Macro- and microvascular alterations in patients with metabolic syndrome: sugar makes the difference

Metabolic syndrome (MS) is associated with adverse cardiovascular events, although its prognostic significance over and beyond the clustering risk factors is controversial. Moreover, there are no data on the possible differentiation of target organ damage among patients with MS according to the grade of its distinct components. We studied 500 hypertensive patients with MS and we assessed vascular damage according to glucose metabolic status (1, normal glucose metabolism (NG); 2, impaired fasting glucose (IFG); 3, impaired glucose tolerance (IGT); and 4, diabetes mellitus II (DM II)). Macrovascular damage was assessed with arterial stiffness by measuring carotid-femoral pulse wave velocity (PWV). Microvascular damage was assessed with albumin excretion by estimating the albumin-creatinine ratio (ACR). There was a significant progressive increase in PWV from group 1 to group 4 (from 7.97 to 8.83 to 8.94 to 10.27ms(-1), respectively) that remained statistically significant even after adjustment for several confounders (P<0.001). Similar trends were also observed for ACR (from 27.44 to 29.94 to 36.26 to 73.07 mgg(-1), P<0.001). In multiple regression analysis, both PWV and ACR were independently related to glucose metabolic status (P= 0.001 and P<0.001, respectively). Vascular alterations among patients with MS differ according to the grade of glucose dysregulation. Considering the adverse prognostic role of arterial stiffness and microalbuminuria, it might be argued that the cardiovascular risk is not homogeneously distributed among patients with MS but is largely determined by glucose metabolic status

Relationship between low-grade inflammation and arterial stiffness in patients with essential hypertension

Background Arterial stiffness is an independent cardiovascular risk factor in hypertensive individuals. Inflammation is associated with increased arterial stiffness and is implicated in the pathogenesis of hypertension. Objectives To examine whether low-grade inflammation contributes to arterial stiffness and wave reflections independently of blood pressure, in patients with essential hypertension and in controls. Methods We studied 235 consecutive patients with uncomplicated, never-treated essential hypertension and 103 sex- and age-matched controls. The level of inflammation was evaluated with high-sensitivity C-reactive protein (hsCRP) and serum amyloid A (SAA Arterial stiffness was assessed with carotid-femoral (c-f) and carotid-radial (c-r) pulse wave velocity (PWV), and wave reflections with augmentation index (Alx). Results In the hypertensive group, in multiple regression analysis, both PWVc-f and PWVc-r were independently correlated with log hsCRP (beta = 0.56, P = 0.006 and beta = 0.45, P = 0.016, respectively), whereas no correlation was found between PWV and log SAA (P = NS). No significant correlation was observed between heart-rate-corrected Aix and log hsCRP (P = NS) and log SAA (P = 0.07) in the same group. Similarly, in the control group, an independent association was observed between PWVc-f and PWVc-r with log hsCRP (beta = 0.68, P = 0.05 and beta = 0.74, P = 0.05 respectively), but not with log SAA (P = NS). Furthermore, no significant association was shown between heart-rate-corrected Alx and log hsCRP or log SAA (P = NS) in the control group. (P = 0.07) in the same group. Similarly, in the control group, an independent association was observed between PWVc-f and PWVc-r with log hsCRP (beta = 0.68, P = 0.05 and beta = 0.74, P = 0.05 respectively), but not with log SAA (P = NS). Furthermore, no significant association was shown between heart-rate-corrected Alx and log hsCRP or log SAA (P = NS) in the control group. Conclusions In hypertensive individuals, hsCRP is related to PWV, a direct marker of arterial stiffness, but not to Alx, a measure of wave reflections. Whether inflammation might act as a pathogenetic or modulating factor in arterial stiffening in chronic hypertension has to be confirmed

Correlation of 24-Hour Blood Pressure and Heart Rate Variability to Renal Function Parameters in Hypertensive Patients. The Effect of Smoking

Intrarenal hemodynamics depend on blood pressure (BP), heart rate (HR), and smoking. Although BP levels have been associated with kidney function, the effect of HR levels, BP, and HR variability on renal function are less well clarified. This cross-sectional study sought to determine the association of 24-hour BP and HR variability with kidney function in hypertensive patients, stratified by smoking. The study comprised 9600 nondiabetic, never-treated hypertensive individuals without evident renal impairment examined from 1985 to 2014 (aged 53.3 +/- 13.4 years, 55.3% males). The 24-hour systolic BP (SBP) and HR variability were estimated via their coefficient of variation (C-V=standard deviation x 100/mean value) derived from ambulatory recording. The CVSBP-to-CVHR ratio (CVR) was used as a marker of the interplay between 24-hour SBP and HR variability. Renal function was estimated via 24-hour urine creatinine clearance (CrCl), estimated glomerular filtration rate (eGFR), albumin-to-creatinine ratio (ACR), and 24-hour urine alpha(1)-microglobulin. After adjustment for age, sex, and smoking, CVSBP was found to be weakly correlated to eGFR (r=-0.017, P=.1) and somewhat more strongly to CrCl, ACR, and alpha 1-microglobulin (r=-0.032, 0.072, and 0.065; P=.002, <.001 and <.001, respectively). CVHR was much better related to renal function, with stronger adjusted correlations to CrCl, eGFR, ACR, and alpha 1-microglobulin (r=0.185, 0.134, -0.306, -0.247; all P<.001, respectively). CVR also showed equally good adjusted correlations (r=-0.175, -0.125, 0.336, 0.262; all P<.001, respectively). Most adjusted correlations for CVHR and CVR were even better in smokers (r=0.213, 0.158, -0.332, -0.272 and -0.183, -0.118, 0.351, 0.275, respectively; all P<.001). CVHR and CVR emerge as better related to kidney function than CVSBP, especially in smokers. The correlation of CVHR and CVSBP to renal function is inverse to each other. ACR and alpha 1-microglobulin are better related to variability indices than CrCl and eGFR. However, causal relations cannot be proved. (C) 2015 Wiley Periodicals, Inc

Office blood pressure is a predictor of aortic elastic properties and urinary protein excretion in subjects with white coat hypertension

Background: White coat hypertension (WCH) is related to target organ damage and increased cardiovascular risk. Arterial elastic properties and urinary protein excretion are determinants of cardiovascular performance and predictors of outcomes. We investigated whether office blood pressure (BP) is a better determinant of arterial and renal function than the ambulatory BP in WCH patients. Methods: We studied 440 consecutive untreated non-diabetic patients with WCH (office BP > 140/90 mm Hg, mean daytime ambulatory BP < 135/85 mm Hg). Arterial function was evaluated with carotid-femoral pulse wave velocity (cfPWV), an index of aortic stiffness, and aortic augmentation index (AIx), a composite marker of aortic stiffness and wave reflections. In 24-hour urine, albumin excretion and albumin/creatinine ratio (ACR) were measured as markers of glomerular function and urinary alpha(1)-microglobulin was measured as a marker of renal tubular function. Results: In univariate analysis, office systolic BP correlated significantly with cfPWV (r = 0.245, P < 0.001), AIx (r = 0.31, P < 0.001), albumin (r = 0.134, P = 0.005), ACR (r = 0.199, P < 0.001) and alpha(1)-microglobulin (r = 0.118, P = 0.013). In contrast, mean ambulatory systolic BP did not correlate with arterial function or urinary proteins (all P > 0.5). Hierarchical multilevel linear regression analysis showed that office systolic BP is an independent determinant of cfPWV(P=0.050), AIx (P=0.029), albumin (P=0.002) and ACR (P=0.001) and has a borderline association with alpha(1)-microglobulin (P=0.088). Conclusions: In non-diabetic WCH individuals, office systolic BP is an independent predictor of aortic elastic properties and urinary protein excretion, whereas ambulatory BP is not. This finding suggests that office BP may be a marker of cardiovascular risk in subjects with WCH. (C) 2015 Elsevier Ireland Ltd. All rights reserved

Early adverse effect of abnormal glucose metabolism on arterial stiffness in drug naive hypertensive patients

Arterial stiffness is independently related to increased cardiovascular risk in the hypertensive population. The aim of the present study was to investigate whether various stages of abnormal glucose metabolism may differently affect arterial stiffness in hypertensive patients and whether there is any difference in arterial stiffness among patients with normal glucose regulation. We studied 1375 never-treated hypertensive subjects. Participants were divided into four metabolic groups: normal glucose regulation (NG), impaired fasting glucose, impaired glucose tolerance and type-2 diabetes mellitus (DM 2). Hypertensive subjects with NG were subdivided into three groups according to glucose levels. Arterial stiffness was estimated by carotid-femoral pulse wave velocity (PWV). PWV showed a significant increase from patients with NG to DM 2 (from 7.74 +/- 1.38 to 8.40 +/- 1.30 to 8.86 +/- 1.30 to 10.09 +/- 2.07 m/s respectively, p<0.001). Among hypertensive subjects with NG there was an increase in PWV from low normal to high normal values of glucose (p<0.01). PWV was independently related to all glucose metabolic parameters (p<0.001 for all). In the present study, we demonstrated an association between arterial stiffness and glucose tolerance in hypertensive subjects. Given the prognostic significance of arterial stiffness, aims should be towards closer monitoring and intensive care of hypertensive patients with abnormal glucose metabolism

Twenty-Four-Hour Urine (1)-Microglobulin as a Marker of Hypertension-Induced Renal Impairment and Its Response on Different Blood Pressure-Lowering Drugs

The purpose of this study was to assess the role of urine (1)-microglobulin as a marker of hypertension-induced renal damage compared with estimated glomerular filtration rate, (eGFR), urine albumin, and urine albumin-to-creatinine ratio (ACR). Its response on different blood pressure (BP)-lowering drugs was also studied. Sixty never-treated hypertensive patients (65.0% men, 46.9 years, BP 141.4/94.0 mm Hg) were randomized to an irbesartan (an angiotensin receptor blocker [ARB]) or a diltiazem (a nondihydropyridine calcium channel blocker [CCB])-based regimen. Patients with diabetes or established cardiovascular, renal, or liver disease were excluded. Blood samples and 24-hour urine were analyzed at baseline and 6 months after pharmaceutical BP normalization. Serum creatinine was measured and eGFR was calculated. Urine albumin, creatinine, and (1)-microglobulin were measured and ACR was calculated. Minor changes (P=not significant [NS]) in eGFR were noted during follow-up in both groups (from 111.0 mL/min/1.73 m(2) to 108.4 mL/min/1.73 m(2) in the ARB group and from 111.3 mL/min/1.73 m(2) to 114.0 mL/min/1.73 m(2) in the CCB group). Twenty-four-hour urine indices were all significantly improved (P<.01) in the ARB group (albumin from 19.4 mg/L to 8.2 mg/L, ACR from 21.5 mg/g to 10.0 mg/g, (1)-microglobulin from 5.06 mg/L to 3.64 mg/L) but not (P=NS) in the CCB group (albumin from 15.6 mg/L to 13.9 mg/L, ACR from 17.6 mg/g to 17.1 mg/g, (1)-microglobulin from 4.94 mg/L to 4.79 mg/L). These differences between groups remained significant (P<.05) after adjusting for office heart rate and BP. (1)-Microglobulin was significantly correlated (P<.05) with albumin and ACR both at baseline (r=0.283 and 0.299, respectively) and at the end of follow-up (r=0.432 and 0.465, respectively) but not (P=NS) with eGFR. It was also significantly related (P<.05) to cardiovascular risk scores (Framingham and HeartScore) both at baseline (r=0.264 and 0.436, respectively) and at the end of follow-up (r=0.308 and 0.472, respectively). Urine (1)-microglobulin emerges as a potentially usable marker of hypertension-induced renal impairment. Its excretion rate and its response to treatment appears similar to that of albumin. Irbesartan but not diltiazem seems to be associated with reduced excretion of alpha(1)-microglobulin in urine. (C) 2016 Wiley Periodicals, Inc

Changes in aortic root function after valve replacement in patients with aortic stenosis

Background: Aortic elastic properties are compromised in various states that induce functional and histological changes in the aortic wall. Aortic stenosis is frequent and often requires replacement of the stenotic valve. The purpose of this study was to examine the effect of aortic valve replacement on the aortic root function. Methods: 31 patients, mean +/- SD age 67.2 +/- 9.1 years with severe aortic stenosis, who underwent aortic valve replacement with a bileaflet mechanical prosthesis, were studied. Aortic root function indices such as aortic cross-sectional compliance (CSC), aortic root distensibility (ARD), and aortic stiffness index (ASI) were calculated with the use of M-mode echocardiography in three sessions: one preoperatively (pre-op), one on day 7 postoperatively (early post-op), and one 6 months postoperatively (late post-op). Results: Aortic root function deteriorated early post-op (p < 0.001 for all) and returned towards pre-op levels late post-op (p = NS for all). CSC changed from 2.84 +/- 1.98 to 1.37 +/- 0.92, and 2.30 +/- 1.11 cm(2)/mmHg, ARD from 2.21 +/- 5.60 to 1.01 +/- 0.67, and 1.79 +/- 0.96 cm(2)/dyne, and ASI from 9.72 +/- 5.60 to 24.65 +/- 19.10, and 11.51 +/- 7.85, respectively. Correlations were found between early changes in some aortic root indices and the degree of aortic stenosis, denoting that aortic function deteriorated less in more severe cases of aortic stenosis. None of the late changes were related to aortic valve or left ventricular indices. Conclusions: Aortic valve replacement with a mechanical valve results in a significant but transient impairment of aortic distensibility. (c) 2005 Elsevier Ireland Ltd. All rights reserved

Atherosclerosis of the Aorta in Patients With Acute Thoracic Aortic Dissection

Background The role of atherosclerosis in thoracic aortic dissection has not been established yet. Transesophageal echocardiography (TEE) is an imaging modality widely used in the diagnostic evaluation of thoracic aortic dissection, and it can detect aortic atherosclerotic plaques and assess their size and specific characteristics. Methods and Results One hundred consecutive patients with thoracic aortic dissection and adequate imaging of the thoracic aorta by TEE were studied. The type of dissection (proximal or distal) and the presence and the degree of aortic atherosclerosis were defined. Proximal aortic dissection (Stanford type A) was found in 64 patients. Patients with proximal dissection were younger than those with distal (type B; 58 +/- 13 vs 67 +/- 11 years, p < 0.001). The prevalence of arterial hypertension was higher in patients with distal dissection compared with those with proximal. Aortic atherosclerosis was present in less patients with proximal than with distal dissection (67% vs 94%, p < 0.002). Logistic regression analysis revealed that patients with severe atherosclerosis were 7.6-fold more probable to have type B than type A dissection (p < 0.001). Conclusion Aortic atherosclerosis is more associated with distal than with proximal aortic dissection. (Circ J 2008; 72: 1773-1776