Elli Stefanadi

Thermal Heterogeneity Within Human Atherosclerotic Coronary Arteries Detected In Vivo A New Method of Detection by Application of a Special Thermography Catheter

BACKGROUNDnActivated macrophages play an important role in the pathogenesis of acute ischemic syndromes. It has been postulated that detection of heat released by activated inflammatory cells of atherosclerotic plaques may predict plaque rupture and thrombosis. Previous ex vivo studies have shown that there is thermal heterogeneity in human carotid atherosclerotic plaques.nnnMETHODS AND RESULTSnTo measure the temperature of human arteries in vivo, we developed a catheter-based technique. Ninety patients (45 with normal coronary arteries, 15 with stable angina [SA], 15 with unstable angina [UA], and 15 with acute myocardial infarction [AMI]) were studied. The thermistor of the thermography catheter has a temperature accuracy of 0.05 degrees C, a time constant of 300 ms, and a spatial resolution of 0.5 mm. Temperature was constant within the arteries of the control subjects, whereas most atherosclerotic plaques showed higher temperature compared with healthy vessel wall. Temperature differences between atherosclerotic plaque and healthy vessel wall increased progressively from SA to AMI patients (difference of plaque temperature from background temperature, 0. 106+/-0.110 degrees C in SA, 0.683+/-0.347 degrees C in UA, and 1. 472+/-0.691 degrees C in AMI). Heterogeneity within the plaque was shown in 20%, 40%, and 67% of the patients with SA, UA, and AMI, respectively, whereas no heterogeneity was shown in the control subjects.nnnCONCLUSIONSnThermal heterogeneity within human atherosclerotic coronary arteries was shown in vivo by use of a special thermography catheter. This heterogeneity is larger in UA and AMI, suggesting that it may be related to the pathogenesis.

ADMA, C-Reactive Protein, and Albuminuria in Untreated Essential Hypertension: A Cross-sectional Study

BACKGROUNDnAsymmetric dimethylarginine (ADMA) and subclinical inflammation are associated with atherosclerosis progression, whereas microalbuminuria is an established index of hypertensive organ damage.nnnSTUDY DESIGNnCross-sectional.nnnSETTING & PARTICIPANTSnIn an outpatient hypertensive unit, 296 nondiabetic and untreated participants with hypertension were studied. Participants with atherosclerotic cardiovascular disease, severe valvulopathy, congestive heart failure, presence of neoplastic or other concurrent systemic disease, atrial fibrillation, serum creatinine level > 1.5 mg/dL in men and > 1.4 mg/dL in women, and urinary albumin excretion > 300 mg/24 h were excluded.nnnPREDICTORSnADMA and high-sensitivity C-reactive protein (hs-CRP) levels.nnnOUTCOME VARIABLEnAlbuminuria assessed using albumin-creatinine ratio (ACR).nnnMEASUREMENTSnParticipants underwent ambulatory blood pressure monitoring, echocardiography, routine assessment of metabolic profile, ADMA, and hs-CRP, whereas ACR was determined as the mean of 3 values in nonconsecutive morning spot urine samples.nnnRESULTSn64 participants had an ACR of 30-300 mg/g. Stratification based on ADMA level showed that participants with hypertension in quartile [Q] 4 compared with those in Q3, Q2, and Q1 showed the highest ACRs (53.2 vs 31.2 vs 30.4 vs 16.7 mg/g; P < 0.008 for all). Moreover, stratification based on hs-CRP level showed that participants with hypertension in Q4 (69.8% had microalbuminuria) showed the highest ACRs (72.2 vs 25.6, 16.2, and 19.2 mg/g for Q3, Q2, and Q1, respectively; P < 0.008 for all). Stepwise regression analysis showed that age, 24-hour systolic blood pressure, hs-CRP level, ADMA level, and the interaction of hs-CRP with ADMA were independent predictors of ACR (R(2) = 0.674; P < 0.001).nnnLIMITATIONSnCross-sectional study.nnnCONCLUSIONSnIn patients with untreated essential hypertension, increased hs-CRP and ADMA levels are associated with microalbuminuria, suggesting the involvement of inflammation and endothelial dysfunction in vascular and kidney damage.

Exercise Blood Pressure Response, Albuminuria and Arterial Stiffness in Hypertension

BACKGROUNDnA hypertensive response to exercise is associated with high cardiovascular risk, whereas the data about its relation to surrogates of subclinical atherosclerosis are scarce. We investigated the relationships of a hypertensive response to exercise with urinary albumin excretion and arterial stiffness in hypertensives.nnnMETHODSnThere were 171 untreated males (mean age 52 years, all Caucasian) with stage I-II essential hypertension and a negative treadmill exercise test divided into those with a hypertensive response to exercise (n=48) (peak exercise systolic blood pressure > or =210 mm Hg) and to those with normal blood pressure response (n=123). Albumin-to-creatinine ratio values were determined as the mean of 3 nonconsecutive morning spot urine samples, and arterial stiffness was evaluated on the basis of carotid-to-femoral pulse wave velocity.nnnRESULTSnPatients with a hypertensive response to exercise compared with those with normal blood pressure response exhibited greater log albumin-to-creatinine ratio (1.52+/-0.59 vs 0.97+/-0.33 mg/g) and higher pulse wave velocity (8.7+/-1.6 vs 7.7+/-1.2 m/s), independent of potentially confounding demographic and clinical factors. Resting systolic blood pressure (odds ratio [OR] 1.11, 95% confidence interval [CI], 1.06-1.16), body mass index (OR 1.12, 95% CI, 1.02-1.23), resting heart rate (OR 0.96, 95% CI, 0.93-0.99), and albumin-to-creatinine ratio (OR 7.45, 95% CI, 2.54-21.83) were independently associated with a hypertensive response to exercise.nnnCONCLUSIONnA hypertensive response to exercise is related to augmented albumin-to-creatinine ratio and arterial stiffness, reflecting accelerated subclinical atherosclerosis. The association of albumin excretion with exercise blood pressure response suggests that albuminuria constitutes an important factor in the interpretation of the hypertensive response to exercise-associated risk.

Oxidative stress and inflammatory process in patients with atrial fibrillation: The role of left atrium distension

BACKGROUNDnAtrial fibrillation has been associated with increased oxidative stress, elevated inflammatory status and endothelial dysfunction. However, the underlying mechanisms regulating the expression of inflammatory markers or oxidative stress status are unclear. We searched for clinical determinants of oxidative stress status, endothelial function and inflammatory process in patients with chronic atrial fibrillation.nnnMETHODSnSixty nine patients with chronic atrial fibrillation at a stable clinical state were recruited. Ejection fraction of the left ventricle and the dimensions of the left atrium were determined echocardiographically. Flow mediated dilatation (FMD) was evaluated in the brachial artery, while serum oxidized LDL (ox-LDL), matrix metalloproteinase-9 (MMP-9), soluble CD40-ligand (sCD40L) and C-reactive protein (CRP) were measured.nnnRESULTSnFMD was correlated with CRP (r=-0.423, p=0.028), independently of other clinical parameters (beta(SE): -0.0039(0.00159), p=0.022). Ox-LDL was significantly correlated with left atrium diameter(r=0.358, p=0.005) independently of other clinical variables (beta(SE):1.288(0.455), p=0.007). The only independent predictors of MMP-9 were sCD40L (beta(SE):17.232(7.654), p=0.028), CRP (beta(SE):4.249(2.186), p=0.05) and gender (beta(SE):204.657(68.153), p=0.004), but not left atrium dimensions. Independent predictors of CRP were hypertension (beta(SE): 8.531(3.973), p=0.036), sCD40L (beta(SE): 0.779(0.408), p=0.06) and age (beta(SE): 0.381(0.201), p=0.063).nnnCONCLUSIONSnThere is a strong link between inflammation and endothelial function, in patients with atrial fibrillation. The maximum diameter of left atrium is the only independent predictor of oxidized LDL, suggesting that left atrium distension may predict oxidative stress status in these patients.

Stents covered by an autologous arterial graft in porcine coronary arteries: feasibility, vascular injury and effect on neointimal hyperplasia

OBJECTIVEnThe use of stents has improved results after balloon coronary angioplasty. Several materials have been proposed for covering the metallic surface of the stent to reduce the rate of subacute thrombosis and restenosis. In our institution, an autologous arterial graft was used for covering the external surface of a conventional stent. The angiographic and histological response in a porcine coronary artery model was investigated.nnnMETHODSnAn autologous arterial graft was removed from the femoral artery and carefully prepared. Subsequently, a conventional stent was covered externally by the arterial graft. Twenty-two covered stents and 22 uncovered regular stents were implanted alternatively in the coronary arteries of 22 pigs. One animal died immediately after the procedure, due to thrombus formation in the uncovered stent. Six animals were sacrificed at seven days and the remaining animals were sacrificed at two months. Before the sacrifice, coronary angiography was performed in all animals.nnnRESULTSnThrombosis was detected in two control segments and in one covered stented segment. After seven days, the luminal surface of the covered stents was covered by a new endothelial layer in contrast to partial endothelial cell appearance in the control group. The angiographic parameters were similar between the two groups. Histologically, the covered stents were associated with less vascular injury compared to uncovered stents. In covered stents a trend towards reduction of maximal intimal hyperplasia was detected (covered: 116.6 +/- 47.75 vs uncovered: 150.25 +/- 46.81 microns, p = 0.08); also the thickness of the arterial media was reduced (covered: 21.34 +/- 10.28 vs uncovered: 102.63 +/- 18.71 microns, p = 0.02). The luminal and vessel areas were similar in the two groups.nnnCONCLUSIONSnThe preparation and implantation of the autologous arterial graft-covered stent is technically safe and feasible. This type of covered stent results in accelerated endothelialization, less vascular injury, thinning of the arterial media and a trend to reduce the intimal hyperplasia in normal coronary arteries.

Early initiation of low-dose atorvastatin treatment after an acute ST-elevated myocardial infarction, decreases inflammatory process and prevents endothelial injury and activation

BACKGROUNDnHigh-dose statin treatment improves clinical outcome of ST-elevated myocardial infarction (STEMI). However, the effect of low-dose atorvastatin treatment on inflammatory and pro-thrombotic molecules during the post-STEMI period is unclear. We investigated the effect of low-dose atorvastatin treatment on the kinetics of cytokine IL-6, vascular cell adhesion molecule (sVCAM-1) and endothelium-derived markers of thrombosis/fibrinolysis such as von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA), post STEMI.nnnMETHODSnTwenty-four normocholesterolemic patients with STEMI were randomised to receive atorvastatin 10mg/day or no statin treatment for 6 weeks after the event. Blood samples were obtained by their admission to the hospital as well as at weeks 1 and 6. Circulating levels of IL-6, sVCAM-1, vWF, PAI-1 and tPA were determined by ELISA.nnnRESULTSnAtorvastatin induced a decrease of IL-6 at 1 week, an effect which reached significance compared to baseline at 6 weeks post STEMI (p<0.05 vs baseline). Serum sVCAM-1 was increased in controls both at 1 and 6 weeks post-STEMI (p<0.05 vs baseline), an effect prevented by atorvastatin. Plasma vWF was increased 1 week post-STEMI in controls (p<0.05 vs baseline) and returned to baseline at 6 weeks, an effect prevented by atorvastatin. Plasma PAI-1, tPA and the PAI-1/tPA ratio remained unchanged in both groups.nnnCONCLUSIONnEarly initiation of low-dose atorvastatin treatment decreases the expression of IL-6 and sVCAM-1 and the release of vWF in patients with STEMI. Therefore, low-dose atorvastatin, modulates inflammatory response and decreases endothelial injury and activation in patients with recent STEMI.

Impact of waist circumference on cardiac phenotype in hypertensives according to gender.

Our aim was to assess the differential effect of waist circumference on left‐ventricular (LV) structural and functional alterations, in hypertensive males and females. One thousand seven hundred and eighty nine consecutive, nondiabetic, essential hypertensives (aged 55.8 ± 13.5 years, 966 females), included in the 3H Study, an ongoing registry of hypertension‐related‐target‐organ damage, were classified to obese and nonobese groups according to Adult Treatment Panel III criteria. All participants underwent complete echocardiographic study including LV diastolic function evaluation by means of conventional and tissue Doppler imaging (TDI) methods, averaging early and late diastolic mitral annular peak velocities (Em, Am, Em/Am) from four separate sites of measurement. Hypertensive obese women compared with nonobese exhibited significantly greater LV mass index and prevalence of LV hypertrophy (by 5.5 g/m2, P = 0.003, and 8.8%, P = 0.005, respectively), while such differences were not present among men. Obese women compared to nonobese ones were accompanied by lower transmitral E/A (by 0.08, P < 0.001), TDI‐derived Em/Am (by 0.12, P < 0.001), and higher E/Em ratio (by 0.8, P = 0.016). In contrast, hypertensive obese men compared to nonobese ones exhibited lower E and Em (by 0.04 m/s and 0.6 cm/s, both P < 0.05). A significant interaction between sex and abdominal obesity was observed only regarding TDI‐derived Am and Em/Am. Furthermore, waist circumference was a predictor of E/A (β = −0.097, P = 0.002) and Em/Am (β = −0.116, P = 0.001), independently of body size, in females but not in males. The adverse effect of abdominal obesity on LV alterations is more pronounced among female hypertensives, suggesting that routine measurement of waist circumference provides additional information on cardiac phenotype especially in women.

The dominant role of the systolic component of nondipping status on target-organ damage in never-treated hypertensives.

BACKGROUNDnBlood pressure (BP) nondipping has been associated with target-organ damage (TOD) and adverse outcomes in hypertension. Diverse definitions of nondipping status appear in the literature, regarding the BP components taken into account. Aim of this study was to compare the effects of isolated nondipping of systolic, diastolic and combined systolic and diastolic BP on various indices of TOD.nnnMETHODSnFrom 630 consecutive subjects with never-treated essential hypertension stage I-II, we selected 279 subjects who were consistently isolated systolic nondippers (SND, n=76) isolated diastolic nondippers (DND, n=64) and combined systolic and diastolic nondippers (SDND, n=139) in two ambulatory BP monitoring sessions. All three subgroups were subjected to echocardiographic examination, carotid-femoral pulse wave velocity (PWV(c-f)) and albumin-to-creatinine ratio (ACR) determination. Metabolic profile was determined in a morning blood sample.nnnRESULTSnSND compared to DND and SDND exhibited higher left ventricular mass/height(2.7) (42.4 ± 9.9 vs. 38.0 ± 9.1 vs. 40.9 ± 11.0 g/m(2.7), P < 0.05), higher log(10)(PWV(c-f)) (0.94 ± 0.07 vs. 0.86 ± 0.05 vs. 0.91 ± 0.07 m/s, P < 0.005), and higher log(10)(ACR) (1.2 ± 0.5 vs. 0.9 ± 0.3 vs. 1.1 ± 0.4 mg/g, P < 0.05). Isolated systolic BP nondipping was an independent determinant of all the studied indices of TOD whereas isolated diastolic BP nondipping was not.nnnCONCLUSIONSnIsolated systolic as compared to diastolic and to combined systolic/diastolic BP nondipping is associated with higher left ventricular mass, stiffer arteries, and pronounced urinary albumin excretion.

The conjoint detrimental effect of chronic periodontal disease and systemic inflammation on asymmetric dimethyl-arginine in untreated hypertensive subjects

OBJECTIVEnTo investigate the relationship between periodontal disease indexes (PDI) and endothelial dysfunction by means of asymmetric dimethyl-arginine (ADMA) in conditions of both increased and decreased systemic inflammation in the setting of hypertension.nnnMETHODSnWe studied 108 - aged 52+/-9 years - untreated hypertensive subjects (24 h systolic/diastolic blood pressure [BP] 131+/-11/83+/-9 mmHg) with diverse severity of periodontal disease (i.e. mean clinical loss of attachment, maximum probe depth and gingival index). Subjects underwent office and ambulatory BP measurements, echocardiography, periodontal examination; while from fasting venous blood samples we assessed metabolic profile, and we measured ADMA and high sensitivity C reactive protein (hsCRP) levels.nnnRESULTSnWith respect to the median of hsCRP and ADMA (1.79 mg/l and 0.81 micromol/l, respectively) the study population was divided in four groups: low-ADMA/low-hsCRP (n=30), low-ADMA/high-hsCRP (n=27), high-ADMA/low-hsCRP (n=21) and high-ADMA/high-hsCRP (n=30). High-ADMA/high-hsCRP group resulted significantly older compared with both low-ADMA/low-hsCRP and high-ADMA/high-hsCRP groups, while high compared with low-ADMA groups demonstrated increased low-density lipoprotein cholesterol. PDIs were increased in those with high compared with those with low-hsCRP, while the addition of high-ADMA contributed significantly to that comparison. After adjustment for confounders, high-ADMA/high-hsCRP was significantly associated--by means of adjusted z-scores--with mean clinical loss of attachment, maximum probe depth and gingival index by 10.33, 8.84 and 2.74 times more often with respect to the low-ADMA/low-hsCRP pattern.nnnCONCLUSIONnPDI are associated in a dose-dependent manner with ADMA in untreated hypertensives and increased systemic inflammation further contributes to that phenomenon.

Association of resistin with urinary albumin excretion in nondiabetic patients with essential hypertension.

BACKGROUNDnEvidence suggests that resistin, a recently described protein, is associated with subclinical atherosclerosis in different clinical settings. In this study, we investigated the relationship of increased resistin levels with urinary albumin excretion, expressed as the albumin-to-creatinine ratio (ACR), an established index of diffuse vascular damage, in hypertensives.nnnMETHODSnOur population consisted of 132 untreated nondiabetic subjects with stage I-II essential hypertension (49 males, mean age = 54 years, mean office blood pressure (BP) = 159/100 mm Hg). In all patients, ACR was determined as the average of three nonconsecutive morning spot urine samples, and venous blood sampling was performed for estimation of resistin concentrations. The distribution of resistin was split by the median (4.63 ng/ml), and accordingly, subjects were stratified into those with high and low values.nnnRESULTSnHypertensive patients with high (n = 66) compared to those with low resistin (n = 66) exhibited higher ACR values (21.8 + or - 15.3 vs. 10.3 + or - 3.8 mg/g, P < 0.01), even after adjustment for confounders. In the total population, resistin was associated with 24-h systolic BP (r = 0.244, P < 0.05), serum creatinine (r = 0.311, P = 0.007), and ACR (r = 0.499, P < 0.01). Multiple regression analysis revealed that age (b = 0.193, P = 0.02), body mass index (b = 0.237, P = 0.02), 24-h systolic BP (b = 0.338, P < 0.0001), 24-h heart rate (b = 0.169, P = 0.04), and resistin (b = 0.77, P < 0.01) were independently associated with ACR (R(2) = 0.471, P < 0.01).nnnCONCLUSIONSnHypertensive subjects with augmented resistin levels exhibit higher albuminuria, independently of established risk factors. Moreover, the association of resistin with ACR suggests a link between resistin and microvascular disease in the early stages of essential hypertension.