By Jeffrey Norris
Having important numbers at your fingertips can instill a false sense of security. When it comes to warding off arterial disease and associated heart attack and stroke risk, you are well advised to watch your cholesterol. Still, roughly half of the people who have heart attacks have normal cholesterol measures.
Most physicians are familiar with a risk scale developed through the Framingham Heart Study, a multigenerational study of men that began in 1948. The risk factors - including total cholesterol, high LDL cholesterol, low HDL cholesterol, age, diabetes, smoking and high systolic blood pressure - contribute to an overall estimated risk of having a heart attack within 10 years. For instance, a concentration of HDL in the bloodstream of less than 50 milligrams per deciliter may contribute to heart disease risk, according to this gauge.
A 2003 JAMA study of people who had prior heart attacks revealed that from 80 percent to 90 percent had one or more of these conventional risks, as calculated using the Framingham scale. On the other hand, it is rare for individuals under age 50 without any of the identified risks to have a heart attack.
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Mark Pletcher |
As scientific understanding of the epidemiology and biology of arterial disease grows, these guidelines will likely need to be revisited more often.
In fact, according to Thomas Bersot, MD, PhD, clinical professor of medicine at UCSF, cholesterol researcher at the Gladstone Institute of Cardiovascular Disease (GICD) and head of the Lipid Clinic at San Francisco General Hospital Medical Center, the Framingham risk score calculation could be further refined, based on what scientists have learned about cholesterol in recent years.
The problem with the use of HDL and LDL measures to score risk is that they are absolute. It is better to use a ratio, Bersot says. "The best predictor of risk related to cholesterol is a ratio you get by dividing your total cholesterol level by your HDL cholesterol level.
"A person who has an HDL level that's twice the average can get by with a much higher LDL than a person who has a normal HDL level. Even if you have an average or normal LDL level, if you have too little HDL, you are going to have excess LDL getting into the walls of your arteries."
A Statin When Lifestyle Change Is Deemed Inadequate
Not surprisingly, people who have survived a first heart attack or clot-induced stroke generally get treatment to boost the odds of preventing a repeat of the life-threatening event.
Both for people who have already had heart attacks or strokes and for people who have not - but are deemed to be at elevated risk - the most consulted guidelines for treating cardiovascular disease are the National Cholesterol Education Program's Adult Treatment Guidelines: Adult Treatment Panel III (ATP III). These guidelines, prepared under the auspices of the National Heart, Lung and Blood Institute, were last updated in 2004, and are scheduled to be updated again next year.
The updated ATP III puts the strongest emphasis ever on using LDL-lowering statins to combat atherosclerosis. The revisions are based largely on recent studies showing that statins can not only lower cholesterol, but also lower heart attack risk. Because of the success of statins, LDL lowering remains a major focus of treatment when diet and exercise fail, or when risk is deemed to be too high when first calculated.
The lowest recommended LDL goal in the guidelines is 70 - for individuals with diabetes who already have had a heart attack.
John Kane, MD, PhD, and his UCSF clinical practice colleagues treat extremely high-risk patients, many of whom do not respond to common therapeutic regimens. "The goal for LDL has progressively come down," he says. "We're very aggressive in the clinic in anyone with overt disease or a bad family history or other risk factors. We like to get the LDL down to 70 or even 60. That is not harmful in our view. For these people, we think this is a reasonable objective to reduce risk."
Through the GICD Lipid Disorders Training Center, Bersot teaches courses for physicians, nurse practitioners, pharmacists and dietitians. He covers heart disease risk, prevention and treatment, including diet, exercise and medicines.
It's clear to Bersot that many of these health care providers are predisposed to think that if a little LDL lowering is good, more must be better.
"Physicians think that if it's good to have an LDL below 70 if you're a really high-risk patient, then that should be good for everyone. That's not true. Higher doses of statins are being overprescribed," he says.
In a recent meta-analysis of five clinical trials, statin treatment appeared to reduce by 27 percent the number of medical events - such as heart attack, stroke or hospital visits for unstable angina - associated with coronary artery disease. But this "relative risk" reduction is less impressive when one considers that there were still 1,490 such events in the treated group, compared with 2,042 in the placebo group. About 30 people had to be treated to prevent one medical event.
Aspirin and Atherosclerosis
What about aspirin, compared with statins? Instead of targeting cholesterol, aspirin helps keep blood cells called platelets from clumping together and forming blockages in diseased arteries. Large clinical trials have demonstrated the health benefits of low-dose aspirin.
The Physicians' Health Study demonstrated that aspirin can help prevent first heart attacks in men at high risk, while the Nurses' Health Study showed that aspirin can prevent strokes in women at high risk.
But despite its easy availability and affordability, aspirin's well-known potential to cause gastrointestinal bleeding and interactions with other medications is of significant concern. Aspirin also can increase one's risk for bleeding in the brain - a hemorrhagic stroke.
Nobody is advised to self-medicate with aspirin daily without consulting a doctor. But in general, the American Heart Association (AHA), for one, recommends low-dose aspirin for individuals who have had heart attacks, unstable angina, strokes caused by blood clots or stroke-like episodes called transient ischemic attacks. The AHA also recommends daily aspirin for individuals whose estimated 10-year risk of having a coronary heart disease-related medical event is greater than 10 percent. For women age 65 and older, the AHA also recommends daily aspirin regardless of cardiovascular risk.
Aspirin, not surprisingly, is much cheaper than any of the statins.
Mark Pletcher, MD, MPH, a UCSF internist and epidemiologist, recently led a study in which he and his collaborators used published clinical trial data to model the costs and health benefits of treating middle-aged men with different levels of 10-year risk for developing coronary heart disease. The researchers compared treatment using a statin alone with treatment using aspirin alone, or with treatment using a combination of the two.
"National guidelines recommend aspirin or statin drugs individually to reduce first coronary heart disease events, but there are no guidelines about taking both," Pletcher notes.
Based on the cost-benefit analysis, "Aspirin is more cost-effective at lower levels of risk," Pletcher says. "Statins become more cost-effective as risk increases. When men are estimated to have a risk of a heart attack of 7.5 percent over 10 years, then aspirin is cost-effective, compared with no treatment. At current prices, adding a statin makes sense if the estimated 10-year risk is 10 percent or higher."
Research Aims for More Accurate Risk Prediction and Diagnosis
Pletcher's research on weighing the costs and benefits of treatment to counter risk of heart attack or stroke highlights the fact that it would be better to have more powerful, refined risk measures.
There are more people at lower or moderate risk of heart attack, as measured by the Framingham risk scale, than there are people at high risk. Many heart attacks occur among this larger group of low- to moderate-risk individuals, but this group is less likely to be the target of preventive treatment strategies.
Fortunately, only a minority with identified risk factors will have a heart attack in any given year. Unfortunately, that still adds up to a lot of people. Furthermore, the risk stratification provided by the Framingham scale is not good enough to identify who is probably going to have a heart attack.
People with some degree of heart disease risk by this measure do not necessarily rate an actual diagnosis of heart disease, as might be revealed by a range of lab tests. Heart attack - with or without sudden death - is the first evidence of heart disease for about half the individuals identified with heart disease.
"A large minority of these people - close to 30 percent - die during their first episode," Kane says. "They will never have the benefit of any diagnostic procedures that might predict risk." At the UCSF Cardiovascular Research Institute, Kane and his colleagues are working to identify proteins and genetic markers that are powerfully associated with elevated risk, and that can be measured simply and accurately.
Aspirin, Statins, or Both Drugs for the Primary Prevention of Coronary Heart Disease Events in Men: A Cost-Utility Analysis
Michael Pignone, MD, MPH; Stephanie Earnshaw, PhD; Jeffrey A. Tice, MD; and Mark J. Pletcher, MD, MPH
Annals of Internal Medicine (March 7, 2006), vol. 144, issue 5, pp. 326-336
Summary |
"Good" Cholesterol, Heart Attack Risk and Prevention
UCSF Today, April 3, 2008
Does It Matter How You Lower Your Cholesterol?
UCSF Today, March 7, 2008
National Heart, Lung and Blood Institute: Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)
Framingham Heart Study
UCSF Cardiovascular Research Institute
Gladstone Institute of Cardiovascular Disease
