Metabolic Risk Factors
Blood Cholesterol: “Good” and “Bad”
The particles in the blood that carry cholesterol are called lipoproteins. Most cholesterol is carried in low density lipoproteins (LDL) and excess LDL leads to the deposition of cholesterol on the walls of arteries. High density lipoproteins (HDL) play an important role in picking up cholesterol from the walls of the arteries and taking it back to the liver for excretion into bile. The best index of heart disease risk is the total cholesterol divided by the HDL-cholesterol (TC/HDL-C ratio). An ideal ratio is less than 3.5.
Triglycerides are produced in the liver from the fat, carbohydrates, and alcohol in our diets and are also produced as the fatty acids from fat stores returned to the liver. High levels of blood triglycerides result in a reduction in HDL and are a risk factor for heart disease. Very high blood triglycerides (chylomicronemia) can cause an inflammation of the pancreas (pancreatitis).
High blood levels of a genetically determined cholesterol-carrying particle called lipoprotein (a), or Lp(a), promote the development of cholesterol deposits in arteries (atherosclerosis) and interfere with the breakdown of blood clots (thrombolysis) in arteries, thus increasing the risk of heart attack and stroke. Lp(a) levels > 25 mg/dL (>250 mg/L) are associated with a significant increase in the risk of heart disease and stroke, and the risk increases further with levels above 50 mg/dL. Lp(a) appears to be a heart disease risk factor in the presence of elevated plasma levels of LDL-cholesterol or other risk factors. In patients without evidence of heart disease, Lp(a) measurement can help determine whether or not cholesterol-lowering medication is necessary. A plasma concentration of lipoprotein(a) above 30 mg/dL may indicate that LDL-C-lowering therapy is warranted, even in patients with only borderline elevations in LDL-C.
The inflammatory marker C-reactive protein (hsCRP) has been shown to be an independent marker of heart disease risk. CRP may help to assess the risk of CVD in asymptomatic, and apparently healthy, men and women. In several recent studies, the rates of coronary events increased significantly with increases in baseline levels of C-reactive protein and patients with high levels of CRP benefit from statin therapy. An optimal hsCRP level is < 1.0 mg/L; and levels above 3.0 mg/L indicate higher risk for heart disease and stroke.
Diabetes has become a leading cause of death by disease in the Canadian population. People with diabetes have a three to five times higher risk for heart disease. There are three types of diabetes:
- Type 1 diabetes, seen in about 10 per cent of people with diabetes and most commonly in children, occurs when the pancreas has been damaged by immune-mediated injury, sometimes related to a viral infection. This type of diabetes requires insulin treatment.
- Type 2 diabetes, affecting 90 per cent of people with diabetes, occurs when fat, muscle, and other cells in the body become resistant to the effects of insulin and the pancreas does not produce enough insulin to compensate. This type of diabetes often responds well to weight loss and exercise.
- Gestational diabetes is a form of diabetes that occurs in 2 to 4 per cent of women during pregnancy. Gestational diabetes is a risk factor for type 2 diabetes later in life.
Diabetes is defined as a fasting blood glucose level of 7.0 mmol/L or higher. Most people with type 2 diabetes have two metabolic abnormalities that raise their fasting blood glucose: insulin resistance and a deficiency in production of insulin by the pancreas. Treatment of type 2 diabetes consists of weight loss, exercise, and medications to control blood sugar. Most patients with diabetes also require statin treatment to lower LDL levels to below 2.0 mmol/L.
Blood Test (Ideal Cholesterol Profile)
Optimal levels are lowest for individuals with a history of cardiovascular disease or diabetes and hence a higher risk of future heart problems.
|Optimal Levels of Blood Tests|
|People with a History of Heart Disease, Stroke, Sub-Clinical Atherosclerosis
|Cholesterol||< 5.0||< 4.0|
|Triglycerides||< 1.7||< 1.7|
|LDL-C||< 2.5||< 2.0|
|HDL-C||> 1.0 (M)
> 1.2 (F)
|> 1.2 (M)
> 1.3 (F)
|Chol/HDL-C ratio||< 4.5||< 3.5|
All patients who already have coronary heart disease or diabetes should be treated with a statin. Statins are safe and effective drugs for lowering cholesterol, with an overall risk of significant elevations in liver enzymes in one in 1,000 patients and in muscle enzymes in one in 5,000 patients. Some patients may require the addition of a second medication, such as ezetimibe, which is an anti-hyperlipidemic that acts by reducing cholesterol absorption in the intestine.
Elevated triglycerides are a risk factor for coronary heart disease (CHD), particularly when HDL-C concentrations are low or when LDL-C is elevated. In patients with fasting triglycerides above 6.0 mmol/L, there is a risk of pancreatitis. Successful treatment requires optimization of blood sugar control in diabetes and avoidance of alcohol, oral estrogen, and retinoids. The most potent statins can lower triglycerides by 40 per cent. Niacin, a B vitamin, lowers triglycerides by 30 to 40 per cent, but its use may be limited by side effects and exacerbation of insulin resistance. Fibrates lower triglycerides by a similar amount and are generally well-tolerated.
Treatment of Low HDL-C
The B vitamin niacin is capable of increasing HDL-C by 30 per cent (and often by an even higher percentage with prolonged treatment) and is the most effective agent for increasing low HDL-C. Immediate-release niacin must be taken three times a day to allow tolerance to side effects such as flushing. Extended-release niacin is taken once daily at bedtime, usually with 325 mg of ASA.
Statins are used to treat high levels of LDL-cholesterol. Statins include medications such as rosuvastatin (Crestor®), atorvastatin (Lipitor®), fluvastatin (Lescol®), lovastatin (Mevacor®), pravastatin (Pravachol®), and simvastatin (Zocor®).
Fibrates are used to treat high levels of blood triglycerides with or without high levels of LDL-cholesterol and to treat low levels of HDL-cholesterol. Among the fibrates are bezafibrate (Bezalip®), fenofibrate (Lipidil®), and gemfibrozil (Lopid®).
Niacin is used to treat low levels of HDL-cholesterol, elevated triglycerides, and LDL-cholesterol. Niacin is a B vitamin.
Resins are used to lower LDL-cholesterol and are often used in combination therapy. An example of a resin is cholestyramine (Questran® and Colestid®).
Ezetimibe (Ezetrol®) inhibits cholesterol absorption.
Clinical trials have demonstrated clearly that lowering serum LDL-cholesterol and increasing serum HDL-cholesterol reduce major coronary events in patients, irrespective of the presence of clinically evident CHD or hypercholesterolemia. The number of patients requiring treatment to prevent one major coronary event is dependent on the absolute level of risk, making statin treatment of patients with documented cardiovascular disease or diabetes highly cost effective. Statin treatment decreases the incidence of stroke and total mortality in high risk patients. A reduction in coronary events is evident for patients with and without clinically evident CHD and with average or elevated LDL-cholesterol concentrations.
LDL reduction is associated with decreased progression of mild and moderate blockages in coronary arteries and regression of moderate to severe blockages by coronary angiography. Reduction in serum LDL and/or an increase in serum HDL results in a decrease in the lipid content of the atherosclerotic plaque, increased plaque stability, reduced likelihood of plaque rupture, and, hence, reduced risk for heart attack.
Eicosapentaenoic acid (EPA) and docosahexaenoic acid acid (DHA), available in the form of salmon oil capsules (1,000 mg three to four times/day), can be a useful dietary supplement to lower triglycerides.
Psyllium (Metamucil®), hemp, flaxseed, oat bran, guar gum, and pectin help to lower LDL-cholesterol.
Replacement of animal protein with soy-based protein can also reduce LDL-cholesterol levels.