David Rubinson had a heart attack at age 39.  But he blames himself for that.  As a record producer and manager of such acts as Santana and the Pointer Sisters, he thought he was Superman.  An eventually the late nights in the studio, the rich foods and the extreme stress caught up with him.  A poor lifestyle, combined with a family history of heart disease, became his kryptonite.

But he considers himself blameless for what happened next.  In the ensuing decade, he transformed his life.  He downsized his business, became a vegetarian, stopped smoking, started exercising, lost weight, and took up yoga.  His total cholesterol plummeted from 380 to 210, he qualified for $2 million worth of new life insurance, he passed his treadmill stress tests, and his doctors gave him nothing but back pats.  Then one night at dinner, almost 10 years to the day after his heart attack and just 12 hours after running 9!/2 miles across the Golden Gate Bridge, he felt a familiar dread.

“It wasn’t a real pain,” he recalls.  “It was more a sense of depletion, like somebody had pulled the plug and all the water was running out of the tub.  Later, after I put everyone to bed, I went into my office at home and took a nitroglyerin tablet.  And when it made me feel better, I knew I was in trouble.  I woke my wife and told her we had to go to the hospital.”

When doctors did an angiogram to assess the situation, Rubinson couldn’t believe what he saw.  “The grafts from my original bypass were completely dried up,” he says.  “They looked like black strings.  I’d been running across that bridge on nothing.  It’s hard to describe what I felt.  Rage, betrayal, terror.  My son asked the doctors, ‘How could this happen?  My God, look at everything he’s done!’”

So there was more surgery, five bypasses this time, and when Rubinson left the hospital, he was depressed and desperate.  That’s when he heard of a cardiologist named Roger Superko, M.D., who was perfecting a new type of blood analysis at a fledgling Bay-area clinic.  It identified 12 different subclasses of cholesterol-carrying particles, plus other substances that influence heart disease.  Dr. Superko claimed that total cholesterol and even levels of HDL and LDL were too general to be dependable predictors of  cardiovascular trouble.  In fact, he said, they were often misleading, creating a false sense of worry or security.

Rubinson had never heard this theory before, even though he had been seeing some of the country’s best cardiologists.  So, with nothing to lose, he submitted a blood sample and, to his amazement found an apparent explanation for his heart disease.  “Dr. Superko showed me al these new numbers,” he explains; “things like small, dense lipoprotein and homocysteine.  Then he told me, ‘You can diet and exercise all you want, but there are genetic factors at work here that must be managed in other ways.’”

With Dr. Superko’s guidance, Rubinson continued his healthful lifestyle and started taking medication to thwart the most lethal of these new types of cholesterol.  Now, almost 10 years after his second bypass surgery, Rubinson has all these new numbers within acceptable ranges and can claim, with confidence and authority this time, that his disease is under control.

“When I talk about Superko, tears come to my eyes,” says Rubinson.  “Because he saved me.  Without this man, I’m gone.”

Without realizing it, you may be in a situation similar to Rubinson’s.  You may think you’re taking good care of heart: exercising, eating right, and having your cholesterol checked.  And your numbers may be good.  Even your doctor may say you have nothing to worry about.  But should you believe him?

· The landmark Framingham Heart Study, which has been tracking thousands of people since 1948, found that 80 percent of those who develop coronary disease have the same basic cholesterol numbers as those who don’t.
· At least 50 percent of arteriosclerosis (narrowing of the arteries) can’t be explained by the standard risk factors (smoking, diet, lifestyle, high cholesterol).  There are other agents at work that routine lab tests miss.
· For 25 percent of men with a family history of cardiovascular problems, the first sign of heart disease is sudden death.

Getting nervous?

You should be.  Despite all the advances in heart-disease treatment within the last decade (new drugs, surgeries, preventions), it remains the country’s number-one killer.  A staggering 60 million Americans (one I every five persons) has some form of it, and each year 725,000 men and women die of it – the equivalent of one victim very 44 seconds.  And although science has arrested its growth, there’s still been no sign of a precipitous drop-off.

Statistics like these contradict the impression most people develop at the doctor’s office, where basic cholesterol numbers, treadmill stress tests, and lifestyle factors parade as ironclad predictors of risk and benchmarks for treatment.  On its Web site, the American Heart Association (AHA) encourages people to think of high cholesterol as a “leading risk factor for heart disease … a vital sign, similar to blood pressure.”  It makes the following recommendations:

· Total cholesterol – below 200 milligrams per decilitre (mg/dl)
· HDL (good cholesterol) – above 35 mg/dl
· LDL (bad cholesterol) – below 130 mg/dl
· Triglycerides – below 200 mg/dl

These four components of cholesterol, the so-called basic panel, are the only ones the AHA mentions.  When your blood-test results fall within these guidelines, your doctor will probably conclude that you have nothing to worry about.  Conversely, when your numbers exceed these boundaries, he’ll recommend lifestyle changes and maybe even cholesterol-lowering drugs.  But as we’ve seen, heart disease isn’t so clear-cut.  In fact, some impressive research refutes the dependability of guidelines::

Total cholesterol.  Drawing from a study of 360,000 men, researchers found that 24 percent of those who died of hart attacks had total cholesterol levels below 200.  “Total cholesterol is really a very bad test,” says Christie Ballantyne, M.D., director of the center for cardiovascular prevention at Methodist Hospital/Baylor school of medicine.  “If you’re judging the health of your heart by it, you’re way off.”

HDL.  According to data from the Framingham study, the average HDL cholesterol of men with coronary artery disease was 43.  That’s 23 percent higher than what the guidelines say is protective.

LDL.  Based on data from Framingham, the average LDL cholesterol of those having heart attacks was 150.  The guidelines call that only “borderline-high” risk.

Triglycerides.  Research from Framingham and other studies suggests that the AHA’s threshold is too lenient.  Keeping it below 150 appears to be the new consensus for safety.  (As this issue went to press, new national screening guidelines were being discussed.  For the latest information, visit www.nhlbi.nih.gov.)

For these reasons and more, the basic cholesterol panel can predict coronary artery disease in only 20 percent of cases.  “HDL, LDL, triglycerides – that’s the bare minimum”, says Dr. Ballantyne.  “And before you think you’re safe, remember that ideally you want an LDL less than 100, an HDL over 45, and triglycerides less than 150.  Unfortunately, most people don’t fit nicely into these categories.  Anyone in the gray zone needs more information.”  And that’s where the new blood tests come in.

Small, dense lipoprotein.  Fibrinogen.  C-reactive protein.  Homocysteine.  Lipoprotein(a).  HDL2b.  These are just a few of the measures that appear on reports from the Berkeley Heart Lab, an advanced cardiovascular diagnostics center in San Mateo, California, headed by Dr. Superko.  These gauges are unfamiliar, for patients as well as many doctors, but they represent the cutting edge of heart-disease prevention.  Dr. Superko has published more than 100 scientific articles on the topic and is a fellow in the American College of Cardiology.

When asked why anyone needs such detailed blood work, especially when he often must pay $150 to $700 to get it, he points to two substances, the preponderance of which can dramatically increase your risk of coronary disease.

The first is small, dense lipoprotein, and it’s the worst of the seven types of LDL cholesterol that can now be measured.  It’s dangerous because it’s the most likely of all the particles to worm its way into artery walls and plaques.  This creates arterial lesions, contributes to the growth of existing ones, and may make plaque less stable and more susceptible to rupture.  The combined results of three major studies found that small, dense lipoprotein conveys a threefold increase in cardiovascular risk.

The second substance is called lipoprotein(a), or Lp(a) for short.  This is a bastard form of LDL that’s so predictive of coronary disease that it’s been called “heart attack cholesterol.”  Researchers at Oxford University in England found that among 5,400 people with heart disease, those with the highest levels had a 70 percent greater chance of having a heart attack.

As you’ll learn in the accompanying article, “Will He Live or Will He Die?” other rarely measured blood components can have similar dire consequences.  Even though the mechanisms by which they all work are not fully understood, clinical evidence is mounting that they play influential roles in heart disease.  How vital it is to know yours depends on your family history and the lifestyle you lead.  But what’s disturbing is that so few doctors are offering their patients this opportunity.

“It’s a national scandal,” says Thomas Yannios, M.D., associate director of critical care and nutritional support at Ellis Hospital in Schenectady, New York.  “I’d estimate that only 5 percent of doctors in the United States are using these specialized blood tests.  There’s an incredible lack of understanding of this science on the part of the medical profession.  It’s exasperating to me, because we now have the ability to look into a person’s metabolic soul.”

The Berkeley Heart Lab isn’t the only business of its kind.  LipoMed in Raleigh, North Carolina, and Atherotech in Birmingham, Alabama, offer similar analyses, using different methodologies.  One independent study, which utilized the Berkeley program, reduced the risk of future heart events by 43 percent over 4 years.  And Atherotech claims it can raise a physician’s ability to predict cardiovascular disease from 40 percent to 90 percent.  These are bold promises the AHA is still considering; but some doctors are already convinced.

Dr. Yannios is one of them.  After attending lectures on the subject at American College of Cardiology conferences, he started doing some anecdotal research.  While making rounds in the intensive-care ward at his hospital, he began asking patients about their cholesterol profiles.

“I was horrified to find so many who had been through the mill of cardiac specialists, and others who supposedly had zero risk, hospitalized with heart problems,” he says, “Something big was being missed.”

Dr. Yannios subsequently wrote a book called The Heart Disease Breakthrough, in which he pulls together much of the supporting research for these specialized blood tests.  In the book he points out that this is neither flimsy science nor recent theory.  The foundational research dates to the 1950s, when scientists at the University of California at Berkeley discovered multiple cholesterol-carrying particles.  And what’s more, the Framingham Study has for decades been citing connections between many of these components and heart disease (fibrinogen in 1987, homocysteine in 1990, and lipoprotein(a) in 1994).  So why aren’t more people, and especially more doctors, ordering these tests?  There are a number of reasons:

1. The science is very complex.

“Traditionally, biochemistry is one of the first subjects you take in medical school,” explains Dr. Yannios, :and the cholesterol stuff is at the end.  It’s not a very glamorous topic, and that mentality gets carried on.  A lot of doctors either don’t want to or don’t have the time to master this biochemistry because it seems so complex.”

2. Cardiologists are mainly plumbers.

 When you develop a clog, they’ll scour it out, but traditionally they haven’t offered much advice on keeping your pipes clean.  “Doctors tend to treat what they can see, not what is potential,” says Dr. Yannios.  “And when the issue becomes more complex, that reinforces the behavior.”

3. Insurance may not pay for it.

Although the price of these tests is much cheaper than the bill for a bypass, health-insurance plans don’t typically reward prevention.  Unless you belong to a progressive provider or have a cardiologist who insists upon these tests, you probably won’t have much luck with reimbursement.

4. The prescription is a vitamin.

The antidote to many of these evil new particles is not a high-tech drug but a B vitamin called niacin.  It reduces triglycerides and LDL cholesterol (including Lp(a) and small, dense lipoprotein) at the same time it raises beneficial HDL.  In fact, niacin can be more effective at treating these things than popular cholesterol-busting drugs, which tend to act more generally on total cholesterol and gross LDL.  (Be careful, though.  Niacin has serious side effects and should be taken only under a doctor’s supervision.)

The point of all this is that doctors are so busy they often rely on drug-company salesmen for information about new treatments.  Because niacin has historically been the prescription when these new numbers are out of line, “there was never any fat wallet promoting it”, says Dr. Yannios.  In other words, unlike the commercial anti-cholesterol drugs that generate $16 billion in annual global sales for pharmaceutical companies, there was never any business reason for anyone to educate doctors about these other blood components.  This is changing, however.  A company named Kos makes a timed release prescription product called Niaspan, and Kos has recently partnered with DuPont to promote it.

But in the meantime, doctors across the country continue dispensing basic cholesterol tests and writing prescriptions for anti-cholesterol drugs that may not target the patient’s specific problem.  Dr. Superko points out that even though people taking cholesterol-reducing medication experience a 25 percent reduction in cardiovascular events, “there are still an awful lot of people on them having heart attacks.”

Bob Bakke is a classic example of this.  Despite a strong family history of heart disease, he thought he had everything under control – just like Rubinson – running 3 to 5 miles daily, eating a low-fat diet, keeping all his standard cholesterol numbers within recommended ranges.  In fact, just for insurance he was taking one of the most popular cholesterol-busting drugs on the market (Mevacor) and had recently passed a cardiac stress test.  Yes, life as a healthy, slim, 44-year old university research administrator in Chico, California, was good.  Then, while running on a gym treadmill and chatting with his 14-year old daughter, Bakke suddenly passed out.  The treadmill flung him against the wall so hard, emergency personnel initially though he had injured his neck.  But later, in the hospital, it was discovered that three of his major coronary arteries were 90 percent blocked.  Four days later he had a quintuple bypass.

“It was devastating,” he says.  “Suddenly I didn’t know whether I’d  live or die.”

With Dr. Superko’s help, Bakke, now 52, has gotten his heart disease under control.

He takes 4 to 5 grams of niacin daily and has continued with his healthful lifestyle.  A series of ultrasounds of his once-narrowed arteries has shown a 36 percent improvement in circulation.  No, he’s not going to be surprised again.  And neither should you.

“These tests are a way to know for sure,” he says.  “With the information available now, I believe you can actually beat this thing.”
 

Testing for the Villains and Heroes

There is nothing special about the way blood is drawn for these tests.  You fast for 12 hours, then roll up your sleeve for the usual needle prick.  Afterward, the sample is packed with ice in an insulated container and shipped to the Testing Center.  Ten days later, you have the results and the bill is approximately $700, but is not usually covered by health insurance.

Apoprotein B (107 mg/dl):  This is the protein cap that each LDL particle wears.  By counting these, you get a precise measure of the LDL particles in the bloodstream, a truer indication of your genetic predisposition to heart disease.  These particles may damage your arteries and cause blockages, so it helps to know how many you’ve got.

Lipoprotein(a), or Lp(a) (3 mg/dl).  It is recommended that Lp(a) be kept below 20.  This is a bastard form of LDL that’s so predictive of coronary disease that it’s been called “heart attack cholesterol.”  Researchers at Oxford University in England found that among 5,400 people with heart disease, those with the highest levels had a 70 percent greater chance of having a heart attack.  It accumulates around arterial lesions and promotes clotting.  Lp(a) alone can raise your risk of heart attack by as much as 70 percent.  Furthermore, it does not respond to diet and exercise.  Niacin is the best way to treat it – 4 to 5 grams of niacin daily is recommended.

Fibrinogen (324 mg/dl):  This is a protein molecule that promotes clotting and also thickens the blood.  The more there is, the greater the likelihood that your heart is struggling to pump sludge.  High levels seem to correlate with cigarette smoking, obesity, inactivity, aging, and diabetes.  Levels above 350 double the risk of coronary disease.

C-reactive protein (0.07 mg/dl):  This substance is produced in the liver when arteries become inflamed.  The more of it there is, the greater the chance of arterial plaque rupturing and causing a heart attack.  Levels above 2.5 mg/dl convey a two-to fourfold increase in risk and are capable of predicting first heart attacks 6 to 8 years in advance.

Homocysteine (11.9 micromoles per liter):  This is an amino acid that promotes clotting.  It appears to work in conjunction with fibrinogen and Lp(a).  Levels above 14 can increase your risk of  heart attack and stroke by two to four times.  Fortunately, it’s one of the easiest of the new blood components to control.  It responds well to folate and B vitamins.

Insulin (4 micrograms per mililiter – 12 mcg/ml):  This is a hormone secreted by the pancreas to regulate blood sugar and it is important in regulating diabetes.  However, when combined with high triglycerides, low HDL, high fibrinogen, and high levels of small, dense lipoprotein, high insulin levels strongly predispose you to atherosclerosis.  Keep this under 12 mcg/ml.  Testing for insulin isn’t new, but it’s important.

LDL IIIa and IIIb (15.6 percent): Dense lipoprotein.There are seven subclasses of LDL particles, with such catchy names as I, Iia, Iib, IIIa, IIIb, Iva, and Ivb.  Overall, LDL is bad cholesterol, but IIIa and IIIb are the most destructive types.  They are the most dangerous because they are the smallest, densest particles – the ones most likely to work their way into artery walls and form plaques. This creates arterial lesions, contributes to the growth of existing ones, and may make plaque less stable and more susceptible to rupture. They are the worst of the seven types of LDL cholesterol that can now be measured.  People with lots of small, dense lipoprotein are dubbed pattern B and have a threefold greater risk of developing heart disease.

Triglycerides:  Triglycerides are the primary form of fat and comprise the bulk of fat in foods, stored fat in the body, and are a
primary form of fat in the blood. Triglycerides are the lipids that provide calories or energy to the body. Triglycerides exist in many shapes and sizes, but they all exhibit a similar structure which is glycerol molecule with three fatty acids attached. The physical characteristics of a given fat are determined by the degree of saturation of its fatty acids.  Keeping it below 150 appears to be the new consensus for safety.  The Rush Medical College in Chicago has shown that levels of triglycerides above 190mg/100 ml significantly increases the thickness of blood. Viscous blood is more prone to produce blood clots, which can result in cardiac and / or cerebrovascular problems. (Remember, an aspirin a day helps thin blood.)  As with cholesterol, most cases of extremely high triglycerides are the result of genetics as opposed to diet. A mildly overweight individual could have levels in the range of 18,000 mg/dL (milligrams per deciliter) and above.

HDL2b (21 percent):  There are five subclasses of HDL particles, labelled 2a, 2b, 3a, 3b, and 3c.  Overall, HDL is good cholesterol, but 2b is the most beneficial.  The more you have it, the less likely you are to suffer a heart attack.

If you have a family history of heart disease and/or basic cholesterol numbers that are suspicious, ask your doctor about these specialized tests.  Take niacin only under a doctor’s care; it can cause liver damage in the large doses that are necessary to be effective.