“理想”血压对慢性肾病患者可能有害
《内科学年鉴》8月19日发表的一项针对美国退伍军人的大型全国队列研究显示,在非透析依赖性慢性肾病患者中,收缩压和舒张压较低者的死亡率确实更低,但是一旦舒张压低于70 mmHg,这一关联就不复存在了。
不仅如此,主要研究者、孟菲斯退伍军人事务部医疗中心肾病科主任Csaba P. Kovesdy医生指出,具有“理想”血压值(低于130/80 mmHg)的患者的死亡率明显升高,“原因是其中包含了收缩压和舒张压较低的患者”。
上述结果意味着,现行的慢性肾病指南提出的收缩压降至130 mmHg或以下的建议,“需要以收缩压降至70 mmHg或以下为代价,可能是有害的”。不过,鉴于本项研究只是观察性研究,“尚需开展临床试验以确定慢性肾病患者接受降压治疗的理想血压目标值”。
研究者分析了2005~2012年期间约652,000例非透析依赖性的退伍军人慢性肾病患者的1,800万次血压检测值,以评估收缩压和/或舒张压与全因死亡率之间的关系。受试者的平均年龄为74岁,97%为男性,88%为白人,43%患有冠心病,43%患有糖尿病。基线时平均收缩压为135 mmHg,平均舒张压为72 mmHg。平均肾小球滤过率(GFR)为50.4 ml/min·1.73 m2。在研究期间共有238,640例患者死亡。
研究者在单独分析收缩压和舒张压时发现存在U型曲线:水平过高和过低均与死亡风险明显升高有关。基于联合分析收缩压与舒张压的校正后危险比(aHR),血压介于130~139/90~99 mmHg者的死亡率最低;在校正年龄、性别、种族、糖尿病、心脑血管疾病和用药情况等因素后,血压介于130~159/70~89 mmHg者的死亡率最低。
不过,收缩压和舒张压均较低与死亡率降低的关联,仅存在于舒张压高于70 mmHg的患者中。
在根据JNC 7(美国高血压预防、检测、评估与治疗联合委员会)分类评估风险时,研究者发现,患有1期高血压(收缩压介于140~159 mmHg或舒张压介于90~99 mmHg)的患者具有最低的死亡率,而血压正常(收缩压低于120 mmHg,舒张压低于80 mmHg)的患者死亡率最高。“这一结果不受混淆因素的影响,而且具有统计学显著性。”
研究者称,高收缩压+低舒张压(在慢性肾病患者中较常见)是“一种尤其麻烦的血压模式”。在收缩压高于140 mmHg且舒张压低于70 mmHg的患者中,33%在研究期间死亡。
这项研究的优点在于样本量很大,但也具有明显的局限性,包括受试者主要为男性和观察性研究设计。研究者指出,在获得相关临床试验证据之前,“低血压都应被视为慢性肾病患者的潜在威胁,而且我们建议不要盲目地将血压降至获益不明确的水平”。
Kovesdy医生承认获得了国立卫生研究院和国立糖尿病、消化病与肾病研究所的补助金,并在研究期间获得了退伍军人事务部的非经济支持。4名合著者无利益冲突披露,1名合著者承认接受了国立卫生研究院的补助金。其余2名合著者报告称从某些药企获得了资金。
随刊述评:由观察性数据得出的结论力度有限
加州大学圣迭戈分校的Dena Rifkin博士和波士顿Tufts医疗中心肾病科的Mark Sarnak医生在随刊述评中指出:“一个看似合理的收缩压加上一个较低的舒张压可能会引起担忧,尤其是当这种血压组合出现在老年慢性肾病患者身上时。但是,较低的收缩压和舒张压可能是慢性疾病或血管疾病严重程度的标志。上述研究结果可能难以外推至3A期慢性肾病老年白人患者之外的人群。并且,由于该研究中仅少数患者有蛋白尿数据可查,因此难以判断研究结果是否适用于有蛋白尿的慢性肾病患者。”(Ann. Intern. Med. 2013;159:302-3)
Rifkin博士无利益冲突披露。Sarnak医生是KDIGO慢性肾病血压管理临床实践指南的撰写组成员。
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By: ELIZABETH MECHCATIE, Cardiology News Digital Network
In a large, national cohort study of U.S. veterans with non–dialysis dependent chronic kidney disease, lower systolic and diastolic blood pressures were associated with lower mortality rates – but only when the diastolic value was higher than about 70 mm Hg.
In addition, mortality rates were significantly increased among those patients with "ideal" blood pressure values (less than 130/80 mm Hg), "because of the inclusion of patients with low SBP and DBP," reported Dr. Csaba P. Kovesdy, chief of nephrology at the Memphis Veterans Affairs Medical Center, and his associates. The study was published in the Annals of Internal Medicine on Aug. 19.
The results indicate that current guidelines for patients with chronic kidney disease (CKD), which recommend a systolic blood pressure (SBP) of 130 mm Hg or lower "at the expense of lowering DBP [diastolic blood pressure] to less than approximately 70 mm Hg," may be harmful, they concluded. However, one of the limitations of the study was that it was an observational study and cannot establish a causal association, so "clinical trials are needed to inform us about the ideal BP target for antihypertensive therapy in patients with CKD," they added.
Using more than 18 million BP readings, the study evaluated the association of SBP and DBP values separately and SBP/DBP combinations on all-cause mortality in almost 652,000 U.S. veterans with CKD, who were not dependent on dialysis, between 2005 and 2012. Their mean age was 74 years, most were male (97%), 88% were white, 9% were black, 43% had coronary artery disease, and 43% had diabetes. The mean SBP values at baseline were 135 mm Hg while the mean DBP was 72 mm Hg; the mean glomerular filtration rate (GFR) was 50.4 mL/min per 1.73 m2. The study looked at 96 different SBP/DBP combinations. During the time period of the study, 238,640 patients died.
They identified a U-shaped curve when analyzing mortality with SBP and DBP separately, "with both lower and higher levels showing a substantial and statistically significant association" with mortality risk. Based on the adjusted hazard ratios for the combinations of SBP and DBP, the lowest mortality rates were associated with blood pressures of 130-139/90-99 mm Hg, and 130-159/70-89 mm Hg, adjusted for factors that included age, sex, race, diabetes, and cardiovascular and cerebrovascular disease, age and medication use).
But combinations of lower SBP and DBP values "were associated with relatively lower mortality rates only if the lower DBP component was greater than approximately 70 mm Hg," they said.
When evaluating risk based on JNC 7 (Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) categories,they found that that those with stage 1 hypertension (SBP of 140-159 mm Hg or DBP of 90-99 mm Hg) were associated with the lowest mortality rates, while those in the normal category (an SBP lower than 120 and a DBP below 80) had the highest mortality rates," results that were independent of confounding factors and were statistically significant.
The authors described an elevated SBP combined with a low DBP, which is common in CKD patients, as "an especially problematic BP pattern," they said, pointing out that 33% of the patients had an SBP greater than 140 mm Hg and a DBP less than 70 mm Hg at some point during the study period.
The study strengths included the large size and the representation of the U.S. veterans’ population, but the limitations included the mostly male population and the observational design of the study, so more studies are needed, the authors said. "Until such trials become available, low BP should be regarded as potentially deleterious in this patient population, and we suggest caution in lowering BP to less than what has been demonstrated as beneficial in randomized controlled trials," they concluded.
Dr. Kovesdy, professor of medicine at University of Tennessee Health Science Center, Memphis, disclosed having received grants from the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, and nonfinancial support from the Department of Veterans Affairs while the study was conducted. Four authors had no disclosures, and one author disclosed having received NIH grants during the study. The remaining two authors disclosed having received research grants or personal fees from different pharmaceutical companies.
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Observational data limit conclusions
While the study results raise questions about the optimal BP targets in patients with CKD, "these are observational data with attendant limitations," Dr. Dena Rifkin and Dr. Mark Sarnak wrote in an accompanying editorial,
"A seemingly acceptable SBP combined with a low DBP may be a cause for concern, especially in older patients with CKD and comorbid conditions." However, "lower [systolic blood pressure] and [diastolic blood pressure] may be markers of the severity of chronic illness or vascular disease," they wrote, adding that the results "may not generalize beyond older white men with stage 3A CKD, and the fact that only a small percentage of persons had proteinuria measurements makes it difficult to draw any conclusions regarding applicability to proteinuric CKD." (Ann. Intern. Med. 2013;159:302-3).
Dr. Rifkin is a nephrologist and epidemiologist at the University of California, San Diego, and the Veterans Affairs Healthcare System, San Diego; and Dr. Sarnak is with the division of nephrology, Tufts Medical Center, Boston. Dr. Rifkin had no disclosures. Dr. Sarnak disclosed having been a member of the KDIGO (Kidney disease improving global outcomes) Clinical Practice Guideline for the Management of Blood Pressure in CKD workgroup.
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来源: EGMN
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