勃起功能障礙是心血管事件與死亡的警訊

作者：Norra MacReady  
出處：WebMD醫學新聞

　　March 19, 2010 — 新資料顯示，勃起功能障礙(Erectile dysfunction，ED)是心血管疾病男性患者以及那些有風險因素男性之各種原因死亡和心血管事件的強力預測因子。
　　
　　ED和心血管疾病兩者都與內皮功能不佳有關，所以ED和心血管結果有關的假設是合理的，且可能和心血管相關死亡及各種原因死亡都有關。德國Saarbrucken Saarland大學的Michael Bohm醫師等人發表於3月15日線上版循環(Circulation)期刊的研究結果支持前述假設。
　　
　　研究對象是1,519名男性，來自參與「ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET)」研究以及「Telmisartan Randomized AssessmeNt Study in ACE [angiotensin-converting enzyme] INtolerant subjects with cardiovascular Disease (TRANSCEND)」試驗之「ED次研究」的13個國家，兩項研究的多數研究對象都有心血管疾病，在ONTARGET研究中，這些男性病患被隨機指派接受ACE抑制劑ramipril、telmisartan或併用這兩種藥物，在TRANSCEND試驗中，對於ACE抑制劑無法耐受者被隨機指派接受telmisartan或安慰劑。
　　
　　至於ED次研究，每位男性回覆一個有5個項目的國際勃起功能指標(IIEF)問卷，以及有6個項目的Kolner氏勃起功能障礙評估問卷，Kolner量表分數越高、IIEF分數越低都表示惡化的ED，在研究開始時、兩年後、倒數第二次追蹤訪視時(中位數為48個月之後)進行這些問卷檢測。
　　
　　ED的整體盛行率為55% — 約是一般人的兩倍高 —且ONTARGET或TRANSCEND的試驗組之間並無差異，ED男性的年紀中位數為66歲，無ED或輕微ED男性之年紀中位數為63歲(P < .0001)。開始時，ED男性的各種原因死亡率為11.3%，無ED或輕微ED男性則是5.6%，風險比為2.04 (95%信心區間為1.40 - 2.97；P = .0002)。合併心血管死亡、心肌梗塞、中風、心衰竭住院等初級結果，ED男性的發生率為16.2%，無ED或輕微ED男性則是10.3%，風險比為1.62 (95%信心區間為1.22 - 2.17；P = .0001)。
　　
　　研究者寫道，開始時有ED的病患比較可能死於心血管原因(P=0.0009)或心肌梗塞(P=0.04)，他們觀察發現，此一風險隨著ED的嚴重度而逐漸增加，有ED之男性的心衰竭和中風風險傾向較高，但是未達統計上的顯著程度。
　　
　　在研究期間，IIEF分數和Kolner量表分數並無明顯改變，認為這些治療對於研究對象的ED沒有任何影響。
　　
　　紐約大學醫學院心臟科教授Richard A. Stein醫師受邀發表獨立評論時向Medscape Cardiology表示，我們早就已經知道控制動脈粥狀硬化的主要細胞是位於血管內層的內皮細胞，陰莖海綿組織上也有這種細胞，因此我們知道勃起障礙和心臟病之間有某種關聯，本研究追蹤一群已經知道有心血管疾病的男性達將近5年，提出令人印象深刻的結果：勃起功能障礙是實際風險增加的一種標記。
　　
　　未參與該研究的Stein醫師表示，這類病患的治療應和心臟病患相同：控制體重、運動、戒菸、改善血清脂質，至於這些方法是否可以緩解ED則還無定論，不過，他表示，可以合理的認為，心臟風險因素增加的病患若減少這些風險因素一定可以有所幫助，我們希望這也可以減少勃起功能障礙，更重要的是，減少病患後來發生心臟病的風險。
　　
　　研究作者相信，這些研究發現認為，ED是心血管風險的主要表徵，他們結論表示，ED是高風險病患與粥狀動脈硬化和內皮功能不佳者，心血管原因死亡與嚴重心血管事件的強力預測因子。
　　
　　ONTARGET/TRANSCEND ED次研究接受德國Boehringer-Ingelheim藥廠的支持 ，所有研究作者都接受來自Boehringer-Ingelheim藥廠的資金或基金。Stein醫師宣告沒有相關財務關係。
　　
　　Circulation. 線上發表於2010年3月15日。


Erectile Dysfunction a Red Flag for Mortality, Cardiovascular Events

By Norra MacReady
Medscape Medical News

March 19, 2010 — Erectile dysfunction (ED) is a robust predictor of all-cause mortality and cardiovascular events in men with cardiovascular disease or those with risk factors, new data show.

ED and cardiovascular disease both are associated with endothelial dysfunction, "so it was reasonable to assume that ED was related to cardiovascular outcomes and possibly both cardiovascular-related and all-cause death." These findings, published online March 15 in Circulation, support that assumption, write the investigators, led by Michael Bohm, MD, of the University of the Saarland, Saarbrucken, Germany.

The study subjects were 1519 men from 13 countries participating in an ED substudy of the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) and the Telmisartan Randomized AssessmeNt Study in ACE [angiotensin-converting enzyme] INtolerant subjects with cardiovascular Disease (TRANSCEND) trial. Most of the subjects in both trials had cardiovascular disease. In ONTARGET, the men had been randomly assigned to receive the ACE inhibitor ramipril, telmisartan, or a combination of the 2 agents. In TRANSCEND, people intolerant to ACE inhibitors were randomly assigned to treatment with telmisartan or a placebo.

For the ED substudy, each man answered the 5-item International Index of Erectile Function (IIEF) and the 6-item Kolner Evaluation of Erectile Dysfunction questionnaires. Worsening ED is indicated by higher scores on the Kolner scale and lower scores on the IIEF. The questionnaires were administered at baseline; 2 years later; and on the penultimate follow-up visit, which occurred at a median of 48 months later.

The overall prevalence of ED was 55% — approximately twice as high as in the general population — with no difference between the ONTARGET or TRANSCEND groups. The median age of the men with ED was 66 years vs a median age of 63 years for the men with no or mild ED (P < .0001). All-cause mortality occurred in 11.3% of the men with ED at baseline vs 5.6% of the men with no or mild ED at baseline, for a hazard ratio of 2.04 (95% confidence interval, 1.40 - 2.97; P = .0002). The composite primary outcome of cardiovascular death, myocardial infarction, stroke, and hospitalization for heart failure occurred in 16.2% of the men with ED vs 10.3% of the men with no or mild ED, for a hazard ratio of 1.62 (95% confidence interval, 1.22 - 2.17; P = .0001).

"Patients with ED at baseline also were more likely to die of cardiovascular causes (P=0.0009) or myocardial infarction (P=0.04)," the investigators write. They observed a stepwise increase in risk depending on the severity of the ED. A tendency toward a higher risk for heart failure and stroke was observed in the men with ED but did not attain statistical significance.

Scores on the IIEF and Kolner scales did not change appreciably during the course of the study, suggesting that none of the treatments had any effect on ED among the participants.

"We've known for many years that the major cell that controls the development of atherosclerosis is the endothelial cell, which lines the blood vessels" as well as the spongy tissue of the penis," Richard A. Stein, MD, professor of cardiology at New York University School of Medicine in New York, NY, told Medscape Cardiology when asked for independent comment. "So we've known there should be a relationship between erectile dysfunction and heart disease. This study, which followed a group of men with known cardiovascular disease for nearly five years, showed in an impressive way that erectile dysfunction is a marker of substantial increased risk."

Treatment of these patients should be the same as for any patient with heart disease: weight control, exercise, smoking cessation, and improving the serum lipid profile, says Dr. Stein, who was not involved in the study. It still is not known conclusively if these measures can resolve ED. Still, he says, "there’s a reasonable basis to think that this patient has increased cardiac risk factors and would benefit from reducing them. Hopefully, that might reduce the erectile dysfunction, but more clearly, it will reduce the patient's risk of having a downstream cardiac event."

These findings suggest that ED is a manifestation of cardiovascular risk, the study authors believe. They conclude: "ED is a powerful predictor of cardiovascular death and of major cardiovascular events in high-risk patients and represents a symptom of more advanced atherosclerosis and endothelial dysfunction."

The ONTARGET/TRANSCEND ED Substudy was supported by Boehringer-Ingelheim, Germany. All of the study authors have received grants or funds from Boehringer-Ingelheim for the conduct of these trials. Dr. Stein has disclosed no relevant financial relationships.

Circulation. Published online March 15, 2010.