|What is cholesterol?
Cholesterol is a soft white/yellow waxy substance that is one of the fats that are found in the blood. Cholesterol is used in the body for formation of hormones, nerve tissue and cell membranes. We commonly talk about two type of cholesterol in the blood, High Density or good cholesterol and Low Density or bad cholesterol.
Why are we concerned about cholesterol?
Persons with diabetes have two to four times the risk of non diabetics for cardiovascular disease and 80% will have a cardiovascular death. This is because diabetes is a vascular disease. A famous research paper by Dr. Stephen Hafner has demonstrated that diabetics who have not had a heart attack have the same cardiovascular risk as non diabetics who have had a heart attack. Because of this reduction of risk of blood vessel disease is of primary importance in improving quantity and quality of life for those affected by diabetes.
What can we do?
Glucose control is important in reducing cardiovascular risk and studies have shown that a 1% reduction in A1c reduces the risk of a heart attach by 14%. There are; however other measures that taken together can reduce cardiovascular risk by close to 80%.
Lipid (Cholesterol) control is a significant way of lowering risk in diabetes. We know that over half of diabetics have abnormal cholesterol levels (dyslipidemia) and that after 15 years of diabetes over 2/3 have dyslipidemia. This dyslipidemia is one contributing factor to the high risks of diabetes. This has been recognised for some time and the Canadian Diabetes Association has had lipid targets in the treatment guidelines. Because of recent research studies that have given us new insights, the Canadian Diabetes Association felt that the new knowledge was sufficiently important that they revised this area of the 2003 Canadian Diabetes Assoc Guidelines in Sept 2006 (2 years before the publication of a complete guideline revision.) These new guideline changes relate to vascular protection and most specifically to Cholesterol.
One of the most significant risk factors for heart disease (5) has always been high Cholesterol levels (6), the higher the level, the higher the risk (7) and we have known for many years that lowering cholesterol by 1%, lowers heart disease risk by 2%. The question has been how low should we go. We also know that there are several cholesterol sub types. Within our total cholesterol we have High Density Cholesterol (HDL-C), otherwise known as good cholesterol. This form of cholesterol scavenges the dangerous cholesterol particles and reduces risk of heart disease. A 1% increase in HDL-C decreases cardiovascular risk by 3%. Diabetics typically have low levels of LDL-C or good cholesterol. We can reduce risk by raising HDL-C and we can do this by decreasing weight, increasing exercise and cutting out smoking. There are also medications which have a modest effect on HDL-C.
Low Density Cholesterol (LDL-C) or bad cholesterol levels are directly related to risk of cardiovascular disease. Low Density Cholesterol (LDL-C) is the portion of cholesterol most closely associated with cardiovascular risks. Heart attack risks are independently and directly associated with LDL levels. A 1% decrease in LDL level translates to a 2% reduction in risk. Knowing that the higher the cholesterol, the higher the risk, at what point should we intervene with lifestyle or medication. We know that all diabetics are at very high risk, extensive studies have shown that the lower the cholesterol, the lower the risk so how low should we go?
Recent research in diabetics the Collaborative Atorvastatin Research in Diabetes Study (CARDS) trial enrolled diabetics with one other risk factor, age, hypertension, obesity, heart or other vascular disease with Atorvastatin (Lipitor) 10 mg a day irrespective of their previous LDL level, the average pre-treatment LDL level was fairly normal at 3.1 and fell to 2 mmol/L during the study. 5 years of Atorvastatin treatment lowered the rate of heart attacks and other vascular events by 37% and strokes by 48%. Our interpretation of this is that all diabetics with risk factors should be treated with a statin. Since this study and several other risk reduction studies achieved LDL levels of below 2, we make this our primary target. 10 mg Atorvastatin lowers LDL levels by about 40%, we set a 40% LDL lowering as a target in this group of people who has no previous history of heart disease. We call this Primary Prevention, that is, preventing a first event in someone not known to have disease. In the person who has already had a heart attack or evidence of heart disease (secondary prevention) our LDL target is still less than 2 mmol/L but we try to achieve a 50% LDL lowering which takes larger doses of statin drugs. Another even more sensitive & specific indicators of cardiac risk is the Total Cholesterol/HDL Ratio and the CDA target is to have this value at less than 4; this is a secondary target. That is to say that we first try to achieve an LDL less than 2, then we look at the TC/HDL ratio and if this is greater than 4 we target this value. We can reduce the TC/HDL ratio by either lowering the total cholesterol with statin drugs or by raising HDL.
||less than 2
||less than 4
Lifestyle interventions remain a key component of cardiovascular disease prevention strategies and diabetes management in general. Most Type 2 Diabetics are obese and even modest 5-10% weight reduction can result in improved lipid profiles. Reduction in dietary fat especially animal fat and exercise for 30 minutes a day can improve lipid profiles, glucose levels and overall risk. There are considerable variations but on average in large well controlled trials; lifestyle modifications have only resulted in an average 5% LDL reduction. Since the evidence shows that for maximal risk reduction we need a 40% LDL reduction, medications are often suggested.
In most cases we start treatment with a statin type drug to lower LDL to less than 2 mmol/L. Generally these drugs are extremely safe and free of side effects although occasional instances of muscle pains are associated with this class of drug. There are a number of different drugs and each has its own properties, in particular there is a difference in potency (the amount of LDL lowering) that we get out of a fixed dose of the drug. Frequently if one drug or strength cannot be tolerated, we can lower the dose or change to another member of the class.
Statin doses to achieve 40% LDL lowering
- Simvastatin (Zocor) 40 mg
- Atorvastatin (Lipitor) 10 mg
- Rosuvastatin (Crestor) 10 mg
Note: Doubling statin doses gives an additional 6% LDL lowereing
If we cannot achieve LDL <2 with statin alone we may consider adding a cholesterol absorption inhibitor such as Ezetimibe (Ezetrol) 10 mg which will lower LDL a further 25%.
After achieving the primary goal of LDL <2 then we try to achieve Total Chol/HDL of less than 4. In diabetes, there is frequently low HDL. Lifestyle measures are best to raise HDL, increase exercise, stop smoking, lose weight. If we still do not achieve the TC/HDL target of <4, we may consider Fibrates (Fenofibrate or Bezafibrate) which may raise HDL by up to 25% and modestly lower cholesterol.
Niacin (Nicotinic acid) a naturally occurring Vitamin of the Vitamin B family may also raise HDL by up to 20% (and lower triglycerides by 25%). Niacin is taken with meals in doses of 100 to 500 mg. It may cause flushing that some people find very unpleasant and this may limit dose. There is also a 500 mg extended action form. Dose is from 100 to 1500 mg, doses higher than this in diabetes may worsen glucose control.
How are we doing?
The DICE (Diabetes in Canada Evaluation) in 2006 showed that only half of diabetics are treated with statin and only a small proportion (15%) of those treated achieve target values.
What can you do?
- Are you at risk? (Diabetic +1 risk factor: age, smoking, high BP)
- Are you on statin?
- Are you on the right statin?
- Are you taking the right dose?
- Have you achieved target LDL <2 mmol/L?
- Is your Total Cholesterol/HDL <4