Ambulatory arterial stiffness index or pulse pressure: which correlates better with arterial stiffness in resistant hypertension?

The ambulatory arterial stiffness index (AASI) is a recently proposed index derived from 24-h ambulatory blood pressure monitoring (ABPM) for the evaluation of arterial stiffness. In this cross-sectional study we investigated whether AASI reflects arterial stiffness in patients with resistant hypertension by comparing AASI and ambulatory pulse pressure (PP) with aortic pulse wave velocity (PWV), a measure of arterial stiffness, in 391 resistant hypertensives. Clinical, laboratory and echocardiographic variables, 24-h ABPM and aortic PWV (measured using the Complior device) were obtained. AASI was calculated as 1--the regression slope of 24-h diastolic on systolic blood pressure (BP). Statistical analysis involved single and multiple linear regressions to assess the correlations between the two ABPM variables and PWV, both unadjusted and adjusted for potential confounders (age, gender, body height, presence of diabetes, 24-h mean arterial pressure [MAP], heart rate, and nocturnal BP reduction). Ambulatory PP and aortic PWV were independently associated with age, gender, presence of diabetes, and 24-h MAP, whereas AASI was associated with age, diabetes, and nocturnal diastolic BP reduction. PP showed stronger unadjusted (r=0.39, p<0.001) and adjusted (r=0.22, p<0.001) correlations with aortic PWV than AASI (r=0.12, p=0.032 and r= -0.04, p=0.47, respectively). In the analysis of subgroups stratified by gender, age, presence of atherosclerotic diseases and diabetes, dipping pattern, and ambulatory BP control, the superiority of PP over AASI was apparent in all subgroups. In conclusion, 24-h ambulatory PP was better correlated to arterial stiffness, as evaluated by aortic PWV, than the novel AASI, in patients with resistant hypertension.     

Pulse wave velocity is increased in patients with transient myocardial ischemia

OBJECTIVE: We have recently shown that mean pulse pressure is higher in patients with transient myocardial ischemia. Pulse pressure elevation might be an important consequence of increased arterial stiffness. The aim of this study was to prove if arterial stiffness is changed in patients with transient myocardial ischemia who bear a high cardiovascular risk. Additionally we investigated whether arterial stiffness or wave reflection is the best indicator for transient myocardial ischemia. Aortic pulse wave velocity (PWV) is a measure of arterial stiffness, and augmentation index (AIx) an indication of arterial wave reflection. Both are indicators for cardiovascular risk. METHODS: PWV (carotid-femoral) and AIx (SphygmoCor) were assessed in 74 hypertensive patients. Transient myocardial ischemia was detected using an ST-triggered 24-h ambulatory blood pressure monitoring device. RESULTS: ST-segment depressions were recorded in 30 of 74 patients. There were no significant differences with regard to age, mean arterial pressure, systolic blood pressure, diastolic blood pressure or heart rate. PWV was seen to be higher in patients with transient myocardial ischemia (10.6 versus 9.5 m/s, P = 0.036). There was no significant difference in AIx between the two groups. PWV (r = 0.36, P = 0.002) but not AIx correlated with pulse pressure. CONCLUSIONS: PWV is higher in hypertensive individuals (age > 60 years) with transient myocardial ischemia, suggesting that PWV is an indicator of increased cardiovascular risk. Although AIx is known to be associated with several cardiovascular diseases, it was not seen to be associated with silent myocardial ischemia. Our results suggest that the clinical significance of parameters of arterial stiffness and arterial wave reflection change with age, with a higher clinical importance of PWV indicated in patients over the age of 60.     

Arterial stiffness and wave reflections in patients with sickle cell disease

We tested the hypothesis that lower blood pressure and increased vasodilatation reported in sickle cell disease (SCD) patients with hemoglobin SS genotype (SS) are translated by lower arterial stiffness determined by pulse wave velocity (PWV) and wave reflections assessed by augmentation index (AI). We enrolled 20 SS (8 females; 12 male) patients closely matched for age, gender, height, and body mass index to 20 subjects with hemoglobin AA genotype (AA). Carotid-femoral PWV (PWV(CF)) and carotid-radial PWV (PWV(CR)) were recorded with the Complior device. Aortic AI was derived from pressure wave analysis (SphygmocoR). PWV(CF) and PWV(CR) were lower in SS than in AA (4.5+/-0.7 m/s versus 6.9+/-0.9 m/s, P<0.0001 and 6.6+/-1.2 m/s versus 9.5+/-1.4 m/s, P<0.0001, respectively). AI was lower in SS than in AA (2+/-14% versus 11+/-8%, P=0.02). Multivariate analysis revealed that both PWV(CF) and PWV(CR) were negatively associated with hemoglobin SS type and positively related to mean arterial pressure (MAP), whereas AI was positively associated with MAP and total cholesterol (all P<0.0001). Multivariate analysis restricted to SS indicated a positive association between PWV(CF) and PWV(CR) with age but a negative association with MAP (R2=0.57 and 0.51, respectively, both P<0.001), whereas MAP and heart rate were independently associated with AI (R2=0.65, P<0.001). This study provides the first evidence that SCD is associated with both lower arterial stiffness and wave reflections. SS patients have a paradoxical negative association between PWV and MAP, suggesting that low MAP does not protect them against arterial stiffness impairment.     

The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation provides a better definition of cardiovascular burden associated with CKD than the Modification of Diet in Renal Disease (MDRD) Study formula in subjects with type 2 diabetes

Differences in 24 h blood pressure (BP) monitoring parameters such as average 24 h BP, day to night BP ratio and BP variability could have an impact in arterial stiffness. The study hypothesis was that despite similar average BP values in ambulatory blood pressure monitoring subjects with increased 24 h BP variability may have increased arterial stiffness. The study population consisted of 115 consecutive young healthy volunteers. Carotid-femoral PWV was measured in all subjects. Clinic BP was measured and an appropriate cuff was fitted on the non-dominant arm of each subject for a 24 h ambulatory blood pressure monitoring session. Waist to hip ratio as well as BMI was measured. Family history and smoking habits were recorded. In univariate analysis, estimated carotid-femoral PWV showed a significant correlation with age, weight, waist circumference, height, clinic systolic and diastolic BP, 24-h systolic and diastolic BP, 24-h pulse pressure, 24-h systolic and diastolic BP variability, daytime systolic and diastolic BP, daytime pulse pressure, daytime systolic and diastolic BP variability, nighttime systolic BP, nighttime pulse pressure and nighttime systolic BP variability. In multivariate regression analysis, age (B=0.95, P<0.001) and 24 h systolic BP variability (B=0.28, P<0.001) were independent determinanats of arterial stiffness. In conclusions, increased 24 h systolic BP variability is associated with arterial stiffness in young healthy volunteers. Pulse wave velocity in a young healthy population is useful to identify determinants of premature arterial stiffness, thus further elucidating the aspects of early vascular ageing.     

A modified ambulatory arterial stiffness index is independently associated with all-cause mortality

Dependence of the ambulatory arterial stiffness index (AASI) on data scattering interferes with its potential clinical relevance. We assessed the correlates and all-cause mortality associations of a modified AASI (s-AASI). AASI was derived from the 24-h diastolic vs. systolic blood pressure linear regression line, whereas s-AASI was derived by symmetric regression (bisecting the line of diastolic vs systolic and systolic vs. diastolic). Of 2918 patients 55% were women; age was 56 +/- 16 years and body mass index was 27.3 +/- 4.5 kg/m(2). Average 24-h ambulatory blood pressure was 138 +/- 16/78 +/- 10 mm Hg. Applying the modified method for calculating AASI yielded a different measure: the negative correlation between AASI and blood pressure dipping (r = -0.304, P < 0.0001) was abolished (r = +0.223, P < 0.0001), s-AASI was more dependent on age (r = 0.266 vs. r = 0.089 for AASI), and prediction of all-cause mortality was enhanced; hazard ratio (95% confidence intervals) 1.17 (1.00-1.36) per 1 s.d. increase in s-AASI in the fully adjusted model as compared with 1.15 (0.97-1.36) for AASI.     

Gender-specific brachial artery blood pressure-independent relationship between pulse wave velocity and left ventricular mass index in a group of African ancestry

AIM: As it is uncertain whether arterial stiffness is related to left ventricular mass and left ventricle mean wall thickness independent of blood pressure measured at the brachial artery, we aimed to ascertain this effect in never-treated participants with a high prevalence of risk factors for large artery dysfunction. METHODS: The conventional and ambulatory blood pressure-independent relations between indices of large artery function and either left ventricular mass or mean wall thickness were determined in 309 never-treated randomly recruited South Africans of African ancestry with prevalent risk factors for large artery changes [24% were hypertensive, 63% were overweight/obese, and 17% had diabetes mellitus or abnormal blood glucose control (glycosylated hemoglobin A1c > 6.1%)]. Large artery function was assessed from applanation tonometry performed at the carotid, radial and femoral arteries and central augmentation index and aortic pulse wave velocity (carotid femoral pulse wave velocity) derived from these measures. Left ventricular mass indexed for height (left ventricular mass index) and mean wall thickness were determined using echocardiography. RESULTS: Pulse wave velocity was associated with left ventricular mass index (r = 0.67, P < 0.0001) and mean wall thickness (r = 0.61, P < 0.0001) in women, but not in men (r = 0.04-0.08) (P < 0.0001 for the interaction between pulse wave velocity and gender). On multivariate analysis with appropriate adjustments including either conventional systolic blood pressure, pulse pressure or mean arterial pressure, pulse wave velocity was independently associated with left ventricular mass index (partial r = 0.25, P < 0.005 after adjustments for systolic blood pressure) and with mean wall thickness (partial r = 0.17, P < 0.05 after adjustments for systolic blood pressure) in women, but not in men. With the inclusion of 24-h ambulatory rather than conventional systolic blood pressure, pulse pressure or mean arterial pressure in the regression equation, pulse wave velocity was similarly independently associated with left ventricular mass index (partial r = 0.39, P < 0.001 after adjustments for 24-h systolic blood pressure) and mean wall thickness (partial r = 0.33, P < 0.003 after adjustments for 24-h systolic blood pressure) in women, but not in men. Central augmentation index was not independently associated with left ventricular mass index or mean wall thickness. In women, the contribution of pulse wave velocity to left ventricular mass index or mean wall thickness independent of systolic blood pressure (standardized beta-coefficient for left ventricular mass index=0.37 +/- 0.13, P < 0.005) was equivalent to the contribution of systolic blood pressure (standardized beta-coefficient for left ventricular mass index = 0.38 +/- 0.13, P < 0.005). Moreover, after adjusting for clinic or ambulatory systolic blood pressure and other confounders, in women every one standard deviation increase in pulse wave velocity (2.1 m/s) translated into a 4.3 or 6.2 g/m increase in left ventricular mass index, respectively. CONCLUSION: Arterial stiffness is associated with left ventricular mass index and left ventricle wall thickness independent of conventional or ambulatory blood pressure and additional confounders in a never-treated population sample of women, but not men, of African ancestry with prevalent risk factors for large artery dysfunction.     

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.     

Influence of the metabolic syndrome on aortic stiffness in never treated hypertensive patients

BACKGROUND AND AIM: Metabolic syndrome (MS) carries an increased risk for cardiovascular events and there is a growing awareness that large artery stiffening is a powerful predictor of cardiovascular morbidity and mortality. Little is known about the relationship of MS with aortic stiffness. The aim of our study was to analyze, in patients with essential hypertension, the influence of MS, defined according to the criteria proposed by the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP-ATP III), on carotid-femoral pulse wave velocity (PWV), a measure of aortic stiffness. METHODS: Ninety-three untreated essential hypertensives, aged between 23 and 61 years, without diabetes mellitus, were studied. All subjects underwent routine blood chemistry, oral glucose tolerance test with glucose and insulin determinations, albumin excretion rate (AER) measurement, 24-h ambulatory blood pressure monitoring, and measurement of carotid-femoral PWV, by means of a computerized method. RESULTS: Patients with MS (n = 28) showed higher age-adjusted carotid-femoral PWV (10.1 +/- 1.4 vs 9.3 +/- 1.4 m/s; p = 0.01) when compared to subjects without MS. This difference held after controlling for gender and for 24-h mean blood pressure (MBP) (p = 0.02) and lost its statistical significance after further adjustment for AER. In a multiple regression model, excluding the individual components of MS, in which metabolic syndrome was added along with age, gender, smoking habit, LDL cholesterol, HOMA index, 24-h MBP and 24-h heart rate, MS remained independently associated with carotid-femoral PWV (beta = 0.29; p = 0.002). The statistical significance of this association disappeared after the inclusion into this model of AER. CONCLUSIONS: Metabolic syndrome is associated with an increased aortic stiffness. Main explanatory factors of this association are age, systolic blood pressure and albumin excretion rate.     

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

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

Associations between reactive oxygen species, blood pressure and arterial stiffness in black South Africans: the SABPA study

Many mechanisms, including oxidative stress, contribute to hypertension. This study investigated the possible associations between oxidative stress, blood pressure and arterial stiffness in black South Africans. Ambulatory blood pressure measurements were taken for 101 black South African men and 99 women. The stiffness indices included ambulatory arterial stiffness index (AASI) and pulse pressure (PP). Reactive oxygen species (ROS) levels (P<0.0001) were higher in the African women compared with men. ROS levels were also higher in hypertensive compared with normotensive men. The 24?h systolic blood pressure (SBP; P<0.01), 24?h diastolic blood pressure (DBP; P<0.0001) and pulse wave velocity (PWV; P<0.01) were significantly higher in African men compared with women. There were unadjusted positive associations of 24?h SBP (r=0.33; P=0.001), 24?h DBP (r=0.26; P=0.008) and 24?h PP (r=0.29; P=0.003) with ROS in African men only. A positive association between AASI and ROS existed only in hypertensive men (r=0.27; P=0.035), but became nonsignificant (B=0.0014; P=0.14) after adjustments. Adjusted, positive associations of 24?h SBP (B=0.181; P=0.018) and 24?h PP (B=0.086; P=0.050) with ROS were again only evident in African men. ROS is positively associated with SBP and PP in African men, suggesting that increased ROS levels may contribute to hypertension in this population group.     

Cardiovascular characteristics in American youth with prehypertension

BACKGROUND: Cardiovascular structure and function in youth with prehypertension have been incompletely investigated. METHODS: Casual and ambulatory blood pressure (BP) measurement, arterial stiffness, noninvasive hemodynamic profiles, and cardiac structure were studied in a twin cohort of American black and white youth (n = 942; mean age, 17.6 +/- 3.3 years SD). A family history of essential hypertension was used as a proxy to study genetic susceptibility to prehypertension. RESULTS: The occurrence of prehypertension was approximately 12% in the entire sample. Body mass index and waist circumference were significantly greater in prehypertensive subjects than in normotensive subjects. The 24-h ambulatory systolic BP (SBP), 24-h ambulatory diastolic BP (DBP), nighttime ambulatory SBP, and nighttime ambulatory DBP were significantly elevated in prehypertensive subjects compared with normotensive subjects. In whites, prehypertensive subjects compared with normotensive subjects showed increased radial (6.8 +/- 0.1 v 6.2 +/- 0.1 m/sec, P < .001) and foot pulse-wave velocity (PWV) (7.4 +/- 0.1 v 7.0 +/- 0.1 m/sec, P = .001). In whites, the total peripheral resistance index was greater in prehypertensive subjects than in normotensive subjects (P = .005). White prehypertensive subjects had a significantly greater heart rate than white normotensive subjects (69.0 +/- 1.4 v 64.0 +/- 0.6 bpm). In contrast, in blacks, the cardiac index was higher in prehypertensive subjects than in normotensive subjects (3.3 +/- 0.1 v 3.0 +/- 0.1 L/min/m2, P = .004). In blacks and whites, there were no statistical differences in the parameters of left-ventricular structure between normotensive subjects and prehypertensive subjects. Finally, prehypertensive subjects were more likely to have a positive family history of essential hypertension, especially in blacks. CONCLUSIONS: Prehypertension compared with normotension exhibited unfavorable cardiovascular phenotypes. Cardiovascular characteristics of prehypertension appear to be race-dependent.     

Relationship between albumin excretion rate and aortic stiffness in untreated essential hypertensive patients

OBJECTIVES: To evaluate, in a group of nondiabetic essential hypertensive patients with normal renal function, the relationship between albumin excretion rate (AER) and carotid-femoral pulse wave velocity (PWV), as an index of aortic stiffness. DESIGN: Cross-sectional study. SETTING: Outpatient hypertension clinic. SUBJECTS: Seventy patients with mild-to-moderate essential hypertension, aged 42 +/- 8 years, never pharmacologically treated. All subjects underwent routine laboratory tests, 24-h ambulatory blood pressure (BP) monitoring, measurement of carotid-femoral PWV, by means of a computerized method, and AER. RESULTS: Microalbuminuric patients (AER > or = 20 microg min(-1); n = 19), when compared with normoalbuminuric subjects, showed more elevated 24-h BP (136/88 +/- 10/10 vs. 128/83 +/- 7/6 mmHg; P < 0.001 and P = 0.013, for systolic and diastolic BP respectively) and higher values of carotid-femoral PWV (10.4 +/- 2 m s(-1) vs. 9.2 +/- 1.3; P = 0.006). This latter difference remained statistically significant, even after correction by ancova for 24-h systolic and diastolic BP, and body mass index (BMI, P = 0.016). Univariate regression analysis disclosed a tight correlation between AER and carotid-femoral PWV (r = 0.42; P = 0.0003). This association was confirmed in a multiple regression model (beta = 0.35; P = 0.009) in which, as independent variables, besides PWV, 24-h BP, age, serum glucose values, smoking status, gender and BMI, were added. CONCLUSIONS: Our results seem to confirm that microalbuminuria may represent the early renal manifestation of a widespread vascular dysfunction, and therefore it is an integrated marker of cardiovascular risk.     

Circadian blood pressure variation: relationship between dipper status and measures of arterial stiffness

BACKGROUND: Compared with dippers, hypertensive individuals with a nondipping nocturnal blood pressure (BP) profile have more target organ damage and a worse cardiovascular prognosis, potentially mediated through arterial stiffness. OBJECTIVE: To examine arterial stiffness and dipping in a population of 314 untreated hypertensive individuals, mean age 48 +/- 8 years, 55% men. METHODS: Dipping was defined as a 10-20% fall in nocturnal BP; extreme dipping as greater than 20%, nondipping as less than 10%, and reverse-dipping as 0% at most fall in nocturnal BP. Aortic pulse wave velocity (PWV) (Complior) and augmentation index (Sphygmocor) were measured. RESULTS: Groups did not differ by age, gender, 24-h or daytime mean BP, body mass index, smoking, cholesterol, glucose, renin or aldosterone. The relationship between PWV and dipper-status was J-shaped, with extreme-dippers and reverse-dippers having the highest PWV. Nondippers and reverse-dippers had significantly higher age and sex-adjusted PWV compared with dippers. Following multivariate adjustment for age, gender, mean arterial pressure, heart rate and smoking, reverse-dippers had significantly higher PWV than either dippers or nondippers (P = 0.005 and P = 0.006, respectively). Dipper status was not associated with augmentation index. CONCLUSIONS: A reverse-dipper pattern, corresponding to the 95% percentile of the night: day BP ratio on ambulatory BP monitoring, identifies a population group with increased PWV. This difference could not be explained by the measured risk factors. Reverse-dippers had significantly less day: night variability in heart rate and wider pulse pressures at night than any of the other groups, suggesting altered sympathetic tone at night as a potential mechanism.     

Inverse relationship between ambulatory arterial stiffness index and glomerular filtration rate in arterial hypertension

BACKGROUND: Arterial stiffness and mild-to-moderate renal dysfunction are predictors of cardiovascular (CV) morbidity and mortality. Recently, the ambulatory arterial stiffness index (AASI) has been proposed as a surrogate index of arterial stiffness. It has been associated with an enhanced risk of stroke. The aim of our study was to assess the relationship between AASI and glomerular filtration rate (GFR) in a group of hypertensive patients with no CV complications. METHODS: A total of 143 untreated hypertensive subjects (mean age: 44 +/- 12 years; men 57%), with serum creatinine <1.5 mg/dl, were enrolled. AASI was calculated as one minus the regression slope of diastolic on systolic blood pressure (BP) obtained by individual 24-h BP recordings. GFR was computed from the scintigraphic determination of the technetium-99m diethylenetriaminepentaacetic acid uptake within the kidneys, by the Gates' method. RESULTS: Hypertensive patients with AASI above the median value (n = 71) had lower GFR than those with AASI below the median (n = 72) (98.3 +/- 31 vs. 122.4 +/- 32 ml/min/1.73 m(2); P < 0.001). This difference held even after adjustment for age and gender. The linear regression analysis disclosed a significant inverse correlation between GFR and AASI (r = -0.30; P < 0.001), that was replicated (beta = -0.19; P = 0.02) in a multiple regression model including, as independent variables (besides AASI), age, gender, high-density lipoprotein cholesterol, body mass index, 24-h pulse pressure (PP) and nocturnal reduction in BP. CONCLUSIONS: AASI is inversely related to GFR in arterial hypertension. This may help to explain the increased CV risk associated with mild-to-moderate renal dysfunction.     

Autonomic nervous function, arterial stiffness and blood pressure in patients with Type I diabetes mellitus and normal urinary albumin excretion

Type I diabetic patients (DM-1) with an elevated urinary albumin excretion (UAE>30 mg/24 h) have a high cardiovascular risk. However, DM-1 patients with normal UAE have incipient abnormalities of the cardiovascular and nervous systems, such as elevations of blood pressures, increases in arterial stiffness and deterioration of autonomic nervous function. We studied the interrelationships of these abnormalities in normoalbuminuric DM-1 patients. In 76 patients, we performed two cardiovascular reflex tests (deep in- and expiration test (IE test) and lying-to-standing test (LS test)), and determined aortic pulse wave velocity (PWV), local arterial compliances of the common carotid, femoral and brachial arteries, and 24-h blood pressures. The DeltaRRmax value of the LS test was associated with aortic PWV (negatively) and the compliance coefficients of the carotid, femoral and brachial arteries. Per 100-ms increase in DeltaRRmax, pulse wave velocity decreased by 0.39 m/s, compliance coefficients of the carotid, femoral and brachial arteries increased by 0.06, 0.08 and 0.05 mm2/kPa, respectively. These associations were independent of age, 24-h mean arterial pressure and 24-h heart rate. Increases in arterial stiffness were associated with increases in 24-h systolic and pulse pressure (per 1 m/s increase in PWV, systolic and pulse pressure increased by 2.1 and 1.7 mmHg, respectively). In normoalbuminuric DM-1 patients, deterioration of autonomic nervous function is associated with an increase in arterial stiffness, which, in turn, was associated with, and may cause, increased systolic and pulse pressure. These findings suggest that preventive strategies targeting autonomic dysfunction may reduce cardiovascular morbidity in diabetes.     

Low-grade inflammation and hypoadiponectinaemia have an additive detrimental effect on aortic stiffness in essential hypertensive patients.

AIMS: In this study, we investigated the combined effect of increased high-sensitivity C-reactive protein (hs-C-reactive protein) and hypoadiponectinaemia on aortic stiffness in essential hypertensive subjects. METHODS AND RESULTS: A total of 267 untreated patients with stage I-II essential hypertension underwent ambulatory BP and carotid-femoral pulse wave velocity (c-f PWV) evaluation. The distributions of hs-C-reactive protein and adiponectin were split by the median (1.3 mg/L and 7.8 microg/mL, respectively) and accordingly subjects were stratified into those with high and low values. Patients with high (n = 134) compared with those with low hs-C-reactive protein (n = 133) values exhibited greater c-f PWV levels (by 0.8 m/s, P < 0.0001), whereas patients with low (n = 133) compared with those with high (n = 134) adiponectin levels had higher c-f PWV (by 0.9 m/s, P < 0.0001). Stepwise regression analysis revealed that age, 24 h systolic BP, hs-C-reactive protein and adiponectin were independent predictors of arterial stiffness. In patients with low hs-C-reactive protein, hypoadiponectinaemia (n = 46) compared with high adiponectin (n = 87) was accompanied by increased c-f PWV (by 0.8 m/s, P < 0.0001). Similarly in patients with high hs-C-reactive protein, hypoadiponectinaemia (n = 84) compared with high adiponectin (n = 50) was related to heightened c-f PWV (by 0.7 m/s, P = 0.008). CONCLUSION: In essential hypertension, pronounced low-grade inflammation in conjunction with hypoadiponectinaemia exerts an additive detrimental effect on aortic stiffness, accelerating the vascular ageing process.     

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.     

Effects of amlodipine and valsartan on vascular damage and ambulatory blood pressure in untreated hypertensive patients

The present study was performed to compare the long-term effects of 24-h ambulatory blood pressure (BP) control with amlodipine versus valsartan on vascular damage in untreated hypertensive patients. Amlodipine and valsartan have benefits on cardiovascular mortality and morbidity in hypertensive patients. Although ambulatory BP is associated with severity of target-organ damage in hypertensive patients, beneficial effects of ambulatory BP control with amlodipine versus valsartan on vascular damage have not been compared. Pulse wave velocity (PWV), intima-media thickness (IMT) of the carotid arteries, urinary albumin excretion (UAE) and 24-h ambulatory BP were determined in 100 untreated hypertensive patients before and 12 months after the start of antihypertensive therapy with amlodipine or valsartan. Amlodipine and valsartan decreased ambulatory BP similarly, but the variability of 24-h and daytime ambulatory systolic BP was significantly reduced by amlodipine but not by valsartan. The reduced variability of ambulatory systolic BP caused by amlodipine significantly contributed to the improvement of PWV, although both drugs decreased PWV similarly. Carotid IMT was unaffected by treatment with either drug. Valsartan significantly decreased UAE independently of its depressor effect, but amlodipine had no effect on UAE. These results suggest that the 24-h control of ambulatory BP with amlodipine had functionally improved the stiffened arteries of hypertensive patients by the end of 12 months of treatment, in part through reducing BP variability, whereas ambulatory BP control with valsartan decreased the arterial stiffness to the same degree as amlodipine without affecting BP variability maybe through some pleiotropic effects.     

Increased arterial wall stiffness in primary aldosteronism in comparison with essential hypertension

BACKGROUND: Aldosterone has been shown to substantially contribute to the accumulation of collagen fibers and growth factors in the arterial wall, which can increase wall stiffness. This study aimed at comparing arterial stiffness between patients with primary aldosteronism (PA), essential hypertension (EH), and normotensive controls using carotid-femoral pulse wave velocity (PWV) and central augmentation index (AI). METHODS: Thirty-six patients with confirmed PA, 28 patients with EH, and 20 normotensive subjects were investigated by Sphygmocor applanation tonometer. RESULTS: The office blood pressure (BP) at the time of the measurement (PA 167+/-34/92+/-12 mm Hg; EH 166+/-19/91+/-10 mm Hg), age, body mass index (BMI), cholesterol, triglyceride, blood glucose levels were comparable between PA and EH groups. The patients with PA had significantly higher PWV than the EH patients and control subjects (9.8+/-2.6 m/sec v 7.5+/-1.0 m/sec v 5.9+/-0.7 m/sec, respectively; all mutual differences P<.001). The difference in PWV between PA and EH remained statistically significant also after the adjustment for all clinical variables including 24-h BP using multivariate analysis (P=.001). CONCLUSIONS: Arterial wall stiffness is independently increased in PA compared to EH. This could be caused by the deleterious effects of aldosterone excess (potentially modulated by hypernatremia) on the fibrosis and remodeling of the arterial wall.     

Arterial stiffness assessed by pulse wave analysis in essential hypertension: relation to 24-h blood pressure profile

BACKGROUND: Arterial stiffness is a risk factor for cardiovascular morbidity and mortality and appears to be increased in arterial hypertension. The purpose of the present study was to relate systemic arterial stiffness assessed by pulse wave analysis to variables of 24-h ambulatory blood pressure monitoring (ABPM) in patients with essential hypertension. METHODS: Seventy-two subjects with untreated mild to moderate arterial hypertension underwent evaluation with 24-h ambulatory blood pressure monitoring. In the same subjects, applanation tonometry and pulse wave analysis was performed for evaluation of systemic arterial stiffness expressed as augmentation index and estimated aortic pulse wave velocity. RESULTS: Clinic systolic blood pressure, mean heart rate during 24-h blood pressure monitoring and height were independent predictors of augmentation index and estimated aortic pulse wave velocity. The 41 patients with blunted reduction in nighttime blood pressure (nondippers) showed higher mean systolic blood pressure (p=0.02), lower systolic and diastolic blood pressure variability (p<0.001), higher pulse pressure during 24-h monitoring (p=0.05) and higher estimated aortic pulse wave velocity (p=0.03), indicating stiffer arteries in this group. CONCLUSIONS: These results suggest that blood pressure change from day- to nighttime is an important determinant of arterial stiffness assessed by pulse wave analysis; this association could contribute to the higher cardiovascular risk in nondippers.