound intima-media thickness of carotid arteries and pharmacologically stimulated peak systolic velocity of cavernous arteries were used to assess vascular damage. Measures of ECA were higher in men with ED but no VRFs than in controls (p <0.01) and all were comparable among groups of men with ED. Levels of endothelin-1 in men with ED and no VRFs versus healthy men of the same age resulted in the best independent predictor for ED after adjusting for the confounding effect of increased body mass index and smoking (OR 5.37, 95% CI 2.12 to 19.70). Intima-media thickness of carotid arteries was comparable in controls and in men with ED but no VRFs, and ruled out the bias of overt damage of large arteries in the latter. Peak systolic velocity of cavernous arteries excluded vasculogenic ED in the majority of patients with no VRFs. Increased biochemical measures of ECA were associated with ED independent of coexisting VRFs and overt vascular damage, suggesting that ED is a sentinel of early atherosclerosis.

Aortic pulse wave velocity as an independent marker of coronary artery disease

Background: Arterial stiffness has been known as a major contributory factor to cardiovascular (CV) morbidity and mortality in patients with hypertension. Pulse wave velocity (PWV), a surrogate measurement of large artery damage, has not been ascertained as an independent risk factor of coronary artery disease (CAD). The aim of this study was to assess whether PWV is associated with CV risk. Methods and results: We prospectively enrolled 326 consecutive patients undergoing coronary angiography for the assessment of suspected CAD. Arterial stiffness was assessed through aorto‐femoral PWV using fluid‐filled system. PWV was higher in patients with CAD than those without CAD (12.5 ± 5.1 vs 10.2 ± 3.1 m/s, p < 0.001). In multivariate logistic regression analysis, after entering for age, diabetes and other CV risk factors, PWV remained the significant independent variable for CAD (p = 0.050). When the severity of CAD was expressed as one‐, two‐ or three‐vessel disease, PWV was a significantly associated with the severity of CAD (p < 0.001). Conclusion: Our findings suggest that PWV is an independent risk marker for CAD, as well as strongly associated with the severity of CAD.

Impact of carotid intima-media thickening on risk stratification in elderly hypertensives.

It has been shown that aging and arterial hypertension are both associated with an increased prevalence of carotid structural abnormalities, such as intima-media (IM) thickening or plaques, which are a powerful independent predictor of cardiovascular (CV) events. We investigated the impact of carotid IM thickening in profiling the absolute CV risk stratification according the 1999 World Health Organization/International Society of Hypertension (WHO/ISH) guidelines in elderly hypertensive patients. Two hundred and thirty untreated elderly patients (>65 years) referred to our outpatient hospital clinic were included in the study. They underwent the following procedures: (i) medical history, physical examination and clinic blood pressure measurement; (ii) routine blood chemistry and urine analysis; (iii) electrocardiogram. The risk was initially stratified according to the routine procedures indicated by WHO/ISH guidelines and subsequently reassessed by adding the results of carotid ultrasonography (IM thickening as diffuse IM thickness >0.9 and <1.3 mm). According to routine classification 56% (=129) were medium-risk patients, 29% (n = 67) high-risk and 15% (n = 34) very-high-risk patients. The overall prevalence of carotid IM thickening was 54% (49% in medium-risk vs 60% in high or very high-risk patients, p < 0.05). A marked change in risk stratification was observed when IM thickening was taken in consideration: medium-risk patients decreased to 29% and high-risk rose to 56% (p < 0.01). Ultrasound assessment of large artery damage is extremely useful for a more accurate estimate of global CV risk in elderly hypertensives, because stratification based on diagnostic routine procedures can underestimate the overall risk in a large fraction of medium-risk subjects.

Prognostic significance of arterial stiffness measurements in end-stage renal disease patients.

As epidemiological and clinical studies have shown that damage of large arteries is a major contributory factor to the high cardiovascular morbidity of patients with end-stage renal disease, such a population is particularly appropriate for analysis the impact of arterial stiffness on cardiovascular risk assessment and reduction strategies. Aortic pulse wave velocity, a marker of aortic stiffness, has been shown to be a strong independent predictor of cardiovascular and all-cause mortality in patients with end-stage renal disease on hemodialysis. Local arterial stiffness assessment, namely carotid distensibility was also shown to predict cardiovascular risk, both in end-stage renal disease patients and in renal transplant recipients. Furthermore, it was shown in a therapeutic trial that the lack of aortic pulse wave velocity attenuation, despite significant drug-induced reduction in mean blood pressure, was a significant predictor of cardiovascular death in subjects with end-stage renal disease. These results support the hypothesis that measurement of aortic pulse wave velocity could help, not only in risk assessment strategies, but also in risk reduction strategies by monitoring arterial stiffness under different pharmacological regimens. The drug-related reduction of aortic pulse wave velocity could then give prognostic information, in addition to blood pressure reduction. Aortic stiffness measurements could serve as an important tool in identifying end-stage renal disease patients at higher risk of cardiovascular disease. The ability to identify these patients would lead to better risk stratification and earlier and more cost-effective preventive therapy.

Central pulse pressure and mortality in end-stage renal disease.

Damage of large arteries is a major factor in the high cardiovascular morbidity and mortality of patients with end-stage renal disease (ESRD). Increased aortic pulse wave velocity (PWV) and brachial pulse pressure (PP) are the principal arterial markers of cardiovascular mortality described in these patients. Whether central (carotid) PP and brachial-carotid PP amplification may predict all-cause (including cardiovascular) mortality has never been investigated. A cohort of 180 patients with ESRD who were undergoing hemodialysis was studied between January 1990 and March 2000. The mean duration of follow-up was 52+/-36 months (mean+/-SD). Mean age at entry was 51.5+/-16.3 years. Seventy deaths occurred, including both cardiovascular and noncardiovascular fatal events. At entry, patients underwent carotid PP measurements (pulse wave analysis), echocardiography, and aortic PWV (Doppler ultrasonography), together with standard clinical and biochemical analyses. On the basis of Cox analyses, after adjustment of age, time on dialysis before inclusion, and previous cardiovascular events, 3 factors emerged as predictors of all-cause mortality: carotid PP, brachial/carotid PP, and aortic PWV. Adjusted hazard ratios for 1-SD increments were 1.4 (1.1 to 1.8) for carotid PP, 0.5 (0.3 to 0.8) for brachial/carotid PP, and 1.3 (1.0 to 1.7) for PWV. Brachial blood pressure, including PP, had no predictive value for mortality after adjustment. These results provide the first direct evidence that in patients with ESRD, the carotid PP level and, mostly, the disappearance of PP amplification are strong independent predictors of all-cause (including cardiovascular) mortality.