葦の髄から循環器の世界をのぞく

高血圧の話題（？）としては、CKD、ARB、血圧日内変動が中心です。
学術集会はともかく、製薬メーカーの講演会は薬剤（降圧剤）販促という目論見が見え隠れして食傷気味のテーマが続きます。
私もブログを２年前に初めて、取材も兼ねて積極的に講演会に参加して来ました。
嬉々として参加していたのですが最近はさすがに講演者も一回りしてテーマも新鮮味に欠けてきました。

温故知新ではないのですが、「血圧と左室肥大」といったテーマは妙に新鮮味と懐かしさを感じてしまいます。
＃厳密な血圧コントロールは左室肥大を退縮させる
収縮期血圧の厳密なコントロールは通常の治療より左室肥大のリスクを低減するだけでなく、所定の心血管イベントのエンドポイントも減少させた。この結果は新たな仮説の創出に結び付き、まだ詳しい研究が必要であると研究者らは言う。

収縮期血圧の厳密なコントロールは通常の血圧コントロールに比べて左室肥大発症のリスクを有意に低下させることがCARDIO-SIS試験の結果で明らかとなった。
さらに、収縮期血圧を通常の目標値140 mm Hg未満ではなく130 mm Hg未満に抑えることで、臨床イベントが有意に減少することも分かったと研究者らは報告する。

「一般集団と臨床試験の血圧コントロール量は十分でないし、心血管の保護と血圧低下は直接関係している。このため、CARDIO-SISの結果は糖尿病を合併していない高血圧患者で厳密な血圧コントロールを行うことの潜在的効果に目を向けさせた」と主席研究者であるDr Paolo Verdecchia (ANMCOリサーチセンター、イタリア、フィレンツェ) らは2009年8月15日発行の『Lancet』に書く。
心血管リスクの高くない患者で130 mmHg未満という収縮期血圧目標値が心血管に与える影響を初めて評価したことは重要である、とDr Bo Carlberg (ウメオ大学付属病院、スウェーデン) らは発表された研究の付随論説に 書く。
しかし研究結果を拡大解釈しないよう注意する。

「この周到に実施された試験は左室肥大に対する治療の影響を調べるために計画された」とCarlberg博士は書く。
「心血管のアウトカムは主要評価項目ではなかった。したがって心血管疾患への影響を調べる検出力はなかった。よって治療効果の大きさは不明確である」。

＃低リスクの患者
欧州心臓病学会 (European Society of Cardiology) と米国合同高血圧委員会 (JNC：US Joint National Committee in Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) 第7次報告による最新の高血圧ガイドラインは、収縮期および拡張期血圧を140/80 mm Hg未満に抑えるよう推奨している。
2型糖尿病患者については目標値を下げることを支持するデータがある。

CARDIO-SISでは、収縮期血圧150 mm Hg以上の非糖尿病患者1111例を目標収縮期血圧140 mm Hg未満または130 mm Hg未満のより厳しい目標値にランダムに割り付けた。

降圧薬には様々な組み合わせがあり、目標値に近づけるため担当医師が個別に処方した。
ランダム化の後、2年間の追跡が行われた。
この期間、収縮期血圧および拡張期血圧は通常コントロール群でそれぞれ23.5 mm Hg、8.9 mm Hg低下し、厳密コントロール群で27.3 mm Hg、10.4 mm Hg低下した。

主要エンドポイントである心電図上の左室肥大発生率は、通常の収縮期血圧目標値群で17%、目標130 mm Hg未満の厳密目標値群で11.4%であった。
これは37%という有意なリスク低下となった。
所定の副次エンドポイントは全死因死亡、MI、脳卒中、一過性脳虚血発作、心房細動、ならびに心不全、狭心症、冠動脈再潅流療法による入院の複合項目であったが、これらは通常目標値群の9.4%、厳密目標値群の4.8%に認められた。
左室肥大は心エコーよりも感度が低い心電図で診断したと研究者らは記している。
もうひとつの限界は、試験が二重盲検でなかったため治療群の自覚が二次イベントにかかわる臨床決定、特に心不全と冠動脈再潅流療法の入院に影響した可能性があることだという。

「最後に、我々の試験の副次臨床アウトカムは主要アウトカムである左室肥大と一貫性があったが、症例数がきわめて少なかったうえに追跡が2年間に限られていたことから、ほとんど臨床イベントが起こらなかった」とVerdecchia博士らは書く。
「したがって我々のアウトカム結果は仮説創出の土台として見るべきであるが、臨床イベントに焦点を当てた大規模なアウトカム試験の計画にも役立つかもしれない」。

Carlberg博士は、今回の結果から収縮期血圧150 mm Hgを超える治療患者の収縮期血圧目標値を低く設定すべきであることが確認された、と論説で述べた。

「ただしリスクの低い高血圧患者のガイドラインを変更する前に、十分な検出力がある臨床試験で130 mm Hg未満の収縮期血圧目標値を評価するべき」と博士は書く。
「どの患者群にこのような治療が有効か、費用対効果はどうかを評価するのはそれからである」。

現在、Systolic Pressure Intervention Trial (SPRINT) が計画されている。
SPRINTは米国立衛生研究所の研究費を助成した試験で、120 mm Hg未満と140 mm Hg未満の降圧目標値を比較検討する臨床アウトカム試験である。

Medscape Medical News 2009. (C) 2009 Medscape
http://www.m3.com/news/SPECIALTY/2009/8/20/106063/?Mg=8a57bd916fb02ec5f9e1972729423a60&Eml=31ef79e7aaf65fca34f0f116a57fd65d&F=h&portalId=mailmag
Usual versus tight control of systolic blood pressure in non-diabetic patients with hypertension (Cardio-Sis): an open-label randomised trial
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)61340-4/abstract

出典　Medscape　2009.8.20

＜CARDIO-SIS　関連サイト＞
Cardio-Sis: Tight BP control bested usual control among patients without diabetes
http://www.cardiologytoday.com/view.aspx?rID=42962
■Study results from the Cardio-Sis open-label trial show that patients who have hypertension but no diabetes respond well to tight control (<130 mm Hg), suggesting the recommended goal of <140 mm Hg could be reduced.
■In 44 Italian centers, researchers randomized patients without diabetes with systolic BP >150 mm Hg to usual control (goal systolic BP of <140 mm Hg; n=553) or tight control (goal of systolic BP <130 mm Hg; n=558).
According to the study, the primary endpoint was prevalence of ECG left ventricular hypertrophy after two years; The secondary endpoint was a number of cardiovascular outcomes, including all-cause mortality, NYHA III or IV congestive HF requiring hospitalization, fatal or nonfatal MI, transient ischemic attack, coronary revascularization and new onset atrial fibrillation.
■“Findings from our trial have shown that setting a systolic target of <130 mm HG instead of the usual 140 mm HG in patients with treatment-resistant systolic hypertension was feasible and well tolerated,” the researchers said in their discussion.

Cardio-Sis in the Lancet: is 130 the new 140?
http://cardiobrief.org/2009/08/13/cardio-sis-in-the-lancet-is-130-the-new-140/
■Cardio-Sis, a large trial from Italy, provides the first good evidence that systolic blood pressure goals in non-diabetic patients should be lowered to 130 mm Hg.
■Most guidelines now recommend that systolic blood pressure be reduced to below 140 mm Hg, though in diabetics it is now generally accepted that the target should be 130 mm Hg.
■The findings are published today in the Lancet.
The Italian investigators randomized 1,111 non-diabetic patients with systolic BP 150 mm Hg or greater to usual control, with a target systolic blood pressure of 140 mm Hg, or tight control, with a target systolic blood pressure of 130 mm Hg.
■The primary endpoint, the rate of left ventricular hypertrophy at two years, occurred in 17% of the usual control group and 11.4% of the tight control group.
■Adverse cardiovascular events were also reduced, occurring in 9.4% of the usual care group and 4.8% of the tight control group.
■“The findings support a lower systolic blood pressure goal in treated patients with systolic blood pressure above 150 mm Hg,” writes Bo Carlberg, in an accompanying editorial.
■“However, before changing guidelines in low-risk patients with hypertension, a systolic blood pressure treatment goal below 130 mm Hg should be evaluated in adequately powered randomised trials.
■Only after that will it be possible to evaluate in which groups of patients such treatment is beneficial, and the cost-effectiveness of such treatment.”

■Franz Messerli, who has taken a prominent role in reviving the concept of the J-curve, sent the following comment to CardioBrief:
The Lewington meta-analysis in 1 million subjects showed that a usual blood pressure of 110/70 is associated with less heart attack or stroke than a blood pressure of 130/80. However, little if any evidence is available showing that lowering blood pressure from 130/80 to 110/70 confers any benefit.
To the contrary, several large prospective, randomized studies, among them VALUE, INVEST, TNT and ONTARGET, have shown evidence of a J-shaped curve between blood pressure and cardiovascular events.
The nadir of INVEST in which all patients had coronary disease was 119/84 mmHg.
The study of Verdeccia et al is provocative in that it shows a relatively small blood pressure difference (3.8/1.5mmHg) can make a differenced in terms of left ventricular hypertrophy and new onset atrial fibrillation in patients who, by current standards, are well controlled i.e., have their blood pressure distinctly below 140/90. However, no difference in myocardial infarction, heart failure, stroke or death was observed between the 2 groups.
Though diastolic pressure is of particular concern in patients with coronary artery disease because coronaries are perfused during diastole and too low a diastolic pressure hampers coronary perfusion.
In the present study only 12% of patients had coronary artery disease. Before we accept the author’s conclusions that these findings lend support to a lower blood pressure goal than is recommended at present, I would like to see an adequately powered randomized trial assessing this hypothesis.
Such a trial (SPRINT) is currently in progress and hopefully will give us an answer to this problem in a few years.
Until then, clinicians should remain vigilant with regard to a too aggressive blood pressure control particularly in patient with coronary artery disease and be mindful of the dictum: “Too low a blood pressure can be dangerous to your health.”

Here is the Lancet press release:
TREATING HIGH SYSTOLIC BLOOD PRESSURE IN NON-DIABETIC PATIENTS COULD BE BENEFICIAL
Treatment to lower high systolic blood pressure in non-diabetic patients is associated with a reduction in left ventricular hypertrophy (LVH), a thickening of the heart muscle that can lead to heart failure and rhythm problems. Thus, a lowering of systolic blood pressure targets from the currently recommended 140 mm/Hg or less to below 130 mm Hg should be the treatment goal in low-risk patients with high blood pressure, concludes an Article published in this week’s edition of The Lancet.
Despite a lack of evidence, hypertension guidelines recommend that blood pressure be lowered to less than 140/90 mm Hg. Evidence from previous trials does lend support to a blood pressure target of below 130/80mm Hg in high-risk patients with cardiovascular disease or diabetes. However, the level to which systolic blood pressure should be lowered in patients without high cardiovascular risk has not been evaluated in clinical trials. Indeed, there is currently no evidence to support a lower treatment target in patients with high blood pressure without diabetes.
For the first time, Paolo Verdecchia from the Hospital S. Maria della Misericordia and ANMO Research Centre in Italy and colleagues conducted a randomised trial to examine the cardiovascular effects of a systolic blood pressure target below 130 mm Hg (tight control) compared with a target below 140 mm Hg (usual control) in non-diabetic patients with hypertension.
In total, 1111 non-diabetic patients aged 55 years or older with a systolic blood pressure of 150 mm Hg or higher were recruited from 44 centres in Italy between 2005 and 2007. Patients were randomly assigned to a target systolic blood pressure of less than 140 mm Hg (553) or less than 130 mm Hg (558).
Antihypertensive drugs were used to lower blood-pressure and tailored to individual patients’ needs. Blood pressure was checked every 4 months for 2 years and at the final 2-year visit patients were tested for LVH.
Over 2 years, tight (<130 mm Hg) compared to usual (<140 mm Hg) blood-pressure control reduced systolic blood pressure and decreased the likelihood of LVH and clinical events.
Overall, systolic blood pressure was 3.8 mm Hg lower and diastolic blood pressure 1.5 mm Hg lower in the tight-control group.
In addition, patients in the usual-control group were more likely to have LVH (17%) than in the tight-control group (11.4%) at 2 years. Although the number of events of clinical outcome was small, coronary revascularisation and new-onset atrial fibrillation were significantly less frequent in the tight–control group.
The authors conclude: “Because of the poor amount of blood-pressure control in the general population and clinical trials, and because of the direct relation between cardiovascular protection and blood-pressure lowering, the results…lend support to a lower blood pressure goal than is recommended at present in non-diabetic patients with hypertension.”
In an accompanying Comment, Bo Carlberg from University Hospital, Umeå, Sweden, cautions that before changing guidelines in low-risk patients with hypertension: “A systolic blood pressure treatment goal below 130 mm Hg should be evaluated in adequately powered randomised trials.
Only after that will it be possible to evaluate in which groups of patients such treatment is beneficial and the cost effectiveness of such treatment.”

＜SPRINT　関連サイト＞
Systolic Blood Pressure Intervention Trial (SPRINT) Clinical Center Networks
https://www.fbo.gov/index?s=opportunity&mode=form&tab=core&id=72ab0277cccdb4aab5ed766316021e8b&_cview=0&cck=1&au=&ck=

Systolic Blood Pressure Intervention Trial (SPRINT) ?Clinical Center Networks
http://www.fbodaily.com/archive/2007/10-October/03-Oct-2007/FBO-01425892.htm

＜きょうの一曲＞　All My Life
Karla Bonoff - All My Life
http://www.youtube.com/watch?v=2xUCHcM9duw&hl=ja

http://wavemusic.jp/jacket/850/P2_G4252850W.JPG

その他
ふくろう医者の診察室http://blogs.yahoo.co.jp/ewsnoopy
（一般の方または患者さん向き）　
 「井蛙内科/開業医診療録（３）」2008.12.１１～ http://wellfrog3.exblog.jp/
「井蛙内科/開業医診療録（２）」2008.5.21～ http://wellfrog2.exblog.jp/
「井蛙内科/開業医診療録」　～2008.5.21 http://wellfrog.exblog.jp/　
（内科医向き）
があります。