Yae Min Park

How to control residual cardiovascular risk despite statin treatment: Focusing on HDL–cholesterol

Lowering low-density lipoprotein-cholesterol (LDL-C) is the primary target in the management of dyslipidemia in patients at high risk of cardiovascular disease. However, patients who have achieved LDL-C levels below the currently recommended targets may still experience cardiovascular events. This may result, in part, from elevated triglyceride (TG) levels and low levels of high-density lipoprotein-cholesterol (HDL-C). Low HDL-C and high TG levels are common and are recognized as independent risk factors for cardiovascular morbidity and mortality. Furthermore, atherogenic dyslipidemia, characterized by low levels of HDL-C, high TG, and small, dense LDL particles, is a typical phenotype of dyslipidemia in subjects with insulin resistance and metabolic syndrome. Therefore, to reduce further the risk of coronary heart disease (CHD), raising HDL-C and lowering TG may be the secondary therapeutic target for patients who achieve LDL-C levels below the currently recommended targets but are still at risk of CHD. However, whether increasing HDL-C levels alone reduces CHD has not yet been confirmed in large randomized clinical trials, and whether functional HDL is more important than HDL-C in reducing CHD remains controversial. Large CHD endpoint trials that include many patients with diabetes are underway to compare combination treatments with statin and niacin, fibrates, or cholesteryl ester transfer protein inhibitors with statin alone treatments. In this review, we discuss the rationale and importance of increasing HDL-C levels with and without lowering TG levels in the treatment and prevention of cardiovascular events.

Vascular and metabolic effects of ezetimibe combined with simvastatin in patients with hypercholesterolemia

BACKGROUND Ezetimibe demonstrates decreasing visceral fat and improving insulin sensitivity (IS) in animals and humans. We first reported that simvastatin dose-dependently worsens insulin sensitivity. Whether ezetimibe may compensate untoward effects of simvastatin, depending on dosages of simvastatin has not been investigated in patients with hypercholesterolemia, compared with simvastatin alone. METHODS This was a randomized, single-blind, placebo-controlled, parallel study. Fifty-one in each group were given placebo, ezetimibe 10mg combined with simvastatin 10mg (Vyto10), ezetimibe 10mg combined with simvastatin 20mg (Vyto20), or simvastatin 20mg alone (Simva20) daily for 2months. RESULTS Placebo, Vyto10, Vyto20, and Simva20 improved flow-mediated dilation relative to baseline measurements. Placebo therapy did not significantly change insulin and IS and adiponectin levels and visceral fat area (VFA) and VFA/subcutaneous fat area (SFA) relative to baseline measurements. Vyto10 therapy significantly decreased CRP and insulin levels and increased adiponectin levels and IS, and reduced VFA, VFA/SFA, and blood pressure. Vyto20 therapy did not significantly change insulin levels and IS and adiponectin levels but significantly reduced CRP levels and VFA, VFA/SFA, and blood pressure. Simva20 therapy significantly decreased adiponectin levels and IS but did not significantly change VFA, VFA/SFA, and blood pressure. Of note, these different effects of each therapy were significant by ANOVA. CONCLUSIONS Vyto10, Vyto20, and Simva20 showed significant reduction of LDL cholesterol levels and improvement of flow-mediated dilation in patients with hypercholesterolemia. However, Vyto10, Vyto20, and Simva20 showed significantly differential metabolic effects, depending on dosages of simvastatin.

Diffuse multi-vessel coronary artery spasm: Incidence and clinical prognosis

BACKGROUND The incidence and clinical prognosis of diffuse and multivessel coronary spasm has not been reported. METHODS Patients with suspected vasospastic angina were prospectively enrolled. Left and right coronary angiogram was performed simultaneously after intravenous ergonovine injection. Spasm (>70% luminal narrowing) was sub-classified as diffuse (more than 20mm length), multivessel (more than 2 epicardial arteries). Clinical characteristics and prognosis were analyzed. RESULTS Patients (96 consecutive patients, 56 males, mean age 48 years) were divided into 3 groups: diffuse-multivessel spasm (group I, n=16, 16.7%), other types of spasm (group II, n=12, 12.5%) and control group (group III, n=68, 70.8%). The rates of males, alcohol drinkers and the mean triglyceride were higher, and high density lipoprotein was lower in group I compared to group III (all p<0.05), but similar to group II (all p=NS). Hard cardiovascular event rates did not differ among groups (one cardiac arrest but successful resuscitation in group I, one non-fatal myocardial infarction in group III) during follow up periods (mean, 41.2 ± 13.7 months). Chest pain free survivals during 1 year were lower in group I (66.7%) compared to group III (90%), but similar to group II (58.3%) (group I vs III, p<0.05 and group I vs II, p=NS). CONCLUSIONS Diffuse-multivessel spasm was not rare in patients with vasospastic angina and its prognosis is pretty good similar to patients with previously known variant angina with recommended medical treatment.

Rosuvastatin combined with ramipril significantly reduced atheroma volume by anti-inflammatory mechanism: comparative analysis with rosuvastatin alone by intravascular ultrasound.

BACKGROUND We tested the effects of rosuvastatin combined with ramipril on atheroma volume and its mechanism in de novo, intermediate coronary artery disease. METHODS Subjects were randomly assigned to 2 treatment groups (rosuvastatin alone group; 20mg/day, combined group; rosuvastatin 20mg/day and ramipril 10mg/day). Total atheroma volume per 10mm segment (TAV/10mm), percent atheroma volume per 10mm segment (PAV/10mm) in entire indexed segments and TAV(most10), PAV(most10) in a 10mm subsegment with the greatest disease by intravascular ultrasound, and lipids, metabolic parameters (adiponectin, insulin sensitivity), biomarkers (hsCRP, matrix metalloproteinase-9) were analyzed at baseline and at 9-12 months follow-up. RESULTS A total of 40 patients (rosuvastatin group; 21, combined group; 19), 46 lesions (rosuvastatin group; 24, combined group; 22) were finally analyzed. Rosuvastatin alone significantly reduced TAV/10mm (-7.8 ± 17.4%, p<0.001) but did not change PAV/10mm, TAV(most10), PAV(most10) after therapy. In combined group, TAV/10mm, TAV(most10), PAV(most10) were significantly reduced after therapy (-10.7 ± 11.5%, -13.4 ± 14.5%, -2.7 ± 5.8%, p<0.001, <0.001 and p=0.04) but PAV/10mm did not change. The magnitude of changes of all IVUS derived parameters did not differ significantly between 2 groups. Of interest, the most important factor for the changes of PAV(most10) was the percent changes of LDL cholesterol (β=0.23, 95% CI [0.07-0.39], p=0.007) in rosuvastatin alone group and the changes in hsCRP (β=1.89, 95% CI [0.63-3.14], p=0.005) and baseline fasting blood glucose (β=0.06, 95% CI [0.01-0.11], p=0.02) in combined group by multivariate analysis. CONCLUSIONS Rosuvastatin combined ramipril therapy significantly reduced atheroma volume that was related with anti-inflammatory effects.

Comparison of edge vascular response after sirolimus- and paclitaxel-eluting stent implantation.

BACKGROUND To compare the edges vascular response, we analyzed the intravascular ultrasound (IVUS) parameters after implantation of the sirolimus-eluting stent (SES) or the paclitaxel-eluting stent (PES). METHODS Two hundred-two angina patients (123 men; 61.5 ± 9.2 years of age, SES: n = 91, PES: n=111) were enrolled. Both edge segments of the stent were analyzed. The change (Δ) of each parameter at follow-up was calculated. RESULTS The edge restenosis rate was higher in the PES group. However, the Δ Vessel, Δ Plaque and Δ Lumen volume at 5mm edge segments were not different between the two groups except the Δ Plaque volume at the distal segment, higher in the PES than the SES group (6.6 ± 15.7 vs. 1.0 ± 13.1mm(3), P=.016). In the PES group, lumen area at the both 1mm edge segments decreased because of plaque progression (proximal, 1.9 ± 1.5 to 2.2 ± 2.0mm(2), P=.095; distal, 0.6 ± 1.1 to 1.0 ± 1.4mm(2), P=.018) with negative remodeling (proximal, 9.9 ± 2.4 to 9.4 ± 2.6mm(2), P=.004; distal, 7.6 ± 2.4 to 7.2 ± 2.4mm(2), P=.052). Conversely, lumen area at these segments increased due to plaque regression (proximal, 3.2 ± 1.8 to 2.1 ± 1.6mm(2), P=.000; distal, 1.5 ± 1.4 to 0.9 ± 1.3mm(2), P=.000) even though there was negative remodeling in the SES group (proximal, 10.1 ± 2.4 to 9.6 ± 2.3mm(2), P=.019; distal, 7.8 ± 2.3 to 7.5 ± 2.3mm(2), P=.074). The Δ Plaque and Δ Lumen area at the both 1mm edge segments were more prominent in the PES group. CONCLUSIONS Compared to SES, PES was associated with luminal reduction accompanied by plaque progression with negative remodeling at edge segments.

Successful management of portopulmonary hypertension with beraprost

Portopulmonary hypertension is a complication of chronic liver disease, which has significant effects on survival and prognosis. Although the pathogenesis of pulmonary arterial hypertension has been well known, portopulmonary hypertension is often underestimated in patients with chronic liver disease. Every clinician who manages patients with chronic liver disease complaining of dyspnea should consider portopulmonary hypertension because this disorder requires special treatment. Herein, a 40-year-old woman with liver cirrhosis who complained of dyspnea on exercise is presented. She was diagnosed with portopulmonary hypertension by echocardiography and right-heart catheterization. Beraprost was used to reduce the pulmonary arterial pressure and improve the symptoms. Her symptoms were improved after 2 weeks, and improved symptoms and reduced pulmonary arterial pressure were sustained for 18 months.

Comparison of Outcomes after Device Closure and Medication Alone in Patients with Patent Foramen Ovale and Cryptogenic Stroke in Korean Population

Purpose To compare the effectiveness of device closure and medical therapy in prevention of recurrent embolic event in the Korean population with cryptogenic stroke and patent foramen ovale (PFO). Materials and Methods Consecutive 164 patients (men: 126 patients, mean age: 48.1 years, closure group: 72 patients, medical group: 92 patients) were enrolled. The primary end point was a composite of death, stroke, transient ischemic attack (TIA), or peripheral embolism. Results Baseline characteristics were similar in the two groups, except age, which was higher in the medical group (45.3±9.8 vs. 50.2±6.1, p<0.0001), and risk of paradoxical embolism score, which was higher in the closure group (6.2±1.6 vs. 5.7±1.3, p=0.026). On echocardiography, large right-to-left shunt (81.9% vs. 63.0%, p=0.009) and shunt at rest/septal hypermobility (61.1% vs. 23.9%, p<0.0001) were more common in the closure group. The device was successfully implanted in 71 (98.6%) patients. The primary end point occurred in 2 patients (2 TIA, 2.8%) in the closure group and in 2 (1 death, 1 stroke, 2.2%) in the medical group. Event-free survival rate did not differ between the two groups. Conclusion Compared to medical therapy, device closure of PFO in patients with cryptogenic stroke did not show difference in reduction of recurrent embolic events in the real worlds setting. However, considering high risk of echocardiographic findings in the closure group, further investigation of the role of PFO closure in the Asian population is needed.

Effect of patent foramen ovale closure for prevention on recurrent stroke or transient ischemic attack in selected patients with cryptogenic stroke

OBJECTIVES This study was sought to evaluate the effectiveness of patent foramen ovale (PFO) closure in selected patients (PFO shunt grade more than moderate) with cryptogenic stroke (CS). BACKGROUND Whether closure of PFO is an effective treatment for prevention of CS is still unclear. METHODS Consecutive 158 patients (mean age: 49.9 years old, closure group: 67 patients, medication group: 91 patients) were enrolled. The primary end point was a composite of recurrent stroke and transient ischemic attack. RESULTS Baseline characteristics were similar between the two groups, except age which was younger in the closure group (47.7 ± 10.8 vs 51.9 ± 9.9, P = 0.013), and the presence of shunt at rest was more common in the closure group (35.8% vs 10.4%, P = 0.000). Procedural success was 94.0%. Over a mean follow-up of 27.8 months, a total of six primary end point, all of which were strokes, occurred only in the medication group (6.6% vs 0%, P = 0.039). Stroke-free survival rate was significantly higher in the closure group (P = 0.026) CONCLUSIONS: Our study showed that PFO closure may be an effective treatment strategy to prevent recurrent stroke or TIA for patients with CS if it is conducted in selective patients who have PFO shunt more than moderate grade.

Repeated Aborted Sudden Cardiac Death with Long QT Syndrome in a Patient with Anomalous Origin of the Right Coronary Artery from the Left Coronary Cusp

A 15-year-old female with a prior history of aborted cardiac death and surgical correction of anomalous origin of the right coronary artery (RCA) presented with polymorphic ventricular tachycardia. Her electrocardiogram after defibrillation was suggestive of congenital long QT syndrome (LQTS). The patient was treated with a β-blocker and remained free from ventricular arrhythmia during the follow-up of more than 6 months. Here, we present the case of a young female with repeated aborted cardiac death accompanied by anomalous origin of the RCA and congenital LQTS for the first time.

Repeated sudden cardiac death in coronary spasm: Is IVUS helpful to decide treatment strategy?

Coronary spasm is thought to be the main pathogenic mechanism of variant angina. Despite medical treatment, ischemic events are continued in some patients, often associated with serious complications [1,2]. Ventricular arrhythmias and sudden cardiac death have been predominantly reported in cases of multivessel coronary artery spasm [3]. In medically intractable coronary spasm, coronary stent or Implantable cardioverter defibrillators (ICD) have suggested as a treatment strategy, but optimal therapy is still unknown. We report a young patient of medically intractable vasospastic angina who experienced sudden cardiac death twice and successfully treated with stent after intravascular ultrasound study. A 27-year-old male patient came to emergency room because of sudden cardiovascular collapse during sleeping. He was a non smoker and other cardiovascular risk factors were absent. Initial electrocardiogram (ECG) showed ventricular fibrillation. Basic life support including defibrillation (biphasic 200 J) successfully restored sinus rhythm without neurologic sequel. Follow up ECG showed markedly elevated ST segments at all leads (Fig. 1A) and cardiac enzymes were elevated. Emergency coronary angiography, however, showed no significant coronary artery stenosis (Fig. 1B and C). He was started on intravenous administration of nitrates, and calcium antagonist under suspicion of coronary spasm. Echocardiography ruled out myocarditis or pericarditis. Duringhospital stay, no signs of rhythmdisturbances or