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[APCH2011]利尿剂的应用指征——Lars H Lindholm教授专访
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Lars H Lindholm,瑞典于默大学公共健康和临床医学部主任、教授,在高级期刊上发表过250篇论文,约200篇摘要,其主要研究领域为高血压、心血管疾病、糖尿病、癌症及健康问题。
International Circulation: In recent years, there seems to have been a decline in the importance of diuretics in the treatment of hypertension. How do you recognize the indication for diuretics in hypertension and in which circumstances should it be the therapy of choice?
《国际循环》:近年来,利尿剂在治疗高血压的中的地位似乎呈下降趋势。请谈谈利尿剂的应用指征,何种情况下应该选择利尿剂来治疗?
Prof Lindholm: Diuretics are an older means of treating hypertension and especially in the United States they are very fond of them and even more so since the ALLHAT trial where the diuretics performed very well. It was almost obligatory in the United States to use a diuretic. Recent recommendations, particularly from the NICE (National Institute for Health and Clinical Excellence) group in the United Kingdom, have downgraded diuretics mainly because there is a risk of diabetes linked to the use of diuretics. Certainly calcium channel blockers seem to do better than diuretics; they are metabolically neutral and more cost effective. There has also been a change in diuretics. We have moved from the thiazides to the so-called thiazide-like diuretics (chlortalidone and indapamide). So the diuretics are not the first-line therapy anymore but they are not without their merits.
Lindholm教授:利尿剂是治疗高血压的老药,受到美国医生的格外钟爱,使用利尿剂几乎是一种常规,尤其是在ALLHAT试验更显示利尿剂降压作用非常出色之后,近期的的一些建议降低了利尿剂在降压中的地位,主要是因为试验观察到应用利尿剂会导致糖尿病的患病风险增加,英国国家卫生与临床优化研究所(National Institute for Health and Clinical Excellence,NICE)的建议格外明显。由于钙通道阻滞剂的代谢产物无明显副作用而且性价比更高,其地位似乎高于利尿剂。但利尿剂本身也已经有所变化,已经从噻嗪类利尿剂转向所谓的噻嗪样利尿剂(氯噻酮和吲达帕胺)。所以,虽然利尿剂已经不再是一线治疗药物,但仍具有其独特的优点。
International Circulation: A target for the very elderly with hypertension has been set at below 150/90 mm Hg. Is there further need for blood pressure lowering in your opinion and how do you weigh up the benefits and risks?
《国际循环》:老年高血压患者的降压目标血压为150/90 mm Hg,在您看来是否有必要进一步降低血压,应怎样权衡利弊?
Prof Lindholm: No. Remember that age takes care of diastolic blood pressure on its own. I think it is more reasonable to use that as a threshold in the elderly. The problem with blood pressure lowering is that, in people with really elevated blood pressure, the efficacy of treatment is fantastic, but the further down you come it becomes more difficult to prove that what you are doing is efficient. If blood pressure is higher than 150 mm Hg we can lower it without much problem with good effect because we know that the higher the blood pressure the higher the risk, but to continue lowering to gain further advantage is very difficult to prove. The absolute risk is low but you would need an enormous group of patients, maybe millions, to show a significant effect. This is why we get so nervous when we get below a certain level because the effect has not been proven but we assume that the risk goes up as blood pressure goes up and so we also assume that as the pressure falls the risk falls also, but we just don’t know. It is even more difficult in women because they are low risk to start with. The analogy would be that women are like men but ten years older; a fifty year old man has the cardiovascular risk of a sixty year old woman.
Lindholm教授:年龄本身就与舒张压相关。我认为将150/90 mm Hg作为老年人群降压的起始门槛更为合理。对于血压明显升高的患者,治疗效果非常好,但很难证明进一步降低血压是有益的。如果血压高于150 mm Hg,理所当然应该进行降压治疗时,且效果良好,因为血压越高风险越高,但继续降压的获益就很难证明了。绝对风险肯定是降低的,但需要数百万的庞大的患者群体才能显示出显著的效果。我们一直假设风险随血压上升而增高,随血压下降而降低,但这并没有被证实,所以将血压降低到一定水平以下时,我们会非常谨慎。推理认为男性与比其年长10岁的女性的风险是相同的,即女性的起始时风险较低,其进一步降压的获益更难证实。
International Circulation: Physicians have been concerned about the relationship of ARBs and an increasing morbidity of tumors. Would you say that ARBs are currently safe for clinical practice?
《国际循环》:医生一直在关注ARB类药物与肿瘤发病率增加之间的关系。你会认为ARB类药物在目前临床实践中是安全的吗?
Prof Lindholm: Yes. You are referring to a paper that was rejected by the Lancet but published by Lancet Oncology about a year ago which was duly discredited by a follow-up paper for which I wrote the editorial comments. It would have to be a potent poison for a blood pressure pill to cause clinically significant cancer within three or four years as was the suggestion, when oncologists treat cancer with full body radiation and only start getting worried about a cancer risk from excess radiation after ten years. It is totally unrealistic. Hypertensive patients as a group have a higher incidence of cancer in any case, but that could be caused by any type of treatment.
Lindholm教授:是的。你指的是大约一年前1篇被《柳叶刀》拒稿,但在《柳叶刀肿瘤学》上发表的文章,之后我写的一篇编辑评论对其进行了充分反驳。高血压患者的肿瘤发病率是升高的,这有可能是由任何一种治疗导致的,而不仅是ARB类降压药。按照那篇文章的结果,ARB类降压药将会是一种强力毒药,能在3、4年内可导致有临床意义的肿瘤显著增加。这是根本不可能的。但即使是肿瘤科医生应用全身放射治疗,也要10年后才开始担心因过度辐射而导致肿瘤的风险。