Predictability of Cardiovascular Risk Scores for Carotid Atherosclerosis in Community-Dwelling Middle-Aged and Elderly Adults.

Background: The assessment of future risk of cardiovascular diseases (CVD) is strongly recommended for all asymptomatic adults without CVD history. Carotid atherosclerosis (CA) is a preclinical phenotype of CVDs. However, data on estimated future CVD risks with respect to preclinical atherosclerosis are limited. This community-based study aimed to assess the relationships between predicted CVD risks and CA. Methods: We enrolled 3908 subjects aged 40-74 years without CVD history and calculated their 10-year CVD risks using the Framingham Risk Score (FRS) and the Pooled Cohort Equations (PCE). Carotid plaque (CP) at the extracranial carotid arteries was determined by high-resolution B-mode ultrasonography and further classified into mild or advanced CA. Results: The means of FRS for CP-negative and mild and advanced CA were 9.0%, 14.4%, and 22.1%, respectively (p-value < 0.0001). The corresponding values for PCE score were 4.8%, 8.8%, and 15.0%, respectively (p-value < 0.0001). The odds ratios (ORs) of having CP per 5.0% increase in FRS and PCE score were 1.23 (95% CI, 1.19-1.28) and 1.36 (95% CI, 1.28-1.44), respectively. The corresponding values of having advanced CA were 1.24 (95% CI, 1.19-1.29) and 1.38 (95% CI, 1.30-1.48), respectively. Among the models of FRS or PCE plus other conventional CVD risk factors, the FRS + age model had the highest discrimination for the presence of CP (AUROC, 0.7533; 95% CI, 0.7375-0.7691) as well as for the presence of advanced CA (AUROC, 0.8034; 95% CI, 0.7835-0.8232). The calibration of the FRS + age models for the presences of CP and advanced CA was excellent (χ2 = 8.45 [p = 0.49] and 10.49 [p = 0.31], respectively). Conclusions: Estimated future CVD risks were significantly correlated with risks of having CA. Both FRS and PCE had good discrimination for the presences of CP and advanced CA.

Personal Experience of Daboia siamensis Envenomation.

Reports of envenomation induced by Daboia siamensis, a medically important venomous snake in Taiwan, are rare, and species identification might not be definitive. This article reports the complete course of a definite D. siamensis bite. The patient in this report was one of the authors who was bitten on the right palm near the base of the index finger by D. siamensis. The patient experienced local effects, neurological manifestations, and acute kidney injury. The laboratory analysis revealed elevated D-dimer and coagulopathy. The patient was administered 8 vials of antivenom and did not undergo surgical intervention or endotracheal tube intubation, but serum sickness occurred 8 days after antivenom administration. The horse immunoglobulin produced by the Centers for Disease Control, R. O. C. (Taiwan), against D. siamensis was effective and safe in the treatment of the patient. However, the best antivenom administration strategy remains unclear and requires further study.

Segment-specific prevalence of carotid artery plaque and stenosis in middle-aged adults and elders in Taiwan: A community-based study.

BACKGROUND: Plaque in carotid arteries (CAs) is a major factor of systemic atherosclerosis and cardiovascular disease (CVD). The left and right CAs have different anatomic and geometric features and may influence the predictability of CVD. However, the site- and segment-specific prevalence of carotid plaques (CP) and study on severity of carotid atherosclerosis with CVD risks was very limited. METHODS: We enrolled 1539 healthy residents aged 40-to-74 years from two northern districts in Taiwan. All volunteers received high resolution B-mode carotid ultrasound scans and CVD risk factors evaluations. RESULTS: The prevalence rate of extracranial CP was 21.9% in females and 33.8% in males. Carotid bifurcation is the most affected segment. As compared with the right CAs, the age-sex-adjusted matched odds ratio of having plaques in the left CAs was 1.32 (95% confidence interval = 1.02-1.73). The proportions of subjects had a total plaque number≥2, maximum stenosis≥30%, and plaque score≥3 were 8.9, 10.3, and 7.2%, respectively, in females and were 17.7, 17.2, and 15.1%, respectively, in males. Among subjects with moderate and severe carotid atherosclerosis, the mean ± SD of estimated 10-year CVD risk was 19.1 ± 14.6% and more than 65% of them need intensive blood pressure, lipids, or sugar controls. CONCLUSION: We found that bifurcation was the most prevalent segment, and left CAs was more likely to form plaque than right CAs. The major CVD risk factors were highly prevalent and the estimated CVD risks were high in subjects with more advanced carotid atherosclerosis. The study provides further direction for CVD prevention and treatment.

Genetic profiling of young and aged endothelial progenitor cells in hypoxia.

Age is a major risk factor for diseases caused by ischemic hypoxia, such as stroke and coronary artery disease. Endothelial progenitor cells (EPCs) are the major cells respond to ischemic hypoxia through angiogenesis and vascular remodeling. However, the effect of aging on EPCs and their responses to hypoxia are not well understood. CD34+ EPCs were isolated from healthy volunteers and aged by replicative senescence, which was to passage cells until their doubling time was twice as long as the original cells. Young and aged CD34+ EPCs were exposed to a hypoxic environment (1% oxygen for 48hrs) and their gene expression profiles were evaluated using gene expression array. Gene array results were confirmed using quantitative polymerase chain reaction, Western blotting, and BALB/c female athymic nude mice hindlimb ischemia model. We identified 115 differentially expressed genes in young CD34+ EPCs, 54 differentially expressed genes in aged CD34+ EPCs, and 25 common genes between normoxia and hypoxia groups. Among them, the expression of solute carrier family 2 (facilitated glucose transporter), member 1 (SLC2A1) increased the most by hypoxia in young cells. Gene set enrichment analysis indicated the pathways affected by aging and hypoxia most, including genes "response to oxygen levels" in young EPCs and genes involved "chondroitin sulfate metabolic process" in aged cells. Our study results indicate the key factors that contribute to the effects of aging on response to hypoxia in CD34+ EPCs. With the potential applications of EPCs in cardiovascular and other diseases, our study also provides insight on the impact of ex vivo expansion might have on EPCs.

Improvements in Left Ventricular Diastolic Mechanics After Parachute Device Implantation in Patients With Ischemia Heart Failure: A Cardiac Computerized Tomographic Study.

BACKGROUND: Percutaneous ventricular restoration therapy with the use of a left ventricle (LV)-partitioning Parachute device has emerged as a clinical treatment option for LV apical aneurysm after extensive anterior myocardial infarction (AMI). We assessed changes of diastolic mechanics and functional improvements following LV Parachute device implantation by means of cardiac computerized tomography (CCT). METHODS AND RESULTS: CCT data were obtained from 28 patients before and after LV Parachute device implantation. Diastolic functional indices were determined by means of quantitative CCT assessment: 1) transmitral velocities in early (E) and late (A) diastole and ratio (E/A); 2) early diastolic mitral septal tissue velocity (Ea) and E/Ea; and 3) vortex formation time (VFT). Functional improvements were assessed with the use of New York Heart Association (NYHA) functional classification. Among the study patients, there were no significant differences in all transmitral velocities and E/A, though there was significantly increased Ea, reduced E/Ea, and greater VFT 6 months after LV Parachute device implantation. Finally, the improvement of diastolic functional indices after Parachute treatment correlated with observed clinical functional alterations (Δ E/Ea and Δ NYHA functional class:, r = 0.563; P = .002; Δ VFT and Δ NYHA functional class: r = -0.507; P = .006). CONCLUSIONS: LV Parachute device implantation therapy in heart failure caused by AMI and LV apical aneurysm formation showed improvements in several diastolic functional mechanics according to CCT-based measures.

Associations of Cardiovascular Risk Factors with Carotid Intima-Media Thickness in Middle-Age Adults and Elders.

AIMS: Elevated carotid intima-media thickness (cIMT) is a preclinical phenotype of atherosclerotic diseases. There are significant sex differences in the morbidities of cardiovascular diseases and their major determinants, and we explored the sex-specific effects of cardiovascular factors on cIMT by a community-based study. METHODS: We measured the cIMT and cardiovascular profiles of 1579 residents aged 40-74 years in northern Taiwan. Multivariate regression analyses were used to assess the effects and contributions of these factors on cIMT. RESULTS: Males had significantly higher mean (±SD) of cIMT than females (0.668±0.113 vs. 0.632± 0.100 nm, p＜0.0001). The common factors of the best-fit regression models in both sexes were age, BMI, and LDL-/HDL-C ratio; however, their contributions and effects were different. The partial coefficients of determination (r2) were 17.9, 5.8, and 4.1%, respectively, for males and were 27.8, 1.4, and 1.2%, respectively, for females. Test statistics showed that the regression coefficients of BMI and LDL-/HDL-C ratio of males were significantly higher than those of females. As compared with females, per 1.0 SD increases of BMI and LDL-/HDL-C in males resulted in 0.0971 (p=0.030) and 0.1177 (p=0.0087), respectively, SD increases in cIMT. There was no difference in the means of cIMT between pre- and post-menopausal women of the same age groups. CONCLUSIONS: There was a significant sex difference in cIMT. The contributions and effects of LDL-/HDL-C ratio and BMI on cIMT were more profound in males. Our findings indicate that sex-specific factors, but possibly not menstrual status-related factors, contribute to thicker cIMT.

Nicotine: A Double-Edged Sword in Atherosclerotic Disease.

UNLABELLED: Chronic cigarette smoking is well-known to damage vascular endothelium, which initiates atherosclerosis by first manifesting as endothelial dysfunction and later progressing to cardiovascular diseases (CVD). Nicotine, a major component of tobacco smoke, is traditionally thought to be responsible for increased cardiovascular events through stimulation of the sympathetic nervous system, increased myocardial metabolic demand, impaired lipid metabolism, and activated platelet function. However, recent studies have demonstrated that nicotine, at lower doses, may be beneficial to the cardiovascular system. With binding to specific nicotinic acetylcholine receptors, nicotine can induce migration and proliferation of vascular cells, and hence enhances angiogenesis. Therefore, these seemingly inconsistent properties of nicotine may in fact give rise to novel and efficacious management strategies of CVD. KEY WORDS: Angiogenesis; Atherosclerosis; nicotinic acetylcholine receptors (nAChRs); Nicotine.

Caffeic acid phenethyl ester as an adjuvant therapy for advanced prostate cancer.

Prostate cancer is the second most frequently diagnosed cancer of men. Androgen ablation therapy is the primary treatment for metastatic prostate cancer. However, the majority of prostate cancer patients receiving the androgen ablation therapy will ultimately develop recurrent castration-resistant tumors within 3 years. Chemotherapy shows little effect on prolonging survival for patients with metastatic hormone-refractory prostate cancer. More than 80% of prostate tumors acquire mutation or deletion of tumor suppressor phosphatase and tensin homolog (PTEN), a negative regulator of PI3K/Akt signaling. Caffeic acid phenethyl ester (CAPE) is a strong antioxidant extracted from honeybee hive propolis. Recent studies indicate that CAPE treatment suppresses tumor growth and Akt signaling in human prostate cancer cells. Combined treatments of CAPE with chemotherapeutic drugs exhibit synergistic suppression effects. Pharmacokinetic studies suggest that intraperitoneal injection of CAPE at concentration of 10mg/kg is not toxic. CAPE treatment sensitizes cancer cells to chemotherapy and radiation treatments. In addition, CAPE treatment protects therapy-associated toxicities in animal models. We therefore propose that administration of CAPE is a potential adjuvant therapy for patients with castration-resistant prostate cancer.

Caffeic Acid phenethyl ester as a potential treatment for advanced prostate cancer targeting akt signaling.

Prostate cancer is the fifth most common cancer overall in the world. Androgen ablation therapy is the primary treatment for metastatic prostate cancer. However, most prostate cancer patients receiving the androgen ablation therapy ultimately develop recurrent castration-resistant tumors within 1-3 years after treatment. The median overall survival time is 1-2 years after tumor relapse. Chemotherapy shows little effect on prolonging survival for patients with metastatic hormone-refractory prostate cancer. More than 80% of prostate tumors acquire mutation or deletion of tumor suppressor phosphatase and tensin homolog (PTEN), a negative regulator of PI3K/Akt signaling, indicating that inhibition of PI3K/Akt might be a potential therapy for advanced prostate tumors. Caffeic acid phenethyl ester (CAPE) is a strong antioxidant extracted from honeybee hive propolis. CAPE is a well-known NF-κB inhibitor. CAPE has been used in folk medicine as a potent anti-inflammatory agent. Recent studies indicate that CAPE treatment suppresses tumor growth and Akt signaling in human prostate cancer cells. We discuss the potential of using CAPE as a treatment for patients with advanced prostate cancer targeting Akt signaling pathway in this review article.