Experts debate genetics vs lifestyle in cardiovascular disease

ATLANTA, Georgia – The influence of genetics and lifestyle on the development of cardiovascular disease was debated at a satellite symposium during the 51st Annual Scientific Session of the American College of Cardiology (ACC 2002).

Dr. Thomas Unger, chairman of the Institute of Pharmacology and Toxicology at Charité, Humboldt University in Berlin, Germany, moderator of the debate, said, "We have been debating genetics versus lifestyle for many years. We know that both factors are involved in cardiovascular disease."

"But what we have to learn is what the respective roles are for genetics and lifestyle. We also need to know which patients will benefit from therapies based on their genetic background and which patients primarily need alterations in their lifestyles," Unger added.

The influence of genetic factors was presented by Dr. Richard Lifton, professor and Department of Genetics chairman at Yale University School of Medicine in Connecticut.

Strong genetic component

Lifton said, "We now recognize that virtually every human disease has a strong genetic component. The exciting aspect of this is that we now have the tools to identify these genes, which will guide us in diagnosis and treatment in the future."

Supporting the role of lifestyle in cardiovascular disease was Salim Yusuf of the Division of Cardiology of McMaster University in Ontario, Canada.

Yusuf said, "The tenfold rise in cardiovascular disease from 1900 to the 1960s in the United States and in several other countries, followed by large declines, simply means that non-genetic factors are dominant in the causation and hence, the prevention of most cardiovascular diseases."

After the debate, symposium attendees listened to three presentations on the use of antihypertensive drugs to prevent heart disease and catastrophic cardiac events such as heart attacks.

For many years, doctors assumed that the benefits of antihypertensives were strictly related to their ability to lower blood pressure. However, other factors are involved in cardiovascular disease. For example, angiotensin II has been implicated in atherosclerosis.

ACE inhibitors

The angiotensin-converting enzyme (ACE) inhibitors seem to protect against attacks and prevent death due to heart failure to a greater extent than can be explained by their ability to lower blood pressure.

Because it is known that ACE inhibitors not only lower blood pressure but actually protect patients from cardiovascular disease, doctors have been inspired to look beyond mere blood pressure reduction in treating patients with hypertension.

Dr. Stephen Ball, head of the academic unit of cardiovascular medicine of Leeds University in the United Kingdom, said, "There has been a shift away from using just the level of blood pressure to determine treatment. We now focus on the patient’s overall risk profile."

"With ACE inhibitors, there are abundant data showing that these drugs reduce the risk for cardiovascular events, particularly myocardial infarction (heart attack). An important part of this benefit may be independent of blood pressure lowering," he added.

Dr. William White, chief of the hypertension and clinical pharmacology section of the University of Connecticut School of Medicine, reported that a newer antihypertensive drug class, the angiotensin II receptor blockers (ARBs), is expected to provide similar cardioprotection as the ACE inhibitors.

While in the past, cardio-renal outcome data were only available for the ACE inihibitor, he said this has changed with the ARBs.

Data support

Data from ELITE II (Evaluation of Losartan in the Elderly II study), Val-HeFT (Valsartan Heart Failure Trial), RENAAL (the Reduction in End Points with NIDDM with the Angiotensin II Antagonist Losartan study), and IDNT (the Irbesartan Diabetic Nephropathy Trial) support the use of ARBs in patients with hypertension, heart failure and diabetes as primary therapeutic endpoints.

"ARBs reduce cardiovascular events and are renoprotective. Thus, these impressive data have modified the paradigm for the treatment of the hypertensive patient," White said.

Despite the impressive data on ACE inhibitors and ARBs, very few studies have directly compared these two types of drugs for protecting patients from heart disease.

In the final presentation, Unger spoke about the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial program, also known as the ONTARGET Trial Program, an extensive and long-term study that will directly compare an ACE inhibitor (ramipril), an ARB (telmisartan Boehringer Ingelheim’s Micardis) and a combination treatment using both agents for protecting patients against cardiovascular disease and death.

The 5.5-year ONTARGET study will enroll 28,400 patients at risk of developing serious complications from heart disease, at 793 centers in 40 countries.

A parallel trial – Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease (TRANSCEND) – is the largest cardiovascular protection trial ever conducted among patients intolerant to ACE inhibitors due to their specific side-effects, such as dry cough.