In Suck Choi

Additive Beneficial Effects of Losartan Combined With Simvastatin in the Treatment of Hypercholesterolemic, Hypertensive Patients

Background—Biological mechanisms underlying statin and angiotensin II type 1 receptor blocker therapies differ. Therefore, we compared vascular and metabolic responses to these therapies either alone or in combination in hypercholesterolemic, hypertensive patients. Methods and Results—This was a randomized, double-blind, placebo-controlled crossover trial with 3 treatment arms (each 2 months) and 2 washout periods (each 2 months). Forty-seven hypertensive, hypercholesterolemic patients were given simvastatin 20 mg and placebo, simvastatin 20 mg and losartan 100 mg, or losartan 100 mg and placebo daily during each 2-month treatment period. Losartan alone or combined therapy significantly reduced blood pressure compared with simvastatin alone. Compared with losartan alone, simvastatin alone or combined therapy significantly changed lipoproteins. All 3 treatment arms significantly improved flow-mediated dilator response to hyperemia and decreased plasma malondialdehyde and monocyte chemoattractant protein-1 levels relative to baseline measurements. However, these parameters were changed to a greater extent with combined therapy compared with simvastatin or losartan alone (both P<0.001 and P=0.030 for monocyte chemoattractant protein-1 by ANOVA). Combined therapy or losartan alone significantly increased plasma adiponectin levels and insulin sensitivity (determined by QUICKI) relative to baseline measurements. These changes were significantly greater than in the group treated with simvastatin alone (P<0.001 for adiponectin, P=0.029 for QUICKI by ANOVA). Conclusions—Simvastatin combined with losartan improves endothelial function and reduces inflammatory markers to a greater extent than monotherapy with either drug in hypercholesterolemic, hypertensive patients.

Pleiotropic effects of angiotensin II receptor blocker in hypertensive patients.

OBJECTIVES We investigated the vascular effects of candesartan in hypertensive patients. BACKGROUND The renin-angiotensin system may contribute to atherogenesis through the promotion of endothelial dysfunction. The plausible mechanisms are that angiotensin II promotes superoxide anion generation, endothelial dysfunction, inflammation, and impaired fibrinolysis. The effects of candesartan on these conditions have not been clearly observed. METHODS We administered placebo or candesartan 16 mg daily during two months to 45 patients with mild-to-moderate hypertension. This was a randomized, double-blind, placebo-controlled, crossover study in design. RESULTS Candesartan did not significantly change lipoprotein levels. However, compared with placebo, candesartan significantly reduced plasma levels of malondialdehyde from 1.50 +/- 0.07 to 1.29 +/- 0.09 microM (p = 0.009); improved the percent flow-mediated dilator response to hyperemia from 5.17 +/- 0.24 to 6.22 +/- 0.26% (p < 0.001); and, furthermore, reduced plasma levels of monocyte chemoattractant protein (MCP-1) from 213 +/- 8 to 190 +/- 7 pg/ml (p = 0.003), tumor necrosis factor-alpha from 2.93 to 2.22 pg/ml (p = 0.026), and plasminogen activator inhibitor type 1 from 74 +/- 4 to 53 +/- 4 ng/ml (p < 0.001) but not C-reactive protein (CRP), matrix metalloproteinase protein, and fibrinogen. There were no significant correlations between these changes and reduction of systolic blood pressure (BP) (-0.247 < or = r < or = 0.195) and between these changes and reduction of diastolic BP (-0.262 < or = r < or = 0.197). There were no significant correlations between markers of inflammation and flow-mediated dilation percent or reduction of oxidant stress (-0.119 < or = r < or = 0.127). Furthermore, we observed no significant correlations between CRP and MCP-1 levels (r = -0.162). CONCLUSIONS Inhibition of the angiotensin II type 1 (AT1) receptor in hypertensive patients reverses endothelial dysfunction, measured as an improvement in flow-mediated dilation and fibrinolysis and reduction of oxidant stress and inflammatory cytokines, suggesting that AT1 receptor blocker therapy has antiatherogenic effects.

Vascular Effects of Synthetic or Natural Progestagen Combined With Conjugated Equine Estrogen in Healthy Postmenopausal Women

BackgroundSynthetic, not natural, progestagen may negate the favorable effects of estrogen. Nonetheless, observational studies report no differences in risk for clinical cardiovascular events between users of unopposed estrogen and users of estrogen combined with synthetic progestin. Methods and ResultsIn a double-blind study, we randomly assigned 20 healthy postmenopausal women to micronized progesterone (MP) 200 mg or medroxyprogesterone acetate (MPA) 10 mg for 10 days with conjugated equine estrogen (CEE) 0.625 mg for 25 days and the remaining 5 days off cyclically during 2 months, followed by crossover to the alternate therapy. CEE+MP and CEE+MPA significantly improved the percent flow-mediated dilator response to hyperemia relative to baseline measurements (P =0.004 by ANOVA) by a similar degree (P =0.863). Both therapies significantly decreased E-selectin, intercellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1 levels from baseline values (P <0.001, P =0.048, and P =0.016 by ANOVA, respectively) by a similar degree (P =0.977 for ICAM-1 and P =0.541 for VCAM-1, respectively). CEE+MPA decreased E-selectin levels more than CEE+MP did (P =0.040). Both therapies significantly decreased monocyte chemoattractant protein-1 levels from baseline values (P <0.005 by ANOVA) by a similar degree (P =0.194). Both therapies significantly decreased tissue factor antigen and increased tissue factor activity levels from baseline values (P =0.003 and P <0.001 by ANOVA, respectively) by a similar degree (P =0.652 for antigen and P =0.173 for activity). Both therapies significantly lowered plasma plasminogen activator inhibitor-1 levels from baseline values (P <0.001 by ANOVA) by a similar degree (P =0.533). ConclusionsCEE+MP and CEE+MPA provide similar improvement in endothelium-dependent vasodilator responsiveness and effects on markers of inflammation, hemostasis, and fibrinolysis inhibition in healthy postmenopausal women.

Effects of hormone replacement therapy on plaque stability, inflammation, and fibrinolysis in hypertensive or overweight postmenopausal women ☆

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Non-lipid effects of statin on hypercholesterolemic patients established to have coronary artery disease who remained hypercholesterolemic while eating a step-II diet.

BackgroundResults of clinical trials of statin therapy demonstrate that an improvement in incidence of cardiovascular end points and coronary stenosis can be achieved. The beneficial effects of statins on clinical events may involve nonlipid mechanisms that affect endothelial function, such as inflammatory responses, formation of thrombi, and stabilization of plaque. ObjectiveTo investigate levels of serologic markers, which may be useful surrogates for activity of vascular disease after administration of statin. MethodsWe administered 20–40 mg simvastatin daily for 14 weeks to 13 patients established to have coronary artery disease who remained hypercholesterolemic during step‐II diet therapy. ResultsAdministration of simvastatin significantly lowered lipoprotein levels and the low : high‐density lipoprotein cholesterol level ratio and apolipoprotein B : A‐I level ratio compared with pretreatment values (P  < 0.01). Administration of simvastatin significantly lowered plasma levels of matrix metalloproteinase‐9 (MMP‐9) and monocyte chemoattractant protein‐I [33 ± 46 and 13 ± 19%, respectively (P  = 0.027 and 0.020, respectively)]. Furthermore, administration of simvastatin tended to lower plasma levels of plasminogen activator inhibitor type‐1 and tumor necrosis factor‐α [by 20 ± 44 and 13 ± 29%, respectively (P  = 0.066 and 0.110, respectively)]. There were significant inverse correlations between pretreatment levels of MMP‐9 and the degree of change in those levels after administration of simvastatin (r  = –0.714, P  = 0.005). However, there was no significant correlation between levels of lipoprotein and levels of MMP‐9, monocyte chemoattractant protein‐I, and plasminogen activator inhibitor type‐1 during administration of simvastatin. ConclusionsOur current data support the hypothesis that nonlipid mechanisms elicited by administration of simvastatin contribute to the decrease in incidence of cardiovascular events and explain the early clinical benefit observed in clinical trials, independent of changes in levels of lipoprotein.

Echocardiographic Assessments of Left Atrial Strain and Volume in Healthy Patients and Patients With Mitral Valvular Heart Disease by Tissue Doppler Imaging and 3-Dimensional Echocardiography

Background and Objectives The purpose of the current study was to assess left atrial (LA) physiology in relation to associations between LA volume change and regional tissue velocities and strains, and to extend this information to patients with mitral stenosis (MS) or mitral regurgitation (MR). Subjects and Methods Twenty-two healthy persons, 22 patients with moderate-to-severe MS, and 22 patients with moderate-to-severe MR were studied. Tissue velocities, strains, and time-volume curves of the LA were acquired using tissue Doppler imaging and 3-dimensional echocardiography. Results In healthy controls, the maximal LA volume was negatively correlated with the posterior wall longitudinal systolic strain (r=-0.45, p=0.03). The time-to-maximal LA volume was positively correlated with the time-to-posterior wall longitudinal peak strain (r=0.46, p=0.03) and the time-to-circumferential peak strain (r=0.59, p=0.004). The LA active emptying fraction (LAactEF) was positively correlated with the posterior wall longitudinal peak systolic and late diastolic tissue velocities. In patients with MS, the maximal LA volume was negatively correlated with the posterior wall radial peak systolic velocity and the longitudinal late diastolic velocity. In patients with MS, the LAactEF had an additional positive correlation with the anterior wall longitudinal and circumferential systolic velocities, whereas the patients with MR had an additional positive correlation between the LAactEF and the lateral wall longitudinal peak strain as compared with the healthy cantrols. Conclusion LA longitudinal and circumferential deformations are more related than radial deformation to determining LA volume and function. The LA of patients with MS revealed a greater pathologic physiology than those of patients with MR.

Recurrent restenosis following stent and rotational atherectomy of coronary artery stenosis in Takayasu's arteritis

We report a patient with Takayasus arteritis who had recurrent restenosis following intracoronary bifurcation stenting of proximal left anterior descending and first diagonal arteries, and rotational atherectomy for in-stent restenosis. After all, the patient underwent coronary artery bypass grafts (CABG) and has remained asymptomatic during 3 months without damaging myocardium. We suggest that endoluminal stenting or rotational atherectomy may be an alternative treatment for the patients with coronary artery stenosis due to active Takayasus arteritis as a therapy to postpone CABG.

Efficacy and safety of aspirin, clopidogrel, and warfarin after coronary artery stenting in Korean patients with atrial fibrillation.

There are limited data on the optimal antithrombotic therapy for patients with atrial fibrillation (AF) who undergoing coronary stenting. We reviewed 203 patients (62.6 % men, mean age 68.3 ± 10.1 years) between 2003 and 2012, and recorded clinical and demographic characteristics of the patients. Clinical follow-up included major adverse cardiac and cerebrovascular events (MACCE) (cardiac death, myocardial infarction, target lesion revascularization, and stroke), stent thrombosis, and bleeding. The most commonly associated comorbidities were hypertension (70.4 %), diabetes mellitus (35.5 %), and congestive heart failure (26.6 %). Sixty-three percent of patients had stroke risk higher than CHADS2 score 2. At discharge, dual-antiplatelet therapy (aspirin, clopidogrel) was used in 166 patients (81.8 %; Group I), whereas 37 patients (18.2 %) were discharged with triple therapy (aspirin, clopidogrel, warfarin; Group II). The mean follow-up period was 42.0 ± 29.0 months. The mean international normalized ratio (INR) in group II was 1.83 ± 0.41. The total MACCE was 16.3 %, with stroke in 3.4 %. Compared with the group II, the incidence of MACCE (2.7 % vs 19.3 %, P = 0.012) and cardiac death (0 % vs 11.4 %, P = 0.028) were higher in the group I. Major and any bleeding, however, did not differ between the two groups. In multivariate analysis, no warfarin therapy (odds ratio 7.8, 95 % confidence interval 1.02–59.35; P = 0.048) was an independent predictor of MACCE. By Kaplan–Meier survival analysis, warfarin therapy was associated with a lower risk of MACCE (P = 0.024). In patients with AF undergoing coronary artery stenting, MACCE were reduced by warfarin therapy without increased bleeding, which might be related to tighter control with a lower INR value.

Predictors of Recovery of Left Ventricular Systolic Dysfunction after Acute Myocardial Infarction: From the Korean Acute Myocardial Infarction Registry and Korean Myocardial Infarction Registry

Background and Objectives We investigated the predictors of the recovery of depressed left ventricular ejection fraction (LVEF) in patients with moderate or severe left ventricular (LV) systolic dysfunction after acute myocardial infarction (MI). Subjects and Methods We analyzed 1307 patients, who had moderately or severely depressed LVEF (<45%) on echocardiography soon after acute MI and who underwent a follow-up echocardiography, among 27369 patients from the Korea Working Group on the Myocardial Infarction Registry. Patients were categorized into two groups according to recovery of LVEF: group I with consistently depressed LVEF (<45%) at the follow-up echocardiography and group II with a recovery of LVEF (≥45%). Results Recovery of LV systolic dysfunction was observed in 51% of the subjects (group II, n=663; ΔLVEF, 16.2±9.3%), whereas there was no recovery in the remaining subjects (group I, n=644; ΔLVEF, 0.6±7.1%). In the multivariate analysis, independent predictors of recovery of depressed LVEF were as follows {odds ratio (OR) [95% confidence interval (CI)]}: moderate systolic dysfunction {LVEF ≥30% and <45%; 1.73 (1.12-2.67)}, Killip class I-II {1.52 (1.06-2.18)}, no need for diuretics {1.59 (1.19-2.12)}, non-ST-segment elevation MI {1.55 (1.12-2.16)}, lower peak troponin I level {<24 ng/mL, median value; 1.55 (1.16-2.07)}, single-vessel disease {1.53 (1.13-2.06)}, and non-left anterior descending (LAD) culprit lesion {1.50 (1.09-2.06)}. In addition, the use of statin was independently associated with a recovery of LV systolic dysfunction {OR (95% CI), 1.46 (1.07-2.00)}. Conclusion Future contractile recovery of LV systolic dysfunction following acute MI was significantly related with less severe heart failure at the time of presentation, a smaller extent of myonecrosis, or non-LAD culprit lesions rather than LAD lesions.

The Effects of Statin and Niacin on Plaque Stability, Plaque Regression, Inflammation and Oxidative Stress in Patients With Mild to Moderate Coronary Artery Stenosis

Background and Objectives The aim of this study was to compare the effects of a combination of niacin and simvastatin to simvastatin alone, on plaque regression and inflammatory makers. Subjects and Methods The study had a prospective, randomized design. Subjects were patients with intermediate coronary artery stenosis. A total of 28 patients received a combination of niacin 1,000 mg plus simvastatin 40 mg (N+S group, n=14); the other group received simvastatin 40 mg alone (S group, n=14). All patients had a baseline and a 9-month follow-up coronary angiogram and an intravascular ultrasound procedure. Parameters such as normalized total atheroma volume (nTAV) and percent atheroma volume (PAV) were analyzed before and after treatment as were inflammatory markers such as high sensitivity C-reactive protein (hs-CRP), Matrix me-talloproteinase-9 (MMP-9) and soluble CD40 ligand (sCD40L). Results There was no difference in baseline characteristics between the two groups. The nTAV and PAV in the N+S group before and after treatment were not different than those in the S group. But the degree of changes (delta) in nTAV in the N+S group was greater than that in the S group (-21.6±10.68 vs. 5.25±42.19, respectively, p=0.024). Also, the change in PAV in the NS group was higher than that in the S group (-1.2±2.5 vs. -0.6±5, respectively, p=0.047. Changes in hs-CRP, MMP-9, and sCD40L in the NS group were significantly greater than those of the S group (-0.71±1.25, 73.5±64.9, -1,970±1,925 vs. -0.32±0.96, 62.5±30.6, -1,673±2,628, respectively). Conclusion The combination of niacin plus simvastatin decreases coronary plaque volume and attenuates the inflammatory response in patients with intermediate coronary artery stenosis.