可可黃烷醇與ESRD患者的血管保護有關


  【24drs.com】根據線上發表於12月17日美國腎臟醫學會臨床期刊的一篇新研究,攝取可可黃烷醇(cocoa flavanols,CF)可以減輕末期腎病患者(end-stage renal disease,ESRD)因血液透析(hemodialysis,HD)引起的或慢性的內皮功能障礙,且改善高風險患者的血管功能。
  
  可可黃烷醇是可可所含的植物多酚。
  
  德國Essen西德心血管中心心臟科Tienush Rassaf 醫師等人指出,ESRD被認為是一個重要的心血管危險因子。研究者寫道,這導致這群患者的發病率和死亡率大幅增加,是一般人的8倍。在ESRD患者,血管功能障礙與心衰竭及心因性猝死有關。
  
  研究者指出,心臟troponin值升高對此有影響,是ESRD患者各種原因死亡率的一個重要預測因子。ESRD患者中,對一氧化氮的生體可用率不佳,會進一步助長血管功能障礙。重要的是,血液透析會降低[一氧化氮]生體可用率,更加重內皮功能不良。
  
  飲食補充富含可可黃烷醇的食物可以改善血管功能;不過,評估血管功能不佳對ESRD患者之影響的研究相當稀少,因此,研究者在2012-2013年進行了這篇隨機雙盲安慰劑控制試驗,以評估富含黃烷醇生物活性成分的食物對於ESRD患者之急性與慢性血液透析引起之血管功能障礙的影響。他們納入57名進行血液透析治療潛在的腎臟疾病-包括高血壓和糖尿病腎病變、腎小球腎炎和多囊腎的患者。
  
  這57名研究對象中,研究者隨機指定52人到慢性平行組試驗,他們提供其中26人富含黃烷醇(研究期間每天900 mg的黃烷醇)的飲料,另外26人則是接受營養成分相當但沒有黃烷醇的安慰劑。Rassaf 醫師等人解釋,這篇研究中,初級與次級結果測量包括流量調節之舒張功能(FMD)和血流動力學的改變。
  
  患者對攝取黃烷醇的耐受良好,急性期攝取可使FMD改善達53% (3.2% ± 0.6%到4.8% ± 0.9%,安慰劑組為:3.2% ± 0.7% 到3.3% ± 0.8%;P < .001),不會影響心律與血壓。
  
  相較於安慰劑,攝取黃烷醇30天之後,研究者指出,基本FMD增加達18%(3.4% ± 0.9%到3.9% ± 0.8%,安慰劑組為3.5% ± 0.7%到3.5% ± 0.7%;P < .001);這和舒張壓降低(73 ± 12到69 ± 11 mm Hg,安慰劑組為70 ± 11到73 ± 13 mm Hg;P = .03)與心律增加(70 ± 12到74 ± 13 bpm,安慰劑組為75 ± 15到74 ± 13 bpm;P = .01)有關。
  
  研究者也指出,在血液透析時,急性期攝取黃烷醇可緩和血液透析引起的血管功能障礙(3.4% ± 0.9%到2.7% ± 0.6%,安慰劑組為3.5% ± 0.7%到2.0% ± 0.6%;P < .001),且這影響持續整個研究(急性到慢性,3.9% ± 0.9%到3.0% ± 0.7%,安慰劑組為3.5% ± 0.7%到2.2% ± 0.6%;P =.01)。
  
  根據Rassaf醫師等人表示,該研究獲得四個主要結論,在ESRD患者,攝取黃烷醇(每天900 mg)耐受良好,急性期與慢性期攝取黃烷醇可以部分逆轉內皮功能障礙,慢性期攝取黃烷醇可造成舒張壓降低且不會影響主動脈硬化的標記,攝取黃烷醇可減輕血管透析引起的血管功能障礙。
  
  作者們寫道,黃烷醇發揮心臟保護作用的確切機轉,仍尚未被完全闡明。研究者解釋,亞硝基硫醇血漿值增加、細胞信號級聯放大、基因表現和酶活性改變等對[一氧化氮]動態平衡之影響,被認為是潛在途徑。在這篇研究中,我們在血漿亞硝酸鹽或硝酸鹽值並沒有觀察到差異,可能是因為樣本數少,或是因為ESRD患者的[誘導型一氧化氮合成酶]的活化。
  
  在編輯評論中,義大利Reggio Calabria Ospedali Riuniti的Carmine Zoccali醫師和Francesca Mallamaci醫師寫道,在一些替代FMD或脈搏波速度的研究中,儘管有證據顯示,類黃酮對心血管系統可發揮良好效果,也可能可以降低高血壓患者的[血壓],看來似乎是強大且可信的,不過,迄今為止,還沒有依據臨床終點進行的大型研究顯示這些成份的好處。因此,儘管可能,類黃酮用於預防和治療心血管疾病的治療益處仍是個懸而未決的問題。
  
  不過,在過去20年,並未提出對ESRD患者有意義的心血管預後。考量接受血液透析患者之心血管疾病的嚴重負擔,腎臟病醫學界需要留意有意義的預防方法,如可可黃烷醇,他們結論表示,這篇研究的結果或許是進行血液透析之患者,在預防心血管疾病之戰鬥、提供其他研究(根據相同的替代物),以及根據臨床終點確認研究結果之試驗的一個轉折點。
  
  資料來源: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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