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.

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.

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.