Heart Disease and Cholesterol Management
By Dr. Shafiq Qaadri, MD
Is it true that the incidence of heart disease is increasing, but that the mortality rate is decreasing?
Actually, the incidence of both is decreasing. In fact, the incidence of coronary artery disease peaked in the late 50s, early 60s, and has been decreasing ever since... Some people have raised the possibility of a rebound with the increase in obesity and diabetes. Interestingly, there has been a prediction of a future increase, as the current number of overweight adolescents age.
The decreased mortality rate is due to better medical care—the availability of ICUs, CCUs, angioplasty, and the more aggressive care of hypertension and lipids.
Is it true that half of all Canadians will die of cardiovascular disease?
Pretty close to half, although the number for myocardial infarction is about one-third. But if we add to this strokes and peripheral vascular disease, you get a number between 40 to 50%.
Is it true that diet doesn’t really work, doesn’t really get you to your targets?
This is somewhat controversial. It is true that dietary studies that show decreases in overall mortality are practically non-existent. The only study which comes close to this is the Mediterranean Diet Study, but even that was flawed.
Most of the dietary studies do not answer the question regarding overall mortality.
What was the major finding of the INTER-Heart study?
The INTER-Heart study was done by Salim Yusuf and his group in Hamilton—12,500 patients in 52 countries with all ethnicities. The remarkable conclusion of this groundbreaking study is that 90% of heart attacks can be attributed to 9 factors. This is valid for every nation and every ethnic group considered.
The number one factor was lipids. Then came smoking, hypertension, diabetes, lack of fruits and vegetables in the diet, lack of physical activity, psychosocial factors such as stress, and lack of alcohol in the diet.
We understand from this that 50% of all heart attacks are due to blood fats, lipids, or the ratio between atherogenic and antiatherogenic lipid particles—the LDL and HDL.
If the ratio of Total Cholesterol/HDL is greater than 4, patients are considered to be at high risk for cardiovascular disease. What is this ratio trying to say?
The balance between lipoprotein particles which deliver cholesterol to tissues and atheromatous plaque, versus the antiatherogenic particles which is the HDL--the denominator of this ratio.
What is the importance of HDL in coronary heart disease?
The HDL is responsible for the reverse transport of cholesterol from the tissues and plaque back to the liver for excretion in the form of cholesterol or bile acids.
Not only this, HDL also has important anti-inflammatory and antioxidant properties. This was perhaps best demonstrated by the discovery of apolipoprotein (a1) Milano. In Northern Italy, there is a group of patients with relatively low HDL levels, but they live forever, more or less, never dying of heart disease.
What was discovered was that this population has a special type of HDL which is particularly efficient at getting rid of bad cholesterol from tissues and plaques.
Do triglycerides matter, as there seems to be very little discussion of them?
For good reason. In most of the studies, once you had accounted for the HDL, triglycerides seemed to be less important.
What I usually try to tell people when I discuss this issue is that once you have triglycerides over 1.5 or 1.7 mmol/L, chances are you have a more atherogenic LDL.
Should we as clinicians be treating, modifying, both the LDL and the HDL together?
Definitely. I try to tell whoever will listen, when we measure apolipoprotein B, which is a good measure of the atherogenic particles, and the triglycerides, which is a good assessment of the size of the particles, we know the relative risk of the patient pretty well.
If we have something that will reduce both the numbers—namely apo B and the LDL—and at the same time change the quality of the particles, from smaller to bigger, we’ll be doing a good job.
Do you anticipate that cardiovascular societies will recommend combination therapy soon—to reduce LDL and raise HDL?
I sincerely hope so, as I think this follows the parallel of hypertension in many cases. Dr. Greg Brown in Seattle published the HADS Study, the HDL Atherosclerosis Study, in THE NEW ENGLAND JOURNAL OF MEDICINE. It was an angiography, reangiography study over three years; the patients were in four groups—one treated with statins and niacin, another with antioxidants, the third with statins, niacin, and antioxidants, and the fourth was placebo.
The results were absolutely staggering. It confirms the hypothesis of your question: that simultaneously lowering LDL and raising HDL works. There was a 90% reduction in cardiovascular events, something you have never seen in a single therapy trial—90%! There was a net decrease in the atherosclerosis measured in 52 segments of the coronary arteries, and a remarkable change in the ratio between Total cholesterol/HDL.
Family doctors sense that they can stop the progression of coronary artery disease. But how reasonable is it to expect regression?
I think most people agree that stopping progression of the disease also includes stabilization of the lesion—when a vulnerable and fragile plaque becomes a lesion that has a good cap on it, that is unlikely to rupture and cause the acute event.
The HADS study showed that regression is also possible, but would require much more aggressive treatment than what we are currently practising.
What is the place of niacin, one of the B vitamins, in cardiovascular disease management?
Niacin, or nicotinic acid, used to be called vitamin B3, and was discovered by Dr. Altshul, a compatriot of mine who worked in Saskatchewan. It has been used over the last 50 years, and can be considered a broad spectrum lipid agent. The difficulty is that to achieve good LDL lowering, HDL raising, and triglyceride lowering, you have to use very high doses.
For example, the vitamin dose of niacin is something like 50 mg per day. For lipid therapy, we usually use doses from 1500 mg to 2000 mg per day.
The principal action of niacin is that it decreases the release of fatty acids from adipose tissue, and therefore limits the synthesis of triglycerides and lipoproteins in the liver. It also changes the activity of cholesterol ester transfer protein, which allows for improvement in the amount of HDL cholesterol.
Previous discussions of niacin have talked about intolerable side effects such as flushing. How is this caused and do the extended-release versions of niacin address this problem?
The flushing is caused by the release of prostaglandins. The way we used to deal with it was to ask the patient to take aspirin 15 minutes before they took the niacin. Aspirin will actually stop the production of the prostaglandins, which will limit the flushing.
There are essentially three types of niacin that are used. Only two of them are available in Canada at the moment. One is something called the immediate-release or crystalline niacin—this is a known cause of flushing, which tends to decrease after the first week of use.
There are also SR, sustained-release, niacins. These differ in the formulation, which causes a different dissolution of the powder compound. The problem with the sustained-release versions is that it is metabolized somewhat differently than the crystalline niacin, and the metabolites which are produced are less effective against lipids, and also cause abnormalities of liver function tests.
The third formulation, which is available in the USA and in Europe, is called extended-release niacin. This has the great advantage of being taken once a day in the evening, aiming for doses between 1 to 2 grams. This doesn’t cause much flushing, it doesn’t cause liver function abnormalities, and it’s generally quite well-tolerated.
Is this meant to use as monotherapy, or in combination with a statin?
Both are possible.
I think the combination is extremely effective in preventing vascular events…In fact, in the USA a combination pill is available now. I think this would be more or less the ideal treatment.
Where would the extended-release niacin fit into our choice of therapy?
The extended-release niacin, known as Niaspan in the USA, will probably not divert people from prescribing statins, which indeed have been very effective. But it is particularly suited to an isolated, low HDL levels, and mild to moderate hypertriglyceridemia.
I think it is also particularly well-suited for combination treatments.
What is your final message regarding lipid management?
We have to know why we are treating the patient, what are the targets we’re striving for, and make sure that we impact the overall risk of cardiovascular disease. We should also make sure that we don’t either overtreat or undertreat.
Dr. Shafiq Qaadri is a Toronto family physician and Continuing Medical Education lecturer. www.doctorQ.ca
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