Pang-Yen Liu

Therapeutic modification of arterial stiffness: An update and comprehensive review

Arterial stiffness has been recognized as a marker of cardiovascular disease and associated with long-term worse clinical outcomes in several populations. Age, hypertension, smoking, and dyslipidemia, known as traditional vascular risk factors, as well as diabetes, obesity, and systemic inflammation lead to both atherosclerosis and arterial stiffness. Targeting multiple modifiable risk factors has become the main therapeutic strategy to improve arterial stiffness in patients at high cardiovascular risk. Additionally to life style modifications, long-term ω-3 fatty acids (fish oil) supplementation in diet may improve arterial stiffness in the population with hypertension or metabolic syndrome. Pharmacological treatment such as renin-angiotensin-aldosterone system antagonists, metformin, and 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors were useful in individuals with hypertension and diabetes. In obese population with obstructive sleep apnea, weight reduction, aerobic exercise, and continuous positive airway pressure treatment may also improve arterial stiffness. In the populations with chronic inflammatory disease such as rheumatoid arthritis, a use of antibodies against tumor necrosis factor-alpha could work effectively. Other therapeutic options such as renal sympathetic nerve denervation for patients with resistant hypertension are investigated in many ongoing clinical trials. Therefore our comprehensive review provides knowledge in detail regarding many aspects of pathogenesis, measurement, and management of arterial stiffness in several populations, which would be helpful for physicians to make clinical decision.

Association of body mass index with all-cause mortality in patients with diabetes: a systemic review and meta-analysis

BACKGROUND The obesity paradox phenomenon has been found in different populations, such as heart failure and coronary heart disease, which suggest that patients with established cardiovascular disease (CVD) and with normal weight had higher risk of mortality than those with overweight or obesity. However, the obesity paradox is controversial among patients with diabetes which has been considered as the coronary heart disease equivalent. The aim of our study was to summarize current findings on the relationship between body mass index (BMI) and all-cause mortality in patients with diabetes and make a meta-analysis. METHODS We searched previous studies from MEDLINE, EMBASE, and the Cochrane databases using the keywords: BMI, mortality, diabetes, and obesity paradox or reverse epidemiology. Finally, sixteen studies were identified and 385,925 patients were included. Patients were divided into five groups based on BMI (kg/m(2)) levels: underweight (<18.5), normal weight (18.5-24.9), overweight (25-29.9), mild obesity (30-34.9), and morbid obesity (>35). A random effect meta-analysis was performed by the inverse variance method. RESULTS As compared with the normal weight, the underweight had higher risk of mortality [hazard ratio (HR): 1.59, 95% confidence interval (CI): 1.32-1.91]. In contrast, the overweight and the mild obesity had lower risk of mortality than the normal weight (HR: 0.86, 95% CI: 0.78-0.96, and 0.88, 95% CI: 0.78-1.00, respectively), but the morbid obesity did not (HR: 0.99, 95% CI: 0.84-1.16). In addition, the subgroup analysis by sex showed that the overweight had the lowest mortality as compared with the normal weight (HR: 0.82, 95% CI: 0.74-0.90) and the obesity in males, but the risk of mortality did not differ among groups in females. Notably, the heterogeneity was significant in most of group comparisons. CONCLUSIONS Our meta-analysis showed a U-shaped relationship between BMI and all-cause mortality in patients with diabetes. The significant heterogeneity among studies suggested that many confounders such as sex difference may affect the association.

Potentiating effect of fluphenazine decanoate and risperidone on development of neuroleptic malignant syndrome

We present the case of a woman with paranoid schizophrenia who was receiving oral risperidone. She developed neuroleptic malignant syndrome (NMS) following the addition of depot fluphenazine for the treatment of refractory delusions. NMS subsided and psychotic features were controlled after both antipsychotics were discontinued and the patient was treated instead with olanzapine.

Gentiana scabra Reduces SR-A Expression and Oxidized-LDL Uptake in Human Macrophages.

BACKGROUND Macrophages can imbibe low-density lipoprotein (LDL) through scavenger receptors to become foam cells, which is critical in the initiation and progression of atherosclerosis. Mounting evidence suggests that the anti-inflammatory nature of Chinese herbs have the capacity to halt the complex mechanisms underlying atherosclerosis. This study examined the effects of Chinese herbs on foam cell formation. METHODS Chinese herbs were obtained from the Sun Ten pharmaceutic company. Using oxidized LDL (OxLDL) uptake and a cell toxicity assay, we screened more than 30 types of Chinese herbs. Western blotting was used to determine expressions of scavenger receptors (SRs) and extracellular-signal-regulated kinase (ERK) activities. RESULTS We found that Gentiana scabra reduced oxidized LDL uptake effectively in THP-1 macrophages (p < 0.05 vs. OxLDL treated control). Moreover, treatment with Gentiana scabra in THP-1 macrophages resulted in decreased expression of scavenger receptor- A (SR-A) (p < 0.05 vs. control). Molecular investigation revealed that Gentiana scabra inhibited SR-A protein expression, possibly by regulating ERK signaling pathways (p < 0.05 vs. control). CONCLUSIONS By regulating SR-A expression, Gentiana scabra reduced oxidized LDL uptake in human macrophages. These results support the potential use of Gentiana scabra in treating atherosclerosis.

Reverse epidemiology in patients with heart failure: The role of circulatory power and cardiac reserve

a Department of Medicine, Hualien-Armed Forces General Hospital, Hualien, Taiwan b Department of Public Health, Tzu-Chi University, Hualien, Taiwan c Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan d Department of Internal Medicine, Mennorite Christian Hospital, Hualien, Taiwan e Department of Medicine, Tri-Service General Hospital-SongShan Branch, National Defense Medical Center, Taipei, Taiwan f Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

Postobstructive pulmonary edema associated with a substernal goitre

A 50-year-old woman had experienced 6 months of mild shortness of breath and noise while breathing. She was obese with a body mass index of 32. Her primary care physician found a neck mass; results of a serum thyroid function test were normal. Her symptoms remitted spontaneously, and she ignored

Electrocardiographic characteristics in young male patients with left primary spontaneous pneumothorax estimated by the collins equation

Objective To investigate the 12-lead surface electrocardiographic (ECG) findings in young male patients with left primary spontaneous pneumothorax (PSP) estimated by the Collins equation. Methods From 2003 through 2008, 60 young male patients who had left PSP and 61 age-matched unaffected males were included for 12-lead ECG analyses. The PSP size was estimated by the Collins equation. Those with left PSP were divided into two groups: 1) large PSP ≥30% (n = 37), and 2) small PSP <30% (n = 23). The ECG in the unaffected was used as the normal control. Baseline demographic, anthropometric, and electrocardiographic findings including heart rate, P-QRS-T axes, wave intervals, and RS voltages were compared among three groups. Results As compared to the unaffected, patients with left PSP had faster heart rate, longer QTc interval, greater QRS and T axes. With regard to RS amplitudes, greater R in lead aVR and V1, and deeper S in lead II indicating predominant rightward forces, and smaller R in lead I and V3-V6 indicating inferior leftward forces were present in patients with left PSP. Of these ECG findings, heart rate, S voltage in lead II and R voltage in V1 in the large PSP but not in the small PSP had greater values than that in the unaffected group. Conclusion Among young male patients with left PSP estimated by the Collins method, the ECG showed faster heart beat and predominant rightward forces especially for those with large PSP.

Chest Pain with Normal Thallium-201 Myocardial Perfusion Image - Is It Really Normal?

BACKGROUND Thallium-201 myocardial perfusion image (MPI) is commonly used to detect coronary artery disease in patients with chest pain. Although a normal thallium-201 MPI result is generally considered to be a good prognosis and further coronary angiogram is not recommended, there are still a few patients who suffer from unexpected acute coronary events. The aim of this study was to investigate the clinical prognosis in patients with normal thallium-201 MPI. METHODS From January 2006 to August 2012, a total 22,003 patients undergoing thallium-201 MPI in one tertiary center were screened. Of these, 8092 patients had normal results and were investigated retrospectively. During follow-up, 54 patients underwent coronary angiogram because of refractory typical angina pectoris or unexpected acute coronary events. These 54 patients were divided into 2 groups: group I consisted of 26 (48.1%) patients with angiography-proven significant coronary artery stenosis, and group II consisted of 28 (51.9%) patients without significant stenosis. RESULTS Patients in group I had a higher prevalence of prior coronary stenting and electrocardiographic features of ST depression compared with patients in group II. The multivariate analysis demonstrated that both prior coronary stenting and ST depression were risk predictors of unexpected acute coronary events in the patients with normal thallium-201 MPI [odds ratio (OR), 5.93; 95% confidence interval (CI): 1.03-34.06, p = 0.05 and OR, 7.10; 95% CI: 1.28-39.51, p = 0.03,respectively]. CONCLUSIONS Although there is a low incidence of unexpected acute coronary events in patients with chest pain and normal thallium-201 MPI, physicians should be aware of the potentials risk in certain patients in this specific population.

Perspective of future drugs targeting sterile 20/SPS1-related proline/alanine-rich kinase for blood pressure control.

According to a genome-wide association study, intronic SNPs within the human sterile 20/SPS1-related proline/alanine-rich kinase (SPAK) gene was linked to 20% of the general population and may be associated with elevated blood pressure. As cell volume changes, mammalian SPAK kinases respond to phosphorylate and regulate cation-coupled chloride co-transporter activity. To our knowledge, phosphorylation of upstream with-no-lysine (K) (WNK) kinases would activate SPAK kinases. The activation of WNK-OSR1/SPAK cascade on the kidneys and aortic tissue is related to the development of hypertension. Several regulators of the WNK pathway such as the Kelch kinase protein 3 - Cullin 3 E3 ligase, hyperinsulinemia, and low potassium intake to mediate hypertension have been identified. In addition, the SPAK kinases may affect the action of renin-angiotensin-aldosterone system on blood pressure as well. In 2010, two SPAK knock-in and knock-out mouse models have clarified the pathogenesis of lowering blood pressure by influencing the receptors on the kidneys and aortic smooth muscle. More recently, two novel SPAK inhibitors for mice, Stock 1S-14279 and Closantel were discovered in 2014. Targeting of SPAK seems to be promising for future antihypertensive therapy. Therefore we raised some viewpoints for the issue for the antihypertensive therapy on the SPAK (gene or kinase).

Clinical and prognostic correlates of ST-elevation myocardial infarction patients with normal coronary angiography

Background: Revascularization within a 90-min door-to-balloon time is a strict policy enacted in Taiwan. Prompt diagnosis is critical to avoid an unnecessary procedure and catheterization laboratory activation. This study was aimed to investigate the clinical and prognostic characteristics of the patients with ST-elevation myocardial infarction (STEMI) referred for primary percutaneous coronary intervention (PCI) and normal coronary arteries found following coronary angiography (CAG). Materials and Methods: From October 2009 to December 2012, 216 consecutive patients with STEMI referred for primary PCI were enrolled. The data of clinical history, physical examination, laboratory results, electrocardiography, echocardiography, CAG findings, diagnosis, and outcomes were collected and analyzed. Results: A total of 17 patients were proved normal coronaries angiographically. The incidence of the conditions mimicking as STEMI is 7.9%. Alternative diagnosis was coronary spasm (n = 7), peri-myocarditis (n = 6), apical ballooning syndrome (n = 3), anaphylactic shock (n = 1). Compared with STEMI group, patients in normal coronaries group were younger, with a less premature family history of coronary artery disease (CAD), and reported angina. The 30-day mortality rate in the normal coronaries group was 5.9%. Conclusions: Cautiously evaluating CAD risk factors and symptoms of angina and awareness of alternative diagnosis are important to make a prompt diagnosis without compromising accuracy in the patients presenting as suspected STEMI.