Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients

Although various studies reported that pulse pressure, an indirect index of arterial stiffening, was an independent risk factor for mortality, a direct relationship between arterial stiffness and all-cause and cardiovascular mortality remained to be established in patients with essential hypertension. A cohort of 1980 essential hypertensive patients who attended the outpatient hypertension clinic of Broussais Hospital between 1980 and 1996 and who had a measurement of arterial stiffness was studied. At entry, aortic stiffness was assessed from the measurement of carotid-femoral pulse-wave velocity (PWV). A logistic regression model was used to estimate the relative risk of all-cause and cardiovascular deaths. Selection of classic risk factors for adjustment of PWV was based on their influence on mortality in this cohort in univariate analysis. Mean age at entry was 50+/-13 years (mean+/-SD). During an average follow-up of 112+/-53 months, 107 fatal events occurred. Among them, 46 were of cardiovascular origin. PWV was significantly associated with all-cause and cardiovascular mortality in a univariate model of logistic regression analysis (odds ratio for 5 m/s PWV was 2.14 [95% confidence interval, 1.71 to 2.67, P<0.0001] and 2.35 [95% confidence interval, 1.76 to 3.14, P<0.0001], respectively). In multivariate models of logistic regression analysis, PWV was significantly associated with all-cause and cardiovascular mortality, independent of previous cardiovascular diseases, age, and diabetes. By contrast, pulse pressure was not significantly and independently associated to mortality. This study provides the first direct evidence that aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in patients with essential hypertension.     

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.     

Brachial arterial stiffness predicts coronary atherosclerosis in patients at risk for cardiovascular diseases

Aortic pulse wave velocity (PWV) is a predictor of atherosclerosis. The percent mean pulse amplitude of the artery (%MPA) has been proposed as a novel marker of atherosclerosis. The present study evaluated the predictive value of PWV and the %MPA for coronary atherosclerosis. The severity of coronary atherosclerosis was evaluated using both the Gensini score and coronary calcium grade. Thirty-three patients with cardiovascular risk factors were assigned to those with significant coronary artery stenosis ((+)stenosis) group with the presence of > or = 75% coronary artery stenosis (n = 15; age: 68 +/- 7 years, mean +/- SD) or those without significant coronary artery stenosis ((-)stenosis) group (n = 18; age: 66 +/- 8 years). In each patient, the PWV and %MPA at the right brachial artery and both sides of the ankle were obtained using a non-invasive vascular screening device. The Gensini score and coronary calcium grade were higher in the +stenosis group than they were in the (-)stenosis group (P < 0.01 and P < 0.05, respectively). The brachial %MPA was lower in the (+)stenosis group than it was in the -stenosis group (P < 0.005). Both the Gensini score and the coronary calcium grade correlated with the brachial %MPA (r = 0.62, P = 0.0001 and P = 0.33, P = 0.030, respectively). Our observations suggest that brachial %MPA provides predictive values for coronary atherosclerosis in subjects at risk for cardiovascular disease.     

Assessment of vascular aging and atherosclerosis in hypertensive subjects: second derivative of photoplethysmogram versus pulse wave velocity

The pulse wave velocity (PWV) and the photoplethysmogram (PTG) are noninvasive methods for evaluating the pulse wave. The PWV has been associated with age and arterial hypertension, and an index of the second derivative of PTG (SDPTG) is correlated with age and other risk factors for atherosclerosis. The aim of this study was to compare SDPTG and PWV concerning the influencing factors of vascular compliance, including age and atherosclerosis, in a large hypertensive population. We studied consecutively 524 essential hypertensives, 140 with atherosclerotic alterations (AA), defined on the basis of clinical events including coronary heart disease, peripheral vascular disease, stroke, and abdominal aorta aneurysm. The PWV carotid-femoral was measured by a Complior device and the SDPTG was recorded by Fukuda FCP-3166. The augmentation index (AUI) of PTG was defined as the ratio of the late systolic peak to that of the early systolic peak in the pulse. The SDPTG consists of an a,b,c, and d wave in systole and an e wave in diastole; an SDPTG aging index (AI) was calculated as (b-c-d-e)/a. The patients with AA presented a higher PWV (14.9 +/- 4 m/sec v 12.4 +/- 2 m/sec, P < .001), PTG AUI (0.322 +/- 0.16 v 0.252 +/-0.09, P < .001), and SDPTG AI (-0.093 +/- 0.03 v -0.271 +/- 0.018, P < .001). However, in patients 60 years of age, only PWV remained higher in those with AA, whereas in patients >60 yr, both PWV and SDPTG AI remained higher in those with AA. The PWV was independently influenced by age, systolic blood pressure, glucose, AA, and plasma creatinine, whereas the PTG AUI was influenced by age and systolic pressure and the SDPTG AI by age and AA. In a logistic regression model for the presence of AA, including age, plasma creatinine, smoking, and diastolic BP, PWV was a significant independent determinant of AA, whereas SDPTG-AI weakly entered into the model. This study provides evidence that the aortic PWV reflects better than the SDPTG the modifications of the arterial compliance related to age, blood pressure, and atherosclerosis. However, the SDPTG AI may be useful for evaluation of vascular aging in hypertensives.     

Aortic Stiffening Does Not Predict Coronary and Extracoronary Atherosclerosis in Asymptomatic Men at Risk for Cardiovascular Disease

Stiffness of aortic walls has been shown to be a marker of coronary and cerebrovascular diseases in patients with myocardial infarction or stroke. However, its value for predicting preclinical atherosclerosis has not been demonstrated. Therefore, this study tested the association of aortic wall stiffness and coronary and extracoronary atherosclerosis in the absence of clinical cardiovascular disease.In 190 asymptomatic men at cardiovascular risk, carotid-to-femoral pulse wave velocity (PWV) was measured mecanographically and the compliance of the aorta (C), as well as the intrinsic compliance (C_i), was deduced after correction for the effect of blood pressure. Also determined noninvasively were 1) the degree of coronary calcium deposit coded as grade 0, 1, 2, or 3 using ultrafast computed tomography; 2) the extent of extracoronary plaque detected by B-mode echography at three different sites (carotid, abdominal aorta, and femoral) coded as 0, 1, 2, or 3 diseased sites; and 3) the estimated Framingham coronary risk. The grade of coronary calcium was not associated with any aortic elastic parameter. The number of extracoronary diseased sites was not associated with PWV and C but correlated negatively with C_i before but not after age adjustment. The coronary risk correlated positively with PWV and negatively with C before but not after age adjustment and was not associated with C_i.In symptom-free subjects aortic stiffening does not predict the presence of coronary and extracoronary atheroma and therefore cannot be considered as a useful surrogate marker of early atherosclerosis.     

Prognostic application of arterial stiffness: task forces

Epidemiologic and clinical studies have shown that increased pulse pressure is an independent cardiovascular risk factor in general population. Pulse pressure is determined by combined effects of cardiac factors (stroke volume) and the arterial stiffness. Arterial stiffness can be more directly evaluated by several measurements including the measure of pulse wave velocity (PWV). Aortic PWV, 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 (ESRD) on hemodialysis as well as in patients with essential hypertension and older subjects over 80 years. Local arterial stiffness assessment, namely carotid distensibility was also shown to predict cardiovascular risk, both in ESRD patients and in renal transplant recipients. Furthermore, it has been shown in a therapeutic trial that the lack of aortic PWV attenuation despite significant drug-induced reduction in mean blood pressure was a significant predictor of cardiovascular death in subjects with ESRD. These results support the hypothesis that measurement of aortic PWV could then help, not only in risk assessment strategies, but also in risk reduction strategies by monitoring arterial stiffness under different pharmacologic regimens. The drug-related reduction of aortic PWV could then give prognostic information, additionally to blood pressure reduction. Aortic stiffness measurements could serve as an important tool in identifying ESRD 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.     

Gender influence on metabolic syndrome's effects on arterial stiffness and pressure wave reflections in treated hypertensive subjects

BACKGROUND: In hypertensive subjects, aortic stiffness, an independent predictor of cardiovascular (CV) risk, measured from pulse wave velocity (PWV), contributes to enhance augmentation index (AI), a marker of the timing and amplitude of wave reflections. Whether PWV and AI are correlated and reflect CV risk in hypertensive men and women with metabolic syndrome (MS) remains unknown. METHODS: In a cohort of 613 (364 males) treated hypertensive subjects with and without MS (41% MS) pulse wave analysis was used to determine aortic PWV and carotid AI. CV risk was estimated from standard Framingham equations. RESULTS: In females, but not in males, aortic PWV was higher in subjects with MS, when compared with those without MS (12.7+/-0.3m/s versus 11.1+/-0.4m/s, p<0.001). This result was independent of age and blood pressure. Only in females AI was independently related to the presence of MS; AI did not differ between subjects with or without MS, both males and females. AI did not correlate with PWV, except in males without MS. The overall CV risk was strongly associated to PWV independently of MS and gender, but AI was associated to CV risk only in males. CONCLUSION: In treated hypertensive subjects, the effect of MS on PWV and AI is modulated by gender. The dissociation between PWV and AI observed in women with MS was due to "blunted" wave reflections. This finding is associated with the fact that PWV, but not AI, was a constant marker of CV risk in subjects with MS, whether men and women.     

Matrix metalloproteinase-9 polymorphism contributes to blood pressure and arterial stiffness in essential hypertension

Arterial stiffness is an independent predictor of cardiovascular events in a hypertensive population. Serum levels of matrix metalloproteinase (MMP)-9 are associated with arterial stiffness and predict cardiovascular risk. We investigated the role of MMP-9 polymorphism -1562C>T on blood pressure (BP) and arterial stiffness in a newly diagnosed hypertensive population. Untreated hypertensive patients (n=215, mean age 46+/-13 years) were studied. Supine BP, carotid-femoral pulse wave velocity (PWV) and augmentation index were assessed. Serum biochemistry and plasma MMP-9 concentrations were measured and genotyping performed following extraction of genomic DNA. BP, aortic PWV and serum MMP-9 levels were significantly higher in T-allele carriers of the -1562C>T polymorphism with a significant gene-dose effect (P<0.0001). In a stepwise regression model adjusting for known or likely determinants, the 1562C>T polymorphism emerged as an independent predictor of systolic BP (R(2)=0.25, P<0.0001), diastolic BP (R(2)=0.16, P<0.0001) and PWV (R(2)=0.47,P<0.0001). This is the first study to show the effect of MMP-9 polymorphism on BP and aortic stiffness in a hypertensive population. These results suggest that hypertensive patients carrying the T allele may be at increased risk of cardiovascular events.     

Stiffness of capacitive and conduit arteries: prognostic significance for end-stage renal disease patients

The aorta is the principal capacitive element of the arterial tree and its increased stiffness, determined by measurement of aortic pulse wave velocity (PWV), is a strong independent predictor of cardiovascular mortality in the general population and end-stage renal disease (ESRD) patients. Whether stiffness of ESRD patients' peripheral arteries has the same prognostic value has never been investigated. A cohort of 305 ESRD patients was followed for 70+/-49 months (mean+/-SD). Ninety-six deaths of cardiovascular origin occurred. At entry into the study, together with standard clinical and biochemical analyses, patients' aortic, brachial artery, and femorotibial PWV were determined. Based on Kaplan-Meier survival curve analyses and Cox proportional hazards analyses, adjusted for age, pulse pressure, and clinical data, aortic PWV was a significant and independent predictor of outcome. Neither brachial artery nor femotibial artery stiffness was able to predict cardiovascular outcome. Receiver operating characteristic curve analysis of aortic PWV indicated the cutoff value of 10.75 m/s, with 84% sensitivity, 73% specificity, 87% negative predictive value, and 72% positive predictive value. These results provide evidence that, in ESRD, increased stiffness of capacitive arteries, like the aorta, is an independent strong predictor of cardiovascular mortality, whereas stiffness of peripheral conduit arteries had no prognostic value.     

Aortic pulse wave velocity as a marker of cardiovascular disease in subjects over 70 years old

BACKGROUND: Aortic pulse wave velocity (PWV) is a significant and independent predictor of cardiovascular diseases (CVD) in hypertensive subjects and in patients with end-stage renal disease, but its contribution to cardiovascular risk in subjects between 70 and 100 years old has never been tested. PATIENTS: A cohort of 124 subjects (mean age: 87 +/- 7 years) was studied in two geriatric departments in a Paris suburb. Together with sphygmomanometric blood pressure measurements, aortic PWV was measured using a validated automatic device. RESULTS: Blood pressure, heart rate and body mass index, but not age, explained 48% of the PWV variability in this cohort. Furthermore, PWV was the major factor predicting the presence of CVD. The adjusted odds ratio was 17.44 (95% confidence intervals: 2.52-120.55). Antihypertensive drug therapy and low plasma albumin level had only an additive role. Blood pressure, particularly pulse pressure, had no predictive value. CONCLUSION: In 70-100-year-old subjects, aortic PWV is a strong independent marker of CVD, a finding that remains to be to confirmed by long-term longitudinal studies.     

Functional and structural markers of atherosclerosis in human immunodeficiency virus-infected patients.

OBJECTIVES: We investigated functional and structural markers of atherosclerosis in human immunodeficiency virus (HIV)-infected patients in relation to the presence of the metabolic syndrome (MS). BACKGROUND: Antiretroviral combination therapy in HIV has been associated with cardiovascular risk factors that cluster in the MS. METHODS: Thirty-seven HIV-infected patients underwent assessment of flow-mediated vasodilation (FMD), aortic pulse-wave velocity (PWV), and carotid intima-media thickness (IMT). Age-matched type 2 diabetic patients (n = 13) and healthy controls (n = 14) served as reference groups. RESULTS: Fifteen HIV-infected patients (41%) fulfilled the National Cholesterol Education Program criteria of the MS. The FMD was similarly impaired in HIV-infected patients without the MS (MS- group) and the diabetic patients (5.1 +/- 0.4% and 4.9 +/- 0.6%, respectively) compared with controls (8.8 +/- 0.7%). The HIV-infected patients with the MS (MS+ group) had even more impaired FMD (2.5 +/- 0.3%). Carotid IMT was similarly increased in the MS+ group and the diabetic patients compared with the other groups. Aortic PWV was increased in the diabetic patients only. In HIV-infected patients, FMD was related to metabolic parameters, whereas aortic PWV and IMT were related to parameters of HIV infection, time on antiretroviral combination therapy, inflammatory (C-reactive protein and leukocytes) and metabolic parameters. CONCLUSIONS: The data of the present study suggest an increased cardiovascular risk in HIV-infected patients, even in the absence of clustering of metabolic risk variables. The presence of the MS in HIV is associated with even more advanced atherosclerotic changes. Presumably, both HIV infection and antiretroviral therapy may promote atherosclerosis through mechanisms involving endothelial cells, either directly or indirectly via metabolic risk factors.     

Arterial stiffness and osteoporosis in chronic obstructive pulmonary disease

RATIONALE: Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of cardiovascular events and osteoporosis. Increased arterial stiffness is an independent predictor of cardiovascular disease. OBJECTIVES: We tested the hypothesis that patients with COPD would have increased arterial stiffness, which would be associated with osteoporosis and systemic inflammation. METHODS: We studied 75 clinically stable patients with a range of severity of airway obstruction and 42 healthy smoker or ex-smoker control subjects, free of cardiovascular disease. All subjects underwent spirometry, measurement of aortic pulse wave velocity (PWV) and augmentation index, dual-energy X-ray absorptiometry, and blood sampling for inflammatory mediators. MEASUREMENTS AND MAIN RESULTS: Mean (SD) aortic PWV was greater in patients, 11.4 (2.7) m/s, than in control subjects, 8.95 (1.7) m/s, p < 0.0001. Inflammatory mediators and augmentation index were also greater in patients. Patients with osteoporosis at the hip had a greater aortic PWV, 13.1 (1.8) m/s, than those without, 11.2 (2.7) m/s, p < 0.05. In patients, aortic PWV was related to age (r = 0.63, p < 0.0001) and log(10) IL-6 (r = 0.31, p < 0.01), and inversely to FEV(1) (r = -0.34, p < 0.01). The strongest predictors of aortic PWV in all subjects were age (p < 0.0001), percent predicted FEV(1) (p < 0.05), mean arterial pressure (p < 0.05), and log(10) IL-6 (p < 0.05). CONCLUSIONS: Increased arterial stiffness was related to the severity of airflow obstruction and may be a factor in the excess risk for cardiovascular disease in COPD. The increased aortic PWV in patients with osteoporosis and the association with systemic inflammation suggest that age-related bone and vascular changes occur prematurely in COPD.     

Plasma adrenomedullin is closely correlated with pulse wave velocity in middle-aged and elderly patients.

Arterial stiffness as measured by pulse wave velocity (PWV) is a major predictor of cardiovascular disease. Adrenomedullin (AM), a hypotensive peptide, works as a compensatory factor for arterial sclerosis. The aim of this study was to investigate the relationship between PWV and the plasma concentration of AM in risk-loading patients. One hundred and twenty-six inpatients aged 30 to 75 years with or without varying degrees of atherosclerosis were investigated. Patients with heart and/or renal failure were excluded. The PWV was measured using an automatic waveform analyzer, and the plasma AM level was measured using a newly developed, hypersensitive immunoenzymometric assay system. The PWV increased with the increasing number of cardiovascular risk factors and organ damage in the patients. A positive correlation between the PWV and AM level was observed (r=0.375, p<0.0001, n=126). Seventy-four patients were receiving antihypertensive medications; medication did not affect the correlation. Multivariate regression analysis revealed that the PWV was significantly and independently associated with age, systolic blood pressure, and AM level. These results indicate that the plasma AM concentration could serve as a marker of advanced arterial sclerosis as estimated by increased PWV.     

Sex differences in age-related stiffening of the aorta in subjects with type 2 diabetes

Hypertension and type 2 diabetes are associated with increased aortic pulse wave velocity (PWV), a measure of aortic stiffness and a powerful risk factor for cardiovascular events. The association of hypertension with type 2 diabetes may obscure the degree to which diabetes rather than hypertension contributes to an elevated PWV. The objective of this study was to determine whether the presence of type 2 diabetes is associated with an elevated PWV compared with nondiabetic subjects matched for mean arterial blood pressure. PWV was determined by measuring carotid to femoral transit time using applanation tonometry in 186 subjects (104 women) with (n=93) and without (n=93) type 2 diabetes. Diabetic and nondiabetic subjects were matched for age and mean arterial pressure (to +/-5 years and 5 mm Hg, respectively). PWV was strongly correlated with age and mean arterial blood pressure (R=0.59 and 0.29 respectively, each P<0.0001). PWV increased significantly more with age in women with diabetes (slope of regression line+/-SE: 0.19+/-0.03 m x s(-1) x year(-1)) than in nondiabetic women (0.08+/-0.02 m x s(-1) x year(-1), P<0.01 for difference). In men, however, the age-related increase in PWV was similar in diabetic (0.15+/-0.03 m x s(-1) x year(-1)) and nondiabetic subjects (0.13+/-0.03 m. s(-1) x year(-1), P=NS). The interaction of diabetic status with age and with sex was significant (P=0.01). Type 2 diabetes is associated with a greater age-related stiffening of the aorta in women compared with men, and this is not explained by hypertension.     

Takayasu's arteritis: a cause of prolonged arterial stiffness

OBJECTIVES: Cardiovascular disease is a major cause of mortality and morbidity in patients with Takayasu's arteritis (TA). Increased arterial stiffness is an independent risk factor and predictor of cardiovascular mortality in a variety of diseases. Pulse wave velocity (PWV) and the augmentation index (AI) are used as clinical measurements of arterial stiffness. METHODS: Data are presented from 10 patients with TA and 11 normal controls obtained between 2000 and 2004. Arterial compliance was assessed non-invasively by measurement of PWV, using the Complior system, and calculation of the aortic AI. RESULTS: TA patients (mean age 40.8+/-13.2 yr) were compared with a control group of healthy women from a parallel study (mean age 32.3+/-5.5 yr). The mean carotid-femoral PWV (PWV-CF) was higher in TA patients (P = 0.03). In addition, both aortic AI derived from the radial artery (P = 0.002) and carotid AI (P = 0.03) were higher in TA patients compared with controls. PWV-CF did not correlate with CRP (r = - 0.23, P = 0.23) or ESR (r = - 0.19, P = 0.27). Similar results were obtained for the correlation of carotid-radial PWV with CRP (r = 0.15, P = 0.32) and ESR (r = 0.33, P = 0.14). CONCLUSIONS: Our data show that TA is associated with elevated arterial stiffness in the central aorta, which may persist when the disease is quiescent. These data suggest that PWV represents a means by which cardiovascular risk can be detected and monitored in TA, and highlights the importance of effective management of cardiovascular risk factors in these patients.     

Association between mitral annulus calcification and aortic atheroma: a prospective transesophageal echocardiographic study

BACKGROUND AND PURPOSE: Although mitral annulus calcification (MAC) has been reported to be a significant independent predictor of stroke, no causative relationship was proven. It is also known that aortic atheroma (AA), especially those >/=5 mm thick and/or protruding and/or mobile are associated with stroke. This study was designed to determine whether an association exists between MAC and AA. METHODS: We prospectively evaluated the records of 279 consecutive patients who underwent transesophageal echocardiography (TEE) for various indications to measure the presence and characteristics of AA. The 105 patients in whom a diagnosis of MAC was made on transthoracic echocardiography (TTE) immediately preceding the TEE, were compared with 174 age-matched patients without MAC. MAC was defined as a dense, localized, highly reflective area at the base of the posterior mitral leaflet. We measured MAC thickness with two-dimensional-TTE in four-chamber view and AA thickness, protrusion and mobility with TEE. AA was defined as localized intimal thickening of >/=3 mm. A lesion was considered complex if there was plaque extending >/=5 mm into the aortic lumen and/or if it was protruding, mobile or ulcerated. RESULTS: No differences were found between the groups in risk factors for atherosclerosis or in indications for referral for TEE. Significantly higher rates were found in the MAC group for prevalence of AA (91 vs. 44%, P<0.001), atheromas >/=5 mm thick (68 vs. 19%, P<0.001), protruding atheromas (44 vs. 15%, P<0.001), ulcerated atheromas (10 vs. 1%, P<0.001) and complex atheroma (74 vs. 22%, P<0.001). Sixty patients had MAC thickness >/=6 mm and 45<6 mm. AA thickness was significantly greater in the patients with a MAC thickness of >/=6 mm (6.1+/-2.8 vs. 5.0+/-2.6 mm, P=0.03). On multivariate analysis MAC, hypertension and age were the only independent predictors of AA (P=0.0001, 0.005 and 0.007, respectively). CONCLUSIONS: There is a significant association between the presence and severity of MAC and AA. MAC may be an important marker for atherosclerosis of the aorta. This association may explain in part the high prevalence of systemic emboli and stroke in patients with MAC.     

Aortic stiffness in untreated adult patients with human immunodeficiency virus infection

HIV infection is associated with chronic immune activation, subclinical inflammation, and an atherogenic metabolic profile. It remains controversial whether HIV infection is a risk factor for accelerated arteriosclerosis independent from the effects of antiretroviral drugs. We investigated whether aortic stiffness, an early marker of arteriosclerosis, is increased in HIV patients who were not under antiretroviral treatment. In 39 untreated HIV-infected patients and 78 individually matched age-, sex-, and blood pressure-matched HIV-uninfected control subjects, we determined aortic pulse wave velocity (PWV), a direct noninvasive measure of aortic stiffness, by tonometric method. Subjects with overt cardiovascular disease or major cardiovascular risk factors were excluded from the study. Prevalence of the metabolic syndrome was higher in HIV patients (18% versus 5%; P=0.025). HIV patients had a higher aortic PWV (7.5+/-1.4 versus 6.7+/-1.1 m.s(-1); P=0.001) than control subjects. Age, mean arterial pressure as a measure of distending pressure, and HIV infection (all P<0.05) independently predicted aortic PWV when a consistent number of cardiovascular risk factors was simultaneously controlled for. Among HIV-infected subjects, serum gamma-glutamyl transpeptidase concentration (beta=0.46; P=0.003) and mean arterial pressure (beta=0.32; P=0.03) were independent determinants of aortic PWV. In conclusion, aortic stiffness is increased in HIV-infected individuals who have never received antiretroviral therapy. PWV increases with increasing serum gamma-glutamyl transpeptidase concentration. Our data support the hypothesis that HIV infection is a risk factor for arteriosclerosis.     

Elevated serum lipoprotein(a) level is an independent marker of severity of thoracic aortic atherosclerosis

STUDY OBJECTIVE: Lipoprotein(a) (Lp[a]) level is a risk factor for ischemic heart disease, cerebrovascular disease, and peripheral vascular disease. However, few data are available concerning the relationship between Lp(a) level and severity of thoracic aortic atherosclerosis. We hypothesized in this transesophageal echocardiography (TEE) study that Lp(a) level is a marker of severity of thoracic aortic atherosclerosis. DESIGN: Cross-sectional study. SETTING: University hospital. PATIENTS: Risk factors, coronary angiographic features, and TEE findings were analyzed prospectively in 119 patients with valvular disease. MEASUREMENTS AND RESULTS: The following risk factors were recorded: age, gender, hypertension, smoking, lipid parameters, diabetes, body mass index, and family history of coronary artery disease. Serum levels of Lp(a) were measured for each patient. By univariate analysis, age, diabetes, hypertension, smoking, Lp(a), total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels were significant predictors of thoracic aortic atherosclerosis. There was a positive and significant correlation between the Lp(a) levels and the score of severity of thoracic aortic atherosclerosis (p = 0.0001). Multivariate regression analysis revealed that Lp(a) was an independent predictor of severity of thoracic aortic atherosclerosis (p = 0.0001). CONCLUSION: This prospective study indicates that serum Lp(a) level is an independent marker of severity of thoracic aortic atherosclerosis detected by multiplane TEE. These findings emphasize the role of Lp(a) as a marker of atherosclerotic lesions in the major arterial locations.     

Relationship between cardio-ankle vascular index (CAVI) and carotid atherosclerosis in patients with essential hypertension.

Aortic stiffness measured by aorta-iliac or carotid-femoral pulse wave velocity (PWV) predicts all-cause and cardiovascular mortality. Brachial-ankle PWV (baPWV) has been developed as a more convenient assessment of arterial stiffness. However, the problem with clinical use of baPWV is that the index itself is closely dependent on blood pressure. Recently, a new method, termed the cardio-ankle vascular index (CAVI), has been proposed in Japan to overcome the disadvantages associated with measuring PWV. However, its clinical usefulness has not yet been fully clarified. In the present study, we compared the usefulness of CAVI with that of ultrasound for evaluating atherosclerosis in patients with essential hypertension. CAVI was measured in 70 hypertensive patients. The intima-media thickness (IMT), cross-sectional distensibility coefficient (CSDC), stiffness parameter beta, and mean diastolic (V(d)) and systolic (V(s)) flow velocities were evaluated by carotid ultrasound. The V(d)/V(s) ratio, an index of peripheral arterial resistance, was also calculated. CAVI was positively correlated with IMT (r=0.360, p=0.0022) and stiffness beta (r=0.270, p=0.0239) and negatively correlated with V(d)/V(s) (r=-0.471, p<0.0001) and CSDC (r=-0.315, p=0.0079). Stepwise regression analysis revealed that age (r=0.475, p<0.0001) and pulse pressure (r=0.492, r<0.0001) were independent determinants of CAVI. These results suggest that CAVI is a useful clinical marker for evaluating atherosclerosis and arteriolosclerosis in patients with essential hypertension.     

Reduced pulmonary function is associated with central arterial stiffness in men.

The association of impaired pulmonary function with cardiovascular morbidity and mortality has been reported in several prospective studies. The nature of this association and the mechanisms underlying it are unknown. Both atherosclerosis and central arterial stiffness might be involved. We recently reported, in a 4-yr longitudinal study, that reduced lung function predicts the development of carotid atherosclerotic plaques. In the present study, we report the associations of aortic stiffness with lung function measurements. One hundred and ninety-four men, aged 30 to 70 yr and free of coronary heart disease, who volunteered for a standard health examination were included. FEV(1) and FVC were used to assess lung function. Aortic stiffness was estimated from the carotid-femoral pulse-wave velocity (PWV), which increases proportionally with an increase in aortic stiffness. PWV was significantly and negatively associated with FEV(1) and FVC (partial correlation coefficients adjusted for age and height: -0.27 [p < 0.001] and -0.24 [p < 0.001], respectively). For every 1 SD increase in PWV (2.5 m/s), FEV(1) decreased by 195.2 +/- 50.1 ml (p < 0.001) in an age- and height-adjusted analysis. The corresponding decrease in FVC was 190.4 +/- 55.0 ml (p < 0.001). Further adjustment for cardiovascular risk factors (weight, smoking habits, hypercholesterolemia, diabetes, and hypertension) did not markedly alter these results. In addition, negative associations of PWV with lung function measurements were observed within each category of cardiovascular risk factors. This study suggests that reduced pulmonary function is independently associated with aortic stiffness in men. The interrelations between pulmonary and vascular alterations should be thoroughly investigated.