“Impotence is a strong predictor of heart attack and death among men who already have heart disease,” says the BBC.
The news is based on a well-conducted international study of 1,519 men with cardiovascular disease. The study found that those who had erectile dysfunction were twice as likely to be at risk of a heart attack or death compared to those who were not impotent. This was after taking into account risk factors such as smoking.
The study confirms previous findings and the researchers say that this makes a case for screening men with impotence for the co-existence of vascular disease and for including questions about impotence in routine health and vascular checks.
The study confirms that erectile dysfunction could be a useful indicator of future vascular disease, but more study will be required to decide exactly how to integrate such an assessment into current vascular risk tests.
Where did the story come from?
This research was carried out by Dr Michael Böhm from Germany and international colleagues from the Erectile Dysfunction Study Investigator research group. The study was financially supported by Boehringer-Ingelheim, manufacturers of the drug telmisartan, and published in the peer-reviewed medical journal Circulation.
The BBC was one of a few sources to report this study and it includes several quotes from British experts who stress the importance of making questions about erectile dysfunction a routine part of medicals and vascular checks.
What kind of research was this?
Erectile dysfunction (ED) is a type of impotence that is known to be more common in men with vascular risk factors and narrowing of the arteries. The researchers were interested in seeing if the presence of ED is a predictor of future heart attacks or strokes in men with existing vascular disease.
The study investigators have already published the results of two randomised clinical trials that tested the drugs ramipril and telmisartan in people with vascular disease or high-risk diabetes without heart failure. These trials followed people for almost five years to assess the rates of heart disease and death.
In this extension study, called the Erectile Dysfunction Substudy, the researchers used an impotence questionnaire delivered at the start of the original studies and related the answers to the cardiovascular outcomes they had previously observed. They then analysed these results to see if ED was predictive of mortality, heart attacks or strokes.
The substudy was designed before either main study started, as the researchers had intended to look at the relationship between ED and cardiovascular outcomes.
What did the research involve?
The ED substudy subjects were 1,519 men (842 men with ED, 677 without) from 13 countries. These subjects had been recruited from a pair of studies on high blood-pressure drugs: the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) or the Telmisartan Randomized Assessment Study in ACE-Intolerant Subjects with Cardiovascular Disease (TRANSCEND) studies.
Most of the subjects in both trials had cardiovascular disease, although some in ONTARGET had high-risk diabetes only. In ONTARGET, the men were randomised to receive the ACE inhibitor ramipril, the angiotensin-receptor blocker telmisartan, or a combination of the two drugs. In TRANSCEND, people who experienced side effects with ACE inhibitors were randomised to treatment with telmisartan or a placebo.
In the ED substudy the researchers gave each man two questionnaires, which were:
- a five-item International Index of Erectile Function (IIEF) questionnaire
- a six-item Kölner Evaluation of Erectile Dysfunction questionnaire
More severe ED is indicated by higher scores on the Kölner scale and lower scores on the IIEF. The questions were asked at the start of the study, two years later, and on a penultimate follow-up visit, which occurred about 48 months later.
The researchers analysed the data appropriately, testing the significance of any differences they found between the survival patterns of men with or without erectile dysfunction. This technique allowed the researchers to report the significance of any difference in the length of time it took the men to suffer one of several outcomes, which were:
- death from vascular disease
- heart attack
- hospitalisation for heart failure
The risks of outcomes were reported as hazard ratios (HR), a type of measure that compares relative risk between two groups over time. The researchers adjusted the HR values for a range of factors that could also explain the relationship between cardiovascular outcomes and ED. The factors were: age, blood pressure, smoking, history of hypertension, diabetes, heart attack, stroke/transient ischaemic attack, alcohol consumption, use of drugs known to cause ED, surgery to the lower urinary tract and a combination of any of these.
What were the basic results?
Among the 1,176 patients in ONTARGET, 400 participants were randomised to receive ramipril, 395 telmisartan, and 381 the drugs combined. In TRANSCEND, 171 participants were randomised to receive telmisartan while 202 received a placebo.
Of the 1,519 participants in the subsequent ED study, 842 had ED and 677 did not. Those with ED were older and were more likely to have diabetes, high blood pressure and to be taking a calcium channel blocker for blood pressure control.
The researchers found that ED was predictive of death from any cause, with a man with ED being around 80% more likely to die at any given point in time compared to a man without ED (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.21 to 2.81). When looking at specific events individually:
- ED was predictive of vascular death (HR 1.93, 95% CI 1.13 to 3.29).
- ED was predictive of a heart attack (HR 2.02, 95% CI 1.13 to 3.58).
- ED was not a statistically significant predictor of hospitalisation for heart failure or stroke.
The study medications did not affect whether men developed new or worse erectile dysfunction.
How did the researchers interpret the results?
The researchers say that their study shows that ED is “highly predictive” of all-cause deaths and the combination of cardiovascular deaths, myocardial infarction, stroke, and heart failure in the type of patient studied.
They call for evaluation of ED in the medical history as an early symptom of problems with blood vessels and say it might be relevant in identifying patients ata particularly high risk of experiencing a cardiovascular event.
This was a well-conducted study that confirms previous observational studies on erectile dysfunction and heart disease. There are some points to consider when interpreting the results.
- Participants in the two trials that originally provided data for this study were randomly assigned to treatment groups (randomised), but those in the substudy were not. They were instead grouped according to their history of impotence, making this an observational study rather than a randomised trial. This means that it is prone to the biases that occur in observational studies, although the researchers have correctly taken these into account in their reporting and analysis.
- At the start of the study, there were differences between the two groups in terms of the numbers of men with diabetes, high blood pressure or taking some other drugs. This will have contributed to the differences in unadjusted mortality when men with ED are compared to those without. It is also unclear whether the later adjustments fully took these differences into account.
- This study has not investigated how adding ED to the other major predictors of heart attack or stroke risk (such as age, smoking, high blood pressure, cholesterol or diabetes) would improve predictive accuracy of these assessments. For example, they did not assess how useful ED would have been as a predictor of vascular disease when all these major factors were taken into account.
- The studies both included men who were already known to be at high risk of cardiovascular events. Their results may not be representative of what would be seen in men who were at lower risk of cardiovascular events.
Overall, this study confirms that ED could be a useful indicator of future vascular disease, but more study will be required to decide exactly how to include it in current vascular risk scores.
Analysis by Bazian
Edited by NHS Website
Links to the science
Circulation [Published Online], March 15, 2010