Hiu-Ting Chan

Reduction of C-reactive protein with isoflavone supplement reverses endothelial dysfunction in patients with ischaemic stroke.

AIMS To investigate the effect of oral isoflavone supplement on vascular endothelial function in patients with established cardiovascular disease. METHODS AND RESULTS A randomized, double-blinded, placebo-controlled trial was performed to determine the effects of isoflavone supplement (80 mg/day, n = 50) vs. placebo (n = 52) for 12 weeks on brachial flow-mediated dilatation (FMD) in patients with prior ischaemic stroke. Compared with controls, FMD at 12 weeks was significantly greater in isoflavone-treated patients [treatment effect 1.0%, 95% confidence interval (95% CI) 0.1-2.0, P = 0.035]. Adjusted for baseline differences in FMD, isoflavone treatment was independently associated with significantly less impairment of FMD at 12 weeks (odds ratio 0.32, 95% CI 0.13-0.80, P = 0.014). The absolute treatment effect of isoflavone on brachial FMD was inversely related to baseline FMD (r = -0.51, P < 0.001), suggesting that vasoprotective effect of isoflavone was more pronounced in patients with more severe endothelial dysfunction. Moreover, isoflavone treatment for 12 weeks resulted in a significant decrease in serum high-sensitivity (hs)-C-reactive protein level (treatment effect -1.7 mg/L, 95% CI -3.3 to -0.1, P = 0.033). Nevertheless, isoflavone did not have any significant treatment effects on nitroglycerin-mediated dilatation, blood pressure, heart rate, serum levels of fasting glucose and insulin, haemoglobin A1c, and oxidative stress as determined by serum superoxide dismutase, 8-isoprostane, and malondialdehyde (all P > 0.05). CONCLUSION This study demonstrated that 12 week isoflavone treatment reduced serum hs-C-reactive protein and improved brachial FMD in patients with clinically manifest atherosclerosis, thus reversing their endothelial dysfunction status. These findings may have important implication for the use of isoflavone for secondary prevention in patients with cardiovascular disease, on top of conventional interventions.

Effect of exercise training on vascular endothelial function in patients with stable coronary artery disease: a randomized controlled trial.

Background: We aim to investigate the effect of exercise training on endothelial function and exercise capacity in patients with coronary artery disease. Methods and results: A randomized, controlled trial was conducted to determine the effects of an 8-week exercise training programme (n = 32) vs. controls (n = 32) on brachial flow-mediated dilation (FMD) in patients with stable CAD. After 8 weeks, patients received exercise training had significant improvements in FMD (1.84%, p = 0.002) and exercise capacity (2.04 metabolic equivalents, p < 0.001) compared with controls. The change in FMD correlated inversely with baseline FMD (r = −0.41, p = 0.001) and positively with the increase in exercise capacity (r = 0.35, p = 0.005). After adjusting for confounders, every 1 metabolic equivalent increase in exercise capacity was associated with 0.55% increase in FMD. Furthermore, patients received exercise training had significantly increased high-density lipoprotein cholesterol and decreased diastolic blood pressure and resting heart rate compared with controls. However, exercise training did not alter high-sensitivity C-reactive protein, oxidative stress measured as superoxide dismutase and 8-isoprostane, and CD34/KDR + endothelial progenitor cell count. Subgroup analysis showed that FMD was significantly improved only in CAD patients with baseline low exercise capacity (<median value of 7.65 metabolic equivalents, p = 0.004) but not in those with normal exercise capacity. Conclusion: Exercise training improved FMD and exercise capacity in stable CAD patients independent of the changes in inflammation, oxidative stress, or endothelial progenitor cells. The beneficial effects of exercise training on FMD and exercise capacity are inter-related, and more pronounced in those with baseline impaired exercise capacity.

Increased arterial stiffness in patients with psoriasis is associated with active systemic inflammation.

Background  Psoriasis is associated with premature atherosclerosis although the underlying mechanism remains unclear.

Habitual physical activity is associated with endothelial function and endothelial progenitor cells in patients with stable coronary artery disease

Background Exercise training reduces mortality in patients with coronary artery disease (CAD); however, the impact of habitual physical activity level (PAL) on vascular endothelial function and circulating endothelial progenitor cells (EPCs) remain unknown. Methods We assessed habitual PAL using a validated International Physical Activity Questionnaire in 116 patients (67.8 ± 9.5 years; 81% male) with stable CAD and preserved left ventricular ejection fraction ≥ 45%. The number of circulating CD34/KDR+ and CD133/KDR+ EPCs was determined by flow cytometry, and brachial artery flow-mediated dilation (FMD) was measured. Results The mean PAL of CAD patients with 1644 MET min/week (where MET is metabolic equivalents). With higher habitual PAL tertiles, there were significant linear trends of increased FMD (P = 0.001) and CD133/KDR+ EPCs (P = 0.03), but not of CD34/KDR+ EPCs. Patients with the highest tertile of PAL were associated with an absolute increase of 1.89% in FMD (relative increase 68%, P = 0.003) and 0.12% in CD133/KDR+ EPCs (relative increase 44%, P = 0.01) compared with those in the lowest tertile of PAL, after adjusting for age, sex, presence of hypertension, diabetes mellitus, hypercholesterolemia, smoking, and the use of medications including statins. However, neither CD34/KDR+ nor CD133/KDR+ EPCs significantly correlated with FMD. Conclusion This study showed that higher habitual PAL in patients with CAD was associated with higher FMD and EPC count. Nonetheless, FMD only significantly correlated with increased PAL, but not EPC, suggesting that increased physical activity improves endothelial function through mechanisms other than increasing EPC count.

Effect of herbal consumption on time in therapeutic range of warfarin therapy in patients with atrial fibrillation.

It has been established that herbal intake affects the anticoagulation effects of warfarin, but the long-term impact on anticoagulation control is unclear. We sought to investigate the effect of concomitant herbal intake on anticoagulation control in patients with nonvalvular atrial fibrillation (AF) treated with warfarin. The effects of common herbs were determined by monitoring the international normalized ratio in 250 patients with AF (69 ± 10 years, 50% male). All the patients had been prescribed warfarin therapy for at least 6 months before enrollment, and their dietary intake, including the type and the frequency of common herbs, was recorded using a standardized questionnaire. Up to 50% of the patients reported consumption of foods with herbal ingredients, including garlic (80.4%), ginger (74.8%), green tea (50.4%), and papaya (55.2%) but rarely herbal drugs such as danshen (1.2%), dong guai (0.8%), fenugreek (1.2%), psyllium seed (0.4%), and ginseng (4%). Infrequent users (1 kind of herb for <4 times per week and nonusers) were more likely to have an international normalized ratio within the optimal therapeutic range (2.0-3.0) than frequent users (>1 kind of herb for ≥4 times per week) (58.1% vs 51.1%, P = 0.046). In conclusion, the patients with AF treated with warfarin had little knowledge about the potential interaction of herbal substances in foods with warfarin. The patients who consumed common herbs at least 4 times per week had suboptimal anticoagulation control with warfarin.

Daily intake of thiamine correlates with the circulating level of endothelial progenitor cells and the endothelial function in patients with type II diabetes

Our objective was to determine the relationships between levels of different dietary nutrients intake with circulating endothelial progenitor cells (EPC) and vascular endothelial function in type II diabetic patients. We studied the daily dietary nutrients intake, the numbers of circulating CD34(+)/KDR(+) EPC and CD133(+)/KDR(+) EPC and brachial artery flow-mediated dilation (FMD) in 88 diabetic patients without prior cardiovascular diseases and 91 sex- and age-matched controls. Compared with controls, diabetic patients had lower CD133(+)/KDR(+) EPC count (48.3 +/- 5.2 vs. 84.6 +/- 7.6/microL, p < 0.001), CD34(+)/KDR(+) EPC count (311 +/- 41 vs. 412 +/- 36/microL, p = 0.045), and FMD (2.54 +/- 0.37% vs. 5.46 +/- 0.47%, p < 0.001). After adjusted for age, sex, smoking history, body weight, hemoglobin A1c level, total calorie intake, other dietary vitamin intake, use of antihypertensives, and lipid lowering agents, a higher intake of thiamine was significantly associated with a higher level of circulating CD34(+)/KDR(+) EPC (beta = 0.49, p = 0.028) and CD133(+)/KDR(+) EPC (beta = 0.45, p = 0.037) in diabetic patients, but not in controls. Furthermore, an increased intake of thiamine from 1st to 4th quartile in diabetic patients independently predicted an absolute increase in FMD by 1.29% (p = 0.026, relative increase = 63.5%). This study demonstrated that daily thiamine intake was positively correlated with the circulating number of EPCs and FMD in patients with type II diabetes, independent of other dietary nutrients intake.

Generalized vitiligo after lymphocyte infusion for relapsed leukaemia

Vitiligo is an autoimmune disease caused by T‐lymphocyte‐mediated destruction of melanocytes. We describe two patients with generalized vitiligo caused iatrogenically after donor lymphocyte infusion (DLI) for leukaemia relapse over 3 years after bone marrow transplantation (BMT). Neither the sibling donor nor the recipient had vitiligo or other autoimmune diseases, and vitiligo did not occur after the first BMT. DLI was accompanied by skin graft‐versus‐host disease in both cases, which was controlled with immunosuppression. However, over several months, progressive generalized and persistent skin depigmentation occurred in both patients. Peripheral blood molecular studies showed the complete disappearance of host haematolymphopoiesis. The specific destruction of melanocytes in both patients was therefore probably mediated by new alloreactive lymphocytes infused from the donors.

Dietary intake of phytoestrogen is associated with increased circulating endothelial progenitor cells in patients with cardiovascular disease

Endogenous estrogen is known to positively influence the level and functionality of endothelial progenitor cells (EPC). However, the effect of phytoestrogen on EPC is unknown. Isoflavone is a major component of phytoestrogen. This study aims to investigate if the intake of isoflavone has any impact on the circulating level of EPC. We studied 102 consecutive patients (mean age: 66.5 ± 9.5 years, 78% male, all female post-menopausal) with cardiovascular disease (atherothrombotic stroke 62%, coronary artery disease 38%). Circulating levels of CD133+ EPC were determined by flow cytometry. Non-invasive pulse wave velocity (PWV) was measured. Long-term intake of isoflavone was determined by a validated food frequency questionnaire. Isoflavone intake was positively associated with circulating CD133+ EPC (r = 0.31, p = 0.001). Patients with circulating CD133+ EPC <10th percentile had significantly lower isoflavone intake than patients with CD133+EPC ≥10th percentile (4.6 ± 3.7 mg/day versus 19.3 ± 30.2 mg/day, p < 0.001). A significant overall linear trend of circulating EPC across increasing tertiles of isoflavone intake was observed (p = 0.004). Adjusted for potential confounders, increased isoflavone intake from the 1st to the 3rd tertile independently predicted increased circulating CD133+ EPC level by 221 cells/µl (95%CI: 71.4 to 369.8, relative increase 160%, p = 0.004). Gender was not a significant factor (p > 0.05). Furthermore, circulating CD133+ EPC <10th percentile was independently predictive of increased PWV by 261.7 cm/s (95% CI: 37.1 to 486.2, p = 0.024). The study demonstrated that circulating EPC increased by more than one fold in patients with cardiovascular disease who had higher intake of isoflavone, suggesting that isoflavone may confer vascular protection through enhanced endothelial repair.

CD30-positive cutaneous T-cell lymphoma with concurrent solid tumour.

Summary Extranodal CD30+ T‐cell lymphomas seldom carry classical t(2;5) translocation and are usually anaplastic large cell lymphoma kinase protein negative. They cover a wide spectrum of histological and clinical behaviour. The prognosis of CD30+ cutaneous T‐cell lymphoma (CTCL) is good in the absence of nodal primary or disseminated disease. These lesions can undergo spontaneous regression, and overlap with the group of lesions of lymphomatoid papulosis. Although an increased incidence of solid tumours has been reported in patients with CD30+ non‐Hodgkin lymphoma of the skin, reports of concurrent malignancies are rare in CD30+ CTCL. We report two patients with CD30+ CTCL who, respectively, had concurrent disseminated gastric carcinoma and bilateral ovarian teratoma. Despite an aggressive clinical and histological appearance, both cases ran favourable clinical courses. The CTCL responded completely to chemotherapy in one patient, who eventually succumbed to gastric cancer. In the other patient, lesions regressed spontaneously after bilateral oophorectomy. A possible relationship between the lymphoma and the solid tumours is discussed.

Worsened arterial stiffness in high-risk cardiovascular patients with high habitual carbohydrate intake: a cross-sectional vascular function study

BackgroundPrevious studies suggested that high dietary carbohydrate intake is associated with increased cardiovascular risk through raised triglyceride and decreased high-density lipoprotein-cholesterol levels. However, the relation between carbohydrate intake and arterial stiffness has not been established. The purpose of this study was to examine this relation among high-risk cardiovascular patients.MethodsWe studied the relation between dietary macronutrient intake and arterial stiffness in 364 patients with documented cardiovascular diseases or risk equivalent (coronary artery diseases 62%, ischemic stroke 13%, diabetes mellitus 55%) and in 93 age-and-sex matched control subjects. Dietary macronutrient intake was assessed using a validated food-frequency questionnaire (FFQ) for Chinese. Heart-ankle pulse wave velocity (PWV) was measured non-invasively with a Vascular Profiling System (VP2000, Colin Corp. USA). A dietary pattern with ≥60% total energy intake derived from carbohydrates was defined as a high-carbohydrate diet according to the Dietary Reference Intakes (DRI) for Chinese.ResultsSubjects who consumed a high-carbohydrate diet had significantly higher mean PWV than those who did not consume a high-carbohydrate diet (P = 0.039). After adjustment for potential confounders, high-carbohydrate diet was associated with significantly increased PWV [B = 73.50 (10.81 to 136.19), P = 0.022]. However, there was no significant association between high-carbohydrate diet and PWV in controls (P = 0.634).ConclusionsHigh-carbohydrate diet is associated with increased arterial stiffness in patients with established cardiovascular disease or risk equivalent.