Association between 10-Year Atherosclerotic Cardiovascular Disease Risk and Vascular Endothelial Function in Patients with Vasospastic Angina.

BACKGROUND: Endothelial dysfunction is a predictor of atherosclerotic cardiovascular disease (ASCVD) and plays an important role in vasospastic angina (VA). OBJECTIVES: This study evaluated whether flow-mediated dilation (FMD) is also a good marker of 10-year ASCVD risk (10Y-ASCVDR) in patients with VA. METHODS: Based on their clinical history and coronary artery diameter stenosis (DS), patients were retrospectively enrolled into VA (DS <50% and positive ergonovine provocation), minor coronary artery disease (mCAD, DS <30%), and significant coronary artery disease (sCAD, DS ≥50%) groups. Endothelial function was evaluated by FMD. RESULTS: Each group contained 50 patients. The 10Y-ASCVDR was significantly higher in the sCAD group than in the VA and mCAD groups (10.86 ± 7.30, 4.71 ± 4.04, and 4.77 ± 4.30, respectively, p < 0.001). The FMD was significantly higher in the mCAD group than in the VA and sCAD groups (6.37 ± 4.25, 3.10 ± 2.23, and 3.07 ± 1.89, respectively, p < 0.001). A significant correlation was found between the FMD and 10Y-ASCVD in the mCAD group (r = -0.622, p < 0.001) and the sCAD group (r = -0.557, p < 0.001) but not in the VA group (r = -0.193, p = 0.179). After adjusting for potential confounders such as BMI, C-reactive protein, maximal coronary stenosis, and brachial-ankle pulse wave velocity, multivariate analysis showed that FMD was independently associated with 10Y-ASCVDR in all patients. However, when looking only at the VA group, FMD did not correlate independently with 10Y-ASCVDR. CONCLUSIONS: Unlike mCAD and sCAD, we found no correlation between 10Y-ASCVDR and endothelial function in VA. Thus, our results support that FMD is not a good marker of atherosclerotic cardiovascular risk in VA.

Clinical Meaning of the Ratio of Brachial Pre-Ejection Period to Brachial Ejection Time in Patients with Left Ventricular Systolic Dysfunction.

An increase in the ratio of the brachial pre-ejection period to brachial ejection time [pre-ejection period (PEP)/ET] is correlated with a decrease of left ventricular ejection fraction (LVEF). The current study was designed to test the hypothesis that the change value (Δ) of PEP/ET is a useful indicator of Δ LVEF in patients with left ventricular systolic dysfunction.We consecutively enrolled 104 patients with left ventricular systolic dysfunction (LVEF < 45%). PEP/ET, B-type natriuretic peptide (BNP), and LVEF were evaluated at baseline and at 6-month follow-up. Compared with the baseline measurements, the 6-month values of ΔLVEF, ΔBNP, and ΔPEP/ET were 9.8% ± 9.0% (from 36.3% ± 9.2% to 46.3% ± 12.5%, P < 0.001), -168.5 ± 255.4 (from 271.4 ± 282.5 to 104.1 ± 129.6, P < 0.001), and -0.060 ± 0.069 (from 0.413 ± 0.097 to 0.358 ± 0.079, P < 0.001), respectively. There were significant correlations between LVEF and PEP/ET and between LVEF and BNP in both the initial (r = -0.316, P = 0.001 and r = -0.598, P < 0.001, respectively) and 6-month follow-up (r = -0.307, P = 0.003 and r = -0.701, P < 0.001, respectively). The Steiger's Z test showed that BNP had a significantly stronger correlation with LVEF compared with the correlations between LVEF and PEP/ET in both the initial and 6-month studies (Z = 2.471, P = 0.013 and Z = 3.575, P < 0.001, respectively). There were also significant correlations between ΔLVEF and ΔPEP/ET (r = -0.515, P < 0.001) and between ΔLVEF and ΔBNP (r = -0.581, P < 0.001); however, there was no difference between the correlations for ΔLVEF and ΔPEP/ET versus ΔLVEF and ΔBNP (Steiger's Z = 0.600, P = 0.545).In patients with left ventricular systolic dysfunction not only ΔBNP but also ΔPEP/ET could be a simple indicator of predicting change of LVEF.

Endothelial Function and Cardiovascular Autonomic Activity in Neurally Mediated Syncope.

OBJECTIVES: The aim of this study was to investigate endothelial function and cardiovascular autonomic activity in patients with neurally mediated syncope (NMS). METHODS: Patients with a typical history of NMS were divided according to the result of a head-up tilt (HUT) test. There were 25 patients each in the HUT-positive (HUT+), HUT-negative (HUT-) and control groups. Flow-mediated dilation (FMD) and 24-hour ambulatory electrocardiography (AECG) were performed before the HUT tests. RESULTS: The HUT+ group had a significantly higher FMD than that of the HUT- group and the control group (8.8 ± 3.3 vs. 6.4 ± 2.9%, p = 0.006, and 8.8 ± 3.3 vs. 5.7 ± 2.2%, p = 0.001, respectively). On a 24-hour AECG, the parasympathetic indexes of time domain, such as rMSSD and the pNN50, were significantly higher in the HUT+ group than in the HUT- group (39.0 ± 9.6 vs. 31.6 ± 9.6 ms, p = 0.016, and 16.5 ± 8.1 vs. 10.2 ± 7.2%, p = 0.002, respectively) and the control group (39.0 ± 9.6 vs. 28.9 ± 9.6%, p = 0.001 and 16.5 ± 8.1 vs. 8.7 ± 6.7%, p = 0.001, respectively). High-frequency spectra (parasympathetic activity) of the frequency domain showed similar results. CONCLUSIONS: Not only parasympathetic activity, but also endothelial function may affect the results of HUT tests in patients with NMS.

Quantitative assessment of aortic elasticity with aging using velocity-vector imaging and its histologic correlation.

OBJECTIVE: Velocity-vector imaging (VVI) represents a valuable new method for noninvasive quantification of vascular properties associated with aging. The purpose of this study was to assess the correlations between VVI parameters and histological changes with aging. APPROACH AND RESULTS: Fourteen mongrel dogs were classified as either young (n=7; age, 1-2 years; female; weighing 22-29 kg) or senescent (n=7; age, 8-12 years; female; weighing 36-45 kg). The short-axis image of the descending thoracic aorta was obtained for VVI analysis with transesophageal echocardiography. The location of the image was identified using fluoroscopic guidance, and the aortic tissue was extracted. After dividing the aortic wall into 6 segments, both regional and segmental tissue collagen and elastin contents were quantified and correlated with the aortic elastic properties. In the regional analysis, the M-mode-derived aortic dimensions and elastic moduli except for intima-media thickness were not significantly different between the groups, whereas the VVI-derived aortic area and fractional area changes showed more dilated and stiffer aorta in senescent dogs. Also, fractional area change was significantly correlated with the tissue collagen content unlike the M-mode-derived elastic moduli. In the segmental analysis, the radial velocity, circumferential strain, and strain rates of VVI were more reduced in senescent dogs than young dogs, and the radial velocity and circumferential strain showed independent associations with the collagen content of the corresponding aortic wall. CONCLUSIONS: VVI was a feasible method for direct quantification of aortic elastic properties with a significant histological correlation.

Impact of Framingham risk score, flow-mediated dilation, pulse wave velocity, and biomarkers for cardiovascular events in stable angina.

Although the age-adjusted Framingham risk score (AFRS), flow-mediated dilation (FMD), brachial-ankle pulse wave velocity (baPWV), high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and free fatty acid (FFA) can predict future cardiovascular events (CVEs), a comparison of these risk assessments for patients with stable angina has not been reported. We enrolled 203 patients with stable angina who had been scheduled for coronary angiography (CAG). After CAG, 134 patients showed significant coronary artery disease. During 4.2 yr follow-up, 36 patients (18%) showed CVEs, including myocardial infarction, de-novo coronary artery revascularization, in-stent restenosis, stroke, and cardiovascular death. ROC analysis showed that AFRS, FMD, baPWV, and hsCRP could predict CVEs (with AUC values of 0.752, 0.707, 0.659, and 0.702, respectively, all P<0.001 except baPWV P=0.003). A Cox proportional hazard analysis showed that AFRS and FMD were independent predictors of CVEs (HR, 2.945; 95% CI, 1.572-5.522; P=0.001 and HR, 0.914; 95% CI, 0.826-0.989; P=0.008, respectively). However, there was no difference in predictive power between combining AFRS plus FMD and AFRS alone (AUC 0.752 vs. 0.763; z=1.358, P=0.175). In patients with stable angina, AFRS and FMD are independent predictors of CVEs. However, there is no additive value of FMD on the AFRS in predicting CVEs.

Alpha-lipoic acid for the prevention of contrast-induced nephropathy in patients undergoing coronary angiography: the ALIVE study - a prospective randomized trial.

OBJECTIVES: α-Lipoic acid (ALA) is widely used for diabetic neuropathy due to its antioxidant properties. We evaluated its potential for preventing contrast-induced nephropathy (CIN). METHODS: We conducted a prospective randomized controlled trial to evaluate the efficacy of ALA in CIN prevention. Two hundred and two patients with basal renal insufficiency who received elective coronary angiography were randomized to the ALA group [ALA treatment for 2 days (600 mg orally three times a day before and after coronary catheterization, n = 100)] or the control group (n = 102). The primary end point was the maximum increase in serum creatinine (sCr) and the secondary end point was the incidence of CIN defined as an increase in sCr of either ≥ 25% or ≥ 44.2 µmol/l. RESULTS: Mean maximum increase in sCr was not different between the ALA and the control group (-1.32 ± 30.5 vs. -1.19 ± 30.1 µmol/l, respectively; p = 0.977). sCr did not significantly change from baseline (120.8 ± 69.8 vs. 122 ± 88.1 µmol/l) in the ALA group and the simple saline hydration group (108.2 ± 37.5 vs. 110 ± 49 µmol/l). There was a lower rate of CIN in the ALA group than in the control group, but the difference was not statistically significant (3.0 vs. 6.9%, respectively; p = 0.332). CONCLUSION: ALA showed no benefit in CIN prevention.

Functional changes of the myocardium in survivors of high-voltage electrical injury.

INTRODUCTION: There are limited long-term follow-up data on functional changes in the myocardium after high-voltage electrical injury (HVEI). METHODS: Twenty-three patients who had been exposed to HVEI (>20,000 volts) and preserved left ventricular ejection fraction (≥55%) were enrolled in the study. Echocardiographic parameters, including peak systolic strain (S) and strain rate (SR), were evaluated at baseline, six weeks and six months later. These data were compared with a healthy control group who were matched in terms of age, sex and body mass index. RESULTS: The systolic and diastolic blood pressure and the heart rate were significantly higher in the HVEI group compared with the control group at baseline and at six weeks, but not at the six-month follow-up. Conventional echocardiographic data showed no differences between the groups during the study period. In contrast to the S, the baseline and six weeks, SR was significantly increased in the HVEI group compared with the control group. However, at the six-month follow-up, there was no difference in the SR between the groups. Among the 23 patients with HVEI, 17 of the patients had vertical current injury, and 6 patients had horizontal current injury. There was no difference in terms of the conventional echocardiography, S and SR between the patients with vertical injury and those with horizontal injury at baseline and at the six-month follow-up. CONCLUSIONS: The long-term contractile performance of the myocardium is preserved when patient do not experience left ventricular dysfunction in the early stages after HVEI.

Left Atrial Velocity Vector Imaging Can Assess Early Diastolic Dysfunction in Left Ventricular Hypertrophy and Hypertrophic Cardiomyopathy.

BACKGROUND: The function of left atrium (LA) is difficult to assess because of its ventricle-dependent, dynamic movement. The aim of this study was to assess LA function using velocity vector imaging (VVI) and compare LA function in patients with hypertrophic cardiomyopathy (HCMP) and left ventricular hypertrophy (LVH) with normal controls. METHODS: Fourteen patients with HCMP (72% male, mean age of 52.6 ± 9.8), 15 hypertensive patients with LVH (88% male, mean age of 54.0 ± 15.3), and 10 age-matched controls (83% male, mean age of 50.0 ± 4.6) were prospectively studied. Echocardiographic images of the LA were analyzed with VVI, and strain rate (SR) was compared among the 3 groups. RESULTS: The e' velocity (7.7 ± 1.1; 5.1 ± 0.8; 4.5 ± 1.3 cm/sec, p = 0.013), E/e' (6.8 ± 1.6; 12.4 ± 3.3; 14.7 ± 4.2, p = 0.035), and late diastolic SR at mid LA (-1.65 ± 0.51; -0.97 ± 0.55; -0.82 ± 0.32, p = 0.002) were significantly different among the groups (normal; LVH; HCMP, respectively). The e' velocity, E/e', and late diastolic SR at mid LA were significantly different between normal and LVH (p = 0.001; 0.022; 0.018), whereas LA size was similar between normal and LVH (p = 0.592). The mean late diastolic peak SR of mid LA was significantly correlated with indices of diastolic function (E/e', e', and LA size). CONCLUSIONS: The SR is a useful tool for detailed evaluation of LA function, especially early dysfunction of LA in groups with normal LA size.

Vascular Alterations Preceding Arterial Wall Thickening in Overweight and Obese Children.

BACKGROUND: Childhood obesity is linked to adverse cardiovascular outcomes in adulthood. This study aimed to assess the impact of childhood obesity on the vasculature and to investigate whether vascular alteration precedes arterial wall thickening in childhood. METHODS: A total of 295 overweight (body mass index [BMI] 85th to 95th percentile, n = 30) and obese (BMI ≥ 95th percentile, n = 234) children aged 7-17 years and 31 normal-weight controls with similar age and gender were prospectively recruited. We assessed anthropometric data and laboratory findings, and measured the carotid intima-media thickness (IMT), carotid artery (CA) diameter, M-mode-derived arterial stiffness indices, and velocity vector imaging parameters, including the CA area, fractional area change, circumferential strain, and circumferential strain rate (SR). RESULTS: The mean ± standard deviation age of the participants was 10.8 ± 2.1 years; 172 (58%) children were male. Regarding structural properties, there was no difference in the IMT between the three groups. The CA diameter was significantly increased in obese children, whereas the CA area showed a significant increase beginning in the overweight stage. Regarding functional properties, contrary to ß stiffness and Young's elastic modulus, which were not different between the three groups, the circumferential SR showed a significant decrease beginning in the overweight stage and was independently associated with BMI z-scores after adjusting for covariates. CONCLUSION: We have demonstrated that arterial stiffening and arterial enlargement precede arterial wall thickening, and that these vascular alterations begin at the overweight stage in middle childhood or early adolescence.

Mechanism of mitral regurgitation in the acute phase of inferior wall myocardial infarction: reduced closing force as a consequence of left ventricular systolic dysfunction in the presence of tethering as a determinant of mitral regurgitation.

BACKGROUND: To delineate the mechanism of mitral regurgitation (MR) in the acute phase of inferior wall myocardial infarction (MI). METHODS AND RESULTS: In 97 patients (age 59 ± 12 years) with acute inferior wall MI, the severity of MR, left ventricular (LV) geometric changes and function within 1.7 ± 1.3 days after MI by echocardiography was retrospectively evaluated. Infarct size was measured within 3.9 ± 1.7 days by cardiac magnetic resonance. Mild MR was present in 16 (16.5%) and moderate MR in 12 (12.4%) of 97 patients. There were no significant differences in mitral annular area, sphericity and distances between papillary muscle tips and the contralateral mitral annulus. However, patients with moderate MR had significantly larger LV end-systolic volume, tenting area and infarct size. There was a graded relationship between the severity of MR and LV ejection fraction. In a multivariable regression analysis, LV ejection fraction and tenting area were found to be independent predictors of the severity of MR (r(2)=0.180, P=0.001). CONCLUSIONS: MR was associated with LV systolic dysfunction, increase in end-systolic LV volume and tethering of mitral leaflet, suggesting reduced closing force as a consequence of LV systolic dysfunction in the presence of leaflet tethering would play a more pivotal role in the development of MR.

Dynamic change of mitral apparatus as potential cause of left ventricular outflow tract obstruction in hypertrophic cardiomyopathy.

AIMS: the geometry of the mitral apparatus changes dynamically throughout systole and diastole. We investigated how geometric dynamics of the mitral apparatus could affect the haemodynamics of the outflow tract in patients with hypertrophic cardiomyopathy presenting with systolic anterior motion (HCM(SAM)) using three-dimensional (3D) echocardiography. METHODS AND RESULTS: we obtained transthoracic volumetric images in 21 patients with HCM(SAM) with differing trans-left ventricular (LV) outflow tract pressure gradient (PG(LVOT)) and in 23 controls. Original software was used to crop the 3D data into 18 radial planes; the mitral annulus, leaflets, coaptation point, protruding septum, and papillary muscles (PMs) tips were traced in each plane. The data were then reconstructed for 3D distance measurements and volumetric assessment. Shorter coaptation-septal distance (12 ± 4 vs. 21 ± 3 mm, P < 0.001), shorter inter-PM distance (13 ± 5 vs. 18 ± 4 mm, P = 0.02), and larger mitral tenting volume/body surface area (TVindex) (2.1 ± 1 vs. 0.5 ± 0.3 mL/m(2), P < 0.001) were associated with HCM(SAM) vs. control. PG(LVOT) increased with TVindex (r = 0.51, P = 0.01), and decreased with coaptation-septal distance(r = -0.83, P < 0.001) and the inter-PM distance (r = -0.69, P < 0.001) at mid-systole but not at mid-diastole (all P> 0.05). In addition, the coaptation-septal distance, TVindex, and inter-PM distance correlated each other (all P < 0.05). After adjustment for measures of mitral geometric change, the coaptation-septal distance was closely associated with PG(LVOT) (ß = -0.73, P < 0.001). CONCLUSION: these findings suggest that dynamic geometric changes by interaction of PMs, mitral tenting, and the coaptation point at mid-systole may be important contributors to outflow obstruction in HCM(SAM).

Assessment of mechanical properties of common carotid artery in Takayasu's arteritis using velocity vector imaging.

BACKGROUND: Alteration of arterial elastic properties is known to occur in patients with arteritis. Velocity vector imaging (VVI) is a new technology to assess multi-dimensional regional mechanics in terms of velocity, strain, strain rate and displacement. The aim of the present study was to investigate the mechanical properties of the common carotid artery using VVI in patients with Takayasu's arteritis (TA). METHODS AND RESULTS: Vascular properties of the carotid artery were assessed in 12 patients with TA (11 female, age 38+/-10 years) and 12 healthy age- and sex-matched controls. Velocity, strain, strain rate and displacement were decreased significantly in TA compared with controls. Standard deviations, however, of time to peak velocity (Tv), strain (Ts), strain rate (Tsr), and displacement (Td) of multiple arterial wall segments were significantly higher in TA (P<0.0001), suggesting disturbance of symmetric arterial expansion during systole. The severity of carotid stenosis was also positively correlated with standard deviations of Tv, Ts, Tsr and Td. CONCLUSIONS: Arterial assessment using VVI may represent a new noninvasive method for quantifying vascular alteration associated with arteritis.

Predictors of survival following veno-arterial extracorporeal membrane oxygenation in patients with acute myocardial infarction-related refractory cardiogenic shock: clinical and coronary angiographic factors.

BACKGROUND: This study aimed to identify the determinant factors of survival in patients with acute myocardial infarction (AMI) and refractory cardiogenic shock (RCS) who underwent veno-arterial extracorporeal membrane oxygenation (ECMO). METHODS: Sixty-nine consecutive patients with AMI-related RCS were enrolled in the study. They were treated with ECMO and primary percutaneous coronary intervention (PCI). The clinical scores and coronary angiography (CAG) factors related to 100-day survival were evaluated. RESULTS: Thirty patients (43.5%) survived for more than 100 days. The CAG showed that 19 (27.5%) patients had left main disease (LMD). There were 17 (24.6%), 27 (39.1%), and 25 (36.3%) patients with one-vessel, two-vessel, and three-vessel disease, respectively. There were significant differences between the survivors and non-survivors in the simplified acute physiology score II (SAPSII) (65.4±17.2 vs. 83.1±13.0, P<0.001), sepsis-related organ failure assessment score (SOFA) (10.4±2.7 vs. 12.3±2.5, P=0.004), survival after veno-arterial extracorporeal membrane oxygenation score (SAVE) (-4.4±4.3 vs. -8.4±3.1, P<0.001), CPR time (15.8±16.6 vs. 30.0±29.5, P=0.048), LMD [4 (13.3%) vs. 15 (38.5%), P=0.029], and number of coronary artery disease (NCAD) (P<0.001). Multivariate logistic regression analysis showed that NCAD (OR 3.788, P=0.008) was one of the independent predictors of mortality. The ROC analysis showed that SAPSII (AUC 0.786, P<0.001), SOFA (AUC 0.715, P=0.002), and SAVE (AUC 0.766, P<0.001) equally predict mortality. The combined NCAD parameters more accurately predicted mortality and differences in the AUC values (d-AUC) between SAPSII plus NCAD vs. SAPSII (d-AUC 0.073, z=2.256, P=0.024), SOFA plus NCAD vs. SOFA (d-AUC 0.058, z=2.773, P=0.006), and SAVE plus NCAD vs. SAVE (d-AUC 0.036, z=2.332, P=0.020). CONCLUSIONS: The SAPSII, SOFA, and SAVE scores predict the prognosis of ECMO-treated AMI patients with RCS. The CAG findings reinforce the predictive power of each score.

Patterns of late gadolinium enhancement are associated with ventricular stiffness in patients with advanced non-ischaemic dilated cardiomyopathy.

AIMS: Despite the prognostic importance of ventricular filling and ventricular-arterial interaction in patients with advanced systolic heart failure, the structural determinants of these parameters have not been fully studied. We aimed to investigate whether patterns of late gadolinium enhancement (LGE) on cardiac magnetic resonance affect ventricular elastic properties or performance in patients with non-ischaemic dilated cardiomyopathy (DCM). METHODS AND RESULTS: Patients (n = 49) with markedly reduced systolic function (left ventricular (LV) ejection fraction <35%) due to longstanding non-ischaemic DCM underwent contrast-enhanced cardiac magnetic resonance after comprehensive echo-Doppler evaluations. The single beat-derived end-diastolic elastance, end-systolic elastance, arterial elastance, and dyssynchrony indices were measured by echo. On the basis of LGE patterns, patients could be divided into three groups: non-LGE (n = 18), non-midwall LGE (n = 13), and midwall LGE (n = 18). The midwall LGE group had lower LV systolic longitudinal velocity (4.6 +/- 1.7 for non-LGE vs. 4.3 +/- 1.2 for non-midwall LGE vs. 3.5 +/- 1.0 cm/s for midwall LGE, P = 0.025), higher end-diastolic elastance index (0.41 +/- 0.21 vs. 0.46 +/- 0.31 vs. 0.85 +/- 0.51 respectively, P = 0.008), and a more impaired ventriculoarterial coupling index (3.14 +/- 1.53 vs. 2.88 +/- 1.94 vs. 5.52 +/- 3.18, P = 0.006) than other subgroups. CONCLUSION: Patients with midwall LGE had a higher ventricular stiffness index and more impaired ventriculoarterial coupling when compared with other non-ischaemic DCM patients.

Value of ventricular stiffness index and ventriculoarterial interaction in patients with nonischemic dilated cardiomyopathy.

BACKGROUND: Whether echo-Doppler-derived index of ventricular elastance or ventriculoarterial interaction can reliably reflect circulatory efficiency in various conditions was investigated in the present study and whether they can be helpful in predicting exercise capacity in patients with dilated cardiomyopathy (DCM). METHODS AND RESULTS: The 25 patients with DCM, 25 age- and gender-matched hypertensive patients, and 25 marathon runners underwent symptom-limited graded supine bicycle exercise echocardiography after resting echo-Doppler evaluation. Echo-Doppler-derived left ventricular (LV) diastolic elastance index (Ed), ventricular-vascular coupling index (10 x Ea/Ees), based on arterial elastance index (Ea) to LV end-systolic elastance index (Ees), and hemodynamic parameters were measured during rest and exercise. DCM patients had lower Ees, higher Ed and Ea/Ees with blunted exercise responses of Ees than the other groups, and the hypertensive patients had lower Ees and DeltaEes compared with the marathon runners. Resting Ed, Ea/Ees, and total stiffness index (10 x Ed x Ea/Ees) correlated with exercise duration independent of age and gender. A stiffness index of 0.8 could reliably predict impaired exercise capacity. CONCLUSIONS: Echo-derived elastance is predictive of exercise capacity in patients with DCM.

Self-blood pressure monitoring is associated with improved awareness, adherence, and attainment of target blood pressure goals: Prospective observational study of 7751 patients.

We investigated whether self-blood pressure monitoring (SBPM) can improve the control rate of blood pressure (BP), adherence of antihypertensive medications, and the awareness of the importance of BP control in hypertensive patients. A total of 7751 patients who visited the outpatient clinics of private and university hospitals in Korea were given automatic electronic BP monitors and were recommended to measure their BP daily at home for 3 months. Changes in office BP, attainment of target BP, adherence to taking antihypertensive drugs, and awareness of BP were compared before and after SBPM. Patients and physicians were surveyed on their perception of BP and SBPM. Mean BP significantly decreased from 142/88 to 129/80 mm Hg (P < .001), and attainment of the target BP increased from 32% to 59% (P < .001) after SBPM. Drug non-adherence, which was defined as patient's not taking medication days per week, decreased significantly from 0.86 days to 0.53 days (P < .001). The rate of awareness of the BP goal increased from 57% to 81% (P < .001). Patients estimated that their mean BP was 125/81 mm Hg, but their actual mean BP was 142/88 mm Hg. Awareness about the importance of SBPM increased from 90% to 98%. The rate of SBPM ≥ once per week further increased, from 34% to 96%. In conclusion, SBPM is associated with reduced BP, better BP control rate, greater drug adherence, and improved perception of BP by the patients.

Association Between Intra-arterial Invasive Central and Peripheral Blood Pressure and Endothelial Function (Assessed by Flow-Mediated Dilatation) in Stable Coronary Artery Disease.

BACKGROUND: Endothelial function is an independent predictor of coronary artery disease (CAD) and is regulated by a number of factors, including blood pressure. OBJECTIVES: The current study was designed to test the hypothesis that intra-arterial invasive central blood pressure is strongly associated with endothelial function in patients with CAD. METHODS: In patient with CAD (diameter stenosis ≥30%), invasive central (aortic) and left peripheral (brachial) blood pressures were determined during transradial coronary angiography. The endothelial function was evaluated by way of flow-mediated dilatation (FMD) of the brachial artery. RESULTS: We enrolled 413 consecutive patients. There were 260 patients with significant CAD (sCAD, diameter stenosis ≥50%) and 153 patients with nonsignificant CAD (nsCAD, diameter stenosis <50% and ≤30%). FMD was significantly and inversely correlated with central and peripheral parameters in terms of systolic blood pressure, mean arterial pressure, and pulse pressure (PP) (r = -0.332, r = -0.184, and r = -0.407, respectively, all P < 0.001) and (r = -0.303, r = -0.190, and r = -0.319, respectively, all P < 0.001). Compared with sCAD, there was closer correlation between central PP with FMD in nsCAD (r = -0.548 vs. r = -0.345, both P < 0.001). After adjusting potential confounders such as age, body mass index and high-sensitivity C-reactive protein, multivariate analysis showed that FMD remained independently associated with central PP, degree of coronary artery stenosis, and brachial-ankle pulse wave velocity in all patients. In patients with nsCAD, the multivariate analysis showed that only central PP was independently correlated with FMD. CONCLUSIONS: In patients with stable CAD, a decline in endothelial function is most closely associated with invasive central pulse pressure.

Efficacy and safety profiles of a new S(-)-amlodipine nicotinate formulation versus racemic amlodipine besylate in adult Korean patients with mild to moderate hypertension: an 8-week, multicenter, randomized, double-blind, double-dummy, parallel-group, phase III, noninferiority clinical trial.

BACKGROUND: "Chiral switching" from an existing racemate to a pure enantiomeric compound is a popular theme in drug development, especially when the enantiomer is found to have better efficacy and safety profiles. Amlodipine is a racemic mixture, composed of the S(-)-enantiomer, which is the pharmacologically active isomer, and the R(+)-enantiomer, which is 1000-fold less active. S(-)-amlodipine nicotinate, a chirally switched form of amlodipine nicotinate, has been developed and found to be bioequivalent to amlodipine besylate in Phase I clinical trials in Korea. OBJECTIVE: The aim of this study was to compare the efficacy and safety profiles of S(-)-amlodipine nicotinate with those of amlodipine besylate in adult Korean patients with mild to moderate hypertension (diastolic blood pressure [DBP] >or=90 mm Hg and or=90 and or=90 mm Hg). The primary end point was noninferiority of the difference in mean SiDBP from baseline to week 8 for S(-)-amlodipine nicotinate compared with amlodipine besylate. Secondary end points were as follows: (1) noninferiority of the difference in mean sitting systolic blood pressure (SiSBP) from baseline to week 8 between the study groups; and (2) SiDBP response rate (defined as the proportion of patients whose SiDBP was <90 mm Hg or whose SiDBP reduction was >or=10 mm Hg from baseline) after the 8-week treatment. Also, the incidence and severity of adverse events (AEs) and adverse drug reactions (ADRs) were reported. Severe AEs/ADRs were defined as those associated with any of the following: death; an event associated with a high risk of mortality; an event requiring hospitalization; or development of a permanent disability or congenital malformation. RESULTS: One hundred fifty-seven patients were assessed for inclusion in the study. Of these, 124 patients were randomly allocated to receive S(-)-amlodipine nicotinate (42 men, 21 women; mean [SD] age, 52.4 [10.3] years [range, 23-70 years]; weight, 67.7 [10.8] kg [range, 44-92 kg]) or amlodipine besylate (45 men, 16 women; mean [SD] age, 54.5 [10.0] years [range, 30-73]; weight, 68.9 [9.8] kg [range, 49-95 kg]). One hundred sixteen patients completed the study, but 11 patients (8.9%) were dropped from the per-protocol analysis due to violations; therefore, 105 patients were included in the modified intent-to-treat population analysis (S[-]-amlodipine nicotinate, 55 patients; amlodipine besylate, 50 patients). There were no significant between-group differences in the baseline characteristics. Baseline mean (SD) SiSBP and SiDBP were 142.6 (11.3) and 94.9 (4.8) mm Hg in the S(-)-amlodipine nicotinate group, and 141.8 (8.3) and 96.1 (4.9) mm Hg in the amlodipine besylate group. Mean (SD) changes in SiSBP were 17.6 (11.2) mm Hg in the S(-)-amlodipine nicotinate group and 18.6 (12.3) mm Hg in the amlodipine besylate group. The SiDBP response rates were 92.7% in the S(-)-amlodipine nicotinate group and 88.0% in the amlodipine besylate group. There were no significant between-group differences in the prevalence of AEs and ADRs. In the S(-)-amlodipine nicotinate group, 15 patients (23.8%) reported a total of 28 AEs, and 19 patients (31.1%) reported a total of 27 AEs in the amlodipine besylate group. Six patients (9.5%) in the S(-)-amlodipine nicotinate group and 7 patients (11.4%) in the amlodipine besylate group experienced a total of 19 ADRs (11 and 8, respectively). The most common ADRs were liver enzyme elevation (3/63 [4.8%]) in the S(-)-amlodipine nicotinate group and facial flushing (3/61 [4.9%]) in the amlodipine besylate group. No cases of severe AEs or ADRs were reported in either group. CONCLUSIONS: The reduction of SiDBP after 8 weeks of treatment with S(-)-amlodipine nicotinate was noninferior compared with that of racemic amlodipine besylate in these adult Korean patients with mild to moderate hypertension. The SiDBP response rate and the reduction of SiSBP after 8 weeks of treatment with S(-)-amlodipine nicotinate were not significantly different from those with racemic amlodipine besylate. Both treatments were generally well tolerated.

Changes of body composition after valve surgery in patients with mitral valve disease.

BACKGROUND: Patients with chronic heart failure have alteration in body composition as a reduction in fat mass, lean body mass and bone mass. However, body wasting in valvular heart disease and the impact of corrective valvular surgery on body composition has not been investigated. OBJECTIVES: We hypothesized that body wasting in severe mitral valve (MV) diseases is reversible through MV surgery. METHODS: Forty eight patients who were scheduled to undergo MV surgery were consecutively enrolled after excluding patients with combined valvular heart disease, ischemic heart disease, cardiomyopathies, and diseases or who were taking medications that could affect metabolism. All patients were subjected to simplified nutritional assessment questionnaire (SNAQ) for appetite, laboratory tests, echocardiography, and dual-energy X-ray absorptiometry (DXA) before and one year after MV surgery. RESULTS: One year after MV surgery, the patients showed increased appetite and improved laboratory data as well as hemodynamic improvement.When we classified the patients according to the primary MV lesion, no changes in body weight were observed in both patients with mitral regurgitation (MR) and mitral stenosis (MS). However, significant increase in bone mineral density and body fat percentage were observed in patients with MR and not in patients with MS. In patients with MR, patients with Δfat ≥ 2% showed significantly higher pre-operative estimated right ventricular systolic pressure (eRVSP) level and greater decrease in eRVSP after surgery than those with Δfat < 2% and both ΔSNAQ and Δfat showed significant negative relationship with ΔeRVSP, respectively. CONCLUSIONS: In patients with severe MV disease, corrective MV surgery led to favorable outcomes in wasting process as well as hemodynamic improvement. Particularly, right ventricular pressure overload showed a close association with the changes in appetite and body fat percentage in patients with MR.