可可黄烷醇与ESRD患者的血管保护有关


  【24drs.com】根据在线发表于12月17日美国肾脏医学会临床期刊的一篇新研究,摄取可可黄烷醇(cocoa flavanols,CF)可以减轻末期肾病患者(end-stage renal disease,ESRD)因血液透析(hemodialysis,HD)引起的或慢性的内皮功能障碍,且改善高风险患者的血管功能。
  
  可可黄烷醇是可可所含的植物多酚。
  
  德国Essen西德心血管中心心脏科Tienush Rassaf 医师等人指出,ESRD被认为是一个重要的心血管危险因子。研究者写道,这导致这群患者的发病率和死亡率大幅增加,是一般人的8倍。在ESRD患者,血管功能障碍与心衰竭及心因性猝死有关。
  
  研究者指出,心脏troponin值升高对此有影响,是ESRD患者各种原因死亡率的一个重要预测因子。ESRD患者中,对一氧化氮的生体可用率不佳,会进一步助长血管功能障碍。重要的是,血液透析会降低[一氧化氮]生体可用率,更加重内皮功能不良。
  
  饮食补充富含可可黄烷醇的食物可以改善血管功能;不过,评估血管功能不佳对ESRD患者之影响的研究相当稀少,因此,研究者在2012-2013年进行了这篇随机双盲安慰剂控制试验,以评估富含黄烷醇生物活性成分的食物对于ESRD患者之急性与慢性血液透析引起之血管功能障碍的影响。他们纳入57名进行血液透析治疗潜在的肾脏疾病-包括高血压和糖尿病肾病变、肾小球肾炎和多囊肾的患者。
  
  这57名研究对象中,研究者随机指定52人到慢性平行组试验,他们提供其中26人富含黄烷醇(研究期间每天900 mg的黄烷醇)的饮料,另外26人则是接受营养成分相当但没有黄烷醇的安慰剂。Rassaf 医师等人解释,这篇研究中,初级与次级结果测量包括流量调节之舒张功能(FMD)和血流动力学的改变。
  
  患者对摄取黄烷醇的耐受良好,急性期摄取可使FMD改善达53% (3.2% ± 0.6%到4.8% ± 0.9%,安慰剂组为:3.2% ± 0.7% 到3.3% ± 0.8%;P < .001),不会影响心律与血压。
  
  相较于安慰剂,摄取黄烷醇30天之后,研究者指出,基本FMD增加达18%(3.4% ± 0.9%到3.9% ± 0.8%,安慰剂组为3.5% ± 0.7%到3.5% ± 0.7%;P < .001);这和舒张压降低(73 ± 12到69 ± 11 mm Hg,安慰剂组为70 ± 11到73 ± 13 mm Hg;P = .03)与心律增加(70 ± 12到74 ± 13 bpm,安慰剂组为75 ± 15到74 ± 13 bpm;P = .01)有关。
  
  研究者也指出,在血液透析时,急性期摄取黄烷醇可缓和血液透析引起的血管功能障碍(3.4% ± 0.9%到2.7% ± 0.6%,安慰剂组为3.5% ± 0.7%到2.0% ± 0.6%;P < .001),且这影响持续整个研究(急性到慢性,3.9% ± 0.9%到3.0% ± 0.7%,安慰剂组为3.5% ± 0.7%到2.2% ± 0.6%;P =.01)。
  
  根据Rassaf医师等人表示,该研究获得四个主要结论,在ESRD患者,摄取黄烷醇(每天900 mg)耐受良好,急性期与慢性期摄取黄烷醇可以部分逆转内皮功能障碍,慢性期摄取黄烷醇可造成舒张压降低且不会影响主动脉硬化的标记,摄取黄烷醇可减轻血管透析引起的血管功能障碍。
  
  作者们写道,黄烷醇发挥心脏保护作用的确切机转,仍尚未被完全阐明。研究者解释,亚硝基硫醇血浆值增加、细胞信号级联放大、基因表现和酶活性改变等对[一氧化氮]动态平衡之影响,被认为是潜在途径。在这篇研究中,我们在血浆亚硝酸盐或硝酸盐值并没有观察到差异,可能是因为样本数少,或是因为ESRD患者的[诱导型一氧化氮合成酶]的活化。
  
  在编辑评论中,意大利Reggio Calabria Ospedali Riuniti的Carmine Zoccali医师和Francesca Mallamaci医师写道,在一些替代FMD或脉搏波速度的研究中,尽管有证据显示,类黄酮对心血管系统可发挥良好效果,也可能可以降低高血压患者的[血压],看来似乎是强大且可信的,不过,迄今为止,还没有依据临床终点进行的大型研究显示这些成份的好处。因此,尽管可能,类黄酮用于预防和治疗心血管疾病的治疗益处仍是个悬而未决的问题。
  
  不过,在过去20年,并未提出对ESRD患者有意义的心血管预后。考量接受血液透析患者之心血管疾病的严重负担,肾脏病医学界需要留意有意义的预防方法,如可可黄烷醇,他们结论表示,这篇研究的结果或许是进行血液透析之患者,在预防心血管疾病之战斗、提供其它研究(根据相同的替代物),以及根据临床终点确认研究结果之试验的一个转折点。
  
  资料来源:http://www.24drs.com/
  
  Native link:Cocoa Flavanols Linked to Vascular Protection in ESRD

Cocoa Flavanols Linked to Vascular Protection in ESRD

By Sanjeet Bagcchi, MBBS
Medscape Medical News

Ingestion of cocoa flavanols (CF) can attenuate hemodialysis (HD)-induced and chronic endothelial dysfunction in patients with end-stage renal disease (ESRD) and improve vascular function in high-risk patients, according to a new study published online December 17 in the Clinical Journal of the American Society of Nephrology.

Cocoa flavanols are plant-derived polyphenols that are present in cocoa.

Tienush Rassaf, MD, from the Department of Cardiology, West German Heart and Vascular Center, Essen, Germany, and colleagues note that ESRD is regarded as an important cardiovascular risk factor. "This leads to a dramatic increase in morbidity and mortality in this population, which is eight times greater than in the general population," the researchers write. In ESRD, vascular dysfunctions are linked with heart failure and sudden cardiac deaths.

"Elevated cardiac troponin levels reflect this, an important predictor of all-cause mortality in ESRD," the researchers note. They also point out that in patients with ESRD, impaired bioavailability of nitric oxide further perpetuates vascular dysfunctions. "Importantly, HD acutely impairs endothelial function through reduction of [nitric oxide] bioactivity," they explain.

Dietary supplements rich in CF could lead to improvement in vascular function; however, studies assessing the effect on vascular dysfunction in patients with ESRD are "sparse." Therefore, the researchers conducted a randomized, double-blind, placebo-controlled trial during 2012 to 2013 to assess "the impact of flavanol-rich bioactive food ingredients on acute and chronic HD-induced vascular dysfunction in ESRD." They enrolled 57 participants undergoing HD for underlying renal diseases, including hypertensive and diabetic nephropathy, glomerulonephritis, and polycystic kidney disease.

Of the 57 participants, the researchers randomly assigned 52 to a chronic parallel group trial. They provided 26 participants with beverages rich in CF (900 mg CF per study day) and 26 participants with a nutrient-matched, CF-free placebo. In the study, "[p]rimary and secondary outcome measures included changes in [flow-mediated dilation (FMD)] and hemodynamics," Dr Rassaf and colleagues explain.

The patients tolerated ingestion of CF well, and acute ingestion led to an FMD improvement by 53% (3.2% ± 0.6% to 4.8% ± 0.9% vs placebo, 3.2% ± 0.7% to 3.3% ± 0.8%; P < .001), without affecting heart rate and blood pressure.

Compared with placebo, after a 30-day ingestion of CF, the researchers noted an increase in baseline FMD of 18% (3.4% ± 0.9% to 3.9% ± 0.8% vs placebo, 3.5% ± 0.7% to 3.5% ± 0.7%; P < .001); this was associated with a decrease in diastolic blood pressure (73 ± 12 to 69 ± 11 mm Hg vs placebo, 70 ± 11 to 73 ± 13 mm Hg; P = .03) and an increase in heart rate (70 ± 12 to 74 ± 13 bpm vs placebo, 75 ± 15 to 74 ± 13 bpm; P = .01).

The researchers also note that during HD, acute ingestion of CF led to an alleviation of HD-induced vascular dysfunction (3.4% ± 0.9% to 2.7% ± 0.6% vs placebo, 3.5% ± 0.7% to 2.0% ± 0.6%; P < .001), and the effect was sustained "throughout the study" (acute-on-chronic, 3.9% ± 0.9% to 3.0% ± 0.7% vs placebo, 3.5% ± 0.7% to 2.2% ± 0.6%; P = .01).

According to Dr Rassaf and colleagues, the study yields four major findings: in patients with ESRD, ingestion of CF (at 900 mg per day) is well tolerated, endothelial dysfunction is partly reversed by acute and chronic ingestion of CF, chronic ingestion of CF leads to decrease in diastolic blood pressure without "affecting markers of aortic stiffness," and CF ingestion mitigates vascular dysfunction induced by HD.

"The exact mechanisms through which CF exert putative cardioprotective effects still remain incompletely elucidated," the authors write. "Impacts on [nitric oxide] homeostasis with increased nitrosothiol plasma levels, cellular signal cascades, altered gene-expression and enzyme activity are considered potential pathways. In the present study we did not observe differences in plasma nitrite or nitrate levels possibly due to small sample size or due to activation of [inducible nitric oxide synthase] as suggested for ESRD patients," the researchers explain.

In an accompanying editorial, Carmine Zoccali, MD, and Francesca Mallamaci, MD, from the Ospedali Riuniti, Reggio Calabria, Italy, write, "While the evidence that flavonoids exert favorable effects on the cardiovascular system in studies based on surrogates like FMD or pulse wave velocity and may lower [blood pressure] in human hypertension seems robust and credible, until now there is no large trial based on clinical end-points showing a benefit by these compounds. Thus, although likely, the therapeutic benefit of flavonoids for the prevention and treatment of cardiovascular disease remains an open question."

However, in the last 2 decades, no meaningful cardiovascular prognosis has been noted in patients with ESRD, they point out. The nephrology community needs to be attentive to a "promising intervention" such as CF, considering the serious burden of cardiovascular disease among patients receiving HD, they write. The findings of this study might be a turning point in the battle against cardiovascular disease in patients undergoing HD, provided other studies (based on same surrogates) and a trial based on clinical end-points confirm the findings, they conclude.

This work was funded in part by the European Commission. MARS Symbioscience provided the CF test products and analytical standards. The authors and editorialists have disclosed no relevant financial relationships.

CJASN. Published online December 17, 2015.

    
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