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

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

Ageing and blood pressure modulate the relationship between metabolic syndrome and aortic stiffness in never-treated essential hypertensive patients. A comparative study

OBJECTIVE: The aim of this study was to evaluate the impact of the metabolic syndrome (MS) and its components as defined by the National Cholesterol Education Program Adult Treatment Panel III on arterial stiffness in untreated hypertensive patients. METHODS: This was a cross sectional multi-center study performed in 46 healthcare centers, from 14 countries involved in the Complior study. Four hundred and forty patients (55% male) aged 18-73 years, with untreated essential hypertension were selected at inclusion. All patients underwent a full evaluation for all the risk factors representing the MS and an assessment of arterial stiffness using automatic measurement of carotid-femoral pulse wave velocity (PWV). RESULTS: In the overall population significant correlations were found, respectively, between PWV, MS (R=0.2, P<0.001) and gender (R=0.11, P=0.023) where PWV was higher in women. After adjustment for age and systolic blood pressure (SBP), analysis of covariance showed an independent effect of the MS on PWV, this effect increased with ageing and SBP especially after 47 years (age median, P=0.0047). Moreover, increase of mean PWV was highly associated with the number of MS factors in global population (P<0.001). These findings suggest that MS leads to early arterial wall ageing. CONCLUSIONS: Presence of MS induces an increase of arterial stiffness in untreated hypertensive patients independently from age and SBP. The increase of PWV is proportional to number of risk factors and affects principally patients after mid-age of 47 years where MS has ageing effects on arterial stiffness.     

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

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

Insulin resistance is associated with hypertensive response to exercise in non-diabetic hypertensive patients

AIM: Insulin resistance is associated with increased sympathetic activity and elevated angiotensin II which may contribute to the excessive increase in arterial blood pressure during exercise. In this study, we hypothesized that increased insulin resistance will be significantly associated with hypertensive response to exercise (HRE) in non-diabetic hypertensive patients. METHOD: Two hundred seventy-five hypertensive patients were included in this study. HOMA-IR index using serum fasting glucose and insulin was calculated for insulin resistance. There were 79 patients with hypertensive response (age 56.1+/-9.4 years) and 196 patients without hypertensive response (age 53.9+/-8.9 years). RESULTS: Insulin resistance, assessed by HOMA index, was significantly higher in hypertensive response group as compared to control (HOMA=2.60+/-1.54 versus 1.76+/-0.86, P<0.001). HOMA was an independent predictor of HRE when controlled for age, sex, BMI and baseline SBP (odds ratio=2.008, P<0.001). Also, HOMA was significantly correlated with the magnitude of SBP elevation controlled for age, sex, BMI and baseline SBP as well (beta=0.293, P<0.001). In conclusion, this study shows that insulin resistance is a significant determinant of hypertensive response to exercise. Further studies to determine the prognostic significance of this finding is warranted.     

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

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

Prediction of incident hypertension and arterial stiffness using the non–insulin‐based metabolic score for insulin resistance (METS‐IR) index

Hypertension is associated with insulin resistance (IR), metabolic syndrome (MS), and arterial stiffness. Non–insulin‐based IR indexes were developed as tools for metabolic screening. Here, we aimed to evaluate the novel non–insulin‐based Metabolic Score for IR (METS‐IR) index for the prediction of incident hypertension and arterial stiffness evaluated using pulse wave velocity (PWV) analysis, compared with other non–insulin‐based IR indexes. We evaluated two populations, a cross‐sectional evaluation of high‐risk individuals (n = 305) with a wide range of metabolic comorbidities and dyslipidemia in whom PWV measurement was performed and a 3‐year prospective cohort of normotensive individuals (N = 6850). We observed a positive correlation between METS‐IR and PWV in the cross‐sectional cohort, which was higher compared with other non–insulin‐based fasting IR indexes; furthermore, PWV values >75th percentile were associated with the upper tercile of METS‐IR values. In the prospective cohort, we observed an increased risk for incident hypertension for the upper METS‐IR tercile (METS‐IR ≥ 46.42; HR: 1.81, 95% CI: 1.41‐2.34), adjusted for known cardiovascular risk factors, and observed that METS‐IR had greater increases in the predictive capacity for hypertension along with SBP and the Framingham Hypertension Risk Prediction Model compared with other non–insulin‐based IR indexes. Therefore, METS‐IR is a novel non–insulin‐based IR index which correlates with arterial stiffness and is a predictor of incident hypertension, complementary to previously validated risk prediction models.     

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.     

Advanced glycation end-products and arterial stiffness in hypertension

BACKGROUND: The formation of advanced glycation end-products is associated with arterial stiffness in experimental models and alagebrium (formerly known as ALT-711), an advanced glycation end-product cross-link breaker, has been shown to reduce arterial stiffness in elderly subjects. METHODS: We related plasma concentrations of advanced glycation end-products (AGEs), measured using a noncompetitive immunoassay, and markers of aortic stiffness-pulse wave velocity (PWV) and augmentation index (AIx), a measure of aortic wave reflection-in 46 subjects, aged 47 +/- 2 years, comprising 30 untreated hypertensive and 16 normotensive subjects. Results were analyzed using univariate and multiple logistic regression analysis. RESULTS: Plasma AGEs were significantly higher in hypertensive than in normotensive subjects (7.8 +/- 1 v 3 +/- 1 mug/ml; P < .0001). There was a significant relationship between plasma AGEs and aortic PWV (r = 0.49, P < .01), but not with AIx. In a stepwise regression model age, plasma AGE levels, smoking status, and total cholesterol explained 67% of the variability in PWV. For AIx, the only variables that entered the model were age, gender, and heart rate (R(2) = 0.53, P < .0001) with no contribution from plasma AGEs. CONCLUSIONS: Concentration of plasma AGEs is significantly higher in hypertensive than in normotensive subjects and related to aortic stiffness independent of age and blood pressure, with no relationship with aortic wave reflection. Plasma AGEs may play a blood pressure-independent role in large but not small vessel remodeling in essential hypertension.     

Arterial wall stiffness is associated with peripheral circulation in patients with type 2 diabetes

The prevalence of peripheral vascular disease (PVD) in diabetic patients is manyfold higher than that of age- and sex-matched nondiabetic subjects. This study was designed to evaluate the relationship between quantitatively determined peripheral circulation in the lower extremities and arterial wall thickness or stiffness in 68 patients with type 2 diabetes. Peripheral circulation during treadmill-exercise was monitored by transcutaneous oxygen tension (TcPO2) and was expressed as percentage of post-exercise TcPO2 adjusted by that of pre-exercise (TcPO2 index). Arterial wall thickness (intima-media thickness; IMT) and stiffness (stiffness beta) were measured by ultrasonography. TcPO2 index was negatively (r=-0.350, P=0.0007) correlated with stiffness beta, not with IMT, of the femoral artery. In patients without insulin therapy (n=52), both fasting plasma insulin concentration (r=-0.323, P=0.0023) and HOMA IR, an insulin resistance index, (r=-0.281, P=0.0084) were negatively correlated with TcPO2 index. Multiple regression analyses showed that association of stiffness beta of the femoral artery or HOMA IR with the TcPO2 index was independent of other factors including age, smoking index, ankle brachial pressure index and IMT of femoral artery. Thus, arterial wall stiffness of femoral artery appears to be a major determinant of peripheral circulation in patients with type 2 diabetes.     

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.     

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.     

Metabolic syndrome is associated with greater histologic severity, higher carbohydrate, and lower fat diet in patients with NAFLD

OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is considered as the hepatic manifestation of metabolic syndrome. Insulin resistance (IR) is a key component of metabolic syndrome. The aim was to determine the dietary composition, physical activity, and histologic severity between NAFLD patients with and without metabolic syndrome. METHODS: Ninety-one patients with NAFLD completed the Block Food Frequency Questionnaire and the Paffenbarger Physical Activity Questionnaire. IR was assessed by the homeostasis model assessment (HOMA) index. Metabolic syndrome was defined by the ATP III clinical definition. Nonalcoholic steatohepatitis (NASH) Clinical Network Scoring System was used to determine the histologic severity of NAFLD. RESULTS: Thirty-one patients (34%) had metabolic syndrome. Patients with metabolic syndrome had a higher HOMA index (7.66 vs 4.45, p = 0.04), and consumed more carbohydrates (51%vs 45%, p = 0.03) and less fat (34%vs 40%, p = 0.01) compared with those without metabolic syndrome; total daily calorie, protein consumption, and physical activity were similar between the two groups. Patients with metabolic syndrome had higher scores for steatosis (2.0 +/- 0.8 vs 1.37 +/- 1, p = 0.02), NASH activity (4.13 +/- 1.4 vs 3.13 +/- 1.7, p = 0.004), and global NASH score (5.9 +/- 1.7 vs 4.4 +/- 2.3, p = 0.0006) compared with those without metabolic syndrome. When controlled for other factors including dietary composition and physical activity, the presence of metabolic syndrome was a significant risk factor for global NASH severity in addition to HOMA index and female gender. CONCLUSION: Metabolic syndrome in patients with NAFLD is associated with a diet containing more carbohydrate and less fat and greater histologic severity. The role of a carbohydrate-restricted diet in decreasing the risk for metabolic syndrome and histologic severity should be assessed in patients with NAFLD.     

The influence of serum aldosterone and the aldosterone-renin ratio on pulse wave velocity in hypertensive patients

OBJECTIVE: The aldosterone-renin ratio (ARR) is widely used to screen for primary aldosteronism, and may reflect a relative excess of aldosterone secretion compared with renin secretion. Excess aldosterone may have a detrimental effect on vascular stiffness. We therefore hypothesized that ARR and aldosterone are independently correlated with pulse wave velocity (PWV) in hypertensive patients. METHODS: The study consisted of 438 hypertensive patients. Serum aldosterone and plasma renin activity were measured in a sitting position using standard techniques. The PWV was determined by measuring the heart to femoral PWV (hfPWV) and brachial to ankle PWV with a VP-2000 pulse wave unit. RESULTS: Group 1 was defined as patients with ARR of at least 20 (n = 53) with serum aldosterone >or= 12 ng/dl, while the remainder comprised group 2. Comparisons between the two groups reveal group 1 tended to have higher age, significantly higher proportion of women and higher systolic/diastolic blood pressure. Patients in group 1 also had a significantly higher index of central arterial stiffness (hfPWV 1048 +/- 202 vs 978 +/- 182, P = 0.010) compared with group 2. Multiple linear regression revealed that aldosterone, but not the ARR, is significantly associated with hfPWV but not brachial to ankle PWV, after controlling for age, systolic blood pressure and heart rate at the time of PWV measurement, body mass index, gender, low-density lipoprotein-cholesterol, triglyceride, high-density lipoprotein-cholesterol, blood pressure medication and statins. CONCLUSIONS: Serum aldosterone is significantly associated with central aortic PWV in hypertensive patients. The results demonstrate a possible role for aldosterone in developing central aortic stiffness and increased PWV in hypertensive patients.     

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.     

脉搏波传导速度临床意义及其与代谢综合征相关性研究进展

脉搏波传导速度(pulse wave velocity,PWV)作为评估动脉僵硬度的指标其重要意义在于其是心血管事件的独立预测因子。本文就PWV的监测原理、种类、测量方法、影响因素及其与代谢综合征的相关性研究进展进行综述。     

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.     

Arterial stiffness mediates the effect of salt intake on systolic blood pressure

Accumulating evidence indicates that higher levels of salt intake are associated with higher blood pressure levels. The aim of our analysis was to test the hypothesis that the effect of urinary sodium excretion (UNaV) on systolic blood pressure (SBP) is mediated through estimated glomerular filtration rate (eGFR) and arterial stiffness and also to test the direction of the relationship between eGFR and arterial stiffness, in both hypertensive and normotensive patients. We assessed the potential for connection between UNaV and SBP and mediators (eGFR and pulse wave velocity [PWV]) of this relationship using structural equation models of data from 1599 adults ≥18 years of age and without chronic kidney disease who participated in the Third Epidemiologic Study concerning the Prevalence of Arterial Hypertension and Cardiovascular Risk in Romania (SEPHAR III). In hypertensive patients, the indirect effect, mediated through PWV, of UNaV on SBP was 23.9% and 27.7% of the total effect of UNaV on SBP, while in normotensive patients the contribution of PWV to the total effect of UNaV on SBP was slightly lower (15.9% and 18.3% of the total effect of UNaV on SBP). Taken together, our findings support the conclusion that UNaV influences SBP, both directly and indirectly, through the effect on PWV.     

Metabolic syndrome and age-related progression of aortic stiffness.

Aortic stiffness measured from pulse wave velocity (PWV) was studied during a six-year period in a population of subjects with zero to three and more cardiovascular (CV) factors involving hypertension, body mass index, dyslipidemia, hypertriglyceridemia, and hyperglycemia. During the follow-up, the increase in PWV was significantly higher in subjects with three and more CV risk factors (i.e., in subjects with metabolic syndrome) than in subjects with zero, one, or two factors, even after adjustments for confounding factors. Metabolic syndrome involves an increased progression of arterial stiffness with age and, thus, favors premature senescence. OBJECTIVES: The purpose of the study was to evaluate whether a clustering of metabolic risk factors might accelerate the progression of arterial stiffness with age in subjects with metabolic syndrome (MS). BACKGROUND: Arterial stiffness is increased in MS, but the genetic and environmental factors that might influence its progression are unknown. METHODS: Four hundred seventy-six subjects were classified at baseline according to their number of cardiovascular (CV) risk factors (from zero to three and more), after adjustment for smoking habits. The CV risk factors were: hypertension, body mass index, dyslipidemia, hypertriglyceridemia, and hyperglycemia, classified according to traditional criterions. Subjects were followed for six years and had, at the beginning and end of the survey, determinations of blood pressure (BP), heart rate (HR), and aortic pulse wave velocity (PWV). RESULTS: At baseline, BP, HR, plasma creatinine, and PWV were significantly higher (p < 0.001) in the group with three and more CV risk factors than in groups with zero to two risk factors. During the follow-up, the increase in PWV, but not in pulse pressure, was significantly higher (p < 0.01) in the group with three and more risk factors (i.e., metabolic syndrome) than in other groups. Results were unmodified after adjustments for age, gender, baseline values, drug treatment, smoking habits, and mean arterial pressure. CONCLUSIONS: Metabolic syndrome is associated with an increased progression of aortic stiffness with age, supporting premature senescence in these patients.     

Overweight women with polycystic ovary syndrome have evidence of subclinical cardiovascular disease

CONTEXT: Polycystic ovary syndrome (PCOS) is associated with insulin resistance (IR) and the metabolic syndrome. There are no adequate data demonstrating significantly increased cardiovascular disease (CVD) mortality. In the absence of clinical outcome studies, surrogate markers of early CVD can provide insight into early CVD. OBJECTIVE: The aim of this study was to clarify whether overweight women with PCOS have an increased prevalence of cardiovascular risk factors and early CVD, compared with age- and body mass index-matched controls, to determine the contribution of PCOS per se to CVD status. DESIGN AND PATIENTS: This was a case control study of 100 overweight women with PCOS and 20 subjects of similar body mass index and age. MAIN OUTCOME MEASURES: Noninvasive markers of early CVD [carotid intimal media thickness, pulse wave velocity (PWV), and brachial arterial flow-mediated vasodilation] were measured. Metabolic parameters studied included insulin, glucose, C-reactive protein, lipids, and androgens. RESULTS: Subjects with PCOS had elevated testosterone (2.5 +/- 0.2 vs. 1.3 +/- 0.1 nmol/liter), dehydroepiandrosterone sulfate (4.9 +/- 0.3 vs. 3.6 +/- 0.4 mmol/liter), fasting insulin (19.6 +/- 1.4 vs. 6.8 +/- 0.8 microU/ml), and homeostasis model assessment of IR (4.1 +/- 0.3 vs. 1.3 +/- 0.2), compared with controls. In addition, those with PCOS had elevated cholesterol (5.1 +/- 0.1 vs. 4.6 +/- 0.2 mmol/liter) and triglycerides (1.4 +/- 0.1 vs. 0.9 +/- 0.1 mmol/liter), whereas there were no differences in either C-reactive protein or 24-h ambulatory blood pressure parameters. Subjects with PCOS also had increased arterial stiffness (PWV, 7.4 +/- 0.1 vs. 6.6 +/- 0.2 m/sec) and endothelial dysfunction (flow-mediated vasodilation, 9.8 +/- 0.4 vs. 13.3 +/- 0.9), compared with controls. There was no difference in mean intimal media thickness between the groups. Stepwise regression in PCOS subjects showed that IR and lipids were independent predictors of PWV. CONCLUSION: Overweight women with PCOS have increased cardiovascular risk factors and evidence of early CVD, compared with weight-matched controls, potentially related to IR.     

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.