The Efficacy and Tolerability of Irbesartan/Amlodipine Combination Therapy in Patients With Essential Hypertension Whose Blood Pressure Were not Controlled by Irbesartan Monotherapy.

PURPOSE: This study aimed to evaluate the efficacy and tolerability of irbesartan (IRB) and amlodipine (AML) combination therapy in patients with essential hypertension whose blood pressure (BP) was not controlled by IRB monotherapy. METHODS: Two multicenter, randomized, double-blind, placebo-controlled, phase III studies were conducted in Korea (the I-DUO 301 study and the I-DUO 302 study). After a 4-week run-in period with either 150 mg IRB (I-DUO 301 study) or 300 mg IRB (I-DUO 302 study), patients with uncontrolled BP (ie, mean sitting systolic BP [MSSBP] ≥140 mmHg to <180 mmHg and mean sitting diastolic BP <110 mmHg) were randomized to the placebo, AML 5 mg, or AML 10 mg group. A total of 428 participants were enrolled in the 2 I-DUO studies. In the I-DUO 301 study, 271 participants were randomized in a 1:1:1 ratio to receive either IRB/AML 150/5 mg, IRB/AML 150/10 mg, or IRB 150 mg/placebo. In the I-DUO 302 study, 157 participants were randomized in a 1:1 ratio to receive IRB/AML 300/5 mg or IRB 300 mg/placebo. The primary endpoint was the change in MSSBP from baseline to week 8. Tolerability was assessed according to the development of treatment-emergent adverse events (TEAEs) and clinically significant changes in physical examination, laboratory tests, pulse, and 12-lead electrocardiography. FINDINGS: In I-DUO 301, the mean (SD) changes of MSSBP at week 8 from baseline were -14.78 (12.35) mmHg, -21.47 (12.78) mmHg, and -8.61 (12.19) mmHg in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively. In I-DUO 302, the mean (SD) changes of MSSBP at week 8 from baseline were -13.30 (12.47) mmHg and -7.19 (15.37) mmHg in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively. In both studies, all combination groups showed a significantly higher reduction in MSSBP than the IRB monotherapy groups (P < 0.001 for both). TEAEs occurred in 10.00%, 10.99%, and 12.22% of participants in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively, in I-DUO 301 and in 6.33% and 10.67% of participants in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively, in I-DUO 302, with no significant between-group differences. Overall, there was one serious adverse event throughout I-DUO study. IMPLICATIONS: The combination of IRB and AML has superior antihypertensive effects compared with IRB alone over an 8-week treatment period, with placebo-like tolerability. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05476354 (I-DUO 301), NCT05475665 (I-DUO 302).

Effectiveness of low-intensity atorvastatin 5 mg and ezetimibe 10 mg combination therapy compared with moderate-intensity atorvastatin 10 mg monotherapy: A randomized, double-blinded, multi-center, phase III study.

BACKGROUND: We compared the efficacy and safety of low-intensity atorvastatin and ezetimibe combination therapy with moderate-intensity atorvastatin monotherapy in patients requiring cholesterol-lowering therapy. METHODS: At 19 centers in Korea, 290 patients were randomized to 4 groups: atorvastatin 5 mg and ezetimibe 10 mg (A5E), ezetimibe 10 mg (E), atorvastatin 5 mg (A5), and atorvastatin 10 mg (A10). Clinical and laboratory examinations were performed at baseline, and at 4-week and 8-week follow-ups. The primary endpoint was percentage change from baseline in low-density lipoprotein (LDL) cholesterol levels at the 8-week follow-up. Secondary endpoints included percentage changes from baseline in additional lipid parameters. RESULTS: Baseline characteristics were similar among the study groups. At the 8-week follow-up, percentage changes in LDL cholesterol levels were significantly greater in the A5E group (49.2%) than in the E (18.7%), A5 (27.9%), and A10 (36.4%) groups. Similar findings were observed regarding the percentage changes in total cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B levels. Triglyceride levels were also significantly decreased in the A5E group than in the E group, whereas high-density lipoprotein levels substantially increased in the A5E group than in the E group. In patients with low- and intermediate-cardiovascular risk, 93.3% achieved the target LDL cholesterol levels in the A5E group, 40.0% in the E group, 66.7% in the A5 group, and 92.9% in the A10 group. In addition, 31.4% of patients in the A5E group, 8.1% in E, 9.7% in A5, and 7.3% in the A10 group reached the target levels of both LDL cholesterol < 70 mg/dL and reduction of LDL ≥ 50% from baseline. CONCLUSIONS: The addition of ezetimibe to low-intensity atorvastatin had a greater effect on lowering LDL cholesterol than moderate-intensity atorvastatin alone, offering an effective treatment option for cholesterol management, especially in patients with low and intermediate risks.

A Paradigm Shift in Dyslipidemia Management in Primary Care: A 12-Month Cohort Study.

PURPOSE: LDL-lowering therapy is beneficial to reduce the risk of cardiovascular disease (CVD). Higher statin doses lower LDL-C levels and prevent CVD; however, they increase adverse events, such as muscle-related adverse events and new-onset diabetes mellitus (DM). Ezetimibe combined with statin therapy improves LDL-C-lowering levels and tolerability in patients with established CVD. We aimed to analyze the efficacy and safety of a fixed-dose rosuvastatin and ezetimibe (R+E) combination therapy in intermediate-risk patients with hypercholesterolemia and no DM after 12 months of visiting a primary physician. METHODS: This multicenter, open-label, single-arm, prospective observational study involved 5717 patients from 258 primary health care centers in Korea enrolled between 2016 and 2018. Patients had no DM or previous CVD but had cardiovascular risk factors and were taking a statin or a fixed-dose combination of E (10 mg) + R (5, 10, or 20 mg). We analyzed 700 patients using propensity score matching. FINDINGS: A fixed-dose R+E combination therapy significantly reduced LDL-C in 5/10 mg R+E (29.35%), 10/10 mg R+E (36.19%), and 20/10 mg R+E (41.83%) compared with statin monotherapy (19.09%) at 12-month follow-up (P = 0.017). Compared with statin monotherapy, HDL-C levels increased in 5/10 mg R+E (mean change at 12 months; P = 0.004), and triglyceride levels decreased in 10/10 mg R+E (mean change at 12 months; P = 0.033). The fixed-dose R+E combination therapy was associated with fewer adverse events and a neutral effect on glucose deterioration compared with statin monotherapy at 12 months of follow-up. IMPLICATIONS: In a possible paradigm shift, a fixed-dose R+E combination therapy may be beneficial for primary cardiovascular prevention with potent LDL-lowering efficacy and tolerability; however, further large prospective studies are needed.

Apparent treatment-resistant hypertension among ambulatory hypertensive patients: a cross-sectional study from 13 general hospitals.

BACKGROUND/AIMS: To examine the prevalence and clinical characteristics of apparent treatment-resistant hypertension among ambulatory hypertensive patients. METHODS: We enrolled adult ambulatory hypertensive patients at 13 well-qualified general hospitals in Korea from January to June 2012. Apparent resistant hypertension was defined as an elevated blood pressure > 140/90 mmHg with the use of three antihypertensive agents, including diuretics, or ≥ 4 antihypertensives, regardless of the blood pressure. Controlled hypertension was defined as a blood pressure within the target using three antihypertensives, including diuretics. RESULTS: Among 16,915 hypertensive patients, 1,172 (6.9%) had controlled hypertension, and 1,514 (8.9%) had apparent treatment-resistant hypertension. Patients with apparent treatment-resistant hypertension had an earlier onset of hypertension (56.8 years vs. 58.8 years, p = 0.007) and higher body mass index (26.3 kg/m2 vs. 24.9 kg/m2, p < 0.001) than those with controlled hypertension. Drug compliance did not differ between groups. In the multivariable analysis, earlier onset of hypertension (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.97 to 0.99; p < 0.001) and the presence of comorbidities (OR, 2.06; 95% CI, 1.27 to 3.35; p < 0.001), such as diabetes mellitus, ischemic heart disease, heart failure, and chronic kidney disease, were independent predictors. Among the patients with apparent treatment-resistant hypertension, only 5.2% were receiving ≥ 2 antihypertensives at maximally tolerated doses. CONCLUSION: Apparent treatment-resistant hypertension prevalence is 8.9% among ambulatory hypertensive patients in Korea. An earlier onset of hypertension and the presence of comorbidities are independent predictors. Optimization of medical treatment may reduce the rate of apparent treatment-resistant hypertension.

Office blood pressure threshold of 130/80 mmHg better predicts uncontrolled out-of-office blood pressure in apparent treatment-resistant hypertension.

The objective of this study was to compare the diagnostic accuracy of office blood pressure (BP) threshold of 140/90 and 130/80 mmHg for correctly identifying uncontrolled out-of-office BP in apparent treatment-resistant hypertension (aTRH). We analyzed 468 subjects from a prospectively enrolled cohort of patients with resistant hypertension in South Korea (clinicaltrials.gov: NCT03540992). Resistant hypertension was defined as office BP ≥ 130/80 mmHg with three different classes of antihypertensive medications including thiazide-type/like diuretics, or treated hypertension with four or more different classes of antihypertensive medications. We conducted different types of BP measurements including office BP, automated office BP (AOBP), home BP, and ambulatory BP. We defined uncontrolled out-of-office BP as daytime BP ≥ 135/85 mmHg and/or home BP ≥ 135/85 mmHg. Among subjects with office BP < 140/90 mmHg and subjects with office BP < 130/80 mmHg, 66% and 55% had uncontrolled out-of-office BP, respectively. The prevalence of controlled and masked uncontrolled hypertension was lower, and the prevalence of white-coat and sustained uncontrolled hypertension was higher, with a threshold of 130/80 mmHg than of 140/90 mmHg, for both office BP and AOBP. The office BP threshold of 130/80 mmHg was better able to diagnose uncontrolled out-of-office BP than 140/90 mmHg, and the net reclassification improvement (NRI) was 0.255. The AOBP threshold of 130/80 mmHg also revealed better diagnostic accuracy than 140/90 mmHg, with NRI of 0.543. The office BP threshold of 130/80 mmHg showed better than 140/90 mmHg in terms of the correspondence to out-of-office BP in subjects with aTRH.

Relation between the Change in Mean Platelet Volume and Clopidogrel Resistance in Patients Undergoing Percutaneous Coronary Intervention.

We aimed to determine the association between the change in mean platelet volume (MPV) over time and aspirin/ clopidogrel resistance in patients undergoing percutaneous coronary intervention (PCI). The MPV and platelet function were analysed in 302 patients who underwent PCI. MPV changes were associated with increased aspirin reaction units (ARU, r = 0.114; P = 0.047), increased P2Y12 reaction units (PRU, r = 0.193; P = 0.001), and decreased P2Y12% inhibition (PI%, r = - 0.273; P < 0.001). The group with increasing MPV values showed significantly higher PRU values and lower PI% compared with the group with decreasing MPV values (222.5 ± 73.9 vs. 195.6 ± 63.7 PRU, P = 0.001; 24.1 ± 21.0 vs. 32.8 ± 18.5 PI%, P < 0.001, respectively). The clopidogrel resistant group (≥235 PRU or ≤15% of PI%) showed a significantly higher positive change in MPV (ΔMPV) values than the clopidogrel responder group (0.53 ± 0.78 vs. 0.13 ± 0.69 fL, P < 0.001). When the ΔMPV cut-off level was set at 0.20 fL using the receiver operating characteristic curve, the sensitivity and specificity for differentiating between the clopidogrel resistant and responder groups were 72.6% and 59.3%, respectively. After adjusting for traditional risk factors, the odds ratio in the clopidogrel resistant group with ΔMPV ≥0.2 fL was 4.10 (95% confidence interval; 1.84-9.17). In conclusion, ΔMPV was associated with PRU and PI%; a positive ΔMPV was an independent predictive marker for clopidogrel resistance after PCI.

Massive thoracoabdominal aortic thrombosis in a patient with iatrogenic Cushing syndrome.

Massive thoracoabdominal aortic thrombosis is a rare finding in patients with iatrogenic Cushing syndrome in the absence of any coagulation abnormality. It frequently represents an urgent surgical situation. We report the case of an 82-year-old woman with massive aortic thrombosis secondary to iatrogenic Cushing syndrome. A follow-up computed tomography scan showed a decreased amount of thrombus in the aorta after anticoagulation therapy alone.

Prediction of infarct severity from triiodothyronine levels in patients with ST-elevation myocardial infarction.

BACKGROUND/AIMS: The aim of the present study was to evaluate the relationship between thyroid hormone levels and infarct severity in patients with ST-elevation myocardial infarction (STEMI). METHODS: We retrospectively reviewed thyroid hormone levels, infarct severity, and the extent of transmurality in 40 STEMI patients evaluated via contrast-enhanced cardiac magnetic resonance imaging. RESULTS: The high triiodothyronine (T3) group (≥ 68.3 ng/dL) exhibited a significantly higher extent of transmural involvement (late transmural enhancement > 75% after administration of gadolinium contrast agent) than did the low T3 group (60% vs. 15%; p = 0.003). However, no significant difference was evident between the high- and low-thyroid-stimulating hormone/free thyroxine (FT4) groups. When the T3 cutoff level was set to 68.3 ng/dL using a receiver operating characteristic curve, the sensitivity was 80% and the specificity 68% in terms of differentiating between those with and without transmural involvement. Upon logistic regression analysis, high T3 level was an independent predictor of transmural involvement after adjustment for the presence of diabetes mellitus (DM) and the use of glycoprotein IIb/IIIa inhibitors (odds ratio, 40.62; 95% confidence interval, 3.29 to 502; p = 0.004). CONCLUSIONS: The T3 level predicted transmural involvement that was independent of glycoprotein IIb/IIIa inhibitor use and DM positivity.

Clinical Outcomes in Patients with Intermediate Coronary Stenoses: MINIATURE Investigators (Korea MultIceNter TrIal on Long-Term Clinical Outcome According to the Plaque Burden and Treatment Strategy in Lesions with MinimUm Lumen ARea lEss Than 4 mm(2) Using Intravascular Ultrasound).

BACKGROUND AND OBJECTIVES: We evaluated the two-year clinical outcomes in patients with angiographically intermediate lesions according to the plaque burden and treatment strategy. SUBJECTS AND METHODS: We prospectively enrolled patients with angiographically intermediate lesions (diameter stenosis 30-70%) with an intravascular ultrasound (IVUS) minimum lumen area (MLA) <4 mm(2) with 50-70% plaque burden of 16 Korean percutaneous coronary intervention centers. Patients were divided into medical therapy group (n=85) and zotarolimus-eluting stent group (ZES; Resolute) group (n=74). We evaluated the incidences of two-year major adverse cardiovascular events (MACE). RESULTS: A two-year clinical follow-up was completed in 143 patients and MACE occurred in 12 patients. There were no significant differences in the incidences of death (1.3% vs. 3.0%, p=0.471), target vessel-related non-fatal myocardial infarction (0.0% vs. 0.0%, p=1.000) and target vessel revascularizations (7.8% vs. 4.5%, p=0.425) between medical and ZES groups. Independent predictors of two-year MACE included acute myocardial infarction {odds ratio (OR)=2.87; 95% confidence interval (CI) 1.43-6.12, p=0.014}, diabetes mellitus (OR=2.46; 95% CI 1.24-5.56, p=0.028) and non-statin therapy (OR=2.32; 95% CI 1.18-5.24, p=0.034). CONCLUSION: Medical therapy shows comparable results with ZES, and myocardial infarction, diabetes mellitus and non-statin therapy were associated with the occurrence of two-year MACE in patients with intermediate lesion with IVUS MLA <4 mm(2) with 50-70% of plaque burden.

Stroke prevention in patients with non-valvular atrial fibrillation: new insight in selection of rhythm or rate control therapy and impact of mean platelet volume.

The aim of this study was to determine the impact of mean platelet volume (MPV) on the strategy for treatment of atrial fibrillation (AF) with respect to stroke prevention. MPV was analyzed in 265 patients with AF who were undergoing treatment using rhythm or rate control. The primary endpoint was ischemic stroke or a transient ischemic attack (TIA) event. Kaplan-Meier analysis revealed a significantly higher stroke rate in the rate control group compared to the rhythm control group. A significantly higher stroke rate was observed in the higher tertile MPV group (≥7.9 fL) compared to the lower tertile MPV group (<7.3 fL). When the MPV cut-off level was set to 7.85 fL using the receiver operating characteristic curve, the sensitivity was 80.0% and the specificity was 70.4% for differentiating between the group with stroke and the group without stroke. In the Cox proportional hazard analysis, after adjusting for sex, treatment strategy for AF, high MPV level, antithrombotic treatment, and high CHADS2 score, higher MPV, rate control strategy for treatment of AF, and high CHADS2 score were found to be independent predictors of stroke risk. In addition, patients with AF who were treated using rate control had high stroke risk with an MPV over 7.85 fL and high CHADS2 score. The results of this study demonstrate that the MPV and the rate control strategy for treatment of AF were predictive markers for stroke; its predictive power for stroke was independent of female sex and high CHADS2 score in patients with AF.

Stroke or coronary artery disease prediction from mean platelet volume in patients with type 2 diabetes mellitus.

The aim of this study was to determine the association of mean platelet volume (MPV) with the development of stroke or coronary artery disease (CAD) in diabetes mellitus (DM). MPV was analyzed in 200 Korean patients with DM. The primary endpoint was composite of ischemic stroke/CAD events. The mean MPV was 7.6 ± 0.8 fl. There were 14 ischemic stroke events and 8 CAD events during a mean of 28.4 months of follow-up. The Kaplan-Meier analysis revealed that the higher tertile MPV group (≥7.9 fl) had a significantly higher stroke/CAD rate compared to the lower tertile MPV group (≤7.3 fl) (29.9% vs. 2.8%, log-rank: p < 0.001). Higher MPV was an independent predictor of stroke/CAD risk after adjusting for 10-year risk ≥10%, hypertension, dyslipidemia, and previous stroke or transient ischemic attack history (hazard ratio: 11.92, 95% confidence interval 2.68-52.92, p = 0.001) in the Cox proportional hazard analysis. When the MPV cut-off level was set to 7.95 fl using the receiver operating characteristic curve, the sensitivity was 91% and the specificity was 80% for differentiating between the group with stroke/CAD and the group without stroke/CAD. This value was more useful in patients with hypertension. The results of this study show that MPV is a predictive marker for stroke/CAD; its predictive power for stroke/CAD is independent of age, gender, hypertension, and hemoglobin A1C.

Predictive value of brachial-ankle pulse wave velocity for cardiovascular events.

BACKGROUND: The aim of this study was to determine the association of pulse wave velocity or left ventricular diastolic function with the development of cardiovascular (CV) events. METHODS: Brachial-ankle pulse wave velocity (baPWV) and E/E' were analyzed in 185 patients. The primary end point was CV events including ischemic stroke, coronary arterial disease (CAD), peripheral arterial disease and aortic dissection. RESULTS: There were 30 CV events during a mean follow-up period of 19.8 months. When the baPWV cutoff level was set to 1704 cm/s using the receiver operating characteristic curve, the sensitivity was 70/92% and the specificity 63/62% for differentiating between the group with and without CV events or ischemic stroke. In univariate analysis with the Cox proportional hazard model, higher baPWV was a predictor for CV events and ischemic stroke events. However, high E/E' (>15) was not a predictor for CV, ischemic stroke events or CAD. A higher baPWV was an independent predictor for CV and ischemic stroke risk after adjusting for age, sex, hypertension and diabetes in the Cox proportional hazard analysis. In subgroup analysis, diabetic patients with a baPWV >1704 cm/s had a high CV event and ischemic stroke risk. CONCLUSIONS: The results of this study show that higher baPWV was a predictive marker for CV events, especially ischemic stroke. The subgroup analysis suggests that antiplatelet therapy may be needed in diabetic patients with a high baPWV for prevention of ischemic stroke.

Stroke prediction using mean platelet volume in patients with atrial fibrillation.

Platelet size, measured as mean platelet volume (MPV), is associated with platelet reactivity. MPV has been identified as an independent risk factor for future stroke and myocardial infarction. The aim of this study was to determine the association of MPV with the development of stoke in patients with atrial fibrillation (AF). MPV, N-terminal pro B-type natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hsCRP) were analysed in 200 patients with AF (mean age 69 years; 56% male). The primary endpoint was ischaemic stroke event. The mean MPV was 8.5 ± 1.0 fL and the median NT-proBNP was 1916.5 (IQR 810-4427) pg/mL. The median hsCRP was 0.47 (IQR 0.32-2.46) mg/dL. There were 14 stroke events during a mean of 15.1 months of follow up. Kaplan-Meier analysis revealed that the higher tertile MPV group (≥8.9 fL) had a significantly higher stroke rate compared to the lower tertile MPV group (<8.0 fL) (14.7% vs. 3.1%, log-rank: P = 0.01). A higher MPV was an independent predictor of stroke risk after adjusting for age, gender, and other CHADS(2) (congestive heart failure, hypertension, diabetes, and previous stroke or transient ischemic attack (TIA) history) score components (hazard ratio: 5.03, 95% CI 1.05-24.05, P = 0.043) in Cox proportional hazard analysis. When the MPV cut-off level was set to 8.85 fL using the receiver operating characteristic curve, the sensitivity was 71% and the specificity was 69% for differentiating between the group with stroke and the group without stroke. This value was more useful in patients with a low to intermediate traditional thromboembolic risk (CHADS(2) score <2). Furthermore, AF patients with an MPV over 8.85 fL had high stroke risk without anticoagulation, especially in the low thromboembolic risk group (Log-Rank <0.0001). The results of this study show that MPV was a predictive marker for stroke; its predictive power for stroke was independent of age, gender, and other CHADS(2) score components in patients with AF. These findings suggest that anticoagulation may be needed in patients with a high MPV, even if they have low to intermediate traditional thromboembolic risk (CHADS(2) score <2).

Effects of lovastatin on the pharmacokinetics of diltiazem and its main metabolite, desacetyldiltiazem, in rats: possible role of cytochrome P450 3A4 and P-glycoprotein inhibition by lovastatin.

OBJECTIVES: The purpose of this study was to examine the effects of lovastatin on cytochrome P450 (CYP) 3A4 and P-glycoprotein (P-gp) in vitro and then to determine the effects of lovastatin on the pharmacokinetics of diltiazem and its main metabolite, desacetyldiltiazem, in rats. METHODS: The pharmacokinetic parameters of diltiazem and desacetyldiltiazem were determined after orally administering diltiazem (12 mg/kg) to rats in the presence and absence of lovastatin (0.3 and 1.0 mg/kg). The effect of lovastatin on P-gp as well as CYP3A4 activity was also evaluated. KEY FINDINGS: Lovastatin inhibited CYP3A4 enzyme activity with a 50% inhibition concentration of 6.06 µM. In addition, lovastatin significantly enhanced the cellular accumulation of rhodamine-123 in MCF-7/ADR cells overexpressing P-gp. Compared with the control (given diltiazem alone), the presence of lovastatin significantly altered the pharmacokinetic parameters of diltiazem. The areas under the plasma concentration-time curve (AUC) and the peak concentration of diltiazem were significantly increased (P < 0.05, 1.0 mg/kg) in the presence of lovastatin. Consequently, the absolute bioavailability values of diltiazem in the presence of lovastatin (11.1% at 1.0 mg/kg) were significantly higher (P < 0.05) than that of the control group (7.6%). The metabolite-parent AUC ratio in the presence of lovastatin (1.0 mg/kg) was significantly (P < 0.05) decreased compared with the control group. CONCLUSIONS: It might be considered that lovastatin resulted in reducing the first-pass metabolism in the intestine and/or in the liver via inhibition of CYP3A4 and increasing the absorption of diltiazem in the intestine via inhibition of P-gp by lovastatin.

N-terminal pro B-type natriuretic peptide and the evaluation of cardiac dysfunction and severity of disease in cirrhotic patients.

PURPOSE: Cardiac dysfunction and hyperdynamic systemic circulation may be present in patients with cirrhosis. The purpose of this study was to identify relations between plasma levels of N-terminal-proBNP (NT-proBNP), reflecting early ventricular dysfunction, and the severity of liver disease and cardiac dysfunction in cirrhotic patients. MATERIALS AND METHODS: Sixty-three cirrhotic patients and 15 controls (group 1) were enrolled in this study. Plasma levels of NT-proBNP were determined in echocardiographically examined patients, which were allocated to 1 of 3 groups according to Child-Pugh classification or into 2 groups, i.e., a compensated group without ascites (group 2) and decompensated group with ascites (group 3). RESULTS: Plasma NT-proBNP levels were significantly higher in cirrhotic patients (groups 2 and 3) than in age-matched controls (155.9 and 198.3 vs. 40.3 pg/mL, respectively, p < 0.05). NT-proBNP levels were significantly increased in Child class C patients than in classes B and A (250.0 vs. 168.6 and 119.6 pg/mL, respectively, p < 0.05). Left atrial dimension, wall thickness of left ventricle, and EF or E/E' were significantly increased, and EDT was prolonged in cirrhotic patients than in controls. Increased LVMI and decreased E/A ratio were noted in the group of patients with ascites as compared with the other groups. CONCLUSION: Plasma NT-proBNP levels were high in cirrhotic patients and are likely to be related to the severity of disease. Advanced cirrhosis is associated with advanced cardiac dysfunction, and NT-proBNP levels has predictive value for concomitant cardiac dysfunction and cirrhosis progression.

One month follow-up C-reactive protein may be a useful predictor of angiographic restenosis and long-term clinical outcomes after bare metal stent implantation.

We report C-reactive protein (CRP) measured 1 month after stenting was an independent predictor of angiographic restenosis, and patients with both elevated preprocedural CRP and CRP 1 month after stenting had the worst long-term clinical outcomes. Measurement of CRP during follow-up in addition to preprocedural CRP may improve risk stratification after coronary stenting.

Differences in the immediate effects of smoking on left ventricular diastolic function between healthy volunteers and patients with type 2 diabetes mellitus.

BACKGROUND: In contrast to in-depth studies on the chronic hazardous effects of smoking, the immediate effects of smoking on left ventricular function have not been evaluated in detail. OBJECTIVES: We aimed to assess the hypothesis that smoking a cigarette might have more deleterious immediate impacts on left ventricular function in patients with diabetes mellitus than in healthy volunteers. METHODS: In all, 20 patients with type 2 diabetes mellitus and 25 healthy volunteers were consecutively enrolled. Mitral inflow parameters (peak early and late diastolic velocities, and deceleration time of early diastolic mitral inflow) and mitral annulus velocity parameters (systolic, late, and early diastolic velocity [E']) were obtained together with heart rate and blood pressure before and 5, 15, 30, 45, 60, and 75 minutes after smoking a cigarette. RESULTS: Transient elevations in heart rate and blood pressure were observed after smoking in both groups. In terms of mitral inflow parameters, transient trends toward abnormal relaxation were noted in both groups. For mitral annulus velocity parameters, in contrast to a temporary decrease in E' in healthy volunteers, reduction in E' persisted throughout the study for patients with diabetes. No significant change in peak early diastolic velocity/E' ratio was observed in healthy volunteers; however, a significant increase in peak early diastolic velocity/E' ratio lasted throughout the study period for patients with diabetes. Systolic velocity had no significant change during the study in either group. CONCLUSIONS: Even one cigarette can induce more protracted and more severe left ventricular diastolic dysfunction in patients with type 2 diabetes mellitus than in healthy volunteers. Our results have clinically relevant implications in the current era of increasing recognition of the diabetes epidemic and of the associated cardiovascular risks.

Impact of left ventricular diastolic function on exercise capacity in patients with chronic mitral regurgitation: an exercise echocardiography study.

BACKGROUND: Mitral regurgitation (MR) is known as one of the most frequent causes of heart failure and sudden death. In spite of increasing prevalence of MR, there have been no available data on cardiac determinants of exercise capacity in patients with chronic MR. HYPOTHESIS: This study aimed to investigate cardiac determinants of exercise capacity in patients with chronic MR. METHODS: We consecutively enrolled 32 patients (11 men, mean age: 44 +/- 14 years) who had greater than moderate MR with normal left ventricular (LV) systolic function (LV ejection fraction >50%). Conventional echocardiographic indices and parameters measured by Doppler tissue imaging at septal side of mitral annulus were obtained before exercise. Mitral regurgitation fraction, forward stroke volume, pulmonary venous flow velocities, and systolic pulmonary artery pressure (sPAP) were also obtained with standard methods. RESULTS: Left ventricular ejection fraction was 61 +/- 6% and MR fraction was 48 +/- 13%. All patients finished a symptom-limited treadmill exercise test with a peak heart rate of >85% of predicted maximum heart rate. Mean exercise time was 9.95 +/- 2.17 min, corresponding to 11 +/- 2 metabolic equivalents. Among pre-exercise echocardiographic variables, only early diastolic mitral annulus velocity (E') and pulmonary venous reversal flow velocity (PVa) showed a significant correlation with exercise time (r = 0.44, p = 0.011, and r = -0.40, p = 0.040, respectively), which persisted after multivariate analysis (p = 0.011 and 0.038, respectively). Other parameters such as systolic mitral annulus velocity, resting and postexercise sPAP, forward stroke volume, LV size, LV ejection fraction, left atrial size, and regurgitant fraction showed no significant correlation. CONCLUSIONS: Left ventricular diastolic function is an important determinant of exercise capacity in patients with chronic MR. Both E' and PVa, accepted surrogate estimates for LV diastolic function, may be useful for identifying patients with chronic MR and with poor exercise capacity.