Letter from Barbara Alving, Acting Director, National Heart, Lung and Blood 
Institute sent to a reporter from the British Medical Journal on request.


Friday, September 24, 2004       NHLBI Communications Office(301) 496-4236


Nhlbi_news@nhlbi.nih.gov <mailto:Nhlbi_news@nhlbi.nih.gov>


Cholesterol Guidelines:  The Strength of the Science Base

and the Integrity of the Development Process


Statement from Barbara Alving, M.D., Acting Director,

National Heart, Lung, and Blood Institute


A letter initiated by the Center for Science in the Public Interest

(CSPI)calls on the National Cholesterol Education Program (NCEP) to form an

independent panel to review the Adult Treatment Panel III (ATP III,

2001)recommendations for cholesterol management and a 2004 update to these

recommendations.  The September 23 letter, signed by CSPI Executive

Director Michael Jacobson, PhD, and 34 physicians and researchers, questions the

scientific basis and objectivity of these clinical practice guidelines.

The National Institutes of Health and the National Heart, Lung, and Blood

Institute (NHLBI), which coordinates the NCEP, are preparing a detailed

response to the letter.  The ATP III recommendations and the update are

based on a careful analysis of strong and abundant scientific evidence.

The guidelines are objective and the process by which they were developed

has high integrity.


Since its creation in 1985, the NCEP has sought to educate health

professionals and the public about high blood cholesterol as a risk

factor for coronary heart disease (CHD) and the benefits of lowering

cholesterol in the prevention of CHD.  The NCEP is a partnership.  At its core is the

Coordinating Committee, composed of representatives of over 35 partner

organizations including major medical and health professional

associations, voluntary health organizations, community programs, and governmental

agencies.  The NCEP, under the sponsorship of the Coordinating

Committee, has developed a series of science-based clinical guidelines on

cholesterol management, known as Adult Treatment Panel reports.  These reports are

drafted by a panel of scientific experts and undergo thorough review by

the Coordinating Committee and other recognized scientific authorities

outside NIH.


ATP III, like the two previous guideline reports from the NCEP, was

based on an extensive examination of the scientific evidence by a panel of

leading scientific experts.  This report has been well received and widely

implemented by the medical community.  In July of 2004, the NCEP issued

an update to ATP III, based on an analysis of 5 new clinical trials of

cholesterol lowering with statin drugs.  The update was drafted by a

working group selected for their expertise from the members of the original ATP

III, and an expert representative of the American Heart Association (AHA) and

of the American College of Cardiology (ACC).  The update paper was reviewed

by the NCEP Coordinating Committee and by the scientific and steering

committees of AHA and ACC, and was endorsed by NHLBI, AHA, and ACC.


The update offered therapeutic options for the physician's consideration

rather than firm recommendations for the most part.  This was done in

recognition of the fact that there are a number of ongoing clinical

trials that will address the benefits of lowering LDL cholesterol well below

currently recommended goal levels.


The CSPI-initiated letter specifically calls into question the ATP III

clinical recommendations for cholesterol lowering in moderately high

risk women and the elderly who do not have heart disease.  NHLBI affirms the

scientific rationale for these recommendations.  Using all available

clinical trial and epidemiological evidence is a well-founded and widely

accepted approach to the development of clinical practice guidelines.

NCEP applies this approach to all recommendations to lower cholesterol - both

lifestyle changes and medication - as well as to all populations,

including women and the elderly.


There is abundant clinical trial and epidemiological evidence showing

that lowering LDL cholesterol (by statins or other means) prevents heart

attacks in men with or without prior coronary heart disease. In addition, there

is considerable evidence from trials of patients with coronary heart

disease or other high risk conditions that statins benefit women and men, older and

younger patients, and those with and without diabetes.  Since narrowing

of the coronary arteries is a lifelong gradual process, there is no

scientific basis to believe that cholesterol lowering suddenly becomes beneficial

the moment a person has a heart attack.  It is far more consistent with the

entire body of scientific evidence to hold that cholesterol lowering is

also beneficial in people without heart disease, but becomes even more

critical after a heart attack, when the person's risk for a future heart attack

rises significantly.


Recent clinical trials, including the Heart Protection Study, strengthen

ATP III recommendations for older persons, an age group which exhibits the

highest risk for heart attacks.  Regarding research on women, this same

large trial included over 5,000 high-risk women and showed the same

benefit of LDL-lowering therapy as observed in men.  In this trial, over 1,800

women had diabetes and they too benefited from LDL lowering.  Although

clinical trials have not included large numbers of moderately high risk women

(without heart disease), epidemiological studies show that these women

are just as likely to develop cardiovascular disease as men.  ATP III thus

applied the same guidelines to both men and women at moderately high



It is imperative that we apply what we have learned from research in

order to prevent or delay the development of heart disease, the leading killer

of women and men.  For tens of thousands of Americans, including women and

the elderly, the first sign of heart disease is sudden death.  Sound public

health policy demands that the significant risk for illness and death in

women and the elderly be addressed with science-based prevention



The letter also questions the ATP III recommendation that high-risk

patients with diabetes should be considered for cholesterol-lowering drug

therapy. In fact, there is conclusive clinical trial evidence that

cholesterol-lowering drug therapy significantly reduces cardiovascular

risk for patients with diabetes, both those with and without existing heart

disease.  This finding has been amply documented by a major primary

prevention trial in patients with diabetes that was published after the

ATP III update.  Once a person with diabetes develops cardiovascular

disease, the mortality rate is very high, so the objective in diabetes treatment

is to prevent the development of cardiovascular disease in the first place.

Clinical trials show that cholesterol lowering contributes significantly

to attaining this objective.


The letter questions the objectivity of ATP III and the update, stating

that the recommendations "may not be scientifically justified" since panel

members have had interactions with the pharmaceutical industry.  We have

noted before that the experts who are most knowledgeable in a subject

area are also the same people whose advice is sought by industry, and most

guideline panels include experts who interact with industry.  To ensure

that the guidelines are objective and science-based, NHLBI employs a rigorous

development and review process. Expert panel members are carefully

selected for their scientific and medical expertise and their integrity, multiple

levels of reviewers scrutinize the drafts of the guidelines from a

variety of scientific perspectives, and financial disclosure is published by the

peer-reviewed journal.


Many journals and organizations are currently reexamining their

approaches to managing disclosure of financial interests.  NHLBI is developing

further policy in this area to refine the process for management of potential

conflict of interest.


In summary, the ATP III guidelines and update were developed using a

thorough evidence-based process that has high integrity.  The guidelines

are derived from an objective analysis of the substantial scientific

evidence and NHLBI stands behind them. There are several clinical trials in

high-risk individuals currently underway.  The results of these trials will help

determine whether revisions to the current recommendations are

scientifically warranted.  At that time, NCEP will consider establishing

another panel.


More detailed information on the issues raised by the letter and the

NHLBI response to the letter will be made available after the response to the

letter has been finalized. The ATP III guidelines and update can be found online at:


<http://www.nhlbi.nih.gov/guidelines/cholesterol/index.htm>  .


NHLBI is part of the National Institutes of Health (NIH), the Federal

Government's primary agency for biomedical and behavioral research. NIH

is a component of the U.S. Department of Health and Human Services. NHLBI

press releases and fact sheets can be found online at www.nhlbi.nih.gov

<http://www.nhlbi.nih.gov> .


Read also Malcolm Kendrick´s comment